Cationic Albumin Nanoparticles for Enhanced Drug Delivery to Treat Breast Cancer: Preparation and In Vitro Assessment

PubMed Central

Abbasi, Sana; Paul, Arghya; Shao, Wei; Prakash, Satya

2012-01-01

Most anticancer drugs are greatly limited by the serious side effects that they cause. Doxorubicin (DOX) is an antineoplastic agent, commonly used against breast cancer. However, it may lead to irreversible cardiotoxicity, which could even result in congestive heart failure. In order to avoid these harmful side effects to the patients and to improve the therapeutic efficacy of doxorubicin, we developed DOX-loaded polyethylenimine- (PEI-) enhanced human serum albumin (HSA) nanoparticles. The formed nanoparticles were ~137 nm in size with a surface zeta potential of ~+15 mV, prepared using 20 μg of PEI added per mg of HSA. Cytotoxicity was not observed with empty PEI-enhanced HSA nanoparticles, formed with low-molecular weight (25 kDa) PEI, indicating biocompatibility and safety of the nanoparticle formulation. Under optimized transfection conditions, approximately 80% of cells were transfected with HSA nanoparticles containing tetramethylrhodamine-conjugated bovine serum albumin. Conclusively, PEI-enhanced HSA nanoparticles show potential for developing into an effective carrier for anticancer drugs. PMID:22187654

Enhanced tolerance and antitumor efficacy by docetaxel-loaded albumin nanoparticles.

PubMed

Tang, Xiaolei; Wang, Guijun; Shi, Runjie; Jiang, Ke; Meng, Lingtong; Ren, Hao; Wu, Jinhui; Hu, Yiqiao

2016-10-01

Docetaxel is one of the most active chemotherapeutic agents for cancer treatment. The traditional docetaxel injection (TAXOTERE®) is currently formulated in the surfactant polysorbate 80, which has been associated with severe adverse reactions. To avoid the use of polysorbate 80 as well as to reduce the systemic toxicity of docetaxel, in this study, docetaxel-loaded albumin nanoparticles were fabricated by a novel simple self-assembly method. The resulting nanoparticles showed a mean diameter size of 150 nm. After being encapsulated into nanoparticles, docetaxel displayed similar cytotoxicity to traditional injection. Since polysorbate 80 was not involved in nanoparticles, the hemolysis was completely eliminated. The maximal tolerance dose of nanoparticles was also increased, which allowed a higher dose to be safely intravenously injected and produced ideal antitumor effects. The 150 nm diameter also allowed the nanoparticles to accumulate in tumor tissue via the enhanced permeability and retention effect. The passive targeting ability further caused the higher antitumor effects of nanoparticles than that of traditional injection at the same dose (7.5 mg/kg). Therefore, docetaxel-loaded albumin nanoparticles fabricated by our strategy showed higher promise in their safety and effectiveness than the traditional docetaxel injection.

Stabilization of hyperforin dicyclohexylammonium salt with dissolved albumin and albumin nanoparticles for studying hyperforin effects on 2D cultivation of keratinocytes in vitro.

PubMed

Füller, J; Kellner, T; Gaid, M; Beerhues, L; Müller-Goymann, C C

2018-05-01

Due to the limited chemical stability of the natural hyperforin molecule, a more stable form of hyperforin, i.e., the hyperforin dicyclohexylammonium salt (HYP-DCHA) has been used for ex vivo and in vitro experiments in recent years, but its actual stability under typical cell culture conditions has never been studied before. In this contribution the stability of HYP-DCHA was examined under typical cell culture conditions. Different cell culture media with and without fetal calf serum (FCS) supplementation were studied with regard to further stabilization of HYP-DCHA determined with HPLC analysis. Furthermore, albumin nanoparticles were examined as a stabilizing carrier system for HYP-DCHA. In this context, the interaction between HYP-DCHA and albumin nanoparticles (ANP) was examined with regard to size and loading with HYP . The effects of HYP-DCHA either supplied in cell culture medium or loaded on ANP on viability and cytotoxicity were studied in vitro on HaCaT monolayers (human keratinocyte cell line). HYP-DCHA supplied in FCS-containing medium was recovered completely after 24h of incubation. However, a lack of FCS caused a total loss of HYP-DCHA after less than 24h incubation time. Supplying HYP-DCHA loaded on ANP in an FCS-free medium resulted in a recovery of about 60% after 24h incubation. HYP-DCHA supplied in medium along with FCS showed a slow dose-dependent decrease in viability of HaCaT cells without any cytotoxic effects (antiproliferative effect). Treatment with HYP-DCHA with a lack of FCS resulted in a significantly faster decrease in viability which was mainly due to cytotoxicity. The latter was true for HYP-DHCA-loaded ANP where increased cytotoxicity was observed despite the presence of FCS. The results show that the stability of the widely used HYP-DCHA is rather limited under cell culture conditions. Especially a lack of FCS leads to degradation and/or oxidation of HYP-DCHA probably causing an increased cytotoxicity. In contrast, FCS supplementation fairly stabilizes HYP-DCHA under cell culture conditions while albumin nanoparticles may serve the same stabilization purpose despite increasing cytotoxic effects onto the cells themselves. Copyright © 2017 Elsevier B.V. All rights reserved.

Fundamental and applied studies in nanoparticle biomedical imaging, stabilization, and processing

NASA Astrophysics Data System (ADS)

Pansare, Vikram J.

Nanoparticle carrier systems are gaining importance in the rapidly expanding field of biomedical whole animal imaging where they provide long circulating, real time imaging capability. This thesis presents a new paradigm in imaging whereby long wavelength fluorescent or photoacoustically active contrast agents are embedded in the hydrophobic core of nanocarriers formed by Flash NanoPrecipitation. The long wavelength allows for improved optical penetration depth. Compared to traditional contrast agents where fluorophores are placed on the surface, this allows for improved signal, increased stability, and molecular targeting capabilities. Several types of long wavelength hydrophobic dyes based on acene, cyanine, and bacteriochlorin scaffolds are utilized and animal results obtained for nanocarrier systems used in both fluorescent and photoacoustic imaging modes. Photoacoustic imaging is particularly promising due to its high resolution, excellent penetration depth, and ability to provide real-time functional information. Fundamental studies in nanoparticle stabilization are also presented for two systems: model alumina nanoparticles and charge stabilized polystyrene nanoparticles. Motivated by the need for stable suspensions of alumina-based nanocrystals for security printing applications, results are presented for the adsorption of various small molecule charged hydrophobes onto the surface of alumina nanoparticles. Results are also presented for the production of charge stabilized polystyrene nanoparticles via Flash NanoPrecipitation, allowing for the independent control of polymer molecular weight and nanoparticle size, which is not possible by traditional emulsion polymerization routes. Lastly, methods for processing nanoparticle systems are explored. The increasing use of nanoparticle therapeutics in the pharmaceutical industry has necessitated the development of scalable, industrially relevant processing methods. Ultrafiltration is particularly well suited for concentrating and purifying macromolecular suspensions. Processing parameters are defined and optimized for PEGylated nanoparticles, charge stabilized latices, and solutions of albumin. The fouling characteristics are compared and scale-up recommendations made. Finally, a pilot scale spray drying system to produce stable nanocrystalline powders of highly crystalline drugs which cannot be stably formulated by traditional spray drying methods is presented. To accomplish this, a novel mixing device was developed and implemented at pilot scale, demonstrating feasibility beyond the lab scale.

Artemisinin nanoformulation suitable for intravenous injection: Preparation, characterization and antimalarial activities.

PubMed

Ibrahim, Nehal; Ibrahim, Hany; Sabater, Alicia Moreno; Mazier, Dominique; Valentin, Alexis; Nepveu, Françoise

2015-11-30

More than 40 years after its discovery, artemisinin has become the most promising antimalarial agent. However, no intravenous formulation is available due to its poor aqueous solubility. Here, we report the preparation, characterization, and in vitro and in vivo biological evaluation of biodegradable albumin-bound artemisinin nanoparticles. The nanoparticles were prepared by a combination of a bottom-up and a top-down processes and characterized by different spectroscopic techniques. The preparation process was optimized to develop a nanoformulation with the smallest possible diameter and good homogeneity suitable for intravenous injection enabling direct contact of artemisinin with infected erythrocytes. Chemically and physically stable artemisinin nanoparticles were obtained with excellent entrapment efficiency. In in vitro experiments, the artemisinin nanoformulation was interestingly more effective than non-formulated artemisinin. In Plasmodiumm falciparum-infected 'humanized' mice, the nanoparticles proved to be highly effective with 96% parasitemia inhibition at 10mg/kg/day, prolonging mean survival time without recrudescence. This nanoparticulate albumin-bound system allows the intravenous administration of artemisinin for the first time without harsh organic solvents or cosolvents with 100% bioavailability. Copyright © 2015 Elsevier B.V. All rights reserved.

Stability of silver nanoparticles: agglomeration and oxidation in biological relevant conditions

NASA Astrophysics Data System (ADS)

Valenti, Laura E.; Giacomelli, Carla E.

2017-05-01

Silver nanoparticles (Ag-NP) are the most used nanomaterial in consumer products due to the intrinsic antimicrobial capacity of silver. However, Ag-NP may be also harmful to algae, aquatic species, mammalian cells, and higher plants because both Ag+ and nanoparticles are responsible of cell damages. The oxidative dissolution of Ag-NP would proceed to completion under oxic conditions, but the rate and extent of the dissolution depend on several factors. This work correlates the effect of the capping agent (albumin and citrate) with the stability of Ag-NP towards agglomeration in simulated body fluid (SBF) and oxidation in the presence of ROS species (H2O2). Capping provides colloidal stability only through electrostatic means, whereas albumin acts as bulky ligands giving steric and electrostatic repulsion, inhibiting the agglomeration in SBF. However, citrate capping protects Ag-NP from dissolution to a major extent than albumin does because of its reducing power. Moreover, citrate in solution minimizes the oxidation of albumin-coated Ag-NP even after long incubation times. H2O2-induced dissolution proceeds to completion with Ag-NP incubated in SBF, while incubation in citrate leads to an incomplete oxidation. In short, albumin is an excellent capping agent to minimize Ag-NP agglomeration whereas citrate provides a mild-reductive medium that prevents dissolution in biological relevant media as well as in the presence of ROS species. These results provide insight into how the surface properties and media composition affect the release of Ag+ from Ag-NP, related to the cell toxicity and relevant to the storage and lifetime of silver-containing nanomaterials.

Development and characterization of voriconazole loaded nanoparticles for parenteral delivery.

PubMed

Füredi, Petra; Kovács, Kristóf; Ludányi, Krisztina; Antal, István; Klebovich, Imre

2016-08-20

Human serum albumin (HSA) has attracted the most attention in the last decades as a new nanocarrier system of active pharmaceutical ingredients (API) due to its biocompatibility and high binding capacity to hydrophobic drugs. Voriconazole (VCZ), an antifungal agent with low water solubility, was selected to produce albumin based nanoparticles using nanoparticle albumin-bound technology (nab™-technology). Aim of our study was to study the development process of VCZ-loaded nanoparticles for parenteral drug delivery, such as homogenizing pressure, homogenizing cycle number and drug loading capacity. The main characters of nanoparticles such as particle size distribution and polydispersity index (PDI) were determined by dynamic light scattering. Six homogenization cycles at 1800bar were ensured the acceptable PDI value (lower than 0.3) of the VCZ content nanoparticles. Optimized formulation process produced 81.2±1nm average particle size which meets the requirements of intravenous administration. Furthermore, the encapsulated concentration of VCZ was 69.7±4.2% and the water solubility was over 2 times greater than the API itself which were determined by the developed HPLC method. The in vivo release behavior can be predicted from our applied in vitro dissolution study. Almost 50% of VCZ was liberated from the nanoparticles in the first 60min. Copyright © 2016 Elsevier B.V. All rights reserved.

Interaction of Water-Soluble CdTe Quantum Dots with Bovine Serum Albumin

PubMed Central

2011-01-01

Semiconductor nanoparticles (quantum dots) are promising fluorescent markers, but it is very little known about interaction of quantum dots with biological molecules. In this study, interaction of CdTe quantum dots coated with thioglycolic acid (TGA) with bovine serum albumin was investigated. Steady state spectroscopy, atomic force microscopy, electron microscopy and dynamic light scattering methods were used. It was explored how bovine serum albumin affects stability and spectral properties of quantum dots in aqueous media. CdTe–TGA quantum dots in aqueous solution appeared to be not stable and precipitated. Interaction with bovine serum albumin significantly enhanced stability and photoluminescence quantum yield of quantum dots and prevented quantum dots from aggregating. PMID:27502633

Interaction of Colloidal Gold Nanoparticles with Model Serum Proteins: The Nanoparticle-Protein 'Corona' from a PhysicoChemical Viewpoint

NASA Astrophysics Data System (ADS)

Dominguez Medina, Sergio

When nanoparticles come in contact with biological fluids they become coated with a mixture of proteins present in the media, forming what is known as the nanoparticle-protein 'corona'. This corona changes the nanoparticles' original surface properties and plays a central role in how these get screened by cellular receptors. In the context of biomedical research, this presents a bottleneck for the transition of nanoparticles from research laboratories to clinical settings. It is therefore fundamental to probe these nanoparticle-protein interactions in order to understand the different physico-chemical mechanisms involved. This thesis is aimed to investigate the exposure of colloidal gold nanoparticles to model serum proteins, particularly serum albumin, the main transporter of molecular compounds in the bloodstream of mammals. A set of experimental tools based on optical microscopy and spectroscopy were developed in order to probe these interactions in situ. First, the intrinsic photoluminescence and elastic scattering of individual gold nanoparticles were investigated in order to understand its physical origin. These optical signals were then used to measure the size of the nanoparticles while in Brownian diffusion using fluctuation correlation spectroscopy. This spectroscopic tool was then applied to detect the binding of serum albumin onto the nanoparticle surface, increasing its hydrodynamic size. By performing a binding isotherm as a function of protein concentration, it was determined that serum albumin follows an anti-cooperative binding mechanism on negatively charged gold nanoparticles. This protein monolayer substantially enhanced the stability of the colloid, preventing their aggregation in saline solutions with ionic strength higher than biological media. Cationic gold nanoparticles in contrast, aggregated when serum albumin was present at a low protein-to-nanoparticle ratio, but prevented aggregation if exposed in excess. Single-molecule fluorescence microscopy revealed that under low protein-to-nanoparticle binding ratios, serum albumin irreversibly unfolds upon adsorption and spreads across the available nanoparticle surface area. Unfolded proteins then interact with one another, triggering nanoparticle aggregation. Fibrinogen and globulin also triggered aggregation when exposed to cationic nanoparticles. In an effort to relate these physico-chemical observations to relevant biological parameters, the uptake of protein coated gold nanoparticles by a model cancer cell line was investigated under different incubation conditions. Those nanoparticles pre-incubated with bovine serum albumin before fetal bovine serum were found to be uptaken three times more than those only incubated in serum.

Fabrication and evaluation of nanoparticle-assembled BSA microparticles for enhanced liver delivery of glycyrrhetinic acid.

PubMed

Wang, Wenping; Lei, Yaya; Sui, Hong; Zhang, Wenping; Zhu, Rongyue; Feng, Jun; Wang, Hong

2017-06-01

The aim of the present study was to prepare and evaluate microparticle formulation encapsulated with glycyrrhetinic acid (GA) based on bovine serum albumin (BSA). The drug-loaded nanoparticles were firstly formed by a simple desolvation method, and were further assembled into microparticles using zinc chloride and glutaraldehyde as crosslinkers. The obtained microparticles contained approximately 30% (w/w) drug and showed as spherical particles with a size of about 2 μm. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis indicated that GA lost its crystallinity during the nano/microencapsulation process. In vitro dissolution study demonstrated a typical sustained-release pattern for 24 h with a burst of 28.1% at the first 30 min, which fitted well by Higuchi model. After intravenous administration into mice, the microparticle formulation remained a higher drug level than the solution formulation in blood and liver for more than 18 h. These results suggested the potential benefit of using the prepared albumin microparticles as a promising vector for enhanced liver delivery of poorly water-soluble drug.

Construction and evaluation of BSA-CaP nanomaterials with enhanced transgene performance via biocorona-inspired caveolae-mediated endocytosis

NASA Astrophysics Data System (ADS)

Ma, Xi-Xi; Gao, Han; Zhang, Ya-Xuan; Jia, Yi-Yang; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

2018-02-01

Non-viral nanovectors have attracted much attention owing to their ability to condense genetic materials and their ease of modification. However, their poor stability, low biocompatibility and gene degradation in endosomes or lysosomes has significantly hampered their application in vivo and in the clinic. In an attempt to overcome these difficulties a series of bovine serum albumin (BSA)-calcium phosphate (CaP) nanoparticles were constructed. The CaP condenses with DNA to form nanocomplexes coated with a biomimetic corona of BSA. Such complexes may retain the inherent endocytosis profile of BSA, with improved biocompatibility. In particular the transgene performance may be enhanced by stimulating the cellular uptake pathway via caveolae-mediated endocytosis. Two methods were employed to construct and optimize the formulation of BSA-CaP nanomaterials. The optimized BSA-CaP-50-M2 nanoparticles prepared by our second method exhibited good stability, negligible cytotoxicity and enhanced transgene performance with long-term expression for 72 h in vivo even with a single dose. Determination of the cellular uptake pathway and Western blot revealed that cellular uptake of the designed BSA-CaP-50-M2 nanoparticles was mainly via caveolae-mediated endocytosis in a non-degradative pathway in which the biomimetic uptake profile of BSA was retained.

Construction and evaluation of BSA-CaP nanomaterials with enhanced transgene performance via biocorona-inspired caveolae-mediated endocytosis.

PubMed

Ma, Xi-Xi; Gao, Han; Zhang, Ya-Xuan; Jia, Yi-Yang; Li, Chen; Zhou, Si-Yuan; Zhang, Bang-Le

2018-02-23

Non-viral nanovectors have attracted much attention owing to their ability to condense genetic materials and their ease of modification. However, their poor stability, low biocompatibility and gene degradation in endosomes or lysosomes has significantly hampered their application in vivo and in the clinic. In an attempt to overcome these difficulties a series of bovine serum albumin (BSA)-calcium phosphate (CaP) nanoparticles were constructed. The CaP condenses with DNA to form nanocomplexes coated with a biomimetic corona of BSA. Such complexes may retain the inherent endocytosis profile of BSA, with improved biocompatibility. In particular the transgene performance may be enhanced by stimulating the cellular uptake pathway via caveolae-mediated endocytosis. Two methods were employed to construct and optimize the formulation of BSA-CaP nanomaterials. The optimized BSA-CaP-50-M2 nanoparticles prepared by our second method exhibited good stability, negligible cytotoxicity and enhanced transgene performance with long-term expression for 72 h in vivo even with a single dose. Determination of the cellular uptake pathway and Western blot revealed that cellular uptake of the designed BSA-CaP-50-M2 nanoparticles was mainly via caveolae-mediated endocytosis in a non-degradative pathway in which the biomimetic uptake profile of BSA was retained.

Rapid microwave-assisted synthesis of sub-30nm lipid nanoparticles.

PubMed

Dunn, Stuart S; Beckford Vera, Denis R; Benhabbour, S Rahima; Parrott, Matthew C

2017-02-15

Accessing the phase inversion temperature by microwave heating may enable the rapid synthesis of small lipid nanoparticles. Nanoparticle formulations consisted of surfactants Brij 78 and Vitamin E TPGS, and trilaurin, trimyristin, or miglyol 812 as nanoparticle lipid cores. Each formulation was placed in water and heated by microwave irradiation at temperatures ranging from 65°C to 245°C. We observed a phase inversion temperature (PIT) for these formulations based on a dramatic decrease in particle Z-average diameters. Subsequently, nanoparticles were manufactured above and below the PIT and studied for (a) stability toward dilution, (b) stability over time, (c) fabrication as a function of reaction time, and (d) transmittance of lipid nanoparticle dispersions. Lipid-based nanoparticles with distinct sizes down to 20-30nm and low polydispersity could be attained by a simple, one-pot microwave synthesis. This was carried out by accessing the phase inversion temperature using microwave heating. Nanoparticles could be synthesized in just one minute and select compositions demonstrated high stability. The notable stability of these particles may be explained by the combination of van der Waals interactions and steric repulsion. 20-30nm nanoparticles were found to be optically transparent. Published by Elsevier Inc.

Sodium deoxycholate-decorated zein nanoparticles for a stable colloidal drug delivery system

PubMed Central

Gagliardi, Agnese; Paolino, Donatella; Iannone, Michelangelo; Palma, Ernesto

2018-01-01

Background The use of biopolymers is increasing in drug delivery, thanks to the peculiar properties of these compounds such as their biodegradability, availability, and the possibility of modulating their physico-chemical characteristics. In particular, protein-based systems such as albumin are able to interact with many active compounds, modulating their biopharmaceutical properties. Zein is a protein of 20–40 kDa made up of many hydrophobic amino acids, generally regarded as safe (GRAS) and used as a coating material. Methods In this investigation, zein was combined with various surfactants in order to obtain stable nanosystems by means of the nanoprecipitation technique. Specific parameters, eg, temperature, pH value, Turbiscan Stability Index, serum stability, in vitro cytotoxicity and entrapment efficiency of various model compounds were investigated, in order to identify the nanoformulation most useful for a systemic drug delivery application. Results The use of non-ionic and ionic surfactants such as Tween 80, poloxamer 188, and sodium deoxycholate allowed us to obtain nanoparticles characterized by a mean diameter of 100–200 nm when a protein concentration of 2 mg/mL was used. The surface charge was modulated by means of the protein concentration and the nature of the stabilizer. The most suitable nanoparticle formulation to be proposed as a colloidal drug delivery system was obtained using sodium deoxycholate (1.25% w/v) because it was characterized by a narrow size distribution, a good storage stability after freeze-drying and significant feature of retaining lipophilic and hydrophilic compounds. Conclusion The sodium deoxycholate-coated zein nanoparticles are stable biocompatible colloidal carriers to be used as useful drug delivery systems. PMID:29430179

Hyaluronic acid/Chitosan nanoparticles as delivery vehicles for VEGF and PDGF-BB.

PubMed

Parajó, Yolanda; D'Angelo, Ivana; Welle, Alexander; Garcia-Fuentes, Marcos; Alonso, María José

2010-11-01

The development of a vascular network in tissue-engineered constructs is a fundamental bottleneck of bioregenerative medicine, particularly when the size of the implant exceeds a certain limit given by diffusion lengths and/or if the host tissue shows a very active metabolism. One of the approaches to achieve the vascularization of tissue constructs is generating a sustained release of proangiogenic factors from the ischemic site. This work describes the formation and characterization of hyaluronic acid-chitosan (HA/CS) nanoparticles for the delivery of two pro-angiogenic growth factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF-BB). These nanoparticles were prepared by an ionic gelification technique, and different formulations were developed by encapsulating the growth factors in association with two stabilizing agents: bovine serum albumin or heparin sodium salt. These carriers were characterized with regard to their physicochemical properties, their stability in biological media, and their cytotoxicity in the C3a hepatoma cell line. The results show that nanoparticles around 200 nm can be prepared by this method. HA/CS nanoparticles were stable when incubated in EMEM cell culture medium or in water at 37°C for 24 h. Cell culture tests confirmed that HA/CS nanoparticles are not cytotoxic within the concentration range used for growth factor delivery. Moreover, HA/CS nanoparticles were able to entrap efficiently both growth factors, reaching association values of 94% and 54% for VEGF and PDGF, respectively. In vitro release studies confirm that PDGF-BB is released from HA/CS nanoparticles in a sustained manner over approximately 1 week. On the other hand, VEGF is completely released within the first 24 h.

Characterisation of the de-agglomeration effects of bovine serum albumin on nanoparticles in aqueous suspension.

PubMed

Tantra, Ratna; Tompkins, Jordan; Quincey, Paul

2010-01-01

This paper describes the use of nanoparticle characterisation tools to evaluate the interaction between bovine serum albumin (BSA) and dispersed nanoparticles in aqueous media. Dynamic light scattering, zeta-potential measurements and scanning electron microscopy were used to probe the state of zinc oxide (ZnO) and titanium dioxide (TiO(2)) nanoparticles in the presence of various concentrations of BSA, throughout a three-day period. BSA was shown to adhere to ZnO but not to TiO(2). The adsorption of BSA led to subsequent de-agglomeration of the sub-micron ZnO clusters into smaller fragments, even breaking them up into individual isolated nanoparticles. We propose that certain factors, such as adsorption kinetics of BSA on to the surface of ZnO, as well as the initial agglomerated state of the ZnO, prior to BSA addition, are responsible for promoting the de-agglomeration process. Hence, in the case of TiO(2) we see no de-agglomeration because: (a) the nanoparticles are more highly agglomerated to begin with and (b) BSA does not adsorb effectively on the surface of the nanoparticles. The zeta-potential results show that, for either ZnO or TiO(2), the presence of BSA resulted in enhanced stability. In the case of ZnO, the enhanced stability is limited to BSA concentrations below 0.5 wt.%. Steric and electrostatic repulsion are thought to be responsible for improved stability of the dispersion.

Stabilising nanofluids in saline environments.

PubMed

Al-Anssari, Sarmad; Arif, Muhammad; Wang, Shaobin; Barifcani, Ahmed; Iglauer, Stefan

2017-12-15

Nanofluids (i.e. nanoparticles dispersed in a fluid) have tremendous potential in a broad range of applications, including pharmacy, medicine, water treatment, soil decontamination, or oil recovery and CO 2 geo-sequestration. In these applications nanofluid stability plays a key role, and typically robust stability is required. However, the fluids in these applications are saline, and no stability data is available for such salt-containing fluids. We thus measured and quantified nanofluid stability for a wide range of nanofluid formulations, as a function of salinity, nanoparticle content and various additives, and we investigated how this stability can be improved. Zeta sizer and dynamic light scattering (DLS) principles were used to investigate zeta potential and particle size distribution of nanoparticle-surfactant formulations. Also scanning electron microscopy was used to examine the physicochemical aspects of the suspension. We found that the salt drastically reduced nanofluid stability (because of the screening effect on the repulsive forces between the nanoparticles), while addition of anionic surfactant improved stability. Cationic surfactants again deteriorated stability. Mechanisms for the different behaviour of the different formulations were identified and are discussed here. We thus conclude that for achieving maximum nanofluid stability, anionic surfactant should be added. Copyright © 2017 Elsevier Inc. All rights reserved.

Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations.

PubMed

Das, Surajit; Ng, Wai Kiong; Tan, Reginald B H

2014-03-14

This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

Filter-feeding bivalves store and biodeposit colloidally stable gold nanoparticles.

PubMed

Hull, Matthew S; Chaurand, Perrine; Rose, Jerome; Auffan, Melanie; Bottero, Jean-Yves; Jones, Jason C; Schultz, Irvin R; Vikesland, Peter J

2011-08-01

Nanoparticles resistant to salt-induced aggregation are continually being developed for biomedical and industrial applications. Because of their colloidal stability these functionalized nanoparticles are anticipated to be persistent aquatic contaminants. Here, we show that Corbicula fluminea, a globally distributed clam that is a known sentinel of aquatic ecosystem contamination, can uptake and biodeposit bovine serum albumin (BSA) stabilized gold nanoparticles. Nanoparticle clearance rates from suspension were dictated by diameter and concentration, with the largest particles cleared most quickly on a mass basis. Particle capture facilitates size-selective 'biopurification' of particle suspensions with nanoscale resolution. Nanoparticles were retained either within the clam digestive tract or excreted in feces. Our results suggest that biotransformation and biodeposition will play a significant role in the fate and transport of persistent nanoparticles in aquatic systems.

Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy

PubMed Central

2012-01-01

Background Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to produce large batches for preclinical and clinical trials. This process is not only critical but also difficult as it involves various formulation parameters to be modulated all in the same process. Methods In our present study, we formulated curcumin loaded poly (lactic acid-co-glycolic acid) nanoparticles (PLGA-CURC). This improved the bioavailability of curcumin, a potent natural anticancer drug, making it suitable for cancer therapy. Post formulation, we optimized our process by Reponse Surface Methodology (RSM) using Central Composite Design (CCD) and scaled up the formulation process in four stages with final scale-up process yielding 5 g of curcumin loaded nanoparticles within the laboratory setup. The nanoparticles formed after scale-up process were characterized for particle size, drug loading and encapsulation efficiency, surface morphology, in vitro release kinetics and pharmacokinetics. Stability analysis and gamma sterilization were also carried out. Results Results revealed that that process scale-up is being mastered for elaboration to 5 g level. The mean nanoparticle size of the scaled up batch was found to be 158.5 ± 9.8 nm and the drug loading was determined to be 10.32 ± 1.4%. The in vitro release study illustrated a slow sustained release corresponding to 75% drug over a period of 10 days. The pharmacokinetic profile of PLGA-CURC in rats following i.v. administration showed two compartmental model with the area under the curve (AUC0-∞) being 6.139 mg/L h. Gamma sterilization showed no significant change in the particle size or drug loading of the nanoparticles. Stability analysis revealed long term physiochemical stability of the PLGA-CURC formulation. Conclusions A successful effort towards formulating, optimizing and scaling up PLGA-CURC by using Solid-Oil/Water emulsion technique was demonstrated. The process used CCD-RSM for optimization and further scaled up to produce 5 g of PLGA-CURC with almost similar physicochemical characteristics as that of the primary formulated batch. PMID:22937885

Scale up, optimization and stability analysis of Curcumin C3 complex-loaded nanoparticles for cancer therapy.

PubMed

Ranjan, Amalendu P; Mukerjee, Anindita; Helson, Lawrence; Vishwanatha, Jamboor K

2012-08-31

Nanoparticle based delivery of anticancer drugs have been widely investigated. However, a very important process for Research & Development in any pharmaceutical industry is scaling nanoparticle formulation techniques so as to produce large batches for preclinical and clinical trials. This process is not only critical but also difficult as it involves various formulation parameters to be modulated all in the same process. In our present study, we formulated curcumin loaded poly (lactic acid-co-glycolic acid) nanoparticles (PLGA-CURC). This improved the bioavailability of curcumin, a potent natural anticancer drug, making it suitable for cancer therapy. Post formulation, we optimized our process by Reponse Surface Methodology (RSM) using Central Composite Design (CCD) and scaled up the formulation process in four stages with final scale-up process yielding 5 g of curcumin loaded nanoparticles within the laboratory setup. The nanoparticles formed after scale-up process were characterized for particle size, drug loading and encapsulation efficiency, surface morphology, in vitro release kinetics and pharmacokinetics. Stability analysis and gamma sterilization were also carried out. Results revealed that that process scale-up is being mastered for elaboration to 5 g level. The mean nanoparticle size of the scaled up batch was found to be 158.5±9.8 nm and the drug loading was determined to be 10.32±1.4%. The in vitro release study illustrated a slow sustained release corresponding to 75% drug over a period of 10 days. The pharmacokinetic profile of PLGA-CURC in rats following i.v. administration showed two compartmental model with the area under the curve (AUC0-∞) being 6.139 mg/L h. Gamma sterilization showed no significant change in the particle size or drug loading of the nanoparticles. Stability analysis revealed long term physiochemical stability of the PLGA-CURC formulation. A successful effort towards formulating, optimizing and scaling up PLGA-CURC by using Solid-Oil/Water emulsion technique was demonstrated. The process used CCD-RSM for optimization and further scaled up to produce 5 g of PLGA-CURC with almost similar physicochemical characteristics as that of the primary formulated batch.

Optimization of Preparation Techniques for Poly(Lactic Acid-Co-Glycolic Acid) Nanoparticles

NASA Astrophysics Data System (ADS)

Birnbaum, Duane T.; Kosmala, Jacqueline D.; Brannon-Peppas, Lisa

2000-06-01

Microparticles and nanoparticles of poly(lactic acid-co-glycolic acid) (PLAGA) are excellent candidates for the controlled release of many pharmaceutical compounds because of their biodegradable nature. The preparation of submicron PLAGA particles poses serious challenges that are not necessarily present when preparing microparticles. We have evaluated several combinations of organic solvents and surfactants used in the formulation of PLAGA nanoparticles. Critical factors such as the ability to separate the nanoparticles from the surfactant, the ability to re-suspend the nanoparticles after freeze-drying, formulation yield and nanoparticle size were studied. The smallest particles were obtained using the surfactant/solvent combination of sodium dodecyl sulfate and ethyl acetate (65 nm) and the largest particles were obtained using poly(vinyl alcohol) and dichloromethane (466 nm). However, the optimal nanoparticles were produced using either acetone or ethyl acetate as the organic solvent and poly(vinyl alcohol) or human serum albumin as the surfactant. This is because the most critical measure of performance of these nanoparticles proved to be their ability to re-suspend after freeze-drying.

Fabrication of curcumin-loaded bovine serum albumin (BSA)-dextran nanoparticles and the cellular antioxidant activity.

PubMed

Fan, Yuting; Yi, Jiang; Zhang, Yuzhu; Yokoyama, Wallace

2018-01-15

Bovine serum albumin (BSA)-dextran conjugate was prepared with glycation. Self-assembly nanoparticles were synthesized with a green, and facile approach. The effects of dry-heating time on the fabrication and characteristics of BSA-dextran conjugate nanoparticles were examined. Stable nanoparticles (<200nm) were formed after only 6h dry-heating because enough dextran was grafted onto the BSA to provide significant steric hindrance. Particle size decreased with the increase of dry-heating time and the lowest particle size (51.2nm) was obtained after 24h dry-heating. The nanoparticles were stable in a wide pH range (pH 2.0-7.0). The particle size of nanoparticles increased to 115nm after curcumin incorporation and was stable even after one-month storage. TEM results demonstrated that curcumin-loaded nanoparticles displayed a spherical structure and were homogeneously dispersed. Curcumin in BSA-dextran nanoparticle showed better stability, compared to free curcumin. In addition, BSA-dextran nanoparticles can improve the cellular antioxidant activity of curcumin in Caco-2 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Doxorubicin-loaded glycyrrhetinic acid modified recombinant human serum albumin nanoparticles for targeting liver tumor chemotherapy.

PubMed

Qi, Wen-Wen; Yu, Hai-Yan; Guo, Hui; Lou, Jun; Wang, Zhi-Ming; Liu, Peng; Sapin-Minet, Anne; Maincent, Philippe; Hong, Xue-Chuan; Hu, Xian-Ming; Xiao, Yu-Ling

2015-03-02

Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells, glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles for targeting liver tumor cells may result in increased therapeutic efficacy and decreased adverse effects of cancer therapy. In this study, doxorubicin (DOX) loaded and glycyrrhetinic acid modified recombinant human serum albumin nanoparticles (DOX/GA-rHSA NPs) were prepared for targeting therapy for liver cancer. GA was covalently coupled to recombinant human serum albumin nanoparticles, which could efficiently deliver DOX into liver cancer cells. The resultant GA-rHSA NPs exhibited uniform spherical shape and high stability in plasma with fixed negative charge (∼-25 mV) and a size about 170 nm. DOX was loaded into GA-rHSA NPs with a maximal encapsulation efficiency of 75.8%. Moreover, the targeted NPs (DOX/GA-rHSA NPs) showed increased cytotoxic activity in liver tumor cells compared to the nontargeted NPs (DOX/rHSA NPs, DOX loaded recombinant human serum albumin nanoparticles without GA conjugating). The targeted NPs exhibited higher cellular uptake in a GA receptor-positive liver cancer cell line than nontargeted NPs as measured by both flow cytometry and confocal laser scanning microscopy. Biodistribution experiments showed that DOX/GA-rHSA NPs exhibited a much higher level of tumor accumulation than nontargeted NPs at 1 h after injection in hepatoma-bearing Balb/c mice. Therefore, the DOX/GA-rHSA NPs could be considered as an efficient nanoplatform for targeting drug delivery system for liver cancer.

Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

ClinicalTrials.gov

2018-02-05

Cervical Adenosarcoma; Cervical Adenosquamous Carcinoma; Cervical Carcinosarcoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Epithelial Tumor; Malignant Peritoneal Neoplasm; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Skin Melanoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma; Uterine Corpus Carcinosarcoma

Resveratrol-loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles: Preparation, characterization, and targeting effect on liver tumors.

PubMed

Wu, Mingfang; Lian, Bolin; Deng, Yiping; Feng, Ziqi; Zhong, Chen; Wu, Weiwei; Huang, Yannian; Wang, Lingling; Zu, Chang; Zhao, Xiuhua

2017-08-01

In this study, glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were prepared to establish a tumor targeting nano-sized drug delivery system. Glycyrrhizic acid was coupled to human serum albumin, and resveratrol was encapsulated in glycyrrhizic acid-conjugated human serum albumin by high-pressure homogenization emulsification. The average particle size of sample nanoparticles prepared under the optimal conditions was 108.1 ± 5.3 nm with a polydispersity index (PDI) of 0.001, and the amount of glycyrrhizic acid coupled with human serum albumin was 112.56 µg/mg. The drug encapsulation efficiency and drug loading efficiency were 83.6 and 11.5%, respectively. The glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles were characterized through laser light scattering, scanning electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses, and gas chromatography. The characterization results showed that resveratrol in glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles existed in amorphous state and the residual amounts of chloroform and methanol in nanoparticles were separately less than the international conference on harmonization (ICH) limit. The in vitro drug-release study showed that the nanoparticles released the drug slowly and continuously. The inhibitory rate of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide method. The IC50 values of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles and resveratrol were 62.5 and 95.5 µg/ml, respectively. The target ability of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles for HepG2 cells was evaluated using fluorescence-modified albumin techniques. The uptake rate of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles was higher than that of pure resveratrol and increased with increased nanoparticles concentration. The in vivo body distribution of glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles labeled with the near-infrared fluorophore Cy5 was monitored in H22 tumor-bearing mice through near-infrared fluorescence imaging systems. Glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles exhibited effective target orientation to liver tumor and sustained-release property.

Silver Nanoparticle Storage Stability in Aqueous and Biological Media

DTIC Science & Technology

2015-06-22

silver nanoparticle stability from the point of synthesis to the point of testing. The recommended conditions of water storage at 4°C protected from... silver nanoparticle formulation for fabrication. (Report No. 2014-73). 13 Métraux, G. S. & Mirkin, C. A. Rapid thermal synthesis of silver ...NAVAL MEDICAL RESEARCH UNIT SAN ANTONIO SILVER NANOPARTICLE STORAGE STABILITY IN AQUEOUS AND BIOLOGICAL MEDIA NATALIE A

Formulating nanoparticles by flash nanoprecipitation for drug delivery and sustained release

NASA Astrophysics Data System (ADS)

Liu, Ying

This dissertation provides a fundamental understanding of the process for generating nanoparticles with controlled size distribution and of predicting nanoparticle stability for drug delivery and sustained release. We developed and characterized a novel technology to generate organic and inorganic nanoparticles protected by biocompatible and biodegradable polymers with precisely controlled size and size distribution. Computational fluid mechanics (CFD) together with experimental results provided details of the micromixing in the mixer. The particle size dependence on Reynolds number and supersaturation was illustrated. The study of the fundamental mass transfer phenomena leading to Ostwald ripening enables quantitative prediction of the time evolution of nanoparticles with monodistribution and relatively broader multi-distribution using beta-carotene and polystyrene-b-poly(ethylene oxide) (PS-b-PEO) as a model system. Negatively charged latex particles were used to exam the attachment of the diblock copolymer, PS-b-PEO, on the surface. The stability provided by the Columbic repulsion was replaced by steric stabilization. The attachment of the block copolymers on the surface of the colloids depends on the flow field, i.e. Reynolds number, of the mixing process. The slow degradation of poly(epsilon-caprolactone) (PCL) and poly(gamma-methyl-epsilon-caprolactone) (PMCL) was demonstrated. The slow degradation ensures long-term stability and long-term blood circulation of the polymeric nanoparticles. As a practical application, we formulate the anti-tuberculosis drug, rifampicin, into nanoparticles by conjugation to other hydrophobic molecules (such as vitamin E, PCL and 2-ethylhexyl vinyl ether) by pH sensitive cleavable chemical bonds to increase the drug loading, return stability of the nanoparticle suspension, and control drug release. The in vitro release profiles were provided by using HPLC and E.coli growth inhibition on LB agar plates. The prodrug nanoparticle suspensions were spray dried to form low density porous micro-particles for the purpose of aerosol drug delivery. The simultaneous encapsulation of imaging agents and therapeutic agents provides a method for studying the fate of nanoparticles and for medical imaging with treatment. As another example, bifenthrin nanoparticle suspensions with various stabilizers were formulated. The pesticide, bifenthrin, was used to test whether nanoparticles provided an advantage in increasing the effectiveness of pesticide formulations. Larvae mortality with the application of nanoparticle suspension was about 2.5 times of the mortality with the application of bifenthrin mineral oil solution. Nanoparticles at very low bifenthrin concentration showed sustained release for fourteen days.

Biochemical stabilization of glucagon at alkaline pH.

PubMed

Caputo, Nicholas; Jackson, Melanie A; Castle, Jessica R; El Youssef, Joseph; Bakhtiani, Parkash A; Bergstrom, Colin P; Carroll, Julie M; Breen, Matthew E; Leonard, Gerald L; David, Larry L; Roberts, Charles T; Ward, W Kenneth

2014-11-01

For patients with type 1 diabetes mellitus, a bihormonal artificial endocrine pancreas system utilizing glucagon and insulin has been found to stabilize glycemic control. However, commercially available formulations of glucagon cannot currently be used in such systems because of physical instability characterized by aggregation and chemical degradation. Storing glucagon at pH 10 blocks protein aggregation but results in chemical degradation. Reductions in pH minimize chemical degradation, but even small reductions increase protein aggregation. We hypothesized that common pharmaceutical excipients accompanied by a new excipient would inhibit glucagon aggregation at an alkaline pH. As measured by tryptophan intrinsic fluorescence shift and optical density at 630 nm, protein aggregation was indeed minimized when glucagon was formulated with curcumin and albumin. This formulation also reduced chemical degradation, measured by liquid chromatography with mass spectrometry. Biological activity was retained after aging for 7 days in an in vitro cell-based bioassay and also in Yorkshire swine. Based on these findings, a formulation of glucagon stabilized with curcumin, polysorbate-80, l-methionine, and albumin at alkaline pH in glycine buffer may be suitable for extended use in a portable pump in the setting of a bihormonal artificial endocrine pancreas.

Biochemical Stabilization of Glucagon at Alkaline pH

PubMed Central

Jackson, Melanie A.; Castle, Jessica R.; El Youssef, Joseph; Bakhtiani, Parkash A.; Bergstrom, Colin P.; Carroll, Julie M.; Breen, Matthew E.; Leonard, Gerald L.; David, Larry L.; Roberts, Charles T.; Ward, W. Kenneth

2014-01-01

Abstract Background: For patients with type 1 diabetes mellitus, a bihormonal artificial endocrine pancreas system utilizing glucagon and insulin has been found to stabilize glycemic control. However, commercially available formulations of glucagon cannot currently be used in such systems because of physical instability characterized by aggregation and chemical degradation. Storing glucagon at pH 10 blocks protein aggregation but results in chemical degradation. Reductions in pH minimize chemical degradation, but even small reductions increase protein aggregation. We hypothesized that common pharmaceutical excipients accompanied by a new excipient would inhibit glucagon aggregation at an alkaline pH. Methods and Results: As measured by tryptophan intrinsic fluorescence shift and optical density at 630 nm, protein aggregation was indeed minimized when glucagon was formulated with curcumin and albumin. This formulation also reduced chemical degradation, measured by liquid chromatography with mass spectrometry. Biological activity was retained after aging for 7 days in an in vitro cell-based bioassay and also in Yorkshire swine. Conclusions: Based on these findings, a formulation of glucagon stabilized with curcumin, polysorbate-80, l-methionine, and albumin at alkaline pH in glycine buffer may be suitable for extended use in a portable pump in the setting of a bihormonal artificial endocrine pancreas. PMID:24968220

Development of Acyclovir-Loaded Albumin Nanoparticles and Improvement of Acyclovir Permeation Across Human Corneal Epithelial T Cells.

PubMed

Suwannoi, Panita; Chomnawang, Mullika; Sarisuta, Narong; Reichl, Stephan; Müller-Goymann, Christel C

2017-12-01

The aim of the present study was to develop acyclovir (ACV) ocular drug delivery systems of bovine serum albumin (BSA) nanoparticles as well as to assess their in vitro transcorneal permeation across human corneal epithelial (HCE-T) cell multilayers. The ACV-loaded BSA nanoparticles were prepared by desolvation method along with physicochemical characterization, cytotoxicity, as well as in vitro transcorneal permeation studies across HCE-T cell multilayers. The nanoparticles appeared to be spherical in shape and nearly uniform in size of about 200 nm. The size of nanoparticles became smaller with decreasing BSA concentration, while the ratios of water to ethanol seemed not to affect the size. Increasing the amount of ethanol in desolvation process led to significant reduction of drug entrapment of nanoparticles with smaller size and more uniformity. The ACV-loaded BSA nanoparticles prepared were shown to have no cytotoxic effect on HCE-T cells used in permeation studies. The in vitro transcorneal permeation results revealed that ACV could permeate through the HCE-T cell multilayers significantly higher from BSA nanoparticles than from aqueous ACV solutions. The ACV-loaded BSA nanoparticles could be prepared by desolvation method without glutaraldehyde in the formulation. ACV could increasingly permeate through the multilayers of HCE-T cells from the ACV-loaded BSA nanoparticles. Therefore, the ACV-loaded BSA nanoparticles could be a highly potential ocular drug delivery system.

Formulation and Evaluation of Solid Lipid Nanoparticles of Ramipril

PubMed Central

Ekambaram, P; Abdul, Hasan Sathali A

2011-01-01

Solid lipid nanoparticles are typically spherical with an average diameter between 1 and 1000 nm. It is an alternative carrier system to tradition colloidal carriers, such as, emulsions, liposomes, and polymeric micro and nanoparticles. Ramipril is an antihypertensive agent used in the treatment of hypertension. Its oral bioavailability is 28% and it is rapidly excreted through the renal route. This drug has many side effects such as, postural hypotension, hyperkalemia, and angioedema, when given as an immediate dosage form. To overcome the side effects and to increase the bioavailability of ramipril, solid lipid nanoparticles of ramipril are prepared by using lipids (glyceryl monostearate and glyceryl monooleate) with stabilizers (tween 80, poloxamer 188, and span 20). The prepared formulations have been evaluated for entrapment efficiency, drug content, in-vitro drug release, particle size analysis, scanning electron spectroscopy, Fourier transform-infrared studies, and stability. A formulation containing glyceryl monooleate, stabilized with span 20 as surfactant showed prolonged drug release, smaller particle size, and narrow particle size distribution, as compared to other formulations with different surfactants and lipids. PMID:21897661

Effect of Formulation Variables on Preparation of Celecoxib Loaded Polylactide-Co-Glycolide Nanoparticles

PubMed Central

Cooper, Dustin L.; Harirforoosh, Sam

2014-01-01

Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV) and 20 mg celecoxib without emulsifier (25.00±0.18 mV). Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively) and without (92.97±0.51 nm and 95.93±0.27%, respectively) emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01). Therefore, our results suggest the use of emulsifier free 5 mg celecoxib drug formulations containing 0.25% w/v didodecyldimethylammonium bromide for production of polymeric NPs that demonstrate enhanced zeta potential, small particle size, and high entrapment efficiency. PMID:25502102

Effect of sugar additives on stability of human serum albumin during vacuum foam drying and storage.

PubMed

Hajare, A A; More, H N; Pisal, S S

2011-11-01

No literature on the protein stabilization of human serum albumin (HSA) by vacuum foam drying (VFD) has been reported. The purpose of this study was to investigate the effect of sugar-additive systems on the stability of HSA by VFD. For the assessment, HSA was formulated with sucrose and mannitol, respectively, alone or in combination with stabilizers, which were vacuum foam dried and stored at 25C. Protein content of the resulting dried formulations was analyzed by Lowry method. Fourier-transform infrared spectroscopy (FT-IR) analysis of the HSA secondary structure showed apparent protein structure-stabilizing effects of the amorphous sugar and phosphate combination during the VFD. In particular, sucrose-sodium phosphate monobasic mixture provide an interesting alternative to pure saccharide formulations due to their high glass transition temperatures and their increased ability to maintain a low melting transition temperature in the presence of small amounts of water. Inhibition of the sucrose crystallization in solutions under vacuum resulted in highly amorphous sucrose. Changes in the endothermic melting transition suggested reduced sucrose molecular mobility with increase in the sodium phosphate ratio. The addition of phosphate salts to sugar systems has several interesting features that merit its consideration in formulations to protect dehydrated labile biomaterials. In conclusion, our data suggest that sucrose and phosphate as additives seem to protect HSA during VFD better than lyophilized products and also maintain its stability in the VFD state during storage.

Influence of Surfactant and Lipid Type on the Physicochemical Properties and Biocompatibility of Solid Lipid Nanoparticles

PubMed Central

Pizzol, Carine Dal; Filippin-Monteiro, Fabíola Branco; Restrepo, Jelver Alexander Sierra; Pittella, Frederico; Silva, Adny Henrique; de Souza, Paula Alves; de Campos, Angela Machado; Creczynski-Pasa, Tânia Beatriz

2014-01-01

Nine types of solid lipid nanoparticle (SLN) formulations were produced using tripalmitin (TPM), glyceryl monostearate (GM) or stearic acid (SA), stabilized with lecithin S75 and polysorbate 80. Formulations were prepared presenting PI values within 0.25 to 0.30, and the physicochemical properties, stability upon storage and biocompatibility were evaluated. The average particle size ranged from 116 to 306 nm, with a negative surface charge around −11 mV. SLN presented good stability up to 60 days. The SLN manufactured using SA could not be measured by DLS due to the reflective feature of this formulation. However, TEM images revealed that SA nanoparticles presented square/rod shapes with an approximate size of 100 nm. Regarding biocompatibility aspects, SA nanoparticles showed toxicity in fibroblasts, causing cell death, and produced high hemolytic rates, indicating toxicity to red blood cells. This finding might be related to lipid type, as well as, the shape of the nanoparticles. No morphological alterations and hemolytic effects were observed in cells incubated with SLN containing TPM and GM. The SLN containing TPM and GM showed long-term stability, suggesting good shelf-life. The results indicate high toxicity of SLN prepared with SA, and strongly suggest that the components of the formulation should be analyzed in combination rather than separately to avoid misinterpretation of the results. PMID:25141003

Development of freeze-dried albumin-free formulation of recombinant factor VIII SQ.

PubMed

Osterberg, T; Fatouros, A; Mikaelsson, M

1997-07-01

To develop a stable freeze-dried formulation of recombinant factor VIII-SQ (r-VIII SQ) without the addition of albumin. Different formulations were evaluated for their protective effect during sterile filtration, freeze-thawing, freeze-drying, reconstitution and long term storage. Factor VIII activity (VIII:C), visual inspection, clarity, solubility, moisture content and soluble aggregates and/ or fragments were assayed. A combination of non-crystallising excipients (L-histidine and sucrose), a non-ionic surfactant (polysorbate 80) and a crystalline bulking agent (sodium chloride) was found to preserve the factor VIII activity during formulation, freeze-drying and storage. Calcium chloride was included to prevent dissociation of the heavy and light chains of r-VIII SQ. Sodium chloride was chosen as the primary bulking agent since the concentration of sodium chloride necessary for dissolution of r-VIII SQ in the buffer will inhibit the crystallization of many potential cake formers. It was found that L-histidine, besides functioning as a buffer, also protected r-VIII SQ during freeze-drying and storage. A pH close to 7 was found to be optimal. Some potential macromolecular stabilisers, PEG 4000, Haes-steril and Haemaccel, were evaluated but they did not improve the recovery of VIII:C. The freeze-dried formulation was stable for at least two years at 7 degrees C and for at least one year at 25 degrees C. The reconstituted solution was stable for at least 100 hours at 25 degrees C. The albumin-free formulation resulted in consistently high recovery of VIII:C, very low aggregate formation and good storage stability. The stability of the reconstituted solution makes the formulation suitable for continuous administration via infusion pump. The formulation strategy described here may also be useful for other proteins which require a high ionic strength.

Erlotinib-loaded albumin nanoparticles: A novel injectable form of erlotinib and its in vivo efficacy against pancreatic adenocarcinoma ASPC-1 and PANC-1 cell lines.

PubMed

Noorani, M; Azarpira, N; Karimian, K; Heli, H

2017-10-05

Erlotinib was loaded on albumin nanoparticles for the first time and the cytotoxic effect of the resulting nanoparticles against ASPC-1 and PANC-1 pancreatic adenocarcinoma cell lines was evaluated. The carrier (albumin nanoparticles, ANPs) was synthesized by desolvation method using a mixed solvent followed by thermal crosslinking for stabilization. ANPs and the drug-loaded ANPs were characterized by field emission scanning and transmission electron microscopies, particle size analysis and Fourier transform infrared spectroscopy. The nanoformulation had a size of <14nm with a good monodispersity. Drug loading and encapsulation efficiencies were evaluated as 27 and 44%. Cytotoxicity assays after 72h revealed the potential of ANPs to improve erlotinib toxicity (54% against 34% of free drug toward ASPC-1 cell line, and 52% against 30% toward PANC-1 cell line). Values of IC 50 were obtained for both cell lines and indicated significant reduction in the erlotinib dose necessary for killing the cells, while, ANPs were completely safe. The results demonstrated that erlotinib-loaded ANPs had a remarkable potential for pancreatic cancer drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of polymeric nanoparticles for intravenous delivery: Focus on stability.

PubMed

Oliveira, Claudia L; Veiga, Francisco; Varela, Carla; Roleira, Fernanda; Tavares, Elisiário; Silveira, Isabel; Ribeiro, Antonio J

2017-02-01

The nano-bio interaction has been of increased focus in the past years but very limited results have been obtained for polymeric nanoparticles (NP). Not only is needed to broaden the results obtained with model NP towards other nano-materials used for clinical application but the colloidal stability of NP as a variable consequence of the formation of the protein corona has been significantly understated. The lack and heterogeneity of assays to study NP stability and represent the biological environment call for the standardization of assays to improve the representativeness and comparability of results. In this paper, uncoated and PAH-coated PLGA NP have been prepared and characterized in regard to their potential for intravenous administration. The comparative study of the stability of NP in three media used to represent the biological environment-bovine serum albumin (BSA) solution, mouse and human plasma - revealed that both formulations were unstable in human plasma as opposed to the results obtained for other media. This unexpected behavior in plasmas of different origins could be correlated with a significant variation of the amount of proteins adsorbed to NP and, ultimately, with an approximately 6-fold difference in total protein concentration between the plasma samples. These results suggest that inter-species variation could impact on the colloidal stability of NP and enhance the need to understand the correlation between biological media and identify protocol-related interferences which, altogether, may evidence a relevant factor compromising in vitro- in vivo correlation and the translation of delivery systems aimed at intravenous administration. Copyright © 2016 Elsevier B.V. All rights reserved.

Paclitaxel Nano-Delivery Systems: A Comprehensive Review

PubMed Central

Ma, Ping; Mumper, Russell J.

2013-01-01

Paclitaxel is one of the most effective chemotherapeutic drugs ever developed and is active against a broad range of cancers, such as lung, ovarian, and breast cancers. Due to its low water solubility, paclitaxel is formulated in a mixture of Cremophor EL and dehydrated ethanol (50:50, v/v) a combination known as Taxol. However, Taxol has some severe side effects related to Cremophor EL and ethanol. Therefore, there is an urgent need for the development of alternative Taxol formulations. The encapsulation of paclitaxel in biodegradable and non-toxic nano-delivery systems can protect the drug from degradation during circulation and in-turn protect the body from toxic side effects of the drug thereby lowering its toxicity, increasing its circulation half-life, exhibiting improved pharmacokinetic profiles, and demonstrating better patient compliance. Also, nanoparticle-based delivery systems can take advantage of the enhanced permeability and retention (EPR) effect for passive tumor targeting, therefore, they are promising carriers to improve the therapeutic index and decrease the side effects of paclitaxel. To date, paclitaxel albumin-bound nanoparticles (Abraxane®) have been approved by the FDA for the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). In addition, there are a number of novel paclitaxel nanoparticle formulations in clinical trials. In this comprehensive review, several types of developed paclitaxel nano-delivery systems will be covered and discussed, such as polymeric nanoparticles, lipid-based formulations, polymer conjugates, inorganic nanoparticles, carbon nanotubes, nanocrystals, and cyclodextrin nanoparticles. PMID:24163786

Transport and Development of Microemulsionand Surfactant Stabilized Iron Nanoparticles for In Situ Remediation

NASA Astrophysics Data System (ADS)

Hsu, Dennis

This work describes the mobility assessments of microemulsion-stabilized iron oxide nanoparticles and anionic surfactant sodium diethyl hexyl phosphate (SDEHP)-stabilized nanoscale zero valent iron (NZVI) particles in laboratory porous media. The two formulations tested in this work achieved stable iron nanoparticle suspensions for months and prepared via a simple "one-pot" synthesis method developed by Wang et al. Both formulations were tested under field scale velocity of 5 m/day with no mechanical aid during the injection. A three-compartment model, involving colloid diffusion theory, diffusion theory and tailing was applied to describe the breakthrough curves of the studies. The obtained breakthrough curves of both formulations implied excellent transport in porous media with steady plateau C/Co at 0.8-0.9 and recovery of up to 0.95 for SDEHP stabilized NZVI. Post analysis on the retention of iron on the porous media implied ideal transport with consistent data to the breakthrough curves.

Characterization of nanoparticle uptake by endothelial cells.

PubMed

Davda, Jasmine; Labhasetwar, Vinod

2002-02-21

Endothelium is an important target for drug or gene therapy because of its important role in the biological system. In this paper, we have characterized nanoparticle uptake by endothelial cells in cell culture. Nanoparticles were formulated using poly DL-lactide-co-glycolide polymer containing bovine serum albumin as a model protein and 6-coumarin as a fluorescent marker. It was observed that the cellular uptake of nanoparticles depends on the time of incubation and the concentration of nanoparticles in the medium. The uptake of nanoparticles was rapid with confocal microscopy demonstrating their localization mostly in the cytoplasm. The mitogenic study demonstrated biocompatability of nanoparticles with the cells. The study thus demonstrates that nanoparticles could be used for localizing therapeutic agents or gene into endothelial cells. Nanoparticles localized in the endothelium could provide prolonged drug effects because of their sustained release characterics, and also could protect the encapsulated agent from enzymatic degradation.

Formulation design space for stable, pH sensitive crystalline nifedipine nanoparticles.

PubMed

Jog, Rajan; Unachukwu, Kenechi; Burgess, Diane J

2016-11-30

Enteric coated formulations protect drugs from degrading in the harsh environment of the stomach (acidic pH and enzymes), and promotes drug delivery to and absorption into the duodenum and/or later parts of the intestine. Four DoE models were applied to optimize formulation parameters for the preparation of pH sensitive nifedipine nanoparticles. Stability studies were performed on the optimized formulations to monitor any possible variation in particle size distribution, homogeneity index, surface charge and drug release (pH 1.2 and pH 6.8). Stability studies were performed for 3 months at 4°C, 25°C and 40°C. A combination of Eudragit ® L 100-55 and polyvinyl alcohol was determined to be the most effective in stabilizing the nanoparticle suspension. The average particle size distribution, polydispersity index and surface charge of the optimized pH sensitive nifedipine nanoparticles were determined to be 131.86±8.21nm, 0.135±0.008 and -7.631±0.146mV, respectively. Following three months storage, it was observed that the formulations stored at 4°C were stable in terms of particle size distribution, polydispersity index, surface charge, drug loading and drug release, whereas those stored at 25°C and 40°C were relatively unstable. A predictive model to prepare stable pH sensitive nifedipine nanoparticles, was successfully developed using multiple linear regression analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Nebulization performance of biodegradable sildenafil-loaded nanoparticles using the Aeroneb Pro: formulation aspects and nanoparticle stability to nebulization.

PubMed

Beck-Broichsitter, Moritz; Kleimann, Pia; Gessler, Tobias; Seeger, Werner; Kissel, Thomas; Schmehl, Thomas

2012-01-17

Polymeric nanoparticles meet the increasing interest for drug delivery applications and hold great promise to improve controlled drug delivery to the lung. Here, we present a series of investigations that were carried out to understand the impact of formulation variables on the nebulization performance of novel biodegradable sildenafil-loaded nanoparticles designed for targeted aerosol therapy of life-threatening pulmonary arterial hypertension. Narrowly distributed poly(D,L-lactide-co-glycolide) nanoparticles (size: ∼200 nm) were prepared by a solvent evaporation technique using poly(vinyl alcohol) (PVA) as stabilizer. The aerodynamic and output characteristics using the Aeroneb Pro nebulizer correlated well with the dynamic viscosity of the employed fluids for nebulization. The nebulization performance was mainly affected by the amount of employed stabilizer, rather than by the applied nanoparticle concentration. Nanoparticles revealed physical stability against forces generated during aerosolization, what is attributed to the adsorbed PVA layer around the nanoparticles. Sildenafil was successfully encapsulated into nanoparticles (encapsulation efficiency: ∼80%). Size, size distribution and sildenafil content of nanoparticles were not affected by nebulization and the in vitro drug release profile demonstrated a sustained sildenafil release over ∼120 min. The current study suggests that the prepared sildenafil-loaded nanoparticles are a promising pharmaceutical for the therapy of pulmonary arterial hypertension. Copyright © 2011 Elsevier B.V. All rights reserved.

Development and characterization of glutathione-conjugated albumin nanoparticles for improved brain delivery of hydrophilic fluorescent marker.

PubMed

Patel, Prerak J; Acharya, Niyati S; Acharya, Sanjeev R

2013-01-01

The glutathione-conjugated bovine serum albumin (BSA) nanoparticles were constructed in the present exploration as a novel biodegradable carrier for brain-specific drug delivery with evaluation of its in vitro and in vivo delivery properties. BSA nanocarriers were activated and conjugated to the distal amine functions of the glutathione via carbodiimide chemistry using EDAC as a mediator. These nanoparticles were characterized for particle shape, average size, SPAN value, drug entrapment and in vitro drug release. Further, presence of glutathione on the surface of BSA nanoparticles was confirmed by Ellman's assay, which has suggested that approximately 750 units of glutathione were conjugated per BSA nanoparticle. To evaluate the brain delivery properties of the glutathione-conjugated BSA nanoparticles fluorescein sodium was used as a model hydrophilic compound. Permeability and neuronal uptake properties of developed formulations were evaluated against the MDCK-MDR1 endothelial and neuro-glial cells, respectively. The permeability of glutathione-conjugated BSA nanoparticles across the monolayer of MDCK-MDR1 endothelial tight junction was shown significantly higher than that of unconjugated nanoparticles and fluorescein sodium solution. Similarly, glutathione-conjugated nanoparticles exhibited considerably higher uptake by neuro-glial cells which was inferred by high fluorescence intensity under microscope in comparison to unconjugated nanoparticles and fluorescein sodium solution. Following an intravenous administration, nearly three folds higher fluorescein sodium was carried to the rat brain by glutathione-conjugated nanoparticles as compared to unconjugated nanoparticles. The significant in vitro and in vivo results suggest that glutathione-conjugated BSA nanoparticles is a promising brain drug delivery system with low toxicity.

Enhanced tumor targeting of cRGD peptide-conjugated albumin nanoparticles in the BxPC-3 cell line.

PubMed

Yu, Xinzhe; Song, Yunlong; Di, Yang; He, Hang; Fu, Deliang; Jin, Chen

2016-08-12

The emerging albumin nanoparticle brings new hope for the delivery of antitumor drugs. However, a lack of robust tumor targeting greatly limits its application. In this paper, cyclic arginine-glycine-aspartic-conjugated, gemcitabine-loaded human serum albumin nanoparticles (cRGD-Gem-HSA-NPs) were successfully prepared, characterized, and tested in vitro in the BxPC-3 cell line. Initially, 4-N-myristoyl-gemcitabine (Gem-C14) was formed by conjugating myristoyl to the 4-amino group of gemcitabine. Then, cRGD-HSA was synthesized using sulfosuccinimidyl-(4-N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC) cross-linkers. Finally, cRGD-Gem-HSA-NPs were formulated based on the nanoparticle albumin-bound (nab) technology. The resulting NPs were characterized for particle size, zeta potential, morphology, encapsulation efficiency, and drug loading efficiency. In vitro cellular uptake and inhibition studies were conducted to compare Gem-HSA-NPs and cRGD-Gem-HSA-NPs in a human pancreatic cancer cell line (BxPC-3). The cRGD-Gem-HSA-NPs exhibited an average particle size of 160 ± 23 nm. The encapsulation rate and drug loading rate were approximately 83 ± 5.6% and 11 ± 4.2%, respectively. In vitro, the cRGD-anchored NPs exhibited a significantly greater affinity for the BxPC-3 cells compared to non-targeted NPs and free drug. The cRGD-Gem-HSA-NPs also showed the strongest inhibitory effect in the BxPC-3 cells among all the analyzed groups. The improved efficacy of cRGD-Gem-HSA-NPs in the BxPC-3 cell line warrants further in vivo investigations.

New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles

PubMed Central

Gossmann, Rebecca; Langer, Klaus; Mulac, Dennis

2015-01-01

Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower cytotoxic activity against Caco-2 cells. In conclusion this study offers a closer and critical point of view on preparation, in vitro and analytical evaluation of DMAB-stabilized PLGA nanoparticles for the physiological use. PMID:26147338

New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles.

PubMed

Gossmann, Rebecca; Langer, Klaus; Mulac, Dennis

2015-01-01

Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower cytotoxic activity against Caco-2 cells. In conclusion this study offers a closer and critical point of view on preparation, in vitro and analytical evaluation of DMAB-stabilized PLGA nanoparticles for the physiological use.

Effect of PLGA as a polymeric emulsifier on preparation of hydrophilic protein-loaded solid lipid nanoparticles.

PubMed

Xie, ShuYu; Wang, SiLiang; Zhao, BaoKai; Han, Chao; Wang, Ming; Zhou, WenZhong

2008-12-01

Most proteins are hydrophilic and poorly encapsulated into the hydrophobic matrix of solid lipid nanoparticles (SLN). To solve this problem, poly (lactic-co-glycolic acid) (PLGA) was utilized as a lipophilic polymeric emulsifier to prepare hydrophilic protein-loaded SLN by w/o/w double emulsion and solvent evaporation techniques. Hydrogenated castor oil (HCO) was used as a lipid matrix and bovine serum albumin (BSA), lysozyme and insulin were used as model proteins to investigate the effect of PLGA on the formulation of the SLN. The results showed that PLGA was essential for the primary w/o emulsification. In addition, the stability of the w/o emulsion, the encapsulation efficiency and loading capacity of the nanoparticles were enhanced with the increase of PLGA concentration. Furthermore, increasing PLGA concentration decreased zeta potential significantly but had no influence on particle size of the SLN. In vitro release study showed that PLGA significantly affected the initial burst release, i.e. the higher the content of PLGA, the lower the burst release. The released proteins maintained their integrity and bioactivity as confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and biological assay. These results demonstrated that PLGA was an effective emulsifier for the preparation of hydrophilic protein-loaded SLN.

Tangential Flow Ultrafiltration Allows Purification and Concentration of Lauric Acid-/Albumin-Coated Particles for Improved Magnetic Treatment.

PubMed

Zaloga, Jan; Stapf, Marcus; Nowak, Johannes; Pöttler, Marina; Friedrich, Ralf P; Tietze, Rainer; Lyer, Stefan; Lee, Geoffrey; Odenbach, Stefan; Hilger, Ingrid; Alexiou, Christoph

2015-08-14

Superparamagnetic iron oxide nanoparticles (SPIONs) are frequently used for drug targeting, hyperthermia and other biomedical purposes. Recently, we have reported the synthesis of lauric acid-/albumin-coated iron oxide nanoparticles SEON(LA-BSA), which were synthesized using excess albumin. For optimization of magnetic treatment applications, SPION suspensions need to be purified of excess surfactant and concentrated. Conventional methods for the purification and concentration of such ferrofluids often involve high shear stress and low purification rates for macromolecules, like albumin. In this work, removal of albumin by low shear stress tangential ultrafiltration and its influence on SEON(LA-BSA) particles was studied. Hydrodynamic size, surface properties and, consequently, colloidal stability of the nanoparticles remained unchanged by filtration or concentration up to four-fold (v/v). Thereby, the saturation magnetization of the suspension can be increased from 446.5 A/m up to 1667.9 A/m. In vitro analysis revealed that cellular uptake of SEON(LA-BSA) changed only marginally. The specific absorption rate (SAR) was not greatly affected by concentration. In contrast, the maximum temperature Tmax in magnetic hyperthermia is greatly enhanced from 44.4 °C up to 64.9 °C by the concentration of the particles up to 16.9 mg/mL total iron. Taken together, tangential ultrafiltration is feasible for purifying and concentrating complex hybrid coated SPION suspensions without negatively influencing specific particle characteristics. This enhances their potential for magnetic treatment.

Polymer Stabilized Nanosuspensions Formed via Flash Nanoprecipitation: Nanoparticle Formation, Formulation, and Stability

NASA Astrophysics Data System (ADS)

Zhu, ZhengXi

Nanoparticles loaded with hydrophobic components (e.g., active pharmaceutical ingredients, medical diagnostic agents, nutritional or personal care chemicals, catalysts, dyes/pigments, and substances with exceptional magnetic/optical/electronic/thermal properties) have tremendous industrial applications. The common desire is to efficiently generate nanoparticles with a desired size, size distribution, and size stability. Recently, Flash NanoPrecipition (FNP) technique with a fast, continuous, and easily scalable process has been developed to efficiently generate hydrophobe-loaded nanoparticles. This dissertation extended this technique, optimized process conditions and material formulations, and gave new insights into the mechanism and kinetics of nanoparticle formation. This dissertation demonstrated successful generation of spherical beta-carotene nanoparticles with an average diameter of 50--100 nm (90 wt% nanoparticles below 200 nm), good size stability (maintained an average diameter below 200 nm for at least one week in saline), and much higher loading (80--90 wt%) than traditional carriers, such as micelles and polymersomes (typically <20 wt%). Moreover, the nanoparticles are amorphous and expected to have a high dissolution rate and bioavailability. To give insights into the mechanism and kinetics of nanoparticle formation, much remarkable evidence supported the kinetically frozen structures of the nanoparticles rather than the thermodynamic equilibrium micelles. Time scales of the particle formation via FNP were proposed. To optimize the material formulations, either polyelectrolytes (i.e., epsilon-polylysine, branched and linear poly(ethylene imine), and chitosan) or amphiphilic diblock copolymers (i.e., polystyrene-b-poly(ethylene glycol) (PS-b-PEG), polycarprolactone-b-poly(ethylene glycol) (PCL-b-PEG), poly(lactic acid)-b-poly(ethylene glycol) (PLA-b-PEG), and poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG)) were selectively screened to study the nanoparticle size, distribution, and stability. The effect of the molecular weight of the polymers and pH were also studied. Chitosan and PLGA-b-PEG best stabilized the beta-carotene nanoparticles. Solubility of the hydrophobic drug solute in the aqueous mixture was considered to dominate the nanoparticle stability (i.e., size and morphology) in terms of Ostwald ripening and recrystallization. The lower solubility the drug is of, the greater stability the nanoparticles have. Chemically bonding drug compounds with cleavable hydrophobic moieties to form prodrugs were used to enhance their hydrophobicity and thus the nanoparticle stability. It opened a generic strategy to enhance the stability of nanoparticles formed via FNP. beta-carotene, paclitaxel, paclitaxel prodrug, betulin, hydrocortisone, and hydrocortisone prodrug as the drugs were studied. Solubility parameter (delta), and octanol/water partition coefficients (LogP), provide hydrophobicity indicators for the compounds. LogP showed a good correlation with the nanoparticle stability. An empirical rule was built to conveniently predict particle stability for randomly selected drugs. To optimize the process conditions, two-stream confined impinging jet mixer (CIJ) and four-stream confined vortex jet mixer were used. The particle size was studied by varying drug and polymer concentrations, and flow rate (corresponding to Reynolds number (Re)). To extend the FNP technique, this dissertation demonstrated successful creation of stabilized nanoparticles by integrating an in-situ reactive coupling of a hydrophilic polymer block with a hydrophobic one with FNP. The kinetics of the fast coupling reaction was studied. This dissertation also introduced polyelectrolytes (i.e., epsilon-polylysine, poly(ethylene imine), and chitosan) into FNP to electrosterically stabilize nanoparticles.

Stabilization of the Nitric Oxide (NO) Prodrugs and Anti-Cancer Leads, PABA/NO and Double JS-K through Incorporation into PEG-Protected Nanoparticles

PubMed Central

Kumar, Varun; Hong, Sam Y.; Maciag, Anna E.; Saavedra, Joseph E.; Adamson, Douglas H.; Prud'homme, Robert K.; Keefer, Larry K.; Chakrapani, Harinath

2009-01-01

Here we report the stabilization of the nitric oxide (NO) prodrugs and anti-cancer lead compounds, PABA/NO (O2-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) and “Double JS-K” (1,5-bis{[1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diol-2-ato]-2,4-dinitrobenzene), through their incorporation into polymer-protected nanoparticles. The prodrugs were formulated in block copolymer-stabilized nanoparticles with sizes from 220 to 450 nm by a novel rapid precipitation process. The block copolymers, with polyethylene glycol (PEG) soluble blocks, provide a steric barrier against NO prodrug activation by glutathione. Too rapid activation and NO release has been a major barrier to effective administration of this class of compounds. The nanoparticle stabilized PABA/NO from attack by glutathione as evidenced by a significant increase in time taken for 50% decomposition from 15 min (unformulated) to 5 h (formulated); in the case of Double JS-K, the 50% decomposition time was extended from 4.5 min (unformulated) to 40 min (formulated). The more hydrophobic PABA/NO produced more stable nanoparticles and correspondingly more extended release times in comparison with Double JS-K. The hydrophobic blocks of the polymer were either polystyrene or polylactide. Both blocks produced nanoparticles of approximately the same size and release kinetics. This combination of PEG-protected nanoparticles with sizes appropriate for cancer targeting by enhanced permeation and retention (EPR) and delayed release of NO may afford enhanced therapeutic benefit. PMID:20000791

Stabilization of the nitric oxide (NO) prodrugs and anticancer leads, PABA/NO and Double JS-K, through incorporation into PEG-protected nanoparticles.

PubMed

Kumar, Varun; Hong, Sam Y; Maciag, Anna E; Saavedra, Joseph E; Adamson, Douglas H; Prud'homme, Robert K; Keefer, Larry K; Chakrapani, Harinath

2010-02-01

We report the stabilization of the nitric oxide (NO) prodrugs and anticancer lead compounds, PABA/NO (O(2)-{2,4-dinitro-5-[4-(N-methylamino)benzoyloxy]phenyl} 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate) and "Double JS-K" 1,5-bis-{1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diol-2-ato}-2,4-dinitrobenzene, through their incorporation into polymer-protected nanoparticles. The prodrugs were formulated in block copolymer-stabilized nanoparticles with sizes from 220 to 450 nm by a novel rapid precipitation process. The block copolymers, with polyethylene glycol (PEG) soluble blocks, provide a steric barrier against NO prodrug activation by glutathione. Too rapid activation and NO release has been a major barrier to effective administration of this class of compounds. The nanoparticle stabilized PABA/NO are protected from attack by glutathione as evidenced by a significant increase in time taken for 50% decomposition from 15 min (unformulated) to 5 h (formulated); in the case of Double JS-K, the 50% decomposition time was extended from 4.5 min (unformulated) to 40 min (formulated). The more hydrophobic PABA/NO produced more stable nanoparticles and correspondingly more extended release times in comparison with Double JS-K. The hydrophobic blocks of the polymer were either polystyrene or polylactide. Both blocks produced nanoparticles of approximately the same size and release kinetics. This combination of PEG-protected nanoparticles with sizes appropriate for cancer targeting by enhanced permeation and retention (EPR) and delayed release of NO may afford enhanced therapeutic benefit.

Novel formulations enhance the thermal stability of live-attenuated flavivirus vaccines

PubMed Central

Wiggan, O’Neil; Silengo, Shawn J.; Kinney, Richard M.; Osorio, Jorge E.; Huang, Claire Y.-H.; Stinchcomb, Dan T.

2011-01-01

Thermal stability is important for the manufacture, distribution and administration of vaccines, especially in tropical developing countries, where particularly adverse field conditions exist. Current live-attenuated flavivirus vaccines exhibit relatively poor liquid stability in clinical settings, and clinicians are instructed to discard the yellow fever vaccine 1h after reconstitution. We have identified novel combinations of excipients that greatly enhance the thermal stability of live-attenuated DEN-2 PDK-53-based flavivirus vaccine candidates. Liquid formulations comprising a sugar, albumin and a pluronic polymer minimized the loss of flavivirus infectious titer to less than 0.5log(10)pfu after storage for at least 8h at 37°C, 7 days at room temperature or at least 11 weeks at 4°C. Additionally, these formulations prevented reduction of viral infectivity after two freeze-thaw cycles of virus. Formulated candidate vaccines were readily lyophilized and reconstituted with minimal loss of viral titers. In mice, the formulations were safe and did not hinder the ability of the vaccine virus to generate a potent, protective immune response. These formulations provided significantly greater liquid-phase stability than has been reported previously for other flavivirus vaccine formulations. The enhanced thermal stability provided by the formulations described here will facilitate the effective distribution of flavivirus vaccines worldwide. PMID:21803103

Electrophoretic properties of BSA-coated quantum dots.

PubMed

Bücking, Wendelin; Massadeh, Salam; Merkulov, Alexei; Xu, Shu; Nann, Thomas

2010-02-01

Low toxic InP/ZnS quantum dots (QDs), ZnS:Mn(2+)/ZnS nanocrystals and CdSe/ZnS nanoparticles were rendered water-dispersible by different ligand-exchange methods. Eventually, they were coated with bovine serum albumin (BSA) as a model protein. All particles were characterised by isotachophoresis (ITP), laser Doppler velocimetry (LDV) and agarose gel electrophoresis. It was found that the electrophoretic mobility and colloidal stability of ZnS:Mn(2+)/ZnS and CdSe/ZnS nanoparticles, which bore short-chain surface ligands, was primarily governed by charges on the nanoparticles, whereas InP/ZnS nanocrystals were not charged per se. BSA-coated nanoparticles showed lower electrophoretic mobility, which was attributed to their larger size and smaller overall charge. However, these particles were colloidally stable. This stability was probably caused by steric stabilisation of the BSA coating.

Enhancing Docetaxel Delivery to Multidrug-Resistant Cancer Cells with Albumin-Coated Nanocrystals.

PubMed

Gad, Sheryhan F; Park, Joonyoung; Park, Ji Eun; Fetih, Gihan N; Tous, Sozan S; Lee, Wooin; Yeo, Yoon

2018-01-29

Intravenous delivery of poorly water-soluble anticancer drugs such as docetaxel (DTX) is challenging due to the low bioavailability and the toxicity related to solubilizing excipients. Colloidal nanoparticles are used as alternative carriers, but low drug loading capacity and circulation instability limit their clinical translation. To address these challenges, DTX nanocrystals (NCs) were prepared using Pluronic F127 as an intermediate stabilizer and albumin as a functional surface modifier, which were previously found to be effective in producing small and stable NCs. We hypothesize that the albumin-coated DTX NCs (DTX-F-alb) will remain stable in serum-containing medium so as to effectively leverage the enhanced permeability and retention effect. In addition, the surface-bound albumin, in its native form, may contribute to cellular transport of NCs through interactions with albumin-binding proteins such as secreted protein acidic and rich in cysteine (SPARC). DTX-F-alb NCs showed sheet-like structure with an average length, width, and thickness of 284 ± 96, 173 ± 56, and 40 ± 8 nm and remained stable in 50% serum solution at a concentration greater than 10 μg/mL. Cytotoxicity and cellular uptake of DTX-F-alb and unformulated (free) DTX were compared on three cell lines with different levels of SPARC expression and DTX sensitivity. While the uptake of free DTX was highly dependent on DTX sensitivity, DTX-F-alb treatment resulted in relatively consistent cellular levels of DTX. Free DTX was more efficient in entering drug-sensitive B16F10 and SKOV-3 cells than DTX-F-alb, with consistent cytotoxic effects. In contrast, multidrug-resistant NCI/ADR-RES cells took up DTX-F-alb more than free DTX with time and responded better to the former. This difference was reduced by SPARC knockdown. The high SPARC expression level of NCI/ADR-RES cells, the known affinity of albumin for SPARC, and the opposing effect of SPARC knockdown support that DTX-F-alb have exploited the surface-bound albumin-SPARC interaction in entering NCI/ADR-RES cells. Albumin-coated NC system is a promising formulation for the delivery of hydrophobic anticancer drugs to multidrug-resistant tumors.

Crosslinking to enhance colloidal stability and redispersity of layered double hydroxide nanoparticles.

PubMed

Zuo, Huali; Gu, Zi; Cooper, Helen; Xu, Zhi Ping

2015-12-01

This article introduces a strategy for stabilizing and redispersing layered double hydroxide (LDH) nanoparticles by crosslinking bovine serum albumin (BSA) coated onto the surface. The strategy involves optimization of the amount of the crosslinking agent glutaraldehyde (GTA) to achieve minimal aggregation and ready redispersion. LDH nanoparticles were prepared by co-precipitation and hydrothermal treatment, with subsequent BSA coating at the BSA/LDH mass ratio of 5:2. BSA coated onto LDH nanoparticles was crosslinked with different amounts of GTA. Aggregation studies using dilution assays, dynamic light scattering, and zeta potential analysis indicated that severe aggregation at lower LDH nanoparticle concentrations can be prevented by proper crosslinking of BSA with GTA. The GTA-crosslinked BSA-coated nanoparticles showed excellent redispersity compared to the non-crosslinked nanoparticles. In vitro cytotoxicity and cell uptake were found to be minimally affected by GTA-crosslinking. The new strategy therefore provides a much more effective method for the prevention of LDH nanoparticle aggregation and improved LDH nanoparticle redispersion for use in a wide variety of bio-applications in vitro and in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

Freeze-drying of nanosuspensions, part 3: investigation of factors compromising storage stability of highly concentrated drug nanosuspensions.

PubMed

Beirowski, Jakob; Inghelbrecht, Sabine; Arien, Albertina; Gieseler, Henning

2012-01-01

On the basis of a previously developed formulation and process guideline for lyophilized, highly concentrated drug nanosuspensions for parenteral use, it was the purpose of this study to demonstrate that the original nanoparticle size distribution can be preserved over a minimum period of 3 months, even if aggressive primary drying conditions are used. Critical factors were evaluated that were originally believed to affect storage stability of freeze-dried drug nanoparticles. It was found that the nature and concentration of the steric stabilizer, such as Poloxamer 338 and Cremophor EL, are the most important factors for long-term stability of such formulations, independent of the used drug compound. The rational choice of an adequate steric stabilizer, namely Poloxamer 338, in combination with various lyoprotectants seems crucial to prevent physical instabilities of the lyophilized drug nanoparticles during short-term stability experiments at ambient and accelerated conditions. A 200 mg/mL concentration of nanoparticles could successfully be stabilized over the investigated time interval. In the course of the present experiments, polyvinylpyrrolidone, type K15 was found superior to trehalose or sucrose in preserving the original particle size distribution, presumably based on its surface-active properties. Lastly, it was demonstrated that lower water contents are generally beneficial to stabilize such systems. Copyright © 2011 Wiley-Liss, Inc.

[Development of Inhalable Dry Powder Formulations Loaded with Nanoparticles Maintaining Their Original Physical Properties and Functions].

PubMed

Okuda, Tomoyuki

2017-01-01

 Functional nanoparticles, such as liposomes and polymeric micelles, are attractive drug delivery systems for solubilization, stabilization, sustained release, prolonged tissue retention, and tissue targeting of various encapsulated drugs. For their clinical application in therapy for pulmonary diseases, the development of dry powder inhalation (DPI) formulations is considered practical due to such advantages as: (1) it is noninvasive and can be directly delivered into the lungs; (2) there are few biocomponents in the lungs that interact with nanoparticles; and (3) it shows high storage stability in the solid state against aggregation or precipitation of nanoparticles in water. However, in order to produce effective nanoparticle-loaded dry powders for inhalation, it is essential to pursue an innovative and comprehensive formulation strategy in relation to composition and powderization which can achieve (1) the particle design of dry powders with physical properties suitable for pulmonary delivery through inhalation, and (2) the effective reconstitution of nanoparticles that will maintain their original physical properties and functions after dissolution of the powders. Spray-freeze drying (SFD) is a relatively new powderization technique combining atomization and lyophilization, which can easily produce highly porous dry powders from an aqueous sample solution. Previously, we advanced the optimization of components and process conditions for the production of SFD powders suitable to DPI application. This review describes our recent results in the development of novel DPI formulations effectively loaded with various nanoparticles (electrostatic nanocomplexes for gene therapy, liposomes, and self-assembled lipid nanoparticles), based on SFD.

