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.

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

Curcumin-loaded hydrogel nanoparticles: application in anti-malarial therapy and toxicological evaluation.

PubMed

Dandekar, Prajakta P; Jain, Ratnesh; Patil, Sushant; Dhumal, Rohit; Tiwari, Dinesh; Sharma, Shobhona; Vanage, Geeta; Patravale, Vandana

2010-12-01

The present investigation involved preparation of hydrogel nanoparticles using a combination of hydroxyl propyl methyl cellulose and polyvinyl pyrrolidone. The objective was to exploit the size and hydrophilic nature of the formulated nanocarriers to enhance absorption and prolong the rapid clearance of curcumin due to possible evasion of the reticulo-endothelial system. Reproducible nanoparticles of size around 100 nm, a fairly narrow distribution and encapsulation efficiency of 72%, were produced by the solvent emulsion-evaporation technique. This optimized system was further subjected to freeze-drying. The freeze-dried product was readily reconstituted with distilled water. The reconstituted product exhibited a size and distribution similar to that before freeze-drying, drug content of greater than 99% and presence of amorphous drug when analyzed by differential scanning calorimetry (DSC) which may result in possible improved absorption of curcumin. In vivo anti-malarial studies revealed significant superior action of nanoparticles over curcumin control suggesting the possibility of the formulation being employed as an adjunct anti-malarial therapy along with the standard therapy. Acute and subacute toxicity studies confirmed the oral safety of the formulation. A battery of genotoxicity studies was conducted to evaluate the nongenotoxic potential of the developed formulation thus indicating the possibility of the formulation being employed for prolonged duration. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Self-assembled gemcitabine-gadolinium nanoparticles for magnetic resonance imaging and cancer therapy.

PubMed

Li, Lele; Tong, Rong; Li, Mengyuan; Kohane, Daniel S

2016-03-01

Nanoparticles with combined diagnostic and therapeutic functions are promising tools for cancer diagnosis and treatment. Here, we demonstrate a theranostic nanoparticle that integrates an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile supramolecular self-assembly synthesis, where the anti-cancer drug gemcitabine-5'-monophosphate (a phosphorylated active metabolite of the anti-cancer drug gemcitabine) was used to coordinate with Gd(III) to self-assemble into theranostic nanoparticles. The formulation exhibits a strong T1 contrast signal for magnetic resonance imaging of tumors in vivo, with enhanced retention time. Furthermore, the nanoparticles did not require other inert nanocarriers or excipients and thus had an exceptionally high drug loading (55 wt%), resulting in the inhibition of MDA-MB-231 tumor growth in mice. Recent advances in nanoparticle-based drug delivery systems have spurred the development of "theranostic" multifunctional nanoparticles, which combine therapeutic and diagnostic functionalities in a single formulation. Developing simple and efficient synthetic strategies for the construction of nanotheranostics with high drug loading remains a challenge. Here, we demonstrate a theranostic nanoparticle that integrates high loadings of an active gemcitabine metabolite and a gadolinium-based magnetic resonance imaging agent via a facile synthesis. The nanoparticles were better T1 contrast agents than currently used Gd-DTPA and had prolonged retention in tumor. Moreover they exhibited enhanced in vivo antitumor activity compared to free drug in a breast cancer xenograft mouse model. The strategy provides a scalable way to fabricate nanoparticles that enables enhancement of both therapeutic and diagnostic capabilities. Published by Elsevier Ltd.

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.

Folate Receptor-targeted Bioflavonoid Genistein-loaded Chitosan Nanoparticles for Enhanced Anticancer Effect in Cervical Cancers

NASA Astrophysics Data System (ADS)

Cai, Limei; Yu, Rufen; Hao, Xi; Ding, Xiangcui

2017-08-01

In this study, novel folic acid-conjugated chitosan nanoparticle was formulated for specific delivery of bioflavonoid, Genistein (GEN), to the cervical cancer cells. The prepared GEN-loaded chitosan nanoparticles (GCN) and folic acid-conjugated GCN (FGCN) showed smaller size with a controlled drug release profile. FGCN exhibited enhanced internalization potential in HeLa cells than that of GCN. The specific internalization of FGCN was mainly due to the affinity of folic acid (FA) with FRs-α which is present in large numbers in HeLa cells. The results revealed that FGCN has a specific affinity towards HeLa cells that will contribute to the better treatment. Folic acid-tagged nanoformulations exhibited a superior cytotoxic effect compared to that of non-targeted formulations. Consistently, IC50 value of GEN decreased from 33.8 to 14.6 μg/ml when treated with FGCN after 24 h incubation. The apoptosis studies indicated that the FGCN nanoparticles were then either GCN or free GEN in terms of anticancer activity. Overall, results revealed that folate conjugation to the delivery system might have great effect on the survival of cervical cancers that will be beneficial for overall cancer treatment.

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

Curcumin loaded pH-sensitive nanoparticles for the treatment of colon cancer.

PubMed

Prajakta, Dandekar; Ratnesh, Jain; Chandan, Kumar; Suresh, Subramanian; Grace, Samuel; Meera, Venkatesh; Vandana, Patravale

2009-10-01

The investigation was aimed at designing pH-sensitive, polymeric nanoparticles of curcumin, a natural anti-cancer agent, for the treatment of colon cancer. The objective was to enhance the bioavailability of curcumin, simultaneously reducing the required dose through selective targeting to colon. Eudragit S100 was chosen to aid targeting since the polymer dissolves at colonic pH to result in selective colonic release of the entrapped drug. Solvent emulsion-evaporation technique was employed to formulate the nanoparticles. Various process parameters were optimized and the optimized formulation was evaluated for particle size distribution and encapsulation efficiency before subjecting to freeze-drying. The freeze dried product was characterized for particle size, drug content, DSC studies, particle morphology. Anti-cancer potential of the formulation was demonstrated by MTT assay in HT-29 cell line. Nanometric, homogeneous, spherical particles were obtained with encapsulation efficiency of 72%. Freeze-dried nanoparticles exhibited a negative surface charge, drug content of > 99% and presence of drug in amorphous form which may result in possible enhanced absorption. MTT assay demonstrated almost double inhibition of the cancerous cells by nanoparticles, as compared to curcumin alone, at the concentrations tested. Enhanced action may be attributed to size influenced improved cellular uptake, and may result in reduction of overall dose requirement. Results indicate the potential for in vivo studies to establish the clinical application of the formulation.

Optimization of controlled release nanoparticle formulation of verapamil hydrochloride using artificial neural networks with genetic algorithm and response surface methodology.

PubMed

Li, Yongqiang; Abbaspour, Mohammadreza R; Grootendorst, Paul V; Rauth, Andrew M; Wu, Xiao Yu

2015-08-01

This study was performed to optimize the formulation of polymer-lipid hybrid nanoparticles (PLN) for the delivery of an ionic water-soluble drug, verapamil hydrochloride (VRP) and to investigate the roles of formulation factors. Modeling and optimization were conducted based on a spherical central composite design. Three formulation factors, i.e., weight ratio of drug to lipid (X1), and concentrations of Tween 80 (X2) and Pluronic F68 (X3), were chosen as independent variables. Drug loading efficiency (Y1) and mean particle size (Y2) of PLN were selected as dependent variables. The predictive performance of artificial neural networks (ANN) and the response surface methodology (RSM) were compared. As ANN was found to exhibit better recognition and generalization capability over RSM, multi-objective optimization of PLN was then conducted based upon the validated ANN models and continuous genetic algorithms (GA). The optimal PLN possess a high drug loading efficiency (92.4%, w/w) and a small mean particle size (∼100nm). The predicted response variables matched well with the observed results. The three formulation factors exhibited different effects on the properties of PLN. ANN in coordination with continuous GA represent an effective and efficient approach to optimize the PLN formulation of VRP with desired properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Amphotericin-B entrapped lecithin/chitosan nanoparticles for prolonged ocular application.

PubMed

Chhonker, Yashpal S; Prasad, Yarra Durga; Chandasana, Hardik; Vishvkarma, Akhilesh; Mitra, Kalyan; Shukla, Praveen K; Bhatta, Rabi S

2015-01-01

Fungal keratitis is the major cause of vision loss worldwide. Amphotericin-B is considered as the drug of choice for fungal infections. However, its use in ophthalmic drug delivery is limited by the low precorneal residence at ocular surface as a result of blinking reflex, tear turnover and nasopharyngeal drainage. We report Amphotericin-B loaded lecithin/chitosan nanoparticles for prolonged ocular application. The prepared nanoparticles were in the size range of 161.9-230.5 nm, entrapment efficiency of 70-75%, theoretical drug loading of 5.71% with positive zeta potential of 26.6-38.3 mV. As demonstrated by antifungal susceptibility against Candida albicans and Aspergillus fumigatus, nanoparticles were more effective than marketed formulation. They exhibited pronounced mucoadhesive properties. In-vivo pharmacokinetic studies in New Zealand albino rabbit eyes indicated improved bioavailablity (∼ 2.04 fold) and precorneal residence time (∼ 3.36 fold) by nanoparticles prepared from low molecular weight chitosan as compared with marketed formulation. Copyright © 2014. Published by Elsevier B.V.

Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

NASA Astrophysics Data System (ADS)

Tarassoli, Sam P.; Martinez de Pinillos Bayona, Alejandra; Pye, Hayley; Mosse, C. Alexander; Callan, John F.; MacRobert, Alexander; McHale, Anthony P.; Nomikou, Nikolitsa

2017-02-01

Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.

Ultra-High Throughput Synthesis of Nanoparticles with Homogeneous Size Distribution Using a Coaxial Turbulent Jet Mixer

PubMed Central

2015-01-01

High-throughput production of nanoparticles (NPs) with controlled quality is critical for their clinical translation into effective nanomedicines for diagnostics and therapeutics. Here we report a simple and versatile coaxial turbulent jet mixer that can synthesize a variety of NPs at high throughput up to 3 kg/d, while maintaining the advantages of homogeneity, reproducibility, and tunability that are normally accessible only in specialized microscale mixing devices. The device fabrication does not require specialized machining and is easy to operate. As one example, we show reproducible, high-throughput formulation of siRNA-polyelectrolyte polyplex NPs that exhibit effective gene knockdown but exhibit significant dependence on batch size when formulated using conventional methods. The coaxial turbulent jet mixer can accelerate the development of nanomedicines by providing a robust and versatile platform for preparation of NPs at throughputs suitable for in vivo studies, clinical trials, and industrial-scale production. PMID:24824296

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

In-vitro and in-vivo assessment of dextran-appended cellulose acetate phthalate nanoparticles for transdermal delivery of 5-fluorouracil.

PubMed

Garg, Ashish; Rai, Gopal; Lodhi, Santram; Jain, Alok P; Yadav, Awesh K

2016-06-01

The aim of this research was transdermal delivery of 5-fluorouracil (5-FU) using dextran-coated cellulose acetate phthalate (CAP) nanoparticulate formulation. CAP nanoparticles were prepared using drug-polymer ratio (1:1 to 1:3) and surfactant ratio (2.5, 5 and 10%). Dextran coating was made using aminodextran. The results showed that the optimized CAP nanoparticles (CNs) and dextran-coated CAP nanoparticles represented core-corona nanoparticles with the mean diameter of 75 ± 3 and 79 ± 2 nm, respectively, and entrapment efficiency was 82.5 ± 0.06 and 78.2 ± 0.12, respectively. Dextran-coated nanoparticles (FDCNs) and CAP nanoparticles (FCNs) showed in vitro 5-FU release upto 31 h and 8 h, respectively. Moreover, the cumulative amount of 5-FU penetrated through excised skin from FDCNs was 2.94 folds than that of the FU cream. Concentration of 5-FU in epidermis and dermis were also studied. In dermis, concentration of 5-FU was found higher in case of FDCN formulation than plain FU cream. FDCNs were found more hemocompatible in comparison to FCNs. The hematological data recommended that FDCNs formulation was less immunogenic compared to FU creams formulation. In blood level study, FDCNs exhibited 153, 12, 16.66 and 16.24-fold higher values for area under the curve, Tmax, Cmax and mean residence time (MRT) compared with those of FU cream, respectively. The in-vitro cytotoxicity was assessed using the MCF-7 by the MTT test and was compared to the plain 5-FU solution. All the detailed evidence showed that FDCNs could provide a promising tuning as a transdermal delivery system of 5-FU.

Development and evaluation of co-formulated docetaxel and curcumin biodegradable nanoparticles for parenteral administration.

PubMed

Pawar, Harish; Wankhade, Shrikant Rameshrao; Yadav, Dharmendra K; Suresh, Sarasija

2016-09-01

Technology for development of biodegradable nanoparticles encapsulating combinations for enhanced efficacy. To develop docetaxel (DTX) and curcumin (CRM) co-encapsulated biodegradable nanoparticles for parenteral administration with potential for prolonged release and decreased toxicity. Modified emulsion solvent-evaporation technique was employed in the preparation of the nanoparticles optimized by the face centered-central composite design (FC-CCD). The uptake potential was studied in MCF-7 cells, while the toxicity was evaluated by in vitro hemolysis test. In vivo pharmacokinetic was evaluated in male Wistar rats. Co-encapsulated nanoparticles were developed of 219 nm size, 0.154 PDI, -13.74 mV zeta potential and 67.02% entrapment efficiency. Efficient uptake was observed by the nanoparticles in MCF-7 cells with decreased toxicity in comparison with the commercial DTX intravenous injection, Taxotere®. The nanoparticles exhibited biphasic release with initial burst release followed by sustained release for 5 days. The nanoparticles displayed a 4.3-fold increase in AUC (391.10 ± 32.94 versus 89.77 ± 10.58 μg/ml min) in comparison to Taxotere® with a 6.2-fold increase in MRT (24.78 ± 2.36 versus 3.58 ± 0.21 h). The nanoparticles exhibited increased uptake, prolonged in vitro and in vivo release, with decreased toxicity thus exhibiting potential for enhanced efficacy.

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

Magnolol Nanoparticles Exhibit Improved Water Solubility and Suppress TNF-α-Induced VCAM-1 Expression in Endothelial Cells.

PubMed

Lee, Chiang-Wen; Hu, Stephen Chu-Sung; Yen, Feng-Lin; Hsu, Lee-Fen; Lee, I-Ta; Lin, Zih-Chan; Tsai, Ming-Horng; Huang, Chieh-Liang; Liang, Chan-Jung; Chiang, Yao-Chang

2017-03-01

The expression of the adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells enables the attachment of leukocytes to the endothelium, which may lead to inflammation and the development of atherosclerosis. Magnolol is a major bioactive compound derived from the plant species Magnolia officinalis. In this study, we synthesized a novel nanoparticle formulation of magnolol to improve its water solubility and physicochemical properties, evaluated its effects on TNF-α-induced VCAM-1 expression in endothelial cells, and determined the signal transduction pathways involved. Our findings demonstrated that the magnolol nanoparticle system showed great improvements in physicochemical properties and water solubility owing to a reduction in particle size, transformation from a crystalline to amorphous structure, and the formation of hydrogen bonds with the nanoparticle carriers. In terms of its biological actions, magnolol nanoparticles attenuated TNF-α-induced VCAM-1 protein expression, promoter activity, and mRNA expression in endothelial cells in vitro. This was found to be mediated by the ERK, AKT, and NF-κB signaling pathways. In addition, magnolol nanoparticles inhibited TNF-α-induced leukocyte adhesion to endothelial cells, and suppressed TNF-α-induced VCAM-1 expression in the aortic endothelium of mice. In summary, since magnolol nanoparticles inhibit endothelial VCAM-1 expression and leukocyte adhesion to endothelial cells, this novel drug formulation may be a potentially useful therapeutic formulation to prevent the development of atherosclerosis and inflammatory diseases.

Formulation, characterization and pharmacokinetics of praziquantel-loaded hydrogenated castor oil solid lipid nanoparticles.

PubMed

Xie, Shuyu; Pan, Baoliang; Wang, Ming; Zhu, Luyan; Wang, Fenghua; Dong, Zhao; Wang, Xiaofang; Zhou, WenZhong

2010-07-01

The purpose of this study was to formulate praziquantel (PZQ)-loaded hydrogenated castor oil (HCO) solid lipid nanoparticles (SLN) to enhance the bioavailability and prolong the systemic circulation of the drug. PZQ was encapsulated into HCO nanoparticles by a hot homogenization and ultrasonication method. The physicochemical characteristics of SLN were investigated by optical microscope, scanning electron microscopy and photon correlation spectroscopy. Pharmacokinetics were studied after oral, subcutaneous and intramuscular administration in mice. The diameter, polydispersivity index, zeta potential, encapsulation efficiency and loading capacity of the nanoparticles were 344.0 +/- 15.1 nm, 0.31 +/- 0.08, -16.7 +/- 0.5 mV, 62.17 +/- 6.53% and 12.43 +/- 1.31%, respectively. In vitro release of PZQ-loaded HCO-SLN exhibited an initial burst release followed by a sustained release. SLN increased the bioavailability of PZQ by 14.9-, 16.1- and 2.6-fold, and extended the mean residence time of the drug from 7.6, 6.6 and 8.2 to 95.9, 151.6 and 48.2 h after oral, subcutaneous and intramuscular administration, respectively. The PZQ-loaded HCO-SLN could be a promising formulation to enhance the pharmacological activity of PZQ.

Phospholipid micelle-based magneto-plasmonic nanoformulation for magnetic field-directed, imaging-guided photo-induced cancer therapy.

PubMed

Ohulchanskyy, Tymish Y; Kopwitthaya, Atcha; Jeon, Mansik; Guo, Moran; Law, Wing-Cheung; Furlani, Edward P; Kim, Chulhong; Prasad, Paras N

2013-11-01

We present a magnetoplasmonic nanoplatform combining gold nanorods (GNR) and iron-oxide nanoparticles within phospholipid-based polymeric nanomicelles (PGRFe). The gold nanorods exhibit plasmon resonance absorbance at near infrared wavelengths to enable photoacoustic imaging and photothermal therapy, while the Fe3O4 nanoparticles enable magnetophoretic control of the nanoformulation. The fabricated nanoformulation can be directed and concentrated by an external magnetic field, which provides enhancement of a photoacoustic signal. Application of an external field also leads to enhanced uptake of the magnetoplasmonic formulation by cancer cells in vitro. Under laser irradiation at the wavelength of the GNR absorption peak, the PGRFe formulation efficiently generates plasmonic nanobubbles within cancer cells, as visualized by confocal microscopy, causing cell destruction. The combined magnetic and plasmonic functionalities of the nanoplatform enable magnetic field-directed, imaging-guided, enhanced photo-induced cancer therapy. In this study, a nano-formulation of gold nanorods and iron oxide nanoparticles is presented using a phospholipid micelle-based delivery system for magnetic field-directed and imaging-guided photo-induced cancer therapy. The gold nanorods enable photoacoustic imaging and photothermal therapy, while the Fe3O4 nanoparticles enable magnetophoretic control of the formulation. This and similar systems could enable more precise and efficient cancer therapy, hopefully in the near future, after additional testing. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Starch mediated CdS nanoparticles and their photocatalytic performance under visible light irradiation

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

Firdaus, Farha, E-mail: Farha-firdaus@yahoo.co.in; Faraz, Mohd

Green synthesis of Cadmium Sulphide (CdS-S) nanoparticles is of considerable interest due to its biocompatible and nontoxicity. Here, we present a biomolecule stimulated chemical method was adopted for the successful synthesis of CdS-S nanoparticles using starch as a capping agent. The CdS-S nanoparticles were characterized by various analytical techniques. The CdS-S nanoparicles exhibit photocatalytic activity against methyl orange (MO) at pH 9 in Visible light and the reaction follows pseudo first-order kinetics. The comparative photocatalytic activity revealed that CdS-S nanoparticles remarkably enhanced activities as compared to the commercial TiO{sub 2} nanoparticles. The outcome of these studies offers valuable for planningmore » CdS-S nanoparticles having photocatalytic activities helpful for the formulation of waste water remediation.« less

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery.

PubMed

Tian, Xi; Lara, Haydee; Wagner, Kyle T; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M; Zhang, Longzhen; Wang, Andrew Z

2015-12-21

Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

NASA Astrophysics Data System (ADS)

Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

2015-11-01

Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

In-vitro release and permeation studies of ketoconazole from optimized dermatological vehicles using powder, nanoparticles and solid dispersion forms of drug

NASA Astrophysics Data System (ADS)

Mohammed, Irfan A.

To optimize the clinical efficacy of Ketoconazole from an externally applied product, this project was undertaken to evaluate the drug release/permeation profile from various dermatological vehicles using regular powder, nanoparticles and solid dispersion forms with reduced level of drug. Nanoparticles of drug were prepared by wet media milling method using Polyvinylpyrrolidone (PVP-10K) as a stabilizer. The nanoparticles were in the size range of 250-300nm. Solid dispersion was prepared by solvent evaporation method using drug to PVP-10K at a weight ratio of (1:2). Formulations containing 1% w/w drug were developed using HPMC gel, Carbomer gel and a cationic cream as the vehicles. Penetration enhancers including propylene glycol (PG), dimethylsulfoxide (DMSO) and polyethylene glycol 400 (PEG-400) at various levels were evaluated. A commercial 2% w/w ketoconazole product was included as a control for comparison. Studies were carried out with Franz Diffusion Cells using cellulose membrane and human cadaver skin for two and six hour studies. Among the formulations evaluated, the general rank order of the drug release through the cellulose membrane was observed to be: HPMC gel base > Anionic gel base > Cationic gel base > Commercial product. The addition of penetration enhancers showed variable effects in all samples evaluated. However, the HPMC gel-based vehicle showed significant effect in enhancing the drug release in the presence of DMSO. The formulation containing 1% w/w ketoconazole and 20% w/w DMSO gave a maximum drug release of 20.21% when compared to only 1.60% from the commercial product. This represents a twelve fold increase in the release of ketoconazole from the formulation. Furthermore, when the optimum gel-based formulation containing 1% w/w ketoconazole was studied over an extended period of 6 hours, it gave 36.01% drug release from the sample formulation compared to only 2.00% from the commercial product. Finally, this formulation was selected to study for its drug release/permeation profile using the human cadaver skin as the diffusion barrier. Here, as expected, the drug release from both the formulations tested was significantly reduced due to the resistance posed by the skin. After 6 hours, the drug release form the commercial product was 0.17% when compared to 2.80% from the optimum formulation. Once again, this indicated that the experimental formulation exhibits superior drug release dynamics. The selected formulations were further evaluated for their in-vitro anti-fungal activities using yeast microorganisms. The results correlated to the in-vitro drug release profile, where HPMC based formulations exhibited a greater area of zone of inhibition for the growth of microorganisms when compared to diminutive area of zone of inhibition for the commercial product. The release data from all the samples were treated to calculate various physical parameters including: diffusion co-efficient, partition co-efficient, steady state flux and lag period etc. Interestingly, the values for the steady state flux and diffusion coefficient were found to be the highest from the optimum formulation and the values for the lag time and partition coefficient were observed to be the lowest. This supports the evidence that the drug from this formulation is readily diffusible to the skin at a steady rate after its application at the site. In-vitro drug diffusion studies and in-vitro anti-fungal studies proved useful in screening various dermatological formulations of ketoconazole compared to the commercial product containing 2% w/w drug. The HPMC based optimum formulation with reduced level of drug represents 15 folds increase through human cadaver skin and also exhibited augmented anti-fungal activity. This supports that by using an appropriate vehicle and proper incorporation of drug, one can optimize the drug release from topical formulation for maximum therapeutic effect.

Nano-sized particles, processes of making, compositions and uses thereof

DOEpatents

O'Brien, Stephen [New York, NY; Yin, Ming [Los Alamos, NM

2012-05-22

The present invention describes methods for preparing high quality nanoparticles, i.e., metal oxide based nanoparticles of uniform size and monodispersity. The nanoparticles advantageously comprise organic alkyl chain capping groups and are stable in air and in nonpolar solvents. The methods of the invention provide a simple and reproducible procedure for forming transition metal oxide nanocrystals, with yields over 80%. The highly crystalline and monodisperse nanocrystals are obtained directly without further size selection; particle size can be easily and fractionally increased by the methods. The resulting nanoparticles can exhibit magnetic and/or optical properties. These properties result from the methods used to prepare them. Also advantageously, the nanoparticles of this invention are well suited for use in a variety of industrial applications, including cosmetic and pharmaceutical formulations and compositions.

Zinc phthalocyanine-loaded PLGA biodegradable nanoparticles for photodynamic therapy in tumor-bearing mice.

PubMed

Fadel, Maha; Kassab, Kawser; Fadeel, Doa Abdel

2010-03-01

Nanoparticles formulated from the biodegradable copolymer poly(lactic-coglycolic acid) (PLGA) were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting of zinc(II) phthalocyanine (ZnPc) for photodynamic therapy. Three ZnPc nanoparticle formulations were prepared using a solvent emulsion evaporation method and the influence of sonication time on nanoparticle shape, encapsulation and size distribution, in vitro release, and in vivo photodynamic efficiency in tumor-bearing mice were studied. Sonication time did not affect the process yield or encapsulation efficiency, but did affect significantly the particle size. Sonication for 20 min reduced the mean particle size to 374.3 nm and the in vitro release studies demonstrated a controlled release profile of ZnPc. Tumor-bearing mice injected with ZnPc nanoparticles exhibited significantly smaller mean tumor volume, increased tumor growth delay and longer survival compared with the control group and the group injected with free ZnPc during the time course of the experiment. Histopathological examination of tumor from animals treated with PLGA ZnPc showed regression of tumor cells, in contrast to those obtained from animals treated with free ZnPc. The results indicate that ZnPc encapsulated in PLGA nanoparticles is a successful delivery system for improving photodynamic activity in the target tissue.

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

Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

PubMed Central

2014-01-01

The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

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.

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer.

PubMed

Carneiro, Marcella Lemos Brettas; Peixoto, Raphael C A; Joanitti, Graziela A; Oliveira, Ricardo G S; Telles, Luis A M; Miranda-Vilela, Ana L; Bocca, Anamélia L; Vianna, Leonora M S; da Silva, Izabel C R; de Souza, Aparecido R; Lacava, Zulmira G M; Báo, Sônia N

2013-02-16

Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications.

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.

Preparation of ultra-fine powders from polysaccharide-coated solid lipid nanoparticles and nanostructured lipid carriers by innovative nano spray drying technology.

PubMed

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

2016-09-10

In this study, five polysaccharides were applied as natural polymeric coating materials to prepare solid lipid nanoparticles (SLN) and nanostructure lipid carriers (NLC), and then the obtained lipid colloidal particles were transformed to solid powders by the innovative nano spray drying technology. The feasibility and suitability of this new technology to generate ultra-fine lipid powder particles were evaluated and the formulation was optimized. The spray dried SLN powder exhibited the aggregated and irregular shape and dimension, but small, uniform, well-separated spherical powder particles of was obtained from NLC. The optimal formulation of NLC was prepared by a 20-30% oleic acid content with carrageenan or pectin as coating material. Therefore, nano spray drying technology has a potential application to produce uniform, spherical, and sub-microscale lipid powder particles when the formulation of lipid delivery system is appropriately designed. Copyright © 2016 Elsevier B.V. All rights reserved.

Diels Alder-mediated release of gemcitabine from hybrid nanoparticles for enhanced pancreatic cancer therapy.

PubMed

Oluwasanmi, Adeolu; Al-Shakarchi, Wejdan; Manzur, Ayesha; Aldebasi, Mohammed H; Elsini, Rayan S; Albusair, Malek K; Haxton, Katherine J; Curtis, Anthony D M; Hoskins, Clare

2017-11-28

Hybrid nanoparticles (HNPs) have shown huge potential as drug delivery vehicles for pancreatic cancer. Currently, the first line treatment, gemcitabine, is only effective in 23.8% of patients. To improve this, a thermally activated system was developed by introducing a linker between HNPs and gemcitabine. Whereby, heat generation resulting from laser irradiation of the HNPs promoted linker breakdown resulting in prodrug liberation. In vitro evaluation in pancreatic adenocarcinoma cells, showed the prodrug was 4.3 times less cytotoxic than gemcitabine, but exhibited 11-fold improvement in cellular uptake. Heat activation of the formulation led to a 56% rise in cytotoxicity causing it to outperform gemcitabine by 26%. In vivo the formulation outperformed free gemcitabine with a 62% reduction in tumor weight in pancreatic xenografts. This HNP formulation is the first of its kind and has displayed superior anti-cancer activity as compared to the current first line drug gemcitabine after heat mediated controlled release. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice.

PubMed

Yadav, Monu; Parle, Milind; Sharma, Nidhi; Dhingra, Sameer; Raina, Neha; Jindal, Deepak Kumar

2017-11-01

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3 2 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNP opt ) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNP opt , with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNP opt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.

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.

Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

PubMed Central

Zou, Peng; Helson, Lawrence; Maitra, Anirban; Stern, Stephan T.; McNeil, Scott E.

2013-01-01

The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle encapsulated (nanocurcumin), and solvent solubilized curcumin formulations in Sprague Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon i.v. administration of nanocurcumin only nanoparticle encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile, but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested rapid, “burst” release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations. PMID:23534919

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.

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.

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

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

Solid lipid nanoparticles bearing oxybenzone: in-vitro and in-vivo evaluation.

PubMed

Gulbake, Arvind; Jain, Aviral; Khare, Piush; Jain, Sanjay K

2010-05-01

In the present project, Solid Lipid Nanoparticles (SLNs) bearing oxybenzone were prepared by ethanol injection method to improve its effectiveness as sunscreen. SLNs were characterized for particle size,polydispersity index, zeta potential and surface morphology. The optimized SLNs bearing oxybenzone were incorporated into water-removable cream base and compared with SLNs unloaded water-removable cream base for in vitro and in vivo parameters. Cream base formulation containing SLNs (Csd) with 5% oxybenzone showed slow drug release and better sun protecting factor (more than 25) compared to cream base containing 5% oxybenzone. Confocal Laser Scanning Microscopy was used to visualize the distribution of developed formulations in skin. CLSM indicated prolonged retention of SLNs in the stratum corneum as compared to plain cream base. These studies revealed that the cream base bearing SLNs exhibited good skin retention as well as enhanced sun protection effect compared to cream base.