Development of PEG-PLGA based Intravenous Low Molecular Weight Heparin (LMWH) Nanoparticles Intended to Treat Venous Thrombosis.

PubMed

Jogala, Satheesh; Rachamalla, Shyam Sunder; Aukunuru, Jithan

2016-01-01

Anticoagulant therapy is effective in the treatment of DVT. In this regard, LMWH demonstrated significant promise. It is widely used clinically. The goal of this study was to prepare and evaluate intravenous sustained release stealth nanoparticles encapsulating LMWH using PLGA (polylactidecoglycolide) and different grades of PEG (poly ethylene glycols). The nanoparticles were prepared using w/o/w solvent evaporation technique. Prepared nanoparticles were evaluated for particle size, encapsulation efficiency, in-vitro drug release, anti-thrombotic activity in venous thrombosis rat model, estimation of aPTT, tissue bio-distribution studies and stability. Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) studies confirmed the formation of smooth spherical particles. FTIR study reveals successful coating of PEG on the nanoparticles. DSC and XRD results demonstrated that drug changed its physical form in the formulation. The encapsulation efficiency was 63-74%. In vitro drug release was 57-75% for 48 hrs. Macrophage uptake of LMWH with pegylated nanoparticles was less compared to conventional PLGA nanoparticles. In vivo drug release was sustained for 48hrs; Optimized formulation exhibited good enhancement in pharmacokinetic parameters when compared to free drug solution. In vivo sustained release was also demonstrated with antithrombotic activity as well aPTT activity. Optimized formulation demonstrated significant stability, excellent antithrombotic activity in venous thrombosis rat model, improved aPTT levels when compared to free drug solution. An effective stealth LMWH nanoparticle formulation to treat venous thrombosis was successfully developed using w/o/w solvent evaporation technique.

Development of double emulsion nanoparticles for the encapsulation of bovine serum albumin.

PubMed

Martinez, Nelida Y; Andrade, Patricia F; Durán, Nelson; Cavalitto, Sebastian

2017-10-01

In the present work, a double emulsion was developed for the encapsulation of Bovine Serum Albumin (BSA) as a model protein for the future encapsulation of viral proteins. The first emulsion polydispersity index (PDI) was studied with increasing concentrations of poly (ε-caprolactone) (PCL) as stabilizer (from 16% w/v to 5% w/v) and polyvinyl alcohol (PVA) as the surfactant in the second emulsion at 1.5% w/v. Results suggest that at decreasing concentrations of PCL the PDI of the emulsion also decrease, indicating that viscosity of the emulsion is crucial in the homogeneity of the resultant size distribution of the nanoparticles. When PVA concentration in the second emulsion was increased from 1.5% w/v to 2.5% w/v the PDI also increased. To study the relationship between the structure of the surfactant in the second emulsion and the resultant BSA encapsulation, emulsions were prepared with Pluronic F68 and PVA both at 1.5% w/v and PCL in the first emulsion at 5% w/v. Results indicated that Pluronic F68 was a better stabilizer because at the same experimental conditions encapsulation of BSA was 1.5 higher than PVA. FTIR studies confirmed the presence of BSA in the nanoparticles. SEM and TEM microscopies showed a size distribution of 300nm-500nm size of nanoparticles. Circular dichroism studies demonstrated that the secondary structure of the protein was conserved after the encapsulation into the nanoparticles. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of endogenous nanoparticles from roasted chicken breasts.

PubMed

Song, Xunyu; Cao, Lin; Cong, Shuang; Song, Yukun; Tan, Mingqian

2018-06-22

Emergence of endogenous nanoparticles in thermally processed food has aroused much attention due to their unique properties and potential biological impact. The aim of this study was to investigate the presence of fluorescence nanoparticles in roasted chicken breasts, elemental composition, physico-chemical properties and their molecular interaction with human serum albumin (HSA). Transmission electron microscopy analysis revealed that the foodborne nanoparticles from roasted chicken were nearly spherical with an average particle size of 1.7 ± 0.4 nm. The elemental analysis of X-ray photoelectron spectroscopy showed the composition of nanoparticles as 47.4% C, 25.8% O and 26.1% N. The fluorescence of HSA was quenched by the nanoparticles following a static mode, and the molecular interaction of nanoparticles with HSA was spontaneous (ΔG°＜0), where hydrogen bonding and van der Waals forces played an important role during HSA-nanoparticles complex stabilization through thermodynamic analysis by isothermal titration calorimetry. The principal location of the nanoparticles binding site on HSA was primarily in site I as determined by site-specific marker competition. The conformational of HSA was also changed and ɑ-helical structure decreased in the presence of nanoparticles. Our studies revealed that fluorescent nanoparticles were produced after roasting of chicken breast at 230 °C for 30 min for the first time. The obtained nanoparticles can interact with HSA in a spontaneous manner, thus providing valuable insight into foodborne NPs as well as their effects to human albumin protein.

Strategies to optimize the biocompatibility of iron oxide nanoparticles - ;SPIONs safe by design;

NASA Astrophysics Data System (ADS)

Janko, Christina; Zaloga, Jan; Pöttler, Marina; Dürr, Stephan; Eberbeck, Dietmar; Tietze, Rainer; Lyer, Stefan; Alexiou, Christoph

2017-06-01

Various nanoparticle systems have been developed for medical applications in recent years. For constant improvement of efficacy and safety of nanoparticles, a close interdisciplinary interplay between synthesis, physicochemical characterizations and toxicological investigations is urgently needed. Based on combined toxicological data, we follow a ;safe-by design; strategy for our superparamagnetic iron oxide nanoparticles (SPION). Using complementary interference-free toxicological assay systems, we initially identified agglomeration tendencies in physiological fluids, strong uptake by cells and improvable biocompatibility of lauric acid (LA)-coated SPIONs (SPIONLA). Thus, we decided to further stabilize those particles by an artificial protein corona consisting of serum albumin. This approach finally lead to increased colloidal stability, augmented drug loading capacity and improved biocompatibility in previous in vitro assays. Here, we show in whole blood ex vivo and on isolated red blood cells (RBC) that a protein corona protects RBCs from hemolysis by SPIONs.

Albumin microparticles as the carriers for allopurinol and applicable for the treatment of ischemic stroke

NASA Astrophysics Data System (ADS)

Aganyants, Hovsep Alexandr; Nikohosyan, Gayane; Danielyan, Kristine Edgar

2016-11-01

Albumin nanoparticles are already used for the treatment of the cancer. In our current work, it is presented the technique for the preparation of small-size 1- to 5-micron particles coated with the allopurinol. We propose that this combination of the compounds might be useful for the ischemic stroke treatment as the agent preventing formation of the brain edema, reactive oxygen species, and initiation of cells regeneration. Glutaraldehyde was used for the polymerization of albumin. Determination of the particle size was performed by the light as well as phase contrast microscopies and analyzed by Pixcavator 6.0 and Image Tool programs. Modification and establishment of iodine-based method served as the base for quantification of bound with the particles and free allopurinol. As a consequence of the experiments, the best formulation of glutaraldehyde ratio and albumin quantity as well as conditions for the formation of the smallest sized spheroid-shaped particles were found for the further in vivo application.

Development, characterization, and evaluation of sunscreen cream containing solid lipid nanoparticles of silymarin.

PubMed

Netto MPharm, Gladyston; Jose, Jobin

2017-12-10

Most of the sunscreen formulations mainly contain chemicals or synthetic molecules. Nowadays, researchers are mainly focussing on herbal formulations due to toxicity of the synthetic molecules. Silymarin is a natural flavonoids having excellent antioxidant properties. Solid lipid nanoparticles are novel drug carriers which improve the drug stability and tolerance effect and also enhance the permeation effect. This study aimed at the preparation of solid lipid nanoparticles containing silymarin that will be incorporated into a sunscreen cream and determine its sun protection factor. The solid lipid nanoparticles were prepared by micro-emulsion method; here, the glyceryl monostearate was used as lipid, and Tween 80 was used as an emulsifier. The solid lipid nanoparticles were evaluated for drug entrapment, particle size and morphology, zeta potential, and polydispersity index. The dispersion was formulated into sunscreen cream and evaluated for various parameters, such as extrudability, viscosity, spreadability, drug content, in vitro drug release, ex vivo permeation of drug, in vitro and in vivo sun protection factor determination, in vivo skin irritation test, and accelerated stability studies. The results suggested that as the concentration of emulsifier increased, the entrapment efficiency of silymarin increased. In vitro and in vivo sun protection factor determination showed that SPF of 13.80 and 14.1, respectively. Stability studies were performed under accelerated conditions, and it did not show any appreciable change in parameters. These results indicated that the sunscreen containing silymarin solid lipid nanoparticles exhibited better photoprotective action. © 2017 Wiley Periodicals, Inc.

Preventing Aggregation of Recombinant Interferon beta-1b in Solution by Additives: Approach to an Albumin-Free Formulation

PubMed Central

Mahjoubi, Najmeh; Fazeli, Mohammad Reza; Dinarvand, Rassoul; Khoshayand, Mohammad Reza; Fazeli, Ahmad; Taghavian, Mohammad; Rastegar, Hossein

2015-01-01

Purpose: Aggregation suppressing additives have been used to stabilize proteins during manufacturing and storage. Interferonβ-1b is prone to aggregation because of being non-glycosylated. Aggregation behavior of albumin-free formulations of recombinant IFNβ-1b was explored using additives such as n-dodecyl-β-D-maltoside, Tween 20, arginine, glycine, trehalose and sucrose at different pH. Methods: Fractional factorial design was applied to select major factors affecting aggregation in solutions. Box-Behnken technique was used to optimize the best concentration of additives and protein. Results: Quadratic model was the best fitted model for particle size, OD350 and OD280/OD260. The optimal conditions of 0.2% n-Dodecyl-β-D-maltoside, 70 mM arginine, 189 mM trehalose and protein concentration of 0.50 mg/ml at pH 4 were achieved. A potency value of 91% ± 5% was obtained for the optimized formulation. Conclusion: This study shows that the combination of n-Dodecyl-β-D-maltoside, arginine and trehalose would demonstrate a significant stabilizing and anti-aggregating effect on the liquid formulation of interferonβ-1b. It can not only reduce the manufacturing costs but will also ease patient compliance. PMID:26819922

Preparation and characterization of liposomal formulations of neurotensin-degrading enzyme inhibitors.

PubMed

van Rooy, Inge; Wu, Shin-Ying; Storm, Gert; Hennink, Wim E; Dinter-Heidorn, Heike; Schiffelers, Raymond M; Mastrobattista, Enrico

2011-09-20

Neurotensin-degrading enzyme (NTDE) inhibitors hold great potential for treating psychotic disorders. However, brain uptake of such compounds in vivo is generally low due to the presence of the blood-brain barrier. In this study, liposomal formulations of two NTDE inhibitors, named compound 1 (C1) and compound 2 (C2) were prepared. Association of these compounds with the liposomal bilayer, subsequent liposomal stability, and compound release in the presence of albumin was studied. Entrapment of the compounds in the liposomal bilayer showed the solubilizing properties of the liposomes. Size and polydispersity index of the compound-entrapped liposomes did not change over 1 month, showing colloidal stability of the liposomal drug formulations. The amount of compounds associated with the liposomes decreased within one day. After this, the association remained stable at 4°C. For C1, association remained stable at 37°C in HEPES buffered saline, and the compound was gradually released in the presence of bovine serum albumin. For C2, the release was rapid in both HBS and BSA at 37°C. In conclusion, the formulation of NTDE inhibitors C1 and C2 in liposomes has been demonstrated and holds promise to deliver NTDE inhibitors in vivo. Copyright © 2011 Elsevier B.V. All rights reserved.

Effect of sterilization on the physical stability of brimonidine-loaded solid lipid nanoparticles and nanostructured lipid carriers.

PubMed

El-Salamouni, Noha S; Farid, Ragwa M; El-Kamel, Amal H; El-Gamal, Safaa S

2015-12-30

Nanoparticulate delivery systems have recently been under consideration for topical ophthalmic drug delivery. Brimonidine base-loaded solid lipid nanoparticles and nanostructured lipid carrier formulations were prepared using glyceryl monostearate as solid lipid and were evaluated for their physical stability following sterilization by autoclaving at 121°C for 15min. The objective of this work was to evaluate the effect of autoclaving on the physical appearance, particle size, polydispersity index, zeta potential, entrapment efficiency and particle morphology of the prepared formulations, compared to non-autoclaved ones. Results showed that, autoclaving at 121°C for 15min allowed the production of physically stable formulations in nanometric range, below 500nm suitable for ophthalmic application. Moreover, the autoclaved samples appeared to be superior to non-autoclaved ones, due to their increased zeta potential values, indicating a better physical stability. As well as, increased amount of brimonidine base entrapped in the tested formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Albumin nanoparticles with synergistic antitumor efficacy against metastatic lung cancers.

PubMed

Kim, Bomi; Seo, Bohyung; Park, Sanghyun; Lee, Changkyu; Kim, Jong Oh; Oh, Kyung Taek; Lee, Eun Seong; Choi, Han-Gon; Youn, Yu Seok

2017-10-01

Albumin nanoparticles are well-known as effective drug carriers used to deliver hydrophobic chemotherapeutic agents. Albumin nanoparticles encapsulating curcumin and doxorubicin were fabricated using slightly modified nanoparticle albumin-bound (nab™) technology, and the synergistic effects of these two drugs were examined. Albumin nanoparticles encapsulating curcumin, doxorubicin, and both curcumin and doxorubicin were prepared using a high pressure homogenizer. The sizes of albumin nanoparticles were ∼130nm, which was considered to be suitable for the EPR (enhanced permeability and retention) effect. Albumin nanoparticles gradually released drugs over a period of 24h without burst effect. To confirm the synergistic effect of two drugs, in vitro cytotoxicity assay was performed using B16F10 melanoma cells. The cytotoxic effect on B16F10 melanoma cells was highest when co-treated with both curcumin and doxorubicin compared to single treatment of either curcumin and doxorubicin. The combined index calculated by medium-effect equation was 0.6069, indicating a synergistic effect. Results of confocal laser scanning microscopy and fluorescence-activated cell sorting corresponded to results from an in vitro cytotoxicity assay, indicating synergistic cytotoxicity induced by both drugs. A C57BL/6 mouse model induced by B16F10 lung metastasis was used to study in vivo therapeutic effects. When curcumin and doxorubicin were simultaneously treated, the metastatic melanoma mass in the lungs macroscopically decreased compared to curcumin or doxorubicin alone. Albumin nanoparticles encapsulating two anticancer drugs were shown to have an effective therapeutic result and would be an excellent way to treat resistant lung cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

Docetaxel-albumin conjugates: preparation, in vitro evaluation and biodistribution studies.

PubMed

Esmaeili, Farnaz; Dinarvand, Rassoul; Ghahremani, Mohammad Hossein; Amini, Mohsen; Rouhani, Hasti; Sepehri, Nima; Ostad, Seyed Nasser; Atyabi, Fatemeh

2009-08-01

Docetaxel (DTX) is one of the most active chemotherapeutic agents for treating metastatic breast cancer. Its aqueous solubility is very low, hence the available formulation of DTX for clinical use consists of high concentrations of tween80, which has been associated with several hypersensitivity reactions. To reduce the systemic toxicity of DTX as well as to avoid the use of tween80, in this study DTX was chemically conjugated with human serum albumin via a succinic spacer. A high-performance liquid chromatography method was developed for the determination of DTX-albumin conjugate. T47D and SKOV3 cells were used for the evaluation of the in vitro cytotoxicity of the conjugate by MTT assay. Studies were then done on balb/c mice to elucidate the tissue distribution of conjugates after intravenous administration. The albumin-conjugated formulation of DTX with the particle size of 90-110 nm showed enhanced solubility and in vivo characteristics and significantly higher cytotoxicity against tumor cells, for example, IC50 of 6.30 +/- 0.73 nM for T47D cell line compared to free DTX with IC50 of 39.4 +/- 1.75 nM. Conjugation also maintained DTX plasma level at 16.19% up to 2 h after injection compared with 2.51% for Taxotere, hence increasing the chance of nanoparticles uptake by tumor cells. Copyright 2009 Wiley-Liss, Inc.

Understanding Acoustic Cavitation Initiation by Porous Nanoparticles: Toward Nanoscale Agents for Ultrasound Imaging and Therapy.

PubMed

Yildirim, Adem; Chattaraj, Rajarshi; Blum, Nicholas T; Goodwin, Andrew P

2016-08-23

Ultrasound is widely applied in medical diagnosis and therapy due to its safety, high penetration depth, and low cost. In order to improve the contrast of sonographs and efficiency of the ultrasound therapy, echogenic gas bodies or droplets (with diameters from 200 nm to 10 µm) are often used, which are not very stable in the bloodstream and unable to penetrate into target tissues. Recently, it was demonstrated that nanobubbles stabilized by nanoparticles can nucleate ultrasound responsive microbubbles under reduced acoustic pressures, which is very promising for the development of nanoscale (<100 nm) ultrasound agents. However, there is still very little understanding about the effects of nanoparticle properties on the stabilization of nanobubbles and nucleation of acoustic cavitation by these nanobubbles. Here, a series of mesoporous silica nanoparticles with sizes around 100 nm but with different morphologies were synthesized to understand the effects of nanoparticle porosity, surface roughness, hydrophobicity, and hydrophilic surface modification on acoustic cavitation inception by porous nanoparticles. The chemical analyses of the nanoparticles showed that, while the nanoparticles were prepared using the same silica precursor (TEOS) and surfactant (CTAB), they revealed varying amounts of carbon impurities, hydroxyl content, and degrees of silica crosslinking. Carbon impurities or hydrophobic modification with methyl groups is found to be essential for nanobubble stabilization by mesoporous silica nanoparticles. The acoustic cavitation experiments in the presence of ethanol and/or bovine serum albumin (BSA) demonstrated that acoustic cavitation is predominantly nucleated by the nanobubbles stabilized at the nanoparticle surface not inside the mesopores. Finally, acoustic cavitation experiments with rough and smooth nanoparticles were suggested that a rough nanoparticle surface is needed to largely preserve surface nanobubbles after coating the surface with hydrophilic macromolecules, which is required for in vivo applications of nanoparticles.

Microheterogeneity in Frozen Protein Solutions

PubMed Central

Twomey, Alan; Kurata, Kosaku; Nagare, Yutaka; Takamatsu, Hiroshi; Aksan, Alptekin

2015-01-01

In frozen and lyophilized systems, the biological to be stabilized (e.g. therapeutic protein, biomarker, drug-delivery vesicle) and the cryo-/lyoprotectant should be co-localized for successful stabilization. During freezing and drying, many factors cause physical separation of the biological from the cryo-/lyoprotectant, called microheterogeneity (MH), which may result in poor stabilization efficiency. We have developed a novel technique that utilized confocal Raman microspectroscopy in combination with counter-gradient freezing to evaluate the effect of a wide range of freezing temperatures (−20 < TF < 0°C) on the MH generated within a frozen formulation in only a few experiments. The freezing experiments conducted with a model system (albumin and trehalose) showed the presence of different degrees of MH in the freeze-concentrated liquid (FCL) in all solutions tested. Mainly, albumin tended to accumulate near the ice interface, where it was physically separated from the cryoprotectant. In frozen 10 wt% trehalose solutions, heterogeneity in FCL was relatively low at any TF. In frozen 20 wt% trehalose solutions, the optimum albumin to trehalose ratio in the FCL can only be ensured if the solution was frozen within a narrow range of temperatures (−16 < TF < −10°C). In the 30 wt% trehalose solutions, freezing within a much more narrow range (−12 < TF < −10°C) was needed to ensure a fairly homogeneous FCL. The method developed here will be helpful for the development of uniformly frozen and stable formulations and freezing protocols for biological as MH is presumed to directly impact stability. PMID:25888798

Timescale of silver nanoparticle transformation in neural cell cultures impacts measured cell response

NASA Astrophysics Data System (ADS)

Hume, Stephanie L.; Chiaramonti, Ann N.; Rice, Katherine P.; Schwindt, Rani K.; MacCuspie, Robert I.; Jeerage, Kavita M.

2015-07-01

Both serum protein concentration and ionic strength are important factors in nanoparticle transformation within cell culture environments. However, silver nanoparticles are not routinely tracked at their working concentration in the specific medium used for in vitro toxicology studies. Here we evaluated the transformation of electrostatically stabilized citrate nanoparticles (C-AgNPs) and sterically stabilized polyvinylpyrrolidone nanoparticles (PVP-AgNPs) in a low-serum ( 0.2 mg/mL bovine serum albumin) culture medium, while measuring the response of rat cortex neural progenitor cells, which differentiate in this culture environment. After 24 h, silver nanoparticles at concentrations up to 10 µg/mL did not affect adenosine triphosphate levels, whereas silver ions decreased adenosine triphosphate levels at concentrations of 1.1 µg/mL or higher. After 240 h, both silver nanoparticles, as well as silver ion, unambiguously decreased adenosine triphosphate levels at concentrations of 1 and 1.1 µg/mL, respectively, suggesting particle dissolution. Particle transformation was investigated in 1:10 diluted, 1:2 diluted, or undiluted differentiation medium, all having an identical protein concentration, to separate the effect of serum protein stabilization from ionic strength destabilization. Transmission electron microscopy images indicated that particles in 1:10 medium were not surrounded by proteins, whereas particles became clustered within a non-crystalline protein matrix after 24 h in 1:2 medium and at 0 h in undiluted medium. Despite evidence for a protein corona, particles were rapidly destabilized by high ionic strength media. Polyvinylpyrrolidone increased the stability of singly dispersed particles compared to citrate ligands; however, differences were negligible after 4 h in 1:2 medium or after 1 h in undiluted medium. Thus low-serum culture environments do not provide sufficient colloidal stability for long-term toxicology studies with citrate- or polyvinylpyrrolidone-stabilized silver nanoparticles.

Comparative evaluation of polymeric and amphiphilic cyclodextrin nanoparticles for effective camptothecin delivery.

PubMed

Cirpanli, Yasemin; Bilensoy, Erem; Lale Doğan, A; Caliş, Sema

2009-09-01

Camptothecin (CPT) is a potent anticancer agent. The clinical application of CPT is restricted by poor water solubility and instability under physiological conditions. Solubilization and stabilization of CPT were realized through nanoparticulate systems of amphiphilic cyclodextrins, poly(lactide-co-glycolide) (PLGA) or poly-epsilon-caprolactone (PCL). Nanoparticles were prepared with nanoprecipitation technique, whereas cyclodextrin nanoparticles were prepared from preformed inclusion complexes of CPT with amphiphilic cyclodextrins. Polymeric nanoparticles, on the other hand, were loaded with CPT:HP-beta-CD inclusion complex to solubilize and stabilize the drug. Mean particle sizes were under 275 nm, and polydispersity indices were lower than 0.2 for all formulations. Drug-loading values were significantly higher for amphiphilic cyclodextrin nanoparticles when compared with those for PLGA and PCL nanoparticles. Nanoparticle formulations showed a significant controlled release profile extended up to 12 days for amphiphilic cyclodextrin nanoparticles and 48h for polymeric nanoparticles. Anticancer efficacy of the nanoparticles was evaluated in comparison with CPT solution in dimethyl sulfoxide (DMSO) on MCF-7 breast adenocarcinoma cells. Amphiphilic cyclodextrin nanoparticles showed higher anticancer efficacy than PLGA or PCL nanoparticles loaded with CPT and the CPT solution in DMSO. These results indicated that CPT-loaded amphiphilic cyclodextrin nanoparticles might provide a promising carrier system for the effective delivery of this anticancer drug having bioavailability problems.

Viscosity of the oil-in-water Pickering emulsion stabilized by surfactant-polymer and nanoparticle-surfactant-polymer system

NASA Astrophysics Data System (ADS)

Sharma, Tushar; Kumar, G. Suresh; Chon, Bo Hyun; Sangwai, Jitendra S.

2014-11-01

Information on the viscosity of Pickering emulsion is required for their successful application in upstream oil and gas industry to understand their stability at extreme environment. In this work, a novel formulation of oil-in-water (o/w) Pickering emulsion stabilized using nanoparticle-surfactant-polymer (polyacrylamide) system as formulated in our earlier work (Sharma et al., Journal of Industrial and Engineering Chemistry, 2014) is investigated for rheological stability at high pressure and high temperature (HPHT) conditions using a controlled-strain rheometer. The nanoparticle (SiO2 and clay) concentration is varied from 1.0 to 5.0 wt%. The results are compared with the rheological behavior of simple o/w emulsion stabilized by surfactant-polymer system. Both the emulsions exhibit non-Newtonian shear thinning behavior. A positive shift in this behavior is observed for surfactant-polymer stabilized emulsion at high pressure conditions. Yield stress is observed to increase with pressure for surfactant-polymer emulsion. In addition, increase in temperature has an adverse effect on the viscosity of emulsion stabilized by surfactant-polymer system. In case of nanoparticle-surfactant-polymer stabilized o/w emulsion system, the viscosity and yield stress are predominantly constant for varying pressure and temperature conditions. The viscosity data for both o/w emulsion systems are fitted by the Herschel-Bulkley model and found to be satisfactory. In general, the study indicates that the Pickering emulsion stabilized by nanoparticle-surfactant-polymer system shows improved and stable rheological properties as compared to conventional emulsion stabilized by surfactant-polymer system indicating their successful application for HPHT environment in upstream oil and gas industry.

Fetuin-A/Albumin-Mineral Complexes Resembling Serum Calcium Granules and Putative Nanobacteria: Demonstration of a Dual Inhibition-Seeding Concept

PubMed Central

Young, David; Young, John D.

2009-01-01

Serum-derived granulations and purported nanobacteria (NB) are pleomorphic apatite structures shown to resemble calcium granules widely distributed in nature. They appear to be assembled through a dual inhibitory-seeding mechanism involving proteinaceous factors, as determined by protease (trypsin and chymotrypsin) and heat inactivation studies. When inoculated into cell culture medium, the purified proteins fetuin-A and albumin fail to induce mineralization, but they will readily combine with exogenously added calcium and phosphate, even in submillimolar amounts, to form complexes that will undergo morphological transitions from nanoparticles to spindles, films, and aggregates. As a mineralization inhibitor, fetuin-A is much more potent than albumin, and it will only seed particles at higher mineral-to-protein concentrations. Both proteins display a bell-shaped, dose-dependent relationship, indicative of the same dual inhibitory-seeding mechanism seen with whole serum. As ascertained by both seeding experiments and gel electrophoresis, fetuin-A is not only more dominant but it appears to compete avidly for nanoparticle binding at the expense of albumin. The nanoparticles formed in the presence of fetuin-A are smaller than their albumin counterparts, and they have a greater tendency to display a multi-layered ring morphology. In comparison, the particles seeded by albumin appear mostly incomplete, with single walls. Chemically, spectroscopically, and morphologically, the protein-mineral particles resemble closely serum granules and NB. These particles are thus seen to undergo an amorphous to crystalline transformation, the kinetics and completeness of which depend on the protein-to-mineral ratios, with low ratios favoring faster conversion to crystals. Our results point to a dual inhibitory-seeding, de-repression model for the assembly of particles in supersaturated solutions like serum. The presence of proteins and other inhibitory factors tend to block apatite nuclei formation or to stabilize the nascent nuclei as amorphous or semi-crystalline spherical nanoparticles, until the same inhibitory influences are overwhelmed or de-repressed, whereby the apatite nuclei grow in size to coalesce into crystalline spindles and films—a mechanism that may explain not only the formation of calcium granules in nature but also normal or ectopic calcification in the body. PMID:19956594

Enzymatic degradation of poly(L-lactide) nanoparticles followed by the release of octenidine and their bactericidal effects.

PubMed

Baier, Grit; Cavallaro, Alex; Friedemann, Kathrin; Müller, Beate; Glasser, Gunnar; Vasilev, Krasimir; Landfester, Katharina

2014-01-01

The enzyme-triggered release of the antimicrobial agent octenidine out of poly(l-lactide)-based nanoparticles (PLLA-NPs) and their in vitro antibacterial activities in the presence of gram-positive and gram-negative bacteria are presented. The formation of the nanoparticles was achieved using a combination of the solvent evaporation and the miniemulsion approach. For the stabilization of the polymeric nanoparticles, non-ionic polymers (polyvinylalcohol [PVA], hydroxyethyl starch [HES], human serum albumin [HSA]) were successfully used for enzymatic degradation; ionic surfactants such as sodium dodecyl sulfate and cetyltrimethylammonium chloride inhibited the enzymatic degradation. The change in pH, size, size distribution and morphology during the degradation process of PLLA-NPs and the release of the antimicrobial agent was studied. The influence of the different amounts of octenidine and of the different stabilizers on the NPs' stability, size, size distribution, morphology, zeta potential and on the surface group's density is discussed. Fluorescently labeled HES-stabilized PLLA-NPs are immobilized by colloidal electrospinning. The observed data from HPLC measurements show that octenidine is released out of PLLA-NPs which are stabilized with PVA, HES or HSA. In bacteria tests the PLLA nanoparticles showed a greater ability to inhibit the growth of Staphylococcus aureus compared to Escherichia coli. This article discusses the enzyme-triggered release and antibacterial effects of octenidine from poly(l-lactide)-based nanoparticles demonstrating the viability of this approach for potential future antibacterial therapy. © 2013.

Development of wheat glutenin nanoparticles and their biodistribution in mice.

PubMed

Reddy, Narendra; Shi, Zhen; Xu, Helan; Yang, Yiqi

2015-05-01

Wheat glutenin nanoparticles intended for targeted drug delivery were biocompatible and were detected in the kidney, liver, and spleen in mice. Protein-based nanoparticles are preferred for therapeutic drug and gene delivery owing to their biocompatibility and ability to load various types of drugs. However, proteins such as a collagen and albumin are unstable in aqueous environments and are not ideal for drug delivery applications. Wheat glutenin has been demonstrated to be biocompatible and have good stability under aqueous conditions. Films and fibers have been made from wheat glutenin for medical applications but there are no reports on developing micro- or nanoparticles. In this research, wheat glutenin nanoparticles (70-140 nm) were prepared and the stability of the nanoparticles under various physiological conditions was investigated. Nanoparticles were fluorescently labeled and later injected into mice and the ability of the nanoparticles to penetrate into the cells in various organs was studied. Strong acidic or alkaline conditions provided glutenin nanoparticles with low diameters and the particles were more stable under the pH 7 rather than pH of 4. Glutenin nanoparticles were predominantly found in the liver in mice. Our in vivo and in vitro studies suggest that glutenin nanoparticles are suitable for drug delivery applications. © 2014 Wiley Periodicals, Inc.

Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis.

PubMed

Guo, Ling; Luo, Shi; Du, Zhengwu; Zhou, Meiling; Li, Peiwen; Fu, Yao; Sun, Xun; Huang, Yuan; Zhang, Zhirong

2017-10-12

Mesangial cells-mediated glomerulonephritis is a frequent cause of end-stage renal disease. Here, we show that celastrol is effective in treating both reversible and irreversible mesangioproliferative glomerulonephritis in rat models, but find that its off-target distributions cause severe systemic toxicity. We thus target celastrol to mesangial cells using albumin nanoparticles. Celastrol-albumin nanoparticles crosses fenestrated endothelium and accumulates in mesangial cells, alleviating proteinuria, inflammation, glomerular hypercellularity, and excessive extracellular matrix deposition in rat anti-Thy1.1 nephritis models. Celastrol-albumin nanoparticles presents lower drug accumulation than free celastrol in off-target organs and tissues, thereby minimizing celastrol-related systemic toxicity. Celastrol-albumin nanoparticles thus represents a promising treatment option for mesangioproliferative glomerulonephritis and similar glomerular diseases.Mesangial cell-mediated glomerulonephritis is a frequent cause of kidney disease. Here the authors show that celastrol loaded in albumin nanoparticles efficiently targets mesangial cells, and is effective in rat models.

Allosteric effects of gold nanoparticles on human serum albumin.

PubMed

Shao, Qing; Hall, Carol K

2017-01-07

The ability of nanoparticles to alter protein structure and dynamics plays an important role in their medical and biological applications. We investigate allosteric effects of gold nanoparticles on human serum albumin protein using molecular simulations. The extent to which bound nanoparticles influence the structure and dynamics of residues distant from the binding site is analyzed. The root mean square deviation, root mean square fluctuation and variation in the secondary structure of individual residues on a human serum albumin protein are calculated for four protein-gold nanoparticle binding complexes. The complexes are identified in a brute-force search process using an implicit-solvent coarse-grained model for proteins and nanoparticles. They are then converted to atomic resolution and their structural and dynamic properties are investigated using explicit-solvent atomistic molecular dynamics simulations. The results show that even though the albumin protein remains in a folded structure, the presence of a gold nanoparticle can cause more than 50% of the residues to decrease their flexibility significantly, and approximately 10% of the residues to change their secondary structure. These affected residues are distributed on the whole protein, even on regions that are distant from the nanoparticle. We analyze the changes in structure and flexibility of amino acid residues on a variety of binding sites on albumin and confirm that nanoparticles could allosterically affect the ability of albumin to bind fatty acids, thyroxin and metals. Our simulations suggest that allosteric effects must be considered when designing and deploying nanoparticles in medical and biological applications that depend on protein-nanoparticle interactions.

Novel formulations of taxanes: a review. Old wine in a new bottle?

PubMed

Hennenfent, K L; Govindan, R

2006-05-01

Over the past two decades, the taxanes have played a significant role in the treatment of various malignancies. However, the poor solubility of these compounds necessitates the inclusion of surfactant vehicles in their commercial formulations. Cremophor EL and polysorbate 80 have long comprised the standard solvent system for paclitaxel and docetaxel, respectively. A number of pharmacologic and biologic effects related to both of these drug formulations have been described, including clinically relevant acute hypersensitivity reactions and peripheral neuropathy. In addition, these solvents affect the disposition of intravenously administered solubilized drugs and leach plasticizers from polyvinylchloride infusion sets. A number of strategies to develop formulations of surfactant-free taxanes have been developed. They include albumin nanoparticles, polyglutamates, taxane analogs and prodrugs, emulsions, and lipsomes. An overview of these novel formulations of taxanes, their mechanisms of action, pharmacokinetics, dose and administration, adverse effects, and clinical efficacy will be discussed.

Computer Optimization of Biodegradable Nanoparticles Fabricated by Dispersion Polymerization.

PubMed

Akala, Emmanuel O; Adesina, Simeon; Ogunwuyi, Oluwaseun

2015-12-22

Quality by design (QbD) in the pharmaceutical industry involves designing and developing drug formulations and manufacturing processes which ensure predefined drug product specifications. QbD helps to understand how process and formulation variables affect product characteristics and subsequent optimization of these variables vis-à-vis final specifications. Statistical design of experiments (DoE) identifies important parameters in a pharmaceutical dosage form design followed by optimizing the parameters with respect to certain specifications. DoE establishes in mathematical form the relationships between critical process parameters together with critical material attributes and critical quality attributes. We focused on the fabrication of biodegradable nanoparticles by dispersion polymerization. Aided by a statistical software, d-optimal mixture design was used to vary the components (crosslinker, initiator, stabilizer, and macromonomers) to obtain twenty nanoparticle formulations (PLLA-based nanoparticles) and thirty formulations (poly-ɛ-caprolactone-based nanoparticles). Scheffe polynomial models were generated to predict particle size (nm), zeta potential, and yield (%) as functions of the composition of the formulations. Simultaneous optimizations were carried out on the response variables. Solutions were returned from simultaneous optimization of the response variables for component combinations to (1) minimize nanoparticle size; (2) maximize the surface negative zeta potential; and (3) maximize percent yield to make the nanoparticle fabrication an economic proposition.

Preparation and evaluation of BSA-based hydrosol nanoparticles cross-linked with genipin for oral administration of poorly water-soluble curcumin.

PubMed

Shahgholian, Narges; Rajabzadeh, Ghadir; Malaekeh-Nikouei, Bizhan

2017-11-01

One of the most interesting functions of albumin is the ability to interact with bioactive compounds. This study describes preparation of protein-based nanoparticles (NPs) for the preparation of solid dispersion of curcumin (CN). Fabrication of hydrosol system of dispersed CN in bovine serum albumin (BSA) was approached, followed by cross-linking with glutaraldehyde (Gta). Response surface methodology (RSM) was used to investigate the influence of input factors (pH, CN content and organic phase ratio (r)), on the particle size and CN entrapment efficiency (EE). Particle size, EE and CN loading efficiency (LE) at optimum condition (pH 7, r 10% and 3.4mg of CN content), were found to be in the range of 153-184.4nm, 72.54%, and 14.508μg/mg, respectively. In the optimum formulation, genipin (Gnp) was used at three different levels (0.1-0.2 and 0.3% w/w of BSA), as a safe, natural cross-linker instead of toxic Gta, to address the limitation of oral delivery purpose. AFM and SEM analysis revealed the spherical and smooth surface of Nps. Ninhydrin (NHD) assay and FT-IR analysis confirmed the cross-linking between BSA and Gnp. In vitro release studies ensure the efficiency of the formulation for sustained release of soluble CN. Copyright © 2017 Elsevier B.V. All rights reserved.

Antimicrobial and cell viability measurement of bovine serum albumin capped silver nanoparticles (Ag/BSA) loaded collagen immobilized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film.

PubMed

Bakare, Rotimi; Hawthrone, Samantha; Vails, Carmen; Gugssa, Ayele; Karim, Alamgir; Stubbs, John; Raghavan, Dharmaraj

2016-03-01

Bacterial infection of orthopedic devices has been a major concern in joint replacement procedures. Therefore, this study is aimed at formulating collagen immobilized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film loaded with bovine serum albumin capped silver nanoparticles (Ag/BSA NPs) to inhibit bacterial growth while retaining/promoting osteoblast cells viability. The nanoparticles loaded collagen immobilized PHBV film was characterized for its composition by X-ray Photoelectron Spectroscopy and Anodic Stripping Voltammetry. The extent of loading of Ag/BSA NPs on collagen immobilized PHBV film was found to depend on the chemistry of the functionalized PHBV film and the concentration of Ag/BSA NPs solution used for loading nanoparticles. Our results showed that more Ag/BSA NPs were loaded on higher molecular weight collagen immobilized PHEMA-g-PHBV film. Maximum loading of Ag/BSA NPs on collagen immobilized PHBV film was observed when 16ppm solution was used for adsorption studies. Colony forming unit and optical density measurements showed broad antimicrobial activity towards Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa at significantly lower concentration i.e., 0.19 and 0.31μg/disc, compared to gentamicin and sulfamethoxazole trimethoprim while MTT assay showed that released nanoparticles from Ag/BSA NPs loaded collagen immobilized PHBV film has no impact on MCTC3-E1 cells viability. Copyright © 2015 Elsevier Inc. All rights reserved.

Fabrication of coated bovine serum albumin (BSA)-epigallocatechin gallate (EGCG) nanoparticles and their transport across monolayers of human intestinal epithelial Caco-2 cells.

PubMed

Li, Zheng; Ha, Jungheun; Zou, Tao; Gu, Liwei

2014-06-01

The bovine serum albumin (BSA)-epigallocatechin gallate (EGCG) nanoparticles were fabricated using a desolvation method, and coated with poly-ε-lysine or chitosan. BSA-EGCG nanoparticles (BEN), poly-ε-lysine coated BSA-EGCG nanoparticles (PBEN), and chitosan coated BSA-EGCG nanoparticles (CBEN) had a spherical morphology and a size of 186, 259, and 300 nm, respectively. The loading efficiency of EGCG in these nanoparticles was 32.3%, 35.4%, and 32.7%, whereas the loading capacity was 18.9%, 17.0%, and 16.0% (w/w), respectively. Poly-ε-lysine or chitosan coating prevented the aggregation of nanoparticles at pH 4.5-5.0. However, they caused particle aggregation at pH 6.5-7.0. BEN had negative zeta-potentials between pH 4.5 and 6.0. Poly-ε-lysine or chitosan coating changed the zeta-potentials to positive. The release study of EGCG from the nanoparticles in the simulated gastric or intestinal fluid with or without digestive enzymes showed that poly-ε-lysine and chitosan coatings delayed EGCG release from the nanoparticles. Poly-ε-lysine or chitosan coating improved the stability of EGCG during storage at 60 °C compared with EGCG in the uncoated particles. EGCG in BEN, PBEN, and CBEN had a decreasing apparent permeability coefficient (Papp) on Caco-2 monolayers, whereas pure EGCG showed relatively stable Papp during the incubation over time. EGCG in CBEN showed significantly higher Papp, suggesting that chitosan coated BSA-EGCG nanoparticles may improve the absorption of EGCG.

Green synthesis of biogenic silver nanoparticles using Solanum tuberosum extract and their interaction with human serum albumin: Evidence of "corona" formation through a multi-spectroscopic and molecular docking analysis.

PubMed

Ali, Mohd Sajid; Altaf, Mohammad; Al-Lohedan, Hamad A

2017-08-01

Biogenic silver nanoparticles (AgNPs) have been synthesized by using Solanum tuberosum (potato) extract (PE) as a reducing as well as stabilizing agent which is reasonably cheaper, non-toxic and easily available material. The green synthesis of silver nanoparticles has been carried out by very simple method and the nanoparticles were characterized by surface plasmon band as well as TEM measurements. The PE-AgNPs were highly dispersed in the solution and found to be spherical with around 10nm in size. Interaction of these nanoparticles was studied with plasma protein HSA by means of various spectroscopies, such as, UV-visible, fluorescence, DLS, CD and FTIR spectroscopies. The HSA was found to form the protein "corona" around the starch-capped PE-AgNPs. Absorption spectroscopy revealed that the interaction between HSA and PE-AgNPs resulted in the ground state complex formation. Due to the strong absorption of PE-AgNPs, the inner filter effect was corrected for the fluorescence data. PE-AgNPs were found to quench the fluorescence of HSA with a small blue shift attributed to the increase in the hydrophobicity near tryptophan residue due to the presence of amylopectin and amylose units in the starch. The value of n, Hill's constant, was found to be >1 which determines the existence of a cooperative binding between nanoparticle and albumin. Several parameters such as Stern-Volmer and binding constants in addition to the thermodynamic parameters have been analyzed and discussed which established that the complex formation has taken place via static quenching mechanism and the corona formation between albumin and PE-AgNPs was entropy driven process. Binding of biogenic PE-AgNPs to the HSA slightly affected the secondary structure of latter with a small decrease in α-helical contents resulting in the partial unfolding of the protein, though the structural motif remained the same. Molecular docking simulations revealed various possible binding modes between PE-AgNPs and albumin. Copyright © 2017 Elsevier B.V. All rights reserved.

Protein coated gold nanoparticles as template for the directed synthesis of highly fluorescent gold nanoclusters

NASA Astrophysics Data System (ADS)

Zhang, Lingyan; Han, Fei

2018-04-01

Bovine serum albumin (BSA) modified gold nanoparticles (AuNPs) was selected as template for the synthesis of AuNPs@gold nanoclusters (AuNCs) core/shell nanoparticles, in which BSA not only acted as dual functions agent for both anchoring and reducing Au3+ ions, but also was employed as a bridge between the AuNPs and AuNCs. Optical properties of AuNPs@AuNCs core/shell nanoparticles were studied using UV-visible and fluorescence spectroscopy. The prepared AuNPs@AuNCs core/shell nanoparticles exhibited sphere size uniformity with improved monodispersity, excellent fluorescence and fluorescent stability. Compared with AuNCs, AuNPs@AuNCs core/shell nanoparticles possessed large size and strong fluorescence intensity due to the effect of AuNPs as core. Moreover, the mechanism of the AuNPs induced fluorescence changes of the core/shell nanoparticles was first explored.

Influence of freeze-drying and γ-irradiation in preclinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using d-(+)-trehalose and polyethylene glycol

PubMed Central

Ramos Yacasi, Gladys Rosario; García López, María Luisa; Espina García, Marta; Parra Coca, Alexander; Calpena Campmany, Ana Cristina

2016-01-01

This study investigated the suspension of poly(ε-caprolactone) nanoparticles as an ocular delivery system for flurbiprofen (FB-PεCL-NPs) in order to overcome the associated problems, such as stability, sterility, tolerance, and efficacy, with two different FB-PεCL-NP formulations. The formulations were stabilized with poloxamer 188 (1.66% and 3.5%) and submitted individually for freeze-drying and γ-irradiation with polyethylene glycol 3350 (PEG3350) and d-(+)-trehalose (TRE). Both formulations satisfied criteria according to all physicochemical parameters required for ocular pharmaceuticals. The FB-PεCL-NP formulations showed non-Newtonian behavior and sustained drug release. Ex vivo permeation analysis using isolated ocular pig tissues suggested that the presence of PEG3350 results in a reduction of FB transcorneal permeation. Moreover, TRE improved the penetration of FB across the cornea, especially after γ-irradiation. In addition, both formulations did not show a significant affinity in increasing FB transscleral permeation. Both formulations were classified as nonirritating, safe products for ophthalmic administration according to hen’s egg test-chorioallantoic membrane and Draize eye test. Furthermore, an in vivo anti-inflammatory efficacy test showed that irradiated FB-PεCL-NPs prepared with PEG3350 (IR-NPsPEG) have longer anti-inflammatory effects than those presented with irradiated FB-PεCL-NPs prepared with TRE (IR-NPsTRE). IR-NPsPEG showed a suitable physical stability after an aqueous reconstitution over >30 days. This study concludes that both formulations meet the Goldman’s criteria and demonstrate how irradiated nanoparticles, with innovative permeation characteristics, could be used as a feasible alternative to a flurbiprofen solution for ocular application in clinical trials. PMID:27601897

Influence of freeze-drying and γ-irradiation in preclinical studies of flurbiprofen polymeric nanoparticles for ocular delivery using d-(+)-trehalose and polyethylene glycol.

PubMed

Ramos Yacasi, Gladys Rosario; García López, María Luisa; Espina García, Marta; Parra Coca, Alexander; Calpena Campmany, Ana Cristina

This study investigated the suspension of poly(ε-caprolactone) nanoparticles as an ocular delivery system for flurbiprofen (FB-PεCL-NPs) in order to overcome the associated problems, such as stability, sterility, tolerance, and efficacy, with two different FB-PεCL-NP formulations. The formulations were stabilized with poloxamer 188 (1.66% and 3.5%) and submitted individually for freeze-drying and γ-irradiation with polyethylene glycol 3350 (PEG3350) and d-(+)-trehalose (TRE). Both formulations satisfied criteria according to all physicochemical parameters required for ocular pharmaceuticals. The FB-PεCL-NP formulations showed non-Newtonian behavior and sustained drug release. Ex vivo permeation analysis using isolated ocular pig tissues suggested that the presence of PEG3350 results in a reduction of FB transcorneal permeation. Moreover, TRE improved the penetration of FB across the cornea, especially after γ-irradiation. In addition, both formulations did not show a significant affinity in increasing FB transscleral permeation. Both formulations were classified as nonirritating, safe products for ophthalmic administration according to hen's egg test-chorioallantoic membrane and Draize eye test. Furthermore, an in vivo anti-inflammatory efficacy test showed that irradiated FB-PεCL-NPs prepared with PEG3350 (IR-NPsPEG) have longer anti-inflammatory effects than those presented with irradiated FB-PεCL-NPs prepared with TRE (IR-NPsTRE). IR-NPsPEG showed a suitable physical stability after an aqueous reconstitution over >30 days. This study concludes that both formulations meet the Goldman's criteria and demonstrate how irradiated nanoparticles, with innovative permeation characteristics, could be used as a feasible alternative to a flurbiprofen solution for ocular application in clinical trials.

Ligand Assisted Stabilization of Fluorescence Nanoparticles; an Insight on the Fluorescence Characteristics, Dispersion Stability and DNA Loading Efficiency of Nanoparticles.

PubMed

Rhouati, Amina; Hayat, Akhtar; Mishra, Rupesh K; Bueno, Diana; Shahid, Shakir Ahmad; Muñoz, Roberto; Marty, Jean Louis

2016-07-01

This work reports on the ligand assisted stabilization of Fluospheres® carboxylate modified nanoparticles (FCMNPs), and subsequently investigation on the DNA loading capacity and fluorescence response of the modified particles. The designed fluorescence bioconjugate was characterized with enhanced fluorescence characteristics, good stability and large surface area with high DNA loading efficiency. For comparison purpose, bovine serum albumin (BSA) and polyethylene glycol (PEG) with three different length strands were used as cross linkers to modify the particles, and their DNA loading capacity and fluorescence characteristics were investigated. By comparing the performance of the particles, we found that the most improved fluorescence characteristics, enhanced DNA loading and high dispersion stability were obtained, when employing PEG of long spacer arm length. The designed fluorescence bioconjugate was observed to maintain all its characteristics under varying pH over an extended period of time. These types of bioconjugates are in great demand for fluorescence imaging and in vivo fluorescence biomedical application, especially when most of the as synthesized fluorescence particles cannot withstand to varying in vivo physiological conditions with decreases in fluorescence response and DNA loading efficiency.

Influence of formulation and processing variables on properties of itraconazole nanoparticles made by advanced evaporative precipitation into aqueous solution.

PubMed

Bosselmann, Stephanie; Nagao, Masao; Chow, Keat T; Williams, Robert O

2012-09-01

Nanoparticles, of the poorly water-soluble drug, itraconazole (ITZ), were produced by the Advanced Evaporative Precipitation into Aqueous Solution process (Advanced EPAS). This process combines emulsion templating and EPAS processing to provide improved control over the size distribution of precipitated particles. Specifically, oil-in-water emulsions containing the drug and suitable stabilizers are sprayed into a heated aqueous solution to induce precipitation of the drug in form of nanoparticles. The influence of processing parameters (temperature and volume of the heated aqueous solution; type of nozzle) and formulation aspects (stabilizer concentrations; total solid concentrations) on the size of suspended ITZ particles, as determined by laser diffraction, was investigated. Furthermore, freeze-dried ITZ nanoparticles were evaluated regarding their morphology, crystallinity, redispersibility, and dissolution behavior. Results indicate that a robust precipitation process was developed such that size distribution of dispersed nanoparticles was shown to be largely independent across the different processing and formulation parameters. Freeze-drying of colloidal dispersions resulted in micron-sized agglomerates composed of spherical, sub-300-nm particles characterized by reduced crystallinity and high ITZ potencies of up to 94% (w/w). The use of sucrose prevented particle agglomeration and resulted in powders that were readily reconstituted and reached high and sustained supersaturation levels upon dissolution in aqueous media.

Evaluation of Organogel Nanoparticles as Drug Delivery System for Lipophilic Compounds.

PubMed

Martin, Baptiste; Brouillet, Fabien; Franceschi, Sophie; Perez, Emile

2017-05-01

The purpose of the study was to evaluate organogel nanoparticles as a drug delivery system by investigating their stability, according to the formulation strategy, and their release profile. The gelled nanoparticles were prepared by hot emulsification (above the gelation temperature) of an organogel in water, and cooling at room temperature. In the first step, we used DLS and DSC to select the most suitable formulations by optimizing the proportion of ingredients (HSA, PVA, castor oil) to obtain particles of the smallest size and greatest stability. Then, two lipophilic drug models, indomethacin and ketoconazole were entrapped in the nanoparticles made of castor oil gelled by 12-hydroxystearic acid. Thermal studies (DSC) confirmed that there was no significant alteration of gelling due to the entrapped drugs, even at 3% w/w. Very stable dispersions were obtained (>3 months), with gelled oil nanoparticles presenting a mean diameter between 250 and 300 nm. High encapsulation efficiency (>98%) was measured for indomethacin and ketoconazole. The release profile determined by in vitro dialysis showed an immediate release of the drug from the organogel nanoparticles, due to rapid diffusion. The study demonstrates the interest of these gelled oil nanoparticles for the encapsulation and the delivery of lipophilic active compounds.

Rheology and stability kinetics of bare silicon nanoparticle inks for low-cost direct printing

DOE Office of Scientific and Technical Information (OSTI.GOV)

More, Priyesh V.; Jeong, Sunho; Seo, Yeong-Hui

2013-12-16

Highly dispersed and stable silicon nanoparticles ink is formulated for its application in direct printing or printable electronics. These dispersions are prepared from free-standing silicon nanoparticles which are not capped with any organic ligand, making it suitable for electronic applications. Silicon nanoparticles dispersions are prepared by suspending the nanoparticles in benzonitrile or ethanol by using polypropylene glycol (PPG) as a binder. All the samples show typical shear thinning behavior while the dispersion samples show low viscosities signifying good quality dispersion. Such thinning behavior favors in fabrication of dense films with spin-coating or patterns with drop casting. The dispersion stability ismore » monitored by turbiscan measurements showing good stability for one week. A low-cost direct printing method for dispersion samples is also demonstrated to obtain micro-sized patterns. Low electrical resistivity of resulting patterns, adjustable viscosity and good stability makes these silicon nanoparticles dispersions highly applicable for direct printing process.« less

Cabazitaxel-loaded human serum albumin nanoparticles as a therapeutic agent against prostate cancer

PubMed Central

Qu, Na; Lee, Robert J; Sun, Yating; Cai, Guangsheng; Wang, Junyang; Wang, Mengqiao; Lu, Jiahui; Meng, Qingfan; Teng, Lirong; Wang, Di; Teng, Lesheng

2016-01-01

Cabazitaxel-loaded human serum albumin nanoparticles (Cbz-NPs) were synthesized to overcome vehicle-related toxicity of current clinical formulation of the drug based on Tween-80 (Cbz-Tween). A salting-out method was used for NP synthesis that avoids the use of chlorinated organic solvent and is simpler compared to the methods based on emulsion-solvent evaporation. Cbz-NPs had a narrow particle size distribution, suitable drug loading content (4.9%), and superior blood biocompatibility based on in vitro hemolysis assay. Blood circulation, tumor uptake, and antitumor activity of Cbz-NPs were assessed in prostatic cancer xenograft-bearing nude mice. Cbz-NPs exhibited prolonged blood circulation and greater accumulation of Cbz in tumors along with reduced toxicity compared to Cbz-Tween. Moreover, hematoxylin and eosin histopathological staining of organs revealed consistent results. The levels of blood urea nitrogen and serum creatinine in drug-treated mice showed that Cbz-NPs were less toxic than Cbz-Tween to the kidneys. In conclusion, Cbz-NPs provide a promising therapeutic for prostate cancer. PMID:27555767

Stabilizers influence drug–polymer interactions and physicochemical properties of disulfiram-loaded poly-lactide-co-glycolide nanoparticles

PubMed Central

Hoda, Muddasarul; Sufi, Shamim Akhtar; Cavuturu, Bindumadhuri; Rajagopalan, Rukkumani

2018-01-01

Aim: Stabilizers are known to be an integral component of polymeric nanostructures. Ideally, they manipulate physicochemical properties of nanoparticles. Based on this hypothesis, we demonstrated that disulfiram (drug) and Poly-lactide-co-glycolide (polymer) interactions and physicochemical properties of their nanoparticles formulations are significantly influenced by the choice of stabilizers. Methodology: Electron microscopy, differential scanning calorimetry, x-ray diffraction, Raman spectrum analysis, isothermal titration calorimetry and in silico docking studies were performed. Results & discussion: Polysorbate 80 imparted highest crystallinity while Triton-X 100 imparted highest rigidity, possibly influencing drug bioavailability, blood-retention time, cellular uptake and sustained drug release. All the molecular interactions were hydrophobic in nature and entropy driven. Therefore, polymeric nanoparticles may be critically manipulated to streamline the passive targeting of drug-loaded nanoparticles. PMID:29379637

Green synthesis and characterization of alginate nanoparticles and its role as a biosorbent for Cr(VI) ions

NASA Astrophysics Data System (ADS)

Geetha, P.; Latha, M. S.; Pillai, Saumya S.; Deepa, B.; Santhosh Kumar, K.; Koshy, Mathew

2016-02-01

Green synthesis of nanoparticles has attained considerable attention in recent years because of its myriad of applications including drug delivery, tissue engineering and water purification. In the present study, alginate nanoparticles stabilized by honey were prepared by cross-linking aqueous solution of alginate with calcium ions. Honey mediated synthesis has been reported earlier for the production of metal nanoparticles. However no literature is available on the use of this technique for polymeric nanoparticles. Highly stable nanoparticles of 10-100 nm size were generated by this technique. The synthesised nanoparticles were characterized by transmission electron microscopy, scanning electron microscopy, atomic force microscopy, dynamic light scattering and Fourier transform infrared spectroscopic techniques. Potential of using these nanoparticles for heavy metal removal was studied by using Cr(VI) from aqueous solution, where a maximum removal efficiency of 93.5% was obtained. This method was also successfully employed for the production of other polymeric nanoparticles like casein, chitosan and albumin.

Stability and Ocular Pharmacokinetics of Celecoxib-Loaded Nanoparticles Topical Ophthalmic Formulations.

PubMed

Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M

2016-12-01

A spontaneous emulsification and/or solvent diffusion method was used for the preparation of celecoxib-loaded nanoparticles (NPs) using polymers, including chitosan (CS), sodium alginate, poly-ε-caprolactone (PCL), poly-l-lactide, and poly-d,l-lactide-co-glycolide. NPs were incorporated into vehicles (eye drops, in situ gelling system, and gel). Formulations were subjected to an accelerated stability study by storing them at elevated temperatures of 30, 35, and 45°C for 6 months. Formulations were evaluated monthly for general appearance, pH, viscosity, particle size, polydispersity index, zeta potential, and drug content. Gels containing CS-NPs and PCL-NPs were selected for an ocular pharmacokinetics study using Sprague-Dawley rats due to their high stability and long shelf lives (24.56 and 33.76 months, respectively). The gel improved NP stability by keeping it inside its network structure, which protected them from aggregation and interacting with water. Our formulations improved celecoxib bioavailability due to their bioadhesivness, thus preventing their rapid removal. Also, NPs acted as drug reservoirs that adhered to eye surface and continuously released the drug. The availability of celecoxib in all eye tissues and its absence in plasma suggests that our formulation could be used for anterior eye disorders and also for treatment of diseases associated with the posterior eye with no systemic side effects. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Ultrasound-assisted interaction between chlorin-e6 and human serum albumin: pH dependence, singlet oxygen production, and formulation effect

NASA Astrophysics Data System (ADS)

Mocanu, Mihaela N.; Yan, Fei

2018-02-01

The interaction between chlorin e6 (Ce6) and human serum albumin (HSA) in the presence and absence of ultrasound have been investigated by ultraviolet-visible absorption spectroscopy and fluorescence spectroscopy. Ce6 is found to bind strongly to HSA at or near physiological pH conditions, but the strength of the binding is significantly weakened at lower pHs. The intrinsic fluorescence of HSA is incrementally quenched with increasing concentration of Ce6, and the quenching is enhanced after exposure to high-frequency ultrasound. Our experimental results suggest that Ce6-induced sonodynamic oxidation of HSA is mainly mediated by singlet oxygen. The formulation of Ce6 by high molecular weight polyvinylpyrrolidone (PVP) increased its stability in aqueous solutions and its quantum yield of singlet oxygen under ultrasound irradiation.

Facile one-pot formulation of TRAIL-embedded paclitaxel-bound albumin nanoparticles for the treatment of pancreatic cancer.

PubMed

Min, Sun Young; Byeon, Hyeong Jun; Lee, Changkyu; Seo, Jisoo; Lee, Eun Seong; Shin, Beom Soo; Choi, Han-Gon; Lee, Kang Choon; Youn, Yu Seok

2015-10-15

Nanoparticle albumin-bound (nab™) technology is an effective way of delivering hydrophobic chemotherapeutics. We developed a one-pot/one-step formulation of paclitaxel (PTX)-bound albumin nanoparticles with embedded tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/PTX HSA-NP) for the treatment of pancreatic cancer. TRAIL/PTX HSA-NPs were fabricated using a high-pressure homogenizer at a TRAIL feeding ratio of 0.2%, 1.0%, and 2.0%. TRAIL/PTX HSA-NPs were spherical and became larger in size (170-230 nm) with increasing TRAIL amount (0.2-2.0%). The loading efficiencies of PTX were in the range of ∼86.4% and significantly low at 2.0% TRAIL (60.4%). Specifically, the inhibitory concentrations (IC50) of TRAIL (1.0 or 2.0%)/PTX HSA-NPs were >20-fold lower than that of plain PTX-HSA NP (0.032±0.06, 0.022±0.005, and 0.96±0.15 ng/ml, respectively) in pancreatic Mia Paca-2 cells. Considering TRAIL loading, bioactivity, and particle size, TRAIL(1.0%)/PTX HSA-NPs were determined as the optimal candidate for further studies. TRAIL(1.0%)/PTX HSA-NPs displayed substantially greater apoptotic activity than plain PTX HSA-NP in both FACS and TUNEL analysis. The loaded PTX and TRAIL were gradually released from the TRAIL(1.0%)/PTX HSA-NPs until ∼24 h, which is considered to be a sufficient time for delivery to the tumor tissue. TRAIL(1.0%)/PTX HSA-NP displayed markedly more antitumor efficacy than plain PTX HSA-NP in Mia Paca-2 cell-xenografted mice in terms of tumor volume (size) and weight (213.9 mm(3) and 0.18 g vs. 1126.8 mm(3) and 0.80 g, respectively). These improved in vitro and in vivo performances were due to the combined synergistic effects of PTX and TRAIL. We believe that this TRAIL/PTX HSA-NP would have potential as a novel apoptosis-based anticancer agent. Copyright © 2015 Elsevier B.V. All rights reserved.

Nifedipine Nanoparticle Agglomeration as a Dry Powder Aerosol Formulation Strategy

PubMed Central

Plumley, Carl; Gorman, Eric M.; Munson, Eric J.; Berkland, Cory

2009-01-01

Efficient administration of drugs represents a leading challenge in pulmonary medicine. Dry powder aerosols are of great interest compared to traditional aerosolized liquid formulations in that they may offer improved stability, ease of administration, and simple device design. Particles 1–5 µm in size typically facilitate lung deposition. Nanoparticles may be exhaled as a result of their small size; however, they are desired to enhance the dissolution rate of poorly soluble drugs. Nanoparticles of the hypertension drug nifedipine were co-precipitated with stearic acid to form a colloid exhibiting negative surface charge. Nifedipine nanoparticle colloids were destabilized by using sodium chloride to disrupt the electrostatic repulsion between particles as a means to achieve the agglomerated nanoparticles of a controlled size. The aerodynamic performance of agglomerated nanoparticles was determined by cascade impaction. The powders were found to be well suited for pulmonary delivery. In addition, nanoparticle agglomerates revealed enhanced dissolution of the drug species suggesting the value of this formulation approach for poorly water soluble pulmonary medicines. Ultimately, nifedipine powders are envisioned as an approach to treat pulmonary hypertension. PMID:19015016

Nanomolar detection of glucose using SERS substrates fabricated with albumin coated gold nanoparticles

NASA Astrophysics Data System (ADS)

Perez-Mayen, Leonardo; Oliva, Jorge; Salas, P.; de La Rosa, Elder

2016-06-01

This work presents the design of substrates for Surface Enhanced Raman Scattering (SERS) using star-like gold nanoparticles synthesized by a wet chemical method. The SERS substrates were used for glucose detection for concentrations as low as 10-7 M, which represents an enhancement factor (EF) of 109, as a result of the hot spot formed by the spike termination and appropriate distribution of the gold nanoparticles. An improvement of two orders of magnitude was obtained by coating the gold nanoparticles with albumin with the configuration: glass/Au nanoparticles/albumin. In this case the lowest detection was at a concentration of 10-9 M for an EF of 1011. The albumin molecule allowed us to enhance the Raman signal because of the formation of peptide bonds (COOH-NH2) generated due to the interaction of glucose with albumin, and the appropriate separation distance between the glucose molecules and gold nanoparticles. The presence of such peptide conjugates was confirmed by FTIR spectra. Thus, our results suggest that our SERS substrates can be useful for the detection of very low concentrations of glucose, which is important for the diagnosis of diabetes in the field of medicine.This work presents the design of substrates for Surface Enhanced Raman Scattering (SERS) using star-like gold nanoparticles synthesized by a wet chemical method. The SERS substrates were used for glucose detection for concentrations as low as 10-7 M, which represents an enhancement factor (EF) of 109, as a result of the hot spot formed by the spike termination and appropriate distribution of the gold nanoparticles. An improvement of two orders of magnitude was obtained by coating the gold nanoparticles with albumin with the configuration: glass/Au nanoparticles/albumin. In this case the lowest detection was at a concentration of 10-9 M for an EF of 1011. The albumin molecule allowed us to enhance the Raman signal because of the formation of peptide bonds (COOH-NH2) generated due to the interaction of glucose with albumin, and the appropriate separation distance between the glucose molecules and gold nanoparticles. The presence of such peptide conjugates was confirmed by FTIR spectra. Thus, our results suggest that our SERS substrates can be useful for the detection of very low concentrations of glucose, which is important for the diagnosis of diabetes in the field of medicine. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00163g

Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

NASA Astrophysics Data System (ADS)

Yu, Zhan; Yu, Min; Zhang, Zhibao; Hong, Ge; Xiong, Qingqing

2014-07-01

Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders.

Zein Nanoparticles as Eco-Friendly Carrier Systems for Botanical Repellents Aiming Sustainable Agriculture.

PubMed

Oliveira, Jhones L de; Campos, Estefânia V R; Pereira, Anderson E S; Pasquoto, Tatiane; Lima, Renata; Grillo, Renato; Andrade, Daniel Junior de; Santos, Fabiano Aparecido Dos; Fraceto, Leonardo Fernandes

2018-02-14

Botanical repellents represent one of the main ways of reducing the use of synthetic pesticides and the contamination of soil and hydric resources. However, the poor stability and rapid degradation of these compounds in the environment hinder their effective application in the field. Zein nanoparticles can be used as eco-friendly carrier systems to protect these substances against premature degradation, provide desirable release characteristics, and reduce toxicity in the environment and to humans. In this study, we describe the preparation and characterization of zein nanoparticles loaded with the main constituents of the essential oil of citronella (geraniol and R-citronellal). The phytotoxicity, cytotoxicity, and insect activity of the nanoparticles toward target and nontarget organisms were also evaluated. The botanical formulations showed high encapsulation efficiency (>90%) in the nanoparticles, good physicochemical stability, and effective protection of the repellents against UV degradation. Cytotoxicity and phytotoxicity assays showed that encapsulation of the botanical repellents decreased their toxicity. Repellent activity tests showed that nanoparticles containing the botanical repellents were highly repellent against the Tetranychus urticae Koch mite. This nanotechnological formulation offers a new option for the effective use of botanical repellents in agriculture, reducing toxicity, protecting against premature degradation, and providing effective pest control.

Curcumin-incorporated albumin nanoparticles and its tumor image

NASA Astrophysics Data System (ADS)

Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

2015-01-01

Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

Curcumin-incorporated albumin nanoparticles and its tumor image.

PubMed

Gong, Guangming; Pan, Qinqin; Wang, Kaikai; Wu, Rongchun; Sun, Yong; Lu, Ying

2015-01-30

Albumin is an ideal carrier for hydrophobic drugs. This paper reports a facile route to develop human serum albumin (HSA)-curcumin (CCM) nanoparticles, in which β-mercaptoethanol (β-ME) acted as an inducer and CCM acted as a bridge. Fluorescence quenching and conformational changes in HSA-CCM nanoparticles occurred during assembly. Disulfide bonds and hydrophobic interactions may play a key role in assembly. HSA-CCM nanoparticles were about 130 nm in size, and the solubility of CCM increased by more than 500 times. The HSA-CCM nanoparticles could accumulate at the cytoplasm of tumor cells and target the tumor tissues. Therefore, HSA nanoparticles fabricated by β-ME denaturation are promising nanocarriers for hydrophobic substances from chemotherapy drugs to imaging probes.

Stability, Intracellular Delivery, and Release of siRNA from Chitosan Nanoparticles Using Different Cross-Linkers

PubMed Central

Abdul Ghafoor Raja, Maria; Katas, Haliza; Jing Wen, Thum

2015-01-01

Chitosan (CS) nanoparticles have been extensively studied for siRNA delivery; however, their stability and efficacy are highly dependent on the types of cross-linker used. To address this issue, three common cross-linkers; tripolyphosphate (TPP), dextran sulphate (DS) and poly-D-glutamic acid (PGA) were used to prepare siRNA loaded CS-TPP/DS/PGA nanoparticles by ionic gelation method. The resulting nanoparticles were compared with regard to their physicochemical properties including particle size, zeta potential, morphology, binding and encapsulation efficiencies. Among all the formulations prepared with different cross linkers, CS-TPP-siRNA had the smallest particle size (ranged from 127 ± 9.7 to 455 ± 12.9 nm) with zeta potential ranged from +25.1 ± 1.5 to +39.4 ± 0.5 mV, and high entrapment (>95%) and binding efficiencies. Similarly, CS-TPP nanoparticles showed better siRNA protection during storage at 4˚C and as determined by serum protection assay. TEM micrographs revealed the assorted morphology of CS-TPP-siRNA nanoparticles in contrast to irregular morphology displayed by CS-DS-siRNA and CS-PGA-siRNA nanoparticles. All siRNA loaded CS-TPP/DS/PGA nanoparticles showed initial burst release followed by sustained release of siRNA. Moreover, all the formulations showed low and concentration-dependent cytotoxicity with human colorectal cancer cells (DLD-1), in vitro. The cellular uptake studies with CS-TPP-siRNA nanoparticles showed successful delivery of siRNA within cytoplasm of DLD-1 cells. The results demonstrate that ionically cross-linked CS-TPP nanoparticles are biocompatible non-viral gene delivery system and generate a solid ground for further optimization studies, for example with regard to steric stabilization and targeting. PMID:26068222

Towards hybrid biocompatible magnetic rHuman serum albumin-based nanoparticles: use of ultra-small (CeLn)3/4+ cation-doped maghemite nanoparticles as functional shell

NASA Astrophysics Data System (ADS)

Israel, Liron L.; Kovalenko, Elena I.; Boyko, Anna A.; Sapozhnikov, Alexander M.; Rosenberger, Ina; Kreuter, Jörg; Passoni, Lorena; Lellouche, Jean-Paul

2015-01-01

Human serum albumin (HSA) is a protein found in human blood. Over the last decade, HSA has been evaluated as a promising drug carrier. However, not being magnetic, HSA cannot be used for biomedical applications such as magnetic resonance imaging (MRI) and magnetic drug targeting. Therefore, subsequent composites building on iron oxide nanoparticles that are already used clinically as MRI contrast agents are extensively studied. Recently and in this context, innovative fully hydrophilic ultra-small CAN-stabilized maghemite ((CeLn)3/4+-γ-Fe2O3) nanoparticles have been readily fabricated. The present study discusses the design, fabrication, and characterization of a dual phase hybrid core (rHSA)-shell ((CeLn)3/4+-γ-Fe2O3 NPs) nanosystem. Quite importantly and in contrast to widely used encapsulation strategies, rHSA NP surface-attached (CeLn)3/4+-γ-Fe2O3 NPs enabled to exploit both rHSA (protein functionalities) and (CeLn)3/4+-γ-Fe2O3 NP surface functionalities (COOH and ligand L coordinative exchange) in addition to very effective MRI contrast capability due to optimal accessibility of H2O molecules with the outer magnetic phase. Resulting hybrid nanoparticles might be used as a platform modular system for therapeutic (drug delivery system) and MR diagnostic purposes.

Gold Nanorod Mediated Mild Hyperthermia and PEGylated Human Serum Albumin Drug Delivery for Cancer Therapies

NASA Astrophysics Data System (ADS)

Mehtala, Jonathan G.

Photothermally active gold nanorods were used to sensitize cells to chemotherapeutic agents by producing mildly hyperthermic effects (42-43 °C). We examined the synergistic effects of GNR-mediated mild hyperthermia (MHT) on cisplatin (CP) activity against SKOV3 ovarian cancer cells. In vitro studies were performed using CP at cytostatic concentrations (5 μM) and mPEG-stabilized GNRs (lambdamax 815 nm) with near-infrared laser excitation for MHT (or external heating as a positive control), followed by 72 hours incubation at 37 °C. The amount of PEG-GNRs needed for GNR-mediated MHT was determined to be 1 μg/mL, several times lower than the loadings used in tumor tissue ablation. A cell viability assay indicated 80% enhancement in CP-mediated cytotoxicity 3 days after GNR-mediated MHT relative to the projected additive effect. A pilot in vivo study showed preliminary results that cisplatin chemotherapy can be developed in combination with low loadings of GNR-mediated MHT for localized MHT to treat tumors. Stable aqueous dispersions of citrate-stabilized gold nanorods were prepared in scalable fashion by surfactant exchange from cetyltrimethylammonium bromide (CTAB)-stabilized GNRs, using sodium polystyrenesulfonate (PSS) as a detergent. Nanoparticle tracking analysis (NTA) was used to measure the size of the Cit-GNR dispersions, which provides particle sizing resolution several times better than that of dynamic light scattering (DLS). Cit-GNRs were further functionalized with human serum albumin (HSA) and thiols and dithiocarbamates (DTCs) of varying molecular weights. The quality of the Cit-GNR dispersions allows us to address fundamental questions relating GNR stabilization to surface adsorption, including insights into the formation of the protein corona in serum-containing media. Mono-PEGylated human serum albumin was synthesized to investigate its ability to improve the bioavailability of the ability of paclitaxel (PTX), a poorly soluble drug. Matrix assisted laser desportion/ionization mass spectrometry was used to confirm the formation of the mono-PEGylated adduct, and HPLC analysis revealed that 70% of native HSA was converted to HSA-mPEG. A cell viability assay with MCF-7 breast cancer cells was used to measure the enhancement of the therapeutic efficacy of a PTX formulation with HSA, HSA-mPEG 5 kDa, or HSA-mPEG 20 kDa compared to PTX in PBS in the absence of HSA. We observed that the therapeutic efficacy of PTX was maximized when it was formulated in a 10:1 molar ratio with HSA, and for intermediate PTX doses (3.3 and 6.6 nM) the therapeutic efficacy of PTX with HSA-mPEG 20 kDa was greater than that for HSA-mPEG 5 kDa. These results suggest that PTX can bind to PEGylated HSA, and that most of the drug can be released.

Synthesis of berberine loaded polymeric nanoparticles by central composite design

NASA Astrophysics Data System (ADS)

Mehra, Meenakshi; Sheorain, Jyoti; Kumari, Santosh

2016-04-01

Berberine is an isoquinoline alkaloid which is extracted from bark and roots of Berberis vulgaris plant. It has been used in ayurvedic medicine as it possess antimicrobial, antidiabetic, anticancer, antioxidant properties etc. But poor solubility of berberine leads to poor stability and bioavailability in medical formulations decreasing its efficacy. Hence nanoformulations of berberine can help in removing the limiting factors of alkaloid enhancing its utilization in pharmaceutical industry. Sodium alginate polymer was used to encapsulate berberine within nanoparticles by emulsion solvent evaporation method using tween 80 as a surfactant. Two factors and three level in central composite design was used to study the formulation. The optimized formulation (1% v/v of Tween 80 and 0.01% w/v of sodium alginate) of polymeric nanoparticles was taken for further evaluations. The size of synthesized nanoparticles was found to be 71.18 nm by particle size analysis (PSA). The berberine loaded polymeric nanoparticles showed better antibacterial activity compared to aqueous solution of berberine by well diffusion assay.

Effect of polymer molecular weight on chitosan-protein interaction.

PubMed

Bekale, L; Agudelo, D; Tajmir-Riahi, H A

2015-01-01

We present a comprehensive study of the interactions between chitosan nanoparticles (15, 100 and 200 kDa with the same degree of deacetylation 90%) and two model proteins, i.e., bovine (BSA) and human serum albumins (HSA), with the aim of correlating chitosan molecular weight (Mw) and the binding affinity of these naturally occurring polymers to protein. The effect of chitosan on the protein secondary structure and the influence of protein complexation on the shape of chitosan nanoparticles are discussed. A combination of multiple spectroscopic methods, transmission electron microscopy (TEM) and thermodynamic analysis were used to assess the polymer-protein complex formation. Results revealed that the three chitosan nanoparticles interact with BSA to form chitosan-BSA complexes, mainly through hydrophobic contacts with the affinity order: 200>100>15 kDa. However, HSA-chitosan complexation is mainly via electrostatic interactions with the stability order: 100>200>15 kDa. Furthermore, the association between polymer and protein causes a partial protein conformational change by a major reduction of α-helix from 63% (free BSA) to 57% (chitosan-BSA) and 57% (free HSA) to 51% (chitosan-HSA). Finally, TEM micrographs clearly revealed that the binding of serum albumins with chitosan nanoparticles induces a significant change in protein morphology and the shape of the polymer. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of the thermal stability of a novel strain of live-attenuated mumps vaccine (RS-12 strain) lyophilized in different stabilizers.

PubMed

Jamil, Razieh Kamali; Taqavian, Mohammad; Sadigh, Zohreh-Azita; Shahkarami, Mohammad-Kazem; Esna-Ashari, Fatemeh; Hamkar, Rasool; Hosseini, Seyedeh-Marzieh; Hatami, Alireza

2014-04-01

The stability of live-attenuated viral vaccines is important for immunization efficacy. Here, the thermostabilities of lyophilized live-attenuated mumps vaccine formulations in two different stabilizers, a trehalose dihydrate-based stabilizer and a stabilizer containing sucrose, human serum albumin and sorbitol were investigated using accelerated stability tests at 4°C, 25°C and 37°C at time points between 4h (every 4h for the first 24h) and 1 week. Even under the harshest storage conditions of 37°C for 1 week, the 50% cell culture infective dose (CCID50) determined from titrations in Vero cells dropped by less than 10-fold using each stabilizer formulation and thus complied with the World Health Organization's requirements for the potency of live-attenuated mumps vaccines. However, as the half-life of the RS-12 strain mumps virus infectivity was lengthened substantially at elevated temperatures using the trehalose dihydrate (TD)-based stabilizer, this stabilizer is recommended for vaccine use. Copyright © 2013 Elsevier B.V. All rights reserved.

Prussian blue/serum albumin/indocyanine green as a multifunctional nanotheranostic agent for bimodal imaging guided laser mediated combinatorial phototherapy.

PubMed

Sahu, Abhishek; Lee, Jong Hyun; Lee, Hye Gyeong; Jeong, Yong Yeon; Tae, Giyoong

2016-08-28

Developing novel nanotheranostic agent using only clinically approved materials is highly desirable and challenging. In this study, we combined three clinically approved materials, Prussian blue (PB), serum albumin (BSA), and indocyanine green (ICG), by a simple and biocompatible method to prepare a multifunctional theranostic PB-BSA-ICG nanoparticle. The multifunctional nanoparticle system could provide dual mode magnetic resonance (MR) and near infrared (NIR) fluorescence imaging as well as combined photothermal and photodynamic (PTT-PDT) therapy in response to a single NIR laser. This nanoparticle showed an excellent stability in physiological solutions and could suppress the photo-instability of ICG. In the absence of light, the nanoparticles showed no cytotoxicity, but significant cell death was induced through combined PTT-PDT effect after irradiation with NIR laser light. A high tumor accumulation and minimal nonspecific uptake by other major organs of PB-BSA-ICG nanoparticle were observed in vivo, analyzed by T1-weighted MR and NIR fluorescence bimodal imaging in tumor xenograft mice after intravenous injection. The nanoparticles efficiently suppressed the tumor growth through combinatorial phototherapy with no tumor recurrence upon a single NIR laser irradiation. These results demonstrated that PB-BSA-ICG is potentially an interesting nanotheranostic agent for imaging guided cancer therapy by overcoming the limitations of each technology and enhancing the therapeutic efficiency as well as reducing side effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers

NASA Astrophysics Data System (ADS)

Subia, B.; Kundu, S. C.

2013-01-01

Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.

ENVIRONMENTAL TRANSPORT, BIODEGRADATION, AND BIOACCUMULATION OF QUANTUM DOTS AND OXIDE NANOPARTICLES

EPA Science Inventory

The proposed work will provide, for the first time, data on the environmental stability and mobility of QD and MO as a function of their formulation. The unique application of capillary electrophoresis in measuring binding constants of nanoparticles with NOM could provide a pr...

Robust one pot synthesis of colloidal silver nanoparticles by simple redox method and absorbance recovered sensing.

PubMed

Salman, Muhammad; Iqbal, Mahwish; El Ashry, El Sayed H; Kanwal, Shamsa

2012-01-01

Conventional synthesis of silver nanoparticles employs a reducing agent and a capping agent. In this report water-soluble silver nanoparticles (AgNPs) were prepared facilely by chemical reduction of Ag(I) ions. 4-Amino-3-(d-gluco-pentitol-1-yl)-4,5-dihydro-1,2,4-triazole-5-thione (AGTT) was used both as reducing and stabilizing agent. Direct heating methodology was found to be more suitable for achieving particles with a hydrodynamic diameter of ~20 nm. AGTT exists as tautomer in solution form and our studies indicate that -NH(2) group is involved in the reduction and stabilization of Ag(+) and thione (Δ=S) group of AGTT is possibly involved in stabilizing the nanoparticles via coordinate covalent linkage. Characterization of synthesized silver nanoparticles was performed by UV-vis, FT-IR and by FESEM. Based on the absorption properties of synthesized AgNPs, we used AgNPs to detect bovine serum albumin (BSA) and AgNPs-BSA composite nanoprobe was further applied to detect Cu(2+) based on absorbance recovery. The proposed method has advantages over existing methods in terms of rapid synthesis and stability of AgNPs and their applications. Analysis is reproducible, cost effective and highly sensitive. The lowest detectable concentration of BSA in this approach is 3 nM, and for Cu(2+) it can detect upto 200 pM. Copyright © 2012 Elsevier B.V. All rights reserved.

Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection.

PubMed

Chu, Dafeng; Gao, Jin; Wang, Zhenjia

2015-12-22

Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

A sustained release formulation of chitosan modified PLCL:poloxamer blend nanoparticles loaded with optical agent for animal imaging

NASA Astrophysics Data System (ADS)

Ranjan, Amalendu P.; Zeglam, Karim; Mukerjee, Anindita; Thamake, Sanjay; Vishwanatha, Jamboor K.

2011-07-01

The objective of this study was to develop optical imaging agent loaded biodegradable nanoparticles with indocynanine green (ICG) using chitosan modified poly(L-lactide-co-epsilon-caprolactone) (PLCL):poloxamer (Pluronic F68) blended polymer. Nanoparticles were formulated with an emulsification solvent diffusion technique using PLCL and poloxamer as blend-polymers. Polyvinyl alcohol (PVA) and chitosan were used as stabilizers. The particle size, shape and zeta potential of the formulated nanoparticles and the release kinetics of ICG from these nanoparticles were determined. Further, biodistribution of these nanoparticles was studied in mice at various time points until 24 h following intravenous administration, using a non-invasive imaging system. The average particle size of the nanoparticles was found to be 146 ± 3.7 to 260 ± 4.5 nm. The zeta potential progressively increased from - 41.6 to + 25.3 mV with increasing amounts of chitosan. Particle size and shape of the nanoparticles were studied using transmission electron microscopy (TEM) which revealed the particles to be smooth and spherical in shape. These nanoparticles were efficiently delivered to the cytoplasm of the cells, as observed in prostate and breast cancer cells using confocal laser scanning microscopy. In vitro release studies indicated sustained release of ICG from the nanoparticles over a period of seven days. Nanoparticle distribution results in mice showing improved uptake and accumulation with chitosan modified nanoparticles in various organs and slower clearance at different time points over a 24 h period as compared to unmodified nanoparticles. The successful formulation of such cationically modified nanoparticles for encapsulating optical agents may lead to a potential deep tissue imaging technique for tumor detection, diagnosis and therapy.

Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA.