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.

Smart Fluid System Dually Responsive to Light and Electric Fields: An Electrophotorheological Fluid.

PubMed

Yoon, Chang-Min; Jang, Yoonsun; Noh, Jungchul; Kim, Jungwon; Jang, Jyongsik

2017-10-24

Electrophotorheological (EPR) fluids, whose rheological activity is dually responsive to light and electric fields (E fields), is formulated by mixing photosensitive spiropyran-decorated silica (SP-sSiO 2 ) nanoparticles with zwitterionic lecithin and mineral oil. A reversible photorheological (PR) activity of the EPR fluid is developed via the binding and releasing mechanism of lecithin and merocyanine (MC, a photoisomerized form of SP) under ultraviolet (UV) and visible (VIS) light applications. Moreover, the EPR fluid exhibits an 8-fold higher electrorheological (ER) performance compared to the SP-sSiO 2 nanoparticle-based ER fluid (without lecithin) under an E field, which is attributed to the enhanced dielectric properties facilitated by the binding of the lecithin and SP molecules. Upon dual application of UV light and an E field, the EPR fluid exhibits high EPR performance (ca. 115.3 Pa) that far exceeds its separate PR (ca. 0.8 Pa) and ER (ca. 57.5 Pa) activities, because of the synergistic contributions of the PR and ER effects through rigid and fully connected fibril-like structures. Consequently, this study offers a strategy on formulation of dual-stimuli responsive smart fluid systems.

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.

Antitumor effect and toxicity of free rhodium (II) citrate and rhodium (II) citrate-loaded maghemite nanoparticles in mice bearing breast cancer

PubMed Central

2013-01-01

Background Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Methods Mice were evaluated with regard to the treatments’ toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry. Results Regarding the treatments’ toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining. Conclusions In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications. PMID:23414068

Analytical detection and method development of anticancer drug Gemcitabine HCl using gold nanoparticles.

PubMed

Menon, Shobhana K; Mistry, Bhoomika R; Joshi, Kuldeep V; Sutariya, Pinkesh G; Patel, Ravindra V

2012-08-01

A simple, rapid, cost effective and extractive UV spectrophotometric method was developed for the determination of Gemcitabine HCl (GMCT) in bulk drug and pharmaceutical formulation. It was based on UV spectrophotometric measurements in which the drug reacts with gold nanoparticles (AuNP) and changes the original colour of AuNP and forms a dark blue coloured solution which exhibits absorption maximum at 688nm. The apparent molar absorptivity and Sandell's sensitivity coefficient were found to be 3.95×10(-5)lmol(-1)cm(-1) and 0.060μgcm(-2) respectively. Beer's law was obeyed in the concentration range of 2.0-40μgml(-1). This method was tested and validated for various parameters according to ICH guidelines. The proposed method was successfully applied for the determination of GMCT in pharmaceutical formulation (parental formulation). The results demonstrated that the procedure is accurate, precise and reproducible (relative standard deviation <2%). As it is simple, cheap and less time consuming, it can be suitably applied for the estimation of GMCT in dosage forms. Copyright © 2012 Elsevier B.V. All rights reserved.

Hansen solubility parameters (HSP) for prescreening formulation of solid lipid nanoparticles (SLN): in vitro testing of curcumin-loaded SLN in MCF-7 and BT-474 cell lines.

PubMed

Doktorovova, Slavomira; Souto, Eliana B; Silva, Amélia M

2018-01-01

Curcumin, a phenolic compound from turmeric rhizome (Curcuma longa), has many interesting pharmacological effects, but shows very low aqueous solubility. Consequently, several drug delivery systems based on polymeric and lipid raw materials have been proposed to increase its bioavailability. Solid lipid nanoparticles (SLN), consisting of solid lipid matrix and a surfactant layer can load poorly water-soluble drugs, such as curcumin, deliver them at defined rates and enhance their intracellular uptake. In the present work, we demonstrate that, despite the drug's affinity to lipids frequently used in SLN production, the curcumin amount loaded in most SLN formulations may be too low to exhibit anticancer properties. The predictive curcumin solubility in solid lipids has been thoroughly analyzed by Hansen solubility parameters, in parallel with the lipid-screening solubility tests for a range of selected lipids. We identified the most suitable lipid materials for curcumin-loaded SLN, producing physicochemically stable particles with high encapsulation efficiency (>90%). Loading capacity of curcumin in SLN allowed preventing the cellular damage caused by cationic SLN on MCF-7 and BT-474 cells but was not sufficient to exhibit drug's anticancer properties. But curcumin-loaded SLN exhibited antioxidant properties, substantiating the conclusions that curcumin's effect in cancer cells is highly dose dependent.

Multifunctional platinum-based nanoparticles for biomedical applications.

PubMed

Cheng, Qinqin; Liu, Yangzhong

2017-03-01

Platinum-based anticancer drugs play a central role in current cancer therapy. However, their applicability and efficacy are limited by drug resistance and adverse effects. Nanocarrier-based platinum drug delivery systems are promising alternatives to circumvent the disadvantages of bare platinum drugs. The various properties of nanoparticle chemistry allow for the trend toward multiple functionality. Nanoparticles preferentially accumulate at the tumor site through passive targeting, and the attachment of tumor targeting moieties further enhances their tumor-specific localization as well as tumor cell uptake. The introduction of stimuli-responsive groups into drug delivery systems can further achieve spatially and temporally controlled drug release in response to specific stimuli. Combination therapy strategies have been used to promote synergetic efficacy and overcome the resistance of platinum drugs. The tumor-localized drug delivery strategies exhibit benefits for preventing local tumor recurrence. In addition, the combination of platinum drugs and imaging agents in one unity allows the cancer diagnostics for real-time monitoring the distribution of drug-loaded nanoparticles inside the body and tumor. This review discusses recent scientific advances in multifunctional nanoparticle formulations of platinum drugs, and these designs exhibit new potential of multifunctional nanoparticles for delivering platinum-based anticancer drugs. WIREs Nanomed Nanobiotechnol 2017, 9:e1410. doi: 10.1002/wnan.1410 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

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

Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam.

PubMed

Khalil, Rawia M; Abd-Elbary, A; Kassem, Mahfoz A; Ghorab, Mamdouh M; Basha, Mona

2014-05-01

The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX). The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application. The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430 nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of -19.1 to -25.7 mV. The release profiles of all formulations exhibited sustained release characteristics over 48 h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorporated in hydrogels. The gels showed adequate pH, non-Newtonian flow with shear-thinning behavior and controlled release profiles. The biological evaluation revealed that MLX-loaded NLC gel showed more pronounced effect compared to MLX-loaded SLN gel. It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application.

In vitro and in vivo anti-tumor efficacy of 10-hydroxycamptothecin polymorphic nanoparticle dispersions: shape- and polymorph-dependent cytotoxicity and delivery of 10-hydroxycamptothecin to cancer cells.

PubMed

Wang, Hongdi; Feng, Jialing; Liu, Guijin; Chen, Baoqiong; Jiang, Yanbin; Xie, Qiuling

2016-05-01

Nanotechnology associated with a crystal engineering approach was proposed for improving the solubility and efficacy of hydrophobic drugs in this study. 10-hydroxycamptothecin polymorphic nanoparticle dispersions (HCPT-PNDs) were prepared using the supercritical anti-solvent technique coupled with the high-pressure homogenization method. Shape- and polymorph-dependent tumor suppression was observed in both in vitro and in vivo models, where needle-shaped HCPT-PND exhibited dramatic improvement of antitumor efficacy. A benefit of controllable size and a large surface-to-volume ratio of needle-shaped nanoparticles is the improvement of dissolution properties, which facilitates enhancing pharmacokinetic and pharmaco-dynamic properties. The needle-shaped HCPT-PND, which with longer blood retention time and more effective cellular uptake, makes it possible to accumulate drug in tumor tissues and exhibit higher cytotoxicity. No severe systemic toxicity was observed due to sustained-dissolution and the low dose of drug in normal tissues. The results suggest that the needle-shaped HCPT-PND is an interesting nano-formulation of HCPT. Nanotechnology has enabled the production of novel therapeutics drugs against cancer. Here, the authors investigated the use of a crystal engineering approach for the modification of camptothecin in order to improve its water solubility. Physicochemical and biological properties were studied. The results would suggest the applicability of this approach for nano-formulation. Copyright © 2016 Elsevier Inc. All rights reserved.

On the Role of Specific Interactions in the Diffusion of Nanoparticles in Aqueous Polymer Solutions

PubMed Central

2013-01-01

Understanding nanoparticle diffusion within non-Newtonian biological and synthetic fluids is essential in designing novel formulations (e.g., nanomedicines for drug delivery, shampoos, lotions, coatings, paints, etc.), but is presently poorly defined. This study reports the diffusion of thiolated and PEGylated silica nanoparticles, characterized by small-angle neutron scattering, in solutions of various water-soluble polymers such as poly(acrylic acid) (PAA), poly(N-vinylpyrrolidone) (PVP), poly(ethylene oxide) (PEO), and hydroxyethylcellulose (HEC) probed using NanoSight nanoparticle tracking analysis. Results show that the diffusivity of nanoparticles is affected by their dimensions, medium viscosity, and, in particular, the specific interactions between nanoparticles and the macromolecules in solution; strong attractive interactions such as hydrogen bonding hamper diffusion. The water-soluble polymers retarded the diffusion of thiolated particles in the order PEO > PVP > PAA > HEC whereas for PEGylated silica particles retardation followed the order PAA > PVP = HEC > PEO. In the absence of specific interactions with the medium, PEGylated nanoparticles exhibit enhanced mobility compared to their thiolated counterparts despite some increase in their dimensions. PMID:24354390

On the role of specific interactions in the diffusion of nanoparticles in aqueous polymer solutions.

PubMed

Mun, Ellina A; Hannell, Claire; Rogers, Sarah E; Hole, Patrick; Williams, Adrian C; Khutoryanskiy, Vitaliy V

2014-01-14

Understanding nanoparticle diffusion within non-Newtonian biological and synthetic fluids is essential in designing novel formulations (e.g., nanomedicines for drug delivery, shampoos, lotions, coatings, paints, etc.), but is presently poorly defined. This study reports the diffusion of thiolated and PEGylated silica nanoparticles, characterized by small-angle neutron scattering, in solutions of various water-soluble polymers such as poly(acrylic acid) (PAA), poly(N-vinylpyrrolidone) (PVP), poly(ethylene oxide) (PEO), and hydroxyethylcellulose (HEC) probed using NanoSight nanoparticle tracking analysis. Results show that the diffusivity of nanoparticles is affected by their dimensions, medium viscosity, and, in particular, the specific interactions between nanoparticles and the macromolecules in solution; strong attractive interactions such as hydrogen bonding hamper diffusion. The water-soluble polymers retarded the diffusion of thiolated particles in the order PEO > PVP > PAA > HEC whereas for PEGylated silica particles retardation followed the order PAA > PVP = HEC > PEO. In the absence of specific interactions with the medium, PEGylated nanoparticles exhibit enhanced mobility compared to their thiolated counterparts despite some increase in their dimensions.

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.

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.

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.

Novel Polysaccharide Based Polymers and Nanoparticles for Controlled Drug Delivery and Biomedical Imaging

NASA Astrophysics Data System (ADS)

Shalviri, Alireza

The use of polysaccharides as building blocks in the development of drugs and contrast agents delivery systems is rapidly growing. This can be attributed to the outstanding virtues of polysaccharides such as biocompatibility, biodegradability, upgradability, multiple reacting groups and low cost. The focus of this thesis was to develop and characterize novel starch based hydrogels and nanoparticles for delivery of drugs and imaging agents. To this end, two different systems were developed. The first system includes polymer and nanoparticles prepared by graft polymerization of polymethacrylic acid and polysorbate 80 onto starch. This starch based platform nanotechnology was developed using the design principles based on the pathophysiology of breast cancer, with applications in both medical imaging and breast cancer chemotherapy. The nanoparticles exhibited a high degree of doxorubicin loading as well as sustained pH dependent release of the drug. The drug loaded nanoparticles were significantly more effective against multidrug resistant human breast cancer cells compared to free doxorubicin. Systemic administration of the starch based nanoparticles co-loaded with doxorubicin and a near infrared fluorescent probe allowed for non-invasive real time monitoring of the nanoparticles biodistribution, tumor accumulation, and clearance. Systemic administration of the clinically relevant doses of the drug loaded particles to a mouse model of breast cancer significantly enhanced therapeutic efficacy while minimizing side effects compared to free doxorubicin. A novel, starch based magnetic resonance imaging (MRI) contrast agent with good in vitro and in vivo tolerability was formulated which exhibited superior signal enhancement in tumor and vasculature. The second system is a co-polymeric hydrogel of starch and xanthan gum with adjustable swelling and permeation properties. The hydrogels exhibited excellent film forming capability, and appeared to be particularly useful in controlled delivery applications of larger molecular size compounds. The starch based hydrogels, polymers and nanoparticles developed in this work have shown great potentials for controlled drug delivery and biomedical imaging applications.

A dual-targeting strategy for enhanced drug delivery and synergistic therapy based on thermosensitive nanoparticles.

PubMed

Wang, Mingxin; You, Chaoqun; Gao, Zhiguo; Wu, Hongshuai; Sun, Baiwang; Zhu, Xiaoli; Chen, Renjie

2018-08-01

The functionalized nanoparticles have been widely studied and reported as carriers of drug transport recently. Furthermore, many groups have focused more on developing novel and efficient treatment methods, such as photodynamic therapy and photothermal therapy, since both therapies have shown inspiring potential in the application of antitumor. The mentioned treatments exhibited the superiority of cooperative manner and showed the ability to compensate for the adverse effects caused by conventional monotherapy in proposed strategies. In view of the above descriptions, we formulated a thermosensitive drug delivery system, which achieved the enhanced delivery of cisplatin and two photosensitizers (ICG and Ce6) by dual-targeting traction. Drawing on the thin film hydration method, cisplatin and photosensitizers were encapsulated inside nanoparticles. Meanwhile, the targeting peptide cRGD and targeting molecule folate can be modified on the surface of nanoparticles to realize the active identification of tumor cells. The measurements of dynamic light scattering showed that the prepared nanoparticles had an ideal dispersibility and uniform particle size of 102.6 nm. On the basis of the results observed from confocal laser scanning microscope, the modified nanoparticles were more efficient endocytosed by MCF-7 cells as a contrast to SGC-7901 cells. Photothermal conversion-triggered drug release and photo-therapies produced a significant apoptosis rate of 85.9% on MCF-7 cells. The distinguished results made it believed that the formulated delivery system had conducted great efforts and innovations for the realization of concise collaboration and provided a promising strategy for the treatment of breast cancer.

Design of pH-responsive nanoparticles of terpolymer of poly(methacrylic acid), polysorbate 80 and starch for delivery of doxorubicin.