PubMed

Jensen, Ditte Krohn; Jensen, Linda Boye; Koocheki, Saeid; Bengtson, Lasse; Cun, Dongmei; Nielsen, Hanne Mørck; Foged, Camilla

2012-01-10

Matrix systems based on biocompatible and biodegradable polymers like the United States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co-glycolide acid) (PLGA) are promising for the delivery of small interfering RNA (siRNA) due to favorable safety profiles, sustained release properties and improved colloidal stability, as compared to polyplexes. The purpose of this study was to design a dry powder formulation based on cationic lipid-modified PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP) was incorporated into the PLGA matrix to potentiate the gene silencing efficiency. The gene knock-down level in vitro was positively correlated to the weight ratio of DOTAP in the particles, and 73% silencing was achieved in the presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression with 54%. This formulation was spray-dried with mannitol into nanocomposite microparticles of an aerodynamic size appropriate for lung deposition. The spray-drying process did not affect the physicochemical properties of the readily re-dispersible nanoparticles, and most importantly, the in vitro gene silencing activity was preserved during spray-drying. The siRNA content in the powder was similar to the theoretical loading and the siRNA was intact, suggesting that the siRNA is preserved during the spray-drying process. Finally, X-ray powder diffraction analysis demonstrated that mannitol remained in a crystalline state upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient might exert its stabilizing effect by sterical inhibition of the interactions between adjacent nanoparticles. This study demonstrates that spray-drying is an excellent technique for engineering dry powder formulations of siRNA nanoparticles, which might enable the local delivery of biologically active siRNA directly to the lung tissue. Copyright © 2011 Elsevier B.V. All rights reserved.

Clinical impact of serum proteins on drug delivery.

PubMed

Kratz, Felix; Elsadek, Bakheet

2012-07-20

Among serum proteins albumin and transferrin have attracted the most interest as drug carriers in the past two decades. Prior to that, their potential use was overshadowed by the advent of monoclonal antibodies that was initiated by Milstein and Koehler in 1975. Meanwhile intensive pursuit of exploiting transferrin, but above all albumin as an exogenous or endogenous carrier protein for treating various diseases, primarily cancer, rheumatoid arthritis, diabetes and hepatitis has resulted in several marketed products and numerous clinical trials. While the use of transferrin has clinically been primarily restricted to immunotoxins, albumin-based drug delivery systems ranging from albumin drug nanoparticles, albumin fusion protein, prodrugs and peptide derivatives that bind covalently to albumin as well as physically binding antibody fragments and therapeutically active peptides are in advanced clinical trials or approved products. For treating diabetes, Levemir and Victoza that are myristic acid derivatives of human insulin or glucagon-like peptide 1 (GLP-1) act as long-acting peptides by binding to the fatty acid binding sites on circulating albumin to control glucose levels. Levemir from Novo Nordisk has already developed into a blockbuster since its market approval in 2004. Abraxane, an albumin paclitaxel nanoparticle as a water-soluble galenic formulation avoiding the use of cremophor/ethanol, transports paclitaxel through passive targeting as an albumin paclitaxel complex to the tumor site and is superior to conventional Taxol against metastatic breast cancer. INNO-206, an albumin-binding doxorubicin prodrug that also accumulates in solid tumors due to the enhanced permeability and retention (EPR) effect but releases the parent drug through acid cleavage, either intra- or extracellularly, is entering phase II studies against sarcoma. An expanding field is the use of albumin-binding antibody moieties which do not contain the fragment crystallizable (Fc) portion of, conventional immunoglobulin G (IgG) but are comprised of monovalent or bivalent light and/or heavy chains and incorporate an additional albumin-binding peptide or antibody domain. The most advanced antibody of this kind is ATN-103 (Ozoralizumab), a trivalent albumin-binding nanobody that neutralizes the pro-inflammatory tumor necrosis factor alpha (TNF-α) as a causative agent for exacerbating rheumatoid arthritis. ATN-103 is currently in multi-center phase II trials against this debilitating disease. In summary, because albumin as the most abundant circulating protein cannot only be used to improve the pharmacokinetic profile of therapeutically relevant peptides and the targeting moiety of antibodies but also for peptide-based targeting as well as low-molecular weight drugs to inflamed or malignant tissue, it is anticipated that R&D efforts of academia and the pharmaceutical industry in this field of drug delivery will prosper. Copyright © 2011 Elsevier B.V. All rights reserved.

Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer.

PubMed

Cohen, Sarit; Margel, Shlomo

2012-08-14

The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors. The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA) in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR). Tumor-targeting ligands such as peanut agglutinin (PNA), anti-carcinoembryonic antigen antibodies (anti-CEA) and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72) were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method. Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis. These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA nanoparticles, in order to use them for both detection as well as therapy of colon cancer and others.

Amorphization strategy affects the stability and supersaturation profile of amorphous drug nanoparticles.

PubMed

Cheow, Wean Sin; Kiew, Tie Yi; Yang, Yue; Hadinoto, Kunn

2014-05-05

Amorphous drug nanoparticles have recently emerged as a promising bioavailability enhancement strategy of poorly soluble drugs attributed to the high supersaturation solubility generated by the amorphous state and fast dissolution afforded by the nanoparticles. Herein we examine the effects of two amorphization strategies in the nanoscale, i.e., (1) molecular mobility restrictions and (2) high energy surface occupation, both by polymer excipient stabilizers, on the (i) morphology, (ii) colloidal stability, (iii) drug loading, (iv) amorphous state stability after three-month storage, and (v) in vitro supersaturation profiles, using itraconazole (ITZ) as the model drug. Drug-polyelectrolyte complexation is employed in the first strategy to prepare amorphous ITZ nanoparticles using dextran sulfate as the polyelectrolyte (ITZ nanoplex), while the second strategy employs pH-shift precipitation using hydroxypropylmethylcellulose as the surface stabilizer (nano-ITZ), with both strategies resulting in >90% ITZ utilization. Both amorphous ITZ nanoparticles share similar morphology (∼300 nm spheres) with the ITZ nanoplex exhibiting better colloidal stability, albeit at lower ITZ loading (65% versus 94%), due to the larger stabilizer amount used. The ITZ nanoplex also exhibits superior amorphous state stability, attributed to the ITZ molecular mobility restriction by electrostatic complexation with dextran sulfate. The higher stability, however, is obtained at the expense of slower supersaturation generation, which is maintained over a prolonged period, compared to the nano-ITZ. The present results signify the importance of selecting the optimal amorphization strategy, in addition to formulating the excipient stabilizers, to produce amorphous drug nanoparticles having the desired characteristics.

Development of albumin-based nanoparticles for the delivery of abacavir.

PubMed

Wilson, Barnabas; Paladugu, Latishkumar; Priyadarshini, S R Brahmani; Jenita, J Josephine Leno

2015-11-01

The study was designed to prepare and evaluate albumin nanoparticles containing antiviral drug abacavir sulphate. Various batches of albumin nanoparticles containing abacavir sulphate were prepared by desolvation method. The abacavir loaded particles were characterized for their yield, percentage of drug loading, surface morphology, particle size, surface charge, pattern of in vitro drug release and release mechanism studies. Drug loading ranged from 1.2 to 5.9%w/w. The mean particle size and the surface charge were 418.2nm and -40.8mV respectively. The in vitro drug release varied between 38.73 and 51.36%w/w for 24h. The n value for Korsmeyer-Peppas was 0.425 indicating Fickian type drug release. The preliminary findings indicated that albumin nanoparticles of abacavir can be prepared by desolvation method with good yield, high drug loading and sustained release. Copyright © 2015 Elsevier B.V. All rights reserved.

Conductive nanomaterials for printed electronics.

PubMed

Kamyshny, Alexander; Magdassi, Shlomo

2014-09-10

This is a review on recent developments in the field of conductive nanomaterials and their application in printed electronics, with particular emphasis on inkjet printing of ink formulations based on metal nanoparticles, carbon nanotubes, and graphene sheets. The review describes the basic properties of conductive nanomaterials suitable for printed electronics (metal nanoparticles, carbon nanotubes, and graphene), their stabilization in dispersions, formulations of conductive inks, and obtaining conductive patterns by using various sintering methods. Applications of conductive nanomaterials for electronic devices (transparent electrodes, metallization of solar cells, RFID antennas, TFTs, and light emitting devices) are also briefly reviewed.

PD-PK evaluation of freeze-dried atorvastatin calcium-loaded poly-ε-caprolactone nanoparticles.

PubMed

Ahmed, Iman S; El-Hosary, Rania; Shalaby, Samia; Abd-Rabo, Marwa M; Elkhateeb, Dalia G; Nour, Samia

2016-05-17

In this work lyophilized poly-ε-caprolactone nanoparticles (NPs) loaded with atorvastatin calcium (AC) were developed in an attempt to improve the in-vivo performance of AC following oral administration. The individual and combined effects of several formulation variables were previously investigated using step-wise full factorial designs in order to produce optimized AC-NPs with predetermined characteristics including particle size, drug loading capacity, drug release profile and physical stability. Four optimized formulations were further subjected in this work to lyophilization to promote their long-term physical stability and were fully characterized. The pharmacodynamics (PD)/pharmacokinetics (PK) properties of two optimized freeze-dried AC-NPs formulations showing acceptable long-term stability were determined and compared to a marketed AC immediate release tablet (Lipitor(®)) in albino rats. PD results revealed that the two tested formulations were equally effective in reducing low density lipoproteins (LDL) and triglycerides (TG) levels when given in reduced doses compared to Lipitor(®) and showed no adverse effects. PK results, on the other hand, revealed that the two freeze-dried AC-NPs formulations were of significantly lower bioavailability compared to Lipitor(®). Taken together the PD and PK results demonstrate that the improved efficacy obtained at reduced doses from the freeze-dried AC-NPs could be due to increased concentration of AC in the liver rather than in the plasma. Copyright © 2016 Elsevier B.V. All rights reserved.

Solid lipid nanoparticles as an efficient drug delivery system of olmesartan medoxomil for the treatment of hypertension.

PubMed

Pandya, Nilima T; Jani, Parva; Vanza, Jigar; Tandel, Hemal

2018-05-01

The aim of the current investigation was to develop solid lipid nanoparticles of olmesartan medoxomil using hot homogenization method to improve its oral bioavailability. Central composite design was applied to optimize the formulation variables; lipid X1 (Glyceryl monostearate) and surfactant X2 (Poloxamer: Tween 80). The particle sizes were in the nanometer range and spherical shaped for all prepared solid lipid nanoparticles formulations and the zeta potential absolute values were high, predicting good long-term stability. In vitro study of olmesartan loaded solid lipid nanoparticle exhibited controlled release profile for at least 24 h. The rate and extent of drug diffusion was studied using dialysis sac, rat's stomach and intestine tissues; study demonstrated that drug release from the solid lipid nanoparticles was significantly higher than drug suspension. In vivo pharmacokinetic study of olmesartan loaded solid lipid nanoparticles revealed higher Cmax of 1610 ng/mL, higher AUC of 15492.50 ng/mL and increased relative bioavailability by almost 2.3 folds compared to marketed formulation. These results clearly indicate that olmesartan loaded solid lipid nanoparticles are shown to have enhanced bioavailability and effective therapeutic result and thus would be an excellent way to treat hypertension. Hence, these solid lipid nanoparticles could represent as a great potential for a possible alternative to conventional oral formulation in the treatment of hypertension. Copyright © 2018 Elsevier B.V. All rights reserved.

Toxicity of silver nanoparticles in zebrafish models

NASA Astrophysics Data System (ADS)

Asharani, P. V.; Lian Wu, Yi; Gong, Zhiyuan; Valiyaveettil, Suresh

2008-06-01

This study was initiated to enhance our insight on the health and environmental impact of silver nanoparticles (Ag-np). Using starch and bovine serum albumin (BSA) as capping agents, silver nanoparticles were synthesized to study their deleterious effects and distribution pattern in zebrafish embryos (Danio rerio). Toxicological endpoints like mortality, hatching, pericardial edema and heart rate were recorded. A concentration-dependent increase in mortality and hatching delay was observed in Ag-np treated embryos. Additionally, nanoparticle treatments resulted in concentration-dependent toxicity, typified by phenotypes that had abnormal body axes, twisted notochord, slow blood flow, pericardial edema and cardiac arrhythmia. Ag+ ions and stabilizing agents showed no significant defects in developing embryos. Transmission electron microscopy (TEM) of the embryos demonstrated that nanoparticles were distributed in the brain, heart, yolk and blood of embryos as evident from the electron-dispersive x-ray analysis (EDS). Furthermore, the acridine orange staining showed an increased apoptosis in Ag-np treated embryos. These results suggest that silver nanoparticles induce a dose-dependent toxicity in embryos, which hinders normal development.

Design and Solidification of Fast-Releasing Clofazimine Nanoparticles for Treatment of Cryptosporidiosis

PubMed Central

2017-01-01

Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and Drug Administration (FDA) with a good safety record, was recently identified as a lead hit for cryptosporidiosis through a high-throughput phenotypic screen. Cryptosporidiosis requires fast-acting treatment as it leads to severe symptoms which, if untreated, result in morbidity for infants and small children. Consequently, a fast-releasing oral formulation of clofazimine in a water-dispersible form for pediatric administration is highly desirable. In this work, clofazimine nanoparticles were prepared with three surface stabilizers, hypromellose acetate succinate (HPMCAS), lecithin, and zein, using the flash nanoprecipitation (FNP) process. Drug encapsulation efficiencies of over 92% were achieved. Lyophilization and spray-drying were applied and optimized to produce redispersible nanoparticle powders. The release kinetics of these clofazimine nanoparticle powders in biorelevant media were measured and compared with those of crystalline clofazimine and the currently marketed formulation Lamprene. Remarkably improved dissolution rates and clofazimine supersaturation levels up to 90 times equilibrium solubility were observed with all clofazimine nanoparticles tested. Differential scanning calorimetry indicated a reduction of crystallinity of clofazimine in nanoparticles. These results strongly suggest that the new clofazimine nanoparticles prepared with affordable materials in this low-cost nanoparticle formulation process can be used as viable cryptosporidiosis therapeutics. PMID:28929769

Freeze drying formulation using microscale and design of experiment approaches: a case study using granulocyte colony-stimulating factor.

PubMed

Grant, Yitzchak; Matejtschuk, Paul; Bird, Christopher; Wadhwa, Meenu; Dalby, Paul A

2012-04-01

The lyophilization of proteins in microplates, to assess and optimise formulations rapidly, has been applied for the first time to a therapeutic protein and, in particular, one that requires a cell-based biological assay, in order to demonstrate the broader usefulness of the approach. Factorial design of experiment methods were combined with lyophilization in microplates to identify optimum formulations that stabilised granulocyte colony-stimulating factor during freeze drying. An initial screen rapidly identified key excipients and potential interactions, which was then followed by a central composite face designed optimisation experiment. Human serum albumin and Tween 20 had significant effects on maintaining protein stability. As previously, the optimum formulation was then freeze-dried in stoppered vials to verify that the microscale data is relevant to pilot scales. However, to validate the approach further, the selected formulation was also assessed for solid-state shelf-life through the use of accelerated stability studies. This approach allows for a high-throughput assessment of excipient options early on in product development, while also reducing costs in terms of time and quantity of materials required.

Use of proteins to minimize the physical aging of EUDRAGIT sustained release films.

PubMed

Kucera, Shawn A; McGinity, James W; Zheng, Weijia; Shah, Navnit H; Malick, A Waseem; Infeld, Martin H

2007-07-01

The objective of this study was to investigate the influence of two proteins, albumin and type B gelatin, on the physical aging of EUDRAGIT RS 30 D and RL 30 D coated theophylline pellets. The physicomechanical properties of sprayed films, thermal properties of cast films, influence of proteins on the zeta potential and particle size of the dispersion, and the release of proteins from cast films under simulated dissolution conditions were investigated. The release rate of theophylline decreased significantly over time from pellets coated with an acrylic dispersion containing 10% albumin when there was no acidification of the acrylic dispersion; however, when pellets were coated with an acidified EUDRAGIT/albumin dispersion, the theophylline release rate was stable for dosage forms stored in the absence of humidity. The drug release rate was faster for pellets coated with acrylic dispersions containing 10% gelatin compared to the albumin-containing formulations. When sprayed films were stored at 40 degrees C/75% RH, the water vapor permeability decreased significantly for both EUDRAGIT films and those containing EUDRAGIT and albumin; however, there was no significant change in this parameter when 10% gelatin was present. Albumin was released from the acrylic films when the pH of the dissolution media was below the isoelectric point of the protein while no quantitative release of gelatin was observed in pH 1.2 or 7.4 media. The effect of gelatin to prevent the decrease in drug release rate was due to stabilization in water vapor permeability of the film. Acidification of the polymeric dispersion resulted in electrostatic repulsive forces between albumin and the acrylic polymer, which stabilized the drug release rate when the dosage forms were stored in aluminum induction sealed containers at both 40 degrees C/75% RH and 25 degrees C/60% RH.

Trehalose limits BSA aggregation in spray-dried formulations at high temperatures: implications in preparing polymer implants for long-term protein delivery.

PubMed

Rajagopal, Karthikan; Wood, Joseph; Tran, Benjamin; Patapoff, Thomas W; Nivaggioli, Thierry

2013-08-01

Polymer implants are promising systems for sustained release applications but their utility for protein delivery has been hindered because of concerns over drug stability at elevated temperatures required for processing. Using bovine serum albumin (BSA) as a model, we have assessed whether proteins can be formulated for processing at elevated temperatures. Specifically, the effect of trehalose and histidine-HCl buffer on BSA stability in a spray-dried formulation has been investigated at temperatures ranging from 80°C to 110°C. When both the sugar and buffer are present, aggregation is suppressed even when exposed to 100°C, the extrusion temperature of poly(lactide-co-glycolide) (PLGA), a bioresorbable polymer. Estimation of aggregation rate constants (k) indicate that though both trehalose and histidine-HCl buffer contribute to BSA stability, the effect because of trehalose alone is more pronounced. BSA-loaded PLGA implants were prepared using hot-melt extrusion process and in vitro release was conducted in phosphate buffered saline at 37°C. Comparison of drug released from implants prepared using four different formulations confirmed that maximal release was achieved from the formulation in which BSA was least aggregated. These studies demonstrate that when trehalose and histidine-HCl buffer are included in spray-dried formulations, BSA stability is maintained both during processing at 100°C and long-term residence within implants. Copyright © 2013 Wiley Periodicals, Inc.

Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer.

PubMed

Cohen, Sarit; Pellach, Michal; Kam, Yossi; Grinberg, Igor; Corem-Salkmon, Enav; Rubinstein, Abraham; Margel, Shlomo

2013-03-01

Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Optimization of β-carotene loaded solid lipid nanoparticles preparation using a high shear homogenization technique

NASA Astrophysics Data System (ADS)

Triplett, Michael D.; Rathman, James F.

2009-04-01

Using statistical experimental design methodologies, the solid lipid nanoparticle design space was found to be more robust than previously shown in literature. Formulation and high shear homogenization process effects on solid lipid nanoparticle size distribution, stability, drug loading, and drug release have been investigated. Experimentation indicated stearic acid as the optimal lipid, sodium taurocholate as the optimal cosurfactant, an optimum lecithin to sodium taurocholate ratio of 3:1, and an inverse relationship between mixing time and speed and nanoparticle size and polydispersity. Having defined the base solid lipid nanoparticle system, β-carotene was incorporated into stearic acid nanoparticles to investigate the effects of introducing a drug into the base solid lipid nanoparticle system. The presence of β-carotene produced a significant effect on the optimal formulation and process conditions, but the design space was found to be robust enough to accommodate the drug. β-Carotene entrapment efficiency averaged 40%. β-Carotene was retained in the nanoparticles for 1 month. As demonstrated herein, solid lipid nanoparticle technology can be sufficiently robust from a design standpoint to become commercially viable.

Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

NASA Astrophysics Data System (ADS)

Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

2014-03-01

Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

Synthesis and Characterization of Protein-Conjugated Silver Nanoparticles/Silver Salt Loaded Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) Film for Prevention of Bacterial Infections and Potential Use in Bone Tissue Engineering Applications

NASA Astrophysics Data System (ADS)

Bakare, Rotimi Ayotunde

Failure of orthopedic implants due to bacterial infection has been a major concern in bone tissue engineering. To this end, we have formulated a potential orthopedic implant made of naturally occurring biodegradable polymer, i.e. poly (3-hydroxylbutyrate-co-3-hydroxylvalerate) (PHBV), modified with BSA conjugated silver nanoparticles and or silver chloride. Upon release of Ag NPs and or Ag+ in the implant region, can promote aseptic environment by inhibition of bacteria growth and also support/maintain bone cell adhesion, growth, and proliferation. For formulating nanoparticles loaded PHBV scaffold, we exploit specific interaction between bovine serum albumin (BSA) of BSA capped silver nanoparticles and collagen of collagen immobilized PHBV scaffold. Therefore, the first part of this study dealt with synthesis and characterization of collagen immobilized PHBV film for loading of BSA stabilized silver (Ag/BSA) nanoparticles. Two different approaches were used to immobilize collagen on macroporous PHBV film. First approach uses thermal radical copolymerization with 2-hydroxyethylmethacrylate (HEMA), while the second approach uses aminolysis to functionalize macroporous PHBV film. Using collagen crosslinker, type I collagen was covalently grafted to formulate collagen immobilized PHEMA-g-PHBV and collagen immobilized NH2-PHBV films, respectively. Spectroscopic (FTIR, XPS), physical (SEM), and thermal (TGA) techniques were used to characterize the functionalized PHBV films. The Ag/BSA nanoparticles were then loaded on collagen immobilized PHBV films and untreated PHBV films. The concentration of nanoparticles loaded on PHBV film was determined by atomic absorption spectrometry and fluorescence spectroscopy. The amount of nanoparticles loaded on collagen immobilized PHBV film was found to be significantly greater than that on untreated PHBV film. The amount of Ag/BSA nanoparticles loaded on collagen immobilized PHBV film was found to depend on the concentration of Ag/BSA nanoparticles solution used for loading and on the molecular weight of type I collagen used in collagen immobilization on PHBV film. At physiological pH, optimum amount of nanoparticles was retained on Type I collagen immobilized PHBV film because at pH 7.4, protonated amino groups of collagen immobilized PHBV film promote strong electrostatic interaction with the carboxylate anions of BSA stabilized silver nanoparticles. The second part of this study dealt with formulating AgCl/PHBV film that can potentially release silver ions for effective antimicrobial activity. In this study, we formulated AgCl/PHBV composite film by a salt exchange mechanism. Thermogravimetric analysis (TGA) was used to quantify the amount of NaCl present before and after salt exchange. The Na content in the pre-washed and partially washed NaCl/PHBV film was found to be 43.60% and 1.24% by mass, respectively. The AgCl/PBHV composite film was acid digested and assayed for Na+ and Ag+ content by using Atomic Absorption Spectrometry (AAS) and was found to be 2.15 and 10.25 ppm, respectively. XPS technique was used to characterize the surface elemental composition of the AgCl/PHBV composite film. The survey spectrum of AgCl/PHBV film showed emergence of Ag 3d and Cl 2s peaks compared to pure PHBV which was predominantly composed of C 1s and O 1s peaks. The release kinetics of silver ions from AgCl/PHBV composite film showed an initial burst of about 1.5 ppm of silver ions during the first day of desorption followed by a gradual release of silver ions at an average rate of 0.3 ppm per day during the span of two weeks studied. Ag/BSA nanoparticles loaded collagen immobilized PHBV films and AgCl/PHBV composite films were tested for antibacterial efficacy against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Colony forming unit and optical density measurements of Ag/BSA nanoparticles loaded collagen immobilized PHBV films showed broad antimicrobial activity at low Ag/BSA nanoparticles concentration (0.19and 0.31 microg) compared to commercially available gentamicin and sulfamethoxazole/trimethoprim which showed sometimes selective antimicrobial activity and antimicrobial activity at high concentration (10 microg and 23.75/1.25 microg/disc). Additionally, a clear zone of inhibition around AgCl/PHBV composite film was noticed on a modified Kirby-Bauer disk diffusion assay. Optical density results and colony forming unit measurements showed that AgCl/PHBV composite film exhibit broad bactericidal activity. Next, we evaluated the cytotoxicity of Ag/BSA nanoparticles loaded collagen immobilized PHBV films and AgCl/PHBV composite films towards MC3T3-E1 cells at the same concentration both films showed broad antimicrobial activity. By using MTT assay, we established that Ag/BSA nanoparticles loaded collagen immobilized PHBV film showed minimal, if any, cytotoxic effect towards MC3T3-E1 cells while AgCl/PHBV composite film showed significant cytotoxic effect compared to tissue culture polystyrene. Our research findings provide several formulations for preparation of scaffold, if properly tuned; it can be used as a potential biocompatible and biodegradable scaffold for the prevention of bacterial infections and promotion of cell attachment and proliferation in bone tissue engineering applications.

Suspension characterization as important key for toxicological investigations

NASA Astrophysics Data System (ADS)

Meißner, Tobias; Potthoff, Annegret; Richter, Volkmar

2009-05-01

To assess potential health risks of nanoparticles by means of in vitro or in vivo assays and to determine dose-action curves a defined and reproducible method of particle administration is required. The interpretation of the toxicological results should be based on a comprehensive chemical-physical characterization of the particles used. Therefore, we developed a method to suspend nanoparticles stably and homogenously in physiological media. Our approach consist of three steps: (1) physical-chemical characterisation of the powders as delivered, (2) preparation and characterization of a non-physiological electro-statically stabilized nanoparticle suspension and (3) assessment of the nanoparticles behaviour in physiological media with or without proteins. This approach is demonstrated on a titanium dioxide and a tungsten carbide nanopowder. Results showed that particles agglomerate in protein-free medium within minutes, whereas in the presence of bovine serum albumin or foetal bovine serum an agglomeration is hindered.

Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

NASA Astrophysics Data System (ADS)

Chu, Michael Kok Loon

Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long-term efficacy up to an 18 day period. Finally, to improve insulin stability within microdevice reservoirs, an in situ gelling zinc-insulin formulation was designed. High concentration insulin gel complexed with zinc provided physical and chemical stability against thermal denaturation over a 30 day period. Long-term stability of the zinc-insulin gel formulation shows potential for sustained release application, providing low-level, basal insulin release. These combined technologies present significant progress towards the goal of an 'artificial pancreas' to combat diabetes through 'smart' insulin therapy.

Application of Fiber Optic ATR-FTIR Methods for In Situ Characterization of Protein Delivery Systems in Real Time

PubMed Central

McFearin, Cathryn L.; Sankaranarayanan, Jagadis; Almutairi, Adah

2011-01-01

Real Time Characterization of Protein Delivery Systems A fiber optic coupled ATR-FTIR spectroscopy technique was applied to the study of two different therapeutic delivery systems, acid degradable hydrogels and nanoparticles. Real time exponential release of a model protein, human serum albumin (HSA), was observed from two different polymeric hydrogels formulated with a pH sensitive crosslinker. Spectroscopic examination of nanoparticles formulated with an acid degradable polymer shell and encapsulated HSA exhibited vibrational signatures characteristic of both particle and payload when exposed to lowered pH conditions demonstrating the ability of this methodology to simultaneously measure phenomena arising from a system with a mixture of components. In addition, thorough characterization of these pH sensitive delivery vehicles without encapsulated protein was also accomplished in order to separate the effects of the payload during degradation. By providing in situ, real time detection in combination with the ability to specifically identify different components in a mixture without involved sample preparation and minimal sample disturbance, the versatility and suitability of this type of experiment for research in the pharmaceutical field is demonstrated. PMID:21476582

Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo.

PubMed

Freimann, Krista; Arukuusk, Piret; Kurrikoff, Kaido; Pärnaste, Ly; Raid, Raivo; Piirsoo, Andres; Pooga, Margus; Langel, Ülo

2018-03-02

Although advances in genomics and experimental gene therapy have opened new possibilities for treating otherwise incurable diseases, the transduction of nucleic acids into the cells and delivery in vivo remain challenging. The high molecular weight and anionic nature of nucleic acids require their packing into nanoparticles for the delivery. The efficacy of nanoparticle drugs necessitates the high bioactivity of constituents, but their distribution in organisms is mostly governed by the physical properties of nanoparticles, and therefore, generation of stable particles with strictly defined characteristics is highly essential. Using previously designed efficient cell-penetrating peptide NF55, we searched for strategies enabling control over the nanoparticle formation and properties to further improve transfection efficacy. The size of the NF55/pDNA nanoparticles correlates with the concentration of its constituents at the beginning of assembly, but characteristics of nanoparticles measured by DLS do not reliably predict the applicability of particles in in vivo studies. We introduce a new formulation approach called cryo-concentration, where we acquired stable and homogeneous nanoparticles for administration in vivo. The cryo-concentrated NF55/pDNA nanoparticles exhibit several advantages over standard formulation: They have long shelf-life and do not aggregate after reconstitution, have excellent stability against enzymatic degradation, and show significantly higher bioactivity in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Design and in vitro haemolytic evaluation of cryptolepine hydrochloride-loaded gelatine nanoparticles as a novel approach for the treatment of malaria.

PubMed

Kuntworbe, Noble; Al-Kassas, Raida

2012-06-01

Cryptolepine hydrochloride-loaded gelatine nanoparticles were developed and characterised as a means of exploring formulation techniques to improve the pharmaceutic profile of the compound. Cryptolepine hydrochloride-loaded gelatine-type (A) nanoparticles were developed base on the double desolvation approach. After optimisation of formulation parameters including temperature, stirring rate, incubation time polymer and cross-linker (glutaraldehyde) concentrations, the rest of the study was conducted at two different formulation pH values (2.5 and 11.0) and by two different approaches to drug loading. Three cryoprotectants--sucrose, glucose and mannitol--were investigated for possible use for the preparation of freeze-dried samples. Nanoparticles with desired size mostly less than 350 nm and zeta potential above ±20 were obtained when formulation pH was between 2.5 and 5 and above 9. Entrapment efficiency was higher at pH 11.0 than pH 2.5 and for products formulated when drug was loaded during the second desolvation stage compared to when drug was loaded onto pre-formed nanoparticles. Further investigation of pH effect showed a new isoelectric point of 6.23-6.27 at which the zeta potential of nanoparticles was zero. Sucrose and glucose were effective in low concentrations as cryoprotectants. The best formulation produced an EC(50) value of 227.4 μM as a haemolytic agent compared to 51.61 μM by the free compound which is an indication of reduction in haemolytic side effect. There was sustained released of the compound from all formulation types over a period of 192 h. Stability data indicated that the nanosuspension and freeze-dried samples were stable at 4 and 25°C, respectively, over a 52-week period, but the former was less stable at room temperature. In conclusion, cryptolepine hydrochloride-loaded gelatine nanoparticles exhibited reduced haemolytic effect compared to the pure compound and can be developed further for parenteral delivery.

Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer

PubMed Central

2012-01-01

Background The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors. Methods The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA) in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR). Tumor-targeting ligands such as peanut agglutinin (PNA), anti-carcinoembryonic antigen antibodies (anti-CEA) and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72) were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method. Results and discussion Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis. Conclusions These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA nanoparticles, in order to use them for both detection as well as therapy of colon cancer and others. PMID:22891637

Application of poly(epsilon-caprolactone) nanoparticles containing atrazine herbicide as an alternative technique to control weeds and reduce damage to the environment.

PubMed

Pereira, Anderson E S; Grillo, Renato; Mello, Nathalie F S; Rosa, Andre H; Fraceto, Leonardo F

2014-03-15

Nanoparticles of poly(epsilon-caprolactone) containing the herbicide atrazine were prepared, characterized, and evaluated in terms of their herbicidal activity and genotoxicity. The stability of the nanoparticles was evaluated over a period of three months, considering the variables: size, polydispersion index, pH, and encapsulation efficiency. Tests on plants were performed with target (Brassica sp.) and non-target (Zea mays) organisms, and the nanoparticle formulations were shown to be effective for the control of the target species. Experiments using soil columns revealed that the use of nanoparticles reduced the mobility of atrazine in the soil. Application of the Allium cepa chromosome aberration assay demonstrated that the nanoparticle systems were able to reduce the genotoxicity of the herbicide. The formulations developed offer a useful means of controlling agricultural weeds, while at the same time reducing the risk of harm to the environment and human health. Copyright © 2014 Elsevier B.V. All rights reserved.

Atorvastatin calcium encapsulated eudragit nanoparticles with enhanced oral bioavailability, safety and efficacy profile.

PubMed

Kumar, Nagendra; Chaurasia, Sundeep; Patel, Ravi R; Khan, Gayasuddin; Kumar, Vikas; Mishra, Brahmeshwar

2017-03-01

Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.

Adsorption of doxorubicin on citrate-capped gold nanoparticles: insights into engineering potent chemotherapeutic delivery systems

NASA Astrophysics Data System (ADS)

Curry, Dennis; Cameron, Amanda; MacDonald, Bruce; Nganou, Collins; Scheller, Hope; Marsh, James; Beale, Stefanie; Lu, Mingsheng; Shan, Zhi; Kaliaperumal, Rajendran; Xu, Heping; Servos, Mark; Bennett, Craig; Macquarrie, Stephanie; Oakes, Ken D.; Mkandawire, Martin; Zhang, Xu

2015-11-01

Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates.Gold nanomaterials have received great interest for their use in cancer theranostic applications over the past two decades. Many gold nanoparticle-based drug delivery system designs rely on adsorbed ligands such as DNA or cleavable linkers to load therapeutic cargo. The heightened research interest was recently demonstrated in the simple design of nanoparticle-drug conjugates wherein drug molecules are directly adsorbed onto the as-synthesized nanoparticle surface. The potent chemotherapeutic, doxorubicin often serves as a model drug for gold nanoparticle-based delivery platforms; however, the specific interaction facilitating adsorption in this system remains understudied. Here, for the first time, we propose empirical and theoretical evidence suggestive of the main adsorption process where (1) hydrophobic forces drive doxorubicin towards the gold nanoparticle surface before (2) cation-π interactions and gold-carbonyl coordination between the drug molecule and the cations on AuNP surface facilitate DOX adsorption. In addition, biologically relevant compounds, such as serum albumin and glutathione, were shown to enhance desorption of loaded drug molecules from AuNP at physiologically relevant concentrations, providing insight into the drug release and in vivo stability of such drug conjugates. Electronic supplementary information (ESI) available: DOX-AuNP absorption spectra and colored solution images, citrate displacement data, original DOX-AuNP loading isotherm, XPS data and TEM micrographs, modelling data. See DOI: 10.1039/c5nr05826k

Supramolecular curcumin-barium prodrugs for formulating with ceramic particles.

PubMed

Kamalasanan, Kaladhar; Anupriya; Deepa, M K; Sharma, Chandra P

2014-10-01

A simple and stable curcumin-ceramic combined formulation was developed with an aim to improve curcumin stability and release profile in the presence of reactive ceramic particles for potential dental and orthopedic applications. For that, curcumin was complexed with barium (Ba(2+)) to prepare curcumin-barium (BaCur) complex. Upon removal of the unbound curcumin and Ba(2+) by dialysis, a water-soluble BaCur complex was obtained. The complex was showing [M+1](+) peak at 10,000-20,000 with multiple fractionation peaks of MALDI-TOF-MS studies, showed that the complex was a supramolecular multimer. The (1)H NMR and FTIR studies revealed that, divalent Ba(2+) interacted predominantly through di-phenolic groups of curcumin to form an end-to-end complex resulted in supramolecular multimer. The overall crystallinity of the BaCur was lower than curcumin as per XRD analysis. The complexation of Ba(2+) to curcumin did not degrade curcumin as per HPLC studies. The fluorescence spectrum was blue shifted upon Ba(2+) complexation with curcumin. Monodisperse nanoparticles with size less than 200dnm was formed, out of the supramolecular complex upon dialysis, as per DLS, and upon loading into pluronic micelles the size was remaining in similar order of magnitude as per DLS and AFM studies. Stability of the curcumin was improved greater than 50% after complexation with Ba(2+) as per UV/Vis spectroscopy. Loading of the supramloecular nanoparticles into pluronic micelles had further improved the stability of curcumin to approx. 70% in water. These BaCur supramolecule nanoparticles can be considered as a new class of prodrugs with improved solubility and stability. Subsequently, ceramic nanoparticles with varying chemical composition were prepared for changing the material surface reactivity in terms of the increase in, degradability, surface pH and protein adsorption. Further, these ceramic particles were combined with curcumin prodrug formulations and optimized the curcumin release properties in the combined formulations. Our proof concept study shows that, the conversion of curcumin to a metal-organic supramolecular prodrug improved the solubility, stability and release profile of curcumin. The prodrug approach with the micellisation strategy appears to be more appropriate to deliver intact curcumin in the presence of ceramic particles of varying surface reactivity. Copyright © 2014 Elsevier B.V. All rights reserved.

Ferritin Decorated PLGA/Paclitaxel Loaded Nanoparticles Endowed with an Enhanced Toxicity Toward MCF-7 Breast Tumor Cells.

PubMed

Turino, Ludmila N; Ruggiero, Maria R; Stefanìa, Rachele; Cutrin, Juan C; Aime, Silvio; Geninatti Crich, Simonetta

2017-04-19

Polylactic and glycolic acid nanoparticles (PLGA-NPs), coated with L-ferritin, are exploited for the simultaneous delivery of paclitaxel and an amphiphilic Gd based MRI contrast agent into breast cancer cells (MCF7). L-ferritin has been covalently conjugated to the external surface of PLGA-NPs exploiting NHS activated carboxylic groups. The results confirmed that nanoparticles decorated with L-ferritin have many advantages with respect to both albumin-decorated and nondecorated particles. Ferritin moieties endow PLGA-NPs with targeting capability, exploiting SCARA5 receptors overexpressed by these tumor cells, that results in an increased paclitaxel cytotoxicity. Moreover, protein coating increased nanoparticle stability, thus reducing the fast and aspecific drug release before reaching the target. The theranostic potential of the nanoparticles has been demonstrated by evaluating the signal intensity enhancement on T 1 -weighted MRI images of labeled MCF7 cells. The results were compared with that obtained with MDA cells used as negative control due to their lower SCARA5 expression.

Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Logie, Jennifer

Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P(LA-co-TMCC)-g-PEG nanoparticles as an effective delivery vehicle for two chemotherapeutics, and presents approaches amenable to the delivery of many other clinically relevant hydrophobic drugs or drug combinations.

Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics.

PubMed

Ahmed, Osama A A; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

2015-01-01

The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid-liquid phase separation method, according to the Box-Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance.

Atovaquone-loaded nanocapsules: influence of the nature of the polymer on their in vitro characteristics.

PubMed

Cauchetier, Emmanuelle; Deniau, M; Fessi, H; Astier, A; Paul, M

2003-01-02

Nanocapsules with atovaquone concentration of 1,000 micrograms/ml were prepared according to the interfacial deposition technique using different polymers: poly- epsilon -caprolactone (PECL), poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLAGA). The following characteristics of nanoparticles were determined: percentage of encapsulation of atovaquone, percentage of encapsulation of benzyl benzoate (BB), nanoparticle size, nanoparticle wall thickness, suspension pH, and in vitro stability. The different formulations showed similar characteristics: maximal percentage of encapsulation (100%), particle size of approximately 230 nm, neutral pH and wall thickness of approximately 20 nm. The type of polymer used was the main factor influencing stability, in decreasing order: PECL>PLA>PLAGA. No release of atovaquone or benzylbenzoate was noted with PECL nanoparticles over 4 months. Release of atovaquone (25.9%) was found with PLA nanoparticles at 4 months. Release of both atovaquone (18.9%) and benzylbenzoate (54.2%) was noted with PLAGA nanoparticles from the third month, indicating a disruption of the nanoparticle membrane.

Spectroscopic exploration of interaction between PEG-functionalized Ag2S nanoparticles with bovine serum albumin

NASA Astrophysics Data System (ADS)

Prasanth, S.; RitheshRaj, D.; Vineeshkumar, T. V.; Sudarsanakumar, C.

2018-05-01

The introduction of nanoparticles into biological fluids often leads to the formation of biocorona over the surface of nanoparticles. For the effective use of nanoparticles in biological applications it is very essential to understand their interactions with proteins. Herein, we investigated the interactions of Poly ethylene glycol capped Ag2S nanoparticles with Bovine Serum Albumin by spectroscopic techniques. By the addition of Ag2S nanoparticles, a ground state complex is formed. The CD spectroscopy reveals that the secondary structure of BSA is altered by complexation with PEG-Ag2S nanoparticles, while the overall tertiary structure remains closer to that of native BSA.

Formulation and evaluation of voriconazole ophthalmic solid lipid nanoparticles in situ gel.

PubMed

Pandurangan, Dinesh Kumar; Bodagala, Prathima; Palanirajan, Vijayaraj Kumar; Govindaraj, Saravanan

2016-01-01

In the present investigation, solid lipid nanoparticles (SLNs)-loaded in situ gel with voriconazole drug was formulated. Further, the formulation was characterized for pH, gelling capacity, entrapment efficiency, in vitro drug release, drug content, and viscosity. Voriconazole is an antifungal drug used to treat various infections caused by yeast or other types of fungi. Film hydration technique was used to prepared SLNs from lecithin and cholesterol. Based on the entrapment efficiency 67.2-97.3% and drug release, the optimized formulation NF1 of SLNs was incorporated into in situ gels. The in situ gels were prepared using viscosity-enhancing polymers such as Carbopol and (hydroxypropyl)methyl cellulose (HPMC). Formulated SLN in situ gel formulations were characterized, which showed pH 4.9-7.1, drug content 65.69-96.3%, and viscosity (100 rpm) 120-620 cps. From the characterizations given above, F6 was optimized and evaluated for microbial assay and ocular irritation studies. Microbial assay was conducted by the cup-plate method using Candida albicans as the test organism. An ocular irritation study was conducted on albino rabbits. The results revealed that there was no ocular damage to the cornea, conjunctiva, or iris. Stability studies were carried out on the F6 formulation for 3 months, which showed that the formulation had good stability. These results indicate that the studied SLNs-loaded in situ gel is a promising vehicle for ocular delivery.

Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis.

PubMed

Rençber, Seda; Karavana, Sinem Yaprak; Yılmaz, Fethiye Ferda; Eraç, Bayri; Nenni, Merve; Özbal, Seda; Pekçetin, Çetin; Gurer-Orhan, Hande; Hoşgör-Limoncu, Mine; Güneri, Pelin; Ertan, Gökhan

2016-01-01

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis.

Enhancing Tumor Cell Response to Chemotherapy through the Targeted Delivery of Platinum Drugs Mediated by Highly Stable, Multifunctional Carboxymethylcellulose-Coated Magnetic Nanoparticles.

PubMed

Medříková, Zdenka; Novohradsky, Vojtech; Zajac, Juraj; Vrána, Oldřich; Kasparkova, Jana; Bakandritsos, Aristides; Petr, Martin; Zbořil, Radek; Brabec, Viktor

2016-07-04

The fabrication of nanoparticles using different formulations, and which can be used for the delivery of chemotherapeutics, has recently attracted considerable attention. We describe herein an innovative approach that may ultimately allow for the selective delivery of anticancer drugs to tumor cells by using an external magnet. A conventional antitumor drug, cisplatin, has been incorporated into new carboxymethylcellulose-stabilized magnetite nanoparticles conjugated with the fluorescent marker Alexa Fluor 488 or folic acid as targeting agent. The magnetic nanocarriers possess exceptionally high biocompatibility and colloidal stability. These cisplatin-loaded nanoparticles overcome the resistance mechanisms typical of free cisplatin. Moreover, experiments aimed at the localization of the nanoparticles driven by an external magnet in a medium that mimics physiological conditions confirmed that this localization can inhibit tumor cell growth site-specifically. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Formulation and in vitro characterization of protein-loaded liposomes

NASA Astrophysics Data System (ADS)

Kuzimski, Lauren

Background/Objective: Protein-based drugs are increasingly used to treat a variety of conditions including cancer and cardio-vascular disease. Due to the immune system's innate ability to degrade the foreign particles quickly, protein-based treatments are generally short-lived. To address this limitation, the objective of the study was to: 1) develop protein-loaded liposomes; 2) characterize size, stability, encapsulation efficiency and rate of protein release; and 3) determine intracellular uptake and distribution; and 4) protein structural changes. Method: Liposomes were loaded with a fluorescent-albumin using freeze-thaw (F/T) methodology. Albumin encapsulation and release were quantified by fluorescence spectroscopic techniques. Flow cytometry was used to determine liposome uptake by macrophages. Epifluorescence microscopy was used to determine cellular distribution of liposomes. Stability was determined using dynamic light scattering by measuring liposome size over one month period. Protein structure was determined using circular dichroism (CD). Result: Encapsulation of albumin in liposome was ˜90% and was dependent on F/T rates, with fifteen cycles yielding the highest encapsulation efficacy (p < 0.05). Albumin-loaded liposomes demonstrated consistent size (<300nm). Release of encapsulated albumin in physiological buffer at 25°C was ˜60% in 72 h. Fluorescence imaging suggested an endosomal route of cellular entry for the FITC-albumin liposome with maximum uptake rates in immune cells (30% at 2hour incubation). CD suggested protein structure is minimally impacted by freeze-thaw methodology. Conclusion: Using F/T as a loading method, we were able to successfully achieve a protein-loaded liposome that was under 300nm, had encapsulation of ˜90%. Synthesized liposomes demonstrated a burst release of encapsulate protein (60%) at 72 hours. Cellular trafficking confirmed endosomal uptake, and minimal protein damage was noticed in CD.

Physical and chemical stability of nanostructured lipid drug carriers (NLC) based on natural lipids from Baikal region (Siberia, Russia).

PubMed

Averina, E S; Müller, R H; Popov, D V; Radnaeva, L D

2011-05-01

At the turn of the millennium, a new generation of lipid nanoparticles for pharmacology was developed, nanostructured lipid carriers (NLC). The features of NLC structure which allow the inclusion of natural biologically active lipids in the NLC matrix open a wide prospect for the creation of high performance drug carriers. In this study NLC formulations were developed based on natural lipids from the Siberia region (Russia): fish oil from Lake Baikal fish; polyunsaturated fatty acid fractions and monounsaturated and saturated fatty acid fractions from fish oil and Siberian pine seed oil. Formulation parameters of NLC such as as type of surfactant and storage conditions were evaluated. The data obtained indicated high physical stability of NLC formulated on the basis of pure fish oil stabilized by Tween 80 and NLC formulated on the basis of free fatty acids stabilized by Poloxamer 188. The good chemical stability of the lipid matrix and the high concentrations of the biologically active polyunsaturated fatty acids in the NLC developed open wide prospects for their use in pharmaceutics and cosmetics.

Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance.

PubMed

Bosquillon, C; Lombry, C; Préat, V; Vanbever, R

2001-02-23

The objective of this study was to determine the effects of formulation excipients and physical characteristics of inhalation particles on their in vitro aerosolization performance, and thereby to maximize their respirable fraction. Dry powders were produced by spray-drying using excipients that are FDA-approved for inhalation as lactose, materials that are endogenous to the lungs as albumin and dipalmitoylphosphatidylcholine (DPPC); and/or protein stabilizers as trehalose or mannitol. Dry powders suitable for deep lung deposition, i.e. with an aerodynamic diameter of individual particles <3 microm, were prepared. They presented 0.04--0.25 g/cm(3) bulk tap densities, 3--5 microm geometric particle sizes, up to 90% emitted doses and 50% respirable fractions in the Andersen cascade impactor using a Spinhaler inhaler device. The incorporation of lactose, albumin and DPPC in the formulation all improved the aerosolization properties, in contrast to trehalose and the mannitol which decreased powder flowability. The relative proportion of the excipients affected aerosol performance as well. The lower the bulk powder tap density, the higher the respirable fraction. Optimization of in vitro aerosolization properties of inhalation dry powders can be achieved by appropriately selecting composition and physical characteristics of the particles.

Repaglinide-loaded solid lipid nanoparticles: effect of using different surfactants/stabilizers on physicochemical properties of nanoparticles.

PubMed

Ebrahimi, Hossein Ali; Javadzadeh, Yousef; Hamidi, Mehrdad; Jalali, Mohammad Barzegar

2015-09-21

Repaglinide is an efficient anti-diabetic drug which is prescribed widely as multi-dosage oral daily regimens. Due to the low compliance inherent to each multi-dosage regimen, development of prolonged-release formulations could enhance the overall drug efficacy in patient populations. Repaglinide-loaded solid lipid nanoparticles (SLNs) were developed and characterized in vitro. Various surfactants were used in this study during the nanocarrier preparation procedure and their corresponding effects on some physicochemical properties of SLNs such as size, zeta potential; drug loading parameters and drug release profiles was investigated. Stearic acid and glyceryl mono stearate (GMS) were used as lipid phase and phosphatidylcholin, Tween80, Pluronic F127, poly vinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP) were used as surfactant/stabilizer. The results showed some variations between formulations; where the Tween80-based SLNs showed smallest size, the phosphatidylcholin-based SLNs indicated most prolonged drug release time and the highest loading capacity. SEM images of these formulations showed morphological variations and also confirmed the nanoscale size of these particles. The FTIR and DSC results demonstrated no interaction between drug and excipients. The invitro release profiles of different formulations were studied and observed slow release of drug from all formulations. However significant differences were found among them in terms of their initial burst release as well as the whole drug release profile. From fitting these data to various statistical models, the Peppas model was proposed as the best model to describe the statistical indices and, therefore, mechanism of drug release. The results of this study confirmed the effect of surfactant type on SLNs physicochemical properties such as morphological features, loading parameters, particle sizes and drug release kinetic. With respect to the outcome data, the mixture of phosphatidylcholin/Pluronic F127 was selected as the best surfactant/stabilizer to coat the lipid core comprising stearic acid and GMS.

Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel

PubMed Central

2013-01-01

Background Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier in tumor targeting but suffer from the high level of opsonization by reticuloendothelial system due to their hydrophobic structure. As a result surface modification of these nanoparticles has been widely studied as an essential step in their development. Among various surface modifications, human serum albumin (HSA) possesses advantages including small size, hydrophilic surface and accumulation in leaky vasculature of tumors through passive targeting and a probable active transport into tumor tissues. Methods PLGA nanoparticles of docetaxel were prepared by emulsification evaporation method and were surface conjugated with human serum albumin. Fourier transform infrared spectrum was used to confirm the conjugation reaction where nuclear magnetic resonance was utilized for conjugation ratio determination. In addition, transmission electron microscopy showed two different contrast media in conjugated nanoparticles. Furthermore, cytotoxicity of free docetaxel, unconjugated and conjugated PLGA nanoparticles was studied in HepG2 cells. Results Size, zeta potential and drug loading of PLGA nanoparticles were about 199 nm, −11.07 mV, and 4%, respectively where size, zeta potential and drug loading of conjugated nanoparticles were found to be 204 nm, −5.6 mV and 3.6% respectively. Conjugated nanoparticles represented a three-phasic release pattern with a 20% burst effect for docetaxel on the first day. Cytotoxicity experiment showed that the IC50 of HSA conjugated PLGA nanoparticles (5.4 μg) was significantly lower than both free docetaxel (20.2 μg) and unconjugated PLGA nanoparticles (6.2 μg). Conclusion In conclusion surface modification of PLGA nanoparticles through HSA conjugation results in more cytotoxicity against tumor cell lines compared with free docetaxel and unconjugated PLGA nanoparticles. Albumin conjugated PLGA nanoparticles may represent a promising drug delivery system in cancer therapy. PMID:23866721

Chemical and Colloidal Stability of Carboxylated Core-Shell Magnetite Nanoparticles Designed for Biomedical Applications

PubMed Central

Szekeres, Márta; Tóth, Ildikó Y.; Illés, Erzsébet; Hajdú, Angéla; Zupkó, István; Farkas, Katalin; Oszlánczi, Gábor; Tiszlavicz, László; Tombácz, Etelka

2013-01-01

Despite the large efforts to prepare super paramagnetic iron oxide nanoparticles (MNPs) for biomedical applications, the number of FDA or EMA approved formulations is few. It is not known commonly that the approved formulations in many instances have already been withdrawn or discontinued by the producers; at present, hardly any approved formulations are produced and marketed. Literature survey reveals that there is a lack for a commonly accepted physicochemical practice in designing and qualifying formulations before they enter in vitro and in vivo biological testing. Such a standard procedure would exclude inadequate formulations from clinical trials thus improving their outcome. Here we present a straightforward route to assess eligibility of carboxylated MNPs for biomedical tests applied for a series of our core-shell products, i.e., citric acid, gallic acid, poly(acrylic acid) and poly(acrylic acid-co-maleic acid) coated MNPs. The discussion is based on physicochemical studies (carboxylate adsorption/desorption, FTIR-ATR, iron dissolution, zeta potential, particle size, coagulation kinetics and magnetization measurements) and involves in vitro and in vivo tests. Our procedure can serve as an example to construct adequate physico-chemical selection strategies for preparation of other types of core-shell nanoparticles as well. PMID:23857054

Nanoengineered drug delivery systems for enhancing antibiotic therapy.

PubMed

Kalhapure, Rahul S; Suleman, Nadia; Mocktar, Chunderika; Seedat, Nasreen; Govender, Thirumala

2015-03-01

Formulation scientists are recognizing nanoengineered drug delivery systems as an effective strategy to overcome limitations associated with antibiotic drug therapy. Antibiotics encapsulated into nanodelivery systems will contribute to improved management of patients with various infectious diseases and to overcoming the serious global burden of antibiotic resistance. An extensive review of several antibiotic-loaded nanocarriers that have been formulated to target drugs to infectious sites, achieve controlled drug release profiles, and address formulation challenges, such as low-drug entrapment efficiencies, poor solubility and stability is presented in this paper. The physicochemical properties and the in vitro/in vivo performances of various antibiotic-loaded delivery systems, such as polymeric nanoparticles, micelles, dendrimers, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles, nanohybirds, nanofibers/scaffolds, nanosheets, nanoplexes, and nanotubes/horn/rods and nanoemulsions, are highlighted and evaluated. Future studies that will be essential to optimize formulation and commercialization of these antibiotic-loaded nanosystems are also identified. The review presented emphasizes the significant formulation progress achieved and potential that novel nanoengineered antibiotic drug delivery systems have for enhancing the treatment of patients with a range of infections. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Pure drug nanoparticles in tablets: what are the dissolution limitations?

NASA Astrophysics Data System (ADS)

Heng, Desmond; Ogawa, Keiko; Cutler, David J.; Chan, Hak-Kim; Raper, Judy A.; Ye, Lin; Yun, Jimmy

2010-06-01

There has been increasing interests for drug companies to incorporate drug nanoparticles into their existing formulations. However, technical knowledge in this area is still in its infancy and more study needs to be done to stimulate growth in this fledging field. There is a need to scrutinize the performance of pure drug nanoparticles in tablets, particularly relating formulation variables to their dissolution performance. Application of the pure form, synthesized without the use of surfactants or stabilizers, is often preferred to maximize drug loading and also to minimize toxicity. Cefuroxime axetil, a poorly water-soluble cephalosporin antibiotic, was used as the model drug in the formulation development. Drug release rate, tablet disintegration time, tensile strength and energy of failure were predominantly influenced by the amount of super-disintegrant, amount of surfactant, compression force and diluent species, respectively. The compression rate had minimal impact on the responses. The main hurdle confronting the effective use of pure drug nanoparticles in tablets is the difficulty in controlling aggregation in solution, which could potentially be aggravated by the tabletting process. Through the use of elevated levels of surfactants (8 w/w% sodium dodecyl sulphate), drug release from the nanoparticle preparation was enhanced from 58.0 ± 2.7% to 72.3 ± 0.7% in 10 min. Hence, it is recommended that physical formulations for pure drug nanoparticles be focused on the particle de-aggregation step in solution, if much higher rates are to be desired. In conclusion, even though pure drug nanoparticles could be easily synthesized, limitations from aggregation may need to be overcome, before successful application in tablets can be fully realized.

Oral delivery of microparticles containing plasmid DNA encoding hepatitis-B surface antigen.

PubMed

Bhowmik, Tuhin; D'Souza, Bernadette; Uddin, Mohammad N; D'Souza, Martin J

2012-05-01

The role of albumin-based chitosan microparticles on enhancing immune response of plasmid DNA (pDNA) to hepatitis-B surface antigen (HBsAg) vaccine after oral administration was investigated in mice. The pDNA encoding HBsAg was entrapped in albumin microparticles using a one-step spray drying technique optimized in our laboratory. The encapsulated particles were also characterized in vitro for their shape, size, encapsulation efficiency, content, and stability. Albumin microparticles could protect the DNA from nuclease degradation as confirmed in our agarose gel study. Further immune modulating effect was studied in our formulation by measuring IgG antibodies in serum as well as IgA antibodies in fecal extracts. The mice were immunized with a prime dose of 100 μg of pDNA in microparticle formulations with and without interleukins biweekly until week 7 followed by a booster dose of equivalent strength on week 33 to compare the response with the subcutaneous group. The oral immunization with the pDNA to HBsAg microparticles gave significantly higher titer level of both sIgA and IgG at week 9 and 34, respectively, in oral vaccine with interleukins group when compared with the subcutaneous group. Thus, we observed an augmentation of both humoral and cellular immune responses for prolonged periods after immunization.

Interaction of silicon nanoparticles with the molecules of bovine serum albumin in aqueous solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anenkova, K A; Sergeeva, I A; Petrova, G P

2011-05-31

Using the method of photon-correlation spectroscopy, the coefficient of translational diffusion D{sub t} and the hydrodynamic radius R of the particles in aqueous solutions of the bovine serum albumin, containing silicon nanoparticles, are determined. The character of the dependence of these parameters on the concentration of the protein indicates the absence of interaction between the studied particles in the chosen range of albumin concentrations 0.2 - 1.0 mg mL{sup -1}. (optical technologies in biophysics and medicine)

Development of a lauric acid/albumin hybrid iron oxide nanoparticle system with improved biocompatibility

PubMed Central

Zaloga, Jan; Janko, Christina; Nowak, Johannes; Matuszak, Jasmin; Knaup, Sabine; Eberbeck, Dietmar; Tietze, Rainer; Unterweger, Harald; Friedrich, Ralf P; Duerr, Stephan; Heimke-Brinck, Ralph; Baum, Eva; Cicha, Iwona; Dörje, Frank; Odenbach, Stefan; Lyer, Stefan; Lee, Geoffrey; Alexiou, Christoph

2014-01-01

The promising potential of superparamagnetic iron oxide nanoparticles (SPIONs) in various nanomedical applications has been frequently reported. However, although many different synthesis methods, coatings, and functionalization techniques have been described, not many core-shell SPION drug delivery systems are available for clinicians at the moment. Here, bovine serum albumin was adsorbed onto lauric acid-stabilized SPIONs. The agglomeration behavior, zeta potential, and their dependence on the synthesis conditions were characterized with dynamic light scattering. The existence and composition of the core-shell-matrix structure was investigated by transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta potential measurements. We showed that the iron oxide cores form agglomerates in the range of 80 nm. Moreover, despite their remarkably low tendency to aggregate even in a complex media like whole blood, the SPIONs still maintained their magnetic properties and were well attractable with a magnet. The magnetic properties were quantified by vibrating sample magnetometry and a superconducting quantum interference device. Using flow cytometry, we further investigated the effects of the different types of nanoparticle coating on morphology, viability, and DNA integrity of Jurkat cells. We showed that by addition of bovine serum albumin, the toxicity of nanoparticles is greatly reduced. We also investigated the effect of the particles on the growth of primary human endothelial cells to further demonstrate the biocompatibility of the particles. As proof of principle, we showed that the hybrid-coated particles are able to carry payloads of up to 800 μg/mL of the cytostatic drug mitoxantrone while still staying colloidally stable. The drug-loaded system exhibited excellent therapeutic potential in vitro, exceeding that of free mitoxantrone. In conclusion, we have synthesized a biocompatible ferrofluid that shows great potential for clinical application. The synthesis is straightforward and reproducible and thus easily translatable into a good manufacturing practice environment. PMID:25364244

Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines

PubMed Central

Hossain, Md Kamal; Wall, Katherine A.

2016-01-01

Aberrantly glycosylated mucin 1 (MUC1) is a recognized tumor-specific antigen on epithelial cell tumors. A wide variety of MUC1 glycopeptide anti-cancer vaccines have been formulated by many research groups. Some researchers have used MUC1 alone as an immunogen whereas other groups used different antigenic carrier proteins such as bovine serum albumin or keyhole limpet hemocyanin for conjugation with MUC1 glycopeptide. A variety of adjuvants have been used with MUC1 glycopeptides to improve their immunogenicity. Fully synthetic multicomponent vaccines have been synthesized by incorporating different T helper cell epitopes and Toll-like receptor agonists. Some vaccine formulations utilized liposomes or nanoparticles as vaccine delivery systems. In this review, we discuss the immunological evaluation of different conjugate or synthetic MUC1 glycopeptide vaccines in different tumor or mouse models that have been published since 2012. PMID:27472370

Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers.

PubMed

Wang, Lulu; Ma, Yingying; Gu, Yu; Liu, Yangyang; Zhao, Juan; Yan, Beibei; Wang, Yancai

2018-04-19

Freeze-drying is an effective way to improve long-term physical stability of nanosuspension in drug delivery applications. Nanosuspension also known as suspension of nanoparticles. In this study, the effect of freeze-drying with different cryoprotectants on the physicochemical characteristics of resveratrol (RSV) nanosuspension and quercetin (QUE) nanosuspension was evaluated. D-α-tocopheryl polyethylene glycol succinate (TPGS) and folate-modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) were selected as functional stabilisers formulated nanosuspension which were prepared by anti-solvent precipitation method. RSV nanoparticle size and QUE nanoparticle size were about 210 and 110 nm, respectively. The AFM and TEM results of nanosuspension showed uniform and irregular shape particles. After freeze-drying, the optimal concentration of four cryoprotectants was determined by the particle size of re-dispersed nanoparticles. The dissolution profile of drug nanoparticle significantly showed approximately at a 6-8-fold increase dissolution rate. Moreover, TPGS and DSPE-PEG-FA stabilised RSV nanosuspension and QUE nanosuspension samples showed better effect on long-term physical stability.

Enhancement of in-vitro drug dissolution of ketoconazole for its optimal in-vivo absorption using Nanoparticles and Solid Dispersion forms of the drug

NASA Astrophysics Data System (ADS)

Syed, Mohammed Irfan

Ketoconazole is one of the most widely prescribed oral antifungal drugs for the systemic treatment of various fungal infections. However, due its hydrophobic nature and poor solubility profiles in the gastro-intestinal fluids, variations in its bioavailability have been documented. Therefore, to enhance its dissolution in the biological fluids, this study was initiated to develop and evaluate Nanoparticles and Solid Dispersion forms of the drug. Nanoparticles of ketoconazole were developed by Wet Bead Milling technique using PVP-10k as the stabilizing material at a weight ratio of (2:1). Solid dispersion powder was prepared by Hot Melt method using PEG-8000 at a weight ratio of (1:2). A commercial product containing 200mg of ketoconazole tablet and pure drug powder were used as the control for comparison purposes. The dissolution studies were carried out in SGF, SIF, USP; and SIF with 0.2% sodium lauryl sulfate using the USP-II method for a 2 hours period. Physical characterizations were carried out using SEM, DSC, XRD and FTIR studies. Wet Bead Milling method yielded nanoparticles in the particles size range of (100-300nm.). First all samples were evaluated for their in-vitro dissolution in SGF at pH=1.2. After 15 minutes, the amounts of drug dissolved were observed to be 27% from both the pure powder and commercial tablet (control), 29% from solid dispersion and 100% from the Nanoparticles dosage form. This supports the fact that Nanoparticles had a strong influence on the dissolution rate of the drug and exhibited much faster dissolution of ketoconazole. When the same formulations were studied in the SIF, USP medium, the control formulation gave 3%, solid dispersion 8% and Nanoparticles 8% drug dissolution after 2 hours period. This could be because the weakly basic ketoconazole drug remained un-dissociated in the alkaline medium. Since this medium was unable to clearly distinguish the dissolution profiles from different formulation of the drug, the SIF solution was modified to include 0.02%, 0.05% and 0.1% sodium lauryl sulfate. Here, after 2 hours, the amount of drug dissolved was calculated to be 10% from controls, 21% from solid dispersion and 36% from nanoparticles in SIF with 0.02% SLS. Drug release was 20% from controls, 41% from solid dispersion and 52% from nanoparticle formulation in SIF with 0.05% SLS. Whereas amount of drug released in SIF with 0.1% SLS showed 21% from the control, 62% from solid dispersion and 85% from Nanoparticles respectively. This data supports that the ketoconazole Nanoparticles and its solid-dispersion exhibit many fold increase in dissolution of the drug, which could lead to a less variable and enhanced in-vivo drug absorption profiles. In addition, the data from the Physical Characterization (DSC, XRD and FTIR) supports that there were no interaction within the ingredients occurred in Nanoparticles and solid-dispersion formulations of the drug sample. Wet Bead Milling and Hot Melt methods proved useful in developing the Nanoparticles and solid dispersion form of ketoconazole. Results from particle size analysis were in correlation with data obtained from Scanning electron Microscopy and size of the nanoparticles was below 100nm. The dissolution studies with the modified simulated intestinal fluid (SIF) exhibited several fold increase in the dissolution of the drug compared to the pure drug powder and the commercial products used as the control. Also, the results from the physical characterization studies clearly support the stability of ketoconazole in both of these formulations.

Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

PubMed Central

Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

2013-01-01

Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher C max than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile. PMID:24058913

Fabrication, appraisal, and transdermal permeation of sildenafil citrate-loaded nanostructured lipid carriers versus solid lipid nanoparticles

PubMed Central

Elnaggar, Yosra SR; El-Massik, Magda A; Abdallah, Ossama Y

2011-01-01

Although sildenafil citrate (SC) is used extensively for erectile dysfunction, oral delivery of SC encounters many obstacles. Furthermore, the physicochemical characteristics of this amphoteric drug are challenging for delivery system formulation and transdermal permeation. This article concerns the assessment of the potential of nanomedicine for improving SC delivery and transdermal permeation. SC-loaded nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were fabricated using a modified high-shear homogenization technique. Nanoparticle optimization steps included particle size analysis, entrapment efficiency (EE) determination, freeze-drying and reconstitution, differential scanning calorimetry, in vitro release, stability study and high-performance liquid chromatography analysis. Transdermal permeation of the nanocarriers compared with SC suspension across human skin was assessed using a modified Franz diffusion cell assembly. Results revealed that SLNs and NLCs could be optimized in the nanometric range (180 and 100 nm, respectively) with excellent EE (96.7% and 97.5%, respectively). Nanoparticles have significantly enhanced in vitro release and transdermal permeation of SC compared with its suspensions. Furthermore, transdermal permeation of SC exhibited higher initial release from both SLN and NLC formulations followed by controlled release, with promising implications for faster onset and longer drug duration. Nanomedicines prepared exhibited excellent physical stability for the study period. Solid nanoparticles optimized in this study successfully improved SC characteristics, paving the way for an efficient topical Viagra® product. PMID:22238508

Combination of grape extract-silver nanoparticles and liposomes: A totally green approach.

PubMed

Castangia, Ines; Marongiu, Francesca; Manca, Maria Letizia; Pompei, Raffaello; Angius, Fabrizio; Ardu, Andrea; Fadda, Anna Maria; Manconi, Maria; Ennas, Guido

2017-01-15

In the present work, silver nanoparticles were prepared using a totally green procedure combining silver nitrate and an extract of grape pomace as a green source. Additionally, nanoparticles were stabilized using phospholipid and water and/or a mixture of water and propylene glycol (PG). To the best of our knowledge, grape-silver nanoparticle stabilized liposomes or PG-liposomes were formulated, for the first time, combining the residual products of wine-made industry, silver nitrate and phospholipids, avoiding the addition of hazardous substances to human health and the environment, in an easy, scalable and reproducible method. The structure and morphology of grape-silver nanoparticle stabilized vesicles were evaluated by transmission electron microscopy (TEM), UV-vis spectroscopy and photon correlation spectroscopy. Samples were designed as possible carrier for skin protection because of their double function: the grape extract acts as antioxidant and the colloidal silver as antimicrobial agent, which might be helpful in eliminating dangerous free radicals and many pathogenic microorganisms. Obtained nanoparticles were small in size and their combination with phospholipids did not hamper the vesicle formation, which were multilamellar and sized ~100nm. TEM images shows a heterogeneous distribution of nanoparticles, which were located both in the intervesicular medium and in the vesicular structure. Further, grape-silver nanoparticles, when stabilized by liposomes, were able to inhibit the proliferation of both Staphylococcus aureus and Pseudomonas aeruginosa and provided a great protection of keratinocytes and fibroblasts against oxidative stress avoiding their damage and death. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics

PubMed Central

Ahmed, Osama AA; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

2015-01-01

The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid–liquid phase separation method, according to the Box–Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance. PMID:25670883

Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment.

PubMed

Barhate, Ganesh; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Pokharkar, Varsha

2014-11-01

Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Structural stability and sustained release of protein from a multilayer nanofiber/nanoparticle composite.

PubMed

Vakilian, Saeid; Mashayekhan, Shohreh; Shabani, Iman; Khorashadizadeh, Mohsen; Fallah, Ali; Soleimani, Masoud

2015-04-01

The cellular microenvironment can be engineered through the utilization of various nano-patterns and matrix-loaded bioactive molecules. In this study, a multilayer system of electrospun scaffold containing chitosan nanoparticles was introduced to overcome the common problems of instability and burst release of proteins from nanofibrous scaffolds. Bovine serum albumin (BSA)-loaded chitosan nanoparticles was fabricated based on ionic gelation interaction between chitosan and sodium tripolyphosphate. Suspension electrospinning was employed to fabricate poly-ɛ-caprolacton (PCL) containing protein-loaded chitosan nanoparticles with a core-shell structure. To obtain the desired scaffold mechanical properties with enough elasticity for expansion and contraction, a hybrid mono and multilayer electrospun scaffold was fabricated using PCL containing protein-loaded chitosan nanoparticles and poly-L-lactic acid (PLLA). According to the BSA release profile, the multi-layered structure of nanofibers with two barrier layers provided a programmable release pattern of the loaded protein. Moreover, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and circular dichroism spectra results showed that the electrospinning process had no significant effect on the primary and secondary structure of the protein. The results indicated a desirable biocompatibility and mechanical cues of the multilayer nanofibrous scaffolds supporting structural stability and controlled release of the protein, which can offer diverse applications in hollow organ tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

Gold nanoparticle assemblies of controllable size obtained by hydroxylamine reduction at room temperature

NASA Astrophysics Data System (ADS)

Tódor, István Sz.; Szabó, László; Marişca, Oana T.; Chiş, Vasile; Leopold, Nicolae

2014-12-01

Colloidal nanoparticle assemblies (NPAs) were obtained in a one-step procedure, by reduction of HAuCl4 by hydroxylamine hydrochloride, at room temperature, without the use of any additional nucleating agent. By changing the order of the reactants, NPAs with mean size of 20 and 120 nm were obtained. Because of their size and irregular popcorn like shape, the larger size NPAs show absorption in the NIR spectral region. The building blocks of the resulted nanoassemblies are spherical nanoparticles with diameters of 4-8 and 10-30 nm, respectively. Moreover, by stabilizing the colloid with bovine serum albumin at different time moments after synthesis, NPAs of controlled size between 20 and 120 nm, could be obtained. The NPAs were characterized using UV-Vis spectroscopy, TEM and SEM electron microscopies. In addition, the possibility of using the here proposed NPAs as surface-enhanced Raman scattering (SERS) substrate was assessed and found to provide a higher enhancement compared to conventional citrate-reduced nanoparticles.

Attachment of an anti-MUC1 monoclonal antibody to 5-FU loaded BSA nanoparticles for active targeting of breast cancer cells.

PubMed

Kouchakzadeh, Hasan; Shojaosadati, Seyed Abbas; Mohammadnejad, Javad; Paknejad, Malihe; Rasaee, Mohammad Javad

2012-01-01

With PR81 as a murine monoclonal antibody (mAb) that was prepared against the human breast cancer, the MUC1 receptor specific targeting is possible. In this study, PR81-conjugated bovine serum albumin (BSA) nanoparticles loaded with anticancer drug 5-fluorouracil (5-FU) were developed. Enzyme linked immunosorbant assay (ELISA) results showed high immunoreactivity of PR81 mAb conjugated to nanoparticles towards MUC1 related peptide or native cancerous MUC1 and almost no cross-reaction to non-specific proteins. In vitro experiments were performed to determine the ability of this new drug delivery system on overcoming MCF-7 breast cancer cells in comparison with four other systems. The results revealed that these cell-type specific drug loaded nanoparticles could achieve more cell death as compared to when the 5-FU was used with no carriers. Stability studies of produced drug delivery system proved high immunoreactivity of conjugated PR81 even after 11 days of storage in room temperature.

Water-in-Oil Microemulsions for Protein Delivery: Loading Optimization and Stability.

PubMed

Perinelli, Diego R; Cespi, Marco; Pucciarelli, Stefania; Vincenzetti, Silvia; Casettari, Luca; Lam, Jenny K W; Logrippo, Serena; Canala, Elisa; Soliman, Mahmoud E; Bonacucina, Giulia; Palmieri, Giovanni F

2017-01-01

Microemulsions are attractive delivery systems for therapeutic proteins and peptides due to their ability to enhance bioavailability. Although different proteins and peptides have been successfully delivered through such ternary systems, no information can be found about protein loading and the formulation stability when such microemulsions are prepared with pharmaceuticallyapproved oils and surfactants. The aim of this work was to optimise a ternary system consisting of water/ ethyl oleate/Span® 80-Tween® 80 and to determine its protein loading capacity and stability, using bovine serum albumin (BSA) as a model of biomolecule. The optimization was carried out using a Central Composite Design and all the prepared formulations were characterised through dynamic light scattering, rheology, optical and polarized microscopy. Subsequently, the maximum loading capacity was determined and the stability of the final microemulsion with the highest content of protein was followed over six months. To investigate the structural features of the protein, BSA was recovered from the microemulsion and analysed through fluorescence spectroscopy. After incorporation of the protein in the microemulsion, a decrease of its aqueous solubility was observed. However, the formulation remained stable over six months and the native-like state of the recovered protein was demonstrated by fluorescence spectroscopy Conclusion: This study demonstrated the feasibility of preparing microemulsions with the highest content of protein and their long-term stability. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lack of a synergistic effect of arginine-glutamic acid on the physical stability of spray-dried bovine serum albumin.

PubMed

Reslan, Mouhamad; Demir, Yusuf K; Trout, Bernhardt L; Chan, Hak-Kim; Kayser, Veysel

2017-09-01

Improving the physical stability of spray-dried proteins is essential for enabling pulmonary delivery of biotherapeutics as a noninvasive alternative to injections. Recently, a novel combination of two amino acids - l-arginine (l-Arg) and l-glutamic acid (l-Glu), has been reported to have synergistic protein-stabilizing effects on various protein solutions. Using spray-dried bovine serum albumin (BSA) reconstituted in solution as a model protein, we investigated the synergistic effect of these amino acids on the physical stability of proteins. Five BSA solutions were prepared: (1) BSA with no amino acids (control); (2) with 50 mM l-Arg; (3) with 200 mM l-Arg, (4) with 50 mM l-Glu and (5) with 25:25 mM of Arg:Glu. All solutions were spray-dried and accelerated studies at high temperatures were performed. Following accelerated studies, monomer BSA loss was measured using SE-HPLC. We found that l-Arg significantly improved the physical stability of spray-dried BSA even at low concentrations, however, when combined with l-Glu, was ineffective at reducing monomer BSA loss. Our findings demonstrate the limitations in using Arg-Glu for the stabilization of spray-dried BSA. Furthermore, we found that a low concentration of l-Glu enhanced monomer BSA loss. These findings may have significant implications on the design of future biotherapeutic formulations.

Formulation and shelf life stability of water-borne lecithin nanoparticles for potential application in dietary supplements field.

PubMed

Edris, Amr E

2012-09-01

ABSTRACT The objective of the present investigation is to formulate commercial soybean lecithin as nanoparticles in solvent-free aqueous system for potential supplementary applications. A mechanical method, which involved two major steps, was used for that purpose. First, lecithin submicron particles (~ 0.5 μm) have been prepared by gradual hydration of lecithin powder using mechanical agitation. Finally, the size of these particles was further reduced to < 100 nm by using high-pressure microfluidization. The physical stability (appearance, particle size distribution, ζ-potential) and the chemical stability (lipid oxidation) of the dispersions carrying lecithin nanoparticles were assessed every 15 days during the 3-month shelf life period at two different temperatures. Results showed that the final particle size of lecithin in the freshly prepared aqueous dispersion was 79.8 ± 1.0 nm and the amount of peroxide detected was 3.5 ± 0.2 meq/kg lipid. At the end of the storage period, dispersions stored at 4°C exhibited physical and chemical stability as evident from the translucent appearance, the small change in particle size (84.1 ± 1.3 nm), and the small amount of generated peroxides (4.1 ± 0.2 meq/kg lipid). On the other hand, dispersions stored at 25°C were physically stable up to 60 days. Over that period, samples became turbid and the particle size increased to 145.0 ± 1.7 nm with a bimodal distribution pattern. This behavior was due to phospholipids (PLs) degradation and hydrolysis under acidic conditions, which proceeds faster at a relatively high temperature (25°C) than at (4°C). The outcome of this investigation may help in developing water-based dispersions carrying lecithin nanoparticles for dietary supplement of PLs.

Radiation-induced preparation of core/shell gold/albumin nanoparticles

NASA Astrophysics Data System (ADS)

Flores, Constanza Y.; Achilli, Estefania; Grasselli, Mariano

2018-01-01

Nanoparticles (NPs) are one of the most promising nanomaterials to be used in the biomedical field. Gold NPs (Au-NPs) have been covered with monolayers of many different molecules and macromolecules to prepare different kinds of biosensors. However, these coatings based on physisorption methods are not stable enough to prepare functional nanomaterials to be used in complex mixtures or in vivo applications. The aim of this work was to prepare a protein coating of Au-NPs based on a protein multilayer covering, stabilized by a novel radiation-induced crosslinking process. Albumins from human and bovine source were added to Au-NPs suspension and followed by ethanol addition to induce protein aggregation. Samples were irradiated with a gamma source at 10 kGy to induce a protein crosslinking according to recent findings. Samples containing 30%v/v ethanol showed a plasmon peak at about 532 nm, demonstrating the presence of non-aggregated Au-NPs. Using higher ethanol concentrations, the absorbance of plasmon peak showed NP aggregation. By Dynamic Light Scattering measurements, a new particle population with an average diameter of about 60 nm was found. Moreover, TEM images showed that the NPs had spherical shape and the presence of a low-density halo around the metal core confirmed the presence of the protein shell. An irradiation dose of one kGy was enough to show changes in the plasmon peak characteristics. The increase in the chemical stability of protein shell was demonstrated by the reduction in the NP dissolution kinetics in presence of cyanate.

Spectroscopic interaction study of human serum albumin and human hemoglobin with Mersilea quadrifolia leaves extract mediated silver nanoparticles having antibacterial and anticancer activity

NASA Astrophysics Data System (ADS)

Maji, Anukul; Beg, Maidul; Mandal, Amit Kumar; Das, Somnath; Jha, Pradeep K.; Kumar, Anoop; Sarwar, Shamila; Hossain, Maidul; Chakrabarti, Pinak

2017-08-01

This study looks into a safe, proficient and low-cost way for the preparation of novel silver nanoparticles by using 5% aqueous leaves extract of a medicinal plant, Marsilea quadrifolia (family: Marsileaceae) without using any external reducing and stabilizing agents. The synthesized AgNPs showed maximum UV-Vis absorbance at 435 nm due to surface plasmon resonance (SPR). The average diameter (∼22.5 nm) of AgNPs was measured from TEM analysis and was also supported by FE-SEM. The existence of a silver signal in EDX spectra supported the AgNPs formation and negative zeta potential value (-18.7 mV) which suggested its stability. FT-IR spectroscopic analysis showed that the functional groups like sbnd Osbnd H, sbnd Nsbnd H and sbnd Cdbnd O were responsible for the synthesis of AgNPs. The antibacterial activity of the AgNPs was tested against E. coli ATCC 25922. The anticancer potential of AgNPs was also assessed using two different cell lines, such as MCF-7 and HeLa. The interaction study of AgNPs with human serum albumin (HSA) and human hemoglobin (Hb) was performed by means of UV-Vis, fluorescence spectroscopy, Circular dichroism (CD) and zeta potential measurement. More negative zeta potential values of AgNPs-HSA/Hb (-21.1/-19.5 mV) complexes than AgNPs (-18.7 mV) indicated corresponding stability of bio-conjugates. The basic structure of HSA/Hb remained unchanged and its secondary structure was slightly changed upon interaction with the AgNPs concluded from Circular dichroism. So, it can be predicted that this AgNPs may be applied in the medical field.

Multifunctional biocompatible coatings on magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Bychkova, A. V.; Sorokina, O. N.; Rosenfeld, M. A.; Kovarski, A. L.

2012-11-01

Methods for coating formation on magnetic nanoparticles used in biology and medicine are considered. Key requirements to the coatings are formulated, namely, biocompatibility, stability, the possibility of attachment of pharmaceutical agents, and the absence of toxicity. The behaviour of nanoparticle/coating nanosystems in the body including penetration through cellular membranes and the excretion rates and routes is analyzed. Parameters characterizing the magnetic properties of these systems and their magnetic controllability are described. Factors limiting the applications of magnetically controlled nanosystems for targeted drug delivery are discussed. The bibliography includes 405 references.

Protonation of epigallocatechin-3-gallate (EGCG) results in massive aggregation and reduced oral bioavailability of EGCG-dispersed selenium nanoparticles.

PubMed

Wu, Shanshan; Sun, Kang; Wang, Xin; Wang, Dongxu; Wan, Xiaochun; Zhang, Jinsong

2013-07-31

The current results show that epigallocatechin-3-gallate (EGCG), in the form of phenolic anions at pH 8.0, can effectively disperse selenium nanoparticles. However, at gastric juice pH (1.0), the EGCG-dispersed selenium nanoparticles (referred to as E-Se) extensively aggregated, so that nano features largely disappeared. This demonstrates that deprotonated phenolic anions of EGCG play an important role in maintaining E-Se stability and suggests that E-Se would suffer from reduced oral bioavailability. To validate this conjecture, size-equivalent E-Se and bovine serum albumin (BSA)-dispersed selenium nanoparticles (B-Se), whose physicochemical properties were not altered at pH 1.0, were orally administered to selenium-deficient mice. In comparison to B-Se, the bioavailabilities of E-Se as indicated with hepatic and renal glutathione peroxidase activity and hepatic selenium levels were significantly (p < 0.01) reduced by 39, 32, and 31%, respectively. Therefore, the present study reveals that size-equivalent selenium nanoparticles prepared by different dispersers do not necessarily guarantee equivalent oral bioavailability.

BSA nanoparticle loaded atorvastatin calcium--a new facet for an old drug.

PubMed

Sripriyalakshmi, S; Anjali, C H; George, Priya Doss C; Rajith, B; Ravindran, Aswathy

2014-01-01

Currently, the discovery of effective chemotherapeutic agents poses a major challenge to the field of cancer biology. The present study focuses on enhancing the therapeutic and anti cancer properties of atorvastatin calcium loaded BSA (ATV-BSA) nanoparticles in vitro. BSA-ATV nanoparticles were prepared using desolvation technique. The process parameters were optimized based on the amount of desolvating agent, stabilization conditions as well as the concentration of the cross linker. The anti cancer properties of the protein coated ATV nanoparticles were tested on MiaPaCa-2 cell lines. In vitro release behavior of the drug from the carrier suggests that about 85% of the drug gets released after 72 hrs. Our studies show that ATV-BSA nanoparticles showed specific targeting and enhanced cytotoxicity to MiaPaCa-2 cells when compared to the bare ATV. We hereby propose that the possible mechanism of cellular uptake of albumin bound ATV could be through caveolin mediated endocytosis. Hence our studies open up new facet for an existing cholesterol drug as a potent anti-cancer agent.

Geraniol encapsulated in chitosan/gum arabic nanoparticles: a promising system for pest management in sustainable agriculture.

PubMed

de Oliveira, Jhones Luiz; Campos, Estefania Vangelie Ramos; Pereira, Anderson E S; Nunes, Lucas E S; da Silva, Camila C L; Pasquoto, Tatiane; Lima, Renata; Smaniotto, Giovani; Polanczyk, Ricardo Antonio; Fraceto, Leonardo F

2018-05-07

The nanoencapsulation of botanical compounds (such as geraniol) is an important strategy that can be used to increase the stability and efficiency of these substances in integrated pest management. In this study, chitosan/gum arabic nanoparticles containing geraniol were prepared and characterized. In addition, evaluation was made of the biological activity of geraniol encapsulated in chitosan/gum arabic nanoparticles towards whitefly (Bemisia tabaci). The optimized formulation showed a high encapsulation efficiency (>90%) and remained stable for about 120 days. The formulation protected the geraniol against degradation by UV radiation, and the in vitro release was according to a diffusion mechanism that was influenced by temperature. An attraction effect was observed for Bemisia tabaci, indicating the potential of this type of system for use in pest management, especially in trap devices.