PubMed

Shalviri, Alireza; Chan, Ho Ka; Raval, Gaurav; Abdekhodaie, Mohammad J; Liu, Qiang; Heerklotz, Heiko; Wu, Xiao Yu

2013-01-01

This work focused on the design of new pH-responsive nanoparticles for controlled delivery of anticancer drug doxorubicin (Dox). Nanoparticles of poly(methacrylic acid)-polysorbate 80-grafted starch (PMAA-PS 80-g-St) were synthesized by using a one-pot method that enabled simultaneous grafting of PMAA and PS 80 onto starch and nanoparticle formation in an aqueous medium. The particles were characterized by FTIR, (1)H NMR, TEM, DLS, and potentiometric titration. Dox loading and in vitro release from the nanoparticles were investigated. The FTIR and (1)H NMR confirmed the chemical composition of the graft terpolymer. The nanoparticles were relatively spherical with narrow size distribution and porous morphology. They exhibited pH-dependent swelling in a physiological pH range. The particle size and magnitude of phase transition were dependent on polymer composition and formulation parameters such as concentrations of surfactant and cross-linking agent and total monomer concentration. The nanoparticles with optimized compositions showed high loading capacity for Dox and sustained Dox release. The results suggest that the new pH-responsive terpolymer nanoparticles are useful in controlled drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

Development and in vitro evaluation of oxytetracycline-loaded PMMA nanoparticles for oral delivery against anaplasmosis.

PubMed

SadguruPrasad, Lakshminarayana Turuvekere; Madhusudhan, Basavaraj; Kodihalli B, Prakash; Ghosh, Prahlad Chandra

2017-02-01

Poly-methyl methacrylate (PMMA) polymer with remarkable properties and merits are being preferred in various biomedical applications due to its biocompatibility, non-toxicity and cost effectiveness. In this investigation, oxytetracycline-loaded PMMA nanoparticles were prepared using nano-precipitation method for the treatment of anaplasmosis. The prepared nanoparticles were characterised using dynamic light scattering (DLS), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. The mean average diameter of the nanoparticles ranged between 190-240 nm and zeta potential was found to be -19 mV. The drug loading capacity and entrapment efficiency of nanoparticles was found varied between 33.7-62.2% and 40.5-60.0%. The in vitro drug release profile exhibited a biphasic phenomenon indicating controlled drug release. The uptake of coumarin-6(C-6)-loaded PMMA nanoparticles in Plasmodium falciparum ( Pf 3D7) culture model was studied. The preferential uptake of C-6-loaded nanoparticles by the Plasmodium infected erythrocytes in comparison with the uninfected erythrocytes was observed under fluorescence microscopy. These findings suggest that oxytetracycline-loaded PMMA nanoparticles were found to be an effective oral delivery vehicle and an alternative pharmaceutical formulation in anaplasmosis treatment, too.

Biodegradable Chitosan Magnetic Nanoparticle Carriers for Sub-Cellular Targeting Delivery of Artesunate for Efficient Treatment of Breast Cancer

NASA Astrophysics Data System (ADS)

Subramanian, Natesan; Abimanyu, Sugumaran; Vinoth, Jeevanesan; Sekar, Ponnusamy Chandra

2010-12-01

Artesunate is a semi-synthetic derivative of artemisinin, the active principle extracted from Artemisia annua. It possesses good anti-proliferative activity and anti-angiogenic activity with very low toxicity to normal healthy cells. The drawback of most cancer drugs is their inability to accumulate selectively in the cancerous cells. So, large quantities of doses have to be administered to get the required therapeutic concentration in the target site and it resulted in many serious side effects due to the exposure of healthy cells to higher concentrations of cytotoxic drugs. The problem may be solved by selectively and quantitatively accumulating the drug at target site using magnetic nanoparticles guided by an externally applied magnetic field. A modest attempt has been made in this present study, the artesunate magnetic nanoparticle was successfully formulated using two forms of chitosan and evaluated for its in-vitro characteristics like surface morphology, particle size and distribution, zeta potential, magnetic susceptibility, encapsulation efficiency, loading capacity and in-vitro drug release. The synthesized magnetite size was 73 nm and the size of developed magnetic nanoparticles of artesunate was in the range of 90 to 575 nm. Acetic acid soluble chitosan at low concentration exhibit highest encapsulation efficiency and drug loading whereas increase in water soluble chitosan concentration increases the encapsulation efficiency and drug loading in formulations. The developed chitosan magnetic nanoparticles of artesunate shows better release characteristics and may be screened for its in-vivo breast cancer activity.

Porous Silicon Nanoparticle Photosensitizers for Singlet Oxygen and Their Phototoxicity Against Cancer Cells

PubMed Central

Xiao, Ling; Gu, Luo; Howell, Stephen B.; Sailor, Michael J.

2011-01-01

Porous Si nanoparticles, prepared from electrochemically etched single crystal Si wafers, function as photosensitizers to generate 1O2 in ethanol and in aqueous media. The preparation conditions for the porous Si nanoparticles were optimized to maximize (1) the yield of material; (2) its quantum yield of 1O2 production; and (3) its in vitro degradation properties. The optimal formulation was determined to consist of nanoparticles 146 ± 7 nm in diameter, with nominal pore sizes of 12 ± 4 nm. The quantum yield for 1O2 production is 0.10 ± 0.02 in ethanol and 0.17 ± 0.01 in H2O. HeLa or NIH-3T3 cells treated with 100 µg/mL porous Si nanoparticles and exposed to 60 J/cm2 white light (infrared filtered, 100 mW/cm2 for 10 min) exhibit ~ 45% cell death, while controls containing no nanoparticles show 10% or 25% cell death, respectively. The dark control experiment yields < 10% cytotoxicity for either cell type. PMID:21452822

Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases

PubMed Central

2012-01-01

Background Alpha 1- antitrypsin (α1AT) belongs to the superfamily of serpins and inhibits different proteases. α1AT protects the lung from cellular inflammatory enzymes. In the absence of α1AT, the degradation of lung tissue results to pulmonary complications. The pulmonary route is a potent noninvasive route for systemic and local delivery. The aerosolized α1AT not only affects locally its main site of action but also avoids remaining in circulation for a long period of time in peripheral blood. Poly (D, L lactide-co glycolide) (PLGA) is a biodegradable and biocompatible polymer approved for sustained controlled release of peptides and proteins. The aim of this work was to prepare a wide range of particle size as a carrier of protein-loaded nanoparticles to deposit in different parts of the respiratory system especially in the deep lung. Various lactide to glycolide ratio of the copolymer was used to obtain different release profile of the drug which covers extended and rapid drug release in one formulation. Results Nonaqueous and double emulsion techniques were applied for the synthesis of nanoparticles. Nanoparticles were characterized in terms of surface morphology, size distribution, powder X-ray diffraction (XRD), encapsulation efficiency, in vitro drug release, FTIR spectroscopy and differential scanning calorimetry (DSC). To evaluate the nanoparticles cytotoxicity, cell cytotoxicity test was carried out on the Cor L105 human epithelial lung cancer cell line. Nanoparticles were spherical with an average size in the range of 100 nm to 1μ. The encapsulation efficiency was found to be higher when the double emulsion technique was applied. XRD and DSC results indicated that α1AT encapsulated in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. The lactic acid to glycolic acid ratio affects the release profile of α1AT. Hence, PLGA with a 50:50 ratios exhibited the ability to release %60 of the drug within 8, but the polymer with a ratio of 75:25 had a continuous and longer release profile. Cytotoxicity studies showed that nanoparticles do not affect cell growth and were not toxic to cells. Conclusion In summary, α1AT-loaded nanoparticles may be considered as a novel formulation for efficient treatment of many pulmonary diseases. PMID:22607686

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.

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

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.

Development of curcumin-loaded poly(hydroxybutyrate- co-hydroxyvalerate) nanoparticles as anti-inflammatory carriers to human-activated endothelial cells

NASA Astrophysics Data System (ADS)

Simion, Viorel; Stan, Daniela; Gan, Ana-Maria; Pirvulescu, Monica Madalina; Butoi, Elena; Manduteanu, Ileana; Deleanu, Mariana; Andrei, Eugen; Durdureanu-Angheluta, Anamaria; Bota, Marian; Enachescu, Marius; Calin, Manuela; Simionescu, Maya

2013-12-01

Curcumin (Cm)-loaded poly(hydroxybutyrate- co-hydroxyvalerate) (PHBV) nanoparticles (CmPN) were obtained and characterized and their effect on human endothelial cells (HEC) was assessed. Different CmPN formulations have been prepared using the emulsion solvent evaporation technique, and characterized for size, structure, Zeta potential, Cm entrapment efficiency, and in vitro Cm release. CmPN cytotoxicity and cellular uptake have been followed using HEC. Also, the effect of CmPN treatment on the p38MAPK signaling pathway in endothelial cells was investigated. The results obtained by electron and atomic force microscopy revealed the spherical shape of the CmPN formulation. Based on size and encapsulation efficiency, the CmPN formulation with the average diameter of 186 nm and with the highest encapsulation efficiency (83 %) has been used in the further studies. The release of Cm from CmPN was 18 % after 8 h of incubation at 37 °C, followed by a slow release until 144 h, when it reached 44 %, indicating a controlled release. CmPN are taken up by HEC and exhibited low cytotoxicity at concentrations up to 10 μM. The pre-treatment of HEC with CmPN before exposure to tumor necrosis factor-alpha (TNF-α) determined a decrease of p38MAPK phosphorylation. In conclusion, Cm encapsulated into PHBV nanoparticles, at concentration up to 10 μM, has low cytotoxicity and display anti-inflammatory activity on TNF-α-activated HEC by suppressing the phosphorylation of p38MAPK.

Preparation, characterization and pharmacokinetics of enrofloxacin-loaded solid lipid nanoparticles: influences of fatty acids.

PubMed

Xie, Shuyu; Zhu, Luyan; Dong, Zhao; Wang, Xiaofang; Wang, Yan; Li, Xihe; Zhou, WenZhong

2011-04-01

Enrofloxacin-loaded solid lipid nanoparticles (SLN) were prepared using fatty acids (tetradecanoic acid, palmitic acid, stearic acid) as lipid matrix by hot homogenization and ultrasonication method. The effect of fatty acids on the characteristics and pharmacokinetics of the SLN were investigated. The results showed that the encapsulation efficiency and loading capacity of nanoparticles varied with fatty acids in the order of stearic acid>palmitic acid>tetradecanoic acid. Furthermore, stearic acid-SLN had larger particle size, bigger polydispersity index (PDI) and higher zeta potential compared with the other two fatty acid formulated SLN. The SLN showed sustained releases in vitro and the released enrofloxacin had the same antibacterial activity as that of the native enrofloxacin. Although in vitro release exhibited similar patterns, within 24 h the releasing rates of the three formulations were significantly different (tetradecanoic acid-SLN>palmitic acid-SLN>stearic acid-SLN). Pharmacokinetic study after a single dose of intramuscular administration to mice demonstrated that tetradecanoic acid-SLN, palmitic acid-SLN, and stearic acid-SLN increased the bioavailability by 6.79, 3.56 and 2.39 folds, and extended the mean residence time (MRT) of the drug from 10.60 h to 180.36, 46.26 and 19.09 h, respectively. These results suggest that the enrofloxacin-fatty acid SLN are promising formulations for sustained release while fatty acids had significant influences on the characteristics and performances of the SLN. Copyright © 2010 Elsevier B.V. All rights reserved.

Poly(vinyl methyl ether/maleic anhydride)-Doped PEG-PLA Nanoparticles for Oral Paclitaxel Delivery To Improve Bioadhesive Efficiency.

PubMed

Wang, Qian; Li, Chan; Ren, Tianyang; Chen, Shizhu; Ye, Xiaoxia; Guo, Hongbo; He, Haibing; Zhang, Yu; Yin, Tian; Liang, Xing-Jie; Tang, Xing

2017-10-02

Bioadhesive nanoparticles based on poly(vinyl methyl ether/maleic anhydride) (PVMMA) and poly(ethylene glycol) methyl ether-b-poly(d,l-lactic acid) (mPEG-b-PLA) were produced by the emulsification solvent evaporation method. Paclitaxel was utilized as the model drug, with an encapsulation efficiency of up to 90.2 ± 4.0%. The nanoparticles were uniform and spherical in shape and exhibited a sustained drug release compared with Taxol. m-NPs also exhibited favorable bioadhesive efficiency at the same time. Coumarin 6 or DiR-loaded nanoparticles with/without PVMMA (C6-m-NPs/DiR-m-NPs or C6-p-NPs/DiR-p-NPs) were used for cellular uptake and intestinal adhesion experiments, respectively. C6-m-NPs were shown to enhance cellular uptake, and caveolae/lipid raft mediated endocytosis was the primary route for the uptake of the nanoparticles. Favorable bioadhesive efficiency led to prolonged retention in the intestine reflected by the fluorescence in isolated intestines ex vivo. In a ligated intestinal loops model, C6-m-NPs showed a clear advantage for transporting NPs across the mucus layer over C6-p-NPs and free C6. The apparent permeability coefficient (Papp) of PTX-m-NPs through Caco-2/HT29 monolayers was 1.3- and 1.6-fold higher than PTX-p-NPs and Taxol, respectively, which was consistent with the AUC 0-t of different PTX formulations after oral administration in rats. PTX-m-NPs also exhibited a more effective anticancer efficacy, with an IC 50 of 0.2 ± 1.4 μg/mL for A549 cell lines, further demonstrating the advantage of bioadhesive nanoparticles. The bioadhesive nanoparticles m-NPs demonstrated both mucus permeation and epithelial absorption, and thus, this bioadhesive drug delivery system has the potential to improve the bioavailability of drugs that are insoluble in the gastrointestinal environment.

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.

Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting.

PubMed

Ma, Yanni; He, Shaolong; Ma, Xueqin; Hong, Tongtong; Li, Zhifang; Park, Kinam; Wang, Wenping

2016-02-29

Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver.

Fabrication and evaluation of valsartan–polymer– surfactant composite nanoparticles by using the supercritical antisolvent process

PubMed Central

Kim, Min-Soo; Baek, In-hwan

2014-01-01

The aim of this study was to fabricate valsartan composite nanoparticles by using the supercritical antisolvent (SAS) process, and to evaluate the correlation between in vitro dissolution and in vivo pharmacokinetic parameters for the poorly water-soluble drug valsartan. Spherical composite nanoparticles with a mean size smaller than 400 nm, which contained valsartan, were successfully fabricated by using the SAS process. X-ray diffraction and thermal analyses indicated that valsartan was present in an amorphous form within the composite nanoparticles. The in vitro dissolution and oral bioavailability of valsartan were dramatically enhanced by the composite nanoparticles. Valsartan–hydroxypropyl methylcellulose–poloxamer 407 nanoparticles exhibited faster drug release (up to 90% within 10 minutes under all dissolution conditions) and higher oral bioavailability than the raw material, with an approximately 7.2-fold higher maximum plasma concentration. In addition, there was a positive linear correlation between the pharmacokinetic parameters and the in vitro dissolution efficiency. Therefore, the preparation of composite nanoparticles with valsartan–hydroxypropyl methylcellulose and poloxamer 407 by using the SAS process could be an effective formulation strategy for the development of a new dosage form of valsartan with high oral bioavailability. PMID:25404856

A simple approach to design chitosan functionalized Fe3O4 nanoparticles for pH responsive delivery of doxorubicin for cancer therapy

NASA Astrophysics Data System (ADS)

Adimoolam, Mahesh G.; Amreddy, Narsireddy; Nalam, Madhusudana Rao; Sunkara, Manorama V.