Cholesteryl oleate-loaded cationic solid lipid nanoparticles as carriers for efficient gene-silencing therapy

PubMed Central

Suñé-Pou, Marc; Prieto-Sánchez, Silvia; El Yousfi, Younes; Boyero-Corral, Sofía; Nardi-Ricart, Anna; Nofrerias-Roig, Isaac; Pérez-Lozano, Pilar; García-Montoya, Encarna; Miñarro-Carmona, Montserrat; Ticó, Josep Ramón; Suñé-Negre, Josep Mª; Hernández-Munain, Cristina; Suñé, Carlos

2018-01-01

Background Cationic solid lipid nanoparticles (SLNs) have been given considerable attention for therapeutic nucleic acid delivery owing to their advantages over viral and other nanoparticle delivery systems. However, poor delivery efficiency and complex formulations hinder the clinical translation of SLNs. Aim The aim of this study was to formulate and characterize SLNs incorporating the cholesterol derivative cholesteryl oleate to produce SLN–nucleic acid complexes with reduced cytotoxicity and more efficient cellular uptake. Methods Five cholesteryl oleate-containing formulations were prepared. Laser diffraction and laser Doppler microelectrophoresis were used to evaluate particle size and zeta potential, respectively. Nanoparticle morphology was analyzed using electron microscopy. Cytotoxicity and cellular uptake of lipoplexes were evaluated using flow cytometry and fluorescence microscopy. The gene inhibition capacity of the lipoplexes was assessed using siRNAs to block constitutive luciferase expression. Results We obtained nanoparticles with a mean diameter of approximately 150–200 nm in size and zeta potential values of 25–40 mV. SLN formulations with intermediate concentrations of cholesteryl oleate exhibited good stability and spherical structures with no aggregation. No cell toxicity of any reference SLN was observed. Finally, cellular uptake experiments with DNA-and RNA-SLNs were performed to select one reference with superior transient transfection efficiency that significantly decreased gene activity upon siRNA complexation. Conclusion The results indicate that cholesteryl oleate-loaded SLNs are a safe and effective platform for nonviral nucleic acid delivery. PMID:29881274

Freeze drying optimization of polymeric nanoparticles for ocular flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability.

PubMed

Ramos Yacasi, Gladys Rosario; Calpena Campmany, Ana Cristina; Egea Gras, María Antonia; Espina García, Marta; García López, María Luisa

2017-04-01

The stabilization of flurbiprofen loaded poly-ɛ-caprolactone nanoparticles (FB-PɛCL-NPs) for ocular delivery under accurate freeze-drying (FD) process provides the basis for a large-scale production and its commercial development. Optimization of the FD to improve long-term stability of ocular administration's FB-PɛCL-NPs. FB-PɛCL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary drying (PD) were studied and optimized through freeze-thawing test and FD microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to study interactions components. Optimized FB-PɛCL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted to precooling at +10 °C for 1 h, freezing at -50 °C for 4 h, PD at +5 °C and 0.140 mbar for 24 h and a SD at +45 °C during 10 h. These conditions showed 188.4 ± 1.3 nm, 0.087 ± 0.014, 85.5 ± 1.4%, 0.61 ± 0.12%, -16.4 ± 0.1 mV and 325 ± 7 mOsm/kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability >12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after FD. An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the FD process.

Human Albumin Fragments Nanoparticles as PTX Carrier for Improved Anti-cancer Efficacy

PubMed Central

Ge, Liang; You, Xinru; Huang, Jun; Chen, Yuejian; Chen, Li; Zhu, Ying; Zhang, Yuan; Liu, Xiqiang; Wu, Jun; Hai, Qian

2018-01-01

For enhanced anti-cancer performance, human serum albumin fragments (HSAFs) nanoparticles (NPs) were developed as paclitaxel (PTX) carrier in this paper. Human albumins were broken into fragments via degradation and crosslinked by genipin to form HSAF NPs for better biocompatibility, improved PTX drug loading and sustained drug release. Compared with crosslinked human serum albumin NPs, the HSAF-NPs showed relative smaller particle size, higher drug loading, and improved sustained release. Cellular and animal results both indicated that the PTX encapsulated HSAF-NPs have shown good anti-cancer performance. And the anticancer results confirmed that NPs with fast cellular internalization showed better tumor inhibition. These findings will not only provide a safe and robust drug delivery NP platform for cancer therapy, but also offer fundamental information for the optimal design of albumin based NPs. PMID:29946256

A tetravalent dengue nanoparticle stimulates antibody production in mice.

PubMed

Silva, Elisângela F; Orsi, Mariana; Andrade, Angela L; Domingues, Rosana Z; Silva, Breno M; de Araújo, Helena R C; Pimenta, Paulo F P; Diamond, Michael S; Rocha, Eliseu S O; Kroon, Erna G; Malaquias, Luiz C C; Coelho, Luiz F L

2012-03-22

Dengue is a major public health problem worldwide, especially in the tropical and subtropical regions of the world. Infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing secondary infection with a different serotype progresses to the severe form of the disease, dengue hemorrhagic fever/dengue shock syndrome. Currently, there are no licensed vaccines or antiviral drugs to prevent or treat dengue infections. Biodegradable nanoparticles coated with proteins represent a promising method for in vivo delivery of vaccines. Here, we used a murine model to evaluate the IgG production after administration of inactivated DENV corresponding to all four serotypes adsorbed to bovine serum albumin nanoparticles. This formulation induced a production of anti-DENV IgG antibodies (p < 0.001). However, plaque reduction neutralization assays with the four DENV serotypes revealed that these antibodies have no neutralizing activity in the dilutions tested. Our results show that while the nanoparticle system induces humoral responses against DENV, further investigation with different DENV antigens will be required to improve immunogenicity, epitope specicity, and functional activity to make this platform a viable option for DENV vaccines.

Preparation of Curcumin Loaded Egg Albumin Nanoparticles Using Acetone and Optimization of Desolvation Process.

PubMed

Aniesrani Delfiya, D S; Thangavel, K; Amirtham, D

2016-04-01

In this study, acetone was used as a desolvating agent to prepare the curcumin-loaded egg albumin nanoparticles. Response surface methodology was employed to analyze the influence of process parameters namely concentration (5-15%w/v) and pH (5-7) of egg albumin solution on solubility, curcumin loading and entrapment efficiency, nanoparticles yield and particle size. Optimum processing conditions obtained from response surface analysis were found to be the egg albumin solution concentration of 8.85%w/v and pH of 5. At this optimum condition, the solubility of 33.57%, curcumin loading of 4.125%, curcumin entrapment efficiency of 55.23%, yield of 72.85% and particles size of 232.6 nm were obtained and these values were related to the values which are predicted using polynomial model equations. Thus, the model equations generated for each response was validated and it can be used to predict the response values at any concentration and pH.

Effects of Gold Salt Speciation and Structure of Human and Bovine Serum Albumin on the Synthesis and Stability of Gold Nanostructures

NASA Astrophysics Data System (ADS)

Miranda, Érica; Tofanello, Aryane; Brito, Adrianne; Lopes, David; Giacomelli, Fernando; Albuquerque, Lindomar; Costa, Fanny; Ferreira, Fabio; Araujo-Chaves, Juliana; de Castro, Carlos; Nantes, Iseli

2016-03-01

The present study aimed to investigate the influence of albumin structure and gold speciation on the synthesis of gold nanoparticles (GNPs). The strategy of synthesis was the addition of HAuCl4 solutions at different pH values (3-12) to solutions of human and bovine serum albumins (HSA and BSA) at the same corresponding pH values. Different pH values influence the GNP synthesis due to gold speciation. Besides the inherent effect of pH on the native structure of albumins, the use N-ethylmaleimide (NEM)-treated and heat-denaturated forms of HSA and BSA provided additional insights about the influence of protein structure, net charge, and thiol group approachability on the GNP synthesis. NEM treatment, heating, and the extreme values of pH promoted loss of the native albumin structure. The formation of GNPs indicated by the appearance of surface plasmon resonance (SPR) bands became detectable from fifteen days of the synthesis processes that were carried out with native, NEM-treated and heat-denaturated forms of HSA and BSA, exclusively at pH 6 and 7. After two months of incubation, SPR band was also detected for all synthesis carried out at pH 8.0. The mean values of the hydrodynamic radius (RH) were 24 and 34 nm for GNPs synthesized with native HSA and BSA, respectively. X-ray diffraction (XRD) revealed crystallites of 13 nm. RH, XRD, and zeta potential values were consistent with GNP capping by the albumins. However, the GNPs produced with NEM-treated and heat-denaturated albumins exhibited loss of protein capping by lowering the ionic strength. This result suggests a significant contribution of non-electrostatic interactions of albumins with the GNP surface, in these conditions. The denaturation of proteins exposes hydrophobic groups to the solvent, and these groups could interact with the gold surface. In these conditions, the thiol blockage or oxidation, the latter probably favored upon heating, impaired the formation of a stable capping by thiol coordination with the gold surface. Therefore, the cysteine side chain of albumins is important for the colloidal stabilization of GNPs rather than as the reducing agent for the synthesis. Despite the presence of more reactive gold species at more acidic pH values, i.e., below

Curcumin-loaded solid lipid nanoparticles have prolonged in vitro antitumour activity, cellular uptake and improved in vivo bioavailability.

PubMed

Sun, Jiabei; Bi, Chao; Chan, Hok Man; Sun, Shaoping; Zhang, Qingwen; Zheng, Ying

2013-11-01

The aim of the present study was to blend liquid lipids with solid lipids to encapsulate curcumin in solid lipid nanoparticles (SLNs), thereby improving the dispersibility and chemical stability of curcumin, prolonging its antitumour activity and cellular uptake and enhancing its bioavailability. Curcumin-loaded SLNs (C-SLNs) were prepared by high-pressure homogenisation with liquid lipid Sefsol-218(®). The morphology, stability and release of curcumin in the optimised formulation were investigated. The anti-cancer activity of the formulation was evaluated in MCF-7 cells. Fluorescence spectrophotometry was used to quantify cellular uptake of the drug. The pharmacokinetic profiles of curcumin in SLNs after intravenous administration were studied in rats. Blending Sefsol-218(®) into a lipid matrix reduced the particle size without improving drug loading. An optimised formulation consisting of Dynasan 114(®), Sefsol-218(®), and Pluronic F68(®) (630:70:300, w/w) loaded with 0.8% drug was prepared. This formulation could be dispersed in water with a mean particle size of 152.8 ± 4.7 nm and a 90% entrapment efficiency. Curcumin displayed a two-phase sustained release profile from C-SLNs with improved chemical stability. Compared to the solubilised solution, C-SLNs exhibited prolonged inhibitory activity in cancer cells, as well as time-dependent increases in intracellular uptake. After intravenous administration to rats, the bioavailability of curcumin was increased by 1.25-fold. C-SLNs with improved dispersibility and chemical stability in an aqueous system have been successfully developed. C-SLNs may represent a potentially useful cancer therapeutic curcumin delivery system. Copyright © 2013 Elsevier B.V. All rights reserved.

Green synthesis of silver nanoparticles using Pongamia pinnata seed: Characterization, antibacterial property, and spectroscopic investigation of interaction with human serum albumin.

PubMed

Beg, Maidul; Maji, Anukul; Mandal, Amit Kumar; Das, Somnath; Aktara, Mt Nasima; Jha, Pradeep K; Hossain, Maidul

2017-01-01

In recent years, green synthesized nanoparticles from plant extract have drawn a great interest due to their prospective nanomedicinal application. This study investigates a proficient, safer, and sustainable way for the preparation of AgNPs using medicinal plant Pongamia pinnata (family: Leguminoseae, species: Pinnata) seeds extract without using any external reducing and stabilizing agent. Both ultraviolet-visible spectrum at λ max  = 439 nm and energy dispersive X-ray spectra proof the formation of AgNPs. An average diameter of the AgNPs was 16.4 nm as revealed from transmission electron microscope. Hydrodynamic size (d = ~19.6 nm) was determined by dynamic light scattering (DLS). Zeta potential of AgNPs was found to be -23.7 mV, which supports its dispersion and stability. Fourier transform infrared study revealed that the O ─ H, C ═ O, and C-O-C groups were responsible for the formation of AgNPs. The antibacterial activity of the synthesized AgNPs was checked against Escherichia coli ATCC 25922. AgNPs at its LD 50 dose exhibited synergistic effect with ampicillin. Because protein-AgNPs association greatly affects its adsorption, distribution, and functionality and can also influence the functions of biomolecules. So in order to understand the adsorption and bioavailability, we investigated by fluorescence, ultraviolet-visible, and circular dichroism spectroscopic methods the interaction of synthesized AgNPs toward human serum albumin. The binding affinity and binding sites of human serum albumin toward AgNPs were measured by using the fluorescence quenching data. The circular dichroism spectroscopic results revealed that there was a negligible change of α-helical content in their native structure. Overall, these AgNPs show versatile biological activities and may be applied in the field of nanomedicine. Copyright © 2016 John Wiley & Sons, Ltd.

Pickering emulsion stabilized by cashew gum- poly-l-lactide copolymer nanoparticles: Synthesis, characterization and amphotericin B encapsulation.

PubMed

Richter, A R; Feitosa, J P A; Paula, H C B; Goycoolea, F M; de Paula, R C M

2018-04-01

In this work, we provide proof-of-concept of formation, physical characteristics and potential use as a drug delivery formulation of Pickering emulsions (PE) obtained by a novel method that combines nanoprecipitation with subsequent spontaneous emulsification process. To this end, pre-formed ultra-small (d.∼10 nm) nanoprecipitated nanoparticles of hydrophobic derivatives of cashew tree gum grafted with polylactide (CGPLAP), were conceived to stabilize Pickering emulsions obtained by spontaneous emulsification. These were also loaded with Amphotericin B (AmB), a drug of low oral bioavailability used in the therapy of neglected diseases such as leishmaniasis. The graft reaction was performed in two CG/PLA molar ratio conditions (1:1 and 1:10). Emulsions were prepared by adding the organic phase (Miglyol 812 ® ) in the aqueous phase (nanoprecipitated CGPLAP), resulting the immediate emulsion formation. The isolation by centrifugation does not destabilize or separate the nanoparticles from oil droplets of the PE emulsion. Emulsions with CGPLAP 1:1 presented unimodal distributions at different CGPLA concentration, lower values in size and PDI and the best stability over time. The AmB was incorporated in the emulsions with a process efficiency of 21-47%, as determined by UV-vis. AmB in CGPLAP emulsions is in less aggregated state than observed in commercial AmB formulation. Copyright © 2018 Elsevier B.V. All rights reserved.

Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer's disease Tg2576 mice.

PubMed

Cheng, Kwok Kin; Yeung, Chin Fung; Ho, Shuk Wai; Chow, Shing Fung; Chow, Albert H L; Baum, Larry

2013-04-01

The therapeutic effects of curcumin in treating Alzheimer's disease (AD) depend on the ability to penetrate the blood-brain barrier. The latest nanoparticle technology can help to improve the bioavailability of curcumin, which is affected by the final particle size and stability. We developed a stable curcumin nanoparticle formulation to test in vitro and in AD model Tg2576 mice. Flash nanoprecipitation of curcumin, polyethylene glycol-polylactic acid co-block polymer, and polyvinylpyrrolidone in a multi-inlet vortex mixer, followed by freeze drying with β-cyclodextrin, produced dry nanocurcumin with mean particle size <80 nm. Nanocurcumin powder, unformulated curcumin, or placebo was orally administered to Tg2576 mice for 3 months. Before and after treatment, memory was measured by radial arm maze and contextual fear conditioning tests. Nanocurcumin produced significantly (p=0.04) better cue memory in the contextual fear conditioning test than placebo and tendencies toward better working memory in the radial arm maze test than ordinary curcumin (p=0.14) or placebo (p=0.12). Amyloid plaque density, pharmacokinetics, and Madin-Darby canine kidney cell monolayer penetration were measured to further understand in vivo and in vitro mechanisms. Nanocurcumin produced significantly higher curcumin concentration in plasma and six times higher area under the curve and mean residence time in brain than ordinary curcumin. The P(app) of curcumin and tetrahydrocurcumin were 1.8×10(-6) and 1.6×10(-5)cm/s, respectively, for nanocurcumin. Our novel nanocurcumin formulation produced highly stabilized nanoparticles with positive treatment effects in Tg2576 mice.

Albumin nanoparticles targeted with Apo E enter the CNS by transcytosis and are delivered to neurones.

PubMed

Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Wagner, Sylvia; Büchel, Claudia; von Briesen, Hagen; Kreuter, Jörg

2009-07-01

The blood-brain barrier (BBB) represents a considerable obstacle to brain entry of the majority of drugs and thus severely restricts the therapy of many serious CNS diseases including brain tumours, brain HIV, Alzheimer and other neurodegenerative diseases. The use of nanoparticles coated with polysorbate 80 or with attached apolipoprotein E has enabled the delivery of drugs across the BBB. However, the mechanism of this enhanced transport is still not fully understood. In this present study, human serum albumin nanoparticles, with covalently bound apolipoprotein E (Apo E) as a targetor as well as without apolipoprotein E, were manufactured and injected intravenously into SV 129 mice. The animals were sacrificed after 15 and 30 min, and their brains were examined by transmission electron microscopy. Only the nanoparticles with covalently bound apolipoprotein E were detected in brain capillary endothelial cells and neurones, whereas no uptake into the brain was detectable with nanoparticles without apolipoprotein E. We have also demonstrated uptake of the albumin/ApoE nanoparticles into mouse endothelial (b.End3) cells in vitro and their intracellular localisation. These findings indicate that nanoparticles with covalently bound apolipoprotein E are taken up into the cerebral endothelium by an endocytic mechanism followed by transcytosis into brain parenchyma.

Cabazitaxel and indocyanine green co-delivery tumor-targeting nanoparticle for improved antitumor efficacy and minimized drug toxicity.

PubMed

Tai, Xiaowei; Wang, Yang; Zhang, Li; Yang, Yuting; Shi, Kairong; Ruan, Shaobo; Liu, Yayuan; Gao, Huile; Zhang, Zhirong; He, Qin

2017-02-01

Cabazitaxel (CBX) is an effective antineoplastic agent for the treatment of many kinds of cancers. However, the poor water solubility remains a serious deterrent to the utilization of CBX as a commercial drug. In this study, we designed a strategy that integrated CBX into albumin nanoparticles (ANs) formed with human serum albumin (HSA) to improve the water solubility and targeting ability. Meanwhile, we utilized a photothermal agent-indocyanine green (ICG), which could cooperate with CBX to enhance the antitumor effect. The obtained ANs containing ICG and CBX (AN-ICG-CBX) exhibited good mono-dispersity. In vitro cytotoxicity study showed the effectiveness of CBX and ICG, respectively, whereas AN-ICG-CBX with irradiation exhibited the most efficient antiproliferative ability (83.7%). In vivo safety evaluation studies demonstrated the safety of AN-ICG-CBX. Furthermore, the in vivo antitumor study indicated that the AN-ICG-CBX with irradiation achieved higher tumor inhibition rate (91.3%) compared with CBX-encapsulated AN (AN-CBX) (83.3%) or ICG-encapsulated AN (AN-ICG) plus irradiation (60.1%) in 4T1 tumor-bearing mice. To sum up, a safety and effective formulation AN-ICG-CBX was developed in this study and successfully reduced the drug toxicity, improved the targeting efficiency and enhanced the therapeutic effects, becoming a promising candidate for clinical application.

Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

NASA Astrophysics Data System (ADS)

Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

2016-03-01

Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

PubMed Central

Gaur, Praveen Kumar; Mishra, Shikha; Bajpai, Meenakshi; Mishra, Anushika

2014-01-01

Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5 ± 3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75 ± 5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (C max⁡) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES). PMID:24967360

B-domain deleted recombinant factor VIII formulation and stability.

PubMed

Osterberg, T; Fatouros, A; Neidhardt, E; Warne, N; Mikaelsson, M

2001-04-01

B-domain deleted recombinant factor VIII (BDDrFVIII) is a deletion form of human coagulation factor VIII. A lyophilized formulation of highly purified BDDrFVIII has been developed that does not require the use of blood-derived products such as human serum albumin (HSA). By avoiding the use of blood-derived products, the BDDrFVIII formulation minimizes the risk of transmitting blood-borne pathogens that may be present in plasma-derived factor VIII or in other recombinant factor VIII products that contain HSA in their formulation. Upon reconstitution with saline (4 mL), the composition of the reconstituted product (62.5 to 250 IU/mL BDDrFVIII) is 18 mg/mL sodium chloride, 3.0 mg/mL sucrose, 1.5 mg/mL L-histidine, 0.25 mg/mL calcium chloride dihydrate, and 0.1 mg/mL polysorbate 80. The optimal combination of these excipients in the lyophilized BDDrFVIII formulation provides long-term stability, as measured by a variety of analytical methods. The formulation preserves factor VIII activity of lyophilized BDDrFVIII during storage for at least 24 months at 8 degrees C, and for up to 6 months at room temperature (25 degrees C). The reconstituted product retains its factor VIII potency for at least 100 hours at 25 degrees C, which would allow it to be continuously administered via an infusion pump, assuming the product is handled under aseptic conditions.

Effects of rare earth doping on multi-core iron oxide nanoparticles properties

NASA Astrophysics Data System (ADS)

Petran, Anca; Radu, Teodora; Borodi, Gheorghe; Nan, Alexandrina; Suciu, Maria; Turcu, Rodica

2018-01-01

New multi-core iron oxide magnetic nanoparticles doped with rare earth metals (Gd, Eu) were obtained by a one step synthesis procedure using a solvothermal method for potential biomedical applications. The obtained clusters were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), energy-dispersive X-ray microanalysis (EDX), X-ray photoelectron spectroscopy (XPS) and magnetization measurements. They possess high colloidal stability, a saturation magnetization of up to 52 emu/g, and nearly spherical shape. The presence of rare earth ions in the obtained samples was confirmed by EDX and XPS. XRD analysis proved the homogeneous distribution of the trivalent rare earth ions in the inverse-spinel structure of magnetite and the increase of crystal strain upon doping the samples. XPS study reveals the valence state and the cation distribution on the octahedral and tetrahedral sites of the analysed samples. The observed shift of the XPS valence band spectra maximum in the direction of higher binding energies after rare earth doping, as well as theoretical valence band calculations prove the presence of Gd and Eu ions in octahedral sites. The blood protein adsorption ability of the obtained samples surface, the most important factor of the interaction between biomaterials and body fluids, was assessed by interaction with bovine serum albumin (BSA). The rare earth doped clusters surface show higher afinity for binding BSA. In vitro cytotoxicity test results for the studied samples showed no cytotoxicity in low and medium doses, establishing a potential perspective for rare earth doped MNC to facilitate multiple therapies in a single formulation for cancer theranostics.

Lipid nanoparticle vectorization of indocyanine green improves fluorescence imaging for tumor diagnosis and lymph node resection.

PubMed

Navarro, Fabrice P; Berger, Michel; Guillermet, Stéphanie; Josserand, Véronique; Guyon, Laurent; Neumann, Emmanuelle; Vinet, Françoise; Texier, Isabelle

2012-10-01

Fluorescence imaging is opening a new era in image-guided surgery and other medical applications. The only FDA approved contrast agent in the near infrared is IndoCyanine Green (ICG), which despites its low toxicity, displays poor chemical and optical properties for long-term and sensitive imaging applications in human. Lipid nanoparticles are investigated for improving ICG optical properties and in vivo fluorescence imaging sensitivity. 30 nm diameter lipid nanoparticles (LNP) are loaded with ICG. Their characterization and use for tumor and lymph node imaging are described. Nano-formulation benefits dye optical properties (6 times improved brightness) and chemical stability (>6 months at 4 degrees C in aqueous buffer). More importantly, LNP vectorization allows never reported sensitive and prolonged (>1 day) labeling of tumors and lymph nodes. Composed of human-use approved ingredients, this novel ICG nanometric formulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.

Improving oral bioavailability of acyclovir using nanoparticulates of thiolated xyloglucan.

PubMed

Madgulkar, Ashwini; Bhalekar, Mangesh R; Dikpati, Amrita A

2016-08-01

Acyclovir a BCS class III drug exhibits poor bioavailability due to limited permeability. The intention of this research work was to formulate and characterize thiolated xyloglucan polysaccharide nanoparticles (TH-NPs) of acyclovir with the purpose of increasing its oral bioavailability. Acyclovir-loaded TH-NPs were prepared using a cross-linking agent. Interactions of formulation excipients were reconnoitered using Fourier transform infrared spectroscopy (FT-IR). The formulated nanoparticles were lyophilised by the addition of a cryoprotectant and characterized for its particle size, morphology and stability and optimized using Box Behnken Design.The optimized TH-NP formulation exhibited particle size of 474.4±2.01 and an entrapment efficiency of 81.57%. A marked enhancement in the mucoadhesion was also observed. In-vivo study in a rat model proved that relative bioavailability of acyclovir TH-NPs is ∼2.575 fold greater than that of the marketed acyclovir drug suspension. Copyright © 2016 Elsevier B.V. All rights reserved.

Albumin-derived perfluorocarbon-based artificial oxygen carriers: A physico-chemical characterization and first in vivo evaluation of biocompatibility.

PubMed

Wrobeln, Anna; Laudien, Julia; Groß-Heitfeld, Christoph; Linders, Jürgen; Mayer, Christian; Wilde, Benjamin; Knoll, Tanja; Naglav, Dominik; Kirsch, Michael; Ferenz, Katja B

2017-06-01

Until today, artificial oxygen carriers have not been reached satisfactory quality for routine clinical treatments. To bridge this gap, we designed albumin-derived perfluorocarbon-based nanoparticles as novel artificial oxygen carriers and evaluated their physico-chemical and pharmacological performance. Our albumin-derived perfluorocarbon-based nanoparticles (capsules), composed of an albumin shell and a perfluorodecalin core, were synthesized using ultrasonics. Their subsequent analysis by physico-chemical methods such as scanning electron-, laser scanning- and dark field microscopy as well as dynamic light scattering revealed spherically-shaped, nano-sized particles, that were colloidally stable when dispersed in 5% human serum albumin solution. Furthermore, they provided a remarkable maximum oxygen capacity, determined with a respirometer, reflecting a higher oxygen transport capacity than the competitor Perftoran®. Intravenous administration to healthy rats was well tolerated. Undesirable effects on either mean arterial blood pressure, hepatic microcirculation (determined by in vivo microscopy) or any deposit of capsules in organs, except the spleen, were not observed. Some minor, dose-dependent effects on tissue damage (release of cellular enzymes, alterations of spleen's micro-architecture) were detected. As our promising albumin-derived perfluorocarbon-based nanoparticles fulfilled decisive physico-chemical demands of an artificial oxygen carrier while lacking severe side-effects after in vivo administration they should be advanced to functionally focused in vivo testing conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation and optimization of coated PLGA – Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency

PubMed Central

Peter Christoper, G.V.; Vijaya Raghavan, C.; Siddharth, K.; Siva Selva Kumar, M.; Hari Prasad, R.

2013-01-01

In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 23 factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28–57%, process yield of 60–76% was achieved and drug release for the formulations were in the range of 50–85%. The drug release from the formulations was found to follow Higuchi release pattern, n–value obtained after Korsemeyer plot was in the range of 0.56–0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition. PMID:24648825

Factors affecting drug encapsulation and stability of lipid-polymer hybrid nanoparticles.

PubMed

Cheow, Wean Sin; Hadinoto, Kunn

2011-07-01

Lipid-polymer hybrid nanoparticles are polymeric nanoparticles enveloped by lipid layers that combine the highly biocompatible nature of lipids with the structural integrity afforded by polymeric nanoparticles. Recognizing them as attractive drug delivery vehicles, antibiotics are encapsulated in the present work into hybrid nanoparticles intended for lung biofilm infection therapy. Modified emulsification-solvent-evaporation methods using lipid as surfactant are employed to prepare the hybrid nanoparticles. Biodegradable poly (lactic-co-glycolic acid) and phosphatidylcholine are used as the polymer and lipid models, respectively. Three fluoroquinolone antibiotics (i.e. levofloxacin, ciprofloxacin, and ofloxacin), which vary in their ionicity, lipophilicity, and aqueous solubility, are used. The hybrid nanoparticles are examined in terms of their drug encapsulation efficiency, drug loading, stability, and in vitro drug release profile. Compared to polymeric nanoparticles prepared using non-lipid surfactants, hybrid nanoparticles in general are larger and exhibit higher drug loading, except for the ciprofloxacin-encapsulated nanoparticles. Hybrid nanoparticles, however, are unstable in salt solutions, but the stability can be conferred by adding TPGS into the formulation. Drug-lipid ionic interactions and drug lipophilicity play important roles in the hybrid nanoparticle preparation. First, interactions between oppositely charged lipid and antibiotic (i.e. ciprofloxacin) during preparation cause failed nanoparticle formation. Charge reversal of the lipid facilitated by adding counterionic surfactants (e.g. stearylamine) must be performed before drug encapsulation can take place. Second, drug loading and the release profile are strongly influenced by drug lipophilicity, where more lipophilic drug (i.e. levofloxacin) exhibit a higher drug loading and a sustained release profile attributed to the interaction with the lipid coat. Copyright © 2011 Elsevier B.V. All rights reserved.

Self-oriented nanoparticles for site-selective immunoglobulin G recognition via epitope imprinting approach.

PubMed

Çorman, Mehmet Emin; Armutcu, Canan; Uzun, Lokman; Say, Rıdvan; Denizli, Adil

2014-11-01

Molecular imprinting is a polymerization technique that provides synthetic analogs for template molecules. Molecularly imprinted polymers (MIPs) have gained much attention due to their unique properties such as selectivity and specificity for target molecules. In this study, we focused on the development of polymeric materials with molecular recognition ability, so molecular imprinting was combined with miniemulsion polymerization to synthesize self-orienting nanoparticles through the use of an epitope imprinting approach. Thus, L-lysine imprinted nanoparticles (LMIP) were synthesized via miniemulsion polymerization technique. Immunoglobulin G (IgG) was then bound to the cavities that specifically formed for L-lysine molecules that are typically found at the C-terminus of the Fc region of antibody molecules. The resulting nanoparticles makes it possible to minimize the nonspecific interaction between monomer and template molecules. In addition, the orientation of the entire IgG molecule was controlled, and random imprinting of the IgG was prevented. The optimum conditions were determined for IgG recognition using the imprinted nanoparticles. The selectivity of the nanoparticles against IgG molecules was also evaluated using albumin and hemoglobin as competitor molecules. In order to show the self-orientation capability of imprinted nanoparticles, human serum albumin (HSA) adsorption onto both the plain nanoparticles and immobilized nanoparticles by anti-human serum albumin antibody (anti-HSA antibody) was also carried out. Due to anti-HSA antibody immobilization on the imprinted nanoparticles, the adsorption capability of nanoparticles against HSA molecules vigorously enhanced. It is proved that the oriented immobilization of antibodies was appropriately succeeded. Copyright © 2014 Elsevier B.V. All rights reserved.

Self-assembled albumin nanoparticles as a nanocarrier for aclacinomycin A

NASA Astrophysics Data System (ADS)

Gong, Guangming; Liu, Wenya; Wang, Shudong

2016-11-01

This study aimed to reduce the cytotoxicity and improve the targeting of aclacinomycin (ACM) by covalently coupling it with amino-oxyacetic acid (AOA) to generate an active intermediate, AOA-ACM. AOA-ACM was conjugated with self-assembled human serum albumin (HSA) nanoparticles constructed using tris(2-carboxyethyl)phosphine (TCEP) as disulfide bond breaking molecules in an ‘opening stage-intermediate-closing stage’ route, in which the hydrophobic interaction, interchange of sulfhydryl and hydrogen bond may be the key factors in the assembling process. Conjugation between ACM and albumin nanoparticles was found to occur at an ACM ketone site using 1H-NMR and 13C-NMR matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass analysis indicated that the drug loading efficiency of ACM conjugated with HSA nanoparticles (NPs-ACM) was 7.4% (molar ratio = 6:1). The release of NPs-ACM was pH dependent. In vivo studies indicated that NPs-ACM exhibited fourfold higher tumor targeting capability on S180-tumor-bearing mice compared with the free ACM (p < 0.05). The cytotoxictiy and cardiotoxicity of NPs-ACM was reduced compared with the free ACM. Albumin carrier altered the blood pharmacokinetics and distribution of ACM. Hence, the NPs-ACM prodrug is ideal tumor targeting drug carriers for ACM, and the easy approach developed in this study for active intermediate and prodrug preparation can be applied to other pharmacological substances containing ketone groups. The method of preparing HSA-blank nanoparticles through TCEP reduction could be adopted to improve the water solubility of lipophilic drugs and their tumor-targeting specificity by fabricating HSA-lipophilic drug nanoparticles.

Multifunctional Core–Shell Nanoparticles: Discovery of Previously Invisible Biomarkers

PubMed Central

2011-01-01

Many low-abundance biomarkers for early detection of cancer and other diseases are invisible to mass spectrometry because they exist in body fluids in very low concentrations, are masked by high-abundance proteins such as albumin and immunoglobulins, and are very labile. To overcome these barriers, we created porous, buoyant, core–shell hydrogel nanoparticles containing novel high affinity reactive chemical baits for protein and peptide harvesting, concentration, and preservation in body fluids. Poly(N-isopropylacrylamide-co-acrylic acid) nanoparticles were functionalized with amino-containing dyes via zero-length cross-linking amidation reactions. Nanoparticles functionalized in the core with 17 different (12 chemically novel) molecular baits showed preferential high affinities (KD < 10–11 M) for specific low-abundance protein analytes. A poly(N-isopropylacrylamide-co-vinylsulfonic acid) shell was added to the core particles. This shell chemistry selectively prevented unwanted entry of all size peptides derived from albumin without hindering the penetration of non-albumin small proteins and peptides. Proteins and peptides entered the core to be captured with high affinity by baits immobilized in the core. Nanoparticles effectively protected interleukin-6 from enzymatic degradation in sweat and increased the effective detection sensitivity of human growth hormone in human urine using multiple reaction monitoring analysis. Used in whole blood as a one-step, in-solution preprocessing step, the nanoparticles greatly enriched the concentration of low-molecular weight proteins and peptides while excluding albumin and other proteins above 30 kDa; this achieved a 10,000-fold effective amplification of the analyte concentration, enabling mass spectrometry (MS) discovery of candidate biomarkers that were previously undetectable. PMID:21999289

A New Carbon Nanotube-Based Breast Cancer Drug Delivery System: Preparation and In Vitro Analysis Using Paclitaxel.

PubMed

Shao, Wei; Paul, Arghya; Rodes, Laetitia; Prakash, Satya

2015-04-01

Paclitaxel (PTX) is one of the most important drugs for breast cancer; however, the drug effects are limited by its systematic toxicity and poor water solubility. Nanoparticles have been applied for delivery of cancer drugs to overcome their limitations. Toward this goal, a novel single-walled carbon nanotube (SWNT)-based drug delivery system was developed by conjugation of human serum albumin (HSA) nanoparticles for loading of antitumor agent PTX. The nanosized macromolecular SWNT-drug carrier (SWNT-HSA) was characterized by TEM, UV-Vis-NIR spectrometry, and TGA. The SWNT-based drug carrier displayed high intracellular delivery efficiency (cell uptake rate of 80%) in breast cancer MCF-7 cells, as examined by fluorescence-labeled drug carriers, suggesting the needle-shaped SWNT-HSA drug carrier was able to transport drugs across cell membrane despite its macromolecular structure. The drug loading on SWNT-based drug carrier was through high binding affinity of PTX to HSA proteins. The PTX formulated with SWNT-HSA showed greater growth inhibition activity in MCF-7 breast cancer cells than PTX formulated with HSA nanoparticle only (cell viability of 63 vs 70% in 48 h and 53 vs 62% in 72 h). The increased drug efficacy could be driven by SWNT-mediated cell internalization. These data suggest that the developed SWNT-based antitumor agent is functional and effective. However, more studies for in vivo drug delivery efficacy and other properties are needed before this delivery system can be fully realized.

Zein nanoparticles and the strategies to improve the colloidal stability: a mini review

NASA Astrophysics Data System (ADS)

Pascoli, Mônica; de Lima, Renata; Fraceto, Leonardo F.

2018-01-01

Zein, a protein extracted from maize, can be employed to easily produce nanoscale particles suitable for use as carrier systems. This review investigates the main methods for obtaining zein nanoparticles, as well as the problems and options available in the development of stable colloidal suspensions. Considerable gaps were identified in the literature concerning this topic, with studies being unclear about the factors that affect the stability of zein particles. In the vast majority of cases, no data are presented in relation to the stability of the formulations over time. It could be concluded that in order to produce a high quality system, detailed evaluation is required, considering factors including the zein concentration, pH, ionic strength, thermal treatment of the protein prior to preparation of the nanoparticles, strategies employing other materials as coatings, and the storage conditions. It is extremely important that these aspects should be considered during product development, prior to commercial-scale manufacture.

Zein Nanoparticles and Strategies to Improve Colloidal Stability: A Mini-Review

PubMed Central

Pascoli, Mônica; de Lima, Renata; Fraceto, Leonardo F.

2018-01-01

Zein, a protein extracted from maize, can be employed to easily produce nanoscale particles suitable for use as carrier systems. This review investigates the main methods for obtaining zein nanoparticles, as well as the problems and options available in the development of stable colloidal suspensions. Considerable gaps were identified in the literature concerning this topic, with studies being unclear about the factors that affect the stability of zein particles. In the vast majority of cases, no data are presented in relation to the stability of the formulations over time. It could be concluded that in order to produce a high quality system, detailed evaluation is required, considering factors including the zein concentration, pH, ionic strength, thermal treatment of the protein prior to preparation of the nanoparticles, strategies employing other materials as coatings, and the storage conditions. It is extremely important that these aspects should be considered during product development, prior to commercial-scale manufacture. PMID:29473032

"Liquid Crystalline Nanoparticles": Rationally Designed Vehicle To Improve Stability and Therapeutic Efficacy of Insulin Following Oral Administration.

PubMed

Agrawal, Ashish Kumar; Kumar, Kuldeep; Swarnakar, Nitin Kumar; Kushwah, Varun; Jain, Sanyog

2017-06-05

In the present article we investigate the feasibility of liquid crystalline nanoparticles (LCNPs) to improve the stability and therapeutic efficacy of insulin following oral administration. Compatibility studies of different formulation ingredients with insulin and extensive optimization of different process variables resulted into the formation of LCNPs with particle size of 245.50 ± 6.36 nm, PDI of 0.220 ± 0.042, and zeta potential of -18.30 ± 1.27 mV with an entrapment efficiency of 44.17 ± 1.47%. Mannitol (5% w/v) was identified as a suitable cryoprotectant to produce freeze-dried LCNPs without affecting their critical quality attributes. LCNPs demonstrated excellent stability in simulated biological fluids by simultaneously retaining the chemical and conformational stability of the insulin entrapped within the LCNPs. A sustained release of insulin was observed for up to 24 h in PBS (pH 7.4). Developed LCNPs demonstrated remarkably higher Caco-2 cell uptake in comparison with free insulin-FITC and more than double the cumulative hypoglycemia in comparison with subcutaneously administered insulin solution in diabetic rats. Data in hand suggest that the proposed formulation strategy can be exploited for improving the therapeutic efficacy of biomacromolecules like insulin.

Nanoparticle fouling and its combination with organic fouling during forward osmosis process for silver nanoparticles removal from simulated wastewater

NASA Astrophysics Data System (ADS)

Zhao, Yanxiao; Wang, Xinhua; Wang, Zhiwei; Li, Xiufen; Ren, Yueping

2016-05-01

The increasing and wide application of silver nanoparticles (Ag NPs) has resulted in their appearance in wastewater. In consideration of their potential toxicity and environmental impacts, it is necessary to find effective technology for their removal from wastewater. Here, forward osmosis (FO) membrane was applied for Ag NPs removal from wastewater, and single and combined fouling of nanoparticles and organic macromolecules were further investigated during the FO process. The findings demonstrated that FO membrane can effectively remove Ag NPs from wastewater due to its high rejection performance. Fouling tests indicated that water flux declined appreciably even at the beginning of the single Ag NPs fouling test, and more remarkable flux decline and larger amounts of deposited Ag NPs were observed with an increase of Ag NPs concentration. However, the addition of bovine serum albumin (BSA) could effectively alleviate the FO membrane fouling induced by Ag NPs. The interaction between Ag NPs and BSA was responsible for this phenomenon. BSA can easily form a nanoparticle-protein corona surrounded nanoparticles, which prevented nanoparticles from aggregation due to the steric stabilization mechanism. Furthermore, the interaction between BSA and Ag NPs occurred not only in wastewater but also on FO membrane surface.

Tailor-made Au@Ag core-shell nanoparticle 2D arrays on protein-coated graphene oxide with assembly enhanced antibacterial activity

NASA Astrophysics Data System (ADS)

Wang, Huiqiao; Liu, Jinbin; Wu, Xuan; Tong, Zhonghua; Deng, Zhaoxiang

2013-05-01

Water-dispersible two-dimensional (2D) assemblies of Au@Ag core-shell nanoparticles are obtained through a highly selective electroless silver deposition on pre-assembled gold nanoparticles on bovine serum albumin (BSA)-coated graphene oxide (BSA-GO). While neither BSA-GO nor AuNP-decorated BSA-GO shows any antibacterial ability, the silver-coated GO@Au nanosheets (namely GO@Au@Ag) exhibit an enhanced antibacterial activity against Gram-negative Escherichia coli (E. coli) bacteria, superior to unassembled Au@Ag nanoparticles and even ionic Ag. Such an improvement may be attributed to the increased local concentration of silver nanoparticles around a bacterium and a polyvalent interaction with the bacterial surface. In addition, the colloidal stability of this novel nano-antimicrobial against the formation of random nanoparticle aggregates guarantees a minimized activity loss of the Au@Ag nanoparticles. The antibacterial efficacy of GO@Au@Ag is less sensitive to the existence of Cl-, in comparison with silver ions, providing another advantage for wound dressing applications. Our research unambiguously reveals a strong and very specific interaction between the GO@Au@Ag nanoassembly and E. coli, which could be an important clue toward a rational design, synthesis and assembly of innovative and highly active antibacterial nanomaterials.

Rifaximin - Chitosan Nanoparticles for Inflammatory Bowel Disease (IBD).

PubMed

Kumar, Jatinder; Newton, Amaldoss M J

2017-01-01

Inflammatory Bowel Disease (IBD) cannot be controlled easily and the recurrence is the most challenging issue for the physicians. There are various controlled and colon targeted drug delivery systems available for the treatment with limited success rate. Nanoparticles prepared by using the colon targeted polymers such as chitosan may improve the IBD due to their smaller size, unique physico chemical properties and targeting potential. The aim of this investigation was designed to formulate and develop a colon targeted polysaccharide nanoparticles of rifaximin (RFX) by using linear polysaccharide chitosan, for the improvement of rifaximin solubility, overall therapeutic efficacy and colon targeting. The research was focused on developing RFX nanoparticles for the treatment of Inflammatory Bowel Disease (IBD) by ionic gelation method. Nanoparticles were subjected to various characterization techniques such as XRD, FTIR and mean particle size (MPS) by Master Sizer and Zeta Sizer. Transmission Electron Microscopy (TEM), drug entrapment efficiency and zeta potential are also determined for the developed formulations. The efficiency of drug release from prepared formulation was studied in vitro by using a dialysis bag diffusion technique in the buffer condition mimicking stomach, intestine and colonic pH conditions. The prepared nanoparticles demonstrated the size in the nano range. The drug release profile was controlled in the upper GI tract and the maximum amount of drug was released in the colonic conditions. The prepared nanoparticles significantly improved the solubility of rifaximin. The zeta potential of the best chitosan preparation was found to be 37.79, which confirms the stability of prepared nanosuspension. Nanoparticles with small particle size found to have high encapsulation efficiency and relatively high loading capacity and predetermined in vitro release profile. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Templated assembly of albumin-based nanoparticles for simultaneous gene silencing and magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Mertz, Damien; Affolter-Zbaraszczuk, Christine; Barthès, Julien; Cui, Jiwei; Caruso, Frank; Baumert, Thomas F.; Voegel, Jean-Claude; Ogier, Joelle; Meyer, Florent

2014-09-01

In this article, we address the design of innovative human serum albumin (HSA)-based nanoparticles loaded with silencing RNA and grafted with gadolinium complexes having average sizes ranging from ca. 50 to 150 nm according to the siRNA/HSA composition. The non-covalent siRNA/HSA assembly is formed on isobutyramide-modified mesoporous silica and the self-supported HSA-based nanoparticles are obtained following the silica template dissolution. These original protein particles provide simultaneous magnetic resonance imaging contrast enhancement and cellular in vitro gene silencing.In this article, we address the design of innovative human serum albumin (HSA)-based nanoparticles loaded with silencing RNA and grafted with gadolinium complexes having average sizes ranging from ca. 50 to 150 nm according to the siRNA/HSA composition. The non-covalent siRNA/HSA assembly is formed on isobutyramide-modified mesoporous silica and the self-supported HSA-based nanoparticles are obtained following the silica template dissolution. These original protein particles provide simultaneous magnetic resonance imaging contrast enhancement and cellular in vitro gene silencing. Electronic supplementary information (ESI) available: Experimental details and supporting Fig. S1-S4. See DOI: 10.1039/c4nr02623c

Gamma Interferon Loaded onto Albumin Nanoparticles: In Vitro and In Vivo Activities against Brucella abortus▿

PubMed Central

Segura, S.; Gamazo, C.; Irache, J. M.; Espuelas, S.

2007-01-01

The aim of this study was to evaluate the activity of gamma interferon (IFN-γ) when it was either adsorbed onto or loaded into albumin nanoparticles. Brucella abortus-infected macrophages and infected BALB/c mice were selected as the models for testing of the therapeutic potentials of these cytokine delivery systems, in view of the well-established role of IFN-γ-activated macrophages for the control of Brucella sp. infections. Whereas the encapsulation of IFN-γ inside the matrix of nanoparticles completely abrogated its activity, adsorbed IFN-γ increased by 0.75 log unit the bactericidal effect induced by RAW macrophages activated with free IFN-γ, along with a higher level of production of nitric oxide. In infected BALB/c-mice, IFN-γ adsorbed onto nanoparticles was also more active than free cytokine in reducing the number of bacteria in the spleens, and the effect was mediated by an increased ratio of IFN-γ-secreting (Th1) to interleukin-4-secreting (Th2) cells. Overall, albumin nanoparticles would be suitable as carriers that target IFN-γ to macrophages and, thus, potentiate their therapeutic activity. PMID:17220401

Synthesis and Characterization of BSA Conjugated Silver Nanoparticles (Ag/BSA Nanoparticles) and Evaluation of Biological Properties of Ag/BSA Nanoparticles and Ag/BSA Nanoparticles Loaded Poly(hydroxy butyrate valerate) PHBV Films

NASA Astrophysics Data System (ADS)

Ambaye, Almaz

Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa are the etiological agents of several infectious diseases. Antibiotic resistance by these three microbes has emerged as a prevalent problem due in part to the misuse of existing antibiotics and the lack of novel antibiotics. Nanoparticles have emerged as an alternative antibacterial agents to conventional antibiotics owing to their high surface area to volume ratio and their unique chemical and physical properties. Among the nanoparticles, silver nanoparticles have gained increasing attention because silver nanoparticles exhibit antibacterial activity against a range of gram positive and gram negative bacteria. Nanoparticles of well-defined chemistry and morphology can be used in broad biomedical applications, especially in bone tissue engineering applications, where bone infection by bacteria can be acute and lethal. It is commonly noted in the literature that the activity of nanoparticles against microorganisms is dependent upon the size and concentration of the nanoparticles as well as the chemistry of stabilizing agent. To the best of our knowledge, a comprehensive study that evaluates the antibacterial activity of well characterized silver nanoparticles in particular Bovine Serum Albumin (BSA) stabilized against S. aureus and E. coli and cytotoxicity level of BSA stabilized silver nanoparticles towards osteoblast cells (MC3T3-E1) is currently lacking. Therefore, the primary objective of this study was to characterize protein conjugated silver nanoparticles prepared by chemical reduction of AgNO3 and BSA mixture. The formation of Ag/BSA nanoparticles was studied by UV-Vis spectroscopy. The molar ratio of silver to BSA in the Ag/BSA nanoparticles was established to be 27+/- 3: 1, based on Thermogravimetric Analysis and Atomic Absorption Spectroscopy. Based on atomic force microscopy, dynamic light scattering,and transmission electron microscopy(TEM) measurements, the particle size (diameter) of Ag/BSA nanoparticles was found to be in a range of 9-13 nm. X-ray photo electron spectroscopy measurements of argon sputtered Ag/BSA nanoparticles provided evidence that the outer and inner region of nanoparticles are mainly composed of BSA and silver, respectively. Having characterized the nanoparticles, the next phase of the study was to evaluate the antibacterial activity and cytotoxicity level of BSA stabilized silver nanoparticles. The antibacterial efficacy of Ag/BSA nanoparticles against E. coli and S. aureus was evaluated, and minimum lethal concentration was found to be 2ppm and 7ppm, respectively. E. coli showed a higher susceptibility to silver nanoparticles than S. aureus, which could be attributed to the difference in the cell wall structure. We have also investigated the cytotoxicity level of Ag/BSA nanoparticles towards MC3T3-E1 osteoblast cells. The minimum bactericidal concentration found for both strains is lower than the silver nanoparticles concentration that was toxic to the osteoblast cells. Preliminary studies of Ag/BSA nanoparticles loaded collagen immobilized PHBV film showed that the Ag/BSA nanoparticles loaded PHBV film inhibit bacterial growth. The findings of our study can be extremely useful in the design of novel scaffold to address the critical needs of bone tissue engineering community.

Estimating conformation content of a protein using citrate-stabilized Au nanoparticles

NASA Astrophysics Data System (ADS)

Deka, Jashmini; Paul, Anumita; Chattopadhyay, Arun

2010-08-01

Herein we report the use of the optical properties of citrate-stabilized gold nanoparticles (Au NPs) for estimation of native or denatured conformation content in a mixture of a protein in solution. The UV-vis extinction spectrum of citrate-stabilized Au NPs is known to broaden differently in the presence of native and denatured states of α-amylase, bovine serum albumin (BSA) or amyloglucosidase (AMG). On the other hand, herein we show that when a mixture of native and denatured protein was present in the medium, the broadening of the spectrum differed for different fractional content of the conformations. Also, the total area under the extinction spectrum varied linearly with the change in the mole fraction content of a state and for a constant total protein concentration. Transmission electron microscopy (TEM) measurements revealed different levels of agglomeration for different fractional contents of the native or denatured state of a protein. In addition, time-dependent denaturation of a protein could be followed using the present method. The rate constants calculated for denaturation indicated a possible fast change in conformation of a protein before complete thermal denaturation. The observations have been explained based on the changes in extinction coefficient (thereby oscillator strength) upon interaction of citrate-stabilized NPs with proteins being in different states and levels of agglomeration.Herein we report the use of the optical properties of citrate-stabilized gold nanoparticles (Au NPs) for estimation of native or denatured conformation content in a mixture of a protein in solution. The UV-vis extinction spectrum of citrate-stabilized Au NPs is known to broaden differently in the presence of native and denatured states of α-amylase, bovine serum albumin (BSA) or amyloglucosidase (AMG). On the other hand, herein we show that when a mixture of native and denatured protein was present in the medium, the broadening of the spectrum differed for different fractional content of the conformations. Also, the total area under the extinction spectrum varied linearly with the change in the mole fraction content of a state and for a constant total protein concentration. Transmission electron microscopy (TEM) measurements revealed different levels of agglomeration for different fractional contents of the native or denatured state of a protein. In addition, time-dependent denaturation of a protein could be followed using the present method. The rate constants calculated for denaturation indicated a possible fast change in conformation of a protein before complete thermal denaturation. The observations have been explained based on the changes in extinction coefficient (thereby oscillator strength) upon interaction of citrate-stabilized NPs with proteins being in different states and levels of agglomeration. Electronic supplementary information (ESI) available: Additional UV-vis and fluorescence spectra and graphs based on UV-vis studies. See DOI: 10.1039/c0nr00154f

Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

NASA Astrophysics Data System (ADS)

Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K.

2012-11-01

Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

Thermo-responsive human α-elastin self-assembled nanoparticles for protein delivery.

PubMed

Kim, Jae Dong; Jung, Youn Jae; Woo, Chang Hee; Choi, Young Chan; Choi, Ji Suk; Cho, Yong Woo

2017-01-01

Self-assembled nanoparticles based on PEGylated human α-elastin were prepared as a potential vehicle for sustained protein delivery. The α-elastin was extracted from human adipose tissue and modified with methoxypolyethyleneglycol (mPEG) to control particle size and enhance the colloidal stability. The PEGylated human α-elastin showed sol-to-particle transition with a lower critical solution temperature (LCST) of 25°C-40°C in aqueous media. The PEGylated human α-elastin nanoparticles (PhENPs) showed a narrow size distribution with an average diameter of 330±33nm and were able to encapsulate significant amounts of insulin and bovine serum albumin (BSA) upon simple mixing at low temperature in water and subsequent heating to physiological temperature. The release profiles of insulin and BSA showed sustained release for 72h. Overall, the thermo-responsive self-assembled PhENPs provide a useful tool for a range of protein delivery and tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Interaction study on bovine serum albumin physically binding to silver nanoparticles: Evolution from discrete conjugates to protein coronas

NASA Astrophysics Data System (ADS)

Guo, Jun; Zhong, Ruibo; Li, Wanrong; Liu, Yushuang; Bai, Zhijun; Yin, Jun; Liu, Jingran; Gong, Pei; Zhao, Xinmin; Zhang, Feng

2015-12-01

The nanostructures formed by inorganic nanoparticles together with organic molecules especially biomolecules have attracted increasing attention from both industries and researching fields due to their unique hybrid properties. In this paper, we systemically studied the interactions between amphiphilic polymer coated silver nanoparticles and bovine serum albumins by employing the fluorescence quenching approach in combination with the Stern-Volmer and Hill equations. The binding affinity was determined to 1.30 × 107 M-1 and the interaction was spontaneously driven by mainly the van der Waals force and hydrogen-bond mediated interactions, and negatively cooperative from the point of view of thermodynamics. With the non-uniform coating of amphiphilic polymer, the silver nanoparticles can form protein coronas which can become discrete protein-nanoparticle conjugates when controlling their molar ratios of mixing. The protein's conformational changes upon binding nanoparticles was also studied by using the three-dimensional fluorescence spectroscopy.

Preparation and evaluation of tilmicosin-loaded hydrogenated castor oil nanoparticle suspensions of different particle sizes.

PubMed

Chen, Xiaojin; Wang, Ting; Lu, Mengmeng; Zhu, Luyan; Wang, Yan; Zhou, WenZhong

2014-01-01

Three tilmicosin-loaded hydrogenated castor oil nanoparticle (TMS-HCO-NP) suspensions of different particle sizes were prepared with different polyvinyl alcohol surfactant concentrations using a hot homogenization and ultrasonic technique. The in vitro release, in vitro antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and stability study were conducted to evaluate the characteristics of the suspensions. The in vitro tilmicosin release rate, antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and stability of the suspensions were evaluated. When prepared with polyvinyl alcohol concentrations of 0.2%, 1%, and 5%, the mean diameters of the nanoparticles in the three suspensions were 920±35 nm, 452±10 nm, and 151±4 nm, respectively. The three suspensions displayed biphasic release profiles similar to that of freeze-dried TMS-HCO-NP powders, with the exception of having a faster initial release. Moreover, suspensions of smaller-sized particles showed faster initial release, and lower minimum inhibitory concentrations and minimum bactericidal concentrations. Time-kill curves showed that within 12 hours, the suspension with the 151 nm particles had the most potent bactericidal activity, but later, the suspensions with larger-sized particles showed increased antibacterial activity. None of the three suspensions were cytotoxic at clinical dosage levels. At higher drug concentrations, all three suspensions showed similar concentration-dependent cytotoxicity. The suspension with the smallest-sized particle showed significantly more acute toxicity in mice, perhaps due to faster drug release. All three suspensions exhibited good stability at 4°C and at room temperature for at least 6 months. These results demonstrate that TMS-HCO-NP suspensions can be a promising formulation for tilmicosin, and that nanoparticle size can be an important consideration for formulation development.

Preparation and evaluation of tilmicosin-loaded hydrogenated castor oil nanoparticle suspensions of different particle sizes

PubMed Central

Chen, Xiaojin; Wang, Ting; Lu, Mengmeng; Zhu, Luyan; Wang, Yan; Zhou, WenZhong

2014-01-01

Three tilmicosin-loaded hydrogenated castor oil nanoparticle (TMS-HCO-NP) suspensions of different particle sizes were prepared with different polyvinyl alcohol surfactant concentrations using a hot homogenization and ultrasonic technique. The in vitro release, in vitro antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and stability study were conducted to evaluate the characteristics of the suspensions. The in vitro tilmicosin release rate, antibacterial activity, mammalian cytotoxicity, acute toxicity in mice, and stability of the suspensions were evaluated. When prepared with polyvinyl alcohol concentrations of 0.2%, 1%, and 5%, the mean diameters of the nanoparticles in the three suspensions were 920±35 nm, 452±10 nm, and 151±4 nm, respectively. The three suspensions displayed biphasic release profiles similar to that of freeze-dried TMS-HCO-NP powders, with the exception of having a faster initial release. Moreover, suspensions of smaller-sized particles showed faster initial release, and lower minimum inhibitory concentrations and minimum bactericidal concentrations. Time-kill curves showed that within 12 hours, the suspension with the 151 nm particles had the most potent bactericidal activity, but later, the suspensions with larger-sized particles showed increased antibacterial activity. None of the three suspensions were cytotoxic at clinical dosage levels. At higher drug concentrations, all three suspensions showed similar concentration-dependent cytotoxicity. The suspension with the smallest-sized particle showed significantly more acute toxicity in mice, perhaps due to faster drug release. All three suspensions exhibited good stability at 4°C and at room temperature for at least 6 months. These results demonstrate that TMS-HCO-NP suspensions can be a promising formulation for tilmicosin, and that nanoparticle size can be an important consideration for formulation development. PMID:24920902

Quantitative Characterization of Magnetic Mobility of Nanoparticle in Solution-Based Condition.

PubMed

Rodoplu, Didem; Boyaci, Ismail H; Bozkurt, Akif G; Eksi, Haslet; Zengin, Adem; Tamer, Ugur; Aydogan, Nihal; Ozcan, Sadan; Tugcu-Demiröz, Fatmanur

2015-01-01

Magnetic nanoparticles are considered as the ideal substrate to selectively isolate target molecules or organisms from sample solutions in a wide variety of applications including bioassays, bioimaging and environmental chemistry. The broad array of these applications in fields requires the accurate magnetic characterization of nanoparticles for a variety of solution based-conditions. Because the freshly synthesized magnetic nanoparticles demonstrated a perfect magnetization value in solid form, they exhibited a different magnetic behavior in solution. Here, we present simple quantitative method for the measurement of magnetic mobility of nanoparticles in solution-based condition. Magnetic mobility of the nanoparticles was quantified with initial mobility of the particles using UV-vis absorbance spectroscopy in water, ethanol and MES buffer. We demonstrated the efficacy of this method through a systematic characterization of four different core-shell structures magnetic nanoparticles over three different surface modifications. The solid nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD) and saturation magnetization (Ms). The surfaces of the nanoparticles were functionalized with 11-mercaptoundecanoic acid and bovine serum albumin BSA was selected as biomaterial. The effect of the surface modification and solution media on the stability of the nanoparticles was monitored by zeta potentials and hydrodynamic diameters of the nanoparticles. Results obtained from the mobility experiments indicate that the initial mobility was altered with solution media, surface functionalization, size and shape of the magnetic nanoparticle. The proposed method easily determines the interactions between the magnetic nanoparticles and their surrounding biological media, the magnetophoretic responsiveness of nanoparticles and the initial mobilities of the nanoparticles.

New nanoparticles obtained by co-assembly of amphiphilic cyclodextrins and nonlamellar single-chain lipids: Preparation and characterization.

PubMed

Nguyễn, Cảnh Hưng; Putaux, Jean-Luc; Santoni, Gianluca; Tfaili, Sana; Fourmentin, Sophie; Coty, Jean-Baptiste; Choisnard, Luc; Gèze, Annabelle; Wouessidjewe, Denis; Barratt, Gillian; Lesieur, Sylviane; Legrand, François-Xavier

2017-10-15

This work aimed at preparing new nanoscale assemblies based on an amphiphilic bio-esterified β-cyclodextrin (β-CD), substituted at the secondary face with n-decanoic fatty acid chains (β-CD-C 10 ), and monoolein (MO) as new carriers for parenteral drug delivery. Stable binary (β-CD-C 10 /MO) and ternary (β-CD-C 10 /MO/stabilizer) nanoscale assemblies close to 100nm in size were successfully prepared in water by the solvent displacement method. The generated nanoparticles were fully characterized by dynamic light scattering, transmission electron microscopy, small-angle X-ray scattering, residual solvent analysis, complement activation and the contribution of each formulation parameter was determined by principal component analysis. The β-CD-C 10 units were shown to self-organize into nanoparticles with a hexagonal supramolecular packing that was significantly modulated by the molar ratio of the constituents and the presence of a steric or electrostatic stabilizer (DOPE-PEG 2000 or DOPA/POPA, respectively). Indeed, nanoparticles differing in morphology and in hexagonal lattice parameters were obtained while the co-existence of multiple mesophases was observed in some formulations, in particular for the β-CD-C 10 /MO/DOPA and β-CD-C 10 /MO/POPA systems. The mixed β-CD-C 10 /MO/DOPE-PEG 2000 nanoparticles (49:49:2 in mol%) appeared to be the most suitable for use as a drug delivery system since they contained a very low amount of residual solvent and showed a low level of complement C3 activation. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and Evaluation of Amphotericin B Loaded Iron Oxide Nanoparticles for Targeted Drug Delivery to Systemic Fungal Infections

NASA Astrophysics Data System (ADS)

Balabathula, Pavan

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and zeta-potential using dynamic light scattering (DLS) technique, morphology with transmission electronic microscopy (TEM), and in vitro drug release profile with dialysis method were evaluated. Second, uptake (with fluorescence microscopy and flow cytometry) and killing efficacy (with susceptibility testing) of AMB-IONP in fungal clinical isolates of Candida species were evaluated and compared with standard drug AMB deoxycholate (AMB-D) data. Third, the cellular uptake mechanisms with endocytosis inhibitors and intracellular trafficking using TEM for design D were evaluated in selected isolates. Fourth, a stable lyophilized AMB-IONP formulation was developed and was suitable for clinical trials. A validated isocratic HPLC method was developed and validated for the quantitative determination of AMB. Design D was determined to be the lead formulation with drug loading of 13.6+/-6.9 of AMB/mg of IONP. The size, zeta-potential, and PDI for all formulation designs were found to be in an optimum range for a nanomedicine with ≤36 nm, ˜ -20 mV, and ≤0.2, respectively. The TEM images confirmed that the nanoparticles were monodispersed and spherical in shape. The drug release profile indicated a burst release up to 3 hours for designs A and B, followed by a sustained drug release profile up to 72 hours. Designs C and D (with and without glutaraldehyde) also had a sustained drug release profile up to 72 hours. The major mechanisms of drug release from these formulations were determined to be Fickian and non-Fickian diffusion with first order and Higuchi kinetic models as best fit. The cellular uptake profile for design D exhibited a time dependent uptake with maximum uptake at 0.5 and 4 hours for C. albicans and C. glabrata, respectively. All designs exhibited improved efficacy over AMB-D in the susceptibility testing conducted on clinical isolates of Candida. Design D was found to have an enhanced killing ability and was 16-25 fold more efficacious than AMB-D. An in vitro cellular association study found the uptake mechanism was energy dependent. An endocytosis inhibitor evaluation determined the major particle uptake pathway for C. albicans was lipid-raft mediated endocytosis, whereas for C. glabrata, it was clathrin-, caveolar-, and lipid-raft-mediated endocytosis. TEM and confocal images provided evidence the AMB-IONP were localized at or near the cell wall and membrane wall and inside the cytoplasm, nucleus and endolysosomal vesicles for tested isolates. The lyophilized formulation of AMB-IONP was successfully prepared using an appropriate amount (1:16 to the weight of IONP) of the lyoprotectant, sucrose. A short term stability study of both formulations (lyophilized and aqueous dispersion) at 5°C and 25°C for up to two months showed the lyophilized form was stable. In conclusion, a targeted nanotheronostic drug delivery system (AMB-IONP) was successfully designed, developed, characterized and evaluated as a potential drug product for IFIs treatment.

Discomfort from an alkaline formulation delivered subcutaneously in humans: albumin at pH 7 versus pH 10.

PubMed

Ward, W Kenneth; Castle, Jessica R; Branigan, Deborah L; Massoud, Ryan G; El Youssef, Joseph

2012-07-01

There is a paucity of data regarding tolerability of alkaline drugs administered subcutaneously. The aim of this study was to assess the tolerability of alkaline preparations of human albumin delivered subcutaneously to healthy humans. We compared the tolerability of neutral versus alkaline (pH 10) formulations of human albumin in ten volunteers. With an intent to minimize the time required to reach physiological pH after injection, the alkaline formulation was buffered with a low concentration of glycine (20 mmol/L). Each formulation was given at two rates: over 5 seconds and over 60 seconds. A six-point scale was used to assess discomfort. For slow injections, there was a significant difference between pH 7.4 and pH 10 injections (0.4 ± 0.2 vs 1.1 ± 0.2, mean ± SEM; p = 0.025), though the degree of discomfort at pH 10 injections was only 'mild or slight'. For fast injections, the difference between neutral and alkaline formulations was of borderline significance. Inflammation and oedema, as judged by a physician, were very minimal for all injections, irrespective of pH. For subcutaneous drug administration (especially when delivered slowly), there was more discomfort associated with alkaline versus neutral formulations of albumin, though the discomfort was mild. This study suggests that there is little discomfort and inflammation resulting from subcutaneous administration of protein drugs formulated with weak buffers at alkaline pH.

Quantitative characterization of colloidal assembly of graphene oxide-silver nanoparticle hybrids using aerosol differential mobility-coupled mass analyses.

PubMed

Nguyen, Thai Phuong; Chang, Wei-Chang; Lai, Yen-Chih; Hsiao, Ta-Chih; Tsai, De-Hao

2017-10-01

In this work, we develop an aerosol-based, time-resolved ion mobility-coupled mass characterization method to investigate colloidal assembly of graphene oxide (GO)-silver nanoparticle (AgNP) hybrid nanostructure on a quantitative basis. Transmission electron microscopy (TEM) and zeta potential (ZP) analysis were used to provide visual information and elemental-based particle size distributions, respectively. Results clearly show a successful controlled assembly of GO-AgNP by electrostatic-directed heterogeneous aggregation between GO and bovine serum albumin (BSA)-functionalized AgNP under an acidic environment. Additionally, physical size, mass, and conformation (i.e., number of AgNP per nanohybrid) of GO-AgNP were shown to be proportional to the number concentration ratio of AgNP to GO (R) and the selected electrical mobility diameter. An analysis of colloidal stability of GO-AgNP indicates that the stability increased with its absolute ZP, which was dependent on R and environmental pH. The work presented here provides a proof of concept for systematically synthesizing hybrid colloidal nanomaterials through the tuning of surface chemistry in aqueous phase with the ability in quantitative characterization. Graphical Abstract Colloidal assembly of graphene oxide-silver nanoparticle hybrids characterized by aerosol differential mobility-coupled mass analyses.

Self-assembled albumin nanoparticles as a nanocarrier for aclacinomycin A.

PubMed

Gong, Guangming; Liu, Wenya; Wang, Shudong

2016-11-18

This study aimed to reduce the cytotoxicity and improve the targeting of aclacinomycin (ACM) by covalently coupling it with amino-oxyacetic acid (AOA) to generate an active intermediate, AOA-ACM. AOA-ACM was conjugated with self-assembled human serum albumin (HSA) nanoparticles constructed using tris(2-carboxyethyl)phosphine (TCEP) as disulfide bond breaking molecules in an 'opening stage-intermediate-closing stage' route, in which the hydrophobic interaction, interchange of sulfhydryl and hydrogen bond may be the key factors in the assembling process. Conjugation between ACM and albumin nanoparticles was found to occur at an ACM ketone site using 1 H-NMR and 13 C-NMR matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass analysis indicated that the drug loading efficiency of ACM conjugated with HSA nanoparticles (NPs-ACM) was 7.4% (molar ratio = 6:1). The release of NPs-ACM was pH dependent. In vivo studies indicated that NPs-ACM exhibited fourfold higher tumor targeting capability on S180-tumor-bearing mice compared with the free ACM (p < 0.05). The cytotoxictiy and cardiotoxicity of NPs-ACM was reduced compared with the free ACM. Albumin carrier altered the blood pharmacokinetics and distribution of ACM. Hence, the NPs-ACM prodrug is ideal tumor targeting drug carriers for ACM, and the easy approach developed in this study for active intermediate and prodrug preparation can be applied to other pharmacological substances containing ketone groups. The method of preparing HSA-blank nanoparticles through TCEP reduction could be adopted to improve the water solubility of lipophilic drugs and their tumor-targeting specificity by fabricating HSA-lipophilic drug nanoparticles.

Inflamed site-specific drug delivery system based on the interaction of human serum albumin nanoparticles with myeloperoxidase in a murine model of experimental colitis.

PubMed

Iwao, Yasunori; Tomiguchi, Izumi; Domura, Ayaka; Mantaira, Yusuke; Minami, Akira; Suzuki, Takashi; Ikawa, Takashi; Kimura, Shin-Ichiro; Itai, Shigeru

2018-04-01

To develop a new strategy for inflamed site-specific drug delivery in the colon for the treatment of ulcerative colitis (UC), we leveraged on the interaction between myeloperoxidase (MPO) and human serum albumin (HSA) and prepared nanoparticles (HSA NPs) conjugated with 5-aminosalicylic acid (5-ASA). The 5-ASA-HSA NPs (nine molecules of 5-ASA per HSA molecule) were uniform particles with an average particle size of 190 nm, a zeta potential of --11.8 mV, and a polydispersity index of 0.35. This was considered a suitable particle characteristic to pass through the mucus layer and accumulate into the mucosa. The specific interaction between the 5-ASA-HSA NPs and MPO was observed using quartz crystal microbalance analysis in vitro. In addition, the 5-ASA-HSA NPs group containing one thousandth of the dose of the 5-ASA (75 μg/kg) showed significantly lower disease activity index values and colon weight/length ratios in UC model mice as similar to large amount of neat 5-ASA group (75 mg/kg), indicating that the therapeutic effect of the 5-ASA-HSA NP formulation was confirmed in vivo. Microscopic images of tissue sections of colon extracted from UC model mice demonstrated that HSA NPs and MPO were both localized in the colon, and this specific interaction between HSA NPs and MPO would be involved the in the therapeutic effect in vivo. Furthermore, in the 5-ASA and 5-ASA-HSA NPs groups, some inflammatory damage was observed in the colon, but the degree of damage was mild compared with the control and HSA NPs groups, suggesting mucosal repair and replacement with fibrous granulation tissue had occurred. Therefore, these data demonstrated that an HSA NP formulation has the potential to specifically deliver 5-ASA to an inflamed site where MPO is highly expressed. Copyright © 2018 Elsevier B.V. All rights reserved.

Tuning aggregation of microemulsion droplets and silica nanoparticles using solvent mixtures.

PubMed

Salabat, Alireza; Eastoe, Julian; Mutch, Kevin J; Tabor, Rico F

2008-02-15

The effect of solvent on stability of water-in-oil microemulsions has been studied with AOT (sodium bis(2-ethylhexyl)sulfosuccinate) and different solvent mixtures of n-heptane, toluene and dodecane. Dynamic light scattering DLS was used to monitor the apparent diffusion coefficient D(A) and effective microemulsion droplet diameter on changing composition of the solvent. Interdroplet attractive interactions, as indicated by variations in D(A), can be tuned by formulation of appropriate solvent mixtures using heptane, toluene, and dodecane. In extreme cases, solvent mixtures can be used to induce phase transitions in the microemulsions. Aggregation and stability of model AOT-stabilized silica nanoparticles in different solvents were also investigated to explore further these solvent effects. For both systems the state of aggregation can be correlated with the effective molecular volume of the solvent V(mol)(eff) mixture.

Suitability of differently formulated dry powder Newcastle disease vaccines for mass vaccination of poultry.

PubMed

Huyge, Katrien; Van Reeth, Kristien; De Beer, Thomas; Landman, Wil J M; van Eck, Jo H H; Remon, Jean Paul; Vervaet, Chris

2012-04-01

Dry powders containing a live-attenuated Newcastle disease vaccine (LZ58 strain) and intended for mass vaccination of poultry were prepared by spray drying using mannitol in combination with trehalose or inositol, polyvinylpyrrolidone (PVP) and/or bovine serum albumin (BSA) as stabilizers. These powders were evaluated for vaccine stabilizing capacity during production and storage (at 6 °C and 25 °C), moisture content, hygroscopicity and dry powder dispersibility. A mixture design, varying the ratio of mannitol, inositol and BSA, was used to select the stabilizer combination which resulted in the desired powder properties (i.e. good vaccine stability during production and storage, low moisture content and hygroscopicity and good dry dispersibility). Inositol-containing powders had the same vaccine stabilizing capacity as trehalose powders, but were less hygroscopic. Incorporation of BSA enhanced the vaccine stability in the powders compared to PVP-containing formulations. However, increasing the BSA concentration increased the hygroscopicity and reduced the dry dispersibility of the powder. No valid mathematical model could be calculated for vaccine stability during production or storage, but the individual experiments indicated that a formulation combining mannitol, inositol and BSA in a ratio of 73.3:13.3:13.3 (wt/wt) resulted in the lowest vaccine titre loss during production (1.6-2.0 log(10) 50% egg infectious dose (EID(50)) and storage at 6 °C (max. 0.8 log(10) EID(50) after 6 months) in combination with a low moisture content (1.1-1.4%), low hygroscopicity (1.9-2.1% water uptake at 60% relative humidity) and good dry dispersibility properties. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of Gold Salt Speciation and Structure of Human and Bovine Serum Albumins on the Synthesis and Stability of Gold Nanostructures

PubMed Central

Miranda, Érica G. A.; Tofanello, Aryane; Brito, Adrianne M. M.; Lopes, David M.; Albuquerque, Lindomar J. C.; de Castro, Carlos E.; Costa, Fanny N.; Giacomelli, Fernando C.; Ferreira, Fabio F.; Araújo-Chaves, Juliana C.; Nantes, Iseli L.

2016-01-01

The present study aimed to investigate the influence of albumin structure and gold speciation on the synthesis of gold nanoparticles (GNPs). The strategy of synthesis was the addition of HAuCl4 solutions at different pH values (3–12) to solutions of human and bovine serum albumins (HSA and BSA) at the same corresponding pH values. Different pH values influence the GNP synthesis due to gold speciation. Besides the inherent effect of pH on the native structure of albumins, the use N-ethylmaleimide (NEM)-treated and heat-denaturated forms of HSA and BSA provided additional insights about the influence of protein structure, net charge, and thiol group approachability on the GNP synthesis. NEM treatment, heating, and the extreme values of pH promoted loss of the native albumin structure. The formation of GNPs indicated by the appearance of surface plasmon resonance (SPR) bands became detectable from 15 days of the synthesis processes that were carried out with native, NEM-treated and heat-denaturated forms of HSA and BSA, exclusively at pH 6 and 7. After 2 months of incubation, SPR band was also detected for all synthesis carried out at pH 8.0. The mean values of the hydrodynamic radius (RH) were 24 and 34 nm for GNPs synthesized with native HSA and BSA, respectively. X-ray diffraction (XRD) revealed crystallites of 13 nm. RH, XRD, and zeta potential values were consistent with GNP capping by the albumins. However, the GNPs produced with NEM-treated and heat-denaturated albumins exhibited loss of protein capping by lowering the ionic strength. This result suggests a significant contribution of non-electrostatic interactions of albumins with the GNP surface, in these conditions. The denaturation of proteins exposes hydrophobic groups to the solvent, and these groups could interact with the gold surface. In these conditions, the thiol blockage or oxidation, the latter probably favored upon heating, impaired the formation of a stable capping by thiol coordination with the gold surface. Therefore, the cysteine side chain of albumins is important for the colloidal stabilization of GNPs rather than as the reducing agent for the synthesis. Despite the presence of more reactive gold species at more acidic pH values, i.e., below 6.0, in these conditions the loss of native albumin structure impaired GNP synthesis. Alkaline pH values (9–12) combined the unfavorable conditions of denaturated protein structure with less reactive gold species. Therefore, an optimal condition for the synthesis of GNPs using serum albumins involves more reactive gold salt species combined with a reducing and negatively charged form of the protein, all favored at pH 6–7. PMID:27066476

Nanoparticle Delivery of Artesunate Enhances the Anti-tumor Efficiency by Activating Mitochondria-Mediated Cell Apoptosis

NASA Astrophysics Data System (ADS)

Liu, Rui; Yu, Xiwei; Su, Chang; Shi, Yijie; Zhao, Liang

2017-06-01

Artemisinin and its derivatives were considered to exert a broad spectrum of anti-cancer activities, and they induced significant anti-cancer effects in tumor cells. Artemisinin and its derivatives could be absorbed quickly, and they were widely distributed, selectively killing tumor cells. Since low concentrations of artesunate primarily depended on oncosis to induce cell death in tumor cells, its anti-tumor effects were undesirable and limited. To obtain better anti-tumor effects, in this study, we took advantage of a new nanotechnology to design novel artesunate-loaded bovine serum albumin nanoparticles to achieve the mitochondrial accumulation of artesunate and induce mitochondrial-mediated apoptosis. The results showed that when compared with free artesunate's reliance on oncotic death, artesunate-loaded bovine serum albumin nanoparticles showed higher cytotoxicity and their significant apoptotic effects were induced through the distribution of artesunate in the mitochondria. This finding indicated that artesunate-loaded bovine serum albumin nanoparticles damaged the mitochondrial integrity and activated mitochondrial-mediated cell apoptosis by upregulating apoptosis-related proteins and facilitating the rapid release of cytochrome C.

Cys34-PEGylated Human Serum Albumin for Drug Binding and Delivery

PubMed Central

Mehtala, Jonathan G.; Kulczar, Chris; Lavan, Monika; Knipp, Gregory; Wei, Alexander

2015-01-01

Polyethylene glycol (PEG) derivatives were conjugated onto the Cys-34 residue of human serum albumin (HSA) to determine their effects on the solubilization, permeation, and cytotoxic activity of hydrophobic drugs such as paclitaxel (PTX). PEG(C34)HSA conjugates were prepared on a multigram scale by treating native HSA (n-HSA) with 5- or 20-kDa mPEG-maleimide, resulting in up to 77% conversion of the mono-PEGylated adduct. Nanoparticle tracking analysis of PEG(C34)HSA formulations in phosphate buffer revealed an increase in nanosized aggregates relative to n-HSA, both in the absence and presence of PTX. Cell viability studies conducted with MCF-7 breast cancer cells indicated that PTX cytotoxicity was enhanced by PEG(C34)HSA when mixed at 10:1 mole ratios, up to a two-fold increase in potency relative to n-HSA. The PEG(C34)HSA conjugates were also evaluated as PTX carriers across monolayers of HUVEC and hCMEC/D3 cells, and found to have nearly identical permeation profiles as n-HSA. PMID:25918947

Enhanced antifouling and antibacterial properties of poly (ether sulfone) membrane modified through blending with sulfonated poly (aryl ether sulfone) and copper nanoparticles

NASA Astrophysics Data System (ADS)

Zhang, Jingjing; Xu, Ya'nan; Chen, Shouwen; Li, Jiansheng; Han, Weiqing; Sun, Xiuyun; Wu, Dihua; Hu, Zhaoxia; Wang, Lianjun

2018-03-01

A series of novel blend ultrafiltration (UF) membranes have been successfully prepared from commercial poly (ether sulfone), lab-synthesized sulfonated poly (aryl ether sulfone) (SPAES, 1 wt%) and copper nanoparticles (0 ∼ 0.4 wt%) via immersion precipitation phase conversion. The micro-structure and separation performance of the membranes were characterized by field emission scanning electron microscopy (SEM) and cross-flow filtration experiments, respectively. Sodium alginate, bovine serum albumin and humic acid were chosen as model organic foulants to investigate the antifouling properties, while E. coil was used to evaluate the antibacterial property of the fabricated membranes. By the incorporation with SPAES and copper nanoparticles, the hydrophilicity, antifouling and antibacterial properties of the modified UF membranes have been profoundly improved. At a copper nanoparticles content of 0.4 wt%, the PES/SPAES/nCu(0.4) membrane exhibited a high pure water flux of 193.0 kg/m2 h, reaching the smallest contact angle of 52°, highest flux recovery ratio of 79% and largest antibacterial rate of 78.9%. Furthermore, the stability of copper nanoparticles inside the membrane matrix was also considerably enhanced, the copper nanoparticles were less than 0.08 mg/L in the effluent during the whole operation.

Disulfiram-loaded mixed nanoparticles with high drug-loading and plasma stability by reducing the core crystallinity for intravenous delivery.

PubMed

Zhuo, Xuezhi; Lei, Tian; Miao, Linlin; Chu, Wei; Li, Xiaowen; Luo, Lifeng; Gou, Jingxin; Zhang, Yu; Yin, Tian; He, Haibing; Tang, Xing

2018-05-30

To develop an injectable formulation and improve the stability of disulfiram (DSF), DSF was encapsulated into mixed nanoparticles (DSF-NPs) through a high-pressure homogenization method. The Flory-Huggins interaction parameters (χ FH ) were calculated to predict the miscibility between DSF and the hydrophobic core, resulting in PCL 5000 selected as the hydrophobic block to encapsulate the DSF, as PCL 5000 had a lower χ FH 3.39 and the drug loading of the nanoparticles prepared by mPEG 5000 -PCL 5000 was relatively higher. mPEG 5000 -PCL 5000 and PCL 5000 were blended to reduce the leakage of DSF during preparation, as well as increase the stability of the nanoparticles. The cargo-loading capacity of the nanoparticles was improved from 3.35% to 5.50% by reducing the crystallinity of the PCL nanoparticle core, and the crystallinity decreased from 51.13% to 25.15% after adding medium chain triglyceride (MCT). The DSF-NPs prepared by the above method had a small particle size of 98.1 ± 10.54 nm, with a polydispersity index (PDI) of 0.036, as well as drug loading of 5.50%. Furthermore, DSF-NPs containing MCT showed higher stability than DSF-NPs without MCT and DSF-sol (DSF dissolved in Cremophor EL and ethanol) in water and 90% plasma-containing PBS. The pharmacokinetics proved that DSF-NPs containing MCT enhanced the DSF concentration in the blood. Finally, DSF-NPs effectively inhibited H22 xenograft tumor growth in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

Improved stability and oral bioavailability of Ganneng dropping pills following transforming lignans of herpetospermum caudigerum into nanosuspensions.

PubMed

Li, Juan-Juan; Cheng, Ling; Shen, Gang; Qiu, Ling; Shen, Cheng-Ying; Zheng, Juan; Xu, Rong; Yuan, Hai-Long

2018-01-01

The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills (GNDP) by transforming lignans of Herpetospermum caudigerum (HL) composed of herpetrione (HPE) and herpetin (HPN) into nanosuspension (HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles (HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy (PCS), zeta potential measurement, and scanning electron microscopy (SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC 0-t , C max and decrease in T max when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability. Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Albumin-stabilized fluorescent silver nanodots

NASA Astrophysics Data System (ADS)

Sych, Tomash; Polyanichko, Alexander; Kononov, Alexei

2017-07-01

Ligand-stabilized Ag nanoclusters (NCs) possess many attractive features including high fluorescence quantum yield, large absorption cross-section, good photostability, large Stokes shift and two-photon absorption cross sections. While plenty of fluorescent clusters have been synthesized on various polymer templates, only a few studies have been reported on the fluorescent Ag clusters on peptides and proteins. We study silver NCs synthesized on different protein matrices, including bovine serum albumin, human serum albumin, egg albumin, equine serum albumin, and lysozyme. Our results show that red-emitting Ag NCs can effectively be stabilized by the disulfide bonds in proteins and that the looser structure of the denatured protein favors formation of the clusters.