2018-02-01

The use of magnetic nanoparticles (MNPs) in cancer therapy offer many advantages due to their unique size, physical and biocompatible properties. In this study we have developed a formulation, comprising of anti-cancer drug doxorubicin (Dox) conjugated to iron oxide nanoparticles via a pH sensitive imine linker. Different amounts of chitosan functionalized superparamagnetic iron oxide nanoparticles (Fe3O4-CHI) were synthesized in-situ by a simple hydrolysis method at room temperature. The synthesized nanoparticles were well characterized by TEM, Zeta Potential, TOC, XPS, TGA and VSM for their physicochemical properties. Dox was conjugated to the Fe3O4-CHI nanoparticles via a glutaraldehyde cross linker with the imine (sbnd Cdbnd Nsbnd) bond, which is sensitive to cleavage in the pH range of 4.4-6.4. The synthesized Fe3O4-Dox nanoparticles exhibited enhanced drug release in lower pH conditions which mimics the tumor microenvironment or intracellular organelles such as endosomes/lysosomes. The cell uptake and therapeutic efficacy of Fe3O4-Dox nanoparticles carried out in ovarian cancer cell (SK-OV-3) and breast cancer cell line (MCF7) showed improved therapeutic efficacy of Dox by nearly four-fold with Fe3O4-Dox nanoparticles.

Optimization of novel pentablock copolymer based composite formulation for sustained delivery of peptide/protein in the treatment of ocular diseases

PubMed Central

Patel, Sulabh P.; Vaishya, Ravi; Patel, Ashaben; Agrahari, Vibhuti; Pal, Dhananjay; Mitra, Ashim K.

2016-01-01

This manuscript is focused on the development of pentablock (PB) copolymer based sustained release formulation for the treatment of posterior segment ocular diseases. We have successfully synthesized biodegradable and biocompatible PB copolymers for the preparation of nanoparticles (NPs) and thermosensitive gel. Achieving high drug loading with hydrophilic biotherapeutics (peptides /proteins) is a challenging task. Moreover, small intravitreal injection volume (≤100 μL) requires high loading to develop a long term (6 months) sustained release formulation. We have successfully investigated various formulation parameters to achieve maximum peptide/protein (octreotide, insulin, lysozyme, IgG-Fab, IgG, and catalase) loading in PB NPs. Improvement in drug loading can facilitate delivery of larger doses of therapeutic proteins via limited injection volume. A composite formulation comprised of NPs in gel system exhibited sustained release (without burst effect) of peptides and proteins, may serve as a platform technology for the treatment of posterior segment ocular diseases. PMID:26964498

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.

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.

Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration.

PubMed

Abrego, Guadalupe; Alvarado, Helen; Souto, Eliana B; Guevara, Bessy; Bellowa, Lyda Halbaut; Parra, Alexander; Calpena, Ana; Garcia, María Luisa

2015-09-01

Two optimized pranoprofen-loaded poly-l-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF-F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formulations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranoprofen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sustained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflammatory efficacy studies suggest that the ocular application of the hydrogels containing azone was more effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of ocular irritancy have been detected for the produced hydrogels. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

Activity and in vivo tracking of Amphotericin B loaded PLGA nanoparticles.

PubMed

Souza, A C O; Nascimento, A L; de Vasconcelos, N M; Jerônimo, M S; Siqueira, I M; R-Santos, L; Cintra, D O S; Fuscaldi, L L; Pires Júnior, O R; Titze-de-Almeida, R; Borin, M F; Báo, S N; Martins, O P; Cardoso, V N; Fernandes, S O; Mortari, M R; Tedesco, A C; Amaral, A C; Felipe, M S S; Bocca, A L

2015-05-05

The development of biocompatible polymeric nanoparticles has become an important strategy for optimizing the therapeutic efficacy of many classical drugs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. In this study, nanoparticles of Amphotericin B entrapped within poly (lactic-co-glycolic) acid and incorporated with dimercaptosuccinic acid (NANO-D-AMB) as a target molecule were evaluated for their physic-chemical characteristics, pharmacokinetics, biocompatibility and antifungal activity. We found high plasma concentrations of Amphotericin B upon treatment with NANO-D-AMB and a high uptake of nanoparticles in the lungs, liver and spleen. NANO-D-AMB exhibited antifungal efficacy against Paracoccidioides brasiliensis and induced much lower cytotoxicity levels compared to D-AMB formulation in vivo and in vitro. Together, these results confirm that NANO-D-AMB improves Amphotericin B delivery and suggest this delivery system as a potential alternative to the use of Amphotericin B sodium deoxycholate. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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.

Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications.

PubMed

Yallapu, Murali M; Othman, Shadi F; Curtis, Evan T; Bauer, Nichole A; Chauhan, Neeraj; Kumar, Deepak; Jaggi, Meena; Chauhan, Subhash C

2012-01-01

The next generation magnetic nanoparticles (MNPs) with theranostic applications have attracted significant attention and will greatly improve nanomedicine in cancer therapeutics. Such novel MNP formulations must have ultra-low particle size, high inherent magnetic properties, effective imaging, drug targeting, and drug delivery properties. To achieve these characteristic properties, a curcumin-loaded MNP (MNP-CUR) formulation was developed. MNPs were prepared by chemical precipitation method and loaded with curcumin (CUR) using diffusion method. The physicochemical properties of MNP-CUR were characterized using dynamic light scattering, transmission electron microscopy, and spectroscopy. The internalization of MNP-CUR was achieved after 6 hours incubation with MDA-MB-231 breast cancer cells. The anticancer potential was evaluated by a tetrazolium-based dye and colony formation assays. Further, to prove MNP-CUR results in superior therapeutic effects over CUR, the mitochondrial membrane potential integrity and reactive oxygen species generation were determined. Magnetic resonance imaging capability and magnetic targeting property were also evaluated. MNP-CUR exhibited individual particle grain size of ~9 nm and hydrodynamic average aggregative particle size of ~123 nm. Internalized MNP-CUR showed a preferential uptake in MDA-MB-231 cells in a concentration-dependent manner and demonstrated accumulation throughout the cell, which indicates that particles are not attached on the cell surface but internalized through endocytosis. MNP-CUR displayed strong anticancer properties compared to free CUR. MNP-CUR also amplified loss of potential integrity and generation of reactive oxygen species upon treatment compared to free CUR. Furthermore, MNP-CUR exhibited superior magnetic resonance imaging characteristics and significantly increased the targeting capability of CUR. MNP-CUR exhibits potent anticancer activity along with imaging and magnetic targeting capabilities. This approach can be extended to preclinical and clinical use and may have importance in cancer treatment and cancer imaging in the future. Further, if these nanoparticles can functionalize with antibody/ligands, they will serve as novel platforms for multiple biomedical applications.

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.

A polymeric nanoparticle consisting of mPEG-PLA-Toco and PLMA-COONa as a drug carrier: improvements in cellular uptake and biodistribution.

PubMed

Yi, Yilwoong; Kim, Jae Hong; Kang, Hye-Won; Oh, Hun Seung; Kim, Sung Wan; Seo, Min Hyo

2005-02-01

To evaluate a new polymeric nanoparticulate drug delivery formulation that consists of two components: i) an amphiphilic diblock copolymer having tocopherol moiety at the end of the hydrophobic block in which the hydrophobic tocopherol moiety increases stability of hydrophobic core of the nanoparticle in aqueous medium; and ii) a biodegradable copolyester having carboxylate end group that is capable of forming ionic complex with positively charged compounds such as doxorubicin. A doxourubicin-loaded polymeric nanoparticle (Dox-PNP) was prepared by solvent evaporation method. The entrapment efficiency, size distribution, and in vitro release profile at various pH conditions were characterized. In vitro cellular uptake was investigated by confocal microscopy, flow cytometry, and MTT assay using drug-sensitive and drug-resistant cell lines. Pharmacokinetics and biodistribution were evaluated in rats and tumor-bearing mice. Doxorubicin (Dox) was efficiently loaded into the PNP (higher than 95% of entrapment efficiency), and the diameter of Dox-PNP was in the range 20-25 nm with a narrow size distribution. In Vitro study showed that Dox-PNP exhibited higher cellular uptake into both human breast cancer cell (MCF-7) and human uterine cancer cell (MES-SA) than free doxorubicin solution (Free-Dox), especially into drug-resistant cells (MCF-7/ADR and MES-SA/Dx-5). In pharmacokinetics and tissue distribution study, the bioavailability of Dox-PNP calculated from the area under the blood concentration-time curve (AUC) was 69.8 times higher than that of Free-Dox in rats, and Dox-PNP exhibited 2 times higher bioavailability in tumor tissue of tumor-bearing mice. Dox-PNP exhibited enhanced cellular uptake of the drug. In the cytotoxic activity study, this improved cellular uptake was proved to be more advantageous in drug-resistant cell. Dox-PNP exhibited much higher bioavailability in blood plasma and more drug accumulation in tumor tissue than conventional doxorubicin formulation. The results of this study suggest that the PNP system is an advantageous carrier for drug delivery.

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.

Hyaluronic acid co-functionalized gold nanoparticle complex for the targeted delivery of metformin in the treatment of liver cancer (HepG2 cells).

PubMed

Kumar, C Senthil; Raja, M D; Sundar, D Sathish; Gover Antoniraj, M; Ruckmani, K

2015-09-05

In this study, green synthesis of gold nanoparticles (AuNPs) was achieved using the extract of eggplant as a reducing agent. Hyaluronic acid (HA) serves as a capping and targeting agent. Metformin (MET) was successfully loaded on HA capped AuNPs (H-AuNPs) and this formulation binds easily on the surface of the liver cancer cells. The synthesized nanoparticles were characterized by UV-Vis spectrophotometer, HR-TEM, particle size analyser and zeta potential measurement. Toxicity studies of H-AuNPs in zebra fish confirmed the in vivo safety of the AuNPs. The in vitro cytotoxicity results showed that the amount of MET-H-AuNPs enough to achieve 50% inhibition (IC50) was much lower than free MET. Flow cytometry analysis showed the significant reduction in G2/M phase after treatment with MET-H-AuNPs, and molecular level apoptosis were studied using western blotting. The novelty of this study is the successful synthesis of AuNPs with a higher MET loading and this formulation exhibited better targeted delivery as well as increased regression activity than free MET in HepG2 cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Paclitaxel Albumin-stabilized Nanoparticle Formulation

Cancer.gov

This page contains brief information about paclitaxel albumin-stabilized nanoparticle formulation and a collection of links to more information about the use of this drug, research results, and ongoing clinical trials.

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.

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.

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.

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.

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.

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

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.

Metal-coated magnetic nanoparticles in an optically active medium: A nonreciprocal metamaterial

NASA Astrophysics Data System (ADS)

Christofi, Aristi; Stefanou, Nikolaos

2018-03-01

We report on the optical response of a nonreciprocal bianisotropic metamaterial, consisting of spherical, metal-coated magnetic nanoparticles embedded in an optically active medium, thus combining gyrotropy, plasmonic resonances, and chirality in a versatile design. The corresponding effective medium is deduced by an appropriate two-step generalized Maxwell-Garnett homogenization scheme. The associated photonic band structure and transmission spectra are obtained through a six-vector formulation of Maxwell equations, which provides an efficient framework for general bianisotropic structures going beyond existing approaches that involve cumbersome nonlinear eigenvalue problems. Our results, analyzed and discussed in the light of group theory, provide evidence that the proposed metamaterial exhibits some remarkable frequency-tunable properties, such as strong, plasmon-enhanced nonreciprocal polarization azimuth rotation and magnetochiral dichroism.

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.

Multifunctional Tannic Acid/Silver Nanoparticle-Based Mucoadhesive Hydrogel for Improved Local Treatment of HSV Infection: In Vitro and In Vivo Studies

PubMed Central

Szymańska, Emilia; Orłowski, Piotr; Tomaszewska, Emilia; Bąska, Piotr; Grobelny, Jarosław; Basa, Anna; Krzyżowska, Małgorzata

2018-01-01

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection. PMID:29382085

Molecular imaging with targeted perfluorocarbon nanoparticles: Quantification of the concentration dependence of contrast enhancement for binding to sparse cellular epitopes

PubMed Central

Marsh, Jon N.; Partlow, Kathryn C.; Abendschein, Dana R.; Scott, Michael J.; Lanza, Gregory M.; Wickline, Samuel A.

2007-01-01

Targeted, liquid perfluorocarbon nanoparticles are effective agents for acoustic contrast enhancement of abundant cellular epitopes (e.g. fibrin in thrombi) and for lower prevalence binding sites, such as integrins associated with tumor neovasculature. In this study we sought to delineate the quantitative relationship between the extent of contrast enhancement of targeted surfaces and the density (and concentration) of bound perfluorocarbon (PFC) nanoparticles. Two dramatically different substrates were utilized for targeting. In one set of experiments, the surfaces of smooth, flat, avidin-coated agar disks were exposed to biotinylated nanoparticles to yield a thin layer of targeted contrast. For the second set of measurements, we targeted PFC nanoparticles applied in thicker layers to cultured smooth muscle cells expressing the transmembrane glycoprotein “tissue factor” at the cell surface. An acoustic microscope was used to characterize reflectivity for all samples as a function of bound PFC (determined via gas chromatography). We utilized a formulation of low-scattering nanoparticles having oil-based cores to compete against high-scattering PFC nanoparticles for binding, to elucidate the dependence of contrast enhancement on PFC concentration. The relationship between reflectivity enhancement and bound PFC content varied in a curvilinear fashion, and exhibited an apparent asymptote (approximately 16 dB and 9 dB enhancement for agar and cell samples, respectively) at the maximum concentrations (~150 μg and ~1000 μg PFOB for agar and cell samples, respectively). Samples targeted with only oil-based nanoparticles exhibited mean backscatter values that were nearly identical to untreated samples (<1 dB difference), confirming the oil particles’ low-scattering behavior. The results of this study indicate that substantial contrast enhancement with liquid perfluorocarbon nanoparticles can be realized even in cases of partial surface coverage (as might be encountered when targeting sparsely populated epitopes), or when targeting surfaces with locally irregular topography. Furthermore, it may be possible to assess the quantity of bound cellular epitopes through acoustic means. PMID:17434667

Effects of Formulation Variables on the Particle Size and Drug Encapsulation of Imatinib-Loaded Solid Lipid Nanoparticles.