PEG-PLA-PEG block copolymeric nanoparticles for oral immunization against hepatitis B.

PubMed

Jain, Arvind K; Goyal, Amit K; Mishra, Neeraj; Vaidya, Bhuvaneshwar; Mangal, Sharad; Vyas, Suresh P

2010-03-15

PLA/PLGA nanoparticles are well known as efficient vaccine delivery systems, but they have got limitation in oral vaccine delivery because of their sensitivity to harsh gastric environment. The aim of present study was to improve the stability of PLA nanoparticles in such environment by copolymerizing PLA with PEG. Nanoparticles were formulated using different block copolymers AB, ABA and BAB (where 'A' is PLA and 'B' is PEG) encapsulating hepatitis B surface antigen (HBsAg) to evaluate their efficacy as oral vaccine delivery system. The results of in vitro studies engrave the efficiency of copolymeric nanoparticles to retain encapsulated antigen and average particle size even after 2 h incubation in simulated gastric fluid and simulated intestinal fluid. Fluorescence microscopic studies indicated efficient uptake of copolymeric nanoparticles by gut mucosa of immunized mice model as compared to control. Finally copolymeric and PLA nanoparticles, encapsulating HBsAg, were evaluated for their adjuvancity in generating immune response after oral administration. PLA nanoparticles could not generate an effective immune response due to stability issues. On the other hand, oral administration of copolymeric nanoparticles exhibited effective levels of humoral immunity along with the mucosal (sIgA) and cellular immune response (T(H)1). The results of in vitro and in vivo studies demonstrate that BAB nanoparticles depict enhanced mucosal uptake leading to effective immune response as compared to other copolymeric nanoparticles. Present study indicates the efficacy of BAB nanoparticles as a promising carrier for oral immunization. 2009 Elsevier B.V. All rights reserved.

Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery.

PubMed

Bhalekar, Mangesh R; Pokharkar, Varsha; Madgulkar, Ashwini; Patil, Nilam; Patil, Nilkanth

2009-01-01

The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.

PEGylation of supercooled smectic cholesteryl myristate nanoparticles.

PubMed

Mengersen, Friederike; Bunjes, Heike

2012-06-01

Supercooled smectic cholesterol ester nanoparticles are under investigation as a new carrier system for lipophilic drugs. The smectic thermotropic liquid crystalline state of the matrix lipid is expected to lead to advantages with respect to physicochemical stability and drug loading capacity. Such nanoparticles can be prepared by high-pressure melt homogenization in the presence of emulsifiers. The purpose of this study was to develop PEGylated supercooled smectic cholesteryl myristate nanoparticles for parenteral administration and to provide evidence of the successful PEGylation by detecting the alterations of particle properties due to the insertion of PEGylated phospholipid into the surface layer of the particles. To achieve PEGylation, MPEG(2000)-DSPE was processed together with the phospholipids used as emulsifiers during particle preparation. The influence of the PEGylated phospholipid on the size, zeta potential, phase behavior and recrystallization tendency of the nanoparticles indicated the insertion of MPEG(2000)-DSPE into the surface layer of the particles. Evidence of the PEGylation was also obtained by (1)H NMR measurements, and the steric stabilization was verified by neutralizing the particle surface charge with calcium chloride or adjusting the pH value. As sterility is an important aspect with regard to parenteral administration of the dispersions their stability upon autoclaving was a further point of interest in the present study. The results indicate that PEGylated particles can be sterilized by autoclaving. In conclusion, the PEGylated particles are a promising formulation with respect to small particle size, stability against recrystallization and upon autoclaving. Copyright © 2012 Elsevier B.V. All rights reserved.

Biomedical Properties Study of Modified Chitosan Nanoparticles for Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Saboktakin, Mohammad Reza

2013-09-01

The purpose of this review is to discuss and summarize some of the interesting findings and applications of modified chitosan (MCS) and their derivatives in different areas of drug delivery. This review highlights the important applications of MCS in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their uses as recipients in drug formulation are also discussed. This review also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting MCS in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized.

Human serum albumin (HSA) nanoparticles: reproducibility of preparation process and kinetics of enzymatic degradation.

PubMed

Langer, K; Anhorn, M G; Steinhauser, I; Dreis, S; Celebi, D; Schrickel, N; Faust, S; Vogel, V

2008-01-22

Nanoparticles prepared from human serum albumin (HSA) are versatile carrier systems for drug delivery and can be prepared by an established desolvation process. A reproducible process with a low batch-to-batch variability is required for transfer from the lab to an industrial production. In the present study the batch-to-batch variability of the starting material HSA on the preparation of nanoparticles was investigated. HSA can build dimers and higher aggregates because of a free thiol group present in the molecule. Therefore, the quality of different HSA batches was analysed by size exclusion chromatography (SEC) and analytical ultracentrifugation (AUC). The amount of dimerised HSA detected by SEC did not affect particle preparation. Higher aggregates of the protein detected in two batches by AUC disturbed nanoparticle formation at pH values below 8.0. At pH 8.0 and above monodisperse particles between 200 and 300 nm could be prepared with all batches, with higher pH values leading to smaller particles. Besides human derived albumin a particle preparation was also feasible based on recombinant human serum albumin (rHSA). Under comparable preparation conditions monodisperse nanoparticles could be achieved and the same effects of protein aggregates on particle formation were observed. For nanoparticulate drug delivery systems the enzymatic degradation is a crucial parameter for the release of an embedded drug. For this reason, besides the particle preparation process, particle degradation in the presence of different enzymes was studied. Under acidic conditions HSA as well as rHSA nanoparticles could be digested by pepsin and cathepsin B. At neutral pH trypsin, proteinase K, and protease were suitable for particle degradation. It could be shown that the kinetics of particle degradation was dependent on the degree of particle stabilisation. Therefore, the degree of particle stabilisation will influence drug release after cellular accumulation of HSA nanoparticles.

Solid lipid nanoparticles for enhancing vinpocetine's oral bioavailability.

PubMed

Luo, YiFan; Chen, DaWei; Ren, LiXiang; Zhao, XiuLi; Qin, Jing

2006-08-10

An ultrasonic-solvent emulsification technique was adopted to prepare vinpocetine loaded Glyceryl monostearate (GMS) nanodispersions with narrow size distribution. To increase the lipid load the process was conducted at 50 degrees C, and in order to prepare nanoparticle using an ultrasonic-solvent emulsification technique. The mean particle size and droplet size distribution, drug loading capacity, drug entrapment efficiency (EE%), zeta potential, and long-term physical stability of the SLNs were investigated in detail respectively. Drug release from two sorts of VIN-SLN was studied using a dialysis bag method. A pharmacokinetic study was conducted in male rats after oral administration of 10 mg kg(-1) VIN in different formulations, it was found that the relative bioavailability of VIN in SLNs was significantly increased compared with that of the VIN solution. The amount of surfactant also had a marked effect on the oral absorption of VIN with SLN formulations. The absorption mechanism of the SLN formulations was also discussed. These results indicated that VIN absorption is enhanced significantly by employing SLN formulations. SLNs offer a new approach to improve the oral bioavailability of poorly soluble drugs.

Development and evaluation of resveratrol, Vitamin E, and epigallocatechin gallate loaded lipid nanoparticles for skin care applications.

PubMed

Chen, Jin; Wei, Ning; Lopez-Garcia, Maria; Ambrose, Dianna; Lee, Jason; Annelin, Colin; Peterson, Teresa

2017-08-01

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied as potential carriers for both dermal and transdermal drug delivery. SLN contain lipid droplets that are fully crystallized and have a highly-ordered crystalline structure. NLC are modified SLN in which the lipid phase contains both solid and liquid lipids at room temperature. SLN and NLC are thought to combine the advantages of polymeric particles, liposomes and emulsions. Therefore they provide high encapsulation percentages, better protection for incorporated actives and allow for control of desired release profile. In this work, Resveratrol, Vitamin E (VE), and Epigallocatechin Gallate (EGCG) all potent antioxidants known to provide protection to the skin, were formulated into lipid nanoparticles. Several different formulations were successfully developed and demonstrated high uniformity and stability. Both resveratrol and VE lipid nanoparticles provided effective protection of actives against UV induced degradation. However, lipid nanoparticles did not show protection from UV degradation for EGCG in this work. An active release study exhibited a sustained release of resveratrol over 70% after 24h. Skin penetration studies showed that lipid nanoparticles directionally improved the penetration of resveratrol through the stratum corneum. Our findings suggest that lipid nanoparticles are promising viable carriers for the delivery of resveratrol and VE to provide longlasting antioxidant benefits to the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate.

PubMed

Uner, M; Wissing, S A; Yener, G; Müller, R H

2005-08-01

The aim of this study was to improve the chemical stability of ascorbyl palmitate (AP) in a colloidal lipid carrier for its topical use. For this purpose, AP-loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, a nanoemulsion (NE) were prepared employing the high pressure homogenization technique and stored at room temperature (RT), 4 degrees C and 40 degrees C. During 3 months, physical stability of these formulations compared to placebo formulations which were prepared by the same production method, was studied including recrystallization behaviour of the lipid with differential scanning calorimetry (DSC), particle size distribution and storage stability with photon correlation spectroscopy (PCS) and laser diffractometry (LD). After evaluating data indicating excellent physical stability, AP-loaded SLN, NLC and NE were incorporated into a hydrogel by the same production method as the next step. Degradation of AP by HPLC and physical stability in the same manner were investigated at the same storage temperatures during 3 months. As a result, AP was found most stable in both the NLC and SLN stored at 4 degrees C (p > 0.05) indicating the importance of storage temperature. Nondegraded AP content in NLC, SLN and NE was found to be 71.1% +/- 1.4, 67.6% +/- 2.9 and 55.2% +/- 0.3 after 3 months, respectively. Highest degradation was observed with NE at all the storage temperatures indicating even importance of the carrier structure.

Albumin-based nanoparticle trehalose lyophilisation stress-down to preserve structure/function and enhanced binding.

PubMed

Siri, Macarena; Grasselli, Mariano; Alonso, Silvia Del V

2016-07-15

The aim of this study was to preserve albumin nanoparticle structure/function during the lyophilisation process. Bovine serum albumin nanoparticles were obtained by γ-irradiation. Nanoparticles were lyophilised in buffer, miliQ water or in trehalose/miliQ solution. The size and charge of the nanoparticles were tested after lyophilisation by light scattering and Z potential. The most relevant results in size of BSA nanoparticle were those lyophilised in PBS between 20 and 350nm, assembled in different aggregates, and negative Z potential obtained was 37±8mV in all, and those nanoparticles lyophilised with trehalose had a size range of 70±2nm and a negative Z potential of 20±5mV. Structure determination of surface aminoacids SH groups in the BSA NP lyophilised in PBS showed an increase in the free SH groups. Different aggregates had different amount of SH groups exposure from 55 to 938 (from smaller to bigger aggregates), whereas BSA NP lyophilised with trehalose showed no significant difference if compared with BSA NP. The binding properties of the BSA nanoparticle with a theragnostic probe (merocyanine 540) were studied after lyophilisation. Results showed more affinity between the BSA NP lyophilised with trehalose than that observed with non lyophilised BSA NP. As a result, the lyophilisation condition in trehalose 100μM solution is the best one to preserve the BSA NP structure/function and the one with the enhance binding affinity of the BSA NP. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation and evaluation of chitosan solid lipid nanoparticles of carbamazepine.

PubMed

Nair, Rahul; Kumar, Ashok C K; Priya, Vishnu K; Yadav, Chakrapani M; Raju, Prasanna Y

2012-06-13

The present work aims at preparing aqueous suspension of Solid lipid Nanoparticles containing Chitosan (CT) which is a biopolymer that exhibits a number of interesting properties which include controlled drug delivery. Carbamezapine (CBZ) is a lipophilic drug which shows it antiepileptic activity by inactivating sodium channels. The solid lipid Nanoparticles (SLN) of Chitosan-CBZ were prepared by using solvent injection method using ethanol as organic solvent. The prepared SLN formulations exhibited high encapsulation efficiency, high physical stability. The drug incorporated SLNs have demonstrated that the controlled release patterns of the drug for prolonged period. The prepared SLNs were characterized for surface morphology by SEM analysis, entrapment efficiency, zeta potential, FTIR, DSC and In-vitro diffusion studies. The hydrodynamic mean diameter and zeta potential were 168.7 ± 1.8 nm and -28.9 ± 2.0 mV for SLN-chitosan-CBZ respectively. Therefore chitosan-SLN can be good candidates to encapsulate CBZ and to increase its therapeutic efficacy in the treatment of Epilepsy.

Formulation and evaluation of chitosan solid lipid nanoparticles of carbamazepine

PubMed Central

2012-01-01

The present work aims at preparing aqueous suspension of Solid lipid Nanoparticles containing Chitosan (CT) which is a biopolymer that exhibits a number of interesting properties which include controlled drug delivery. Carbamezapine (CBZ) is a lipophilic drug which shows it antiepileptic activity by inactivating sodium channels. The solid lipid Nanoparticles (SLN) of Chitosan-CBZ were prepared by using solvent injection method using ethanol as organic solvent. The prepared SLN formulations exhibited high encapsulation efficiency, high physical stability. The drug incorporated SLNs have demonstrated that the controlled release patterns of the drug for prolonged period. The prepared SLNs were characterized for surface morphology by SEM analysis, entrapment efficiency, zeta potential, FTIR, DSC and In-vitro diffusion studies. The hydrodynamic mean diameter and zeta potential were 168.7 ±1.8 nm and −28.9 ±2.0 mV for SLN-chitosan-CBZ respectively. Therefore chitosan-SLN can be good candidates to encapsulate CBZ and to increase its therapeutic efficacy in the treatment of Epilepsy. PMID:22695222

Phase-Change Nanoparticles Using Highly Volatile Perfluorocarbons: Toward a Platform for Extravascular Ultrasound Imaging

PubMed Central

Matsunaga, Terry O.; Sheeran, Paul S.; Luois, Samantha; Streeter, Jason E.; Mullin, Lee B.; Banerjee, Bhaskar; Dayton, Paul A.

2012-01-01

Recent efforts using perfluorocarbon (PFC) nanoparticles in conjunction with acoustic droplet vaporization has introduced the possibility of expanding the diagnostic and therapeutic capability of ultrasound contrast agents to beyond the vascular space. Our laboratories have developed phase-change nanoparticles (PCNs) from the highly volatile PFCs decafluorobutane (DFB, bp =-2 °C) and octafluoropropane (OFP, bp =-37 °C ) for acoustic droplet vaporization. Studies with commonly used clinical ultrasound scanners have demonstrated the ability to vaporize PCN emulsions with frequencies and mechanical indices that may significantly decrease tissue bioeffects. In addition, these contrast agents can be formulated to be stable at physiological temperatures and the perfluorocarbons can be mixed to modulate the balance between sensitivity to ultrasound and general stability. We herein discuss our recent efforts to develop finely-tuned diagnostic/molecular imaging agents for tissue interrogation. We discuss studies currently under investigation as well as potential diagnostic and therapeutic paradigms that may emerge as a result of formulating PCNs with low boiling point PFCs. PMID:23382775

Differently Environment Stable Bio-Silver Nanoparticles: Study on Their Optical Enhancing and Antibacterial Properties

PubMed Central

Balachandran, Yekkuni L.; Girija, Shanmugam; Selvakumar, Rajendran; Tongpim, Saowanit; Gutleb, Arno C.; Suriyanarayanan, Sarvajeyakesavalu

2013-01-01

Generally, limited research is extended in studying stability and applicational properties of silver nanoparticles (Ag NPs) synthesized by adopting ‘green chemistry’ protocol. In this work, we report on the synthesis of stable Ag NPs using plant-derived materials such as leaf extract of Neem (Azadirachta indica) and biopolymer pectin from apple peel. In addition, the applicational properties of Ag NPs such as surface-enhanced Raman scattering (SERS) and antibacterial efficiencies were also investigated. As-synthesized nanoparticles (NPs) were characterized using various instrumentation techniques. Both the plant materials (leaf extract and biopolymer) favored the synthesis of well-defined NPs capped with biomaterials. The NPs were spherical in shape with an average particle size between 14-27 nm. These bio-NPs exhibited colloidal stability in most of the suspended solutions such as water, electrolyte solutions (NaCl; NaNO3), biological solution (bovine serum albumin), and in different pH solutions (pH 7; 9) for a reasonable time period of 120 hrs. Both the bio-NPs were observed to be SERS active through displaying intrinsic SERS signals of the Raman probe molecule (Nile blue A). The NPs were effective against the Escherichia coli bacterium when tested in nutrient broth and agar medium. Scanning and high-resolution transmission electron microscopy (SEM and HRTEM) images confirmed cellular membrane damage of nanoparticle treated E. coli cells. These environmental friendly template Ag NPs can be used as an antimicrobial agent and also for SERS based analytical applications. PMID:24130832

Formulation, Characterization and Stability Assessment of a Food-Derived Tripeptide, Leucine-Lysine-Proline Loaded Chitosan Nanoparticles.

PubMed

Danish, Minna K; Vozza, Giuliana; Byrne, Hugh J; Frias, Jesus M; Ryan, Sinéad M

2017-09-01

The chicken- or fish-derived tripeptide, leucine-lysine-proline (LKP), inhibits the angiotensin converting enzyme and may be used as an alternative treatment for prehypertension. However, it has low permeation across the small intestine. The formulation of LKP into a nanoparticle (NP) has the potential to address this issue. LKP-loaded NPs were produced using an ionotropic gelation technique, using chitosan (CL113). Following optimization of unloaded NPs, a mixture amount design was constructed using variable concentration of CL113 and tripolyphosphate at a fixed LKP concentration. Resultant particle sizes ranged from 120 to 271 nm, zeta potential values from 29 to 37 mV, and polydispersity values from 0.3 to 0.6. A ratio of 6:1 (CL113:TPP) produced the best encapsulation of approximately 65%. Accelerated studies of the loaded NPs indicated stability under normal storage conditions (room temperature). Cytotoxicity assessment showed no significant loss of cell viability and in vitro release studies indicated an initial burst followed by a slower and sustained release. © 2017 Institute of Food Technologists®.

Protease Inhibition by Oleic Acid Transfer From Chronic Wound Dressings to Albumin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edwards, J. V.; Howley, Phyllis; Davis, Rachel M.

High elastase and cathepsin G activities have been observed in chronic wounds. These levels can inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid (18:1) is a non-toxic elastase inhibitor with some potential for redressing the imbalance of elastase activity found in chronic wounds. Cotton wound dressing material was characterized as a transfer carrier for affinity uptake of 18:1 by albumin under conditions mimicking chronic wounds. 18:1-treated cotton was examined for its ability to bind and release the fatty acid in the presence of albumin. The mechanism of 18:1 uptake from cotton and binding bymore » albumin was examined with both intact dressings and cotton fiber-designed chromatography. Raman spectra of the albumin-18:1 complexes under liquid-liquid equilibrium conditions revealed fully saturated albumin-18:1 complexes with a 1:1 weight ratio of albumin:18:1. Cotton chromatography under liquid-solid equilibrium conditions revealed oleic acid transfer from cotton to albumin at 27 mole equivalents of 18:1 per mole albumin. Cotton was contrasted with hydrogel, and hydrocolloid wound dressing for its comparative ability to lower elastase activity. Each dressing material evaluated was found to release 18:1 in the presence of albumin with significant inhibition of elastase activity. The 18:1-formulated wound dressings lowered elastase activity in a dose dependent manner in the order cotton gauze > hydrogel > hydrocolloid. In contrast the cationic serine protease Cathepsin G was inihibited by 18:1 within a narrow range of 18:1-cotton formulations. Four per cent Albumin solutions were most effective in binding cotton bound-18:1. However, 2% albumin was sufficient to transfer quantities of 18:1 necessary to achieve a significant elastase-lowering effect. Formulations with 128 mg 18:1/g cotton gauze had equivalent elastase lowering with 1 - 4% albumin. 18:1 bound to cotton wound dressings may have promise in the selective lowering of cationic serine protease activity useful in topical application for chronic inflammatory pathogenesis.« less

Drug nanosuspensions: a ZIP tool between traditional and innovative pharmaceutical formulations.

PubMed

Leone, Federica; Cavalli, Roberta

2015-01-01

A nanosuspension or nanocrystal suspension is a versatile formulation combining conventional and innovative features. It comprises 100% pure drug nanoparticles with sizes in the nano-scale range, generally stabilized by surfactants or polymers. Nanosuspensions are usually obtained in liquid media with bottom-up and top-down methods or by their combination. They have been designed to enhance the solubility, the dissolution rate and the bioavailability of drugs via various administration routes. Due to their small sizes, nanosuspensions can be also considered a drug delivery nanotechnology for the preparation of nanomedicine products. This review focuses on the state of the art of the nanocrystal-based formulation. It describes theory characteristics, design parameters, preparation methods, stability issues, as well as specific in vivo applications. Innovative strategies proposed to obtain nanomedicine formulation using nanocrystals are also reported. Many drug nanodelivery systems have been developed to increase the bioavailability of drugs and to decrease adverse side effects, but few can be industrially manufactured. Nanocrystals can close this gap by combining traditional and innovative drug formulations. Indeed, they can be used in many pharmaceutical dosage forms as such, or developed as new nano-scaled products. Engineered surface nanocrystals have recently been proposed as a dual strategy for stability enhancement and targeting delivery of nanocrystals.

Parenteral formulation of an antileishmanial drug candidate--tackling poor solubility, chemical instability, and polymorphism.

PubMed

Kupetz, Eva; Preu, Lutz; Kunick, Conrad; Bunjes, Heike

2013-11-01

The paullon chalcone derivative KuRei300 is active against Leishmania donovani, the protozoans causing visceral leishmaniasis. The aim of this study was the development of a parenteral formulation of the virtually water insoluble compound in order to enable future studies in mice. Mixed lecithin/bile salt micelles, liposomes, supercooled smectic cholesterol myristate nanoparticles, cubic phase nanoparticles and a triglyceride emulsion were screened for their solubilizing properties. Due to the limited available amount of KuRei300 a passive loading approach with pre-formulated carriers that were incubated with drug substance deposited onto the walls of glass vials was used. The loading capacities of the nanocarriers, the influence of the solid state properties of the drug and its deposits on the loading results and chemical stability aspects of KuRei300 were investigated. Employed methods included HPLC, UV spectroscopy, (1)H NMR, XRPD, and DSC. All nanocarriers substantially improved the solubility of KuRei300; the mixed micelles exhibited the highest drug load. Related to the lipid matrix, however, the smectic nanoparticles solubilized the significantly highest amount of drug. Loading from physically altered drug deposits improved the obtainable concentration to the threefold compared with untreated drug powder. Formulations with KuRei300 must be stored excluded from light under a nitrogen atmosphere as the substance is susceptible to photoisomerization and decomposition. Copyright © 2013 Elsevier B.V. All rights reserved.

Terbium content affects the luminescence properties of ZrO2:Tb nanoparticles for mammary cancer imaging in mice

NASA Astrophysics Data System (ADS)

Kaszewski, Jarosław; Borgstrom, Emanuel; Witkowski, Bartłomiej S.; Wachnicki, Łukasz; Kiełbik, Paula; Slonska, Anna; Domino, Malgorzata A.; Narkiewicz, Urszula; Gajewski, Zdzislaw; Hochepied, Jean-François; Godlewski, Michał M.; Godlewski, Marek

2017-12-01

The use of nanoparticles in medicine is a rapidly growing research field with numerous potential applications, especially in the field of cancer diagnosis and therapy. Nanoparticles can be intrinsically diagnostic of therapeutic, or they can be conjugated with diagnostic or therapeutic compounds. Nanoparticles may also passively or actively target tumor cells specifically using the enhanced permeation and retention (EPR) effect, or the addition of targeting ligands to their surface. This may provide a diagnostic or/and therapeutic tools to target primary as well as metastatic tumors. The transport, distribution and toxicity of nanoparticles depends greatly on their size and composition, thus every new formulation needs to be extensively researched. This work was focused on the development of Tb-doped ZrO2 nanoparticles (NPs) for application in cancer imaging. Obtained nanoparticles were below 10 nm with very low influence of Tb concentration on size. Terbium stabilization of ZrO2 had influence on the luminescence properties of obtained material. Partially stabilized zirconium dioxide exhibited broad host related emission peaking at 500 nm, disappearing with the terbium content. We confirmed alimentary absorption and wide distribution of luminescent ZrO2:Tb nanoparticles in mice with their gradual accumulation in the experimentally induced mammary cancers. Furthermore, a high concentration of NPs was found within the lung metastases as opposed to healthy lung tissue, where no NPs-related signal was observed.

Development of highly stabilized curcumin nanoparticles by flash nanoprecipitation and lyophilization.

PubMed

Chow, Shing Fung; Wan, Ka Yee; Cheng, Kwok Kin; Wong, Ka Wai; Sun, Changquan Calvin; Baum, Larry; Chow, Albert Hee Lum

2015-08-01

The influence of critical operating parameters on the Flash Nanoprecipitation (FNP) and resulting material properties of curcumin (CUR) nanoparticles has been evaluated using a confined impinging jets-with-dilution mixer (CIJ-D-M). It has been shown that the mixing rate, molecular weight of polymeric stabilizer (i.e., polyethylene glycol-b-poly(dl-lactide) di-block copolymer; PEG-PLA) and drug-to-copolymer mass ratio all exert a significant impact on the particle size and stability of the generated nanosuspensions. The attainable mean particle size and span of the nanoparticles through optimization of these process parameters were approximately 70nm and 0.85 respectively. However, the optimized nanosuspension was only stable for about two hours after preparation. Co-formulation with polyvinylpyrrolidone (PVP) substantially extended the product lifespan to 5days at ambient conditions and two weeks at 4°C. Results from zeta potential measurement and X-ray photoelectron spectroscopy (XPS) suggested that the enhanced stability is probably due to the formation of an additional protective barrier by PVP around the particle surface, thereby suppressing the dissociation of PEG-PLA from the particles and preventing CUR leakage from inside. Long-term storage stability (>1year) could be achieved by lyophilization of the optimized nanosuspension with Kleptose (hydroxypropyl-β-cyclodextrin), which was shown to be the only effective lyoprotectant among all the ones tested for the CUR nanoparticles. At an optimal concentration of Kleptose (1.25% w/v), the redispersibility (Sf/Si; ratio of the final and initial particle sizes) and encapsulation efficiency of lyophilized CUR nanoparticles were about 1.22% and 94%, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Size, Loading Efficiency, and Cytotoxicity of Albumin-Loaded Chitosan Nanoparticles: An Artificial Neural Networks Study.

PubMed

Baharifar, Hadi; Amani, Amir

2017-01-01

When designing nanoparticles for drug delivery, many variables such as size, loading efficiency, and cytotoxicity should be considered. Usually, smaller particles are preferred in drug delivery because of longer blood circulation time and their ability to escape from immune system, whereas smaller nanoparticles often show increased toxicity. Determination of parameters which affect size of particles and factors such as loading efficiency and cytotoxicity could be very helpful in designing drug delivery systems. In this work, albumin (as a protein drug model)-loaded chitosan nanoparticles were prepared by polyelectrolyte complexation method. Simultaneously, effects of 4 independent variables including chitosan and albumin concentrations, pH, and reaction time were determined on 3 dependent variables (i.e., size, loading efficiency, and cytotoxicity) by artificial neural networks. Results showed that concentrations of initial materials are the most important factors which may affect the dependent variables. A drop in the concentrations decreases the size directly, but they simultaneously decrease loading efficiency and increase cytotoxicity. Therefore, an optimization of the independent variables is required to obtain the most useful preparation. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Albumin-based nanoparticles as methylprednisolone carriers for targeted delivery towards the neonatal Fc receptor in glomerular podocytes

PubMed Central

Wu, Lin; Chen, Mingyu; Mao, Huijuan; Wang, Ningning; Zhang, Bo; Zhao, Xiufen; Qian, Jun; Xing, Changying

2017-01-01

Glucocorticoids (GCs) are commonly used in the treatment of nephrotic syndrome. However, high doses and long periods of GC therapy can result in severe side effects. The present study aimed to selectively deliver albumin-methylprednisolone (MP) nanoparticles towards glomerular podocytes, which highly express the specific neonatal Fc receptor (FcRn) of albumin. Bovine serum albumin (BSA) was labeled with a fluorescent dye and linked with modified MP via an amide bond. The outcome nanoparticle named BSA633-MP showed a uniform size with a diameter of approximately 10 nm and contained 12 drug molecules on average. The nanoconjugates were found to be stable at pH 7.4 and acid-sensitive at pH 4.0, with approximately 72% release of the MP drug after 48 h of incubation. The nanoparticle demonstrated a 36-fold uptake in receptor-specific cellular delivery in the FcRn-expressing human podocytes compared to the uptake in the non-FcRn-expressing control cells. Co-localization further confirmed that uptake of the nanoconjugates involved receptor-mediated endocytosis followed by lysosome associated transportation. In vitro cellular experiments indicated that the BSA633-MP ameliorated puromycin aminonucleoside-induced podocyte apoptosis. Moreover, in vivo fluorescence molecular imaging showed that BSA633-MP was mainly accumulated in the liver and kidney after intravenous dosing for 24 h. Collectively, this study may provide an approach for the effective and safe therapy of nephrotic syndrome. PMID:28259932

Laccase-conjugated amino-functionalized nanosilica for efficient degradation of Reactive Violet 1 dye

NASA Astrophysics Data System (ADS)

Gahlout, Mayur; Rudakiya, Darshan M.; Gupte, Shilpa; Gupte, Akshaya

2017-08-01

Immobilization of enzyme with nanostructures enhances its ideal characteristics, which may allow the enzyme to become more stable and resistant. The present investigation deals with the formulation of laccase nanosilica conjugates to overcome the problems associated with its stability and reusability. Synthesized nanosilica and laccase nanoparticles were spherical shaped, with the mean size of 220 and 615 nm, respectively. Laccase nanoparticles had an optimum temperature of 55 °C and pH 4.0 for the oxidation of ABTS. Laccase nanoparticle retained 79% of residual activity till 20th cycle. It also showed 91% of its initial activity at lower temperatures even after 60 days. Laccase nanoparticles were applied for Reactive Violet 1 degradation wherein 96.76% of decolourization was obtained at pH 5.0 and 30 °C within 12 h. Toxicity studies on microbes and plants suggested that the degraded metabolites were less toxic than control dye. Thus, the method applied for immobilization increased storage stability and reusability of laccase, and therefore, it can be utilized for efficient degradation of azo dyes.

Novel pH responsive polymethacrylic acid-chitosan-polyethylene glycol nanoparticles for oral peptide delivery.

PubMed

Sajeesh, S; Sharma, Chandra P

2006-02-01

In present study, novel pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles were prepared under mild aqueous conditions via polyelectrolyte complexation. Free radical polymerization of methacrylic acid (MAA) was carried out in presence of chitosan (CS) and polyethylene glycol (PEG) using a water-soluble initiator and particles were obtained spontaneously during polymerization without using organic solvents or surfactants/steric stabilizers. Dried particles were analyzed by scanning electron microscopy (SEM) and particles dispersed in phosphate buffer (pH 7.0) were visualized under transmission electron microscope (TEM). SEM studies indicated that PCP particles have an aggregated and irregular morphology, however, TEM revealed that these aggregated particles were composed of smaller fragments with size less than 1 micron. Insulin and bovine serum albumin (BSA) as model proteins were incorporated into the nanoparticles by diffusion filling method and their in vitro release characteristics were evaluated at pH 1.2 and 7.4. PCP nanoparticles exhibited good protein encapsulation efficiency and pH responsive release profile was observed under in vitro conditions. Trypsin inhibitory effect of these PCP nanoparticles was studied using casein substrate and these particles displayed lesser inhibitory effect than reference polymer carbopol. Preliminary investigation suggests that these particles can serve as good candidate for oral peptide delivery. Copyright 2005 Wiley Periodicals, Inc.

Biodegradable human serum albumin nanoparticles as contrast agents for the detection of hepatocellular carcinoma by magnetic resonance imaging.

PubMed

Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, Hüdayi; Huebner, Frank; Zeuzem, Stefan; Korf, Hans W; Vogl, Thomas J; Rittmeyer, Claudia; Terfort, Andreas; Piiper, Albrecht; Gelperina, Svetlana; Kreuter, Jörg

2014-05-01

Tumor visualization by magnetic resonance imaging (MRI) and nanoparticle-based contrast agents may improve the imaging of solid tumors such as hepatocellular carcinoma (HCC). In particular, human serum albumin (HSA) nanoparticles appear to be a suitable carrier due to their safety and feasibility of functionalization. In the present study HSA nanoparticles were conjugated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) using carbodiimide chemistry. The nanoparticles had a uniform spherical shape and a diameter of 235±19nm. For better optical visualization in vitro and in vivo, the HSA-Gd nanoparticles were additionally labeled with rhodamine 123. As shown by confocal microscopy and flow cytometry analysis, the fluorescent nanoparticles were readily taken up by Huh-7 hepatocellular carcinoma cells. After 24h incubation in blood serum, less than 5% of the Gd(III) was released from the particles, which suggests that this nanoparticulate system may be stable in vivo and, therefore, may serve as potentially safe T1 MRI contrast agent for MRI of hepatocellular carcinoma. Copyright © 2013 Elsevier B.V. All rights reserved.

Flow cytometry: a promising technique for the study of silicone oil-induced particulate formation in protein formulations.

PubMed

Ludwig, D Brett; Trotter, Joseph T; Gabrielson, John P; Carpenter, John F; Randolph, Theodore W

2011-03-15

Subvisible particles in formulations intended for parenteral administration are of concern in the biopharmaceutical industry. However, monitoring and control of subvisible particulates can be complicated by formulation components, such as the silicone oil used for the lubrication of prefilled syringes, and it is difficult to differentiate microdroplets of silicone oil from particles formed by aggregated protein. In this study, we demonstrate the ability of flow cytometry to resolve mixtures comprising subvisible bovine serum albumin (BSA) aggregate particles and silicone oil emulsion droplets with adsorbed BSA. Flow cytometry was also used to investigate the effects of silicone oil emulsions on the stability of BSA, lysozyme, abatacept, and trastuzumab formulations containing surfactant, sodium chloride, or sucrose. To aid in particle characterization, the fluorescence detection capabilities of flow cytometry were exploited by staining silicone oil with BODIPY 493/503 and model proteins with Alexa Fluor 647. Flow cytometric analyses revealed that silicone oil emulsions induced the loss of soluble protein via protein adsorption onto the silicone oil droplet surface. The addition of surfactant prevented protein from adsorbing onto the surface of silicone oil droplets. There was minimal formation of homogeneous protein aggregates due to exposure to silicone oil droplets, although oil droplets with surface-adsorbed trastuzumab exhibited flocculation. The results of this study demonstrate the utility of flow cytometry as an analytical tool for monitoring the effects of subvisible silicone oil droplets on the stability of protein formulations. Copyright © 2010 Elsevier Inc. All rights reserved.

Enhanced anti-tumoral activity of methotrexate-human serum albumin conjugated nanoparticles by targeting with Luteinizing Hormone-Releasing Hormone (LHRH) peptide.

PubMed

Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

2011-01-01

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120-138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX.

Formulation, characterization and cytotoxicity studies of alendronate sodium-loaded solid lipid nanoparticles.

PubMed

Ezzati Nazhad Dolatabadi, Jafar; Hamishehkar, Hamed; Eskandani, Morteza; Valizadeh, Hadi

2014-05-01

Solid lipid nanoparticles (SLNs) are novel drug delivery system for drug targeting in various routs of administration such as parenteral, oral, ophthalmic and topical. These carriers have some advantages such as high drug payload, increased drug stability, the possibility of incorporation of lipophilic and hydrophilic drugs, and low biotoxicity. In this study, alendronate sodium was used as a hydrophilic model drug and was incorporated into SLNs. Hot homogenization method was used for preparation of alendronate sodium-loaded SLN formulations and the encapsulation efficiency of drug in SLNs was determined by ultrafiltration method using centrifugal devices. Scanning electron microscopy (SEM) was carried out to study the morphological behaviors of prepared SLNs like sphericity. Several cytotoxicity studies including MTT, DAPI staining and DNA fragmentation assays were used for biocompatibility assays. High drug encapsulation efficiency (70-85%) was achieved by drug determination through derivatization with o-phthalaldehyde. The physical stability of drug-loaded SLNs in aqueous dispersions was assessed in terms of size and drug leakage during two weeks. Scanning electron microscopy images showed spherical particles in the nanometer range confirming the obtained data from size analyzer. Several cytotoxicity studies including MTT, DAPI staining and DNA fragmentation assays as well as flow cytometry analysis confirmed the low toxicity of alendronate-loaded SLNs. The cost-efficient procedure, the avoidance of organic solvents application, acceptable reproducibility, ease of manufacturing under mild preparation conditions, high level of drug encapsulation, desirable physical stability and biocompatibility are the advantages of the proposed SLN formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

Formulation of carbapenems loaded gold nanoparticles to combat multi-antibiotic bacterial resistance: In vitro antibacterial study.

PubMed

Shaker, Mohamed A; Shaaban, Mona I

2017-06-15

Despite the fact that carbapenems (powerful β-lactams antibiotics) were able to fight serious infectious diseases, nowadays the spread of carbapenems-resistant bacteria is considered the main challenge in antibacterial therapy. In this study, we focused on evaluating the surface conjugation of carbapenems (imipenem and meropenem) with gold nanoparticles as a delivering strategy to specifically and safely maximize their therapeutic efficacy while destroying the developing resistance of the pathogens. Different particle size formulae (35, 70 and 200nm) were prepared by citrate reduction method. The prepared nanoparticles were functionalized with imipenem (Ipm) or meropenem (Mem) and physico-chemically characterized for loading efficiency, particle size, morphology, and in-vitro release. The antibacterial efficacy was also evaluated against carbapenems resistant Gram-negative bacteria isolated from infected human, through measuring the minimum inhibitory concentration and antibiotic kill test. All the obtained gold nanoparticles showed a distinct nano-size with loading efficiency up to 72% and 74% for Ipm and Mem, respectively. The conjugation and physico-chemical stability of the formulated carbapenems were confirmed by FTIR and X-RPD. Diffusion driven release behavior was observed for both Ipm and Mem from all of the loaded gold nanoparticles. For both Ipm and Mem, formula with 35nm diameter showed the most significant enhancement in antibacterial activity against all the selected isolates including Klebsiella pneumoniae, Proteus mirabilis and Acinteobacter baumanii. Ipm loaded Gold nanoparticles demonstrated decrease in the MIC of Ipm down to four folds, whereas, Mem loaded gold nanoparticles showed decrease in the MIC of Mem down to three folds on the tested bacterial isolates. Based on these results, the formulation of carbapenems-loaded gold nanoparticles demonstrated to be a promising nano-size delivery vehicle for improving the therapeutic activity and destroying the bacterial resistance for carbapenems. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeted chelation therapy with EDTA-loaded albumin nanoparticles regresses arterial calcification without causing systemic side effects

PubMed Central

Lei, Yang; Nosoudi, Nasim; Vyavahare, Naren

2014-01-01

Background and aims Elastin-specific medial arterial calcification (MAC) is an arterial disease commonly referred as Monckeberg’s sclerosis. It causes significant arterial stiffness, and as yet, no clinical therapy exists to prevent or reverse it. We developed albumin nanoparticles (NPs) loaded with disodium ethylene diaminetetraacetic acid (EDTA) that were designed to target calcified elastic lamina when administrated by intravenous injection. Methods and Results We optimized NP size, charge, and EDTA-loading efficiency (150~200 nm, zeta potential of − 22.89 ~ − 31.72 mV, loading efficiency for EDTA ~20 %) for in vivo targeting in rats. These NPs released EDTA slowly for up to 5 days. In both ex-vivo study and in vivo study with injury-induced local abdominal aortic calcification, we showed that elastin antibody-coated and EDTA-loaded albumin NPs targeted the damaged elastic lamina while sparing healthy artery. Intravenous NP injections reversed elastin-specific MAC in rats after four injections over a 2-week period. EDTA-loaded albumin NPs did not cause the side effects observed in EDTA injection alone, such as decrease in serum calcium (Ca), increase in urine Ca, or toxicity to kidney. There was no bone loss in any treated groups. Conclusion We demonstrate that elastin antibody-coated and EDTA-loaded albumin NPs might be a promising nanoparticle therapy to reverse elastin-specific MAC and circumvent side effects associated with systemic EDTA chelation therapy. PMID:25285609

Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography

PubMed Central

Chhour, Peter; Naha, Pratap C.; O’Neill, Sean M.; Litt, Harold I.; Reilly, Muredach P.; Ferrari, Victor A.; Cormode, David P.

2016-01-01

Monocytes are actively recruited from the circulation into developing atherosclerotic plaques. In the plaque, monocytes differentiate into macrophages and eventually form foam cells. Continued accumulation of foam cells can lead to plaque rupture and subsequent myocardial infarction. X-ray computed tomography (CT) is the best modality to image the coronary arteries non-invasively, therefore we have sought to track the accumulation of monocytes into atherosclerotic plaques using CT. Gold nanoparticles were synthesized and stabilized with a variety of ligands. Select formulations were incubated with an immortalized monocyte cell line in vitro and evaluated for cytotoxicity, effects on cytokine release, and cell uptake. These data identified a lead formulation, 11-MUDA capped gold nanoparticles, to test for labeling primary monocytes. The formulation did not the affect the viability or cytokine release of primary monocytes and was highly taken up by these cells. Gold labeled primary monocytes were injected into apolipoprotein E deficient mice kept on Western diet for 10 weeks. Imaging was done with a microCT scanner. A significant increase in attenuation was measured in the aorta of mice receiving the gold labeled cells as compared to control animals. Following the experiment, the biodistribution of gold was evaluated in major organs. Additionally, plaques were sectioned and examined with electron microscopy. The results showed that gold nanoparticles were present inside monocytes located within plaques. This study demonstrates the feasibility of using gold nanoparticles as effective cell labeling contrast agents for non-invasive imaging of monocyte accumulation within plaques with CT. PMID:26914700

Labeling monocytes with gold nanoparticles to track their recruitment in atherosclerosis with computed tomography.

PubMed

Chhour, Peter; Naha, Pratap C; O'Neill, Sean M; Litt, Harold I; Reilly, Muredach P; Ferrari, Victor A; Cormode, David P

2016-05-01

Monocytes are actively recruited from the circulation into developing atherosclerotic plaques. In the plaque, monocytes differentiate into macrophages and eventually form foam cells. Continued accumulation of foam cells can lead to plaque rupture and subsequent myocardial infarction. X-ray computed tomography (CT) is the best modality to image the coronary arteries non-invasively, therefore we have sought to track the accumulation of monocytes into atherosclerotic plaques using CT. Gold nanoparticles were synthesized and stabilized with a variety of ligands. Select formulations were incubated with an immortalized monocyte cell line in vitro and evaluated for cytotoxicity, effects on cytokine release, and cell uptake. These data identified a lead formulation, 11-MUDA capped gold nanoparticles, to test for labeling primary monocytes. The formulation did not the affect the viability or cytokine release of primary monocytes and was highly taken up by these cells. Gold labeled primary monocytes were injected into apolipoprotein E deficient mice kept on Western diet for 10 weeks. Imaging was done with a microCT scanner. A significant increase in attenuation was measured in the aorta of mice receiving the gold labeled cells as compared to control animals. Following the experiment, the biodistribution of gold was evaluated in major organs. Additionally, plaques were sectioned and examined with electron microscopy. The results showed that gold nanoparticles were present inside monocytes located within plaques. This study demonstrates the feasibility of using gold nanoparticles as effective cell labeling contrast agents for non-invasive imaging of monocyte accumulation within plaques with CT. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthetic surfactant- and cross-linker-free preparation of highly stable lipid-polymer hybrid nanoparticles as potential oral delivery vehicles.

PubMed

Wang, Taoran; Xue, Jingyi; Hu, Qiaobin; Zhou, Mingyong; Chang, Chao; Luo, Yangchao

2017-06-05

The toxicity associated with concentrated synthetic surfactants and the poor stability at gastrointestinal condition are two major constraints for practical applications of solid lipid nanoparticles (SLN) as oral delivery vehicles. In this study, a synthetic surfactant-free and cross-linker-free method was developed to fabricate effective, safe, and ultra-stable lipid-polymer hybrid nanoparticles (LPN). Bovine serum albumin (BSA) and dextran varying in molecular weights were first conjugated through Maillard reaction and the conjugates were exploited to emulsify solid lipid by a solvent diffusion and sonication method. The multilayer structure was formed by self-assembly of BSA-dextran micelles to envelope solid lipid via a pH- and heating-induced facile process with simultaneous surface deposition of pectin. The efficiency of different BSA-dextran conjugates was systematically studied to prepare LPN with the smallest size, the most homogeneous distribution and the greatest stability. The molecular interactions were characterized by Fourier transform infrared and fluorescence spectroscopies. Both nano spray drying and freeze-drying methods were tested to produce spherical and uniform pectin-coated LPN powders that were able to re-assemble nanoscale structure when redispersed in water. The results demonstrated the promise of a synthetic surfactant- and cross-linker-free technique to prepare highly stable pectin-coated LPN from all natural biomaterials as potential oral delivery vehicles.

Rapid Recovery of Clofazimine-Loaded Nanoparticles with Long-Term Storage Stability as Anti-Cryptosporidium Therapy.

PubMed

Feng, Jie; Zhang, Yingyue; McManus, Simon A; Ristroph, Kurt D; Lu, Hoang D; Gong, Kai; White, Claire E; Prud'homme, Robert K

2018-05-25

While the formulation of nanoparticle (NP) suspensions has been widely applied in materials and life science, the recovery of NPs from such a suspension into a solid state is practically important to confer long-term storage stability. However, solidification, while preserving the original nanoscale properties, remains a formidable challenge in the pharmaceutical and biomedical applications of NPs. Herein we combined flash nanoprecipitation (FNP) and spray-drying as a nanofabrication platform for NP formulation and recovery without compromising the dissolution kinetics of the active ingredient. Clofazimine was chosen to be the representative drug, which has been recently repurposed as a potential treatment for cryptosporidiosis. Clofazimine was encapsulated in NPs with low-cost surface coatings, hypromellose acetate succinate (HPMCAS) and lecithin, which were required by the ultimate application to global health. Spray-drying and lyophilization were utilized to produce dried powders with good long-term storage stability for application in hot and humid climatic zones. The particle morphology, yield efficiency, drug loading, and clofazimine crystallinity in the spray-dried powders were characterized. The in vitro release kinetics of spray-dried NP powders were compared to analogous dissolution profiles from standard lyophilized NP samples, crystalline clofazimine powder, and the commercially available formulation Lamprene. The spray-dried powders showed a supersaturation level of up to 60 times the equilibrium solubility and remarkably improved dissolution rates. In addition, the spray-dried powders with both surface coatings showed excellent stability during aging studies with elevated temperature and humidity, in view of the dissolution and release in vitro. Considering oral delivery for pediatric administration, the spray-dried powders show less staining effects with simulated skin than crystalline clofazimine and may be made into minitablets without additional excipients. These results highlight the potential of combining FNP and spray-drying as a feasible and versatile platform to design and rapidly recover amorphous NPs in a solid dosage form, with the advantages of satisfactory long-term storage stability, low cost, and easy scalability.

Enhancing intracellular taxane delivery: current role and perspectives of nanoparticle albumin-bound paclitaxel in the treatment of advanced breast cancer.

PubMed

Guarneri, Valentina; Dieci, Maria Vittoria; Conte, Pierfranco

2012-02-01

Docetaxel and paclitaxel are among the most active agents for the treatment of breast cancer. These first-generation taxanes are extremely hydrophobic; therefore, solvents are needed for its parenteral administration. Albumin nanoparticle technology allows for the transportation of such hydrophobic drugs without the need of potentially toxic solvents. Nab-paclitaxel can be administered without premedication, in a shorter infusion time and without the need for a special infusion set. Moreover, this technology allows the selective delivery of larger amounts of anticancer drug to tumors, by exploiting endogenous albumin pathways. An overview of the albumin nanoparticle technology, from a clinical perspective, is reported in this paper. The preclinical and clinical development of nab-paclitaxel is reviewed, in the context of available therapies for advanced breast cancer, with a focus on safety data. Preclinical and clinical data on the prognostic and predictive role of SPARC (secreted protein, acidic and rich in cysteine) are also reported. Nab-paclitaxel is approved at present for the treatment of metastatic breast cancer, after the failure of first-line standard therapy, when anthracyclines are not indicated. Efficacy and safety data, along with a more convenient administration, confirm the potential for nab-paclitaxel to become a reference taxane in breast cancer treatment.

Solid lipid nanoparticles suspension versus commercial solutions for dermal delivery of minoxidil.

PubMed

Padois, Karine; Cantiéni, Céline; Bertholle, Valérie; Bardel, Claire; Pirot, Fabrice; Falson, Françoise

2011-09-15

Solid lipid nanoparticles have been reported as possible carrier for skin drug delivery. Solid lipid nanoparticles are produced from biocompatible and biodegradable lipids. Solid lipid nanoparticles made of semi-synthetic triglycerides stabilized with a mixture of polysorbate and sorbitan oleate were loaded with 5% of minoxidil. The prepared systems were characterized for particle size, pH and drug content. Ex vivo skin penetration studies were performed using Franz-type glass diffusion cells and pig ear skin. Ex vivo skin corrosion studies were realized with a method derived from the Corrositex(®) test. Solid lipid nanoparticles suspensions were compared to commercial solutions in terms of skin penetration and skin corrosion. Solid lipid nanoparticles suspensions have been shown as efficient as commercial solutions for skin penetration; and were non-corrosive while commercial solutions presented a corrosive potential. Solid lipid nanoparticles suspensions would constitute a promising formulation for hair loss treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

Porous mannitol carrier for pulmonary delivery of cyclosporine A nanoparticles.

PubMed

Leung, Sharon Shui Yee; Wong, Jennifer; Guerra, Heloisa Victorino; Samnick, Kevin; Prud'homme, Robert K; Chan, Hak-Kim

2017-03-01

This study employed the ultrasonic spray-freeze-drying technique to prepare porous mannitol carriers that incorporated hydrophobic cyclosporine A (CsA) nanoparticles (NPs) for pulmonary delivery. Two nanosuspension stabilization systems, (1) a combination of lecithin and lactose system and (2) a D-α-tocopheryl polyethylene glycol succinate (TPGS) system, were investigated. The ability of the lecithin and TPGS in anchoring the hydrophobic CsA NPs to the porous hydrophilic mannitol structure was first reported. Formulations stabilized by TPGS provided a much better dose uniformity, suggesting that TPGS is a better anchoring agent compared with lecithin. The effects of mannitol carrier density and CsA loading (4.9-27%) on aerosol performance and dissolution profiles were assessed. The fine particle fraction (FPF) increased from 44 to 63% as the mannitol concentration decreased from 1 to 5%. All formulations achieved full dissolution within an hour without significant influence from the mannitol content and CsA loading. The initial dissolution rates of the present formulations were almost double than that of the spray-dried counterpart, with 90% of the drug dissolved in 10 min. Overall, the CsA NPs were successfully incorporated into the porous mannitol which demonstrated good aerosol performance and enhanced dissolution profiles. These spray-freeze-drying (SFD) powders were stable after 2-year storage under desiccation at 20 ± 3°C.

Enhanced topical delivery of finasteride using glyceryl monooleate-based liquid crystalline nanoparticles stabilized by cremophor surfactants.

PubMed

Madheswaran, Thiagarajan; Baskaran, Rengarajan; Yong, Chul Soon; Yoo, Bong Kyu

2014-02-01

The aim of this study was to investigate the capability of two surfactants, Cremophor RH 40 (RH) and Cremophor EL (EL), to prepare liquid crystalline nanoparticles (LCN) and to study its influence on the topical delivery of finasteride (FNS). FNS-loaded LCN was formulated with the two surfactants and characterized for size distribution, morphology, entrapment efficiency, in vitro drug release, and skin permeation/retention. Influence of FNS-loaded LCN on the conformational changes on porcine skin was also studied using attenuated total reflectance Fourier-transform infrared spectroscopy. Transmission electron microscopical image confirmed the formation of LCN. The average particle size of formulations was in the range of 165.1-208.6 and 153.7-243.0 nm, respectively. The formulations prepared with higher surfactant concentrations showed faster release and significantly increased skin permeation. Specifically, LCN prepared with RH 2.5% presented higher permeation flux (0.100 ± 0.005 μgcm(-2)h(-1)) compared with lower concentration (0.029 ± 0.007 μgcm(-2)h(-1)). Typical spectral bands of lipid matrix of porcine skin were shifted to higher wavenumber, indicating increased degree of disorder of the lipid acyl chains which might cause fluidity increase of stratum corneum. Taken together, Cremophor surfactants exhibited a promising potential to stabilize the LCN and significantly augmented the skin permeation of FNS.

Fabrication and evaluation of SDF-1 loaded galactosylated chitosan nanoparticles for liver targeting

NASA Astrophysics Data System (ADS)

Xue-Hui, Chu; Zhang-Qi, Feng; Qian, Xu; Jiang-Qiang, Xiao; Xian-Wen, Yuan; Xi-Tai, Sun

2017-03-01

Objective. SDF-1 loaded galactosylated chitosan (GC) nanoparticles for liver targeting were synthesized by electrospraying technique, and its biocompatibility and liver targeting effect were evaluated. Method. The SDF-1 loaded GC nanoparticles were constructed and its morphology was observed by the scanning electron microscopy (SEM). Hepatocytes were harvested and cocultured with the nanoparticles, and the albumin secretion and urea synthesis were detected by enzyme-linked immunosorbent assay assay, the concentration of lactate dehydrogenase (LDH) and tumor necrosis factor-α (TNF-α) was also measured. Finally, the nanoparticles were injected intravenously through the caudal vein of rat, and its liver targeting effect was evaluated. Result. SEM showed the nanoparticles distributed uniformly, with an average diameter of 100 nm and a regular spherical shape. There was no significant difference in urea synthesis, albumin secretion, concentration of LDH and TNF-α between two groups (p > 0.05). The nanoparticles were significantly accumulated in the liver tissue after its injection, but seldom fluorescence signals were observed in the lung, spleen, heart and kidney. Conclusion. The SDF-1 loaded GC nanoparticles showed uniform distribution, good biocompatibility and liver targeting effect, and suggested its potential application as a liver targeting delivery system.

Control-release microcapsule of famotidine loaded biomimetic synthesized mesoporous silica nanoparticles: Controlled release effect and enhanced stomach adhesion in vitro.

PubMed

Li, Jing; Wang, Hongyu; Yang, Baixue; Xu, Lu; Zheng, Nan; Chen, Hongtao; Li, Sanming

2016-01-01

In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of Particle Hydrophobicity, Surface Charge, Media pH Value and Complexation with Human Serum Albumin on Drug Release Behavior of Mitoxantrone-Loaded Pullulan Nanoparticles

PubMed Central

Tao, Xiaojun; Jin, Shu; Wu, Dehong; Ling, Kai; Yuan, Liming; Lin, Pingfa; Xie, Yongchao; Yang, Xiaoping

2015-01-01

We prepared two types of cholesterol hydrophobically modified pullulan nanoparticles (CHP) and carboxyethyl hydrophobically modified pullulan nanoparticles (CHCP) substituted with various degrees of cholesterol, including 3.11, 6.03, 6.91 and 3.46 per polymer, and named CHP−3.11, CHP−6.03, CHP−6.91 and CHCP−3.46. Dynamic laser light scattering (DLS) showed that the pullulan nanoparticles were 80–120 nm depending on the degree of cholesterol substitution. The mean size of CHCP nanoparticles was about 160 nm, with zeta potential −19.9 mV, larger than CHP because of the carboxyethyl group. A greater degree of cholesterol substitution conferred greater nanoparticle hydrophobicity. Drug-loading efficiency depended on nanoparticle hydrophobicity, that is, nanoparticles with the greatest degree of cholesterol substitution (6.91) showed the most drug encapsulation efficiency (90.2%). The amount of drug loading increased and that of drug release decreased with enhanced nanoparticle hydrophobicity. Nanoparticle surface-negative charge disturbed the amount of drug loading and drug release, for an opposite effect relative to nanoparticle hydrophobicity. The drug release in pullulan nanoparticles was higher pH 4.0 than pH 6.8 media. However, the changed drug release amount was not larger for negative-surface nanoparticles than CHP nanoparticles in the acid release media. Drug release of pullulan nanoparticles was further slowed with human serum albumin complexation and was little affected by nanoparticle hydrophobicity and surface negative charge. PMID:28344259

Formulation and Stabilization of Concentrated Edible Oil-in-Water Emulsions Based on Electrostatic Complexes of a Food-Grade Cationic Surfactant (Ethyl Lauroyl Arginate) and Cellulose Nanocrystals.

PubMed

Bai, Long; Xiang, Wenchao; Huan, Siqi; Rojas, Orlando J

2018-05-14

We report on high-internal-phase, oil-in-water Pickering emulsions that are stable against coalescence during storage. Viscous, edible oil (sunflower) was emulsified by combining naturally derived cellulose nanocrystals (CNCs) and a food-grade, biobased cationic surfactant obtained from lauric acid and L-arginine (ethyl lauroyl arginate, LAE). The interactions between CNC and LAE were elucidated by isothermal titration calorimetry (ITC) and supplementary techniques. LAE adsorption on CNC surfaces and its effect on nanoparticle electrostatic stabilization, aggregation state, and emulsifying ability was studied and related to the properties of resultant oil-in-water emulsions. Pickering systems with tunable droplet diameter and stability against oil coalescence during long-term storage were controllably achieved depending on LAE loading. The underlying stabilization mechanism was found to depend on the type of complex formed, the LAE structures adsorbed on the cellulose nanoparticles (as unimer or as adsorbed admicelles), the presence of free LAE in the aqueous phase, and the equivalent alkane number of the oil phase (sunflower and dodecane oils were compared). The results extend the potential of CNC in the formulation of high-quality and edible Pickering emulsions. The functional properties imparted by LAE, a highly effective molecule against food pathogens and spoilage organisms, open new opportunities in food, cosmetics, and pharmaceutical applications, where the presence of CNC plays a critical role in achieving synergistic effects with LAE.

Significance of Algal Polymer in Designing Amphotericin B Nanoparticles

PubMed Central

Bhatia, Saurabh; Kumar, Vikash; Sharma, Kiran; Nagpal, Kalpana; Bera, Tanmoy

2014-01-01

Development of oral amphotericin B (AmB) loaded nanoparticles (NPs) demands a novel technique which reduces its toxicity and other associated problems. Packing of AmB in between two oppositely charged ions by polyelectrolyte complexation technique proved to be a successful strategy. We have developed a novel carrier system in form of polyelectrolyte complex of AmB by using chitosan (CS) and porphyran (POR) as two oppositely charged polymers with TPP as a crosslinking agent. Initially POR was isolated from Porphyra vietnamensis followed by the fact that its alkali induced safe reduction in molecular weight was achieved. Formulation was optimized using three-factor three-level (33) central composite design. High concentration of POR in NPs was confirmed by sulfated polysaccharide (SP) assay. Degradation and dissolution studies suggested the stability of NPs over wide pH range. Hemolytic toxicity data suggested the safety of prepared formulation. In vivo and in vitro antifungal activity demonstrated the high antifungal potential of optimized formulation when compared with standard drug and marketed formulations. Throughout the study TPP addition did not cause any significant changes. Therefore, these experimental oral NPs may represent an interesting carrier system for the delivery of AmB. PMID:25478596

Kaempferol loaded lecithin/chitosan nanoparticles: preparation, characterization, and their potential applications as a sustainable antifungal agent.

PubMed

Ilk, Sedef; Saglam, Necdet; Özgen, Mustafa

2017-08-01

Flavonoid compounds are strong antioxidant and antifungal agents but their applications are limited due to their poor dissolution and bioavailability. The use of nanotechnology in agriculture has received increasing attention, with the development of new formulations containing active compounds. In this study, kaempferol (KAE) was loaded into lecithin/chitosan nanoparticles (LC NPs) to determine antifungal activity compared to pure KAE against the phytopathogenic fungus Fusarium oxysporium to resolve the bioavailability problem. The influence of formulation parameters on the physicochemical properties of KAE loaded lecithin chitosan nanoparticles (KAE-LC NPs) were studied by using the electrostatic self-assembly technique. KAE-LC NPs were characterized in terms of physicochemical properties. KAE has been successfully encapsulated in LC NPs with an efficiency of 93.8 ± 4.28% and KAE-LC NPs showed good physicochemical stability. Moreover, in vitro evaluation of the KAE-LC NP system was made by the release kinetics, antioxidant and antifungal activity in a time-dependent manner against free KAE. Encapsulated KAE exhibited a significantly inhibition efficacy (67%) against Fusarium oxysporium at the end of the 60 day storage period. The results indicated that KAE-LC NP formulation could solve the problems related to the solubility and loss of KAE during use and storage. The new nanoparticle system enables the use of smaller quantities of fungicide and therefore, offers a more environmentally friendly method of controlling fungal pathogens in agriculture.

Fluorometric immunoassay for human serum albumin based on its inhibitory effect on the immunoaggregation of quantum dots with silver nanoparticles

NASA Astrophysics Data System (ADS)

Marukhyan, Seda S.; Gasparyan, Vardan K.

2017-02-01

Quantitative determination of HSA was conducted by competitive immunoassay. Inhibition of aggregation of antibody conjugated quantum dots (QD) with albumin conjugated silver nanoparticles (AgNPs) in the presence of HSA was conducted. If antibody-loaded CdSe QDs aggregate with HSA-coated silver nanoparticles the distance between the two kinds of nanoparticles will be reduced enough to cause fluorescence resonance energy transfer (FRET). In this case the yellow fluorescence of the Ab-QDs is quenched. However if HSA (antigen) is added to the Ab-QDs their surface will be blocked and they cannot aggregate any longer with the HSA-AgNPs. Hence, fluorescence will not be quenched. The drop of the intensity of fluorescence (peaking at 570 nm) is inversely correlated with the concentration of HSA in the sample. The method allows to determine HSA in the 30-600 ng·mL-1 concentration range.

Surface chemistry of photoluminescent F8BT conjugated polymer nanoparticles determines protein corona formation and internalization by phagocytic cells.

PubMed

Ahmad Khanbeigi, Raha; Abelha, Thais Fedatto; Woods, Arcadia; Rastoin, Olivia; Harvey, Richard D; Jones, Marie-Christine; Forbes, Ben; Green, Mark A; Collins, Helen; Dailey, Lea Ann

2015-03-09

Conjugated polymer nanoparticles are being developed for a variety of diagnostic and theranostic applications. The conjugated polymer, F8BT, a polyfluorene derivative, was used as a model system to examine the biological behavior of conjugated polymer nanoparticle formulations stabilized with ionic (sodium dodecyl sulfate; F8BT-SDS; ∼207 nm; -31 mV) and nonionic (pegylated 12-hydroxystearate; F8BT-PEG; ∼175 nm; -5 mV) surfactants, and compared with polystyrene nanoparticles of a similar size (PS200; ∼217 nm; -40 mV). F8BT nanoparticles were as hydrophobic as PS200 (hydrophobic interaction chromatography index value: 0.96) and showed evidence of protein corona formation after incubation with serum-containing medium; however, unlike polystyrene, F8BT nanoparticles did not enrich specific proteins onto the nanoparticle surface. J774A.1 macrophage cells internalized approximately ∼20% and ∼60% of the F8BT-SDS and PS200 delivered dose (calculated by the ISDD model) in serum-supplemented and serum-free conditions, respectively, while cell association of F8BT-PEG was minimal (<5% of the delivered dose). F8BT-PEG, however, was more cytotoxic (IC50 4.5 μg cm(-2)) than F8BT-SDS or PS200. The study results highlight that F8BT surface chemistry influences the composition of the protein corona, while the properties of the conjugated polymer nanoparticle surfactant stabilizer used determine particle internalization and biocompatibility profile.

Nano-anisotropic surface coating based on drug immobilized pendant polymer to suppress macrophage adhesion response.

PubMed

Kaladhar, K; Renz, H; Sharma, C P

2015-04-01

Exploring drug molecules for material design, to harness concepts of nano-anisotropy and ligand-receptor interactions, are rather elusive. The aim of this study is to demonstrate the bottom-up design of a single-step and bio-interactive polymeric surface coating, based on drug based pendant polymer. This can be applied on to polystyrene (PS) substrates, to suppress macrophage adhesion and spreading. The drug molecule is used in this coating for two purposes. The first one is drug as a "pendant" group, to produce nano-anisotropic properties that can enable adhesion of the coatings to the substrate. The second purpose is to use the drug as a "ligand", to produce ligand-receptor interaction, between the bound ligand and receptors of albumin, to develop a self-albumin coat over the surface, by the preferential binding of albumin in biological environment, to reduce macrophage adhesion. Our in silico studies show that, diclofenac (DIC) is an ideal drug based "ligand" for albumin. This can also act as a "pendant" group with planar aryl groups. The combination of these two factors can help to harness, both nano-anisotropic properties and biological functions to the polymeric coating. Further, the drug, diclofenac (DIC) is immobilized to the polyvinyl alcohol (PVA), to develop the pendant polymer (PVA-DIC). The interaction of bound DIC with the albumin is a ligand-receptor based interaction, as per the studies by circular dichroism, differential scanning calorimetry, and SDS-PAGE. The non-polar π-π* interactions are regulating; the interactions between PVA bound DIC-DIC interactions, leading to "nano-anisotropic condensation" to form distinct "nano-anisotropic segments" inside the polymeric coating. This is evident from, the thermo-responsiveness and uniform size of nanoparticles, as well as regular roughness in the surface coating, with similar properties as that of nanoparticles. In addition, the hydrophobic DIC-polystyrene (PS) interactions, between the PVA-DIC coating and PS-substrate produce improved coating stability. Subsequently, the PVA-DIC coated substrate has the maximum capacity to suppress the macrophage (RAW 264.7 cell line) adhesion and spreading, which is partly due to wavy-surface topography of hydrophilic PVA and preferential albumin binding capacity of PVA bound DIC. Our result shows that, such surfaces suppress the macrophages, even under stimulation with lipopolysaccharide (LPS). The modified tissue culture plates can be used as an in vitro tool, to study the macrophage response under low spatial cues. Copyright © 2015 Elsevier B.V. All rights reserved.

Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

PubMed

Hadinoto, Kunn; Cheow, Wean Sin

2014-04-01

Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of DNA damage and cytotoxicity of polyurethane-based nano- and microparticles as promising biomaterials for drug delivery systems

NASA Astrophysics Data System (ADS)

Caon, Thiago; Zanetti-Ramos, Betina Giehl; Lemos-Senna, Elenara; Cloutet, Eric; Cramail, Henri; Borsali, Redouane; Soldi, Valdir; Simões, Cláudia Maria Oliveira

2010-06-01

The in vitro cytotoxicity and DNA damage evaluation of biodegradable polyurethane-based micro- and nanoparticles were carried out on animal fibroblasts. For cytotoxicity measurement and primary DNA damage evaluation, MTT and Comet assays were used, respectively. Different formulations were tested to evaluate the influence of chemical composition and physicochemical characteristics of particles on cell toxicity. No inhibition of cells growth surrounding the polyurethane particles was observed. On the other hand, a decrease of cell viability was verified when the anionic surfactant sodium dodecyl sulfate (SDS) was used as droplets stabilizer of monomeric phase. Polyurethane nanoparticles stabilized with Tween 80 and Pluronic F68 caused minor cytotoxic effects. These results indicated that the surface charge plays an important role on cytotoxicity. Particles synthesized from MDI displayed a higher cytotoxicity than those synthesized from IPDI. Size and physicochemical properties of the particles may explain the higher degree of DNA damage produced by two tested formulations. In this way, a rational choice of particles' constituents based on their cytotoxicity and genotoxicity could be very useful for conceiving biomaterials to be used as drug delivering systems.

Self assembled dual responsive micelles stabilized with protein for co-delivery of drug and siRNA in cancer therapy.

PubMed

Aji Alex, M R; Nehate, Chetan; Veeranarayanan, Srivani; Kumar, D Sakthi; Kulshreshtha, Ritu; Koul, Veena

2017-07-01

Design of safe and efficient vehicles for the combinatorial delivery of drugs and genetic agents is an emerging requisite for achieving enhanced therapeutic effect in cancer. Even though several nanoplatforms have been explored for the co-delivery of drugs and genetic materials the translation of these systems to clinical phase is still a challenge, mainly due to tedious synthesis procedures, lack of serum stability, inefficient scalability etc. Here in, we report development of reduction and pH sensitive polymeric graft of low molecular weight poly (styrene -alt -maleic anhydride) and evaluation of its efficacy in co-delivering drug and siRNA. The polymer was modified with suitable components, which could help in overcoming various systemic and cellular barriers for successful co-delivery of drugs and nucleic acids to cancer cells, using simple chemical reactions. The polymeric derivative could easily self assemble in water to form smooth, spherical micellar structures, indicating their scalability. Doxorubicin and PLK-1 siRNA were selected as model drug and nucleic acid, respectively. Doxorubicin could be loaded in the self assembling micelles with an optimum loading content of ∼8.6% w/w and efficient siRNA complexation was achieved with polymer/siRNA weight ratios >40. The polyplexes were stabilized in physiological saline by coating with bovine serum albumin (BSA). Stable drug loaded nanoplexes, for clinical administration, could be easily formulated by gently dispersing them in physiological saline containing appropriate amount of albumin. Drug release from the nanoplexes was significantly enhanced at low pH (5) and in the presence of 10 mM glutathione (GSH) showing their dual stimuli sensitive nature. In vitro cell proliferation assay and in vivo tumor regression study have shown synergistic effect of the drug loaded nanoplexes in inhibiting cancer cell proliferation. Facile synthesis steps, scalability and ease of formulation depict excellent clinical translation potential of the proposed nanosystem. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gamma-radiation induced synthesis of silver nanoparticles in gelatin and its application for radiotherapy dose measurements

NASA Astrophysics Data System (ADS)

Soliman, Y. S.

2014-09-01

A new gel dosimeter based on a radiation-sensitive silver nitrate was formulated and investigated for its potential use in γ-radiation treatment, from 3 to 100 Gy. This gel matrix is analyzed by UV-vis spectrophotometry and X-ray diffraction (XRD). Subjecting the gel to γ-rays produces Ag nanoparticles that exhibit a plasmon resonance absorption band at 450 nm. The intensity of this band increases linearly with the increase of absorbed dose up to 100 Gy. Stability of Ag nanoparticle in the dark at 6 °C is good. The overall uncertainty (2σ) of the gel dosimeter is estimated as ~4.65% in the dose range of 5-100 Gy.

Enhanced Anti-Tumoral Activity of Methotrexate-Human Serum Albumin Conjugated Nanoparticles by Targeting with Luteinizing Hormone-Releasing Hormone (LHRH) Peptide

PubMed Central

Taheri, Azade; Dinarvand, Rassoul; Atyabi, Fatemeh; Ahadi, Fatemeh; Nouri, Farank Salman; Ghahremani, Mohammad Hossein; Ostad, Seyed Nasser; Borougeni, Atefeh Taheri; Mansoori, Pooria

2011-01-01

Active targeting could increase the efficacy of anticancer drugs. Methotrexate-human serum albumin (MTX-HSA) conjugates, functionalized by luteinizing hormone-releasing hormone (LHRH) as targeting moieties, with the aim of specifically targeting the cancer cells, were prepared. Owing to the high expression of LHRH receptors in many cancer cells as compared to normal cells, LHRH was used as the targeting ligand in this study. LHRH was conjugated to MTX-HSA nanoparticles via a cross-linker. Three types of LHRH targeted nanoparticles with a mean particle size between 120–138 nm were prepared. The cytotoxicity of LHRH targeted and non-targeted nanoparticles were determined on the LHRH positive and negative cell lines. The internalization of the targeted and non-targeted nanoparticles in LHRH receptor positive and negative cells was investigated using flow cytometry analysis and fluorescence microscopy. The cytotoxicity of the LHRH targeted nanoparticles on the LHRH receptor positive cells were significantly more than non-targeted nanoparticles. LHRH targeted nanoparticles were also internalized by LHRH receptor positive cells significantly more than non-targeted nanoparticles. There were no significant differences between the uptake of targeted and non-targeted nanoparticles to the LHRH receptor negative cells. The active targeting procedure using LHRH targeted MTX-HSA nanoparticles could increase the anti-tumoral activity of MTX. PMID:21845098

Bovine Serum Albumin Nanoparticles Containing Amphotericin B: Characterization, Cytotoxicity and In Vitro Antifungal Evaluation.

PubMed

Casa, Diani Meza; Karam, Thaysa Ksiaskiewcz; Alves, Aline de Cristo Soares; Zgoda, Aline Aparecida; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

2015-12-01

In this study, nanoparticles based on bovine serum albumin (BSA) containing amphotericin B (AmB) were obtained by the desolvation method and characterized with respect to size, size distribution, AmB encapsulation efficiency, AmB state of aggregation, and AmB in vitro release profile. After, the effect of nanoparticles on the cytotoxicity of human erythrocytes in vitro and efficacy over strains of Candida spp. were evaluated. The mean particle size was 156 nm and the AmB encapsulation efficiency was over 82%. The in vitro release profile revealed a sustained release of approximately 48% of AmB over 5 days. AmB is present in BSA nanoparticles as monomer. AmB-loaded nanoparticles showed very low index of hemolysis (less than 8%) in 72 h of assay compared to free AmB, which presented 100% of hemolysis in 2 h of incubation. The AmB-loaded BSA nanoparticles were as effective as free AmB against Candida albicans and Candida tropicalis, considering their sustained release profile. Thus, BSA nanoparticles are potential carriers for AmB, reducing its molecular aggregation and prolonging its release, resulting in lower cytotoxicity while maintaining its antifungal activity.

Gelatin modified lipid nanoparticles for anti- viral drug delivery.

PubMed

K S, Joshy; S, Snigdha; Kalarikkal, Nandakumar; Pothen, Laly A; Thomas, Sabu

2017-10-01

The major challenges to clinical application of zidovudine are its moderate aqueous solubility and relative short half-life and serious side effects due to frequent administrations. We investigated the preparation of zidovudine-loaded nanoparticles based on lipids which were further modified with the polymer gelatin. Formulation and stability of the modified nanoparticles were analysed from the physico-chemical characterizations. The interactions of nanoparticles with blood components were tested by haemolysis and aggregation studies. The drug content and entrapment efficiencies were assessed by UV analysis. The effect of nanoparticles on protein adsorption was assessed by native polyacrylamide gel electrophoresis (PAGE). In vitro release studies showed a sustained release profile of zidovudine. In vitro cytotoxicity and cellular uptake of the zidovudine-loaded nanoparticles were performed in MCF-7 and neuro 2a brain cells. The enhanced cellular internalization of drug loaded modified nanoparticles in both the cell lines were revealed by fluorescence microscopy. Hence the present study focuses on the feasibility of zidovudine-loaded polymer modified lipid nanoparticles as carriers for safe and efficient HIV/AIDS therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation design for target delivery of iron nanoparticles to TCE zones.

PubMed

Wang, Ziheng; Acosta, Edgar

2013-12-01

Nanoparticles of zero-valent iron (NZVI) are effective reducing agents for some dense non-aqueous phase liquid (DNAPL) contaminants such as trichloroethylene (TCE). However, target delivery of iron nanoparticles to DNAPL zones in the aquifer remains an elusive feature for NZVI technologies. This work discusses three strategies to deliver iron nanoparticles to DNAPL zones. To this end, iron oxide nanoparticles coated with oleate (OL) ions were used as stable analogs for NZVI. The OL-coated iron oxide nanoparticles are rendered lipophilic via (a) the addition of CaCl2, (b) acidification, or (c) the addition of a cationic surfactant, benzethonium chloride (BC). Mixtures of OL and BC show promise as a target delivery strategy due to the high stability of the nanoparticles in water, and their preferential partition into TCE in batch experiments. Column tests show that while the OL-BC coated iron oxide nanoparticles remain largely mobile in TCE-free columns, a large fraction of these particles are retained in TCE-contaminated columns, confirming the effectiveness of this target delivery strategy. © 2013.

Preparation, Characterization and Evaluation of Quetiapine Fumarate Solid Lipid Nanoparticles to Improve the Oral Bioavailability

PubMed Central

Narala, Arjun; Veerabrahma, Kishan

2013-01-01

Quetiapine fumarate is an antipsychotic drug with poor oral bioavailability (9%) due to first-pass metabolism. Present work is an attempt to improve oral bioavailability of quetiapine fumarate by incorporating in solid lipid nanoparticles (SLN). Six quetiapine fumarate SLN formulations were developed using three different lipids by hot homogenisation followed by ultrasonication. The drug excipient compatibility was studied by differential scanning calorimetry (DSC). Stable quetiapine fumarate SLNs having a mean particle size of 200–250 nm with entrapment efficiency varying in between 80% and 92% were developed. The physical stability of optimized formulation F3 was checked at room temperature for 2 months. Comparative bioavailability studies were conducted in male Wistar rats after oral administration of quetiapine fumarate suspension and SLN formulation. The relative bioavailability of quetiapine fumarate from optimized SLN preparation was increased by 3.71 times when compared with the reference quetiapine fumarate suspension. The obtained results are indicative of SLNs as potential lipid carriers for improving the bioavailability of quetiapine fumarate by minimizing first-pass metabolism. PMID:26555970

Macro-aggregates (MAA) of albumin for lung imaging. Studies on better tissue to background ratio, on MAA stability and reuse after its first preparation.

PubMed

Malhotra, Anshoo; Kumar, Pardeep; Sharma, Sarika; Dhawan, Davinder K

2010-01-01

The present study was designed to develop stable and economically competitive radioactive technetium-99m macro-aggregates of albumin ((99m)Tc-MAA) which could be used for imaging of lungs. Macro-aggregates were freshly prepared and labeled with (99m)Tc pertechnetate by following the standard protocol which included incubation of formulation at 80(o) C for 10 min. We studied 7 rats in every experiment. The rats were injected intravenously with (99m)Tc MAA and were sacrificed after 10 min to study its distribution in the lungs and other non target tissues using gamma ray spectrometer. This standard protocol was further experimented upon in order to achieve high target to non target ratio. Different formulations were prepared by incubating them at 80 degrees for different incubation times of 5, 10, 15, 20, 25 and 30 min. Formulation of MAA prepared by incubating at 80 degrees for 20 min labeled with (99m)Tc showed the highest target to non target ratio. Another group of rats that received the above formulation were sacrificed after two additional time intervals of 5 and 15 min. The target to non target ratio was high in animals sacrificed after 5 min of injecting them with (99m)Tc the MAA formulation prepared by heating at 80 degrees for 20 min as compared to animals sacrificed after 10 and 15 min. Formulations of MAA following storage at room temperatures which varied from 5(o)C to 18(o)C, for different time durations 1, 2 and 9 days were also evaluated for their ability to be reused after reheating and labeling with (99m)Tc. The formulation of MAA kept for 9 days showed the best target to non-target ratio. The present study suggests that MAA once prepared can be reused following labeling with (99m)Tc even after 9 days of storage with better target to non target ratio as compared to storage timer period of 1 and 2 days.

Preparation and evaluation of high dispersion stable nanocrystal formulation of poorly water-soluble compounds by using povacoat.

PubMed

Yuminoki, Kayo; Seko, Fuko; Horii, Shota; Takeuchi, Haruka; Teramoto, Katsuya; Nakada, Yuichiro; Hashimoto, Naofumi

2014-11-01

In this study, we reported the application of Povacoat®, a hydrophilic polyvinylalcohol copolymer, as a dispersion stabilizer of nanoparticles of poorly water-soluble compounds. In addition, the influence of aggregation of the nanoparticles on their solubility and oral absorption was studied. Griseofulvin (GF) was used as a model compound with poor water solubility and was milled to nanoparticles by wet bead milling. The dispersion stability of GF milled with Povacoat® or the generally used polymers (polyvinylalcohol, hydroxypropylcellulose SSL, and polyvinylpyrrolidone K30) was compared. Milled GF suspended in Povacoat® aqueous solution with D-mannitol, added to improve the disintegration rate of freeze-dried GF, exhibited high dispersion stability without aggregation (D90 = ca. 0.220 μm), whereas milled GF suspended in aqueous solutions of the other polymers aggregated (D90 > 5 μm). Milled GF with Povacoat® showed improved aqueous solubility and bioavailability compared with the other polymers. The aggregation of nanoparticles had significant impact on the solubility and bioavailability of GF. Povacoat® also prevented the aggregation of the various milled poorly water-soluble compounds (hydrochlorothiazide and tolbutamide, etc.) more effectively than the other polymers. These results showed that Povacoat® could have wide applicability to the development of nanoformulations of poorly water-soluble compounds. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Formulation and optimization of doxorubicin loaded polymeric nanoparticles using Box-Behnken design: ex-vivo stability and in-vitro activity.

PubMed

Shaikh, Muhammad Vaseem; Kala, Manika; Nivsarkar, Manish

2017-03-30

Biodegradable nanoparticles (NPs) have gained tremendous interest for targeting chemotherapeutic drugs to the tumor environment. Inspite of several advances sufficient encapsulation along with the controlled release and desired size range have remained as considerable challenges. Hence, the present study examines the formulation optimization of doxorubicin loaded PLGA NPs (DOX-PLGA-NPs), prepared by single emulsion method for cancer targeting. Critical process parameters (CPP) were selected by initial screening. Later, Box-Behnken design (BBD) was used for analyzing the effect of the selected CPP on critical quality attributes (CQA) and to generate a design space. The optimized formulation was stabilized by lyophilization and was used for in-vitro drug release and in-vitro activity on A549 cell line. Moreover, colloidal stability of the NPs in the biological milieu was assessed. Amount of PLGA and PVA, oil:water ratio and sonication time were the selected independent factors for BBD. The statistical data showed that a quadratic model was fitted to the data obtained. Additionally, the lack of fit values for the models was not significant. The delivery system showed sustained release behavior over a period of 120h and was governed by Fickian diffusion. The multipoint analysis at 24, 48 and 72h showed gradual reduction in IC50 value of DOX-PLGA-NPs (p<0.05, Fig. 9). DOX-PLGA-NPs were found to be stable in the biological fluids indicating their in-vivo applicability. In conclusion, optimization of the DOX-PLGA-NPs by BBD yielded in a promising drug carrier for doxorubicin that could provide a novel treatment modality for cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanoprecipitation process: From encapsulation to drug delivery.

PubMed

Martínez Rivas, Claudia Janeth; Tarhini, Mohamad; Badri, Waisudin; Miladi, Karim; Greige-Gerges, Hélène; Nazari, Qand Agha; Galindo Rodríguez, Sergio Arturo; Román, Rocío Álvarez; Fessi, Hatem; Elaissari, Abdelhamid

2017-10-30

Drugs encapsulation is a suitable strategy in order to cope with the limitations of conventional dosage forms such as unsuitable bioavailability, stability, taste, and odor. Nanoprecipitation technique has been used in the pharmaceutical and agricultural research as clean alternative for other drug carrier formulations. This technique is based on precipitation mechanism. Polymer precipitation occurs after the addition of a non-solvent to a polymer solution in four steps mechanism: supersaturation, nucleation, growth by condensation, and growth by coagulation that leads to the formation of polymer nanoparticles or aggregates. The scale-up of laboratory-based nanoprecipitation method shows a good reproducibility. In addition, flash nanoprecipitation is a good strategy for industrial scale production of nanoparticles. Nanoprecipitation is usually used for encapsulation of hydrophobic or hydrophilic compounds. Nanoprecipitation was also shown to be a good alternative for the encapsulation of natural compounds. As a whole, process and formulation related parameters in nanoprecipitation technique have critical effect on nanoparticles characteristics. Biodegradable or non-biodegradable polymers have been used for the preparation of nanoparticles intended to in vivo studies. Literature studies have demonstrated the biodistribution of the active loaded nanoparticles in different organs after administration via various routes. In general, in vitro drug release from nanoparticles prepared by nanoprecipitation includes two phases: a first phase of "burst release" which is followed by a second phase of prolonged release. Moreover, many encapsulated active molecules have been commercialized in the pharmaceutical market. Copyright © 2017 Elsevier B.V. All rights reserved.