PubMed

Gupta, Biki; Poudel, Bijay Kumar; Pathak, Shiva; Tak, Jin Wook; Lee, Hee Hyun; Jeong, Jee-Heon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2016-06-01

Imatinib (IMT), an anticancer agent, inhibits receptor tyrosine kinases and is characterized by poor aqueous solubility, extensive first-pass metabolism, and rapid clearance. The aims of the current study are to prepare imatinib-loaded solid lipid nanoparticles (IMT-SLN) and study the effects of associated formulation variables on particle size and drug encapsulation on IMT-SLN using an experimental design. IMT-SLN was optimized by use of a "combo" approach involving Plackett-Burman design (PBD) and Box-Behnken design (BBD). PBD screening resulted in the determination of organic-to-aqueous phase ratio (O/A), drug-to-lipid ratio (D/L), and amount of Tween® 20 (Tw20) as three significant variables for particle size (S z), drug loading (DL), and encapsulation efficiency (EE) of IMT-SLN, which were used for optimization by BBD, yielding an optimized criteria of O/A = 0.04, D/L = 0.03, and Tw20 = 2.50% w/v. The optimized IMT-SLN exhibited monodispersed particles with a size range of 69.0 ± 0.9 nm, ζ-potential of -24.2 ± 1.2 mV, and DL and EE of 2.9 ± 0.1 and 97.6 ± 0.1% w/w, respectively. Results of in vitro release study showed a sustained release pattern, presumably by diffusion and erosion, with a higher release rate at pH 5.0, compared to pH 7.4. In conclusion, use of the combo experimental design approach enabled clear understanding of the effects of various formulation variables on IMT-SLN and aided in the preparation of a system which exhibited desirable physicochemical and release characteristics.

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

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.

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.

Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

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

Ying, Bo; Campbell, Robert B., E-mail: robert.campbell@mcphs.edu

2014-04-04

Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carriermore » systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of PEG can sufficiently encapsulate siRNA, improve cellular uptake and the efficiency of gene silencing.« less

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

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.

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.

Acid-activatable oxidative stress-inducing polysaccharide nanoparticles for anticancer therapy.

PubMed

Yoo, Wooyoung; Yoo, Donghyuck; Hong, Eunmi; Jung, Eunkyeong; Go, Yebin; Singh, S V Berwin; Khang, Gilson; Lee, Dongwon

2018-01-10

Drug delivery systems have been extensively developed to enhance the therapeutic efficacy of drugs by altering their pharmacokinetics and biodistribution. However, the use of high quantities of drug delivery systems can cause toxicity due to their poor metabolism and elimination. In this study, we developed polysaccharide-based drug delivery systems which exert potent therapeutic effects and could display synergistic therapeutic effects with drug payloads, leading to dose reduction. Cinnamaldehyde, a major component of cinnamon is known to induce anticancer activity by generating ROS (reactive oxygen species). We developed cinnamaldehyde-conjugated maltodextrin (CMD) as a polymeric prodrug of cinnamaldehyde and a drug carrier. Cinnamaldehyde was conjugated to the hydroxyl groups of maltodextrin via acid-cleavable acetal linkages, allowing facile formulation of nanoparticles and drug encapsulation. CMD nanoparticles induced acid-triggered ROS generation to induce apoptotic cell death. Camptothecin (CPT) was used as a model drug to investigate the potential of CMD nanoparticles as a drug carrier and also evaluate the synergistic anticancer effects with CMD nanoparticles. CPT-loaded CMD nanoparticles exhibited significantly higher anticancer activity than empty CMD nanoparticles and CPT alone in the study of mouse xenograft models, demonstrating the synergistic therapeutic effects of CMD with CPT. Taken together, we believe that CMD nanoparticles hold tremendous potential as a polymeric prodrug of cinnamaldehyde and a drug carrier in anticancer therapy. Copyright © 2017 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.

Advanced imaging approaches for characterizing nanoparticle delivery and dispersion in skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Prow, Tarl W.; Yamada, Miko; Dang, Nhung; Evans, Conor L.

2017-02-01

The purpose of this research was to develop advanced imaging approaches to characterise the combination of elongated silica microparticles (EMP) and nanoparticles to control topical delivery of drugs and peptides. The microparticles penetrate through the epidermis and stop at the dermal-epidermal junction (DEJ). In this study we incorporated a fluorescent lipophilic dye, DiI, as a hydrophobic drug surrogate into the nanoparticle for visualization with microscopy. In another nanoparticle-based approach we utilized a chemically functionalized melanin nanoparticle for peptide delivery. These nanoparticles were imaged by coherent anti-Stoke Raman scattering (CARS) microscopy to characterize the delivery of these nanoparticles into freshly excised human skin. We compared four different coating approaches to combine EMP and nanoparticles. These data showed that a freeze-dried formulation with cross-linked alginate resulted in 100% of the detectable nanoparticle retained on the EMP. When this dry form of EMP-nanoparticle was applied to excised, living human abdominal skin, the EMP penetrated to the DEJ followed by controlled release of the nanoparticles. This formulation resulted in a sustained release profile, whereas a freeze-dried formulation without crosslinking showed an immediate burst-type release profile. These data show that advanced imaging techniques can give unique, label free data that shows promise for clinical investigations.

Synthesis of silica-PAMAM dendrimer nanoparticles as promising carriers in Neuro blastoma cells.

PubMed

Yesil-Celiktas, Ozlem; Pala, Cansu; Cetin-Uyanikgil, E Oyku; Sevimli-Gur, Canan

2017-02-15

Mesoporous silica carriers are emerging as therapeutic drug delivery systems. The objective of this study was to develop a formulation for synthesizing silica-PAMAM dendrimer hybrid nanoparticles with sol-gel technique. Subsequently, black carrot anthocyanins were encapsulated and investigated for their capability in terms of inhibiting the proliferative effects of neuroblastoma (Neuro 2A). In this context, particle size distributions were ascertained followed by thermal analysis (DSC), scanning electron microscopy and encapsulation efficiency. Subsequently, in vitro release kinetics was determined along with cytotoxicity of empty and anthocyanin doped hybrid nanoparticles. The lowest particle size was 134.8 nm with a zeta potential of +19.78 mV which enhanced electrostatic interaction with the cell membrane in the cytotoxicity analyses. As the anthocyanin content was totally released at the end of 6 days, the cytotoxicity was observed for 134 h, reaching an inhibition of 87.9%. On the other hand, Neuro 2A cells incubated with empty nanoparticles exhibited a high proliferation indicating that hybrid nanoparticles were not toxic to the cells and the inhibitory effect was associated with the anthocyanins. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Novel flavonoid-based biodegradable nanoparticles for effective oral delivery of etoposide by P-glycoprotein modulation: an in vitro, ex vivo and in vivo investigations.

PubMed

Fatma, Sharmeen; Talegaonkar, Sushama; Iqbal, Zeenat; Panda, Amulya Kumar; Negi, Lalit Mohan; Goswami, Dinesh Giri; Tariq, Mohammad

2016-01-01

A receptor level interaction of etoposide with P-glycoprotein (P-gp) and subsequent intestinal efflux has an adverse effect on its oral absorption. The present work is aimed to enhance the bioavailability of etoposide by co-administering it with quercetin (a P-gp inhibitor) in dual-loaded polymeric nanoparticle formulation. Poly-lactic-co-glycolic acid (PLGA) nanoparticles were optimized for various parameters like o/w phase volume ratio, poly-vinyl alcohol concentration, PLGA concentration and sonication time. The cytotoxicity studies (MTT assay) revealed a 9- and 11-fold decrease in the IC 50 values for etoposide-loaded nanoparticles (ENP) and etoposide + quercetin dual-loaded nanoparticles (EQNP) when compared to that of free etoposide, respectively, and the results were further supported by florescent-activated cell sorter studies. The confocal imaging of the intestinal sections treated with ENP and EQNP containing fluorescent probe (rhodamine) showed the superiority of the EQNP to permeate deeper. Furthermore, pharmacokinetic studies on rats revealed that EQNP exhibited a 2.4-fold increase in bioavailability of etoposide than ENP with no quercetin. The developed loaded nanoparticles have the high potential to enhance the bioavailability of the etoposide and sensitize the resistant cells.

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.

Combination of Oxaliplatin and Vit.E-TPGS in Lipid Nanosystem for Enhanced Therapeutic Efficacy in Colon Cancers.

PubMed

Wang, Yanlei; Zhang, Xiang; Zhang, Wenqiang; Dong, Hao; Zhang, Wenjie; Mao, Jiajia; Dai, Yong

2018-01-08

The main aim of present study was to prepare the oxaliplatin (OXL)-loaded D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS)-based lipid nanoparticles to enhance the anticancer effect in colon cancer cells. The nanoparticles were nanosized and spherical shaped and exhibited controlled release kinetics. Flow cytometer and confocal laser scanning microscopy (CLSM) showed a remarkable uptake of nanoparticles in cancer cells in a time-dependent manner. The presence of TPGS remarkably increased the anticancer effect of OXL in HT-29 colon cancer cells. The IC50 value of free OXL was 4.25 μg/ml whereas IC50 value of OXL-loaded TPGS-based lipid nanoparticles (OXL/TLNP) was 1.12 μg/ml. The 3-fold lower IC50 value of OXL/TLNP indicates the superior anticancer effect of nanoparticle-based OXL. Consistently, OXL/TLNP induced a remarkable apoptosis of cancer cells. Approximately, ~52% of cells were in early apoptosis phase and ~13% of cells were in late apoptosis phase indicating the potent anticancer effect of the formulations. The findings from this study provide novel insights into the use of TPGS and lipid nanoparticle together for the better antitumor effect in colon cancers. Future studies will involve the detailed in vitro and in vivo studies on clinically relevant animals.

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate.

PubMed

Yang, Xiaoyan; Trinh, Hoang M; Agrahari, Vibhuti; Sheng, Ye; Pal, Dhananjay; Mitra, Ashim K

2016-04-01

This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09 ± 6.21%, 55.74 ± 6.26%, and 62.54 ± 3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.

Microfluidics: a transformational tool for nanomedicine development and production.

PubMed

Garg, Shyam; Heuck, Gesine; Ip, Shell; Ramsay, Euan

2016-11-01

Microfluidic devices are mircoscale fluidic circuits used to manipulate liquids at the nanoliter scale. The ability to control the mixing of fluids and the continuous nature of the process make it apt for solvent/antisolvent precipitation of drug-delivery nanoparticles. This review describes the use of numerous microfluidic designs for the formulation and production of lipid nanoparticles, liposomes and polymer nanoparticles to encapsulate and deliver small molecule or genetic payloads. The advantages of microfluidics are illustrated through examples from literature comparing conventional processes such as beaker and T-tube mixing to microfluidic approaches. Particular emphasis is placed on examples of microfluidic nanoparticle formulations that have been tested in vitro and in vivo. Fine control of process parameters afforded by microfluidics, allows unprecedented optimization of nanoparticle quality and encapsulation efficiency. Automation improves the reproducibility and optimization of formulations. Furthermore, the continuous nature of the microfluidic process is inherently scalable, allowing optimization at low volumes, which is advantageous with scarce or costly materials, as well as scale-up through process parallelization. Given these advantages, microfluidics is poised to become the new paradigm for nanomedicine formulation and production.

Lactosylated Gramicidin-based lipid nanoparticles (Lac-GLN) for targeted delivery of anti-miR-155 to hepatocellular carcinoma

PubMed Central

Zhang, Mengzi; Zhou, Xiaoju; Wang, Bo; Yung, Bryant C.; Lee, Ly J.; Ghoshal, Kalpana; Lee, Robert J.

2013-01-01

Lactosylated gramicidin-containing lipid nanoparticles (Lac-GLN) were developed for delivery of anti-microRNA-155 (anti-miR-155) to hepatocellular carcinoma (HCC) cells. MiR-155 is an oncomiR frequently elevated in HCC. The Lac-GLN formulation contained N-lactobionyl-dioleoyl phosphatidylethanolamine (Lac-DOPE), a ligand for the asialoglycoprotein receptor (ASGR), and an antibiotic peptide gramicidin A. The nanoparticles exhibited a mean particle diameter of 73 nm, zeta potential of +3.5 mV, anti-miR encapsulation efficiency of 88%, and excellent colloidal stability at 4°C. Lac-GLN effectively delivered anti-miR-155 to HCC cells with a 16.1- and 4.1-fold up-regulation of miR-155 targets C/EBPβ and FOXP3 genes, respectively, and exhibited significant greater efficiency over Lipofectamine 2000. In mice, intravenous injection of Lac-GLN containing Cy3-anti-miR-155 led to preferential accumulation of the anti-miR-155 in hepatocytes. Intravenous administration of 1.5 mg/kg anti-miR-155 loaded Lac-GLN resulted in up-regulation of C/EBPβ and FOXP3 by 6.9- and 2.2- fold, respectively. These results suggest potential application of Lac-GLN as a liver-specific delivery vehicle for anti-miR therapy. PMID:23567045

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.

DNA-encapsulated magnesium phosphate nanoparticles elicit both humoral and cellular immune responses in mice

PubMed Central

Bhakta, Gajadhar; Nurcombe, Victor; Maitra, Amarnath; Shrivastava, Anju

2014-01-01

The efficacy of pEGFP (plasmid expressing enhanced green fluorescent protein)-encapsulated PEGylated (meaning polyethylene glycol coated) magnesium phosphate nanoparticles (referred to as MgPi-pEGFP nanoparticles) for the induction of immune responses was investigated in a mouse model. MgPi-pEGFP nanoparticles induced enhanced serum antibody and antigen-specific T-lymphocyte responses, as well as increased IFN-? and IL-12 levels compared to naked pEGFP when administered via intravenous, intraperitoneal or intramuscular routes. A significant macrophage response, both in size and activity, was also observed when mice were immunized with the nanoparticle formulation. The response was highly specific for the antigen, as the increase in interaction between macrophages and lymphocytes as well as lymphocyte proliferation took place only when they were re-stimulated with recombinant green fluorescence protein (rGFP). Thus the nanoparticle formulation elicited both humoral as well as cellular responses. Cytokine profiling revealed the induction of Th-1 type responses. The results suggest DNA-encapsulated magnesium phosphate (MgPi) nanoparticles may constitute a safer, more stable and cost-efficient DNA vaccine formulation. PMID:24936399

Evaluation of bioavailability, efficacy, and safety profile of doxorubicin-loaded solid lipid nanoparticles

NASA Astrophysics Data System (ADS)

Patro, Nagaraju M.; Devi, Kshama; Pai, Roopa S.; Suresh, Sarasija

2013-12-01

We investigated the bioavailability, efficacy, and toxicity of doxorubicin-loaded solid lipid nanoparticles (DOX-SLNs) prepared by a simple modified double-emulsification method. A 3-factor, 3-level Box-Behnken statistical design was adopted in the optimization of DOX-SLN formulation considering dependent factors particle size and entrapment efficiency. Optimized SLN formulation composed of lipid (2 %) consisting of soya lecithin and Precirol ATO 5 (1:3) with Pluronic F68 (0.3 %) resulted in 217.36 ± 3.31 nm particle size and 59.45 ± 1.75 % entrapment efficiency. DOX-SLN exhibited significant enhancement ( p < 0.05) in bioavailability as compared with free DOX in Sprague-Dawley (SD) rats. DOX-SLN exhibited higher peak plasma concentration (6.761 ± 0.08 vs. 2.412 ± 0.04 μg/ml), increased AUC (61.368 ± 3.54 vs. 5.812 ± 0.49 μg/ml h), decreased clearance (36 ± 0.01 vs. 619 ± 0.005 mL/h kg), and volume of distribution (733 ± 0.092 vs. 2,064 ± 0.061 mL/kg) when compared to free DOX. The collective results of cardiac and kidney enzyme assay, antioxidant enzyme levels, hematological parameters, effect on body weight and tumor volume, tumor necrosis factor-α level, histopathological examination, and survival analysis confirmed the improved efficacy and safety profile of DOX-SLN in 7,12-dimethyl benzanthracene-induced breast cancer in SD rats.