Lipid nanoparticles (SLN & NLC) for delivery of vitamin E: a comprehensive review.

PubMed

Saez, V; Souza, I D L; Mansur, C R E

2018-04-01

The antioxidative and photoprotective properties of vitamin E have caused it to be included as an active agent in various pharmaceutical and cosmetic products. However, its lipophilicity, chemical instability and poor skin penetration have limited the effectiveness of these formulations. For that reason, many attempts to include it in different drug delivery systems have been made. In recent decades, lipid nanoparticles have received special attention due to their advantages of compatibility with the skin, ability to enhance penetration of drugs in the stratum corneum, protection of the encapsulated substance against degradation induced by the external medium and control of drug release. This work reviews the current status of the encapsulation of vitamin E in lipid nanoparticles. We describe the most important methods for obtaining and characterizing lipid nanoparticles containing vitamin E (LNP-VE), various techniques for the evaluation of vitamin E's properties after encapsulation, the main in vitro and in vivo studies of the potential effectiveness or toxicity of LNP-VE, the formulations and stability studies of this delivery system, the commercial products based on LNP-VE and the regulatory aspects related to lipid nanoparticles. Finally, we discuss the most relevant advantages of encapsulating vitamin E in such particles and critical aspects that still demand attention to enhance the potential of solid lipid nanoparticles to deliver vitamin E. © 2018 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Successful lyophilization by adopting a fast ramp rate during primary drying in protein formulations.

PubMed

Ohori, Ryo; Akita, Tomomi; Yamashita, Chikamasa

2018-06-15

In the lyophilization process for injections, the shelf temperature (T s ) and chamber pressure (P c ) have mainly been investigated to optimize the primary drying process. The objective of this study was to show that lyophilization of protein formulations can be achieved by adopting a fast ramp rate of T s in the beginning of the primary drying process. Bovine serum albumin was used as the model protein, and seven different lyophilized formulations obtained were stored at elevated temperature. We found that although acceptable cake appearance was confirmed by the fast ramp cycle, all formulations of lyophilized cakes obtained by the slow ramp cycle severely collapsed (macrocollapse). It is thought that the collapse in the slow ramp cycle occurred during the shelf ramp in the beginning of primary drying and that insufficient removal of water from the dried matrix caused viscous flow (product collapse). Regarding storage stability, moisture-induced degradation was confirmed in some of the formulations prepared by the slow ramp cycle, whereas all lyophilized BSA formulations prepared by the fast ramp cycle were stable. Thus, the results indicate that the ramp rate appears to be one of the critical operational parameters required to establish a successful lyophilization cycle. Copyright © 2018. Published by Elsevier B.V.

Biomimetic synthesis of hybrid hydroxyapatite nanoparticles using nanogel template for controlled release of bovine serum albumin.

PubMed

Qin, Jinli; Zhong, Zhenyu; Ma, Jun

2016-05-01

A biomimetic method was used to prepare hybrid hydroxyapatite (HAP) nanoparticles with chitosan/polyacrylic acid (CS-PAA) nanogel. The morphology, structure, crystallinity, thermal properties and biocompatibility of the obtained hybrid nanogel-HAP nanoparticles have been characterized. In addition, bovine serum albumin (BSA) was used as a model protein to study the loading and release behaviors of the hybrid nanogel-HAP nanoparticles. The results indicated that the obtained HAP nanoparticles were agglomerated and the nanogel could regulate the formation of HAP. When the nanogel concentration decreased, different HAP crystal shapes and agglomerate structures were obtained. The loading amount of BSA reached 67.6 mg/g for the hybrid nanoparticles when the mineral content was 90.4%, which decreased when the nanogel concentration increased. The release profile of BSA was sustained in neutral buffer. Meanwhile, an initial burst release was found at pH 4.5 due to the desorption of BSA from the surface, followed by a slow release. The hemolysis percentage of the hybrid nanoparticles was close to the negative control, and these particles were non-toxic to bone marrow stromal stem cells. The results suggest that these hybrid nanogel-HAP nanoparticles are promising candidate materials for biocompatible drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

Batch and continuous production of stable dense suspensions of drug nanoparticles in a wet stirred media mill

NASA Astrophysics Data System (ADS)

Afolabi, Afola we mi

One way to improve the bioavailability of poorly water-soluble drugs is to reduce particle size of drug crystals down to nanoscale via wet stirred media milling. An increase in total surface area per mass loading of the drug and specific surface area as well as reduced external mass transfer resistance allow a faster dissolution of the poorly-water soluble drug from nanocrystals. To prevent aggregation of nanoparticles, polymers and surfactants are dissolved in water acting as stabilizers via adsorption onto the drug crystals. In the last two decades, ample experimental data were generated in the area of wet stirred media milling for the production of drug nanoparticle suspensions. However, a fundamental scientific/engineering understanding of various aspects of this process is still lacking. These challenges include elucidation of the governing mechanism(s) during nanoparticle formation and physical stabilization of the nanosuspension with the use of polymers and surfactants (formulation parameters), understanding the impact of process parameters in the context of first-principle-based models, and production of truly nanosized drug particles (10-100 nm) with acceptable physical stability and minimal contamination with the media. Recirculation mode of milling operation, where the drug suspension in a holding tank continuously circulates through the stirred media mill, has been commonly used in lab, pilot, and commercial scales. Although the recirculation is continuous, the recirculation operation mode is overall a batch operation, requiring significant number of batches for a large-volume pharmaceutical product. Hence, development and investigation of a truly continuous process should offer significant advantages. To explain the impact of some of the processing parameters, stress intensity and stress number concepts were widely used in literature, which do not account for the effect of suspension viscosity explicitly. The impact of the processing parameters has not been explained in a predictive and reliable manner. In this dissertation, a comprehensive investigation of the production of Griseofulvin nanosuspensions in a wet stirred media mill operating in both the recirculation and continuous modes has been conducted to address the aforementioned fundamental challenges. Griseofulvin has been selected as a model poorly water-soluble BCS Class II drug. Impact of various formulation parameters such as stabilizer type and loading as well as processing parameters such as rotor speed, bead loading, bead size, suspension flow rate and drug loading was studied. A major novelty of the present contribution is that the impact of processing and formulation parameters has been analyzed and interpreted using a combined experimental-theoretical (microhydrodynamic model) approach. Such a comprehensive approach allowed us to intensify the process for the production of sub-100 nm drug particles, which could not be produced with top-down approaches in the literature so far. In addition, a multi-pass mode of continuous operation was developed and the so-called "Rehbinder effect", which has not been shown for the breakage of drug particles, was also elucidated. The dissertation work (1) indicated the need for a minimum polymeric stabilizer-to-drug ratio for proper stabilization of drug nanosuspensions as dictated by polymer adsorption and synergistic interactions between a polymeric stabilizer and a surfactant, (2) demonstrated the existence of an optimum polymer concentration from a breakage rate perspective in the presence of a surfactant, which results from the competing effects of viscous dampening and enhanced steric stabilization at higher polymer concentration, (3) developed fundamental understanding of the breakage dynamics-processing-formulation relationships and rationalized preparation of a single highly drug- loaded batch (20% or higher) instead of multiple dilute batches, (4) designed an intensified process for faster preparation of sub-100 nm particles with reduced specific energy consumption and media wear (i.e. minimal drug contamination), and (5) provided first evidence for the proof of Rehbinder effect during the milling of drugs. Not only do the polymers and surfactants allow proper physical stabilization of the nanoparticles in the suspensions, but they also do facilitate drug particle breakage. This dissertation also discusses applications of nanosuspensions and practical issues encountered during wet media milling.

Nanoparticle-Delivered Chemotherapy: Old Drugs in New Packages.

PubMed

Lee, Michael S; Dees, E Claire; Wang, Andrew Z

2017-03-15

Cytotoxic chemotherapies have a narrow therapeutic window, with high peaks and troughs of plasma concentration. Novel nanoparticle formulations of cytotoxic chemotherapy drugs can enhance pharmacokinetic characteristics and facilitate passive targeting of drugs to tumors via the enhanced permeability and retention effect, thus mitigating toxicity. Nanoparticle vehicles currently in clinical use or undergoing clinical investigation for anticancer therapies include liposomes, polymeric micelles, protein-drug nanoparticles, and dendrimers. Multiple nanoparticle formulations of existing cytotoxic chemotherapies are approved for use in several indications, with clinical data indeed showing optimization of pharmacokinetics and different toxicity profiles compared with their parent drugs. There are also many new nanoparticle drug formulations in development and undergoing early- and late-phase clinical trials, including several that utilize active targeting or triggered release based on environmental stimuli. Here, we review the rationale for nanoparticle formulations of existing or previously investigated cytotoxic drugs, describe currently approved nanoparticle formulations of drugs, and discuss some of the most promising clinical trials currently underway.

N-acetyl-l-methionine is a superior protectant of human serum albumin against photo-oxidation and reactive oxygen species compared to N-acetyl-L-tryptophan.

PubMed

Kouno, Yousuke; Anraku, Makoto; Yamasaki, Keishi; Okayama, Yoshiro; Iohara, Daisuke; Ishima, Yu; Maruyama, Toru; Kragh-Hansen, Ulrich; Hirayama, Fumitoshi; Otagiri, Masaki

2014-09-01

Sodium octanoate (Oct) and N-acetyl-l-tryptophan (N-AcTrp) are widely used as stabilizers during pasteurization and storage of albumin products. However, exposure to light photo-degrades N-AcTrp with the formation of potentially toxic compounds. Therefore, we have examined the usefulness of N-acetyl-l-methionine (N-AcMet) in comparison with N-AcTrp for long-term stability, including photo stability, of albumin products. Recombinant human serum albumin (rHSA) with and without additives was photo-irradiated for 4weeks. The capability of the different stabilizers to scavenge reactive oxygen species (ROS) was examined by ESR spectrometry. Carbonyl contents were assessed by a spectrophotometric method using fluoresceinamine and Western blotting, whereas the structure of rHSA was examined by SDS-PAGE, far-UV circular dichroism and differential scanning calorimetry. Binding was determined by ultrafiltration. N-AcMet was found to be a superior ROS scavenger both before and after photo-irradiation. The number of carbonyl groups formed was lowest in the presence of N-AcMet. According to SDS-PAGE, N-AcMet stabilizes the monomeric form of rHSA, whereas N-AcTrp induces degradation of rHSA during photo-irradiation. The decrease in α-helical content of rHSA was the smallest in the presence of Oct, without or with N-AcMet. Photo-irradiation did not affect the denaturation temperature or calorimetric enthalpy of rHSA, when N-AcMet was present. The weakly bound N-AcMet is a superior protectant of albumin, because it is a better ROS-protector and structural stabilizer than N-AcTrp, and it is probable and also useful for other protein preparations. N-AcMet is an effective stabilizer of albumin during photo-irradiation, while N-Ac-Trp promotes photo-oxidative damage to albumin. Copyright © 2014 Elsevier B.V. All rights reserved.

Nanoparticle Additives for Multiphase Systems: Synthesis, Formulation and Characterization

DTIC Science & Technology

2012-01-01

ADDITIVES FOR MULTIPHASE SYSTEMS: SYNTHESIS , FORMULATION AND CHARACTERIZATION Vinod Kanniah University of Kentucky, vinodkanniah@gmail.com This Doctoral...UKnowledge@lsv.uky.edu. Recommended Citation Kanniah, Vinod, "NANOPARTICLE ADDITIVES FOR MULTIPHASE SYSTEMS: SYNTHESIS , FORMULATION AND CHARACTERIZATION...00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Nanoparticle Additives for Multiphase Systems: Synthesis , Formulation and Characterization 5a

Vitamin D3-Loaded Nanostructured Lipid Carriers as a Potential Approach for Fortifying Food Beverages; in Vitro and in Vivo Evaluation.

PubMed

Mohammadi, Maryam; Pezeshki, Akram; Mesgari Abbasi, Mehran; Ghanbarzadeh, Babak; Hamishehkar, Hamed

2017-04-01

Purpose: Nanostructured lipid carriers (NLCs) composed of solid lipid and oil are a new generation of lipid nanoparticles which have exhibited some merits over traditional used lipid nanoparticles in fortifying food and beverages and nutraceuticals delivery systems such as liposomes and solid lipid nanoparticles. Methods: In this study, Precirol and Compritol as solid lipids, Miglyol and Octyloctanoat as liquid lipids, Tween80, Tween20 and Poloxamer407 as surfactants were used to prepare vitamin D 3 -loaded NLC dispersion using hot homogenization method. The particle size and size distribution for all formulations were evaluated by immediately after production and during a storage period of 60 days. Results: The Precirol-based NLC showed superiority over Compritol-based NLC in the point of physical stability. Results clearly suggested that an optimum concentration of 3% of Poloxamer407 or 2% of Tween20 was sufficient to cover the surface of nanoparticles effectively and prevent agglomeration during the homogenization process. Octyloctanoat was introduced for the first time as a good substituent for Miglyol in the preparation of NLC formulations. The vitamin D 3 Intestinal absorption enhanced by the incorporating in NLCs. Conclusion: It was concluded that NLC showed a promising approach for fortifying beverages by lipophilic nutraceuticals such as vitamin D.

Vitamin D3-Loaded Nanostructured Lipid Carriers as a Potential Approach for Fortifying Food Beverages; in Vitro and in Vivo Evaluation

PubMed Central

Mohammadi, Maryam; Pezeshki, Akram; Mesgari Abbasi, Mehran; Ghanbarzadeh, Babak; Hamishehkar, Hamed

2017-01-01

Purpose: Nanostructured lipid carriers (NLCs) composed of solid lipid and oil are a new generation of lipid nanoparticles which have exhibited some merits over traditional used lipid nanoparticles in fortifying food and beverages and nutraceuticals delivery systems such as liposomes and solid lipid nanoparticles. Methods: In this study, Precirol and Compritol as solid lipids, Miglyol and Octyloctanoat as liquid lipids, Tween80, Tween20 and Poloxamer407 as surfactants were used to prepare vitamin D3-loaded NLC dispersion using hot homogenization method. The particle size and size distribution for all formulations were evaluated by immediately after production and during a storage period of 60 days. Results: The Precirol-based NLC showed superiority over Compritol-based NLC in the point of physical stability. Results clearly suggested that an optimum concentration of 3% of Poloxamer407 or 2% of Tween20 was sufficient to cover the surface of nanoparticles effectively and prevent agglomeration during the homogenization process. Octyloctanoat was introduced for the first time as a good substituent for Miglyol in the preparation of NLC formulations. The vitamin D3 Intestinal absorption enhanced by the incorporating in NLCs. Conclusion: It was concluded that NLC showed a promising approach for fortifying beverages by lipophilic nutraceuticals such as vitamin D. PMID:28507938

Application of Albumin-embedded Magnetic Nanoheaters for Release of Etoposide in Integrated Chemotherapy and Hyperthermia of U87-MG Glioma Cells.

PubMed

Babincová, Melánia; Vrbovská, Hana; Sourivong, Paul; Babinec, Peter; Durdík, Štefan

2018-05-01

Malignant gliomas remain refractory to several therapeutic approaches and the requirement for novel treatment modalities is critical to combat this disease. Etoposide is a topoisomerase-II inhibitor, which promotes DNA damage and apoptosis of cancer cells. In this study, we prepared albumin with embedded magnetic nanoparticles and etoposide for in vitro evaluation of combined hyperthermia and chemotherapy. Magnetic nanoparticles were prepared by a modified co-precipitation method in the presence of human serum albumin and etoposide. A cellular proliferation assay was used to determine the effects of these nanostructures on the viability of U87 glioma cells in an alternating magnetic field. The in vitro experiments showed that cell viability decreased to 59.4% after heat treatment alone and to 53.8% on that with free etoposide, while combined treatment resulted in 7.8% cell viability. Integrating hyperthermia and chemotherapy using albumin co-embedded magnetic nanoheaters and etoposide may represent a promising therapeutic option for glioblastoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery.

PubMed

Lu, Wei; Zhang, Yan; Tan, Yu-Zhen; Hu, Kai-Li; Jiang, Xin-Guo; Fu, Shou-Kuan

2005-10-20

In this paper, a novel drug carrier for brain delivery, cationic bovine serum albumin (CBSA) conjugated with poly(ethyleneglycol)-poly(lactide) (PEG-PLA) nanoparticle (CBSA-NP), was developed and its effects were evaluated. The copolymers of methoxy-PEG-PLA and maleimide-PEG-PLA were synthesized by ring opening polymerization of D,L-lactide initiated by methoxy-PEG and maleimide-PEG, respectively, which were applied to prepare pegylated nanoparticles by means of double emulsion and solvent evaporation procedure. Native bovine serum albumin (BSA) was cationized and thiolated, followed by conjugation through the maleimide function located at the distal end of PEG surrounding the nanoparticle's surface. Transmission electron micrograph (TEM) and dynamic light scattering results showed that CBSA-NP had a round and regular shape with a mean diameter around 100 nm. Surface nitrogen was detected by X-ray photoelectron spectroscopy (XPS), and colloidal gold stained around the nanoparticle's surface was visualized in TEM, which proved that CBSA was covalently conjugated onto its surface. To evaluate the effects of brain delivery, BSA conjugated with pegylated nanoparticles (BSA-NP) was used as the control group and 6-coumarin was incorporated into the nanoparticles as the fluorescent probe. The qualitative and quantitative results of CBSA-NP uptake experiment compared with those of BSA-NP showed that rat brain capillary endothelial cells (BCECs) took in much more CBSA-NP than BSA-NP at 37 degrees C, at different concentrations and time incubations. After a dose of 60 mg/kg CBSA-NP or BSA-NP injection in mice caudal vein, fluorescent microscopy of brain coronal sections showed a higher accumulation of CBSA-NP in the lateral ventricle, third ventricle and periventricular region than that of BSA-NP. There was no difference on BCECs' viability between CBSA-conjugated and -unconjugated pegylated nanoparticles. The significant results in vitro and in vivo showed that CBSA-NP was a promising brain drug delivery carrier with low toxicity.

Cubosome formulations stabilized by a dansyl-conjugated block copolymer for possible nanomedicine applications.

PubMed

Murgia, Sergio; Falchi, Angela Maria; Meli, Valeria; Schillén, Karin; Lippolis, Vito; Monduzzi, Maura; Rosa, Antonella; Schmidt, Judith; Talmon, Yeshayahu; Bizzarri, Ranieri; Caltagirone, Claudia

2015-05-01

We present here an innovative, fluorescent, monoolein-based cubosome dispersion. Rather than embedded within the monoolein palisade, the fluorescent imaging agent, namely dansyl, was conjugated to the terminal ethylene oxide moieties of the block copolymer Pluronic F108. We discuss the physicochemical and photophysical properties of this fluorescent Pluronic and of a cubosome formulation stabilized by a mixture of dansyl-conjugated and non-conjugated Pluronic, also including an anticancer drug (quercetin). Furthermore, we performed biocompatibility tests against HeLa cells to assess internalization and cytotoxicity features of this nanoparticles aqueous dispersion. Cryo-TEM, SAXS, and DLS analysis, proved the bicontinuous cubic inner nanostructure and the morphology of this fluorescent cubosome dispersion, while photophysical measurements and biocompatibility results basically validate their potential use for theranostic nanomedicine applications. Copyright © 2015 Elsevier B.V. All rights reserved.

PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery.

PubMed

Chan, Juliana M; Zhang, Liangfang; Yuet, Kai P; Liao, Grace; Rhee, June-Wha; Langer, Robert; Farokhzad, Omid C

2009-03-01

Current approaches to encapsulate and deliver therapeutic compounds have focused on developing liposomal and biodegradable polymeric nanoparticles (NPs), resulting in clinically approved therapeutics such as Doxil/Caelyx and Genexol-PM, respectively. Our group recently reported the development of biodegradable core-shell NP systems that combined the beneficial properties of liposomal and polymeric NPs for controlled drug delivery. Herein we report the parameters that alter the biological and physicochemical characteristics, stability, drug release properties and cytotoxicity of these core-shell NPs. We further define scalable processes for the formulation of these NPs in a reproducible manner. These core-shell NPs consist of (i) a poly(D,L-lactide-co-glycolide) hydrophobic core, (ii) a soybean lecithin monolayer, and (iii) a poly(ethylene glycol) shell, and were synthesized by a modified nanoprecipitation method combined with self-assembly. Preparation of the NPs showed that various formulation parameters such as the lipid/polymer mass ratio and lipid/lipid-PEG molar ratio controlled NP physical stability and size. We encapsulated a model chemotherapy drug, docetaxel, in the NPs and showed that the amount of lipid coverage affected its drug release kinetics. Next, we demonstrated a potentially scalable process for the formulation, purification, and storage of NPs. Finally, we tested the cytotoxicity using MTT assays on two model human cell lines, HeLa and HepG2, and demonstrated the biocompatibility of these particles in vitro. Our data suggest that the PLGA-lecithin-PEG core-shell NPs may be a useful new controlled release drug delivery system.

Microbial surfactants: fundamentals and applicability in the formulation of nano-sized drug delivery vectors.

PubMed

Rodrigues, Ligia R

2015-07-01

Microbial surfactants, so-called biosurfactants, comprise a wide variety of structurally distinct amphipathic molecules produced by several microorganisms. Besides exhibiting surface activity at the interfaces, these molecules present powerful characteristics including high biodegradability, low toxicity and special biological activities (e.g. antimicrobial, antiviral, anticancer, among others), that make them an alternative to their chemical counterparts. Several medical-related applications have been suggested for these molecules, including some reports on their potential use in the formulation of nano-sized drug delivery vectors. However, despite their promises, due to the generalized lack of knowledge on microbial surfactants phase behavior and stability under diverse physicochemical conditions, these applications remain largely unexplored, thus representing an exciting field of research. These nano-sized vectors are a powerful approach towards the current medical challenges regarding the development of efficient and targeted treatments for several diseases. In this review, a special emphasis will be given to nanoparticles and microemulsions. Nanoparticles are very auspicious as their size, shape and stability can be manipulated by changing the environmental conditions. On the other hand, the easiness of formulation, as well as the broad possibilities of administration justifies the recent popularity of the microemulsions. Notwithstanding, both vector types still require further developments to overcome some critical limitations related with toxicity and costs, among others. Such developments may include the search for other system components, as the microbial surfactants, that can display improved features. Copyright © 2015 Elsevier Inc. All rights reserved.

Tailoring sub-micron PLGA particle release profiles via centrifugal fractioning

PubMed Central

Dutta, Dipankar; Salifu, Mariama; Sirianni, Rachael W.; Stabenfeldt, Sarah E.

2016-01-01

Poly(D,L-lactic-co-glycolic) acid (PLGA)-based submicron particles are uniquely posed to overcome limitations of conventional drug delivery systems. However, tailoring cargo/payload release profiles from PLGA micro/nanoparticles typically requires optimization of the multi-parameter formulation, where small changes may cause drastic shifts in the resulting release profiles. In this study, we aimed to establish whether refining the average diameter of submicron particle populations after formulation alters protein release profiles. PLGA particles were first produced via double emulsion-solvent evaporation method to encapsulate bovine serum albumin. Particles were then subjected to centrifugal fractioning protocols varying in both spin time and force to determine encapsulation efficiency and release profile of differently sized populations that originated from a single batch. We found the average particle diameter was related to marked alterations in encapsulation efficiencies (range: 36.4–49.4%), burst release (range: 15.8–49.1%), and time for total cargo release (range: 38–78 days). Our data corroborate previous reports relating PLGA particle size with such release characteristics, however, this is the first study, to our knowledge, to directly compare particle population size while holding all formulation parameters constant. In summary, centrifugal fractioning to selectively control the population distribution of sub-micron PLGA particles represents a feasible tool to tailor release characteristics. PMID:26517011

Discomfort from an Alkaline Formulation Delivered Subcutaneously in Humans

PubMed Central

Ward, W. Kenneth; Castle, Jessica R.; Branigan, Deborah L.; Massoud, Ryan G.; Youssef, Joseph El

2013-01-01

Background and Objective There is a paucity of data regarding tolerability of alkaline drugs administered subcutaneously. The aim of this study was to assess the tolerability of alkaline preparations of human albumin delivered subcutaneously to healthy humans. Methods We compared the tolerability of neutral versus alkaline (pH 10) formulations of human albumin in ten volunteers. With an intent to minimize the time required to reach physiological pH after injection, the alkaline formulation was buffered with a low concentration of glycine (20 mmol/L). Each formulation was given at two rates: over 5 seconds and over 60 seconds. A six-point scale was used to assess discomfort. Results For slow injections, there was a significant difference between pH 7.4 and pH 10 injections (0.4 ± 0.2 vs 1.1 ± 0.2, mean ± SEM; p = 0.025), though the degree of discomfort at pH 10 injections was only ‘mild or slight’. For fast injections, the difference between neutral and alkaline formulations was of borderline significance. Inflammation and oedema, as judged by a physician, were very minimal for all injections, irrespective of pH. Conclusion For subcutaneous drug administration (especially when delivered slowly), there was more discomfort associated with alkaline versus neutral formulations of albumin, though the discomfort was mild. This study suggests that there is little discomfort and inflammation resulting from subcutaneous administration of protein drugs formulated with weak buffers at alkaline pH. PMID:22568666

Physicochemical characterization of engineered nanoparticles under physiological conditions: effect of culture media components and particle surface coating.

PubMed

Fatisson, Julien; Quevedo, Ivan R; Wilkinson, Kevin J; Tufenkji, Nathalie

2012-03-01

The use of engineered nanoparticles (ENPs) in commercial products has increased substantially over the last few years. Some research has been conducted in order to determine whether or not such materials are cytotoxic, but questions remain regarding the role that physiological media and sera constituents play in ENP aggregation or stabilization. In this study, several characterization methods were used to evaluate the particle size and surface potential of 6 ENPs suspended in a number of culture media and in the presence of different culture media constituents. Dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS) were employed for size determinations. Results were interpreted on the basis of ENP surface potentials evaluated from particle electrophoretic mobilities (EPM). Measurements made after 24h of incubation at 37°C showed that the cell culture medium constituents had only moderate impact on the physicochemical properties of the ENP, although incubation in bovine serum albumin destabilized the colloidal system. In contrast, most of the serum proteins increased colloidal stabilization. Moreover, the type of ENP surface modification played a significant role in ENP behavior whereby the complexity of interactions between the ENPs and the medium components generally decreased with increasing complexity of the particle surface. This investigation emphasizes the importance of ENP characterization under conditions that are representative of cell culture media or physiological conditions for improved assessments of nanoparticle cytotoxicity. Copyright © 2011 Elsevier B.V. All rights reserved.

In situ preparation of water-soluble ginsenoside Rh2-entrapped bovine serum albumin nanoparticles: in vitro cytocompatibility studies.

PubMed

Singh, Priyanka; Kim, Yeon Ju; Singh, Hina; Ahn, Sungeun; Castro-Aceituno, Verónica; Yang, Deok Chun

2017-01-01

The present study investigates a simple and convenient one-step procedure for the preparation of bovine serum albumin (BSA)-Rh2 nanoparticles (NPs) at room temperature. In this work, ginsenoside Rh2 was entrapped within the BSA protein to form BSA-Rh2 NPs to enhance the aqueous solubility, stability, and therapeutic efficacy of Rh2. The physiochemical characterization by high-performance liquid chromatography, nuclear magnetic resonance, Fourier transform infrared spectroscopy, field emission transmission electron microscopy, dynamic light scattering, and thermogravimetric analysis confirmed that the prepared BSA-Rh2 NPs were spherical, highly monodispersed, and stable in aqueous systems. In addition, the stability of NPs in terms of different time intervals, pHs, and temperatures (20°C-700°C) was analyzed. The results obtained with different pHs showed that the synthesized BSA-Rh2 NPs were stable in the physiological buffer (pH 7.4) for up to 8 days, but degraded under acidic conditions (pH 5.0) representing the pH inside tumor cells. Furthermore, comparative analysis of the water solubility of BSA-Rh2 NPs and standard Rh2 showed that the BSA nanocarrier enhanced the water solubility of Rh2. Moreover, in vitro cytotoxicity assays including cell viability assays and morphological analyses revealed that Rh2-entrapped BSA NPs, unlike the free Rh2, demonstrated better in vitro cell viability in HaCaT skin cell lines and that BSA enhanced the anticancer effect of Rh2 in A549 lung cell and HT29 colon cancer cell lines. Additionally, anti-inflammatory assay of BSA-Rh2 NPs and standard Rh2 performed using RAW264.7 cells revealed decreased lipopolysaccharide-induced nitric oxide production by BSA-Rh2 NPs. Collectively, the present study suggests that BSA can significantly enhance the therapeutic behavior of Rh2 by improving its solubility and stability in aqueous systems, and hence, BSA-Rh2 NPs may potentially be used as a ginsenoside delivery vehicle in cancer and inflammatory cell lines.

A new strategy based on SmRho protein loaded chitosan nanoparticles as a candidate oral vaccine against schistosomiasis.

PubMed

Oliveira, Carolina R; Rezende, Cíntia M F; Silva, Marina R; Pêgo, Ana Paula; Borges, Olga; Goes, Alfredo M

2012-01-01

Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis.

Development and Optimization of Silver Nanoparticle Formulation for Fabrication

DTIC Science & Technology

2015-08-14

Development and Optimization of Silver Nanoparticle Formulation for Fabrication Publication Type: DJournal/ Paper D Book Chapter ~ Tech Report D...leofPublicationorPresentation: Deve l opment and Optimization of Silver Nanoparticle Formulation for Fabrication 3. Author(s): (List authors starting...fabrication process of silver nanoparticl es could improve future silver containing products , which is i mpor tant to l owering toxicity and improving

Reducing agent-free synthesis of curcumin-loaded albumin nanoparticles by self-assembly at room temperature.

PubMed

Safavi, Maryam Sadat; Shojaosadati, Seyed Abbas; Yang, Hye Gyeong; Kim, Yejin; Park, Eun Ji; Lee, Kang Choon; Na, Dong Hee

2017-08-30

The purpose of this study was to prepare curcumin-loaded bovine serum albumin nanoparticles (CCM-BSA-NPs) by reducing agent-free self-assembly at room temperature. A 2 4 factorial design approach was used to investigate the CCM-BSA-NP preparation process at different pH values, temperatures, dithiothreitol amounts, and CCM/BSA mass ratios. Increasing the ionic strength enabled preparation of CCM-BSA-NPs at 25°C without reducing agent. CCM-BSA-NPs prepared under the optimized conditions at 25°C showed a particle size of 110±6nm, yield of 88.5%, and drug loading of 7.1%. The CCM-BSA-NPs showed strong antioxidant activity and neuroprotective effects in glutamate-induced mouse hippocampal neuronal HT22 cells. This study suggests that ionic strength can be a key parameter affecting the preparation of albumin-based NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation optimization, characterization, and evaluation of in vitro cytotoxic potential of curcumin loaded solid lipid nanoparticles for improved anticancer activity.

PubMed

Rompicharla, Sri Vishnu Kiran; Bhatt, Himanshu; Shah, Aashma; Komanduri, Neeraja; Vijayasarathy, Dhanya; Ghosh, Balaram; Biswas, Swati

2017-11-01

The aim of the present research was to develop a novel, biocompatible, amenable to industrial scale up and affordable solid lipid nanoparticles (SLN) preparation of curcumin and evaluate the therapeutic efficacy in vitro using cancer cells. We have incorporated cholesterol as the lipid to prepare SLN along with the Poloxamer-188 as stabilizer. High shear homogenization was used to prepare the SLN and formulation was optimized using Quality by Design The optimized Chol CUR SLN exhibited a narrow size distribution with a particle size of 166.4±3.5nm. Percentage encapsulation (%EE) was found to be 76.9±1.9%. The SLN were further characterized by DSC, FTIR, XRD and drug release. In vitro cell studies in MDA-MB-231 (Human Breast cancer) cell line revealed that the Chol CUR SLN showed superior cytotoxicity and uptake in comparison to the free curcumin. Furthermore, Chol CUR SLN induced a significantly higher apoptosis compared to free CUR treatment. These results indicated that the curcumin encapsulated in Chol SLN was able to significantly improve the cytotoxic potential and induction of apoptosis in MDA-MB-231 cells. The promising result from our study could lead a further exploration of this nanoparticle formulation to be utilized clinically for cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Adsorption of bovine serum albumin on silicon dioxide nanoparticles: Impact of pH on nanoparticle-protein interactions.

PubMed

Givens, Brittany E; Diklich, Nina D; Fiegel, Jennifer; Grassian, Vicki H

2017-05-03

Bovine serum albumin (BSA) adsorbed on amorphous silicon dioxide (SiO 2 ) nanoparticles was studied as a function of pH across the range of 2 to 8. Aggregation, surface charge, surface coverage, and protein structure were investigated over this entire pH range. SiO 2 nanoparticle aggregation is found to depend upon pH and differs in the presence of adsorbed BSA. For SiO 2 nanoparticles truncated with hydroxyl groups, the largest aggregates were observed at pH 3, close to the isoelectric point of SiO 2 nanoparticles, whereas for SiO 2 nanoparticles with adsorbed BSA, the aggregate size was the greatest at pH 3.7, close to the isoelectric point of the BSA-SiO 2 complex. Surface coverage of BSA was also the greatest at the isoelectric point of the BSA-SiO 2 complex with a value of ca. 3 ±   1 × 10 11 molecules cm -2 . Furthermore, the secondary protein structure was modified when compared to the solution phase at all pH values, but the most significant differences were seen at pH 7.4 and below. It is concluded that protein-nanoparticle interactions vary with solution pH, which may have implications for nanoparticles in different biological fluids (e.g., blood, stomach, and lungs).

Nanocomposite materials based on poly(vinyl chloride) and bovine serum albumin modified ZnO through ultrasonic irradiation as a green technique: Optical, thermal, mechanical and morphological properties.

PubMed

Mallakpour, Shadpour; Darvishzadeh, Marzieh

2018-03-01

In this project, physicochemical properties of poly(vinyl chloride) (PVC) reinforced by ZnO nanoparticles (NPs) were studied. Firstly, ZnO NPs were modified with bovine serum albumin (BSA) as an organo-modifier and biocompatible substance through ultrasound irradiation as environmental friendly, low cost and rapid means. Nanocomposite (NC) films were prepared by loadings of various ratios of ZnO/BSA NPs (3, 6 and 9wt%) inside the PVC. Structural morphology and physical properties of the ZnO-BSA NPs and NC films were investigated via Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis (TGA), transmission electron microscopy and field emission scanning electron microscopy. According to the obtained information from the TGA, an increase in the thermal stability can be clearly observed. Also the results of contact angle analysis indicated with increasing percent of ZnO/BSA NPs into PVC the hydrophilic behaviors of NCs were increased. Copyright © 2017 Elsevier B.V. All rights reserved.

Plant bio-transformable HMG-CoA reductase gene loaded calcium phosphate nanoparticle: in vitro characterization and stability study.

PubMed

Ohadi R, Mehrnaz S; Alvari, Amene; Samim, M; Abdin, Malik Z

2013-03-01

Encapsulation of plasmid DNA in nanoparticle is expected to enhance the stability of DNA, reproducibility and frequency of the genetic transformation in plants. Here we report the formulation of HMG Co-A reductase gene loaded calcium phosphate nanoparticles (Cap nanoparticles) and their in-vitro, in-vivo characterization. The developed Cap nanoparticles were characterized by DSC, FT-IR, and XRD. Developed Cap nanoparticles were spherical in shape having the particle size and zeta potential in the range of 10.86±0.09nm to 33.42±0.18nm and -25.5±0.07mV to -31.7±0.07mV (for Cap-I to Cap-IV). DNA releasing in acidic media showed, initially slow release followed by fast release with a maximum release of Cap-I (95.77±1.39%) > Cap-II (87.32±2.07%) > Cap-III (76.54±2.01%) > Cap-IV (72.93±1.75%) over 60min. Cap nanoparticles were quite stable at storage condition of 40±0.5°C/75±5%RH, 25±0.5°C/60±RH, 4±0.5°C/ambient humidity and the integrity of pDNA encapsulated was confirmed by gel electrophoresis. Compared to wild type C. intybus, transformation efficiency and enhanced biosynthesis of esculin with the DNA nanoparticles in C. intybus were about 10% and 71%, respectively. Antioxidant activity capacity of the biotransformed plants was significantly higher than the normal plant due to high accumulation of esculin.

Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain.

PubMed

Zensi, Anja; Begley, David; Pontikis, Charles; Legros, Celine; Mihoreanu, Larisa; Büchel, Claudia; Kreuter, Jörg

2010-12-01

Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30 min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.

In situ gelling dorzolamide loaded chitosan nanoparticles for the treatment of glaucoma.

PubMed

Katiyar, Shefali; Pandit, Jayamanti; Mondal, Rabi S; Mishra, Anil K; Chuttani, Krishna; Aqil, Mohd; Ali, Asgar; Sultana, Yasmin

2014-02-15

The most important risk associated with glaucoma is the onset and progression of intraocular pressure. The objective of this study was to formulate in situ gel of chitosan nanoparticles to enhance the bioavailability and efficacy of dorzolamide in the glaucoma treatment. Optimized nanoparticles were spherical in shape (particle size: 164 nm) with a loading efficiency of 98.1%. The ex vivo release of the optimized in situ gel nanoparticle formulation showed a sustained drug release as compared to marketed formulation. The gamma scintigraphic study of prepared in situ nanoparticle gel showed good corneal retention compared to marketed formulation. HET-CAM assay of the prepared formulation scored 0.33 in 5 min which indicates the non-irritant property of the formulation. Thus in situ gel of dorzolamide hydrochloride loaded nanoparticles offers a more intensive treatment of glaucoma and a better patient compliance as it requires fewer applications per day compared to conventional eye drops. Copyright © 2013 Elsevier Ltd. All rights reserved.

Simple bioconjugate chemistry serves great clinical advances: albumin as a versatile platform for diagnosis and precision therapy

PubMed Central

2017-01-01

Albumin is the most abundant circulating protein in plasma and has recently emerged as a versatile protein carrier for drug targeting and for improving the pharmacokinetic profile of peptide or protein based drugs. Three drug delivery technologies related to albumin have been developed, which include the coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugating bioactive proteins by albumin fusion technology (AFT), and encapsulation of drugs into albumin nanoparticles. This review article starts with a brief introduction of human serum albumin (HSA), and then summarizes the mainstream chemical strategies of developing HSA binding molecules for coupling with drug molecules. Moreover, we also concisely condense the recent progress of the most important clinical applications of HSA-binding platforms, and specify the current challenges that need to be met for a bright future of HSA-binding. PMID:26771036

Coating of gold nanoparticles for medical application: UV-VIS

NASA Astrophysics Data System (ADS)

Martínez Espinosa, Juan Carlos; Ramírez, Nayem Amtanus Chequer; Funes Oliva, Luis Enrique; Córdova Fraga, Teodoro; Bernal Alvarado, Jesús; Reyes Pablo, Aldelmo; Núñez, Anita Rosa Elvira

2014-11-01

The use of nanostructured materials has gained strength in recent years in the biomedical area; new applications such as the detection of components in living cells have been used in pharmaceutical area, specifically to study the interaction of various antitumor drugs in living tissues, the detection of genes that are closely related to some type of cancer, as well as the detections of protein biomarkers for diseases also have been studied in various research laboratories around of the world. In this work, we characterize the variation of the absorbance of gold nanoparticles (GNPs) coated with different concentration of Bovine Serum Albumin (BSA) protein. We use GNPS of 60 nm of the trademark-TED PELLA, the BSA protein trademark of Sigma Aldrich and based on that proposed protocol by Chithrani et al., 2009 with purposes to obtain an alternative model to determine the optimal stability of the nanoparticles coated with the protein. The colloidal solutions were prepared with BSA at different concentrations (0.25, 0.5, 0.75 and 1% M/V), and were centrifuged at 15,000 rpm for 90 minutes (centrifuge Model Z383K) and a constant temperature of 25 °C. All the spectra sets were obtained within the range from 400 to 700 nm using an UV-VIS spectrophotometer (Thermo Scientific Model 51118650). The results showed a R2 of 0.99 for an exponential curve correlation between the concentration of BSA, and the absorbance measured. We found at higher concentrations of BSA, there is a decrease in the intensity of the absorption spectra in the plasmon resonance. This preliminary model obtained can be used in the stabilization of gold nanoparticles with different proteins of biomedical interest in future experiments and support for functionalization of GNPs with specific membrane markers.

Characterization and evaluation of stabilized particulate formulations as therapeutic oral vaccines for allergy.

PubMed

Kaneko, Kan; McDowell, Arlene; Ishii, Yasuyuki; Hook, Sarah

2017-09-05

Allergic conditions affect more than a quarter of the population in developed countries, but currently available treatments focus more on symptom relief than treating the underlying atopic condition. α-Galactosylceramide (α-GalCer) is a potent immunomodulating compound that has been shown to have a regulatory effect when delivered systemically in nanoparticles. Parenteral delivery is not preferred for chronic conditions, such as allergy, and therefore, the aim of this study was to determine whether a regulatory response could be induced through oral administration in a model of atopy through incorporation of α-GalCer into stable particulate formulations (cationic liposomes, polymerized liposomes and poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs)). The formulations showed only minor changes in particle size, polydispersity index and retention of the model antigen ovalbumin (OVA) during incubation in simulated gastrointestinal (GI) conditions. Oral delivery of α-GalCer in cationic liposomes could induce immunostimulating effects systemically, as seen through increases in serum IgG antibody levels, whereas delivery of α-GalCer in polymerized liposomes and PLGA NPs induced local cytokine changes in the mesenteric lymph nodes (MLNs). The generated responses did not exhibit tolerogenic traits which could be useful for immunoregulation, but the responses generated varied between formulations and suggests that further characterization and optimization could lead to the desired immune response.

Preparation and characterization of nanoparticles of carboxymethyl cellulose acetate butyrate containing acyclovir

NASA Astrophysics Data System (ADS)

Vedula, Venkata Bharadwaz; Chopra, Maulick; Joseph, Emil; Mazumder, Sonal

2016-02-01

Nanoparticles of carboxymethyl cellulose acetate butyrate complexed with the poorly soluble antiviral drug acyclovir (ACV) were produced by precipitation process and the formulation process and properties of nanoparticles were investigated. Two different particle synthesis methods were explored—a conventional precipitation method and a rapid precipitation in a multi-inlet vortex mixer. The particles were processed by rotavap followed by freeze-drying. Particle diameters as measured by dynamic light scattering were dependent on the synthesis method used. The conventional precipitation method did not show desired particle size distribution, whereas particles prepared by the mixer showed well-defined particle size ~125-450 nm before and after freeze-drying, respectively, with narrow polydispersity indices. Fourier transform infrared spectroscopy showed chemical stability and intactness of entrapped drug in the nanoparticles. Differential scanning calorimetry showed that the drug was in amorphous state in the polymer matrix. ACV drug loading was around 10 wt%. The release studies showed increase in solution concentration of drug from the nanoparticles compared to the as-received crystalline drug.

Comparison of PLGA and lecithin/chitosan nanoparticles for dermal targeting of betamethasone valerate.

PubMed

Özcan, Ipek; Azizoğlu, Erkan; Senyiğit, Taner; Özyazici, Mine; Özer, Özgen

2013-07-01

Poly(lactide-co-glycolide) (PLGA) and lecithin/chitosan (LC) nanoparticles were prepared to evaluate the difference in the behavior upon administration on skin, for steroidal treatment. For this purpose, betamethasone-17-valerate (BMV)-loaded nanoparticles with a narrow size distribution and high entrapment efficiency were prepared. Permeation studies showed that both polymeric nanoparticles enhanced the amount of BMV in epidermis, which is the target site of topical steroidal treatment, when compared with commercial formulation. 1.58-Fold increase was determined in the epidermis concentration of BMV by LC nanoparticles with respect to PLGA nanoparticles. Nanoparticles were diluted in chitosan gel (10%, w/w) to prepare suitable formulation for topical application. Accumulation from both gel formulations were found significantly higher than commercial formulation in skin layers (p < 0.05). In addition, pharmacodynamic responses were also investigated as anti-inflammatory and skin-blanching parameters. Both formulations significantly improved these parameters although they contained 10 times less amount of BMV than commercial cream. Moreover, TEWL measurement exhibited no barrier function changes upon the application of nanoparticles on skin. Overall, both nanoparticles improved the localization of BMV within skin layers; but when compared with PLGA nanoparticles, the LC nanoparticles could be classified as a better candidate for topical delivery vehicle in the treatment of various dermatological inflammatory diseases.

A toxic organic solvent-free technology for the preparation of PEGylated paclitaxel nanosuspension based on human serum albumin for effective cancer therapy

PubMed Central

Yin, Tingjie; Dong, Lihui; Cui, Bei; Wang, Lei; Yin, Lifang; Zhou, Jianping; Huo, Meirong

2015-01-01

Clinically, paclitaxel (PTX) is one of most commonly prescribed therapies against a wide range of solid neoplasms. Despite its success, the clinical applicability of PTX (Taxol®) is severely hampered by systemic toxicities induced by Cremophor EL. While attempts to bypass the need for Cremophor EL have been developed through platforms such as Abraxane™, nab™ relies heavily on the use of organic solvents, namely, chloroform. The toxicity introduced by residual chloroform poses a potential risk to patient health. To mitigate the toxicities of toxic organic solvent-based manufacture methods, we have designed a method for the formulation of PTX nanosuspensions (PTX-PEG [polyethylene glycol]-HSA [human serum albumin]) that eliminates the dependence on toxic organic solvents. Coined the solid-dispersion technology, this technique permits the dispersion of PTX into PEG skeleton without the use of organic solvents or Cremophor EL as a solubilizer. Once the PTX-PEG dispersion is complete, the dispersion can be formulated with HSA into nanosuspensions suitable for intravenous administration. Additionally, the incorporation of PEG permits the prolonged circulation through the steric stabilization effect. Finally, HSA-mediated targeting permits active receptor-mediated endocytosis for enhanced tumor uptake and reduced side effects. By eliminating the need for both Cremophor EL and organic solvents while simultaneously increasing antitumor efficacy, this method provides a superior alternative to currently accepted methods for PTX delivery. PMID:26715846

Enhanced colloidal stability, solubility and rapid dissolution of resveratrol by nanocomplexation with soy protein isolate.

PubMed

Pujara, Naisarg; Jambhrunkar, Siddharth; Wong, Kuan Yau; McGuckin, Michael; Popat, Amirali

2017-02-15

The polyphenolic compound resveratrol has received significant attention due to its many pharmacological actions such as anti-cancer, anti-inflammatory, antioxidant and antimicrobial activities. However, poor solubility and stability are major impediments for resveratrol's clinical effectiveness. In this work we have encapsulated resveratrol into soy protein isolate nanoparticles using a simple rotary evaporation technique. Resveratrol-loaded nanoparticles were around 100nm in diameter and negatively charged. Nano-encapsulated resveratrol was found to be in amorphous form and showed more than two times higher solubility with significantly increased dissolution when compared to free resveratrol. Finally, an in-vitro NF-κB inhibition assay revealed that encapsulated resveratrol was stable and retained bioactivity. This new formulation of resveratrol has the potential to boost the clinical effectiveness of this drug and could be utilised for other poorly soluble hydrophobic drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Folate receptor mediated in vivo targeted delivery of human serum albumin coated manganese ferrite magnetic nanoparticles to cancer cells

NASA Astrophysics Data System (ADS)

Zaidan, A.; Ilhami, F.; Fahmi, M. Z.; Purwanto, B.; Kharisma, R. Z.

2017-05-01

Manganese ferrite nanoparticles (MnFe2O4) have received increasing attention due to their remarkable magnetic properties and have been used for various biomedical applications. They have potential applications in magnetic resonance imaging and hyperthermia for cancer. Both novel applications require a delivery system that will allow nanoparticle to move easily and localization of nanoparticle to the target tissue. In our work, we developed human serum albumin coated manganese ferrite magnetic nanoparticles (HSA-MF NPs). The nanoparticles were prepared using solvothermal method and modified with folic acid for targeted delivery. Structure and morphology of manganese ferrite nanoparticle were characterized by X-ray diffraction (XRD) pattern and transmission electron microscopy (TEM). The size of folic acid conjugated HSA-MF NPs (HSA-MF-FA NPs) were studied by dynamic light scattering (DLS). In the in vivo study, we used benzopyrene-induced cancer in mice. We successfully delivered HSA-MF-FA NPs through intravenous tail injection after induction of the tumour. We found that 54% of initial HSA-MF-FA NPs which previously injected localize in the target tissue. While obtained p-value from independent T-test is 0.013 which shows that there is a difference between the control group (HSA-MF NPs) and the treated group (HSA-MF-FA NPs)

One-Pot Approach to Prepare Organo-silica Hybrid Capillary Monolithic Column with Intact Mesoporous Silica Nanoparticle as Building Block.

PubMed

Liu, Shengju; Peng, Jiaxi; Liu, Zheyi; Liu, Zhongshan; Zhang, Hongyan; Wu, Ren'an

2016-10-04

A facile "one-pot" approach to prepare organo-silica hybrid capillary monolithic column with intact mesoporous silica nanoparticle (IMSN) as crosslinker and building block was described. An IMSN crosslinked octadecyl-silica hybrid capillary monolithic column (IMSN-C18 monolithic column) was successfully prepared, and the effects of fabrication conditions (e.g. concentration of intact mesoporous silica nanoparticle, polycondensation temperature, content of vinyltrimethoxysilane and stearyl methacrylate) on the structures of the IMSN-C18 monolithic column were studied in detail. The IMSN-C18 hybrid monolithic column possessed uniform morphology, good mechanical and pH stability (pH 1.1-11), which was applied to the separations of alkyl benzenes, polycyclic aromatic hydrocarbons (PAHs), as well as proteins. The minimum plate height of 10.5 μm (corresponding to 95000 N m -1 ) for butylbenzene and high reproducibility were achieved. The analysis of tryptic digest of bovine serum albumin (BSA) was carried out on the IMSN-C18 monolithic column by cLC coupled mass spectrometry (cLC-MS/MS), with the protein sequence coverage of 87.5% for BSA, demonstrating its potential application in proteomics.

Engineering novel targeted nanoparticle formulations to increase the therapeutic efficacy of conventional chemotherapeutics against multiple myeloma

NASA Astrophysics Data System (ADS)

Ashley, Jonathan D.

Multiple myeloma (MM) is a hematological malignancy which results from the uncontrolled clonal expansion of plasma cells within the body. Despite recent medical advances, this disease remains largely incurable, with a median survival of ˜7 years, owing to the development of drug resistance. This dissertation will explore new advances in nanotechnology that will combine the cytotoxic effects of small molecule chemotherapeutics with the tumor targeting capabilities of nanoparticles to create novel nanoparticle formulations that exhibit enhanced therapeutic indices in the treatment of MM. First, doxorubicin was surfaced conjugated onto micellar nanoparticles via an acid labile hydrazone bond to increase the drug accumulation at the tumor. The cell surface receptor Very Late Antigen-4 (VLA-4; alpha4beta1) is expressed on cancers of hematopoietic origin and plays a vital role in the cell adhesion mediated drug resistance (CAM-DR) in MM. Therefore, VLA-4 antagonist peptides were conjugated onto the nanoparticles via a multifaceted procedure to actively target MM cells and simultaneously inhibit CAM-DR. The micellar doxorubicin nanoparticles were able to overcome CAM-DR and demonstrated improved therapeutic index relative to free doxorubicin. In addition to doxorubicin, other classes of therapeutic agents, such as proteasome inhibitors, can be incorporated in nanoparticles for improved therapeutic outcomes. Utilizing boronic acid chemistry, bortezomib prodrugs were synthesized using a reversible boronic ester bond and then incorporated into liposomes. The different boronic ester bonds that could be potentially used in the synthesis of bortezomib prodrugs were screened based on stability using isobutylboronic acid. The liposomal bortezomib nanoparticles demonstrated significant proteasome inhibition and cytotoxicity in MM cells in vitro, and dramatically reduced the non-specific toxicities associated with free bortezomib while maintaining significant tumor growth inhibition in vivo. Carfilzomib, another proteasome inhibitor, was embedded into the lipid bilayer of liposomes to improve its therapeutic efficacy. VLA-4 antagonist peptides were also incorporated to facilitate MM cell targeting and uptake. The liposomal carfilzomib nanoparticles demonstrated improved therapeutic index and synergy with doxorubicin compared to free carfilzomib. These nanoparticle formulations can significantly improve the efficacy of the respective therapeutic agents and have an immense potential to positively impact the treatment of MM providing for improved patient outcomes.

Combined treatment of tyrosine kinase inhibitor labeled gold nanorod encapsulated albumin with laser thermal ablation in a renal cell carcinoma model

USDA-ARS?s Scientific Manuscript database

This manuscript served to characterize and evaluate Human Serum Albumin-encapsulated Nanoparticles (NPs) for drug delivery of a tyrosine kinase inhibitor combined with induction of photothermal ablation (PTA) combination therapy of Renal Cell Carcinoma (RCC). RCC is the most common type of kidney c...

Protein spheres prepared by drop jet freeze drying.

PubMed

Eggerstedt, Sören N; Dietzel, Mathias; Sommerfeld, Martin; Süverkrüp, Richard; Lamprecht, Alf

2012-11-15

In spray freeze drying (SFD) solutions are frozen by spraying into a very cold environment and subsequently dried by sublimation. In contrast to conventional freeze drying, spray freeze drying has the possibility to produce flowable lyophilizates which offers a variety of new pharmaceutical applications. Here, a drop jet nozzle is proposed as liquid dispenser that is able to produce droplets with a very narrow size distribution compared to standard methods. The drop jet nozzle is mounted in a spray tower designed to prevent direct contact of the product with the freezing medium. Various formulations have been tested containing lysozyme as model protein and stabilizers such as bovine serum albumin, polyvinylpyrrolidone or dextran in various concentrations and mannitol. Excellent free flowing and nearly monodispersed, porous particles are produced where particle properties can be controlled by formulation and process conditions. The particle diameter varied between 231 ± 3 μm and 310 ± 10 μm depending on the formulation composition. The lysozyme activity was >94 ± 5% for all formulations exhibiting a full preservation of enzyme activity. This new method is very promising for the production of nearly monodisperse particulate lyophilizates in various therapeutic applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Multi-stimuli-responsive biohybrid nanoparticles with cross-linked albumin coronae self-assembled by a polymer-protein biodynamer.

PubMed

Wang, Lin; Liu, Li; Dong, Bingyang; Zhao, Hanying; Zhang, Mingming; Chen, Wenjuan; Hong, Yanhang

2017-05-01

A thermoresponsive polymer-protein biodynamer was prepared via the bioconjugation of an aliphatic aldehyde-functionalized copolymer to hydrazine-modified bovine serum albumin (BSA) through reversible pyridylhydrazone linkages. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and size exclusion chromatography (SEC) results indicated that the pyridylhydrazone linkages cleaved in an intracellular-mimicking acidic milieu, thus leading to the release of BSA. The dynamic character of the protein biodynamer was demonstrated by exchange reactions with aldehyde-containing molecules. The biodynamer self-assembled into spherical micelles at a temperature above its lower critical solution temperature (LCST). Subsequently, BSA molecules within the hydrophilic coronae of the micelles were readily cross-linked via reaction with cystamine at 45°C, and multi-stimuli-responsive nanoparticles were generated. The biohybrid nanoparticles reversibly swelled and shrank as the cores of the nanoparticles were solvated below the LCST and desolvated above the LCST. The accessible reversibility of the pyridylhydrazone bonds imparts pH-responsive and dynamic characteristics to the nanoparticles. The nanoparticles displayed glutathione (GSH) responsiveness, and the synergistic effects of pH and GSH resulted in complete disintegration of the nanoparticles under the intracellular-mimicking acidic and reductive conditions. The nanoparticles were also enzyme-responsive and disintegrated rapidly in the presence of protease. In vitro cytotoxicity and cell uptake assays demonstrated that the nanoparticles were highly biocompatible and effectively internalized by HepG2 cells, which make them interesting candidates as vehicles for drug delivery application and biomimetic platforms to investigate the biological process in nature. In this research, we report the synthesis of a temperature and pH dual-responsive polymer-protein biodynamer through reversible pyridylhydrazone formation. The prepared biodynamer can offer a potential platform for intracellular protein delivery. The multi-stimuli-responsive biohybrid nanoparticles containing disulfide functionalities are constructed by cross-linking albumin coronae of the biodynamer micelles. With the combination of a thermoresponsive polymer, protein and reversible covalent bonds, the biohybrid nanoparticles are endowed with highly biocompatible, environmentally responsive and adaptive features. These nanoparticles present the ability to undergo changes in their constitution, hydrodynamic size and nanostructure in response to physical, chemical and biological stimuli, which make them interesting candidates as vehicles for drug delivery application and a biomimetic platform to investigate the biological process in nature. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Protein-silver nanoparticle interactions to colloidal stability in acidic environments.

PubMed

Tai, Jui-Ting; Lai, Chao-Shun; Ho, Hsin-Chia; Yeh, Yu-Shan; Wang, Hsiao-Fang; Ho, Rong-Ming; Tsai, De-Hao

2014-11-04

We report a kinetic study of Ag nanoparticles (AgNPs) under acidic environments (i.e., pH 2.3 to pH ≈7) and systematically investigate the impact of protein interactions [i.e., bovine serum albumin (BSA) as representative] to the colloidal stability of AgNPs. Electrospray-differential mobility analysis (ES-DMA) was used to characterize the particle size distributions and the number concentrations of AgNPs. Transmission electron microscopy was employed orthogonally to provide visualization of AgNPs. For unconjugated AgNPs, the extent of aggregation, or the average particle size, was shown to be increased significantly with an increase of acidity, where a partial coalescence was found between the primary particles of unconjugated AgNP clusters. Aggregation rate constant, kD, was also shown to be proportional to acidity, following a correlation of log(kD) = -1.627(pH)-9.3715. Using ES-DMA, we observe BSA had a strong binding affinity (equilibrium binding constant, ≈ 1.1 × 10(6) L/mol) to the surface of AgNPs, with an estimated maximum molecular surface density of ≈0.012 nm(-2). BSA-functionalized AgNPs exhibited highly-improved colloidal stability compared to the unconjugated AgNPs under acidic environments, where both the acid-induced interfacial dissolution and the particle aggregation became negligible. Results confirm a complex mechanism of colloidal stability of AgNPs: the aggregation process was shown to be dominant, and the formation of BSA corona on AgNPs suppressed both particle aggregation and interfacial dissolution of AgNP samples under acidic environments.

Preparation of finasteride capsules-loaded drug nanoparticles: formulation, optimization, in vitro, and pharmacokinetic evaluation

PubMed Central

Ahmed, Tarek A

2016-01-01

In this study, optimized freeze-dried finasteride nanoparticles (NPs) were prepared from drug nanosuspension formulation that was developed using the bottom–up technique. The effects of four formulation and processing variables that affect the particle size and solubility enhancement of the NPs were explored using the response surface optimization design. The optimized formulation was morphologically characterized using transmission electron microscopy (TEM). Physicochemical interaction among the studied components was investigated. Crystalline change was investigated using X-ray powder diffraction (XRPD). Crystal growth of the freeze-dried NPs was compared to the corresponding aqueous drug nanosuspension. Freeze-dried NPs formulation was subsequently loaded into hard gelatin capsules that were examined for in vitro dissolution and pharmacokinetic behavior. Results revealed that in most of the studied variables, some of the quadratic and interaction effects had a significant effect on the studied responses. TEM image illustrated homogeneity and shape of the prepared NPs. No interaction among components was noticed. XRPD confirmed crystalline state change in the optimized NPs. An enhancement in the dissolution rate of more than 2.5 times from capsules filled with optimum drug NPs, when compared to capsules filled with pure drug, was obtained. Crystal growth, due to Ostwald ripening phenomenon and positive Gibbs free energy, was reduced following lyophilization of the nanosuspension formulation. Pharmacokinetic parameters from drug NPs were superior to that of pure drug and drug microparticles. In conclusion, freeze-dried NPs based on drug nanosuspension formulation is a successful technique in enhancing stability, solubility, and in vitro dissolution of poorly water-soluble drugs with possible impact on the drug bioavailability. PMID:26893559

The fate of a designed protein corona on nanoparticles in vitro and in vivo.

PubMed

Bargheer, Denise; Nielsen, Julius; Gébel, Gabriella; Heine, Markus; Salmen, Sunhild C; Stauber, Roland; Weller, Horst; Heeren, Joerg; Nielsen, Peter

2015-01-01

A variety of monodisperse superparamagnetic iron oxide particles (SPIOs) was designed in which the surface was modified by PEGylation with mono- or bifunctional poly(ethylene oxide)amines (PEG). Using (125)I-labeled test proteins (transferrin, albumin), the binding and exchange of corona proteins was studied first in vitro. Incubation with (125)I-transferrin showed that with increasing grade of PEGylation the binding was substantially diminished without a difference between simply adsorbed and covalently bound protein. However, after incubation with excess albumin and subsequently whole plasma, transferrin from the preformed transferrin corona was more and more lost from SPIOs in the case of adsorbed proteins. If non-labeled transferrin was used as preformed corona and excess (125)I-labeled albumin was added to the reaction mixtures with different SPIOs, a substantial amount of label was bound to the particles with initially adsorbed transferrin but little or even zero with covalently bound transferrin. These in vitro experiments show a clear difference in the stability of a preformed hard corona with adsorbed or covalently bound protein. This difference seems, however, to be of minor importance in vivo when polymer-coated (59)Fe-SPIOs with adsorbed or covalently bound (125)I-labeled mouse transferrin were injected intravenously in mice. With both protein coronae the (59)Fe/(125)I-labelled particles were cleared from the blood stream within 30 min and appeared in the liver and spleen to a large extent (>90%). In addition, after 2 h already half of the (125)I-labeled transferrin from both nanodevices was recycled back into the plasma and into tissue. This study confirms that adsorbed transferrin from a preformed protein corona is efficiently taken up by cells. It is also highlighted that a radiolabelling technique described in this study may be of value to investigate the role of protein corona formation in vivo for the respective nanoparticle uptake.

Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems.

PubMed

Danaei, M; Dehghankhold, M; Ataei, S; Hasanzadeh Davarani, F; Javanmard, R; Dokhani, A; Khorasani, S; Mozafari, M R

2018-05-18

Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.

Synergistically enhanced stability of laccase immobilized on synthesized silver nanoparticles with water-soluble polymers.

PubMed

Cunha, M N M; Felgueiras, H P; Gouveia, I; Zille, A

2017-06-01

Silver nanoparticles (AgNPs) were synthesized by citrate reduction method in the presence of polymers, poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA) and chitosan, used as stabilizing agents, and an oxidoreductase enzyme, laccase (Lac), with the goal of expanding the NPs antimicrobial action. AgNPs were characterized by UV-vis spectrometry, dynamic light scattering and transmission electron microscopy. As protecting agents, PEG and PVA promoted the formation of spherical uniformly-shaped, small-sized, monodispersed AgNPs (≈20nm). High Mw polymers were established as most effective in producing small-sized NPs. Chitosan's viscosity led to the formation of aggregates. Despite the decrease in Lac activity registered for the hybrid formulation, AgNPs-polymer-Lac, a significant augment in stability over time (up to 13days, at 50°C) was observed. This novel formulation displays improved synergistic performance over AgNPs-Lac or polymer-Lac conjugates, since in the former the Lac activity becomes residual at the end of 3days. By enabling many ionic interactions, chitosan restricted the mass transfer between Lac and substrate and, thus, inhibited the enzymatic activity. These hybrid nanocomposites made up of inorganic NPs, organic polymers and immobilized antimicrobial oxidoreductive enzymes represent a new class of materials with improved synergistic performance. Moreover, the Lac and the AgNPs different antimicrobial action, both in time and mechanism, may also constitute a new alternative to reduce the probability of developing resistance-associated mutations. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative examination of adsorption of serum proteins on HSA- and PLGA-based nanoparticles using SDS-PAGE and LC-MS.

PubMed

Gossmann, R; Fahrländer, E; Hummel, M; Mulac, D; Brockmeyer, J; Langer, K

2015-06-01

The behavior of nanosized drug carrier systems under cell culture conditions and therefore also the destiny in the body are highly influenced by the protein corona, which is formed upon entering a biological environment. Some of the adsorbed proteins, named opsonins, lead to a shortened plasma circulation half-life of the nanoparticles. Others are attributed to promote the transport of nanoparticles into other compartments of the body, just to mention two examples. Hence, detailed knowledge concerning the composition of the protein corona is of great importance. The aim of this work was to investigate the influence of the nanoparticle starting material and the surface modification on the composition of the adsorbed serum proteins in a cell culture environment. Therefore, positively charged nanoparticles based on the biodegradable polymer poly(dl-lactide-co-glycolide) (PLGA) stabilized with didodecyldimethylammonium bromide (DMAB) and negatively charged nanoparticles based on human serum albumin (HSA) were prepared and modified with hydrophilic polymers. By incubating the nanoparticles with fetal bovine serum (FBS) the adsorption of serum proteins on the colloidal system was investigated. Using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) a semi-quantitative analysis of the protein corona was performed and after enzymatic in-solution-digestion the adsorbed proteins were identified using high resolution LC-MS. Our study accentuates the influence of the core material, surface charge, and surface modification on the amount and nature of the adsorbed proteins. The combination of SDS-PAGE and LC-MS turns out to be a simple and reliable method to investigate the protein corona of nanoparticles. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of different desolvating agents on BSA nanoparticle properties and encapsulation of curcumin

NASA Astrophysics Data System (ADS)

Sadeghi, R.; Moosavi-Movahedi, A. A.; Emam-jomeh, Z.; Kalbasi, A.; Razavi, S. H.; Karimi, M.; Kokini, J.

2014-09-01

The desolvation method was successfully used to prepare nanoparticles from bovine serum albumin (BSA) using ethanol, acetone, and their mixtures (70:30 and 50:50, respectively). Ethanol and mixtures of ethanol and acetone led to the most spherical nanoparticles, while using pure acetone resulted in a mixture of spherical and rod shape nanoparticle. Acetone was the solvent with higher encapsulation efficiency equal to 99.2 ± 0.36 %. The polydispersity values of BSA NPs in this study were 0.045 ± 0.007, 0.065 ± 0.013, 0.091 ± 0.012, and 0.120 ± 0.016 for ethanol (100) 4×, Et:Ac (70:30) 4×, Et:Ac (50:50) 4×, and acetone (100) 3×, respectively. Encapsulation efficiencies of curcumin inside BSA NPs were 19.4 ± 2.2 and 19.8 ± 1.6 % for 1.0 and 1.5 molar ratios of curcumin to BSA, respectively. Crosslinking using glutaraldehyde improved the stability of BSA NPs and curcumin-loaded BSA NPs and both groups of nanoparticles were stable for 1 month; the lyophilized curcumin-loaded BSA NPs were able to redisperse in water. The particle size and polydispersity index of redispersed NPs were higher than the original NPs before lyophilization. The size distribution study shows that after 10 s of sonication most nanoparticles were well dispersed; however, a small but significant fraction formed aggregates. Sonication for 10 s decreased the effective diameter and polydispersity of the redispersed nanoparticles, while increasing the sonication time to 20 s did not show significant changes. In vitro release study of curcumin from BSA NPs showed that these biocompatible nanoparticles have the ability to be used as a carrier to improve controlled release of curcumin.

Manufacture and Drug Delivery Applications of Silk Nanoparticles.

PubMed

Wongpinyochit, Thidarat; Johnston, Blair F; Seib, F Philipp

2016-10-08

Silk is a promising biopolymer for biomedical and pharmaceutical applications due to its outstanding mechanical properties, biocompatibility and biodegradability, as well its ability to protect and subsequently release its payload in response to a trigger. While silk can be formulated into various material formats, silk nanoparticles are emerging as promising drug delivery systems. Therefore, this article covers the procedures for reverse engineering silk cocoons to yield a regenerated silk solution that can be used to generate stable silk nanoparticles. These nanoparticles are subsequently characterized, drug loaded and explored as a potential anticancer drug delivery system. Briefly, silk cocoons are reverse engineered first by degumming the cocoons, followed by silk dissolution and clean up, to yield an aqueous silk solution. Next, the regenerated silk solution is subjected to nanoprecipitation to yield silk nanoparticles - a simple but powerful method that generates uniform nanoparticles. The silk nanoparticles are characterized according to their size, zeta potential, morphology and stability in aqueous media, as well as their ability to entrap a chemotherapeutic payload and kill human breast cancer cells. Overall, the described methodology yields uniform silk nanoparticles that can be readily explored for a myriad of applications, including their use as a potential nanomedicine.

Development of Cy5.5-Labeled Hydrophobically Modified Glycol Chitosan Nanoparticles for Protein Delivery

NASA Astrophysics Data System (ADS)

Chin, Amanda

Therapeutic proteins are often highly susceptible to enzymatic degradation, thus restricting their in vivo stability. To overcome this limitation, delivery systems designed to promote uptake and reduce degradation kinetics have undergone a rapid shift from macro-scale systems to nanomaterial based carriers. Many of these nanomaterials, however, elicit immune responses and may have cytotoxic effects both in vitro and in vivo. The naturally derived polysaccharide chitosan has emerged as a promising biodegradable material and has been utilized for many biomedical applications; nevertheless, its function is often constrained by poor solubility. Glycol chitosan, a derivative of chitosan, can be hydrophobically modified to impart amphiphilic properties that enable the self-assembly into nanoparticles in aqueous media at neutral pH. This nanoparticle system has shown initial success as a therapeutic agent in several model cell culture systems, but little is known about its stability against enzymatic degradation. Therefore, the goal of this research was to investigate the resistance of hydrophobically modified glycol chitosan against enzyme-catalyzed degradation using an in vivo simulated system containing lysozyme. To synthesize the nanoparticles, hydrophobic cholanic acid was first covalently conjugated to glycol chitosan using of N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS). Conjugates were purified by dialysis, lyophilized, and ultra-sonicated to form nanoparticles. Fourier transform infrared (FT-IR) spectroscopy confirmed the binding of 5beta-cholanic acid to the glycol chitosan. Particle size and stability over time were determined with dynamic light scattering (DLS), and particle morphology was evaluated by transmission electron microscopy (TEM). The average diameter of the nanoparticles was approximately 200 nm, which remained stable at 4°C for up to 10 days. Additionally, a near infrared fluorescent (NIRF) dye, Cy5.5, was used to label the glycol chitosan nanoparticles to enable the noninvasive imaging of living cells. A model protein (bovine serum albumin, BSA) was encapsulated within the glycol chitosan nanoparticles, and its loading efficiency was calculated to be 88%. Release profile of the BSA showed that only 4% (cumulative mass) was achieved by day 7. Minimal cytotoxicity was observed after delivery of the chitosan vehicle alone. To test degradation kinetics, the BSA-loaded nanoparticles were incubated with lysozyme for up to 3 hours and were applied in SDS-PAGE to determine if enzyme-catalyzed degradation triggered premature release of the encapsulated protein. Confocal laser scanning microscopy was used to visualize the spatiotemporal distribution of FITC-BSA-loaded glycol chitosan nanoparticles after delivery to the rat osteosarcoma (ROS17/2.8) and mouse calvaria-derived (MC3T3-E1) cells.

Dry powder inhaler formulation of lipid-polymer hybrid nanoparticles via electrostatically-driven nanoparticle assembly onto microscale carrier particles.

PubMed

Yang, Yue; Cheow, Wean Sin; Hadinoto, Kunn

2012-09-15

Lipid-polymer hybrid nanoparticles have emerged as promising nanoscale carriers of therapeutics as they combine the attractive characteristics of liposomes and polymers. Herein we develop dry powder inhaler (DPI) formulation of hybrid nanoparticles composed of poly(lactic-co-glycolic acid) and soybean lecithin as the polymer and lipid constituents, respectively. The hybrid nanoparticles are transformed into inhalable microscale nanocomposite structures by a novel technique based on electrostatically-driven adsorption of nanoparticles onto polysaccharide carrier particles, which eliminates the drawbacks of conventional techniques based on controlled drying (e.g. nanoparticle-specific formulation, low yield). First, we engineer polysaccharide carrier particles made up of chitosan cross-linked with tripolyphosphate and dextran sulphate to exhibit the desired aerosolization characteristics and physical robustness. Second, we investigate the effects of nanoparticle to carrier mass ratio and salt inclusion on the adsorption efficiency, in terms of the nanoparticle loading and yield, from which the optimal formulation is determined. Desorption of the nanoparticles from the carrier particles in phosphate buffer saline is also examined. Lastly, we characterize aerosolization efficiency of the nanocomposite product in vitro, where the emitted dose and respirable fraction are found to be comparable to the values of conventional DPI formulations. Copyright © 2012 Elsevier B.V. All rights reserved.

Comparison of pharmaceutical nanoformulations for curcumin: Enhancement of aqueous solubility and carrier retention.

PubMed

Allijn, Iris E; Schiffelers, Raymond M; Storm, Gert

2016-06-15

Curcumin, originally used in traditional medicine and as a spice, is one of the most studied and most popular natural products of the past decade. It has been described to be an effective anti-inflammatory and anti-cancer drug and protects against chronic diseases such as rheumatoid arthritis and atherosclerosis. Despite these promising pharmacological properties, curcumin is also very lipophilic, which makes its formulation challenging. Ideally the nanocarrier should additionally also retain the encapsulated curcumin to provide target tissue accumulation. In this study we aimed to tackle this aqueous solubility and carrier retention challenge of curcumin by encapsulating curcumin in different nanoparticles. We successfully loaded LDL (30nm), polymeric micelles (80nm), liposomes (180nm) and Intralipid (280nm) with curcumin. The relative loading capacity was inversely related to the size of the particle. The stability for all formulations was determined in fetal bovine serum over a course of 24h. Although all curcumin-nanoparticles were stable in buffer solution, all leaked more than 70% of curcumin under physiological conditions. Altogether, tested nanoparticles do solve the aqueous insolubility problem of curcumin, however, because of their leaky nature, the challenge of carrier retention remains. Copyright © 2016 Elsevier B.V. All rights reserved.

Flash NanoPrecipitation of organic actives via confined micromixing and block copolymer stabilization

NASA Astrophysics Data System (ADS)

Johnson, Brian K.

This dissertation provides a method and the understanding required to produce nanoparticles of organic actives using Flash NanoPrecipitation . The process comprises mixing a solvent phase containing molecularly dissolved amphiphilic block copolymer and an organic active with an anti-solvent. One block of the copolymer precipitates to alter the nucleation and growth of the organic active while the other remains in solution for particle stabilization. A custom built confined impinging jets (CIJ) mixer provides optimum micromixing at the laboratory or full scale within milliseconds. Comparison to other reactor designs is provided. The resulting nanoparticles have functional surfaces tailored to meet the needs of pharmaceutical or specialty chemical formulations. Example beta-carotene nanoparticles with a polyethylene oxide surface are produced at high concentration, high yield, low stabilizer content, and a size suitable for sterile filtration or larger. The technical challenges in nanoparticle production are explained via the characteristic times for mixing, copolymer aggregation, and organic active particle formation. The time for Flash NanoPrecipitation is shown to depend strongly on the time for copolymer aggregation, and control of the organic nucleation versus growth is critical to achieve nanoparticles. Mixing operating lines explain the impact of solubility differences between the colloidal stabilizer and the organic active as function of mixing rate. Techniques to measure the solubility of the copolymer and DeltaG° , DeltaH°, and DeltaS° of micellization are demonstrated. An analytical CIJ mixer is developed by quantifying the characteristic time and physical mechanism of mixing. The methodology described to find an absolute mixing lifetime is also applied to a vortex mixer at a spectrum of flow ratios away from one. Dimensional analysis using the process Damkohler number, defined as the ratio of the mixing to the process time, is applied to precipitation to quantify the induction time through knowledge of the mixing lifetime. Copolymer aggregation without an organic active to kinetically frozen nanoparticles occurs by a "fusion only" mechanism. By analogy to classical precipitation kinetics, the interfacial free energy of a diblock copolymer nanoparticle is determined for the first time. The composite dissertation provides a clear picture of Flash NanoPrecipitation for future research and applications.

Mechanistic analysis of Zein nanoparticles/PLGA triblock in situ forming implants for glimepiride.

PubMed

Ahmed, Osama Abdelhakim Aly; Zidan, Ahmed Samir; Khayat, Maan

2016-01-01

The study aims at applying pharmaceutical nanotechnology and D-optimal fractional factorial design to screen and optimize the high-risk variables affecting the performance of a complex drug delivery system consisting of glimepiride-Zein nanoparticles and inclusion of the optimized formula with thermoresponsive triblock copolymers in in situ gel. Sixteen nanoparticle formulations were prepared by liquid-liquid phase separation method according to the D-optimal fractional factorial design encompassing five variables at two levels. The responses investigated were glimepiride entrapment capacity (EC), particle size and size distribution, zeta potential, and in vitro drug release from the prepared nanoparticles. Furthermore, the feasibility of embedding the optimized Zein-based glimepiride nanoparticles within thermoresponsive triblock copolymers poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) in in situ gel was evaluated for controlling glimepiride release rate. Through the systematic optimization phase, improvement of glimepiride EC of 33.6%, nanoparticle size of 120.9 nm with a skewness value of 0.2, zeta potential of 11.1 mV, and sustained release features of 3.3% and 17.3% drug released after 2 and 24 hours, respectively, were obtained. These desirability functions were obtained at Zein and glimepiride loadings of 50 and 75 mg, respectively, utilizing didodecyldimethylammonium bromide as a stabilizer at 0.1% and 90% ethanol as a common solvent. Moreover, incorporating this optimized formulation in triblock copolymers-based in situ gel demonstrated pseudoplastic behavior with reduction of drug release rate as the concentration of polymer increased. This approach to control the release of glimepiride using Zein nanoparticles/triblock copolymers-based in situ gel forming intramuscular implants could be useful for improving diabetes treatment effectiveness.

Andrographolide-loaded nanoparticles for brain delivery: Formulation, characterisation and in vitro permeability using hCMEC/D3 cell line.

PubMed

Guccione, Clizia; Oufir, Mouhssin; Piazzini, Vieri; Eigenmann, Daniela Elisabeth; Jähne, Evelyn Andrea; Zabela, Volha; Faleschini, Maria Teresa; Bergonzi, Maria Camilla; Smiesko, Martin; Hamburger, Matthias; Bilia, Anna Rita

2017-10-01

Andrographolide (AG) is a major diterpenoid of the Asian medicinal plant Andrographis paniculata which has shown exciting pharmacological potential for the treatment of inflammation-related pathologies including neurodegenerative disorders. Conversely, the low bioavailability of AG still represents a limiting factor for its use. To overcome these limitations, AG was loaded into human serum albumin based nanoparticles (HSA NPs) and poly ethylcyanoacrylate nanoparticles (PECA NPs). HSA NPs were prepared by thermal (HSAT AG NPs) and chemical cross-linking (HSAC AG NPs), while PECA AG NPs were produced by emulsion-polymerization. NPs were characterized in terms of size, zeta (ζ)-potential, polydispersity, and release studies of AG. In addition, the ability of free AG and AG-loaded in PECA and HSAT NPs to cross the blood-brain barrier (BBB) was assessed using an in vitro BBB model based on human cerebral microvascular endothelial cell line (hCMEC/D3). For BBB drug permeability assays, a quantitative UPLC-MS/MS method for AG in Ringer HEPES buffer was developed and validated according to international regulatory guidelines for industry. Free AG did not permeate the BBB model, as also predicted by in silico studies. HSAT NPs improved by two-fold the permeation of AG while maintaining the integrity of the cell layer, while PECA NPs temporarily disrupted BBB integrity. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of rutile titania dioxide nanoparticles on the mechanical property, thermal stability, weathering resistance and antibacterial property of styrene acrylic polyurethane coating

NASA Astrophysics Data System (ADS)

Vuong Nguyen, Thien; Nguyen, Tuan Anh; Dao, Phi Hung; Phuc Mac, Van; Hiep Nguyen, Anh; Thanh Do, Minh; Nguyen, The Huu

2016-12-01

This study aims to enhance the mechanical properties, thermal stability, weathering resistance and antibacterial property of a styrene acrylic polyurethane coating by adding rutile titania dioxide (R-TiO2) nanoparticles in coating formulation. The styrene acrylic polyurethane/R-TiO2 nanocomposite had been prepared by using ultrasonication. The effects of nanoparticles on the mechanical properties, thermal stability and weathering resistance of as-prepared coatings were investigated by using the adhesion strength and ball impact tests, the Fourier transform infrared and UV-vis analyses, thermogravimetric analysis (TGA), and UV/condensation weathering chamber equipped with UVA-340 fluorescent lamps, respectively. The disperse quality of nanoparticles in the coating was examined by using the field emission scanning electron microscope (FESEM). The mechanical test results showed that suitable content of R-TiO2 nanoparticles in the nanocomposite coating was 2 wt%. The FESEM images indicated that the nanoparticles were dispersed homogeneously into the entire volume of the coating. For the nanocomposite prepared by 3 h of ultrasonication, the average size of nanoparticles was in range of 40-50 nm. The ball impact and adhesion tests showed that the incorporation of nanoparticles into the coating significantly enhanced the impact strength from 120 to 145 kg cm and increased the adhesion from level 1 to level 0. The TGA test illustrated that in presence of nanoparticles, the decomposition temperature of coating increased from 146.9 °C to 154.21 °C. For the temperature at 50% loss in mass (T 50%), it was found that the T 50% of the neat coating is 351.86 °C. Adding the 2 wt% R-TiO2 nanoparticles into coating increased the T 50% value to 360.06 °C. After UV/condensation accelerated weathering test (30 cycles), the significant improvement in weight loss, impact strength and adhesion of the neat coating was observed with the presence of nanoparticles. The antibacterial test showed that in the nanocomposite coating, R-TiO2 nanoparticles exhibited their photocatalytic effect in the inhibition against E. coli bacterial growth. Incorporating 2 wt% of R-TiO2 nanoparticles into the coating reduced the bacterial concentration by 6.1% after 60 min of culture.

Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

PubMed

Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

2014-10-15

Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system. Copyright © 2014 Elsevier B.V. All rights reserved.

Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach.

PubMed

Rose, Fabrice; Wern, Jeanette Erbo; Ingvarsson, Pall Thor; van de Weert, Marco; Andersen, Peter; Follmann, Frank; Foged, Camilla

2015-07-28

The purpose of this study was to design a novel and versatile adjuvant intended for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose-6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity characterized by antibodies and Th1/Th17 responses. Such responses are important for the protection against diseases caused by intracellular bacteria such as Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were engineered using an oil-in-water single emulsion method and a quality-by-design approach was adopted to define the optimal operating space (OOS). Four critical process parameters (CPPs) were identified, including the acetone concentration in the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the lipid-to-total solid ratio, and the total concentration. The CPPs were linked to critical quality attributes consisting of the particle size, polydispersity index (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A central composite face-centered design was performed followed by multiple linear regression analysis. The size, PDI, enthalpy of the phase transition and yield were successfully modeled, whereas the models for the zeta-potential and the stability were poor. Cryo-transmission electron microscopy revealed that the main structural effect on the nanoparticle architecture is caused by the use of PVA, and two different morphologies were identified: i) A PLGA core coated with one or several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid membrane structures. The optimal formulation, identified from the OOS, was evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses that were similar in quality and magnitude to the response induced by DDA/TDB liposomes, showing that the adjuvant properties of DDA/TDB are maintained in the PLGA hybrid matrix. This study demonstrates the complexity of formulation design for the engineering of a hybrid lipid-polymer nanoparticle adjuvant. Copyright © 2015 Elsevier B.V. All rights reserved.

Capillary electrophoresis with indirect UV detection for the determination of stabilizers and citrates present in human albumin solutions.

PubMed

Jaworska, Małgorzata; Cygan, Paulina; Wilk, Małgorzata; Anuszewska, Elzbieta

2009-08-15

Sodium caprylate and N-acetyltryptophan are the most frequently used stabilizers that protect the albumin from aggregation or heat induced denaturation. In turn citrates - excipients remaining after fractionation process - can be treated as by-product favoring leaching aluminum out of glass containers whilst albumin solution is stored. With ionic nature these substances have all the markings of a subject for capillary electrophoresis analysis. Thus CE methods were proposed as new approach for quality control of human albumin solution in terms of determination of stabilizers and citrates residue. Human albumin solutions both 5% and 20% from various manufacturers were tested. Indirect detection mode was set to provide sufficient detectability of analytes lacking of chromophores. As being anions analytes were separated with reversed electroosmotic flow. As a result of method optimization two background electrolytes based on p-hydroxybenzoic acid and 2,6-pyridinedicarboxylic acid were selected for stabilizers and citrates separation, respectively. The optimized methods were successfully validated. For citrates that require quantification below 100microM the method demonstrated the precision less than 4% and the limit of detection at 4microM. In order to check the new methods accuracy and applicability the samples were additionally tested with selected reference methods. The proposed methods allow reliable quantification of stabilizers and citrates in human albumin solution that was confirmed by method validation as well as result comparison with reference methods. The CE methods are considered to be suitable for quality control yet simplifying and reducing cost of analysis.

Characterization of polymer adsorption onto drug nanoparticles using depletion measurements and small-angle neutron scattering.

PubMed

Goodwin, Daniel J; Sepassi, Shadi; King, Stephen M; Holland, Simon J; Martini, Luigi G; Lawrence, M Jayne

2013-11-04

Production of polymer and/or surfactant-coated crystalline nanoparticles of water-insoluble drugs (nanosuspensions) using wet bead milling is an important formulation approach to improve the bioavailability of said compounds. Despite the fact that there are a number of nanosuspensions on the market, there is still a deficiency in the characterization of these nanoparticles where further understanding may lead to the rational selection of polymer/surfactant. To this end small-angle neutron scattering (SANS) measurements were performed on drug nanoparticles milled in the presence of a range of polymers of varying molecular weight. Isotopic substitution of the aqueous solvent to match the scattering length density of the drug nanoparticles (i.e., the technique of contrast matching) meant that neutron scattering resulted only from the adsorbed polymer layer. The layer thickness and amount of hydroxypropylcellulose adsorbed on nabumetone nanoparticles derived from fitting the SANS data to both model-independent and model dependent volume fraction profiles were insensitive to polymer molecular weight over the range Mv = 47-112 kg/mol, indicating that the adsorbed layer is relatively flat but with tails extending up to approximately 23 nm. The constancy of the absorbed amount is in agreement with the adsorption isotherm determined by measuring polymer depletion from solution in the presence of the nanoparticles. Insensitivity to polymer molecular weight was similarly determined using SANS measurements of nabumetone or halofantrine nanoparticles stabilized with hydroxypropylmethylcellulose or poly(vinylpyrrolidone). Additionally SANS studies revealed the amount adsorbed, and the thickness of the polymer layer was dependent on both the nature of the polymer and drug particle surface. The insensitivity of the adsorbed polymer layer to polymer molecular weight has important implications for the production of nanoparticles, suggesting that lower molecular weight polymers should be used when preparing nanoparticles by wet bead milling since nanoparticle formation is more rapid but with no likely consequence on the resultant physical stability of the nanoparticles.

Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release.

PubMed

Chhabra, Resham; Grabrucker, Andreas M; Veratti, Patrizia; Belletti, Daniela; Boeckers, Tobias M; Vandelli, Maria Angela; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara

2014-08-25

Polymeric nanoparticles (NPs) offer a promising approach for therapeutic intracellular delivery of proteins, conventionally hampered by short half-lives, instability and immunogenicity. Remarkably, NPs uptake occurs via endocytic internalization leading to NPs content's release within lysosomes. To overcome lysosomal degradation and achieve NPs and/or loaded proteins release into cytosol, we propose the formulation of hybrid NPs by adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as pH sensitive component in the formulation of poly-lactide-co-glycolide (PLGA) NPs. Hybrid NPs, featured by different DOPE/PLGA ratios, were characterized in terms of structure, stability and lipid organization within the polymeric matrix. Experiments on NIH cells and rat primary neuronal cultures highlighted the safety profile of hybrid NPs. Moreover, after internalization, NPs are able to transiently destabilize the integrity of lysosomes in which they are taken up, speeding their escape and favoring cytoplasmatic localization. Thus, these DOPE/PLGA-NPs configure themselves as promising carriers for intracellular protein delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation and characterization compatible pellets for immobilization of colloidal sulphur nanoparticles

NASA Astrophysics Data System (ADS)

Adlim, M.; Zarlaida, F.; Khaldun, I.; Dewi, R.; Jamilah, M.

2018-03-01

Mercury pollution in atmosphere is dominated by mercury vapour release from coal burning and gold-amalgam separation in gold mining. The initial steps in formulating a compatible mercury absorbent for mercury stabilization was fabrication of pellet supported colloidal sulphur. Sulphur is used to stabilize mercury vapour by formation of metacinnabar that has much lower toxicity. The sulphur reactivity toward mercury vapour can be enhanced by using colloidal sulphur nanoparticles immobilized on compatible pellets. Clay pellets would have heat resistance but in fact, they were less stable in aqueous solution although their stability increased with inclusion of rice husk ash and sawdust or pineapple leaf fibre in the composite. Pellets made of rice husk ash and polyvinyl acetate were stable in water at least for 24 hours. Sulphur from thiosulfate precursor that immobilized onto surface of pellet using chitosan as the stabilizer and the binding agent gave lower sulphur content compared to sulphur from other precursors (sulphur powder and sulphur-CS2). Sulphur from thiosulfate precursor was in form of colloid, has nanosize, and disperse particles on the surface of rice husk ash pellets. Sulphur immobilization methods affect on sulphur particles exposure on the pellet surface.

Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of EPR effect and albumin-protein interactions using S-nitrosated human serum albumin dimer.

PubMed

Kinoshita, Ryo; Ishima, Yu; Chuang, Victor T G; Nakamura, Hideaki; Fang, Jun; Watanabe, Hiroshi; Shimizu, Taro; Okuhira, Keiichiro; Ishida, Tatsuhiro; Maeda, Hiroshi; Otagiri, Masaki; Maruyama, Toru

2017-09-01

In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane ® ). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models. In the high vascular permeability C26 murine colon cancer subcutaneous inoculation model, SNO-HSA Dimer enhanced tumor selectivity of nab-PTX, and attenuated myelosuppression. SNO-HSA Dimer also augmented the tumor growth inhibition of nab-PTX in low vascular permeability B16 murine melanoma subcutaneous inoculation model. Furthermore, nab-PTX therapy combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. In conclusion, SNO-HSA Dimer could enhance the therapeutic effect of nab-PTX even in low vascular permeability or intractable pancreatic cancers. The possible underlying mechanisms of action of SNO-HSA Dimer were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polyhydroxy surfactants for the formulation of lipid nanoparticles (SLN and NLC): effects on size, physical stability and particle matrix structure.

PubMed

Kovacevic, A; Savic, S; Vuleta, G; Müller, R H; Keck, C M

2011-03-15

The two polyhydroxy surfactants polyglycerol 6-distearate (Plurol(®)Stearique WL1009 - (PS)) and caprylyl/capryl glucoside (Plantacare(®) 810 - (PL)) are a class of PEG-free stabilizers, made from renewable resources. They were investigated for stabilization of aqueous solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC) dispersions. Production was performed by high pressure homogenization, analysis by photon correlation spectroscopy (PCS), laser diffraction (LD), zeta potential measurements and differential scanning calorimetry (DSC). Particles were made from Cutina CP as solid lipid only (SLN) and its blends with Miglyol 812 (NLC, the blends containing increasing amounts of oil from 20% to 60%). The obtained particle sizes were identical for both surfactants, about 200 nm with polydispersity indices below 0.20 (PCS), and unimodal size distribution (LD). All dispersions with both surfactants were physically stable for 3 months at room temperature, but Plantacare (PL) showing a superior stability. The melting behaviour and crystallinity of bulk lipids/lipid blends were compared to the nanoparticles. Both were lower for the nanoparticles. The crystallinity of dispersions stabilized with PS was higher, the zeta potential decreased with storage time associated with this higher crystallinity, and leading to a few, but negligible larger particles. The lower crystallinity particles stabilized with PL remained unchanged in zeta potential (about -50 mV) and in size. These data show that surfactants have a distinct influence on the particle matrix structure (and related stability and drug loading), to which too little attention was given by now. Despite being from the same surfactant class, the differences on the structure are pronounced. They are attributed to the hydrophobic-lipophilic tail structure with one-point anchoring in the interface (PL), and the loop conformation of PS with two hydrophobic anchor points, i.e. their molecular structure and its interaction with the matrix surface and matrix bulk. Analysis of the effects of the surfactants on the particle matrix structure could potentially be used to further optimization of stability, drug loading and may be drug release. Copyright © 2011 Elsevier B.V. All rights reserved.

Preparation, structure and magnetic properties of synthetic ferrihydrite nanoparticles

NASA Astrophysics Data System (ADS)

Stolyar, S. V.; Yaroslavtsev, R. N.; Bayukov, O. A.; Balaev, D. A.; Krasikov, A. A.; Iskhakov, R. S.; Vorotynov, A. M.; Ladygina, V. P.; Purtov, K. V.; Volochaev, M. N.

2018-03-01

Superparamagnetic ferrihydrite powders with average nanoparticle sizes of 2.5 nm produced by the chemical deposition method. Static and dynamic magnetic properties are measured. As a result of ultrasonic treatment in the cavitation regime of suspensions of ferrihydrite powders in a solution of the albumin protein, the Fe ions are reduced to the metallic state. A sol of ferrihydrite nanoparticles is prepared in an aqueous solution of arabinogalactan polysaccharide.

[Efficacy of using zinc oxide nanoparticles in nutrition. Experiments on the laboratory animal].

PubMed

Raspopov, R V; Trushina, E N; Mustafina, O K; Tananova, O N; Gmoshinskiĭ, I V; Khotimchenko, S A

2011-01-01

In experiments on rats there was researched bioavailability of zinc oxide (ZnO) nanoparticles. There were determined the content of Zn in blood serum and tibia, intestinal uptake of macromolecules of egg albumin, some hematological, biochemical and immune indices, liver cells apoptosis. The results obtained show that the uptake of nanoparticles of ZnO enables restoration of this microelement status damaged by zinc deficit diet.

Preparation of albumin based nanoparticles for delivery of fisetin and evaluation of its cytotoxic activity.

PubMed

Ghosh, Pooja; Singha Roy, Atanu; Chaudhury, Susmitnarayan; Jana, Saikat Kumar; Chaudhury, Koel; Dasgupta, Swagata

2016-05-01

Fisetin is a well known flavonoid that shows several properties such as antioxidant, antiviral and anticancer activities. Its use in the pharmaceutical field is limited due to its poor aqueous solubility which results in poor bioavailability and poor permeability. The aim of our present study is to prepare fisetin loaded human serum albumin nanoparticles to improve its bioavailability. The nanoparticles were prepared by a desolvation method and characterized by spectroscopic and microscopic techniques. The particles were smooth and spherical in nature with an average size of 220 ± 8 nm. The encapsulation efficiency was found to be 84%. The in vitro release profile showed a biphasic pattern and the release rate increases with increase in ionic strength of solution. We have also confirmed the antioxidant activity of the prepared nanoparticles by a DPPH (2,2-diphenyl-1-picrylhydrazyl) assay. Further its anticancer activity was evaluated using MCF-7 breast cancer cell lines. Our findings suggest that fisetin loaded HSA nanoparticles could be used to transfer fisetin to target areas under specific conditions and thus may find use as a delivery vehicle for the flavonoid. Copyright © 2016 Elsevier B.V. All rights reserved.

Investigation of Stabilised Batu Pahat Soft Soil Pertaining on its CBR and Permeability Properties for Road Construction

NASA Astrophysics Data System (ADS)

Mohd Idrus, M. M.; Singh, J. S. M.; Musbah, A. L. A.; Wijeyesekera, D. C.

2016-07-01

Soil stabilization by adding materials such as cement, lime and bitumen is one of the effective methods for improving the geotechnical properties of soils [11] Nano-particle is one of the newest additives and many studies about using nano-particle in soil improvement has been done but it was given less attention when soft clay soils stabilization is concerned. To evaluate the strength characteristics of stabilized Batu Pahat soft clay, laboratory investigation on early strength gained by the stabilized soil must be conducted to formulate a suitable and economical mix design [10]. To achieve such purpose, the study examined the effect of NanoClay on the California Bearing Ratio and the Permeability of soft clay. The results gained shows that the Nano-Clay is able to increase the strength of the soft clay [9]. The California Bearing Ratio of the soil is increase significantly where the results for the highest percentage of admixture is 14.4% while the permeability of the soil decreases significantly with increasing Nano-Clay whereby the results of the highest percentage of admixture is 2.0187x10-11 m/s. After doing this research, it is proven that Nano-clay can contribute towards better soil stabilization and enhance the quality of soil as subgrade and foundation at large.

A facile route for the synthesis of Co, Ni and Cu metallic nanoparticles with potential antimicrobial activity using novel metallosurfactants

NASA Astrophysics Data System (ADS)

Kaur, Gurpreet; Singh, Prabjot; Mehta, S. K.; Kumar, Sandeep; Dilbaghi, Neeraj; Chaudhary, Ganga Ram

2017-05-01

The work deals with optimizing a methodology for fabrication of monodisperse metallic nanoparticles (active against microbes) using micellar core of amine based metallosurfactant. Novel double chained amine metallosurfactants of the type [M(C12H25NH2)2] (where M is copper, nickel and cobalt) have been synthesized and characterized with elemental analysis, Fourier Transform Infrared spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and thermogravimetric analysis (TGA). Further, study of theaggregated structures (i.e. bilayer) of these lipophilic metallosurfactants in various alcohols has been carried out. Thermodynamics parameters of reverse micellization have also been estimated. The process of micellization is spontaneous and entropy driven. Prepared metallosurfactants have been utilized as precursors for the fabrication of metallic nanoparticles (NPs) of Co, Ni and Cu. The method is validated for all the three studied transition metals for the preparation of metallic nanoparticles. This approach offers better results in terms of size, shape, morphology, distribution and stability of NPs. Characterization of NPs is done by UV-vis, X-Ray Diffraction (XRD), Transmission Emission Microscopy (TEM) and Dynamic light scattering (DLS). Prepared metallosurfactants and NPs have been trialled for antimicrobial activity against three pathogenic microbes viz. Bacillus Cereus (gram +ve bacterium), Klebsiella Pneumoniae (gram -ve bacterium) and Curvularia lunata (fungus) and best results are shown by Cu NPs. Furthermore, interaction of metallic NPs with bovine serum albumin (BSA) has been estimated.

Regulation the morphology of cationized gold nanoparticles for effective gene delivery.

PubMed

Zhang, Peng; Li, Bangbang; Du, Jianwei; Wang, Youxiang

2017-09-01

Recent research indicated that the morphology of nanoparticles could result in distinct biological behaviors, thus played an important role in designing efficient gene delivery systems. Among them, gold nanoparticles (AuNPs) with various shapes were widely studied due to the good biocompatibility and easy modification ability. Our recent research indicated that polyethyleneimine-g-bovine serum albumin (BSA-PEI) as non-viral gene vector showed good colloid stability and high transfection efficiency. In this work, BSA-PEI was utilized to modify gold nanospheres (AuNSs) and gold nanorods (AuNRs) to investigate the influence of the morphology on gene delivery. Both AuNS@BSA-PEI and AuNR@BSA-PEI nanoparticles condensed DNA effectively at N/P ratio above 5 and maintained spherical or rod-like morphology respectively. Due to the higher surface charge density at the tips, the rod-like gene complexes were prone to use the tips to contact with cell membrane, which facilitated to be uptaked by HepG2 cells. The endocytosis inhibition experiments showed some differences in the endocytic pathway. Gene transfection experiment showed that the rod-like complexes had almost 100-fold higher of transfection level than that of spherical complexes at the N/P ratio of 20. This work provided a potential strategy for further design of gene vectors with improved transfection results by adjusting the morphology of gene vectors. Copyright © 2017. Published by Elsevier B.V.

Coalescence of functional gold and monodisperse silver nanoparticles mediated by black Panax ginseng Meyer root extract

PubMed Central

Wang, Dandan; Markus, Josua; Kim, Yeon-Ju; Wang, Chao; Jiménez Pérez, Zuly Elizabeth; Ahn, Sungeun; Aceituno, Verónica Castro; Mathiyalagan, Ramya; Yang, Deok Chun

2016-01-01

A rapid biological synthesis of multifunctional gold nanoparticle (AuNp) and monodisperse silver nanoparticle (AgNp) was achieved by an aqueous extract of black Panax ginseng Meyer root. The physicochemical transformation into black ginseng (BG) greatly enhanced the pharmacological activities of white ginseng and its minor ginsenoside content. The optimal temperature conditions and kinetics of bioreduction were investigated. Formation of BG-AuNps and BG-AgNps was verified by ultraviolet–visible spectrophotometry at 548 and 412 nm, respectively. The biosynthesized BG-AgNps were spherical and monodisperse with narrow distribution, while BG-AuNps were icosahedral-shaped and moderately polydisperse. Synthesized nanoparticles exhibited long-term stability in buffers of pH 7.0–8.0 and biological media (5% bovine serum albumin) at an ambient temperature and at 37°C. BG-AgNps showed effective antibacterial activity against Escherichia coli and Staphylococcus aureus. BG-AuNps and BG-AgNps demonstrated increased scavenging activity against 2,2-diphenyl-1-picrylhydrazyl free radicals. In addition, BG-AuNps and BG-AgNps were nontoxic to HaCaT and MCF-7 cells; the latter showed no cytotoxicity at concentrations lower than 10 µg/mL. At higher concentrations, BG-AgNps exhibited apparent apoptotic activity in MCF-7 breast cancer cell line through reactive oxygen species generation and nuclear fragmentation. PMID:28008248

Silica- and perfluoro-based nanoparticular polymeric network for the skin protection against organophosphates

NASA Astrophysics Data System (ADS)

Bignon, Cécile; Amigoni, Sonia; Guittard, Frédéric

2016-06-01

Due to their small size, nanoparticles possess unique properties such as high absorption or pollutant degradation, making them useful for skin protection against chemicals. By covalently grafting to a hydrophobically modified alkali-soluble emulsion (HASE), a thickening polymer, nanoparticles can be dispersed as gels in water at neutral pH. With this modification the potential aggregation and toxicity typical of nanoparticles are avoided. Once integrated into a cosmetic formula, these gels can be spread onto skin to afford protective barriers. This paper reports (1) the benefit of SiO2 nanoparticles grafted to a perfluorocarbon HASE polymer (HASE-F/SiO2) which is then integrated into a new formula and it is influence on the efficacy against the penetration of paraoxone, as well as (2) the stability of the barrier cream (BC) and (3) how the homogenous dispersion of nanoparticles maintains a high active surface area of SiO2 nanoparticles. The efficiency of the new active topical skin protectant was proved at different doses (5-27 mg cm-2), under occlusive conditions and validated on human skin. Therefore, the combination of the HASE-F polymer, nanoparticle grafting, and polyvinylpyrrolidone and glycerol formulation led to a very effective active BC.

Design of curcumin-loaded PLGA nanoparticles formulation with enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo.

PubMed

Anand, Preetha; Nair, Hareesh B; Sung, Bokyung; Kunnumakkara, Ajaikumar B; Yadav, Vivek R; Tekmal, Rajeshwar R; Aggarwal, Bharat B

2010-02-01

Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with antioxidant, anti-inflammatory, antiproliferative, anticancer, antidiabetic, antirheumatic, and antiviral effects, but its optimum potential is limited by its lack of solubility in aqueous solvents and poor oral bioavailability. We employed a polymer-based nanoparticle approach to improve bioavailability. Curcumin was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and a stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy indicated a particle diameter of 80.9 nm. This curcumin, renamed from hereon "as curcumin (NP)", was characterized for its biological activity. In vitro curcumin (NP) exhibited very rapid and more efficient cellular uptake than curcumin. Estrase staining revealed that curcumin (NP) was at least as potent as or more potent than curcumin in inducing apoptosis of leukemic cells and in suppressing proliferation of various tumor cell lines. When examined by electrophoretic gel shift mobility assay, curcumin (NP) was more active than curcumin in inhibiting TNF-induced NF-kappaB activation and in suppression of NF-kappaB-regulated proteins involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). In mice, curcumin (NP) was more bioavailable and had a longer half-life than curcumin. Overall we demonstrate that curcumin-loaded PLGA nanoparticles formulation has enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo over curcumin.

PEGylated human serum albumin (HSA) nanoparticles: preparation, characterization and quantification of the PEGylation extent

NASA Astrophysics Data System (ADS)

Fahrländer, E.; Schelhaas, S.; Jacobs, A. H.; Langer, K.

2015-04-01

Modification with poly(ethylene glycol) (PEG) is a widely used method for the prolongation of plasma half-life of colloidal carrier systems such as nanoparticles prepared from human serum albumin (HSA). However, the quantification of the PEGylation extent is still challenging. Moreover, the influence of different PEG derivatives, which are commonly used for nanoparticle conjugation, has not been investigated so far. The objective of the present study is to develop a method for the quantification of PEG and to monitor the influence of diverse PEG reagents on the amount of PEG linked to the surface of HSA nanoparticles. A size exclusion chromatography method with refractive index detection was established which enabled the quantification of unreacted PEG in the supernatant. The achieved results were confirmed using a fluorescent PEG derivative, which was detected by photometry and fluorimetry. Additionally, PEGylated HSA nanoparticles were enzymatically digested and the linked amount of fluorescently active PEG was directly determined. All the analytical methods confirmed that under optimized PEGylation conditions a PEGylation efficiency of up to 0.5 mg PEG per mg nanoparticle could be achieved. Model calculations made a ‘brush’ conformation of the PEG chains on the particle surface very likely. By incubating the nanoparticles with fetal bovine serum the reduced adsorption of serum proteins on PEGylated HSA nanoparticles compared to non-PEGylated HSA nanoparticles was demonstrated using sodium dodecylsulfate polyacrylamide gel electrophoresis. Finally, the positive effect of PEGylation on plasma half-life was demonstrated in an in vivo study in mice. Compared to unmodified nanoparticles the PEGylation led to a four times larger plasma half-life.

Continuous microfluidic assembly of biodegradable poly(beta-amino ester)/DNA nanoparticles for enhanced gene delivery.

PubMed

Wilson, David R; Mosenia, Arman; Suprenant, Mark P; Upadhya, Rahul; Routkevitch, Denis; Meyer, Randall A; Quinones-Hinojosa, Alfredo; Green, Jordan J

2017-06-01

Translation of biomaterial-based nanoparticle formulations to the clinic faces significant challenges including efficacy, safety, consistency and scale-up of manufacturing, and stability during long-term storage. Continuous microfluidic fabrication of polymeric nanoparticles has the potential to alleviate the challenges associated with manufacture, while offering a scalable solution for clinical level production. Poly(beta-amino esters) (PBAE)s are a class of biodegradable cationic polymers that self-assemble with anionic plasmid DNA to form polyplex nanoparticles that have been shown to be effective for transfecting cancer cells specifically in vitro and in vivo. Here, we demonstrate the use of a microfluidic device for the continuous and scalable production of PBAE/DNA nanoparticles followed by lyophilization and long term storage that results in improved in vitro efficacy in multiple cancer cell lines compared to nanoparticles produced by bulk mixing as well as in comparison to widely used commercially available transfection reagents polyethylenimine and Lipofectamine® 2000. We further characterized the nanoparticles using nanoparticle tracking analysis (NTA) to show that microfluidic mixing resulted in fewer DNA-free polymeric nanoparticles compared to those produced by bulk mixing. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1813-1825, 2017. © 2017 Wiley Periodicals, Inc.

Preparation and Evaluation of Montelukast Sodium Loaded Solid Lipid Nanoparticles

PubMed Central

Priyanka, K; Sathali, A Abdul Hasan

2012-01-01

Solid lipid nanoparticles (SLNs) are an alternative carrier system used to load the drug for targeting, to improve the bioavailability by increasing its solubility, and protecting the drug from presystemic metabolism. The avoidance of presystemic metabolism is due to the nano-metric size range, so that the liver cannot uptake the drug from the delivery system and is not metabolized by the liver. Montelukast sodium is an anti-asthmatic drug, because of its poor oral bioavailability, presystemic metabolism, and decreased half-life; it was chosen to formulate as the solid lipid nanoparticle (SLN) system by hot homogenization followed by an ultrasonication method, to overcome the above. Compritol ATO 888, stearic acid, and glyceryl monostearate were used as a lipid matrix and polyvinyl alcohol as a surfactant. The prepared formulations have been evaluated for entrapment efficiency, drug content, in vitro drug release, particle size analysis, scanning electron microscopy, Fourier transform-infrared studies (FT-IR), differential scanning calorimetry (DSC), and stability. Particle size analysis revealed that the SLN prepared from the higher melting point lipid showed a larger particle size and with increased carbon chain length of the fatty acids. Entrapment efficiency (EE) was ranging from 42% to 92%. In vitro release studies showed maximum cumulative drug release was obtained for F 1 (59.1%) containing stearic acid, and the lowest was observed for F 18 (28.1%) containing compritol ATO 888 after 12 h and all the formulations followed first-order release kinetics. FT-IR and DSC studies revealed no interaction between drug and lipids. Studies showed that increase in lipid concentration, increased particle size, EE, and maintained the sustained release of drug. Among all, compritol ATO 888 was chosen as the best lipid for formulating SLN because it had high EE and sustained the drug release. PMID:23112531

Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC.

PubMed

Gonzalez-Mira, E; Egea, M A; Garcia, M L; Souto, E B

2010-12-01

Packaging small drug molecules, such as non-steroidal anti-inflammatory drugs (NSAIDs) into nanoparticulate systems has been reported as a promising approach to improve the drug's bioavailability, biocompatibility and safety profiles. In the last 20 years, lipid nanoparticles (lipid dispersions) entered the nanoparticulate library as novel carrier systems due to their great potential as an alternative to other systems such as polymeric nanoparticles and liposomes for several administration routes. For ocular instillation nanoparticulate carriers are required to have a low mean particle size, with the lowest polydispersity as possible. The purpose of this work was to study the combined influence of 2-level, 4-factor variables on the formulation of flurbiprofen (FB), a lipophilic NSAID, in lipid carriers currently named as nanostructured lipid carriers (NLC). NLC were produced with stearic acid (SA) and castor oil (CO) stabilized by Tween® 80 (non-ionic surfactant) in aqueous dispersion. A 2(4) full factorial design based on 4 independent variables was used to plan the experiments, namely, the percentage of SA with regard to the total lipid, the FB concentration, the stabilizer concentration, and the storage conditions (i.e., storage temperature). The effects of these parameters on the mean particle size, polydispersity index (PI) and zeta potential (ZP) were investigated as dependent variables. The optimization process was achieved and the best formulation corresponded to the NLC formulation composed of 0.05 (wt%) FB, 1.6 (wt%) Tween® 80 and a 50:50 ratio of SA to CO, with an average diameter of 288 nm, PI 0.245 of and ZP of -29 mV. This factorial design study has proven to be a useful tool in optimizing FB-loaded NLC formulations. Stability of the optimized NLC was predicted using a TurbiScanLab® and the ocular tolerance was assessed in vitro and in vivo by the Eytex® and Draize test, respectively. The developed systems were shown physico-chemically stable with high tolerance for eye instillation. Copyright © 2010 Elsevier B.V. All rights reserved.

Harmonic responses and cavitation activity of encapsulated microbubbles coupled with magnetic nanoparticles.

PubMed

Gu, Yuyang; Chen, Chuyi; Tu, Juan; Guo, Xiasheng; Wu, Hongyi; Zhang, Dong

2016-03-01

Encapsulated microbubbles coupled with magnetic nanoparticles, one kind of hybrid agents that can integrate both ultrasound and magnetic resonance imaging/therapy functions, have attracted increasing interests in both research and clinic communities. However, there is a lack of comprehensive understanding of their dynamic behaviors generated in diagnostic and therapeutic applications. In the present work, a hybrid agent was synthesized by integrating superparamagnetic iron oxide nanoparticles (SPIOs) into albumin-shelled microbubbles (named as SPIO-albumin microbubbles). Then, both the stable and inertial cavitation thresholds of this hybrid agent were measured at varied SPIO concentrations and ultrasound parameters (e.g., frequency, pressure amplitude, and pulse length). The results show that, at a fixed acoustic driving frequency, both the stable and inertial cavitation thresholds of SPIO-albumin microbubble should decrease with the increasing SPIO concentration and acoustic driving pulse length. The inertial cavitation threshold of SPIO-albumin microbubbles also decreases with the raised driving frequency, while the minimum sub- and ultra-harmonic thresholds appear at twice and two thirds resonance frequency, respectively. It is also noticed that both the stable and inertial cavitation thresholds of SonoVue microbubbles are similar to those measured for hybrid microbubbles with a SPIO concentration of 114.7 μg/ml. The current work could provide better understanding on the impact of the integrated SPIOs on the dynamic responses (especially the cavitation activities) of hybrid microbubbles, and suggest the shell composition of hybrid agents should be appropriately designed to improve their clinical diagnostic and therapeutic performances of hybrid microbubble agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Bovine serum albumin nanoparticles loaded with Photosens photosensitizer for effective photodynamic therapy

NASA Astrophysics Data System (ADS)

Khanadeev, Vitaly; Khlebtsov, Boris; Packirisamy, Gopinath; Khlebtsov, Nikolai

2017-03-01

Polymeric nanoparticles (NPs) are widely used for drug delivery applications due to high biodegradability, low toxicity and high loading capacity. The focus of this study is the development of photosensitizer Photosens (PS) loaded albumin NPs for efficient photodynamic therapy (PDT). To fabricate PS-loaded bovine serum albumin nanoparticles (BSA-PS NPs), we used a coacervation method with glutaraldehyde followed by passive loading of PS. Successful loading of PS was confirmed by appearance of characteristic peak in absorption spectrum which allows to determine the PS loading in BSA NPs. The synthesized BSA-PS NPs demonstrated low toxicity to HeLa cells at therapeutic concentrations of loaded PS. Compared to free PS solution, the synthesized BSA-PS NPs generated the singlet oxygen more effectively under laser irradiation at 660 nm. In addition, due to presence of various chemical groups on the surface of BSA-PS NPs, they are capable to adsorb on cell surface and accumulate in cells due to cellular uptake mechanisms. Owing to combination of PD and cell uptake advantages, BSA-PS NPs demonstrated higher efficacy of photodynamic damage to cancer cells as compared to free PS at equivalent concentrations. These results suggest that non-targeted BSA-PS NPs with high PD activity and low-fabrication costs of are promising candidates for transfer to PD clinic treatments.

Enhanced Cellular Cytotoxicity and Antibacterial Activity of 18-β-Glycyrrhetinic Acid by Albumin-conjugated PLGA Nanoparticles.

PubMed

Darvishi, B; Manoochehri, S; Esfandyari-Manesh, M; Samadi, N; Amini, M; Atyabi, F; Dinarvand, R

2015-12-01

The aim of the present work was to encapsulate 18-β-Glycyrrhetinic acid (GLA) in albumin conjugated poly(lactide-co-glycolide) (PLGA) nanoparticles by a modified nanoprecipitation method. Nanoparticles (NPs) were prepared by different drug to polymer ratios, human serum albumin (HSA) content, dithiothreitol (as producer of free thiol groups) content, and acetone (as non-solvent in nanoprecipitation). NPs with a size ranging from 126 to 174 nm were achieved. The highest entrapment efficiency (89.4±4.2%) was achieved when the ratio of drug to polymer was 1:4. The zeta potential of NPs was fairly negative (-8 to -12). Fourier transform infrared spectroscopy and differential scanning calorimetry proved the conjugation of HSA to PLGA NPs. In vitro release profile of NPs showed 2 phases: an initial burst for 4 h (34-49%) followed by a slow release pattern up to the end. The antibacterial effects of NPs against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa were studied by microdilution method. The GLA-loaded NPs showed more antibacterial effect than pure GLA (2-4 times). The anticancer MTT test revealed that GLA-loaded NPs were approximately 9 times more effective than pure GLA in Hep G2 cells. © Georg Thieme Verlag KG Stuttgart · New York.

Lapatinib nano-delivery systems: a promising future for breast cancer treatment.

PubMed

Bonde, Gunjan Vasant; Yadav, Sarita Kumari; Chauhan, Sheetal; Mittal, Pooja; Ajmal, Gufran; Thokala, Sathish; Mishra, Brahmeshwar

2018-05-01

Breast cancer stands the second prominent cause of death among women. For its efficient treatment, Lapatinib (LAPA) was developed as a selective tyrosine kinase inhibitor of receptors, overexpressed by breast cancer cells. Various explored delivery strategies for LAPA indicated its controlled release with enhanced aqueous solubility, improved bioavailability, decreased plasma protein binding, reduced dose and toxicity to the other organs with maximized clinical efficacy, compared to its marketed tablet formulation. Areas covered: This comprehensive review deals with the survey, performed through different electronic databases, regarding various challenges and their solutions attained by fabricating delivery systems like nanoparticles, micelle, nanocapsules, nanochannels, and liposomes. It also covers the synthesis of novel LAPA-conjugates for diagnostic purpose. Expert opinion: Unfortunately, clinical use of LAPA is restricted because of its extensive albumin binding capacity, poor oral bioavailability, and poor aqueous solubility. LAPA is marketed as the oral tablet only. Therefore, it becomes imperative to formulate alternate efficient multiparticulate or nano-delivery systems for administration through non-oral routes, for active/passive targeting, and to scale-up by pharmaceutical scientists followed by their clinical trials by clinical experts. LAPA combinations with capecitabine and letrozole should also be tried for breast cancer treatment.

Nanocarriers Made from Non-Ionic Surfactants or Natural Polymers for Pulmonary Drug Delivery.

PubMed

Carter, K C; Puig-Sellart, M

2016-01-01

Treatment by the pulmonary route can be used for drugs that act locally in the lungs (e.g. lung cancer) or non-invasive administration of drugs that act systemically (e.g. diabetes). The potential of using drug delivery systems (DDS) formed from non-ionic surfactants or natural products for pulmonary drug delivery are reviewed. The effectiveness of each DDS depends on it ability to not only entrap the relevant drug and alter its bio distribution, but also its ability to withstand the physical stresses during nebulization and for the nebuliser to produce aerosol particles with the size for deposition in the appropriate part of the lungs. Different methods must be used to prepare nanoparticles (NP) using non-ionic surfactants, or biocompatible polymers from natural proteins or sugars, and the aqueous solubility of the drug also influences the manufacture method. NP produced using non-ionic surfactants, proteins such as collagen, albumin or gluten, and polysaccharides such as chitosan, hyaluronate, cellulose, carrageenans, alginate or starch has successfully delivered different types of drugs given by the pulmonary route. Drug entrapment efficiency depends on the DDS constituents and the manufacture method used. Large scale manufacture of DDS from natural products is technically challenging but changing from batch manufacture to continuous manufacturing processes has addressed some of these issues, and inclusion of a spray drying step has been beneficial in some cases. DDS for lung delivery can be produced using natural products but identifying a cost effective manufacture method may be challenging and the impact of using different type of nebulisers on the physiochemical characteristics of the aerosolised formulation should be an essential part of formulation development. This would ensure that some of the development work e.g. stability studies do not have to be repeated as they will identify if a carrier to protect the DDS from the physical trauma caused by nebulisation.

Ultrasmall fluorescent nanoparticles derived from roast duck: their physicochemical characteristics and interaction with human serum albumin.

PubMed

Cong, Shuang; Bi, Jingran; Song, Xunyu; Yu, Chenxu; Tan, Mingqian

2018-04-25

Fluorescent nanoparticles (FNPs) produced from roast meat have drawn widespread attention due to their potential hazards to human health. In this paper, the presence of ultrasmall FNPs in roast duck and their interaction with human serum albumin (HSA) were reported. The processing-induced FNPs have an average size of 1.3 nm with a relative fluorescence quantum yield of 4.4%. X-ray photoelectron spectroscopy showed that the FNPs are composed of carbon (70.48%), nitrogen (6.25%), oxygen (22.17%) and sulfur (1.11%), with hydroxyl, carboxyl and amino groups present on their surface. The presence of FNPs could cause fluorescence quenching of HSA, which was ascribed to the static quenching mechanism via the electrostatic interaction as analyzed by isothermal titration calorimetry. The α-helix contents of HSA decreased after the addition of FNPs, demonstrating that these processing-induced FNPs could cause structural alteration of HSA. These results provided insights into the formation of nanoparticles in roast duck, and offered important information about the binding mechanism of these nanoparticles with HSA, which may have physiological implications.

Interaction of fibrinogen and albumin with titanium dioxide nanoparticles of different crystalline phases

NASA Astrophysics Data System (ADS)

Marucco, Arianna; Fenoglio, Ivana; Turci, Francesco; Fubini, Bice

2013-04-01

TiO2 nanoparticles (NPs) are contained in different kinds of industrial products including paints, self-cleaning glasses, sunscreens. TiO2 is also employed in photocatalysis and it has been proposed for waste water treatment. Micrometric TiO2 is generally considered a safe material, while there is concern on the possible health effects of nanometric titania. Due to their small size NPs may migrate within the human body possibly entering in the blood stream. Therefore studies on the interaction of NPs with plasma proteins are needed. In fact, the interaction with proteins is believed to ultimately influences the NPs biological fate. Fibrinogen and albumin are two of the most abundant plasma proteins. They are involved in several important physiological functions. Furthermore, fibrinogen is known to trigger platelet adhesion and inflammation. For these reasons the study of the interaction between these protein and nanoparticles is an important step toward the understanding of the behavior of NPs in the body. In this study we investigated the interaction of albumin and fibrinogen with TiO2 nanoparticles of different crystal phases (rutile and anatase) using an integrated set of techniques. The amount of adsorbed fibrinogen and albumin for each TiO2 surface was investigated by using the bicinchoninic acid assay (BCA). The variation of the surface charge of the NP-protein conjugates respect to the naked NPs was used to indirectly estimate both surface coverage and reversibility of the adsorption upon dilution. Surface charge was monitored by measuring the ζ potential with a conventional electrophoretic light scattering (ELS) system. The extent of protein deformation was evaluated by Raman Spectroscopy. We found that both proteins adsorb irreversibly against electrostatic repulsion, likely undergoing conformational changes or selective orientation upon adsorption. The size of primary particles and the particles aggregation rather than the crystal phase modulate the affinity of fibrinogen for the TiO2 surfaces.

Localized surface plasmon resonance of gold nanoparticles as colorimetric probes for determination of Isoniazid in pharmacological formulation.

PubMed

Zargar, Behrooz; Hatamie, Amir

2013-04-01

Isoniazid is an important antibiotic, which is widely used to treat tuberculosis. This study presents a colorimetric method for the determination of Isoniazid based on localized surface plasmon resonance (LSPR) property of gold nanoparticles. An LSPR band is produced by reducing gold ions in solution using Isoniazid as the reducing agent. Influences of the following relevant variables were examined and optimized in the experiment, formation time of gold nanoparticles, pH, buffer and stabilizer. These tests demonstrated that under optimum conditions the absorbance of Au nanoparticles at 530 nm related linearly to the concentration of Isoniazid in the range of 1.0-8.0 μg mL(-1) with a detection limit of 0.98 μg mL(-1). This colorimetric method has been successfully applied to the determine Isoniazid in tablets and spiked serum samples. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for analysis of Isoniazid. Copyright © 2013 Elsevier B.V. All rights reserved.

Localized surface plasmon resonance of gold nanoparticles as colorimetric probes for determination of Isoniazid in pharmacological formulation

NASA Astrophysics Data System (ADS)

Zargar, Behrooz; Hatamie, Amir

2013-04-01

Isoniazid is an important antibiotic, which is widely used to treat tuberculosis. This study presents a colorimetric method for the determination of Isoniazid based on localized surface plasmon resonance (LSPR) property of gold nanoparticles. An LSPR band is produced by reducing gold ions in solution using Isoniazid as the reducing agent. Influences of the following relevant variables were examined and optimized in the experiment, formation time of gold nanoparticles, pH, buffer and stabilizer. These tests demonstrated that under optimum conditions the absorbance of Au nanoparticles at 530 nm related linearly to the concentration of Isoniazid in the range of 1.0-8.0 μg mL-1 with a detection limit of 0.98 μg mL-1. This colorimetric method has been successfully applied to the determine Isoniazid in tablets and spiked serum samples. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for analysis of Isoniazid.

Nanoscale coordination polymers for anticancer drug delivery

NASA Astrophysics Data System (ADS)

Phillips, Rachel Huxford

This dissertation reports the synthesis and characterization of nanoscale coordination polymers (NCPs) for anticancer drug delivery. Nanoparticles have been explored in order to address the limitations of small molecule chemotherapeutics. NCPs have been investigated as drug delivery vehicles as they can exhibit the same beneficial properties as the bulk metal-organic frameworks as well as interesting characteristics that are unique to nanomaterials. Gd-MTX (MTX = methotrexate) NCPs with a MTX loading of 71.6 wt% were synthesized and stabilized by encapsulation within a lipid bilayer containing anisamide (AA), a small molecule that targets sigma receptors which are overexpressed in many cancer tissues. Functionalization with AA allows for targeted delivery and controlled release to cancer cells, as shown by enhanced efficacy against leukemia cells. The NCPs were doped with Ru(bpy)32+ (bpy = 2,2'-bipyridine), and this formulation was utilized as an optical imaging agent by confocal microscopy. NCPs containing the chemotherapeutic pemetrexed (PMX) were synthesized using different binding metals. Zr-based materials could not be stabilized by encapsulation with a lipid bilayer, and Gd-based materials showed that PMX had degraded during synthesis. However, Hf-based NCPs containing 19.7 wt% PMX were stabilized by a lipid coating and showed in vitro efficacy against non-small cell lung cancer (NSCLC) cell lines. Enhanced efficacy was observed for formulations containing AA. Additionally, NCP formulations containing the cisplatin prodrug disuccinatocisplatin were prepared; one of these formulations could be stabilized by encapsulation within a lipid layer. Coating with a lipid layer doped with AA rendered this formulation an active targeting agent. The resulting formulation proved more potent than free cisplatin in NSCLC cell lines. Improved NCP uptake was demonstrated by confocal microscopy and competitive binding assays. Finally, a Pt(IV) oxaliplatin prodrug was synthesized and incorporated in different NCPs using various binding metals. A moderate drug loading of 44.9 wt% was determined for Zr-based NCPs. This drug loading, along with a diameter less than 200 nm, make these particles promising candidates for further stabilization via lipid encapsulation.

Comparative evaluation of in vitro parameters of tamoxifen citrate loaded poly(lactide-co-glycolide), poly(epsilon-caprolactone) and chitosan nanoparticles.

PubMed

Cirpanli, Y; Yerlikaya, F; Ozturk, K; Erdogar, N; Launay, M; Gegu, C; Leturgez, T; Bilensoy, E; Calis, S; Capan, Y

2010-12-01

Tamoxifen (TAM), the clinical choice for the antiestrogen treatment of advanced or metastatic breast cancer, was formulated in nanoparticulate carrier systems in the form of poly(lactide-co-glycolide) (PLGA), poly-epsilon-caprolactone (PCL) and chitosan (CS) nanoparticles. The PLGA and PCL nanoparticles were prepared by a nanoprecipitation technique whereas the CS nanoparticles were prepared by the ionic gelation method. Mean particle sizes were under 260 nm for PLGA and PCL nanoparticles and around 400 nm for CS nanoparticles. Polydispersity indices were less than 0.4 for all formulations. Zeta potential values were positive for TAM loaded nanoparticles because of the positive charge of the drug. Drug loading values were significantly higher for PCL nanoparticles when compared to PLGA and CS nanoparticles. All nanoparticle formulations exhibited controlled release properties. These results indicate that TAM loaded PLGA, PCL and CS nanoparticles may provide promising carrier systems for tumor targeting.

Peroxidase-mediated formation of corn fiber gum-bovine serum albumin conjugates: molecular and structural characterization

USDA-ARS?s Scientific Manuscript database

Corn fiber gum (CFG) is a good flavor stabilizer for beverages and food. This study was undertaken to test the hypothesis that binding additional protein to CFG would further improve its flavor stabilizing properties. Conjugates of corn fiber gum (CFG) and bovine serum albumin (BFG) were prepared ...

Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides.

PubMed

Batista, Patrícia; Castro, Pedro M; Madureira, Ana Raquel; Sarmento, Bruno; Pintado, Manuela

2018-03-01

Bioactive proteins and peptides have been used with either prophylactic or therapeutic purposes, presenting inherent advantages as high specificity and biocompatibility. Nanocarriers play an important role in the stabilization of proteins and peptides, offering enhanced buccal permeation and protection while crossing the gastrointestinal tract. Moreover, preparation of nanoparticles as oral delivery systems for proteins/peptides may include tailored formulation along with functionalization aiming bioavailability enhancement of carried proteins or peptides. Oral delivery systems, namely buccal delivery systems, represent an interesting alternative route to parenteric delivery systems to carry proteins and peptides, resulting in higher comfort of administration and, therefore, compliance to treatment. This paper outlines an extensive overview of the existing publications on proteins/peptides oral nanocarriers delivery systems, with special focus on buccal route. Manufacturing aspects of most commonly used nanoparticles for oral delivery (e.g. polymeric nanoparticles using synthetic or natural polymers and lipid nanoparticles) advantages and limitations and potential applications of nanoparticles as proteins/peptides delivery systems will also be thoroughly addressed. Copyright © 2018 Elsevier Inc. All rights reserved.

Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies.

PubMed

Lalani, Jigar; Rathi, Mohan; Lalan, Manisha; Misra, Ambikanandan

2013-06-01

Poly (d,l-lactide-co-glycolide acid) (PLGA) Nanoparticles (NPs) with sustained drug release and enhanced circulation time presents widely explored non-invasive approach for drug delivery to brain. However, blood-brain barrier (BBB) limits the drug delivery to brain. This can be overcome by anchoring endogenous ligand like Transferrin (Tf) and Lactoferrin (Lf) on the surface of NPs, allowing efficient brain delivery via receptor-mediated endocytosis. The aim of the present investigation was preparation, optimization, characterization and comparative evaluation of targeting efficiency of Tf- vs. Lf-conjugated NPs. Tramadol-loaded PLGA NPs were prepared by nanoprecipitation techniques and optimized using 3(3) factorial design. The effect of polymer concentration, stabilizer concentration and organic:aqueous phase ratio were evaluated on particle size (PS) and entrapment efficiency (EE). The formulation was optimized based on desirability for lower PS (<150 nm) and higher EE (>70%). Optimized PLGA NPs were conjugated with Tf and Lf, characterized and evaluated for stability study. Pharmacodynamic study was performed in rat after intravenous administration. The optimized formulation had 100 mg of PLGA, 1% polyvinyl alcohol (PVA) and 1:2 acetone:water ratio. The Lf and Tf conjugation to PLGA NPs was estimated to 186 Tf and 185 Lf molecules per NPs. Lyophilization was optimized at 1:2 ratio of NPs:trehalose. The NPs were found stable for 6 months at refrigerated condition. Pharmacodynamic study demonstrated enhanced efficacy of ligand-conjugated NPs against unconjugated NPs. Conjugated NPs demonstrated significantly higher pharmacological effect over a period of 24 h. Furthermore Lf functionalized NPs exhibited better antinociceptive effect as compared to Tf functionalized NPs.

Radiolabeled inorganic nanoparticles for positron emission tomography imaging of cancer: an overview

PubMed Central

CHAKRAVARTY, Rubel; GOEL, Shreya; DASH, Ashutosh; CAI, Weibo

2017-01-01

Over the last few years, a plethora of radiolabeled inorganic nanoparticles have been developed and evaluated for their potential use as probes in positron emission tomography (PET) imaging of a wide variety of cancers. Inorganic nanoparticles represent an emerging paradigm in molecular imaging probe design, allowing the incorporation of various imaging modalities, targeting ligands, and therapeutic payloads into a single vector. A major challenge in this endeavor is to develop disease-specific nanoparticles with facile and robust radiolabeling strategies. Also, the radiolabeled nanoparticles should demonstrate adequate in vitro and in vivo stability, enhanced sensitivity for detection of disease at an early stage, optimized in vivo pharmacokinetics for reduced non-specific organ uptake, and improved targeting for achieving high efficacy. Owing to these challenges and other technological and regulatory issues, only a single radiolabeled nanoparticle formulation, namely “C-dots” (Cornell dots), has found its way into clinical trials thus far. This review describes the available options for radiolabeling of nanoparticles and summarizes the recent developments in PET imaging of cancer in preclinical and clinical settings using radiolabeled nanoparticles as probes. The key considerations toward clinical translation of these novel PET imaging probes are discussed, which will be beneficial for advancement of the field. PMID:28124549

Characterisation of protein stability in rod-insert vaginal rings.

PubMed

Pattani, Aditya; Lowry, Deborah; Curran, Rhonda M; McGrath, Stephanie; Kett, Vicky L; Andrews, Gavin P; Malcolm, R Karl

2012-07-01

A major goal in vaccine development is elimination of the 'cold chain', the transport and storage system for maintenance and distribution of the vaccine product. This is particularly pertinent to liquid formulation of vaccines. We have previously described the rod-insert vaginal ring (RiR) device, comprising an elastomeric body into which are inserted lyophilised, rod-shaped, solid drug dosage forms, and having potential for sustained mucosal delivery of biomacromolecules, such as HIV envelope protein-based vaccine candidates. Given the solid, lyophilised nature of these insert dosage forms, we hypothesised that antigen stability may be significantly increased compared with more conventional solubilised vaginal gel format. In this study, we prepared and tested vaginal ring devices fitted with lyophilised rod inserts containing the model antigen bovine serum albumin (BSA). Both the RiRs and the gels that were freeze-dried to prepare the inserts were evaluated for BSA stability using PAGE, turbidimetry, microbial load, MALDI-TOF and qualitative precipitate solubility measurements. When stored at 4 °C, but not when stored at 40 °C/75% RH, the RiR formulation offered protection against structural and conformational changes to BSA. The insert also retained matrix integrity and release characteristics. The results demonstrate that lypophilised gels can provide relative protection against degradation at lower temperatures compared to semi-solid gels. The major mechanism of degradation at 40 °C/75% RH was shown to be protein aggregation. Finally, in a preliminary study, we found that addition of trehalose to the formulation significantly reduces the rate of BSA degradation compared to the original formulation when stored at 40 °C/75% RH. Establishing the mechanism of degradation, and finding that degradation is decelerated in the presence of trehalose, will help inform further development of RiRs specifically and polymer based freeze-dried systems in general. Copyright © 2012 Elsevier B.V. All rights reserved.

Analyzing the influence of PEG molecular weight on the separation of PEGylated gold nanoparticles by asymmetric-flow field-flow fractionation.

PubMed

Hansen, Matthew; Smith, Mackensie C; Crist, Rachael M; Clogston, Jeffrey D; McNeil, Scott E

2015-11-01

Polyethylene glycol (PEG) is an important tool for increasing the biocompatibility of nanoparticle therapeutics. Understanding how these potential nanomedicines will react after they have been introduced into the bloodstream is a critical component of the preclinical evaluation process. Hence, it is paramount that better methods for separating, characterizing, and analyzing these complex and polydisperse formulations are developed. We present a method for separating nominal 30-nm gold nanoparticles coated with various molecular weight PEG moieties that uses only phosphate-buffered saline as the mobile phase, without the need for stabilizing surfactants. The optimized asymmetric-flow field-flow fractionation technique using in-line multiangle light scattering, dynamic light scattering, refractive index, and UV-vis detectors allowed successful separation and detection of a mixture of nanoparticles coated with 2-, 5-, 10-, and 20-kDa PEG. The particles coated with the larger PEG species (10 and 20 kDa) were eluted at times significantly earlier than predicted by field-flow fractionation theory. This was attributed to a lower-density PEG shell for the higher molecular weight PEGylated nanoparticles, which allows a more fluid PEG surface that can be greater influenced by external forces. Hence, the apparent particle hydrodynamic size may fluctuate significantly depending on the overall density of the stabilizing surface coating when an external force is applied. This has considerable implications for PEGylated nanoparticles intended for in vivo application, as nanoparticle size is important for determining circulation times, accumulation sites, and routes of excretion, and highlights the importance and value of the use of secondary size detectors when one is working with complex samples in asymmetric-flow field-flow fractionation.

Reversible exposure of hydrophobic residues on albumin as a novel strategy for formulation of nanodelivery vehicles for taxanes

PubMed Central

Garro, AG; Beltramo, DM; Alasino, RV; Leonhard, V; Heredia, V; Bianco, ID

2011-01-01

Background: We report herein a novel strategy for the preparation of protein-based nanode-livery vehicles for hydrophobic active pharmaceutical ingredients. Methods: The procedure consisted of three steps, ie, exposure of hydrophobic residues of a protein to a pH-induced partial unfolding: interaction between hydrophobic residues on the protein and the hydrophobic active pharmaceutical ingredient, and a final step where the structure of the protein was reversed to a native-like state by returning to neutral pH. As proof of concept, the interaction of paclitaxel with partially unfolded states of human serum albumin was evaluated as a potential method for the preparation of water-soluble complexes of the taxane with albumin. Results: We found that paclitaxel readily binds to pH-induced partially unfolded albumin, leading to the formation of optically clear water-soluble complexes. The complexes thus formed were more stable in solution when the albumin native state was at least partially restored by neutralization of the solution to a pH around 7. It was also observed that the hydrodynamic radius of human serum albumin was only slightly increased after the cycle of pH changes, remaining in a monomeric state with a size according to paclitaxel binding. Furthermore, paclitaxel binding did not affect the overall exposure of charged groups of human serum albumin, as evaluated by its interaction with an ionic exchange resin. Conclusion: The in vitro biological activity of the complexes formed was qualitatively equivalent to that of a Cremophor®-based formulation. PMID:21822381

Size-dependent interaction of silica nanoparticles with lysozyme and bovine serum albumin proteins

NASA Astrophysics Data System (ADS)

Yadav, Indresh; Aswal, Vinod K.; Kohlbrecher, Joachim

2016-05-01

The interaction of three different sized (diameter 10, 18, and 28 nm) anionic silica nanoparticles with two model proteins—cationic lysozyme [molecular weight (MW) 14.7 kDa)] and anionic bovine serum albumin (BSA) (MW 66.4 kDa) has been studied by UV-vis spectroscopy, dynamic light scattering (DLS), and small-angle neutron scattering (SANS). The adsorption behavior of proteins on the nanoparticles, measured by UV-vis spectroscopy, is found to be very different for lysozyme and BSA. Lysozyme adsorbs strongly on the nanoparticles and shows exponential behavior as a function of lysozyme concentration irrespective of the nanoparticle size. The total amount of adsorbed lysozyme, as governed by the surface-to-volume ratio, increases on lowering the size of the nanoparticles for a fixed volume fraction of the nanoparticles. On the other hand, BSA does not show any adsorption for all the different sizes of the nanoparticles. Despite having different interactions, both proteins induce similar phase behavior where the nanoparticle-protein system transforms from one phase (clear) to two phase (turbid) as a function of protein concentration. The phase behavior is modified towards the lower concentrations for both proteins with increasing the nanoparticle size. DLS suggests that the phase behavior arises as a result of the nanoparticles' aggregation on the addition of proteins. The size-dependent modifications in the interaction potential, responsible for the phase behavior, have been determined by SANS data as modeled using the two-Yukawa potential accounting for the repulsive and attractive interactions in the systems. The protein-induced interaction between the nanoparticles is found to be short-range attraction for lysozyme and long-range attraction for BSA. The magnitude of attractive interaction irrespective of protein type is enhanced with increase in the size of the nanoparticles. The total (attractive+repulsive) potential leading to two-phase formation is found to be more attractive for larger sized nanoparticles. The nanoparticle aggregates are characterized by mass fractal.

Improved delivery of the anticancer agent citral using BSA nanoparticles and polymeric wafers.

PubMed

White, Benjamin; Evison, Anna; Dombi, Eszter; Townley, Helen E

2017-01-01

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, with a 5-year survival rate of between 30 and 65%. Standard treatment involves surgery, radiation treatment, and chemotherapy. However, there is a high recurrence rate, particularly from locoregional spread. We investigated the use of the natural compound citral (3,7-dimethyl-2,6-octadienal), which can be found in a number of plants, but is particularly abundant in lemon grass ( Cymbopogon citratus ) oil, for activity against immortalized RMS cells. Significant cancer cell death was seen at concentrations above 150 μM citral, and mitochondrial morphological changes were seen after incubation with 10 μM citral. However, since citral is a highly volatile molecule, we prepared albumin particles by a desolvation method to encapsulate citral, as a means of stabilization. We then further incorporated the loaded nanoparticles into a biodegradable polyanhydride wafer to generate a slow release system. The wafers were shown to degrade by 50% over the course of 25 days and to release the active compound. We therefore propose the use of the citral-nanoparticle-polymer wafers for implantation into the tumor bed after surgical removal of a sarcoma as a means to control locoregional spread due to any remaining cancerous cells.

Improved delivery of the anticancer agent citral using BSA nanoparticles and polymeric wafers

PubMed Central

White, Benjamin; Evison, Anna; Dombi, Eszter; Townley, Helen E

2017-01-01

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, with a 5-year survival rate of between 30 and 65%. Standard treatment involves surgery, radiation treatment, and chemotherapy. However, there is a high recurrence rate, particularly from locoregional spread. We investigated the use of the natural compound citral (3,7-dimethyl-2,6-octadienal), which can be found in a number of plants, but is particularly abundant in lemon grass (Cymbopogon citratus) oil, for activity against immortalized RMS cells. Significant cancer cell death was seen at concentrations above 150 μM citral, and mitochondrial morphological changes were seen after incubation with 10 μM citral. However, since citral is a highly volatile molecule, we prepared albumin particles by a desolvation method to encapsulate citral, as a means of stabilization. We then further incorporated the loaded nanoparticles into a biodegradable polyanhydride wafer to generate a slow release system. The wafers were shown to degrade by 50% over the course of 25 days and to release the active compound. We therefore propose the use of the citral-nanoparticle-polymer wafers for implantation into the tumor bed after surgical removal of a sarcoma as a means to control locoregional spread due to any remaining cancerous cells. PMID:29263655

Novel ionically crosslinked casein nanoparticles for flutamide delivery: formulation, characterization, and in vivo pharmacokinetics

PubMed Central

Elzoghby, Ahmed O; Helmy, Maged W; Samy, Wael M; Elgindy, Nazik A

2013-01-01

A novel particulate delivery matrix based on ionically crosslinked casein (CAS) nanoparticles was developed for controlled release of the poorly soluble anticancer drug flutamide (FLT). Nanoparticles were fabricated via oil-in-water emulsification then stabilized by ionic crosslinking of the positively charged CAS molecules below their isoelectric point, with the polyanionic crosslinker sodium tripolyphosphate. With the optimal preparation conditions, the drug loading and incorporation efficiency achieved were 8.73% and 64.55%, respectively. The nanoparticles exhibited a spherical shape with a size below 100 nm and a positive zeta potential (+7.54 to +17.3 mV). FLT was molecularly dispersed inside the nanoparticle protein matrix, as revealed by thermal analysis. The biodegradability of CAS nanoparticles in trypsin solution could be easily modulated by varying the sodium tripolyphosphate crosslinking density. A sustained release of FLT from CAS nanoparticles for up to 4 days was observed, depending on the crosslinking density. After intravenous administration of FLT-CAS nanoparticles into rats, CAS nanoparticles exhibited a longer circulation time and a markedly delayed blood clearance of FLT, with the half-life of FLT extended from 0.88 hours to 14.64 hours, compared with drug cosolvent. The results offer a promising method for tailoring biodegradable, drug-loaded CAS nanoparticles as controlled, long-circulating drug delivery systems of hydrophobic anticancer drugs in aqueous vehicles. PMID:23658490

Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation, physicochemical characterization and cytotoxicity studies.

PubMed

Pradhan, Roshan; Poudel, Bijay Kumar; Ramasamy, Thiruganesh; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2013-08-01

In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid-co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants respectively for stabilization. The NPs were prepared by emulsification/solvent evaporation method. The combination of these surfactants at weight ratio of 1:0.5 was able to produce uniformly distributed small sized NPs and demonstrated the better stability of NP dispersion with high encapsulation efficiency (85.9 +/- 0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively. The optimized formulation of DTX-loaded PLGA NPs had a particle size and polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which was further supported by TEM image. In vitro release study was carried out with dialysis membrane and showed 32% drug release in 192 h. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which suggested the drug was released by anomalous or non-Fickian diffusion. In addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

Generation of fatty acids from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cardiolipin liposomes that stabilize recombinant human serum albumin.

PubMed

Frahm, Grant E; Cameron, Brooke E; Smith, Jeffrey C; Johnston, Michael J W

2013-06-01

At elevated temperatures, studies have shown that serum albumin undergoes irreversible changes to its secondary structure. Anionic fatty acids and/or anionic surfactants have been shown to stabilize human serum albumin (HSA) against thermal denaturation through bridging hydrophobic domains and cationic amino acids residues of the protein. As albumin can readily interact with a variety of liposomes, this study proposes that cardiolipin delivered via 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes can improve the thermal stability of recombinant HSA produced in Saccharomyces cerevisiae (ScrHSA) in a similar manner to anionic fatty acids. Thermal stability and structure of ScrHSA in the absence and presence of DPPC/cardiolipin liposomes was assessed with U/V circular dichroism spectropolarimetry and protein thermal stability was confirmed with differential scanning calorimetry. Although freshly prepared DPPC/cardiolipin liposomes did not improve the stability of ScrHSA, DPPC/cardiolipin liposomes incubated at room temperature for 7 d (7dRT) dramatically improved the thermal stability of the protein. Mass spectrometry analysis identified the presence of fatty acids in the 7dRT liposomes, not identified in freshly prepared liposomes, to which the improved stability was attributed. The generation of fatty acids is attributed to either the chemical hydrolysis or oxidative cleavage of the unsaturated acyl chains of cardiolipin. By modulating the lipid composition through the introduction of lipids with higher acyl chain unsaturation, it may be possible to generate the stabilizing fatty acids in a more rapid manner.

Bendable Electro-chemical Lactate Sensor Printed with Silver Nano-particles

NASA Astrophysics Data System (ADS)

Abrar, Md Abu; Dong, Yue; Lee, Paul Kyuheon; Kim, Woo Soo

2016-07-01

Here we report a flexible amperometric lactate biosensor using silver nanoparticle based conductive electrode. Mechanically bendable cross-serpentine-shaped silver electrode is generated on flexible substrate for the mechanical durability such as bending. The biosensor is designed and fabricated by modifying silver electrode with lactate oxidase immobilized by bovine serum albumin. The in-sensor pseudo Ag/AgCl reference electrode is fabricated by chloridization of silver electrode, which evinced its long-term potential stability against a standard commercial Ag/AgCl reference electrode. The amperometric response of the sensor shows linear dependence with lactate concentration of 1~25 mM/L. Anionic selectivity is achieved by using drop-casted Nafion coated on silver electrode against anionic interferences such as ascorbate. This non-invasive electrochemical lactate sensor also demonstrates excellent resiliency against mechanical deformation and temperature fluctuation which leads the possibility of using it on human epidermis for continuous measurement of lactate from sweat. Near field communication based wireless data transmission is demonstrated to reflect a practical approach of the sensor to measure lactate concentration portably using human perspiration.

Bendable Electro-chemical Lactate Sensor Printed with Silver Nano-particles

PubMed Central

Abrar, Md Abu; Dong, Yue; Lee, Paul Kyuheon; Kim, Woo Soo

2016-01-01

Here we report a flexible amperometric lactate biosensor using silver nanoparticle based conductive electrode. Mechanically bendable cross-serpentine-shaped silver electrode is generated on flexible substrate for the mechanical durability such as bending. The biosensor is designed and fabricated by modifying silver electrode with lactate oxidase immobilized by bovine serum albumin. The in-sensor pseudo Ag/AgCl reference electrode is fabricated by chloridization of silver electrode, which evinced its long-term potential stability against a standard commercial Ag/AgCl reference electrode. The amperometric response of the sensor shows linear dependence with lactate concentration of 1~25 mM/L. Anionic selectivity is achieved by using drop-casted Nafion coated on silver electrode against anionic interferences such as ascorbate. This non-invasive electrochemical lactate sensor also demonstrates excellent resiliency against mechanical deformation and temperature fluctuation which leads the possibility of using it on human epidermis for continuous measurement of lactate from sweat. Near field communication based wireless data transmission is demonstrated to reflect a practical approach of the sensor to measure lactate concentration portably using human perspiration. PMID:27465437

Physicochemical characterization of 3,6-diHydroxyflavone binding BSA immobilized on PEG-coated silver nanoparticles

NASA Astrophysics Data System (ADS)

Voicescu, Mariana; Ionescu, Sorana; Calderon-Moreno, Jose M.; Nistor, Cristina L.

2017-02-01

Studies based on silver nanoparticles (SNPs) and polyethylene glycols (PEGs) are mainly in the pharmaceutical field, with PEG as good "vehicle" to transport protein-based drugs. In this work, physicochemical characteristics of 3,6-diHydroxyflavone (3,6-diHF) binding bovine serum albumin (BSA) on PEG (Tween20, L64, and Myrj52)-coated SNPs have been investigated by steady-state and time-resolved fluorescence spectroscopy. These interactions give rise to the formation of intermolecular and intramolecular H bonds. As a subject of interest, the effect of temperature (30-60 °C) on the H bonds was studied by steady-state fluorescence. The size distribution and zeta potential of SNPs were determined by dynamic light scattering (DLS). Scanning electron microscopy (SEM) analysis revealed the spherical nature of particles with average diameter 40-80 nm. The structure, stability, dynamics, and conformational changes in adsorbed BSA protein on the PEG-coated SNPs surface have been also investigated by steady-state/lifetime fluorescence and circular dichroism spectroscopy. The results have relevance in the oxidative stress and drug delivery processes.

Formulation, characterization, and expression of a recombinant MOMP Chlamydia trachomatis DNA vaccine encapsulated in chitosan nanoparticles

PubMed Central

Cambridge, Chino D; Singh, Shree R; Waffo, Alain B; Fairley, Stacie J; Dennis, Vida A

2013-01-01

Chlamydia trachomatis is a bacterial sexually transmitted infection affecting millions of people worldwide. Previous vaccination attempts have employed the recombinant major outer membrane protein (MOMP) of C. trachomatis nonetheless, with limited success, perhaps, due to stability, degradation, and delivery issues. In this study we cloned C. trachomatis recombinant MOMP DNA (DMOMP) and encapsulated it in chitosan nanoparticles (DMCNP) using the complex coacervation technique. Physiochemical characterizations of DMCNP included transmission and scanning electron microcopy, Fourier transform infrared and ultraviolet-visible spectroscopy, and zeta potential. Encapsulated DMOMP was 167–250 nm, with a uniform spherical shape and homogenous morphology, and an encapsulation efficiency > 90%. A slow release pattern of encapsulated DMOMP, especially in acidic solution, was observed over 7 days. The zeta potential of DMCNP was ~8.80 mV, which indicated that it was highly stable. Toxicity studies of DMCNP (25–400 μg/mL) to Cos-7 cells using the MTT assay revealed minimal toxicity over 24–72 hours with >90% viable cells. Ultra-violet visible (UV-vis) spectra indicated encapsulated DMOMP protection by chitosan, whereas agarose gel electrophoresis verified its protection from enzymatic degradation. Expression of MOMP protein in DMCNP-transfected Cos-7 cells was demonstrated via Western blotting and immunofluorescence microscopy. Significantly, intramuscular injection of BALB/c mice with DMCNP confirmed the delivery of encapsulated DMOMP, and expression of the MOMP gene transcript in thigh muscles and spleens. Our data show that encapsulation of DMOMP in biodegradable chitosan nanoparticles imparts stability and protection from enzymatic digestion, and enhances delivery and expression of DMOMP in vitro and in mice. Further investigations of the nanoencapsulated DMCNP vaccine formulation against C. trachomatis in mice are warranted. PMID:23690681

Polymer-coated albumin microspheres as carriers for intravascular tumour targeting of cisplatin.

PubMed

Verrijk, R; Smolders, I J; McVie, J G; Begg, A C

1991-01-01

We used a poly-lactide-co-glycolide polymer (PLAGA 50:50) to formulate cisplatin (cDDP) into microspheres designed for intravascular administration. Two systems were developed. PLAGA-coated albumin microspheres and microspheres consisting of PLAGA only. PLAGA-coated microspheres displayed a mean diameter of 31.8 +/- 0.9 microns and a payload of 7.5% cDDP (w/w). Solid PLAGA microspheres exhibited a mean diameter of 19.4 +/- 0.6 microns and a payload of 20% cDDP. Release characteristics and in vitro effects on L1210 leukemia and B16 melanoma cell lines were investigated. Both types of microsphere overcame the initial rapid release of cDDP (burst effect), and PLAGA-coated albumin microspheres also showed a lag phase of approximately 30 min before cDDP release began. PLAGA-coated albumin microspheres released most of their payload through diffusion, and the coating eventually cracked after 7 days' incubation in saline supplemented with 0.1% Tween at 37 degrees C, enabling the release of any cDDP remaining. Effects of platinum, pre-released from PLAGA-coated albumin microspheres on the in vitro growth of L1210 cells were comparable with those of standard formulations (dissolved) of cDDP. Material released from non-drug-loaded PLAGA microspheres had no effect on L1210 cell growth, suggesting the absence of cytotoxic compounds in the matrix. The colony-forming ability of B16 cells was also equally inhibited by standard cDDP and pre-released drug. These studies show that formulation of cDDP in PLAGA-based microspheres prevents the rapid burst effect of cDDP seen in previous preparations and offers an improved system of administration for hepatic artery infusion or adjuvant therapy, enabling better clinical handling and the promise of a higher ratio of tumour tissue to normal tissue.

Polymeric and Solid Lipid Nanoparticles for Sustained Release of Carbendazim and Tebuconazole in Agricultural Applications

NASA Astrophysics Data System (ADS)

Campos, Estefânia Vangelie Ramos; Oliveira, Jhones Luiz De; da Silva, Camila Morais Gonçalves; Pascoli, Mônica; Pasquoto, Tatiane; Lima, Renata; Abhilash, P. C.; Fernandes Fraceto, Leonardo

2015-09-01

Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.

Surfactant adsorption and aggregate structure of silica nanoparticles: a versatile stratagem for the regulation of particle size and surface modification

NASA Astrophysics Data System (ADS)

Chaudhary, Savita; Rohilla, Deepak; Mehta, S. K.

2014-03-01

The area of silica nanoparticles is incredibly polygonal. Silica particles have aroused exceptional deliberation in bio-analysis due to great progress in particular arenas, for instance, biocompatibility, unique properties of modifiable pore size and organization, huge facade areas and pore volumes, manageable morphology and amendable surfaces, elevated chemical and thermal stability. Currently, silica nanoparticles participate in crucial utilities in daily trade rationales such as power storage, chemical and genetic sensors, groceries dispensation and catalysis. Herein, the size-dependent interfacial relation of anionic silica nanoparticles with twelve altered categories of cationic surfactants has been carried out in terms of the physical chemical facets of colloid and interface science. The current analysis endeavours to investigate the virtual consequences of different surfactants through the development of the objective composite materials. The nanoparticle size controls, the surface-to-volume ratio and surface bend relating to its interaction with surfactant will also be addressed in this work. More importantly, the simulated stratagem developed in this work can be lengthened to formulate core-shell nanostructures with functional nanoparticles encapsulated in silica particles, making this approach valuable and extensively pertinent for employing sophisticated materials for catalysis and drug delivery.

Effect of lipid types on physicochemical characteristics, stability and antioxidant activity of gamma-oryzanol-loaded lipid nanoparticles.

PubMed

Ruktanonchai, Uracha; Sakulkhu, Usawadee; Bejrapha, Piyawan; Opanasopit, Praneet; Bunyapraphatsara, Nuntavan; Junyaprasert, Varaporn; Puttipipatkhachorn, Satit

2009-11-01

In the present study gamma-oryzanol, an antioxidant, was incorporated into three different types of solid lipid: wax, triglycerides, a mixture of glycerides as solid lipid nanoparticles (SLN) and liquid lipid (Miglyol 812) as nanoemulsion (NE). Instability was found only from NE due to its significant increase in particle size and decreased entrapment efficiency (%EE) at a storage temperature of 45 degrees C. Solid lipid type in SLN plays an important role only on %EE, but not chemical stability. A decrease in crystallinity of SLN was observed with the incorporation of gamma-oryzanol and low recrystallization index were found with two glycerides-based SLN. The in vitro release studies demonstrated that a biphasic release pattern fitted well with the Higuchi model of SLN formulations. In comparison, nearly constant release was observed in NE comprised of similar composition. Wax-based SLN demonstrated the lowest cytotoxicity. NE, wax-based SLN and a mixture of glycerides-based SLN were considered to enhance the antioxidant activity of gamma-oryzanol.

Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

PubMed

Joseph, Emil; Reddi, Satish; Rinwa, Vibhu; Balwani, Garima; Saha, Ranendra

2017-06-15

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Oral Delivery of DMAB-Modified Docetaxel-Loaded PLGA-TPGS Nanoparticles for Cancer Chemotherapy

NASA Astrophysics Data System (ADS)

Chen, Hongbo; Zheng, Yi; Tian, Ge; Tian, Yan; Zeng, Xiaowei; Liu, Gan; Liu, Kexin; Li, Lei; Li, Zhen; Mei, Lin; Huang, Laiqiang

2011-12-01

Three types of nanoparticle formulation from biodegradable PLGA-TPGS random copolymer were developed in this research for oral administration of anticancer drugs, which include DMAB-modified PLGA nanoparticles, unmodified PLGA-TPGS nanoparticles and DMAB-modified PLGA-TPGS nanoparticles. Firstly, the PLGA-TPGS random copolymer was synthesized and characterized. DMAB was used to increase retention time at the cell surface, thus increasing the chances of particle uptake and improving oral drug bioavailability. Nanoparticles were found to be of spherical shape with an average particle diameter of around 250 nm. The surface charge of PLGA-TPGS nanoparticles was changed to positive after DMAB modification. The results also showed that the DMAB-modified PLGA-TPGS nanoparticles have significantly higher level of the cellular uptake than that of DMAB-modified PLGA nanoparticles and unmodified PLGA-TPGS nanoparticles. In vitro, cytotoxicity experiment showed advantages of the DMAB-modified PLGA-TPGS nanoparticle formulation over commercial Taxotere® in terms of cytotoxicity against MCF-7 cells. In conclusion, oral chemotherapy by DMAB-modified PLGA-TPGS nanoparticle formulation is an attractive and promising treatment option for patients.

Effect of Oxygen-containing Functional Groups on Protein Stability in Ionic Liquid Solutions

NASA Technical Reports Server (NTRS)

Turner, Megan B.; Holbrey, John D.; Spear, Scott K.; Pusey, Marc L.; Rogers, Robin D.

2004-01-01

The ability of functionalized ionic liquids (ILs) to provide an environment of increased stability for biomolecules has been studied. Serum albumin is an inexpensive, widely available protein that contributes to the overall colloid osmotic blood pressure within the vascular system. Albumin is used in the present study as a marker of biomolecular stability in the presence of various ILs in a range of concentrations. The incorporation of hydroxyl functionality into the methylimidazolium-based cation leads to increased protein stability detected by fluorescence spectroscopy and circular dichroic (CD) spectrometry.

Current Challenges and Future of Lipid nanoparticles formulations for topical drug application to oral mucosa, skin, and eye.

PubMed

Guilherme, Viviane A; Ribeiro, Ligia N M; Tofoli, Giovana Radomille; Franz-Montan, Michelle; de Paula, Eneida; de Jesus, Marcelo Bispo

2017-11-21

Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanostructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid nanoparticles performance and toxicity. We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded the key points that have to be overcome to help them to reach the market in topical formulations to oral mucosa, skin and eye. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Characterizing the interactions of organic nanoparticles with renal epithelial cells in vivo.

PubMed

Nair, Anil V; Keliher, Edmund J; Core, Amanda B; Brown, Dennis; Weissleder, Ralph

2015-01-01

Nanotechnology approaches are actively being pursued for drug delivery, novel diagnostics, implantable devices, and consumer products. While considerable research has been performed on the effects of these materials on targeted tumor or phagocytic cells, relatively little is known about their effects on renal cells. This becomes critical for supersmall nanoparticles (<10 nm), designed to be renally excreted. The active endocytic machinery of kidney proximal tubules avidly internalizes filtered proteins, which may also be the case for filtered nanoparticles. To test whether such interactions affect kidney function, we injected mice with either 5 nm dextran-based nanoparticles (DNP) that are similar in composition to FDA-approved materials or poly(amido amine) dendrimer nanoparticles (PNP) of comparable size. These fluorescently tagged nanoparticles were both filtered and internalized by renal tubular epithelial cells in a dose- and time-dependent fashion. The biological effects were quantitated by immunocytochemistry, measuring kidney injury markers and performing functional tests. DNP administration resulted in a dose-dependent increase in urinary output, while cellular albumin endocytosis was increased. The expression of megalin, a receptor involved in albumin uptake, was also increased, but AQP1 expression was unaffected. The effects after PNP administration were similar but additionally resulted in increased clathrin expression and increased endocytosis of dextran. We conclude that there are no major detrimental renal effects of DNP on overall kidney function, but changes in endocytosis-mediating protein expression do occur. These studies provide a framework for the testing of additional nanoparticle preparations as they become available.

Pickering emulsions stabilized by biodegradable block copolymer micelles for controlled topical drug delivery.

PubMed

Laredj-Bourezg, Faiza; Bolzinger, Marie-Alexandrine; Pelletier, Jocelyne; Chevalier, Yves

2017-10-05

Surfactant-free biocompatible and biodegradable Pickering emulsions were investigated as vehicles for skin delivery of hydrophobic drugs. O/w emulsions of medium-chain triglyceride (MCT) oil droplets loaded with all-trans retinol as a model hydrophobic drug were stabilized by block copolymer nanoparticles: either poly(lactide)-block-poly(ethylene glycol) (PLA-b-PEG) or poly(caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG). Those innovative emulsions were prepared using two different processes allowing drug loading either inside oil droplets or inside both oil droplets and non-adsorbed block copolymer nanoparticles. Skin absorption of retinol was investigated in vitro on pig skin biopsies using the Franz cell method. Supplementary experiments by confocal fluorescence microscopy allowed the visualization of skin absorption of the Nile Red dye on histological sections. Retinol and Nile Red absorption experiments showed the large accumulation of hydrophobic drugs in the stratum corneum for the Pickering emulsions compared to the surfactant-based emulsion and an oil solution. Loading drug inside both oil droplets and block copolymer nanoparticles enhanced again skin absorption of drugs, which was ascribed to the supplementary contribution of free block copolymer nanoparticles loaded with drug. Such effect allowed tuning drug delivery to skin over a wide range by means of a suitable selection of either the formulation or the drug loading process. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective effects of poly (butyl) cyanoacrylate nanoparticles containing vasoactive intestinal peptide against 6-hydroxydopamine-induced neurotoxicity in vitro.

PubMed

Xu, Zhi-Ran; Wang, Wu-Fang; Liang, Xin-Fang; Liu, Ze-Hua; Liu, Yu; Lin, Liang; Zhu, Xuan

2015-04-01

The present study investigated brain delivery system of vasoactive intestinal peptide (VIP) adsorbed on poly (butyl cyanoacrylate) nanoparticles coated with polysorbate 80 (P80-poly (butyl) cyanoacrylate (PBCA)-nanoparticles (NPs)) and the neuroprotective effects on the formulation in the model of 6-hydroxydopamine (6-OHDA)-induced Parkinsonian dysfunction in the human neuroblastoma cell line SH-SY5Y. Drug-loaded nanoparticles were prepared by emulsion polymerization method using VIP and PBCA and then stirring with polysorbate 80. The resulting nanoparticles possessed high entrapment efficiency and favorable stability against CaCl2 or fetal bovine serum (FBS)-induced aggregation. Use of fluorescein isothiocyanate (FITC)-conjugated polysorbate 80-PBCA nanoparticles in confocal microscopy revealed that nanoparticles are located inside, while the FITC solution could not penetrate into the cells. The blank nanoparticles showed no significant effects on cell viability, indicating that they had no role in protection; however, polysorbate 80-modified VIP-loading PBCA nanoparticles showed enhanced cell viability compared to free VIP in 6-OHDA-mimic cellular model of Parkinson's disease. In addition, the nanoparticles strikingly increased the anti-apoptosis activity and restored the loss of mitochondrial membrane potential (MMP) significantly after the treatment of 6-OHDA. These results demonstrated that the activity of VIP was enhanced by polysorbate 80-PBCA nanoparticles compared to control solutions, suggesting that PBCA nanoparticles coated with polysorbate 80 could be an effective carrier system for VIP.

Evaluation of antitumor activity and development of solid lipid nanoparticles of metronidazole analogue.

PubMed

Lages, Eduardo Burgarelli; de Freitas, Maria Betânia; Gonçalves, Isadora Marques Brum; Alves, Ricardo José; Vianna-Soares, Cristina Duarte; Ferreira, Lucas Antônio Miranda; de Oliveira, Mônica Cristina; de Oliveira, Renata Barbosa

2013-11-01

Nitroheterocyclic compounds have received considerable interest as hypoxia-selective cytotoxins (HSC) for cancer treatment. In the present study, we investigated antitumor activity of an iodide analogue of metronidazole, 1-(2-iodoethyl)-2-methyl-5-nitroimidazole (MTZ-I), using Swiss mice bearing solid Ehrlich tumor. MTZ-I showed potent anti-cancer activity at a dose of 40 mg/kg. MTZ-I loaded solid lipid nanoparticles (SLN) were developed as an alternative colloidal carrier system to enhance tumor drug uptake. SLN were characterized for particle size, polydispersity index, zeta potential and entrapment efficiency. In addition, the influence of presence of the cationic lipid stearylamine (STE) on stability of formulation was assessed. The results of DSC study showed that MTZ-I exhibited interaction with STE.

A new nanospray drying method for the preparation of nicergoline pure nanoparticles

NASA Astrophysics Data System (ADS)

Martena, Valentina; Censi, Roberta; Hoti, Ela; Malaj, Ledjan; Di Martino, Piera

2012-06-01

Three different batches of pure nanoparticles (NPs) of nicergoline (NIC) were prepared by spray drying a water:ethanol solution by a new Nano Spray Dryer Büchi B-90. Spherical pure NPs were obtained, and several analytical techniques such as differential scanning calorimetry and X-ray powder diffractometry permitted to assess their amorphous character. A comparison of the solubility, intrinsic dissolution, and drug release of original particles and pure amorphous NPs were determined, revealing an interesting improvement of biopharmaceutical properties of amorphous NPs, due to both amorphous properties and nanosize dimensions. Since in a previous work, the high-thermodynamic stability of amorphous NIC was demonstrated, this study is addressed toward the formulation of NIC as pure amorphous NPs.

Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

PubMed

Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

2015-02-01

Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

SERS+MEF of the anti-tumoral drug emodin adsorbed on silver nanoparticles

NASA Astrophysics Data System (ADS)

Sevilla, Paz; De Llanos, Raquel; Domingo, Concepción; Sánchez-Cortés, Santiago; García-Ramos, José V.

2010-02-01

Metal nanostructures are known to amplify the spontaneous emission of fluorescent molecules by resonant coupling to external electromagnetic fields. We have used spectroscopy to characterize the structural properties of emodin molecules, a natural anthraquinone dye, and bovine serum albumin, the most abundant protein in plasma, in the presence of silver nanoparticles. Aggregation of emodin at pH=10 and pH=6 gives rise to SERS and MEF effects in silver colloid. We have obtained MEF spectra at acidic pH=2.9 using two different silver nanostructures. We have also studied the change in the secondary structure of bovine serum albumin adsorbed on metal nanoparticles surface. Circular dichroism, fluorescence emission and fluorescence lifetime measurements indicate an increase in the alfa-helical content of the protein and a change in the environment of the tryptophan residues that bury in the interior of the biomolecule. This variation on the secondary structure could have further influence in the binding of the drug to form transport and regulatory complexes.

Date seed oil loaded niosomes: development, optimization and anti-inflammatory effect evaluation on rats.