Minocycline encapsulated chitosan nanoparticles for central antinociceptive activity.

PubMed

Nagpal, Kalpana; Singh, S K; Mishra, D N

2015-01-01

The purpose of the study is to explore the central anti-nociceptive activity of brain targeted nanoparticles (NP) of minocycline hydrochloride (MH). The NP were formulated using the modified ionotropic gelation method (MHNP) and were coated with Tween 80 (T80) to target them to brain (cMHNP). The formulated nanoparticles have already been characterized for particle size, zeta potential, drug entrapment efficiency and in vitro drug release. The nanoparticles were then evaluated for pharmacodynamic activity using thermal methods. The pure drug and the formulation, MHNP were not able to show a statistically significant central analgesic activity. cMHNP on the other hand evidenced a significant central analgesic activity. Animal models evidenced that brain targeted nanoparticles may be utilized for effective delivery of central anti-nociceptive effect of MH. Further clinical studies are required to explore the activity for mankind. Copyright © 2014 Elsevier B.V. All rights reserved.

[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.

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.

Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach.

PubMed

Yerlikaya, Firat; Ozgen, Aysegul; Vural, Imran; Guven, Olgun; Karaagaoglu, Ergun; Khan, Mansoor A; Capan, Yilmaz

2013-10-01

The aims of this study were to develop and characterize paclitaxel nanoparticles, to identify and control critical sources of variability in the process, and to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design (QbD) approach. For this, a risk assessment study was performed with various formulation and process parameters to determine their impact on CQAs of nanoparticles, which were determined to be average particle size, zeta potential, and encapsulation efficiency. Potential risk factors were identified using an Ishikawa diagram and screened by Plackett-Burman design and finally nanoparticles were optimized using Box-Behnken design. The optimized formulation was further characterized by Fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy, atomic force microscopy, and gas chromatography. It was observed that paclitaxel transformed from crystalline state to amorphous state while totally encapsulating into the nanoparticles. The nanoparticles were spherical, smooth, and homogenous with no dichloromethane residue. In vitro cytotoxicity test showed that the developed nanoparticles are more efficient than free paclitaxel in terms of antitumor activity (more than 25%). In conclusion, this study demonstrated that understanding formulation and process parameters with the philosophy of QbD is useful for the optimization of complex drug delivery systems. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

In vitro and in vivo anti-tumor activities of a gemcitabine derivative carried by nanoparticles

PubMed Central

Sloat, Brian R.; Sandoval, Michael A.; Li, Dong; Chung, Woon-Gye; Lansakara-P., Dharmika S. P.; Proteau, Philip J.; Kiguchi, Kaoru; DiGiovanni, John; Cui, Zhengrong

2011-01-01

Gemcitabine (Gemzar®) is the first line treatment for pancreatic cancer and often used in combination therapy for non-small cell lung, ovarian, and metastatic breast cancers. Although extremely toxic to a variety of tumor cells in culture, the clinical outcome of gemcitabine treatment still needs improvement. In the present study, a new gemcitabine nanoparticle formulation was developed by incorporating a previously reported stearic acid amide derivative of gemcitabine into nanoparticles prepared from lecithin/glyceryl monostearate-in-water emulsions. The stearoyl gemcitabine nanoparticles were cytotoxic to tumor cells in culture, although it took a longer time for the gemcitabine in the nanoparticles to kill tumor cells than for free gemcitabine. In mice with pre-established model mouse or human tumors, the stearoyl gemcitabine nanoparticles were significantly more effective than free gemcitabine in controlling the tumor growth. PEGylation of the gemcitabine nanoparticles with polyethylene glycol (2000) prolonged the circulation of the nanoparticles in blood and increased the accumulation of the nanoparticles in tumor tissues (> 6-fold), but the PEGylated and un-PEGylated gemcitabine nanoparticles showed similar anti-tumor activity in mice. Nevertheless, the nanoparticle formulation was critical for the stearoyl gemcitabine to show a strong anti-tumor activity. It is concluded that for the gemcitabine derivate-containing nanoparticles, cytotoxicity data in culture may not be used to predict their in vivo anti-tumor activity, and this novel gemcitabine nanoparticle formulation has the potential to improve the clinical outcome of gemcitabine treatment. PMID:21371545

Preparation and characterization of dutasteride-loaded nanostructured lipid carriers coated with stearic acid-chitosan oligomer for topical delivery.

PubMed

Noor, Norhayati Mohamed; Sheikh, Khalid; Somavarapu, Satyanarayana; Taylor, Kevin M G

2017-08-01

Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using 1 H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimized using a 2 3 full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6±7.0nm to 220.1±11.9nm, and modified surface charge, with zeta potentials being -18.3±0.9mV and +25.8±1.1mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhibited particle size stability over 60days, when stored at 4-8°C. However, NLCs coated with CSO (without conjugation) showed aggregation when stored at 4-8°C after 30days. The measured particle size for all formulations stored at 25°C suggested aggregation, which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All nanoparticle formulations exhibited rapid release in an in vitro release study, with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion cell, no dutasteride permeated through pig ear skin after 48h, such that it was not detected in the receptor chamber for all samples. The amount of dutasteride in the skin was significantly different (p<0.05) for DST-NLCs (6.09±1.09μg/cm 2 ) without coating and those coated with 5% CSO-SA (2.82±0.40μg/cm 2 ), 10% CSO-SA (2.70±0.35μg/cm 2 ) and CSO (2.11±0.64μg/cm 2) . There was a significant difference (p<0.05) in the cytotoxicity (IC 50 ) between dutasteride alone and in the nanoparticles. DST-NLCs coated and uncoated with CSO-SA increased the maximum non-toxic concentration by 20-fold compared to dutasteride alone. These studies indicate that a stearic acid-chitosan conjugate was successfully prepared, and modified the surface charge of DST-NLCs from negative to positive. These stable, less cytotoxic, positively-charged dutasteride-loaded nanostructured lipid carriers, with stearic acid-chitosan oligomer conjugate, are appropriate for topical delivery and have potential for promotion of hair growth. Copyright © 2017. Published by Elsevier B.V.

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

PubMed Central

Yingchoncharoen, Phatsapong; Kalinowski, Danuta S.

2016-01-01

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current standard treatments for a variety of cancers is suboptimal. First, most cancer treatments lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts. Second, many anticancer agents are highly toxic, and thus, limit their use in treatment. Third, a number of cytotoxic chemotherapeutics are highly hydrophobic, which limits their utility in cancer therapy. Finally, many chemotherapeutic agents exhibit short half-lives that curtail their efficacy. As a result of these deficiencies, many current treatments lead to side effects, noncompliance, and patient inconvenience due to difficulties in administration. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems known commonly as nanoparticles. Among these delivery systems, lipid-based nanoparticles, particularly liposomes, have shown to be quite effective at exhibiting the ability to: 1) improve the selectivity of cancer chemotherapeutic agents; 2) lower the cytotoxicity of anticancer drugs to normal tissues, and thus, reduce their toxic side effects; 3) increase the solubility of hydrophobic drugs; and 4) offer a prolonged and controlled release of agents. This review will discuss the current state of lipid-based nanoparticle research, including the development of liposomes for cancer therapy, different strategies for tumor targeting, liposomal formulation of various anticancer drugs that are commercially available, recent progress in liposome technology for the treatment of cancer, and the next generation of lipid-based nanoparticles. PMID:27363439

3D reconstruction of the magnetic vector potential using model based iterative reconstruction

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

Prabhat, K. C.; Aditya Mohan, K.; Phatak, Charudatta

Lorentz transmission electron microscopy (TEM) observations of magnetic nanoparticles contain information on the magnetic and electrostatic potentials. Vector field electron tomography (VFET) can be used to reconstruct electromagnetic potentials of the nanoparticles from their corresponding LTEM images. The VFET approach is based on the conventional filtered back projection approach to tomographic reconstructions and the availability of an incomplete set of measurements due to experimental limitations means that the reconstructed vector fields exhibit significant artifacts. In this paper, we outline a model-based iterative reconstruction (MBIR) algorithm to reconstruct the magnetic vector potential of magnetic nanoparticles. We combine a forward model formore » image formation in TEM experiments with a prior model to formulate the tomographic problem as a maximum a-posteriori probability estimation problem (MAP). The MAP cost function is minimized iteratively to determine the vector potential. Here, a comparative reconstruction study of simulated as well as experimental data sets show that the MBIR approach yields quantifiably better reconstructions than the VFET approach.« less

3D reconstruction of the magnetic vector potential using model based iterative reconstruction.

PubMed

Prabhat, K C; Aditya Mohan, K; Phatak, Charudatta; Bouman, Charles; De Graef, Marc

2017-11-01

Lorentz transmission electron microscopy (TEM) observations of magnetic nanoparticles contain information on the magnetic and electrostatic potentials. Vector field electron tomography (VFET) can be used to reconstruct electromagnetic potentials of the nanoparticles from their corresponding LTEM images. The VFET approach is based on the conventional filtered back projection approach to tomographic reconstructions and the availability of an incomplete set of measurements due to experimental limitations means that the reconstructed vector fields exhibit significant artifacts. In this paper, we outline a model-based iterative reconstruction (MBIR) algorithm to reconstruct the magnetic vector potential of magnetic nanoparticles. We combine a forward model for image formation in TEM experiments with a prior model to formulate the tomographic problem as a maximum a-posteriori probability estimation problem (MAP). The MAP cost function is minimized iteratively to determine the vector potential. A comparative reconstruction study of simulated as well as experimental data sets show that the MBIR approach yields quantifiably better reconstructions than the VFET approach. Copyright © 2017 Elsevier B.V. All rights reserved.

3D reconstruction of the magnetic vector potential using model based iterative reconstruction

DOE PAGES

Prabhat, K. C.; Aditya Mohan, K.; Phatak, Charudatta; ...

2017-07-03

Lorentz transmission electron microscopy (TEM) observations of magnetic nanoparticles contain information on the magnetic and electrostatic potentials. Vector field electron tomography (VFET) can be used to reconstruct electromagnetic potentials of the nanoparticles from their corresponding LTEM images. The VFET approach is based on the conventional filtered back projection approach to tomographic reconstructions and the availability of an incomplete set of measurements due to experimental limitations means that the reconstructed vector fields exhibit significant artifacts. In this paper, we outline a model-based iterative reconstruction (MBIR) algorithm to reconstruct the magnetic vector potential of magnetic nanoparticles. We combine a forward model formore » image formation in TEM experiments with a prior model to formulate the tomographic problem as a maximum a-posteriori probability estimation problem (MAP). The MAP cost function is minimized iteratively to determine the vector potential. Here, a comparative reconstruction study of simulated as well as experimental data sets show that the MBIR approach yields quantifiably better reconstructions than the VFET approach.« less

Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy.

PubMed

Thulasidasan, Arun Kumar T; Retnakumari, Archana P; Shankar, Mohan; Vijayakurup, Vinod; Anwar, Shabna; Thankachan, Sanu; Pillai, Kavya S; Pillai, Jisha J; Nandan, C Devika; Alex, Vijai V; Chirayil, Teena Jacob; Sundaram, Sankar; Kumar, Gopalakrishnapillai Sankaramangalam Vinod; Anto, Ruby John

2017-12-08

Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time. Earlier reports of improvement in bioavailability and retention of drugs upon nanoencapsulation have motivated us in developing various nanoformulations of curcumin, which were found to exhibit significant enhancement in bioavailability and retention time as assessed by our previous in vitro studies. Among the various formulations tested, curcumin-entrapped in PLGA-PEG nanoparticles conjugated to folic acid (PPF-curcumin) displayed maximum cell death. In the present study, we have demonstrated the efficacy of this formulation in augmenting the bioavailability and retention time of curcumin, in vivo , in Swiss albino mice. Further, the acute and chronic toxicity studies proved that the formulation is pharmacologically safe. We have also evaluated its potential in chemosensitizing cervical cancer cells to paclitaxel and have verified the results using cervical cancer xenograft model in NOD-SCID mice. Folic acid conjugation significantly enhanced the efficacy of curcumin in down-regulating various survival signals induced by paclitaxel in cervical cancer cells and have considerably improved its potential in inhibiting the tumor growth of cervical cancer xenografts. The non-toxic nature coupled with improved chemosensitization potential makes PPF-curcumin a promising candidate formulation for clinical trials.

Folic acid conjugation improves the bioavailability and chemosensitizing efficacy of curcumin-encapsulated PLGA-PEG nanoparticles towards paclitaxel chemotherapy

PubMed Central

Shankar, Mohan; Vijayakurup, Vinod; Anwar, Shabna; Thankachan, Sanu; Pillai, Kavya S.; Pillai, Jisha J.; Nandan, C. Devika; Alex, Vijai V.; Chirayil, Teena Jacob; Sundaram, Sankar; Kumar, Gopalakrishnapillai Sankaramangalam Vinod; Anto, Ruby John

2017-01-01

Nanoencapsulation has emerged as a novel strategy to enhance the pharmacokinetic and therapeutic potential of conventional drugs. Recent studies from our lab have established the efficacy of curcumin in sensitizing cervical cancer cells and breast cancer cells towards paclitaxel and 5-FU chemotherapy respectively. Factors that hinder the clinical use of curcumin as a sensitizer or therapeutic agent include its poor bioavailability and retention time. Earlier reports of improvement in bioavailability and retention of drugs upon nanoencapsulation have motivated us in developing various nanoformulations of curcumin, which were found to exhibit significant enhancement in bioavailability and retention time as assessed by our previous in vitro studies. Among the various formulations tested, curcumin-entrapped in PLGA-PEG nanoparticles conjugated to folic acid (PPF-curcumin) displayed maximum cell death. In the present study, we have demonstrated the efficacy of this formulation in augmenting the bioavailability and retention time of curcumin, in vivo, in Swiss albino mice. Further, the acute and chronic toxicity studies proved that the formulation is pharmacologically safe. We have also evaluated its potential in chemosensitizing cervical cancer cells to paclitaxel and have verified the results using cervical cancer xenograft model in NOD-SCID mice. Folic acid conjugation significantly enhanced the efficacy of curcumin in down-regulating various survival signals induced by paclitaxel in cervical cancer cells and have considerably improved its potential in inhibiting the tumor growth of cervical cancer xenografts. The non-toxic nature coupled with improved chemosensitization potential makes PPF-curcumin a promising candidate formulation for clinical trials. PMID:29296172

Nanostructured Lipid Carrier for Topical Application of N-Acetyl Glucosamine.