PubMed

Soliman, Mahmoud S; Abd-Allah, Fathy I; Hussain, Talib; Saeed, Noha M; El-Sawy, Hossam S

2018-07-01

An optimized date seed oil (DSO) loaded niosomes was formulated. Maximize the extract anti-inflammatory efficacy and govern its release characteristics from nanoparticles for osteoarthritis prevention and treatment purposes. By using Box-Behnken Design, the effect of three formulation factors on the entrapment efficiency percentage (Y 1 ), initial DSO release percentage after 2 h (Y 2 ), and cumulative DSO release percentage of DSO after 12 h (Y 3 ), were optimized and studied. The optimized DSO formulation was specified, elaborated, particle size and zeta potential assessed, examined morphologically under electron and light microscope, and in vivo evaluated via carrageenan-induced rat paw edema study. 65.89%, 18.39%, and 58.27% were the measured responses of the optimized niosomes for Y 1 , Y 2 , and Y 3 , respectively. The vesicular structure of the optimized DSO loaded nano-vesicles with nano-size range and good stability features were confirmed. Furthermore, a distinguished anti-inflammatory activity in both prompt and sustained effectiveness were exhibited via the optimized DSO niosomes. Interestingly, the delayed efficacy outcomes of the extract loaded nanoparticles showed a similarity profile as well as the negative control group outcomes. To emphasize, DSO loading in niosomes revealed a significant enhancement toward inflammation alleviation, which offers a promising implement in osteoarthritis remediation and prohibition.

Controlled Fabrication of Gelatin Nanoparticles as Drug Carriers

NASA Astrophysics Data System (ADS)

Jahanshahi, M.; Sanati, M. H.; Minuchehr, Z.; Hajizadeh, S.; Babaei, Z.

2007-08-01

In recent years, significant effort has been devoted to develop nanotechnology for drug delivery since it offers a suitable means of delivering small molecular weight drugs, as well as macromolecules such as proteins, peptides or genes by either localized or targeted delivery to the tissue of interest. Nanotechnology focuses on formulating therapeutic agents in biocompatible nanocomposites such as nanoparticles, nanocapsules, micellar systems, and conjugates. Protein nanoparticles (BSA, HAS and gelatin) generally vary in size from 50-300 nm and they hold certain advantages such as greater stability during storage, stability in vivo, non-toxicity, non-antigen and ease to scale up during manufacture over the other drug delivery systems. The primary structure of gelatin offers many possibilities for chemical modification and covalent drug attachment. Here nanoparticles of gelatin type A were prepared by a two-step desolvation method as a colloidal drug delivery system and the essential parameters in fabrication were considered. Gelatin was dissolved in 25 mL distilled water under room temperature range. Then acetone was added to the gelatin solution as a desolvating agent to precipitate the high molecular weight (HMW) gelatin. The supernatant was discarded and the HMW gelatin re-dissolved by adding 25 mL distilled water and stirring at 600 rpm. Acetone were added drop-wise to form nanoparticles. At the end of the process, glutaraldehyde solution was used for preparing nanoparticles as a cross-linking agent, and stirred for 12h at 600 rpm. For purification stage we use centrifuge with 600rpm for 3 times. The objective of the present study is consideration of some factors such as temperature, gelatin concentration, agitation speed and the amount of acetone and their effects on size and distribution of nanoparticles. Among the all conditions, 60° C, 50 mg/ml gelatin concentration, 75 ml acetone had the best result and the nanoparticle size was under 170 nm. The effect of these factors for synthesis of gelatine nanoparticle is strongly discussed.

Polymeric Nanoparticles as a Metolachlor Carrier: Water-Based Formulation for Hydrophobic Pesticides and Absorption by Plants.

PubMed

Tong, Yujia; Wu, Yan; Zhao, Caiyan; Xu, Yong; Lu, Jianqing; Xiang, Sheng; Zong, Fulin; Wu, Xuemin

2017-08-30

Pesticide formulation is highly desirable for effective utilization of pesticide and environmental pollution reduction. Studies of pesticide delivery system such as microcapsules are developing prosperously. In this work, we chose polymeric nanoparticles as a pesticide delivery system and metolachlor was used as a hydrophobic pesticide model to study water-based mPEG-PLGA nanoparticle formulation. Preparation, characterization results showed that the resulting nanoparticles enhanced "water solubility" of hydrophobic metolachlor and contained no organic solvent or surfactant, which represent one of the most important sources of pesticide pollution. After the release study, absorption of Cy5-labeled nanoparticles into rice roots suggested a possible transmitting pathway of this metolachlor formulation and increased utilization of metolachlor. Furthermore, the bioassay test demonstrated that this nanoparticle showed higher effect than non-nano forms under relatively low concentrations on Oryza sativa, Digitaria sanguinalis. In addition, a simple cytotoxicity test involving metolachlor and metolachlor-loaded nanoparticles was performed, indicating toxicity reduction of the latter to the preosteoblast cell line. All of these results showed that those polymeric nanoparticles could serve as a pesticide carrier with lower environmental impact, comparable effect, and effective delivery.

A novel and organic solvent-free preparation of solid lipid nanoparticles using natural biopolymers as emulsifier and stabilizer.

PubMed

Xue, Jingyi; Wang, Taoran; Hu, Qiaobin; Zhou, Mingyong; Luo, Yangchao

2017-10-05

In this work, a new and novel organic solvent-free and synthetic surfactant-free method was reported to fabricate stable solid lipid nanoparticles (SLNs) from stearic acid, sodium caseinate (NaCas) and pectin, as well as water. Melted stearic acid was directly emulsified into an aqueous phase containing NaCas and pectin, followed by pH adjustment and thermal treatment to induce the formation of a compact and dense polymeric coating which stabilized SLNs. The preparation procedures and formulations were comprehensively optimized. The inter- and intra-molecular interactions among three ingredients were characterized by fluorescence and Fourier transform infrared spectroscopies. The stability of as-prepared SLNs was evaluated under simulated gastrointestinal conditions, and compared with traditional SLNs prepared with organic solvents. Our results revealed that the SLNs prepared from this organic solvent-free method had superior physicochemical properties over the traditional SLNs, including smaller size and better stability. Furthermore, redispersible SLNs powders were obtained by nano spray drying, but only the SLNs prepared by organic solvent-free method had sub-micron scale, uniform and spherical morphology. The organic solvent-free preparation method was proved to be a promising approach to prepare stable and uniform SLNs for potential oral delivery applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Design of Curcumin Loaded PLGA Nanoparticles Formulation with Enhanced Cellular Uptake, and Increased Bioactivity in vitro and Superior Bioavailability in vivo

PubMed Central

Anand, Preeta; Nair, Harish B.; Sung, Bokyung; Kunnumakkara, Ajaikumar B.; Yadav, Vivek R.; Tekmal, Rajeshwar R.; Aggarwal, Bharat B.

2011-01-01

Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with antioxidant, anti-inflammatory, anti-proliferative, anticancer, antidiabetic, antirheumatic, and antiviral effects, but its optimum potential is limited by its lack of solubility in aqueous solvents and poor oral bioavailability. We employed a polymer-based nanoparticle approach to improve bioavailability. Curcumin was encapsulated with 97.5% efficiency in biodegradable nanoparticulate formulation based on poly (lactide-co-glycolide) (PLGA) and a stabilizer polyethylene glycol (PEG)-5000. Dynamic laser light scattering and transmission electron microscopy indicated a particle diameter of 80.9 nm. This curcumin, renamed from hereon “as curcumin (NP)”, was characterized for its biological activity. In vitro curcumin (NP) exhibited very rapid (2 h vs > 72 h) and more efficient cellular uptake then curcumin. Estrase staining revealed that curcumin (NP) was at least as potent as or more potent than curcumin in inducing apoptosis of leukemic cells and in suppressing proliferation of various tumor cell lines. When examined by electrophoretic gel shift mobility assay, curcumin (NP) was more active than curcumin in inhibiting TNF-induced NF-κB activation and in suppression of NF-κB-regulated proteins involved in cell proliferation (cyclin D1), invasion (MMP-9), and angiogenesis (VEGF). In mice, curcumin (NP) was more bioavailable and had a longer half-life than curcumin. Overall we demonstrate that curcumin-loaded PLGA nanoparticles formulation has enhanced cellular uptake, and increased bioactivity in vitro and superior bioavailability in vivo over curcumin. PMID:19735646

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

PubMed Central

Halayqa, Mohammed; Domańska, Urszula

2014-01-01

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles. PMID:25535080

PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

PubMed

Halayqa, Mohammed; Domańska, Urszula

2014-12-22

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

Natural lipids-based NLC containing lidocaine: from pre-formulation to in vivo studies.

PubMed

Ribeiro, Lígia N M; Breitkreitz, Márcia C; Guilherme, Viviane A; da Silva, Gustavo H R; Couto, Verônica M; Castro, Simone R; de Paula, Bárbara O; Machado, Daisy; de Paula, Eneida

2017-08-30

In a nanotechnological approach we have investigated the use of natural lipids in the preparation of nanostructured lipid carriers (NLC). Three different NLC composed of copaiba oil and beeswax, sweet almond oil and shea butter, and sesame oil and cocoa butter as structural matrices were optimized using factorial analysis; Pluronic® 68 and lidocaine (LDC) were used as the colloidal stabilizer and model encapsulated drug, respectively. The optimal formulations were characterized by different techniques (IR-ATR, DSC, and TEM), and their safety and efficacy were also tested. These nanocarriers were able to upload high amounts of the anesthetic with a sustained in vitro release profile for 24h. The physicochemical stability in terms of size (nm), PDI, zeta potential (mV), pH, nanoparticle concentration (particles/mL), and visual inspection was followed during 12months of storage at 25°C. The formulations exhibited excellent structural properties and stability. They proved to be nontoxic in vitro (cell viability tests with Balb/c 3T3 fibroblasts) and significantly improved the in vivo effects of LDC, over the heart rate of zebra fish larvae and in the blockage of sciatic nerve in mice. The results from this study support that the proper combination of natural excipients is promising in DDS, taking advantage of the biocompatibility, low cost, and diversity of lipids. Copyright © 2017 Elsevier B.V. All rights reserved.

Essential Oils Loaded in Nanosystems: A Developing Strategy for a Successful Therapeutic Approach

PubMed Central

Bilia, Anna Rita; Guccione, Clizia; Isacchi, Benedetta; Righeschi, Chiara; Firenzuoli, Fabio; Bergonzi, Maria Camilla

2014-01-01

Essential oils are complex blends of a variety of volatile molecules such as terpenoids, phenol-derived aromatic components, and aliphatic components having a strong interest in pharmaceutical, sanitary, cosmetic, agricultural, and food industries. Since the middle ages, essential oils have been widely used for bactericidal, virucidal, fungicidal, antiparasitical, insecticidal, and other medicinal properties such as analgesic, sedative, anti-inflammatory, spasmolytic, and locally anaesthetic remedies. In this review their nanoencapsulation in drug delivery systems has been proposed for their capability of decreasing volatility, improving the stability, water solubility, and efficacy of essential oil-based formulations, by maintenance of therapeutic efficacy. Two categories of nanocarriers can be proposed: polymeric nanoparticulate formulations, extensively studied with significant improvement of the essential oil antimicrobial activity, and lipid carriers, including liposomes, solid lipid nanoparticles, nanostructured lipid particles, and nano- and microemulsions. Furthermore, molecular complexes such as cyclodextrin inclusion complexes also represent a valid strategy to increase water solubility and stability and bioavailability and decrease volatility of essential oils. PMID:24971152

Preservation of anthocyanins in solid lipid nanoparticles: Optimization of a microemulsion dilution method using the Placket-Burman and Box-Behnken designs.

PubMed

Ravanfar, Raheleh; Tamaddon, Ali Mohammad; Niakousari, Mehrdad; Moein, Mahmoud Reza

2016-05-15

Anthocyanins are the main polyphenol components from red cabbage (Brassica oleracea L. Var. Capitata f. Rubra) extracts that have inherent antioxidant activities. Anthocyanins are effectively stable in acidic gastric digestion conditions, with nearly 100% phenol content recovery. However, the total phenol content recovery after simulated pancreatic digestion was approximately 25%. To protect anthocyanins against harsh environmental conditions (e.g., pH and temperature), solid lipid nanoparticles were prepared by the dilution of water in oil (w/o) microemulsions containing anthocyanins in aqueous media. The formulations were characterized for particle size and encapsulation efficiency. The formulation parameters (e.g., volume of the internal aqueous phase, homogenization time and the percentages of total lipid, total surfactant or stabilizer) were optimized using the Placket-Burman and Box-Behnken experimental designs. Entrapment efficiency (89.2 ± 0.3%) was calculated when the mean particle size was 455 ± 2 nm. A scanning electron microscopy study revealed the spherical morphology of the particles. Copyright © 2015 Elsevier Ltd. All rights reserved.

Physico-chemical characterization of engineered metal oxide nanoparticles: the critical role of microscopy

NASA Astrophysics Data System (ADS)

La Fontaine, A.; Coleman, V. A.; Jämting, A. K.; Lawn, M.; Herrmann, J.; Miles, J. R.

2010-06-01

Three different methods for extracting zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles from commercially available sunscreen were investigated to determine the most appropriate route for producing a sample suitable for measuring the primary particle size. Direct dilution of the formulation, centrifugal methods and chemical washing were trialed in combination with ultrasonic processing and surfactant addition to generate samples that are suitable for particle size analysis. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to monitor the extraction and re-dispersion process. Washing with hexane, methanol and water to remove the formulation, in combination with pulsed high-powered ultrasonication and the addition of a charge-stabilizing surfactant was found to be the most efficient way of producing de-agglomerated samples. DLS measurements gave average hydrodynamic particle diameters of 87 nm for ZnO and 76 nm for TiO2, compared to equivalent spherical particle diameters of 21 +/- 12 nm for ZnO (81 particles) and 19 +/- 14 nm for TiO2 (81 particles) obtained from TEM analysis.

Stability and Reactivity: Positive and Negative Aspects for Nanoparticle Processing.

PubMed

Xu, Liang; Liang, Hai-Wei; Yang, Yuan; Yu, Shu-Hong

2018-04-11

Nanoparticles exist far from the equilibrium state due to their high surface energy. Nanoparticles are therefore extremely unstable and easily change themselves or react with active substances to reach a relatively stable state in some cases. This causes desired changes or undesired changes to nanoparticles and thus makes them exhibit a high reactivity and a poor stability. Such dual nature (poor stability and high reactivity) of nanoparticles may result in both negative and positive effects for nanoparticle processing. However, the existing studies mainly focus on the high reactivity of nanoparticles, whereas their poor stability has been neglected or considered inconsequential. In fact, in some cases the unstable process, which is derived from the poor stability of nanoparticles, offers an opportunity to design and fabricate unique nanomaterials, such as by chemically transforming the "captured" intermediate nanostructures during a changing process, assembling destabilized nanoparticles into larger ordered assemblies, or shrinking/processing pristine materials into the desired size or shape via selective etching. In this review, we aim to present the stability and reactivity of nanoparticles on three levels: the foundation, concrete manifestations, and applications. We start with a brief introduction of dangling bonds and the surface chemistry of nanoparticles. Then, concrete manifestations of the poor stability and high reactivity of nanoparticles are presented from four perspectives: dispersion stability, thermal stability, structural stability, and chemical stability/reactivity. Next, we discuss some issues regarding the stability and reactivity of nanomaterials during applications. Finally, conclusions and perspectives on this field are presented.

Effect of PEG molecular weight on stability, T₂ contrast, cytotoxicity, and cellular uptake of superparamagnetic iron oxide nanoparticles (SPIONs).

PubMed

Park, Yoonjee C; Smith, Jared B; Pham, Tuan; Whitaker, Ragnhild D; Sucato, Christopher A; Hamilton, James A; Bartolak-Suki, Elizabeth; Wong, Joyce Y

2014-07-01

Superparamagnetic iron oxide nanoparticles (SPIONs) are currently unavailable as MRI contrast agents for detecting atherosclerosis in the clinical setting because of either low signal enhancement or safety concerns. Therefore, a new generation of SPIONs with increased circulation time, enhanced image contrast, and less cytotoxicity is essential. In this study, monodisperse SPIONs were synthesized and coated with polyethylene glycol (PEG) of varying molecular weights. The resulting PEGylated SPIONs were characterized, and their interactions with vascular smooth muscle cells (VSMCs) were examined. SPIONs were tested at different concentrations (100 and 500 ppm Fe) for stability, T2 contrast, cytotoxicity, and cellular uptake to determine an optimal formulation for in vivo use. We found that at 100 ppm Fe, the PEG 2K SPIONs showed adequate stability and magnetic contrast, and exhibited the least cytotoxicity and nonspecific cellular uptake. An increase in cell viability was observed when the SPION-treated cells were washed with PBS after 1h incubation compared to 5 and 24h incubation without washing. Our investigation provides insight into the potential safe application of SPIONs in the clinic. Copyright © 2014 Elsevier B.V. All rights reserved.

Drug nanoparticles: formulating poorly water-soluble compounds.

PubMed

Merisko-Liversidge, Elaine M; Liversidge, Gary G

2008-01-01

More than 40% of compounds identified through combinatorial screening programs are poorly soluble in water. These molecules are difficult to formulate using conventional approaches and are associated with innumerable formulation-related performance issues. Formulating these compounds as pure drug nanoparticles is one of the newer drug-delivery strategies applied to this class of molecules. Nanoparticle dispersions are stable and have a mean diameter of less than 1 micron. The formulations consist of water, drug, and one or more generally regarded as safe excipients. These liquid dispersions exhibit an acceptable shelf-life and can be postprocessed into various types of solid dosage forms. Drug nanoparticles have been shown to improve bioavailability and enhance drug exposure for oral and parenteral dosage forms. Suitable formulations for the most commonly used routes of administration can be identified with milligram quantities of drug substance, providing the discovery scientist with an alternate avenue for screening and identifying superior analogs. For the toxicologist, the approach provides a means for dose escalation using a formulation that is commercially viable. In the past few years, formulating poorly water-soluble compounds using a nanoparticulate approach has evolved from a conception to a realization whose versatility and applicability are just beginning to be realized.

High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

PubMed

Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

2011-01-01

Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

Cellular delivery of PEGylated PLGA nanoparticles.

PubMed

Pamujula, Sarala; Hazari, Sidhartha; Bolden, Gevoni; Graves, Richard A; Chinta, Dakshinamurthy Devanga; Dash, Srikanta; Kishore, Vimal; Mandal, Tarun K

2012-01-01

The objective of this study was to investigate the efficiency of uptake of PEGylated polylactide-co-gycolide (PLGA) nanoparticles by breast cancer cells. Nanoparticles of PLGA containing various amounts of polyethylene glycol (PEG, 5%-15%) were prepared using a double emulsion solvent evaporation method. The nanoparticles were loaded with coumarin-6 (C6) as a fluorescence marker. The particles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. Irrespective of the amount of PEG, all formulations yielded smooth spherical particles. However, a comparison of the particle size of various formulations showed bimodal distribution of particles. Each formulation was later passed through a 1.2 µm filter to obtain target size particles (114-335 nm) with zeta potentials ranging from -2.8 mV to -26.2 mV. While PLGA-PEG di-block (15% PEG) formulation showed significantly higher 4T1 cellular uptake than all other formulations, there was no statistical difference in cellular uptake among PLGA, PLGA-PEG-PLGA tri-block (10% PEG), PLGA-PEG di-block (5% PEG) and PLGA-PEG di-block (10% PEG) nanoparticles. These preliminary findings indicated that the nanoparticle formulation prepared with 15% PEGylated PLGA showed maximum cellular uptake due to it having the smallest particle size and lowest zeta potential. © 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

Recent advances in microparticle and nanoparticle delivery vehicles for mucosal vaccination.

PubMed

McNeela, E A; Lavelle, E C

2012-01-01

The great potential of mucosal vaccination is widely accepted but progress in the clinical development of subunit mucosal vaccines has been disappointing. Of the available approaches, the use of polymer-based microparticles is attractive because these delivery vehicles can be specifically tailored for vaccines and they offer the potential for integration of adjuvant. Here we address recent developments in the use of particulates as mucosal vaccines and the potential of novel targeting strategies, formulation approaches and adjuvant combinations to enhance the efficacy of particle-based mucosal vaccines. This review discusses the current status of mucosal vaccines based on particles and highlights several of the strategies that are currently under investigation for improving their immunogenicity. These include enhancing the stability of formulations in the luminal environment, increasing uptake by specifically targeting particles to mucosal inductive sites, and augmenting immunogenicity through co-formulation with immunostimulatory agents.

Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: preparation and characterization.

PubMed

Liu, Jie; Gong, Tao; Wang, Changguang; Zhong, Zhirong; Zhang, Zhirong

2007-08-01

Solid lipid nanoparticles (SLNs) loaded with insulin-mixed micelles (Ins-MMs) were prepared by a novel reverse micelle-double emulsion method, in which sodium cholate (SC) and soybean phosphatidylcholine (SPC) were employed to improve the liposolubility of insulin, and the mixture of stearic acid and palmitic acid were employed to prepare insulin loaded solid lipid nanoparticles (Ins-MM-SLNs). Some of the formulation parameters were optimized to obtain high quality nanoparticles. The particle size and zeta potential measured by photon correlation spectroscopy (PCS) were 114.7+/-4.68 nm and -51.36+/-2.04 mV, respectively. Nanospheres observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed extremely spherical shape. The entrapment efficiency (EE%) and drug loading capacity (DL%) determined with high performance liquid chromatogram (HPLC) by modified ultracentrifuge method were 97.78+/-0.37% and 18.92+/-0.07%, respectively. Differential scanning calorimetry (DSC) of Ins-MM-SLNs indicated no tendency of recrystallisation. The core-shell drug loading pattern of the SLNs was confirmed by fluorescence spectra and polyacrylamide gel electrophoresis (PAGE) which also proved the integrity of insulin after being incorporated into lipid carrier. The drug release behavior was studied by in situ and externally sink method and the release pattern of drug was found to follow Weibull and Higuchi equations. Results of stability evaluation showed a relatively long-term stability after storage at 4 degrees C for 6 months. In conclusion, SLNs with small particle size, excellent physical stability, high entrapment efficiency, good loading capacity for protein drug can be produced by this novel reverse micelle-double emulsion method in present study.

Surface charge effects in protein adsorption on nanodiamonds

NASA Astrophysics Data System (ADS)

Aramesh, M.; Shimoni, O.; Ostrikov, K.; Prawer, S.; Cervenka, J.

2015-03-01

Understanding the interaction of proteins with charged diamond nanoparticles is of fundamental importance for diverse biomedical applications. Here we present a thorough study of protein binding, adsorption kinetics and structure on strongly positively (hydrogen-terminated) and negatively (oxygen-terminated) charged nanodiamond particles using a quartz crystal microbalance by dissipation and infrared spectroscopy. By using two model proteins (bovine serum albumin and lysozyme) of different properties (charge, molecular weight and rigidity), the main driving mechanism responsible for the protein binding to the charged nanoparticles was identified. Electrostatic interactions were found to dominate the protein adsorption dynamics, attachment and conformation. We developed a simple electrostatic model that can qualitatively explain the observed adsorption behaviour based on charge-induced pH modifications near the charged nanoparticle surfaces. Under neutral conditions, the local pH around the positively and negatively charged nanodiamonds becomes very high (11-12) and low (1-3) respectively, which has a profound impact on the protein charge, hydration and affinity to the nanodiamonds. Small proteins (lysozyme) were found to form multilayers with significant conformational changes to screen the surface charge, while larger proteins (albumin) formed monolayers with minor conformational changes. The findings of this study provide a step forward toward understanding and eventually predicting nanoparticle interactions with biofluids.Understanding the interaction of proteins with charged diamond nanoparticles is of fundamental importance for diverse biomedical applications. Here we present a thorough study of protein binding, adsorption kinetics and structure on strongly positively (hydrogen-terminated) and negatively (oxygen-terminated) charged nanodiamond particles using a quartz crystal microbalance by dissipation and infrared spectroscopy. By using two model proteins (bovine serum albumin and lysozyme) of different properties (charge, molecular weight and rigidity), the main driving mechanism responsible for the protein binding to the charged nanoparticles was identified. Electrostatic interactions were found to dominate the protein adsorption dynamics, attachment and conformation. We developed a simple electrostatic model that can qualitatively explain the observed adsorption behaviour based on charge-induced pH modifications near the charged nanoparticle surfaces. Under neutral conditions, the local pH around the positively and negatively charged nanodiamonds becomes very high (11-12) and low (1-3) respectively, which has a profound impact on the protein charge, hydration and affinity to the nanodiamonds. Small proteins (lysozyme) were found to form multilayers with significant conformational changes to screen the surface charge, while larger proteins (albumin) formed monolayers with minor conformational changes. The findings of this study provide a step forward toward understanding and eventually predicting nanoparticle interactions with biofluids. Electronic supplementary information (ESI) available: The FTIR spectrum of nanodiamonds, QCM-D profiles of 50 nm nanodiamond adsorption on silica surfaces, QCM-D profiles of protein desorption after rinsing with water (rinsing experiment) and the full FTIR spectrum of proteins before and after adsorption on ND particles. See DOI: 10.1039/c5nr00250h

Spray-Dried Nanoparticle-in-Microparticle Delivery Systems (NiMDS) for Gene Delivery, Comprising Polyethylenimine (PEI)-Based Nanoparticles in a Poly(Vinyl Alcohol) Matrix.

PubMed

Schulze, Jan; Kuhn, Stephanie; Hendrikx, Stephan; Schulz-Siegmund, Michaela; Polte, Tobias; Aigner, Achim

2018-03-01

Nucleic acid-based therapies rely on efficient formulations for nucleic acid protection and delivery. As nonviral strategies, polymeric and lipid-based nanoparticles have been introduced; however, biological efficacy and biocompatibility as well as poor storage properties due to colloidal instability and their unavailability as ready-to-use systems are still major issues. Polyethylenimine is the most widely explored and promising candidate for gene delivery. Polyethylenimine-based polyplexes and their combination with liposomes, lipopolyplexes, are efficient for DNA or siRNA delivery in vitro and in vivo. In this study, a highly potent spray-dried nanoparticle-in-microparticle delivery system is presented for the encapsulation of polyethylenimine-based polyplexes and lipopolyplexes into poly(vinyl alcohol) microparticles, without requiring additional stabilizing agents. This easy-to-handle gene delivery device allows prolonged nanoparticle storage and protection at ambient temperature. Biological analyses reveal further advantages regarding profoundly reduced cytotoxicity and enhanced transfection efficacies of polyethylenimine-based nanoparticles from the nanoparticle-in-microparticle delivery system over their freshly prepared counterparts, as determined in various cell lines. Importantly, this nanoparticle-in-microparticle delivery system is demonstrated as ready-to-use dry powder to be an efficient device for the inhalative delivery of polyethylenimine-based lipopolyplexes in vivo, as shown by transgene expression in mice after only one administration. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comprehensive study of the drug delivery properties of poly(l-lactide)-poly(ethylene glycol) nanoparticles in rats and tumor-bearing mice.

PubMed

Shalgunov, Vladimir; Zaytseva-Zotova, Daria; Zintchenko, Arkadi; Levada, Tatiana; Shilov, Yuri; Andreyev, Dmitry; Dzhumashev, Dzhangar; Metelkin, Evgeny; Urusova, Alexandra; Demin, Oleg; McDonnell, Kevin; Troiano, Greg; Zale, Stephen; Safarovа, Elmira

2017-09-10

Nanoparticles made of polylactide-poly(ethylene glycol) block-copolymer (PLA-PEG) are promising vehicles for drug delivery due to their biodegradability and controllable payload release. However, published data on the drug delivery properties of PLA-PEG nanoparticles are heterogeneous in terms of nanoparticle characteristics and mostly refer to low injected doses (a few mg nanoparticles per kg body weight). We have performed a comprehensive study of the biodistribution of nanoparticle formulations based on PLA-PEG nanoparticles of ~100nm size at injected doses of 30 to 140mg/kg body weight in healthy rats and nude tumor-bearing mice. Nanoparticle formulations differed by surface PEG coverage and by release kinetics of the encapsulated model active pharmaceutical ingredient (API). Increase in PEG coverage prolonged nanoparticle circulation half-life up to ~20h in rats and ~10h in mice and decreased retention in liver, spleen and lungs. Circulation half-life of the encapsulated API grew monotonously as the release rate slowed down. Plasma and tissue pharmacokinetics was dose-linear for inactive nanoparticles, but markedly dose-dependent for the model therapeutic formulation, presumably because of the toxic effects of released API. A mathematical model of API distribution calibrated on the data for inactive nanoparticles and conventional API form correctly predicted the distribution of the model therapeutic formulation at the lowest investigated dose, but for higher doses the toxic action of the released API had to be explicitly modelled. Our results provide a coherent illustration of the ability of controllable-release PLA-PEG nanoparticles to serve as an effective drug delivery platform to alter API biodistribution. They also underscore the importance of physiological effects of released drug in determining the biodistribution of therapeutic drug formulations at doses approaching tolerability limits. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations.

PubMed

Özcan, Ipek; Azizoğlu, Erkan; Senyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

2013-01-01

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

PubMed Central

Özcan, İpek; Azizoğlu, Erkan; Şenyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

2013-01-01

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders. PMID:23390364

Disintegration of nano-embedded microparticles after deposition on mucus: A mechanistic study.

PubMed

Ruge, Christian A; Bohr, Adam; Beck-Broichsitter, Moritz; Nicolas, Valérie; Tsapis, Nicolas; Fattal, Elias

2016-03-01

The conversion of colloidal drug carriers/polymeric nanoparticles into dry microparticulate powders (e.g., by spray-drying) is a prominent approach to overcome the aerodynamic limitations of these formulations for delivery via inhalation. However, to what extent such nano-embedded microparticles disintegrate into individual/intact nanoparticles after contacting relevant physiological media has so far not been addressed. Polymeric nanoparticles were spray-dried into nano-embedded microparticles (NEMs) using different amounts of trehalose as embedding matrix excipient. Formulations were characterized and then evaluated for their disintegration behavior after aerosolization onto model mucus. Although a rapid and complete aqueous redispersion was observed for specific excipient/nanoparticle weight ratios (i.e., greater than 1/1), the same formulations revealed no disintegration after deposition onto a static mucus layer. Double-labeled NEMs powders (i.e., dual color staining of polymeric nanoparticles and trehalose) demonstrated rapid matrix dissolution, while the nanoparticle aggregates persisted. When deposited onto agitated mucus, however, sufficient disintegration of NEMs into individual polymeric nanoparticles was observed. These findings indicate that mechanical forces are necessary to overcome the attraction between individual nanoparticles found within the NEMs. Thus, it remains questionable whether the lung mechanics (e.g., breathing, mucociliary clearance) acting on these formulations will contribute to the overall disintegration process. Copyright © 2015 Elsevier B.V. All rights reserved.

Duloxetine HCl lipid nanoparticles: preparation, characterization, and dosage form design.

PubMed

Patel, Ketan; Padhye, Sameer; Nagarsenker, Mangal

2012-03-01

Solid lipid nanoparticles (SLNs) of duloxetine hydrochloride (DLX) were prepared to circumvent the problems of DLX, which include acid labile nature, high first-pass metabolism, and high-dosing frequency. The DLX-SLNs were prepared by using two different techniques, viz. solvent diffusion method and ultrasound dispersion method, and evaluated for particle size, zeta potential, entrapment efficiency, physical characteristics, and chemical stability. Best results were obtained when SLNs were prepared by ultrasound dispersion method using glyceryl mono stearate as solid lipid and DLX in ratio of 1:20 and mixture of polysorbate 80 and poloxamer 188 as surfactant in concentration of 3%. The mean particle size of formulation and entrapment efficiency was 91.7 nm and 87%, respectively, and had excellent stability in acidic medium. Differential scanning calorimetry and X-ray diffraction data showed complete amorphization of DLX in lipid. In vitro drug release from SLNs was observed for 48 h and was in accordance with Higuchi kinetics. In vivo antidepressant activity was evaluated in mice by forced swim test. DLX-SLNs showed significant enhancement in antidepressant activity at 24 h when administered orally in comparison to drug solution. These results confirm the potential of SLNs in enhancing chemical stability and improving the efficacy of DLX via oral route. The SLN dispersion was converted into solid granules by adsorbing on colloidal silicon dioxide and characterized for particle size after redispersion, morphology, and flow properties. Results indicated that nanoparticles were successfully adsorbed on the carrier and released SLNs when dispersed in water.

Multimodal Superparamagnetic Nanoparticles with Unusually Enhanced Specific Absorption Rate for Synergetic Cancer Therapeutics and Magnetic Resonance Imaging.

PubMed

Thorat, Nanasaheb D; Bohara, Raghvendra A; Malgras, Victor; Tofail, Syed A M; Ahamad, Tansir; Alshehri, Saad M; Wu, Kevin C-W; Yamauchi, Yusuke

2016-06-15

Superparamagnetic nanoparticles (SPMNPs) used for magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH) cancer therapy frequently face trade off between a high magnetization saturation and their good colloidal stability, high specific absorption rate (SAR), and most importantly biological compatibility. This necessitates the development of new nanomaterials, as MFH and MRI are considered to be one of the most promising combined noninvasive treatments. In the present study, we investigated polyethylene glycol (PEG) functionalized La1-xSrxMnO3 (LSMO) SPMNPs for efficient cancer hyperthermia therapy and MRI application. The superparamagnetic nanomaterial revealed excellent colloidal stability and biocompatibility. A high SAR of 390 W/g was observed due to higher colloidal stability leading to an increased Brownian and Neel's spin relaxation. Cell viability of PEG capped nanoparticles is up to 80% on different cell lines tested rigorously using different methods. PEG coating provided excellent hemocompatibility to human red blood cells as PEG functionalized SPMNPs reduced hemolysis efficiently compared to its uncoated counterpart. Magnetic fluid hyperthermia of SPMNPs resulted in cancer cell death up to 80%. Additionally, improved MRI characteristics were also observed for the PEG capped La1-xSrxMnO3 formulation in aqueous medium compared to the bare LSMO. Taken together, PEG capped SPMNPs can be useful for diagnosis, efficient magnetic fluid hyperthermia, and multimodal cancer treatment as the amphiphilicity of PEG can easily be utilized to encapsulate hydrophobic drugs.

STABILITY OF HEMOGLOBIN AND ALBUMIN ADDUCTS OF BENZENE OXIDE AND 1,4-BENZOQUINONE AFTER ADMINISTRATION OF BENZENE TO F344 RATS

EPA Science Inventory

The stability of cysteinyl adducts of benzene oxide (BO) and mono-S-substituted cysteinyl adducts of 1,4-benzoquinone (1,4-BQ) was investigated in both hemoglobin (Hb) and albumin (Alb) following administration of a single oral dose of 400 mg [U-14C/13C6]benzene/kg body weight ...

Feasibility of haloperidol-anchored albumin nanoparticles loaded with doxorubicin as dry powder inhaler for pulmonary delivery.

PubMed

Varshosaz, Jaleh; Hassanzadeh, Farshid; Mardani, Amin; Rostami, Mahboubeh

2015-03-01

Haloperidol (Hal) is a ligand that can target sigma 2 receptors over-expressed in non-small cell lung cancer. Hal targeted nanoparticles of bovine serum albumin (BSA) were prepared for pulmonary delivery of doxorubicin (DOX). The conjugation was confirmed by Fourier transform infrared spectroscopy (FTIR) and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopic methods. Nanoparticles were prepared by desolvation method from BSA-Hal and were loaded with DOX. They were characterized for their morphology, particle size, zeta potential, drug loading and release efficiency. The optimized nanoparticles were spray-dried using trehalose, l-leucin and mannitol as dry powder inhaler (DPI) in different inlet temperatures between 80 and 120°C. The obtained nanocomposites were characterized for their aerodynamic diameter, specific surface area (cm(2)/g) and fine particle fraction (FPF) by a Cascade Impactor device. The optimized nanoparticles showed particle size of 218 nm, zeta potential of -25.4 mV, drug entrapment efficiency of 89% and release efficiency of 56% until 2 h. After spray drying of these nanoparticles, the best results were obtained from mannitol with an inlet temperature of 80°C which produced a mean aerodynamic diameter of 4.58 μm, FPF of 66% and specific surface area of 6302.99 cm(2)/g. The obtained results suggest that the designed DPI could be a suitable inhaler for targeted delivery of DOX in pulmonary delivery.

Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice

PubMed Central

Kourtis, Iraklis C.; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A.; Swartz, Melody A.

2013-01-01

Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma. PMID:23626707

Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.

PubMed

Kourtis, Iraklis C; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A; Swartz, Melody A

2013-01-01

Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.

Development of biodegradable PLGA nanoparticles surface engineered with hyaluronic acid for targeted delivery of paclitaxel to triple negative breast cancer cells.

PubMed

Cerqueira, Brenda Brenner S; Lasham, Annette; Shelling, Andrew N; Al-Kassas, Raida

2017-07-01

This study aimed at development of poly (lactic-co-glycolic acid) (PLGA) nanoparticles embedded with paclitaxel and coated with hyaluronic acid (HA-PTX-PLGA) to actively target the drug to a triple negative breast cancer cells. Nanoparticles were successfully fabricated using a modified oil-in-water emulsion method. The effect of various formulations parameters on the physicochemical properties of the nanoparticles was investigated. SEM imaging confirmed the spherical shape and nano-scale size of the nanoparticles. A sustained drug release profile was obtained and enhanced PTX cytotoxicity was observed when MDA-MB-231 cells were incubated with the HA-PTX-PLGA formulation compared to cells incubated with the non-HA coated nanoparticles. Moreover, HA-PLGA nanoparticles exhibited improved cellular uptake, based on a possible receptor mediated endocytosis due to interaction of HA with CD44 receptors when compared to non-coated PLGA nanoparticles. The non-haemolytic potential of the nanoparticles indicated the suitability of the developed formulation for intravenous administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Concentrated dispersions of equilibrium protein nanoclusters that reversibly dissociate into active monomers

NASA Astrophysics Data System (ADS)

Truskett, Thomas M.; Johnston, Keith; Maynard, Jennifer; Borwankar, Ameya; Miller, Maria; Wilson, Brian; Dinin, Aileen; Khan, Tarik; Kaczorowski, Kevin

2012-02-01

Stabilizing concentrated protein solutions is of wide interest in drug delivery. However, a major challenge is how to reliably formulate concentrated, low viscosity (i.e., syringeable) solutions of biologically active proteins. Unfortunately, proteins typically undergo irreversible aggregation at intermediate concentrations of 100-200 mg/ml. In this talk, I describe how they can effectively avoid these intermediate concentrations by reversibly assembling into nanoclusters. Nanocluster assembly is achieved by balancing short-ranged, cosolute-induced attractions with weak, longer-ranger electrostatic repulsions near the isoelectric point. Theory predicts that native proteins are stabilized by a self-crowding mechanism within the concentrated environment of the nanoclusters, while weak cluster-cluster interactions can result in colloidally-stable dispersions with moderate viscosities. I present experimental results where this strategy is used to create concentrated antibody dispersions (up to 260 mg/ml) comprising nanoclusters of proteins [monoclonal antibody 1B7, polyclonal sheep Immunoglobin G and bovine serum albumin], which upon dilution in vitro or administration in vivo, are conformationally stable and retain activity.

nab-paclitaxel potentiates gemcitabine activity by reducing cytidine deaminase levels in a mouse model of pancreatic cancer

PubMed Central

Cook, Natalie; Bapiro, Tashinga E.; Lolkema, Martijn P.; Jodrell, Duncan I.; Tuveson, David A.

2016-01-01

nab-paclitaxel, an albumin-stabilized paclitaxel formulation, demonstrates clinical activity when administered in combination with gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma (PDA). The limited availability of patient tissue and exquisite sensitivity of xenografts to chemotherapeutics have limited our ability to address the mechanistic basis of this treatment regimen. Here, we used a mouse model of PDA to show that the co-administration of nab-paclitaxel and gemcitabine uniquely demonstrates evidence of tumor regression. Combination treatment increases intratumoral gemcitabine levels due to a marked decrease in the primary gemcitabine metabolizing enzyme, cytidine deaminase (Cda). Correspondingly, paclitaxel reduced Cda protein levels in cultured cells through reactive oxygen species-mediated degradation, resulting in the increased stabilization of gemcitabine. Our findings support the concept that suboptimal intratumoral concentrations of gemcitabine represent a crucial mechanism of therapeutic resistance in PDA and highlight the advantages of genetically engineered mouse models in preclinical therapeutic trials. PMID:22585996

Novel nanoparticles based on chitosan-dicarboxylate conjugates via tandem ionotropic/covalent crosslinking with tripolyphosphate and subsequent evaluation as drug delivery vehicles.

PubMed

Dmour, Isra; Taha, Mutasem O

2017-08-30

Chitosan-based nanoparticles prepared by ionotropic gelation are prone to stability issues. The aim of this work is to chemically modify chitosan by grafting to succinate, phthalate, glutarate and phenylsuccinate moieties and to investigate the suitability of the resulting polymers as covalently-crosslinked nanocarriers. Corresponding nanoparticles (NPs) were formulated by ionotropic gelation using tripolyphosphate (TPP) anion then they were covalently crosslinked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). Infrared and thermal analysis confirmed the formation of phosphoramide bonds within the NPs indicating the involvement of TPP in covalent crosslinking. This is the first time to report phosphormide covalent crosslinking within nanoparticles matrices. The resulting NPs were found to resist drastic pH and calcium ion conditions. Size analysis indicated the NPs to be spherical and less than 500nm in diameter. Loading studies using Safranine O showed enhanced NPs drug loading upon covalent crosslinking compared to ionotropic gelling. Doxorubicin-loaded NPs were of superior cytotoxic properties compared to free doxorubicin. Copyright © 2017 Elsevier B.V. All rights reserved.

Many Body Effects on Particle Diffusion in Polymer Nanocomposites

NASA Astrophysics Data System (ADS)

Dell, Zachary E.; Schweizer, Kenneth S.

2014-03-01

Recent statistical mechanical theories of nanoparticle motion in polymer melts and networks have focused on the dilute particle limit. By combining PRISM theory predictions for microscopic structural correlations, and a new formulation of self-consistent dynamical mode coupling theory, we extend dilute theories to finite filler loading. As a minimalist model, the polymer dynamics are first assumed to be unperturbed by the presence of the nanoparticles. The long time particle diffusivity in unentangled and entangled melts is determined as a function of polymer tube diameter and radius of gyration, nanoparticle diameter, and polymer-filler attraction strength under both constant volume and constant pressure situations. The influence of nanocomposite statistical structure (depletion, steric stabilization, bridging) on dynamics is also investigated. Using recent theoretical developments for predicting tube diameters in nanocomposites, the consequences of filler-induced tube dilation on nanoparticle motion is established. In entangled melts, increasing filler loading first modestly speeds up diffusion, and then dramatically when the inter-filler separation becomes smaller than the tube diameter. At very high loadings, a filler glass transition is generically predicted.

A New Method for Delivering a Hydrophobic Drug for Photodynamic Therapy Using Pure Nanocrystal Form of the Drug

PubMed Central

Baba, Koichi; Pudavar, Haridas E.; Roy, Indrajit; Ohulchanskyy, Tymish Y.; Chen, Yihui; Pandey, Ravindra; Prasad, Paras N.

2008-01-01

A carrier free method for delivery of a hydrophobic drug in its pure form, using nanocrystals (nano sized crystals) is proposed. To demonstrate this technique, nanocrystals of a hydrophobic photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl)pyropheophorbide (HPPH), have been synthesized using re-precipitation method. The resulting drug nanocrystals were monodispersed and stable in aqueous dispersion, without the necessity of an additional stabilizer (surfactant). As shown by confocal microscopy, these pure drug nanocrystals were taken-up by the cancer cells with high avidity. Though the fluorescence and photodynamic activity of the drug were substantially quenched in the form of nanocrystals in aqueous suspension, both these characteristics were recovered under in vitro and in vivo conditions. This recovery of drug activity and fluorescence is possibly due to the interaction of nanocrystals with serum albumin, resulting in conversion of the drug nanocrystals into the molecular form. This was confirmed by demonstrating similar recovery in presence of Fetal Bovine Serum (FBS) or Bovine Serum Albumin (BSA). Under similar treatment conditions, the HPPH in nanocrystal form or in 1% Tween 80/water formulation showed comparable in vitro and in vivo efficacy. PMID:17266331

Development of magnetic resonance imaging based detection methods for beta amyloids via sialic acid-functionalized magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Kouyoumdjian, Hovig

The development of a non-invasive method for the detection of Alzheimer's disease is of high current interest, which can be critical in early diagnosis and in guiding preventive treatment of the disease. The aggregates of beta amyloids are a pathological hallmark of Alzheimer's disease. Carbohydrates such as sialic acid terminated gangliosides have been shown to play significant roles in initiation of amyloid aggregation. Herein, we report a biomimetic approach using sialic acid coated iron oxide superparamagnetic nanoparticles for in vitro detection in addition to the assessment of the in vivo mouse-BBB (Blood brain barrier) crossing of the BSA (bovine serum albumin)-modified ones. The sialic acid functionalized dextran nanoparticles were shown to bind with beta amyloids through several techniques including ELISA (enzyme linked immunosorbent assay), MRI (magnetic resonance imaging), TEM (transmission electron microscopy), gel electrophoresis and tyrosine fluorescence assay. The superparamagnetic nature of the nanoparticles allowed easy detection of the beta amyloids in mouse brains in both in vitro and ex vivo model by magnetic resonance imaging. Furthermore, the sialic acid nanoparticles greatly reduced beta amyloid induced cytotoxicity to SH-SY5Y neuroblastoma cells, highlighting the potential of the glyconanoparticles for detection and imaging of beta amyloids. Sialic acid functionalized BSA (bovine serum albumin) nanoparticles also showed significant binding to beta amyloids, through ELISA and ex vivo mouse brain MRI experiments. Alternatively, the BBB crossing was demonstrated by several techniques such as confocal microscopy, endocytosis, exocytosis assays and were affirmed by nanoparticles transcytosis assays through bEnd.3 endothelial cells. Finally, the BBB crossing was confirmed by analyzing the MRI signal of nanoparticle-injected CD-1 mice.

Toxicological effects of three types of silver nanoparticles and their salt precursors acting on human U-937 and HL-60 cells.

PubMed

Barbasz, Anna; Oćwieja, Magdalena; Walas, Stanisław

2017-01-01

The growing popularity of nanomaterials requires a systematic study of their effects on the human body. Silver nanoparticles (AgNPs), due to their antiseptic properties, are used in almost every area of life. The purpose of the study was to examine whether the precursor used for the synthesis of nanoparticles affects their bio-influence and modifies their impact on cells of the human immune system. To compare the effects of precursor silver salts (AgNO 3 , CH 3 COOAg and AgClO 4 ) and corresponding nanoparticles (TAN TAA and TAC) cytotoxicity study was conducted on two cell lines U-937 and HL-60. For both cell lines, silver salts are more toxic than the corresponding nanoparticles. Cell viability after treatment with the two forms of silver (salt/particle) is dependent on silver dose and degree of cells differentiation. Addition of the silver salt of doses greater than 5 mg/L results in decreased cell viability by over 60%, whereas nanoparticles' addition reduces cell viability on average by 30%. On the basis of the determined LD 50 values it can be stated that for the tested cells the most toxic are AgClO 4 and TAC. Production of nitric oxide, which is a mediator of inflammation, is the greatest after treatment of the cells by TAC. Different interactions of studied nanoparticles with albumin has been found and it was shown that addition of albumin to the cells treated by nanoparticles reduces their toxic effects. Obtained by us highly purified, mono-disperse AgNPs exhibit diverse effects relative to the biological systems, depending on the precursor salt used.

Photonic monitoring of chitosan nanostructured alginate microcapsules for drug release

NASA Astrophysics Data System (ADS)

Khajuria, Deepak Kumar; Konnur, Manish C.; Vasireddi, Ramakrishna; Roy Mahapatra, D.

2015-02-01

By using a novel microfluidic set-up for drug screening applications, this study examines delivery of a novel risedronate based drug formulation for treatment of osteoporosis that was developed to overcome the usual shortcomings of risedronate, such as its low bioavailability and adverse gastric effects. Risedronate nanoparticles were prepared using muco-adhesive polymers such as chitosan as matrix for improving the intestinal cellular absorption of risedronate and also using a gastric-resistant polymer such as sodium alginate for reducing the gastric inflammation of risedronate. The in-vitro characteristics of the alginate encapsulated chitosan nanoparticles are investigated, including their stability, muco-adhesiveness, and Caco-2 cell permeability. Fluorescent markers are tagged with the polymers and their morphology within the microcapsules is imaged at various stages of drug release.

Albumin nanostructures as advanced drug delivery systems

PubMed Central

Karimi, Mahdi; Bahrami, Sajad; Ravari, Soodeh Baghaee; Zangabad, Parham Sahandi; Mirshekari, Hamed; Bozorgomid, Mahnaz; Shahreza, Somayeh; Sori, Masume; Hamblin, Michael R.

2016-01-01

Introduction One of the biggest impacts that the nanotechnology has made on medicine and biology, has been in the area of drug delivery systems (DDSs). Many drugs suffer from serious problems concerning insolubility, instability in biological environments, poor uptake into cells and tissues, suboptimal selectivity for targets and unwanted side effects. Nanocarriers can be designed as DDSs to overcome many of these drawbacks. One of the most versatile building blocks to prepare these nanocarriers is the ubiquitous, readily available and inexpensive protein, serum albumin. Areas covered This review covers the use of different types of albumin (human, bovine, rat, and chicken egg) to prepare nanoparticle and microparticle-based structures to bind drugs. Various methods have been used to modify the albumin structure. A range of targeting ligands can be attached to the albumin that can be recognized by specific cell receptors that are expressed on target cells or tissues. Expert opinion The particular advantages of albumin used in DDSs include ready availability, ease of chemical modification, good biocompatibility, and low immunogenicity. The regulatory approvals that have been received for several albumin-based therapeutic agents suggest that this approach will continue to be successfully explored. PMID:27216915

A new approach for the delivery of artemisinin: formulation, characterization, and ex-vivo antileishmanial studies.

PubMed

Want, Muzamil Yaqub; Islamuddin, Mohammad; Chouhan, Garima; Dasgupta, Anjan Kumar; Chattopadhyay, Asoke Prasun; Afrin, Farhat

2014-10-15

Artemisinin, a potential antileishmanial compound with poor bioavailability and stability has limited efficacy in visceral leishmaniasis. Encapsulating artemisinin into poly lactic-co glycolic nanoparticles may improve its effectiveness and reduce toxicity. Artemisinin-loaded nanoparticles were prepared, optimized (using Box-Behnken design) and characterized by dynamic light scattering technique, Atomic force microscopy (AFM), Transmission electron microscopy (TEM) and Fourier Transform-Infra Red spectroscopy. Release kinetics of artemisinin from optimized nanoformulation was studied by dialysis method at pH 7.4 and 5.5. Cytotoxicity and antileishmanial activity of these nanoparticles was tested on murine macrophages by MTT assay and macrophage-infested Leishmania donovani amastigotes ex vivo, respectively. Artemisinin-loaded nanoparticles were 221±14nm in diameter, with polydispersity index, zeta potential, drug loading and entrapment efficiency of 0.1±0.015, -9.07±0.69mV, 28.03±1.14 and 68.48±1.97, respectively. AFM and TEM studies indicated that the particles were spherical in shape. These colloidal particles showed a sustained release pattern in vitro. Treatment with artemisinin-loaded nanoparticles significantly reduced the number of amastigotes per macrophage and percent infected macrophages ex vivo compared to free artemisinin. These nanoparticles were also non-toxic to macrophages compared to artemisinin alone. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of biocompatibility and administration site reactogenicity of polyanhydride-particle-based platform for vaccine delivery.

PubMed

Huntimer, Lucas; Ramer-Tait, Amanda E; Petersen, Latrisha K; Ross, Kathleen A; Walz, Katherine A; Wang, Chong; Hostetter, Jesse; Narasimhan, Balaji; Wannemuehler, Michael J

2013-02-01

Efficacy, purity, safety, and potency are important attributes of vaccines. Polyanhydride particles represent a novel class of vaccine adjuvants and delivery platforms that have demonstrated the ability to enhance the stability of protein antigens as well as elicit protective immunity against bacterial pathogens. This work aims to elucidate the biocompatibility, inflammatory reactions, and particle effects on mice injected with a 5 mg dose of polyanhydride nanoparticles via common parenteral routes (subcutaneous and intramuscular). Independent of polymer chemistry, nanoparticles more effectively disseminated away from the injection site as compared to microparticles, which exhibited a depot effect. Using fluorescent probes, the in vivo distribution of three formulations of nanoparticles, following subcutaneous administration, indicated migration away from the injection site. Less inflammation was observed at the injection sites of mice-administered nanoparticles as compared to Alum and incomplete Freund's adjuvant. Furthermore, histological evaluation revealed minimal adverse injection site reactions and minimal toxicological effects associated with the administration of nanoparticles at 30 days post-administration. Collectively, these results demonstrate that polyanhydride nanoparticles do not induce inflammation as a cumulative effect of particle persistence or degradation and are, therefore, a viable candidate for a vaccine delivery platform. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation of Tc-99m-macroaggregated albumin from recombinant human albumin for lung perfusion imaging.

PubMed

Hunt, A P; Frier, M; Johnson, R A; Berezenko, S; Perkins, A C

2006-01-01

Human serum albumin (HSA) extracted from pooled blood taken from human donors is used in the production of (99m)Tc-labelled macroaggregated albumin (MAA) for lung perfusion imaging. However, concerns for the safety of blood-derived products due to potential contamination by infective agents (e.g. new variant CJD), make alternative production methods necessary. Recombinant DNA technology is a promising method of albumin production avoiding problems associated with human-derived HSA. This paper presents results comparing MAA prepared from recombinant human albumin (rHA, Recombumin) (rMAA) with in-house produced HSA MAA (hMAA) and commercially available MAA (cMAA). (99m)Tc-MAA was prepared using previously published production methods by heating a mixture of albumin and stannous chloride in acetate buffer (pH 5.4) at 70 degrees C for 20 min. Parameters investigated include aggregate size, radiolabelling efficiency, radiochemical and aggregate stability at 4 degrees C and in vitro (in whole human blood) at 37 degrees C and biodistribution studies. Results showed that rMAA could be produced with similar morphology, labelling efficiency and stability to hMAA and cMAA. Our findings confirm that rHA shows significant potential as a direct replacement for HSA in commercially available MAA.

Nanoparticle-stabilized CO₂ foam for CO₂ EOR application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ning; Lee, Robert; Yu, Jianjia

The purpose of this project was to develop nanoparticle-stabilized CO₂ foam for CO₂ -EOR application, in which nanoparticles instead of surfactants are used for stabilizing CO₂ foam to improve the CO₂ sweep efficiency and increase oil recovery. The studies included: (1) investigation of CO₂ foam generation nanoparticles, such as silica nanoparticles, and the effects of particle concentration and surface properties, CO₂/brine ratio, brine salinity, pressure, and temperature on foam generation and foam stability; (2) coreflooding tests to understand the nanoparticle-stabilized CO₂ foam for waterflooded residual oil recovery, which include: oil-free coreflooding experiments with nanoparticle-stabilized CO₂ foam to understand the transportationmore » of nanoparticles through the core; measurements of foam stability and CO₂ sweep efficiency under reservoir conditions to investigate temperature and pressure effects on the foam performance and oil recovery as well as the sweep efficiency in different core samples with different rock properties; and (3) long-term coreflooding experiments with the nanoparticle- stabilized CO₂ foam for residual oil recovery. Finally, the technical and economical feasibility of this technology was evaluated.« less

Strategic formulation of apigenin-loaded PLGA nanoparticles for intracellular trafficking, DNA targeting and improved therapeutic effects in skin melanoma in vitro.

PubMed

Das, Sreemanti; Das, Jayeeta; Samadder, Asmita; Paul, Avijit; Khuda-Bukhsh, Anisur Rahman

2013-11-25

The aim of the present study was the evaluation of anti-proliferative potentials of apigenin (Ap), (a dietary flavonoid) loaded in poly (lactic-co-glycolide) nanoparticles (NAp) in A375 cells in vitro. NAp was characterized for particle size, morphology, zeta potential, drug release and encapsulation. Cellular entry and intracellular localization of NAp were assessed by transmission electron and confocal microscopies. Circular dichroic spectral analysis and stability curve for Gibb's free energy of dsDNA of A375 cells were also analyzed. DNA fragmentation, intracellular ROS accumulation, superoxide-dismutase activity, intracellular glutathione-reductase content and mitochondrial functioning through relevant markers like mitochondrial transmembrane potential, ATPase activity, ATP/ADP ratio, volume changes/swelling, cytochrome-c release, expressions of Apaf-1, bax, bcl-2, caspase-9, 3, and PARP cleavage were analyzed. NAp produced better effects due to their smaller size, faster mobility and site-specific action. Photostability studies revealed that PLGA encapsulations were efficient at preserving apigenin ultraviolet-light mediated photodegradation. NAp readily entered cancer cells, could intercalate with dsDNA, inducing conformational change. Corresponding increase in ROS accumulation and depletion of the antioxidant enzyme activities exacerbated DNA damage, mediating apoptosis through mitochondrial dysfunction. Overall results indicate that therapeutic efficacy of NAp may be enhanced by PLGA nanoparticle formulations to have better ameliorative potentials in combating skin melanoma. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

PubMed Central

Li, Mingguang; Panagi, Zoi; Avgoustakis, Konstantinos; Reineke, Joshua

2012-01-01

Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity). Clear and systematic understanding of nanoparticle properties’ effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic) acid (PLGA) nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol) (mPEG) (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34) were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area) and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation) were used to calculate (predict) biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for description of PLGA-mPEG nanoparticle biodistribution. Further, the predicted biodistribution profiles of PLGA-mPEG495 were close to experimental data, reflecting properly developed property–biodistribution relationships. PMID:22419876

Nanoparticle Formulation Derived from Carboxymethyl Cellulose, Polyethylene Glycol, and Cabazitaxel for Chemotherapy Delivery to the Brain.

PubMed

Bteich, Joseph; Ernsting, Mark J; Mohammed, Mohammed; Kiyota, Taira; McKee, Trevor D; Trikha, Mohit; Lowman, Henry B; Sokoll, Kenneth K

2018-05-23

Nanoparticles provide a unique opportunity to explore the benefits of selective distribution and release of cancer therapeutics at sites of disease through varying particle sizes and compositions that exploit the enhanced permeability of tumor-associated blood vessels. Though delivery of larger as opposed to smaller and/or actively transported molecules to the brain is prima facie a challenging endeavor, we wondered whether nanoparticles could improve the therapeutic index of existing drugs for use in treating brain tumors via these vascular effects. We therefore selected a family of nanoparticles composed of cabazitaxel-carboxymethyl cellulose amphiphilic polymers to investigate the potential for delivering a brain-penetrant taxane to intracranial brain tumors in mice. Among a small set of nanoparticle formulations, we found evidence for nanoparticle accumulation in the brain, and one such formulation demonstrated activity in an orthotopic model of glioma, suggesting that such nanoparticles could be useful for the treatment of glioma and brain metastases of other tumor types.

Controlled assembly of silver nano-fluid in Heliotropium crispum extract: A potent anti-biofilm and bactericidal formulation

NASA Astrophysics Data System (ADS)

Khan, Faria; Hashmi, Muhammad Uzair; Khalid, Nauman; Hayat, Muhammad Qasim; Ikram, Aamer; Janjua, Hussnain A.

2016-11-01

The study describes the optimized method for silver nanoparticle (AgNPs) synthesis using Heliotropium crispum (HC) plant extract. Optimization of physicochemical parameters resulted in stable and rapidly assembled AgNPs. FTIR results suggest presence of plant phytochemicals that helped in the reduction, stabilization and capping of AgNPs. The assembled Ag nano-composites displayed the peak surface plasmon resonance (SPR) around 428 nm. The presence of uniquely assembled Ag-biomolecule composites, cap and stabilize nanoparticles in aqueous plant suspension. Spherical, uniform-shaped AgNPs with low poly-dispersion and average particle size of 42 nm and was determined through dynamic light scattering (DLS) and scanning election microscopy (SEM) which present robust interaction with microbes. The study also evaluates the antimicrobial and anti-biofilm properties of biologically synthesized AgNPs on clinical isolates of MRSA, Pseudomonas aeruginosa and Acinetobacter baumannii. Minimum inhibitory concentration (0.5 mg mL-1) of nanoparticles that presented bactericidal effect was made through inhibition assays on bacterial strains. The concentration which presented potent bactericidal response was then evaluated through growth inhibition in liquid medium for anti-biofilm studies at 2.0 mg mL-1. HC-Ag nanoparticles mediated anti-biofilm effects on Pseudomonas aeruginosa was revealed through SEM. Complete breakdown of biofilm's extracellular polymeric substances resulted after incubation with AgNPs. Peptidoglycan cell wall destruction was also revealed on planktonic bacterial images after 24 h of incubation.

Collaborative study for the calibration of the Ph. Eur. prekallikrein activator in albumin BRP batches 4, 5 and 6.

PubMed

Lackner, F; Daas, A; Terao, E

2015-01-01

An international collaborative study was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) to calibrate replacement batches for the current European Pharmacopoeia (Ph. Eur.) prekallikrein activator (PKA) in albumin biological reference preparation (BRP), whose stocks were dwindling. The study was run in the framework of the Biological Standardisation Programme (BSP) of the Council of Europe and the European Union (EU) Commission. Twenty three laboratories from official medicines control authorities and manufacturers in Europe and outside Europe took part in the study. Three candidate replacement batches were produced from the same material as the one used for the World Health Organization (WHO) 2(nd) International Standard (IS) for PKA in albumin (02/168) and the Ph. Eur. PKA in albumin BRP batches 1, 2 and 3. Participants were requested to evaluate the candidate batches against the current WHO IS using their routine assay method. The Ph. Eur. PKA in albumin BRP batch 3 (BRP3) was also included in the test panel to ensure the continuity of the consecutive BRP batches. The study confirmed the stability of the PKA content of the current BRP3. The candidate batches were found to be comparable. Previous data on the starting material support its high stability. Thermal stress study on the candidate batches confirmed the stability of their PKA activity. The Commission of the Ph. Eur. officially adopted in November 2013 the 3 candidate batches as Ph. Eur. PKA in albumin BRP batches 4, 5 and 6 with an assigned content of 38 IU/vial. The activity of the 3 new batches of Ph. Eur. PKA in albumin BRP will be regularly monitored.

Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

PubMed

Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

2018-03-14

Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

Mechanism of Dimercaptosuccinic Acid Coated Superparamagnetic Iron Oxide Nanoparticles with Human Serum Albumin.

PubMed

Zhao, Lining; Song, Wei; Wang, Jing; Yan, Yunxing; Chen, Jiangwei; Liu, Rutao

2015-12-01

To research the mechanism of dimercaptosuccinic acid coated-superparamagnetic iron oxide nanoparticles (SPION) with human serum albumin (HSA), the methods of spectroscopy, molecular modeling calculation, and calorimetry were used in this paper. The inner filter effect of the fluorescence intensity was corrected to obtain the accurate results. Ultraviolet-visible absorption and circular dichroism spectra reflect that SPION changed the secondary structure with a loss of α-helix and loosened the protein skeleton of HSA; the activity of the protein was also affected by the increasing exposure of SPION. Fluorescence lifetime measurement indicates that the quenching mechanism type of this system was static quenching. The isothermal titration calorimetry measurement and molecular docking calculations prove that the predominant force of this system was the combination of Van der Waals' force and hydrogen bonds. © 2015 Wiley Periodicals, Inc.

Size-Tunable Gd2O3@Albumin Nanoparticles Conjugating Chlorin e6 for Magnetic Resonance Imaging-Guided Photo-Induced Therapy.

PubMed

Zhou, Lijuan; Yang, Tao; Wang, Junxing; Wang, Qiaoli; Lv, Xiaoyan; Ke, Hengte; Guo, Zhengqing; Shen, Junkang; Wang, Yong; Xing, Chungen; Chen, Huabing

2017-01-01

Protein nanoparticles as nanocarriers are of particular interest in the field of cancer therapy. Nevertheless, so far a facile fabrication of theranostic protein nanoparticles have been explored with limited success for cancer imaging and therapy. In this work, we demonstrate the controllable synthesis of size-tunable Gd 2 O 3 @albumin conjugating photosensitizer (PS) (GA-NPs) using hollow albumin as the nanoreactor for magnetic resonance imaging (MRI)-guided photo-induced therapy. The growth of Gd 2 O 3 nanocrystals within the hollow nanoreactors is well regulated through reaction time, and a typical PS (e.g. chlorin e6) is further conjugated with the protein corona of the nanoreactor through facile chemical coupling, followed by the formation of theranostic GA-NPs. GA-NPs exhibit good longitudinal relaxivity, ideal photostability, enhanced cellular uptakes, and preferable size-dependent tumor accumulation. Moreover, GA-NPs effectively generate remarkable photothermal effect, intracellular reactive oxygen species from Ce6, and subsequent cytoplasmic drug translocation, thereby leading to severe synergistic photothermal and photodynamic cell damages. Consequently, GA-NPs exhibit an in vivo size-dependent MRI capacity with enhanced imaging contrast for effective tumor localization, and also generate a potent synergistic photodynamic therapy/photothermal therapy efficacy under irradiation owing to their enhanced tumor accumulation and strong photo-induced cytotoxicity. These results suggest that GA-NPs can act as a promising theranostic protein nanoplatform for cancer imaging and photo-induced therapy.

Formulation and evaluation of biodegradable nanoparticles for the oral delivery of fenretinide.

PubMed

Graves, Richard A; Ledet, Grace A; Glotser, Elena Y; Mitchner, Demaurian M; Bostanian, Levon A; Mandal, Tarun K

2015-08-30

Fenretinide is an anticancer drug with low water solubility and poor bioavailability. The goal of this study was to develop biodegradable polymeric nanoparticles of fenretinide with the intent of increasing its apparent aqueous solubility and intestinal permeability. Three biodegradable polymers were investigated for this purpose: two different poly lactide-co-glycolide (PLGA) polymers, one acid terminated and one ester terminated, and one poly lactide-co-glycolide/polyethylene glycol (PLGA/PEG) diblock copolymer. Nanoparticles were obtained by using an emulsification solvent evaporation technique. The formulations were characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and particle size analysis. Dissolution studies and Caco-2 cell permeation studies were also carried out for all formulations. Ultra high performance liquid chromatography coupled with mass spectrometry (UPLC/MS) and ultraviolet detection was used for the quantitative determination of fenretinide. Drug loading and the type of polymer affected the nanoparticles' physical properties, drug release rate, and cell permeability. While the acid terminated PLGA nanoparticles performed the best in drug release, the ester terminated PLGA nanoparticles performed the best in the Caco-2 cell permeability assays. The PLGA/PEG copolymer nanoparticles performed better than the formulations with ester terminated PLGA in terms of drug release but had the poorest performance in terms of cell permeation. All three categories of formulations performed better than the drug alone in both drug release and cell permeation studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation and in vitro evaluation of actively targetable nanoparticles for SN-38 delivery against HT-29 cell lines.

PubMed

Ebrahimnejad, Pedram; Dinarvand, Rassoul; Sajadi, Abolghasem; Jaafari, Mahmoud Reza; Nomani, Ali Reza; Azizi, Ebrahim; Rad-Malekshahi, Mazda; Atyabi, Fatemeh

2010-06-01

SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan, which is 100-to 1000-fold more cytotoxic than irinotecan. Nevertheless, extreme hydrophobicity of SN-38 has prevented its clinical use. One way of improving the solubility and stability of SN-38 is to formulate the drug into nanoparticles. Folic acid has been widely used as a targeting moiety for various anticancer drugs. For folate-receptor-targeted anticancer therapy, SN-38 nanoparticles were produced using poly-lactide-co-glycolide-polyethylene glycol-folate (PLGA-PEG-FOL) conjugate by emulsification/solvent evaporation method. The FOL-conjugated di-block copolymer was synthesized by coupling the PLGA-PEG-NH(2) di-block copolymer with an activated folic acid. The conjugates were used for the formation of SN-38 nanoparticles with an average size of 200 nm in diameter. The SN-38 targeted nanoparticles showed a greater cytotoxicity against HT-29 cancer cells than SN-38 nontargeted nanoparticles. These results suggested that folate-targeted nanoparticles could be a potentially useful delivery system for SN-38 as an anticancer agent. SN-38 is the active metabolite of the chemotherapy agent irinotecan, which is 100-1000 fold more cytotoxic than irinotecan, but its extreme hydrophobicity has prevented its clinical use. In this paper, the authors present a nanotechnology-based approach targeting the folate-receptor with SN-38 loaded nanoparticles, demonstrating stronger cytotoxicity against HT-29 cancer cells than with control nanoparticles.

Development of New Lipid-Based Paclitaxel Nanoparticles Using Sequential Simplex Optimization

PubMed Central

Dong, Xiaowei; Mattingly, Cynthia A.; Tseng, Michael; Cho, Moo; Adams, Val R.; Mumper, Russell J.

2008-01-01

The objective of these studies was to develop Cremophor-free lipid-based paclitaxel (PX) nanoparticle formulations prepared from warm microemulsion precursors. To identify and optimize new nanoparticles, experimental design was performed combining Taguchi array and sequential simplex optimization. The combination of Taguchi array and sequential simplex optimization efficiently directed the design of paclitaxel nanoparticles. Two optimized paclitaxel nanoparticles (NPs) were obtained: G78 NPs composed of glyceryl tridodecanoate (GT) and polyoxyethylene 20-stearyl ether (Brij 78), and BTM NPs composed of Miglyol 812, Brij 78 and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both nanoparticles successfully entrapped paclitaxel at a final concentration of 150 μg/ml (over 6% drug loading) with particle sizes less than 200 nm and over 85% of entrapment efficiency. These novel paclitaxel nanoparticles were stable at 4°C over three months and in PBS at 37°C over 102 hours as measured by physical stability. Release of paclitaxel was slow and sustained without initial burst release. Cytotoxicity studies in MDA-MB-231 cancer cells showed that both nanoparticles have similar anticancer activities compared to Taxol®. Interestingly, PX BTM nanocapsules could be lyophilized without cryoprotectants. The lyophilized powder comprised only of PX BTM NPs in water could be rapidly rehydrated with complete retention of original physicochemical properties, in-vitro release properties, and cytotoxicity profile. Sequential Simplex Optimization has been utilized to identify promising new lipid-based paclitaxel nanoparticles having useful attributes. PMID:19111929

Apoptosis induction and anti-cancer activity of LeciPlex formulations.

PubMed

Dhawan, Vivek V; Joshi, Ganesh V; Jain, Ankitkumar S; Nikam, Yuvraj P; Gude, Rajiv P; Mulherkar, Rita; Nagarsenker, Mangal S

2014-10-01

Cationic agents have been reported to possess anti-neoplastic properties against various cancer cell types. However, their complexes with lipids appear to interact differently with different cancer cells. The purpose of this study was to (i) design and generate novel cationic lecithin nanoparticles, (ii) assess and understand the mechanism underlying their putative cytotoxicity and (iii) test their effect on cell cycle progression in various cancer-derived cell lines. In addition, we aimed to evaluate the in vivo potential of these newly developed nanoparticles in oral anti-cancer delivery. Cationic lecithin nanoparticles were generated using a single step nanoprecipitation method and they were characterized for particle size, zeta potential, stability and in vitro release. Their cytotoxic potential was assessed using a sulforhodamine B assay, and their effect on cell cycle progression was evaluated using flow cytometry. The nanoparticle systems were also tested in vivo for their anti-tumorigenic potential. In contrast to cationic agents alone, the newly developed nanoformulations showed a specific toxicity against cancer cells. The mechanism of toxic cell death included apoptosis, S and G2/M cell cycle phase arrest, depending on the type of cationic agent and the cancer-derived cell line used. Both blank and drug-loaded systems exhibited significant anti-cancer activity, suggesting a synergistic anti-tumorigenic effect of the drug and its delivery system. Both in vitro and in vivo data indicate that cationic agents themselves exhibit broad anti-neoplastic activities. Complex formation of the cationic agents with phospholipids was found to provide specificity to the anti-cancer activity. These formulations thus possess potential for the design of effective anti-cancer delivery systems.

In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery.

PubMed

Şenyiğit, Taner; Sonvico, Fabio; Rossi, Alessandra; Tekmen, Işıl; Santi, Patrizia; Colombo, Paolo; Nicoli, Sara; Özer, Özgen

2016-12-26

The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w / w ), and a sodium deoxycholate gel (CP 0.05% w / w ) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP.

In Vivo Assessment of Clobetasol Propionate-Loaded Lecithin-Chitosan Nanoparticles for Skin Delivery

PubMed Central

Şenyiğit, Taner; Sonvico, Fabio; Rossi, Alessandra; Tekmen, Işıl; Santi, Patrizia; Colombo, Paolo; Nicoli, Sara; Özer, Özgen

2016-01-01

The aim of this work was to assess in vivo the anti-inflammatory efficacy and tolerability of clobetasol propionate (CP) loaded lecithin/chitosan nanoparticles incorporated into chitosan gel for topical application (CP 0.005%). As a comparison, a commercial cream (CP 0.05% w/w), and a sodium deoxycholate gel (CP 0.05% w/w) were also evaluated. Lecithin/chitosan nanoparticles were prepared by self-assembling of the components obtained by direct injection of soybean lecithin alcoholic solution containing CP into chitosan aqueous solution. Nanoparticles obtained had a particle size around 250 nm, narrow distribution (polydispersity index below 0.2) and positive surface charge, provided by a superficial layer of the cationic polymer. The nanoparticle suspension was then loaded into a chitosan gel, to obtain a final CP concentration of 0.005%. The anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema test on Wistar rats, the effect of formulations on the barrier property of the stratum corneum were determined using transepidermal water loss measurements (TEWL) and histological analysis was performed to evaluate the possible presence of morphological changes. The results obtained indicate that nanoparticle-in-gel formulation produced significantly higher edema inhibition compared to other formulations tested, although it contained ten times less CP. TEWL measurements also revealed that all formulations have no significant disturbance on the barrier function of skin. Furthermore, histological analysis of rat abdominal skin did not show morphological tissue changes nor cell infiltration signs after application of the formulations. Taken together, the present data show that the use of lecithin/chitosan nanoparticles in chitosan gel as a drug carrier significantly improves the risk-benefit ratio as compared with sodium-deoxycholate gel and commercial cream formulations of CP. PMID:28035957

Facile and easily popularized synthesis of L-cysteine-functionalized magnetic nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides.

PubMed

Feng, Xiaoyan; Deng, Chunhui; Gao, Mingxia; Zhang, Xiangmin

2018-01-01

Protein glycosylation is one of the most important post-translational modifications. Also, efficient enrichment and separation of glycopeptides from complex samples are crucial for the thorough analysis of glycosylation. Developing novel hydrophilic materials with facile and easily popularized synthesis is an urgent need in large-scale glycoproteomics research. Herein, for the first time, a one-step functionalization strategy based on metal-organic coordination was proposed and Fe 3 O 4 nanoparticles were directly functionalized with zwitterionic hydrophilic L-cysteine (L-Cys), greatly simplifying the synthetic procedure. The easily synthesized Fe 3 O 4 /L-Cys possessed excellent hydrophilicity and brief composition, contributing to affinity for glycopeptides and reduction in nonspecific interaction. Thus, Fe 3 O 4 /L-Cys nanoparticles showed outstanding sensitivity (25 amol/μL), high selectivity (mixture of bovine serum albumin and horseradish peroxidase tryptic digests at a mass ratio of 100:1), good reusability (five repeated times), and stability (room temperature storage of 1 month). Encouragingly, in the glycosylation analysis of human serum, a total of 376 glycopeptides with 393 N-glycosylation sites corresponding to 118 glycoproteins were identified after enrichment with Fe 3 O 4 /L-Cys, which was superior to ever reported L-Cys modified magnetic materials. Furthermore, applying the one-step functionalization strategy, cysteamine and glutathione respectively direct-functionalized Fe 3 O 4 nanoparticles were successfully synthesized and also achieved efficient glycopeptide enrichment in human serum. The results indicated that we have presented an efficient and easily popularized strategy in glycoproteomics as well as in the synthesis of novel materials. Graphical abstract Fe 3 O 4 /L-Cys nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides.

Quantitative characterization of gold nanoparticles by field-flow fractionation coupled online with light scattering detection and inductively coupled plasma mass spectrometry.

PubMed

Schmidt, Bjørn; Loeschner, Katrin; Hadrup, Niels; Mortensen, Alicja; Sloth, Jens J; Koch, Christian Bender; Larsen, Erik H

2011-04-01

An analytical platform coupling asymmetric flow field-flow fractionation (AF(4)) with multiangle light scattering (MALS), dynamic light scattering (DLS), and inductively coupled plasma mass spectrometry (ICPMS) was established and used for separation and quantitative determination of size and mass concentration of nanoparticles (NPs) in aqueous suspension. Mixtures of three polystyrene (PS) NPs between 20 and 100 nm in diameter and mixtures of three gold (Au) NPs between 10 and 60 nm in diameter were separated by AF(4). The geometric diameters of the separated PS NPs and the hydrodynamic diameters of the Au and PS NPs were determined online by MALS and DLS, respectively. The three separated Au NPs were quantified by ICPMS and recovered at 50-95% of the injected masses, which ranged between approximately 8-80 ng of each nanoparticle size. Au NPs adhering to the membrane in the separation channel was found to be a major cause for incomplete recoveries. The lower limit of detection (LOD) ranged between 0.02 ng Au and 0.4 ng Au, with increasing LOD by increasing nanoparticle diameter. The analytical platform was applied to characterization of Au NPs in livers of rats, which were dosed with 10 nm, 60 nm, or a mixture of 10 and 60 nm nanoparticles by intravenous injection. The homogenized livers were solubilized in tetramethylammonium hydroxide (TMAH), and the recovery of Au NPs from the livers amounted to 86-123% of their total Au content. In spite of successful stabilization with bovine serum albumin even in alkaline medium, separation of the Au NPs by AF(4) was not possible due to association with undissolved remains of the alkali-treated liver tissues as demonstrated by electron microscopy images.

Gold nanoparticles: role of size and surface chemistry on blood protein adsorption

NASA Astrophysics Data System (ADS)

Benetti, F.; Fedel, M.; Minati, L.; Speranza, G.; Migliaresi, C.

2013-06-01

Material interaction with blood proteins is a critical issue, since it could influence the biological processes taking place in the body following implantation/injection. This is particularly important in the case of nanoparticles, where innovative properties, such as size and high surface to volume ratio can lead to a behavioral change with respect to bulk macroscopic materials and could be responsible for a potential risk for human health. The aim of this work was to compare gold nanoparticles (AuNP) and planar surfaces to study the role of surface curvature moving from the macro- to the nano-size in the process of blood protein adsorption. In the course of the study, different protocols were tested to optimize the analysis of protein adsorption on gold nanoparticles. AuNP with different size (10, 60 and 200 nm diameter) and surface coatings (citrate and polyethylene glycol) were carefully characterized. The stabilizing action of blood proteins adsorbed on AuNP was studied measuring the variation of size and solubility of the nanoparticles following incubation with single protein solutions (human serum albumin and fibrinogen) and whole blood plasma. In addition, we developed a method to elute proteins from AuNP to study the propensity of gold materials to adsorb plasma proteins in function of dimensional characteristics and surface chemistry. We showed a different efficacy of the various eluting media tested, proving that even the most aggressive agent cannot provide a complete detachment of the protein corona. Enhanced protein adsorption was evidenced on AuNP if compared to gold laminae (bare and PEGylated) used as macroscopic control, probably due to the superior AuNP surface reactivity.

Single Particle Dynamic Imaging and Fe3+ Sensing with Bright Carbon Dots Derived from Bovine Serum Albumin Proteins

NASA Astrophysics Data System (ADS)

Yang, Qingxiu; Wei, Lin; Zheng, Xuanfang; Xiao, Lehui

2015-12-01

In this work, we demonstrated a convenient and green strategy for the synthesis of highly luminescent and water-soluble carbon dots (Cdots) by carbonizing carbon precursors, i.e., Bovine serum albumin (BSA) nanoparticles, in water solution. Without post surface modification, the as-synthesized Cdots exhibit fluorescence quantum yield (Q.Y.) as high as 34.8% and display superior colloidal stability not only in concentrated salt solutions (e.g. 2 M KCl) but also in a wide range of pH solutions. According to the FT-IR measurements, the Cdots contain many carboxyl groups, providing a versatile route for further chemical and biological functionalization. Through conjugation of Cdots with the transacting activator of transcription (TAT) peptide (a kind of cell penetration peptide (CPP)) derived from human immunodeficiency virus (HIV), it is possible to directly monitor the dynamic interactions of CPP with living cell membrane at single particle level. Furthermore, these Cdots also exhibit a dosage-dependent selectivity toward Fe3+ among other metal ions, including K+, Na+, Mg2+, Hg2+, Co2+, Cu2+, Pb2+ and Al3+. We believed that the Cdots prepared by this strategy would display promising applications in various areas, including analytical chemistry, nanomedicine, biochemistry and so on.

Preparation and Characterization of Three Tilmicosin-loaded Lipid Nanoparticles: Physicochemical Properties and in-vitro Antibacterial Activities.

PubMed

Al-Qushawi, Alwan; Rassouli, Ali; Atyabi, Fatemeh; Peighambari, Seyed Mostafa; Esfandyari-Manesh, Mehdi; Shams, Gholam Reza; Yazdani, Azam

2016-01-01

Tilmicosin (TLM) is an important antibiotic in veterinary medicine with low bioavailability and safety. This study aimed to formulate and evaluate physicochemical properties, storage stability after lyophilization, and antibacterial activity of three TLM-loaded lipid nanoparticles (TLM-LNPs) including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid-core nanocapsules (LNCs). Physicochemical parameters such as particle size-mean diameter, polydispersity index, zeta potential, drug encapsulation efficiency (EE), loading capacity, and morphology of the formulations were evaluated and the effects of various cryoprotectants during lyophilization and storage for 8 weeks were also studied. The profiles of TLM release and the antibacterial activities of these TLM-LNPs suspensions (against Escherichia coli and Staphylococcus aureus ) were tested in comparison with their corresponding powders. TLM-LNPs suspensions were in nano-scale range with mean diameters of 186.3 ± 1.5, 149.6 ± 3.0, and 85.0 ± 1.0nm, and also EE, 69.1, 86.3, and 94.3% for TLM- SLNs, TLM-NLCs, and TLM- LNCs respectively. TLM-LNCs gave the best results with significantly low particle size and high EE (p<0.05). Mannitol was the most effective cryoprotectant for lyophilization and storage of TLM-LNPs. The drug release profiles were biphasic and the release times were longer at pH 7.4 where TLM-NLCs and TLM-LNCs powders showed longer release times. In microbiological tests, S. aureus was about 4 times more sensitive than E. coli to TLM-LNPs with minimum inhibitory concentration ranges of 0.5-1.0 and 2-4 µg/mL respectively, and TLM-LNCs exhibited the best antibacterial activities. In conclusion, TLM-LNP formulations especially TLM-LNCs and TLM-NLCs are promising carriers for TLM with better drug encapsulation capacity, release behavior, and antibacterial activity.

A comparison of fate and toxicity of selenite, biogenically, and chemically synthesized selenium nanoparticles to zebrafish (Danio rerio) embryogenesis.

PubMed

Mal, Joyabrata; Veneman, Wouter J; Nancharaiah, Y V; van Hullebusch, Eric D; Peijnenburg, Willie J G M; Vijver, Martina G; Lens, Piet N L

2017-02-01

Microbial reduction of selenium (Se) oxyanions to elemental Se is a promising technology for bioremediation and treatment of Se wastewaters. But a fraction of biogenic nano-Selenium (nano-Se b ) formed in bioreactors remains suspended in the treated waters, thus entering the aquatic environment. The present study investigated the toxicity of nano-Se b formed by anaerobic granular sludge biofilms on zebrafish embryos in comparison with selenite and chemogenic nano-Se (nano-Se c ). The nano-Se b formed by granular sludge biofilms showed a LC 50 value of 1.77 mg/L, which was 3.2-fold less toxic to zebrafish embryos than selenite (LC 50  =   0.55 mg/L) and 10-fold less toxic than bovine serum albumin stabilized nano-Se c (LC 50  =   0.16 mg/L). Smaller (nano-Se cs ; particle diameter range: 25-80 nm) and larger (nano-Se cl ; particle diameter range: 50-250 nm) sized chemically synthesized nano-Se c particles showed comparable toxicity on zebrafish embryos. The lower toxicity of nano-Se b in comparison with nano-Se c was analyzed in terms of the stabilizing organic layer. The results confirmed that the organic layer extracted from the nano-Se b consisted of components of the extracellular polymeric substances (EPS) matrix, which govern the physiochemical stability and surface properties like ζ-potential of nano-Se b . Based on the data, it is contented that the presence of humic acid like substances of EPS on the surface of nano-Se b plays a major role in lowering the bioavailability (uptake) and toxicity of nano-Se b by decreasing the interactions between nanoparticles and embryos.