PubMed

Aliasgharlou, Lavin; Ghanbarzadeh, Saeed; Azimi, Hamideh; Zarrintan, Mohammad Hossein; Hamishehkar, Hamed

2016-12-01

Purpose: Hyperpigmentation occurs when melanin is overproduced in certain spots on the skin and is one of the most challenging skin conditions to treat. Although it is usually harmless, for cosmetic reasons, it is dreadfully bothersome to those who undergo it. It was reported that N-acetyl-glucosamine (NAGA) prevents melanin synthesis and alters the expression of numerous genes related to pigmentation. In spite of these advantages, NAGA cannot be employed in topical formulations due to its extremely polar characteristics. Nanoparticles, especially lipid-based ones, have been introduced as an efficient carrier for dermal drug delivery. Methods: The aim of the present study was to load adequate hydrophilic NAGA to the lipophilic nanostructured lipid carriers (NLCs) for potential dermal application. NAGA-loaded NLCs were formulated, using hot homogenization technique, and the characteristics of the optimized formulation were analyzed by laser light scattering, X-ray diffraction, and scanning electron microscopy methods. Loading capacity percentage and in vitro release study were carried out by applying a validated HPLC method. The optimum formulation was utilized for the in vivo skin lightening evaluations in healthy volunteers. Results: NAGA-loaded NLCs demonstrated promising results (the size of 190 nm, narrow size distribution, loading capacity of 9%, and appropriate NAGA release profile) suitable for dermal delivery. XRD results exhibited a dramatic reduction in the crystalline structure of encapsulated NAGA. Dermoscopy images indicated a considerable decline in melanin distribution pattern in the majority of the cases treated with NAGA-loaded NLCs. Conclusion: Thus, this study has opened new horizons for the potential use of lipid based nanoparticles in the managing of hyperpigmentation.

Design and evaluation of a novel nanoparticulate-based formulation encapsulating a HIP complex of lysozyme.

PubMed

Gaudana, Ripal; Gokulgandhi, Mitan; Khurana, Varun; Kwatra, Deep; Mitra, Ashim K

2013-01-01

Formulation development of protein therapeutics using polymeric nanoparticles has found very little success in recent years. Major formulation challenges include rapid denaturation, susceptibility to lose bioactivity in presence of organic solvents and poor encapsulation in polymeric matrix. In the present study, we have prepared hydrophobic ion pairing (HIP) complex of lysozyme, a model protein, using dextran sulfate (DS) as a complexing polymer. We have optimized the process of formation and dissociation of HIP complex between lysozyme and DS. The effect of HIP complexation on enzymatic activity of lysozyme was also studied. Nanoparticles were prepared and characterized using spontaneous emulsion solvent diffusion method. Furthermore, we have also investigated release of lysozyme from nanoparticles along with its enzymatic activity. Results of this study indicate that nanoparticles can sustain the release of lysozyme without compromising its enzymatic activity. HIP complexation using a polymer may also be employed to formulate sustained release dosage forms of other macromolecules with enhanced encapsulation efficiency.

Surface modification of paclitaxel-loaded tri-block copolymer PLGA- b-PEG- b-PLGA nanoparticles with protamine for liver cancer therapy

NASA Astrophysics Data System (ADS)

Gao, Nansha; Chen, Zhihong; Xiao, Xiaojun; Ruan, Changshun; Mei, Lin; Liu, Zhigang; Zeng, Xiaowei

2015-08-01

In order to enhance the therapeutic effect of chemotherapy on liver cancer, a biodegradable formulation of protamine-modified paclitaxel-loaded poly(lactide- co-glycolide)- b-poly(ethylene glycol)- b-poly(lactide- co-glycolide) (PLGA- b-PEG- b-PLGA) nanoparticles (PTX-loaded/protamine NPs) was prepared. Tri-block copolymer PLGA- b-PEG- b-PLGA was synthesized by ring-opening polymerization and characterized by 1H NMR spectroscopy and gel permeation chromatography. PTX-loaded and PTX-loaded/protamine NPs were characterized in terms of size, size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin 6-loaded/protamine NPs were internalized by hepatocellular carcinoma cell line HepG2. The cellular uptake efficiency of NPs was obviously elevated after protamine modification. With commercial formulation Taxol® as the reference, HepG2 cells were also used to study the cytotoxicity of the NPs. PTX-loaded/protamine NPs exhibited significantly higher cytotoxicity than PTX-loaded NPs and Taxol® did. All the results suggested that surface modification of PTX-loaded PLGA- b-PEG- b-PLGA NPs with protamine boosted the therapeutic efficacy on liver cancer.

Development of Alendronate-conjugated Poly (lactic-co-glycolic acid)-Dextran Nanoparticles for Active Targeting of Cisplatin in Osteosarcoma

PubMed Central

Liu, Ping; Sun, Liang; Zhou, Dong-sheng; Zhang, Peng; Wang, Yong-hui; Li, Dong; Li, Qing-hu; Feng, Rong-jie

2015-01-01

In this study, we developed a novel poly (lactic-co-glycolic acid)-dextran (PLD)-based nanodelivery system to enhance the anticancer potential of cisplatin (CDDP) in osteosarcoma cells. A nanosized CDDP-loaded PLGA-DX nanoparticle (PLD/CDDP) controlled the release rate of CDDP up to 48 h. In vitro cytotoxicity assay showed a superior anticancer effect for PLD/CDDP and with an appreciable cellular uptake via endocytosis-mediated pathways. PLD/CDDP exhibited significant apoptosis of MG63 cancer cells compared to that of free CDDP. Approximately ~25% of cells were in early apoptosis phase after PLD/CDDP treatment comparing to ~15% for free CDDP after 48h incubation. Similarly, PLD/CDDP exhibited ~30% of late apoptosis cells comparing to only ~8% for free drug treatment. PLD/CDDP exhibited significantly higher G2/M phase arrest in MG63 cells than compared to free CDDP with a nearly 2-fold higher arrest in case of PLD/CDDP treated group (~60%). Importantly, PLD/CDDP exhibited a most significant anti-tumor activity with maximum tumor growth inhibition. The superior inhibitory effect was further confirmed by a marked reduction in the number of CD31 stained tumor blood vessels and decrease in the Ki67 staining intensity for PLD/CDDP treated animal group. Overall, CDDP formulations could provide a promising and most effective platform in the treatment of osteosarcoma. PMID:26619950

Lipid nanoparticles based on butyl-methoxydibenzoylmethane: in vitro UVA blocking effect

NASA Astrophysics Data System (ADS)

Niculae, G.; Lacatusu, I.; Badea, N.; Meghea, A.

2012-08-01

The aim of the present study was to obtain efficient lipid nanoparticles loaded with butyl-methoxydibenzoylmethane (BMDBM) in order to develop cosmetic formulations with enhanced UVA blocking effect. For this purpose, two adequate liquid lipids (medium chain triglycerides and squalene) have been used in combination with two solid lipids (cetyl palmitate and glyceryl stearate) in order to create appropriate nanostructured carriers with a disordered lipid network able to accommodate up to 1.5% BMDBM. The lipid nanoparticles (LNs) were characterized in terms of particle size, zeta potential, entrapment efficiency, loading capacity and in vitro UVA blocking effect. The efficiency of lipid nanoparticles in developing some cosmetic formulations has been evaluated by determining the in vitro erythemal UVA protection factor. In order to quantify the photoprotective effect, some selected cream formulations based on BMDBM-LNs and a conventional emulsion were exposed to photochemical UV irradiation at a low energy to simulate the solar energy during the midday. The results obtained demonstrated the high ability of cream formulations based on BMDBM-LNs to absorb more than 96% of UVA radiation. Moreover, the developed cosmetic formulations manifest an enhanced UVA blocking effect, the erythemal UVA protection factor being four times higher than those specific to conventional emulsions.

Dual Agent Loaded PLGA Nanoparticles Enhanced Antitumor Activity in a Multidrug-Resistant Breast Tumor Eenograft Model

PubMed Central

Chen, Yan; Zheng, Xue-Lian; Fang, Dai-Long; Yang, Yang; Zhang, Jin-Kun; Li, Hui-Li; Xu, Bei; Lei, Yi; Ren, Ke; Song, Xiang-Rong

2014-01-01

Multidrug-resistant breast cancers have limited and ineffective clinical treatment options. This study aimed to develop PLGA nanoparticles containing a synergistic combination of vincristine and verapamil to achieve less toxicity and enhanced efficacy on multidrug-resistant breast cancers. The 1:250 molar ratio of VCR/VRP showed strong synergism with the reversal index of approximately 130 in the multidrug-resistant MCF-7/ADR cells compared to drug-sensitive MCF-7 cells. The lyophilized nanoparticles could get dispersed quickly with the similar size distribution, zeta potential and encapsulation efficiency to the pre-lyophilized nanoparticles suspension, and maintain the synergistic in vitro release ratio of drugs. The co-encapsulated nanoparticle formulation had lower toxicity than free vincristine/verapamil combinations according to the acute-toxicity test. Furthermore, the most effective tumor growth inhibition in the MCF-7/ADR human breast tumor xenograft was observed in the co-delivery nanoparticle formulation group in comparison with saline control, free vincristine, free vincristine/verapamil combinations and single-drug nanoparticle combinations. All the data demonstrated that PLGANPs simultaneously loaded with chemotherapeutic drug and chemosensitizer might be one of the most potential formulations in the treatment of multidrug-resistant breast cancer in clinic. PMID:24552875

Self-Assembly of Gold Nanoparticles Shows Microenvironment-Mediated Dynamic Switching and Enhanced Brain Tumor Targeting

PubMed Central

Feng, Qishuai; Shen, Yajing; Fu, Yingjie; Muroski, Megan E.; Zhang, Peng; Wang, Qiaoyue; Xu, Chang; Lesniak, Maciej S.; Li, Gang; Cheng, Yu

2017-01-01

Inorganic nanoparticles with unique physical properties have been explored as nanomedicines for brain tumor treatment. However, the clinical applications of the inorganic formulations are often hindered by the biological barriers and failure to be bioeliminated. The size of the nanoparticle is an essential design parameter which plays a significant role to affect the tumor targeting and biodistribution. Here, we report a feasible approach for the assembly of gold nanoparticles into ~80 nm nanospheres as a drug delivery platform for enhanced retention in brain tumors with the ability to be dynamically switched into the single formulation for excretion. These nanoassemblies can target epidermal growth factor receptors on cancer cells and are responsive to tumor microenvironmental characteristics, including high vascular permeability and acidic and redox conditions. Anticancer drug release was controlled by a pH-responsive mechanism. Intracellular L-glutathione (GSH) triggered the complete breakdown of nanoassemblies to single gold nanoparticles. Furthermore, in vivo studies have shown that nanospheres display enhanced tumor-targeting efficiency and therapeutic effects relative to single-nanoparticle formulations. Hence, gold nanoassemblies present an effective targeting strategy for brain tumor treatment. PMID:28638474

Self-Assembly of Gold Nanoparticles Shows Microenvironment-Mediated Dynamic Switching and Enhanced Brain Tumor Targeting.

PubMed

Feng, Qishuai; Shen, Yajing; Fu, Yingjie; Muroski, Megan E; Zhang, Peng; Wang, Qiaoyue; Xu, Chang; Lesniak, Maciej S; Li, Gang; Cheng, Yu

2017-01-01

Inorganic nanoparticles with unique physical properties have been explored as nanomedicines for brain tumor treatment. However, the clinical applications of the inorganic formulations are often hindered by the biological barriers and failure to be bioeliminated. The size of the nanoparticle is an essential design parameter which plays a significant role to affect the tumor targeting and biodistribution. Here, we report a feasible approach for the assembly of gold nanoparticles into ~80 nm nanospheres as a drug delivery platform for enhanced retention in brain tumors with the ability to be dynamically switched into the single formulation for excretion. These nanoassemblies can target epidermal growth factor receptors on cancer cells and are responsive to tumor microenvironmental characteristics, including high vascular permeability and acidic and redox conditions. Anticancer drug release was controlled by a pH-responsive mechanism. Intracellular L-glutathione (GSH) triggered the complete breakdown of nanoassemblies to single gold nanoparticles. Furthermore, in vivo studies have shown that nanospheres display enhanced tumor-targeting efficiency and therapeutic effects relative to single-nanoparticle formulations. Hence, gold nanoassemblies present an effective targeting strategy for brain tumor treatment.

Pharmacokinetic Studies of Gel System Containing Ibuprofen Solid Nanoparticles.

PubMed

Nagai, Noriaki; Tanino, Tadatoshi; Ito, Yoshimasa

2016-12-01

In the therapy of rheumatoid arthritis, ibuprofen (IBU) is widely used; however, it has been limited the clinical use by its systemic side effect, such as gastrointestinal lesions. Therefore, we prepared topical gel ointment used IBU solid nanoparticles (IBU nano -gel formulation). In addition, we demonstrated their anti-inflammatory effect by using arthritis model rat (adjuvant-induced arthritis rat, AA rat). The gel formulations were prepared using additives (Carbopol 934, 2-hydroxypropyl-β-cyclodextrin and methylcellulose) and bead mill-method. The IBU particle size in the IBU nano -gel formulation was 208 nm. The increase in inflammation of the hind feet of AA rats was attenuated by the treatment with the IBU nano -gel formulation, and preventive effect was higher than that of a gel formulation containing IBUmicroparticles (IBU micro -gel formulation, mean particle size 85.4 μm); the accumulation and permeability through the skin of IBU from the IBU nano -gel formulation were significantly larger in comparison with the IBU micro -gel formulation. Further, no gastrointestinal lesions were observed in AA rats following the repetitive administration of the 5% IBU nano -gel formulation (0.30 g) for 42 days (once a day). These results suggest that the dermal application of IBU-nanoparticles provide effective and efficient therapy that spares patients from unwanted side effects.

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

A novel in situ hydrophobic ion paring (HIP) formulation strategy for clinical product selection of a nanoparticle drug delivery system.

PubMed

Song, Young Ho; Shin, Eyoung; Wang, Hong; Nolan, Jim; Low, Susan; Parsons, Donald; Zale, Stephen; Ashton, Susan; Ashford, Marianne; Ali, Mir; Thrasher, Daniel; Boylan, Nicholas; Troiano, Greg

2016-05-10

The present studies were aimed at formulating AZD2811-loaded polylactic acid-polyethylene glycol (PLA-PEG) nanoparticles with adjustable release rates without altering the chemical structures of the polymer or active pharmaceutical ingredient (API). This was accomplished through the use of a hydrophobic ion pairing approach. A series of AZD2811-containing nanoparticles with a variety of hydrophobic counterions including oleic acid, 1-hydroxy-2-naphthoic acid, cholic acid, deoxycholic acid, dioctylsulfosuccinic acid, and pamoic acid is described. The hydrophobicity of AZD2811 was increased through formation of ion pairs with these hydrophobic counterions, producing nanoparticles with exceptionally high drug loading-up to five fold higher encapsulation efficiency and drug loading compared to nanoparticles made without hydrophobic ion pairs. Furthermore, the rate at which the drug was released from the nanoparticles could be controlled by employing counterions with various hydrophobicities and structures, resulting in release half-lives ranging from about 2 to 120h using the same polymer, nanoparticle size, and nanoemulsion process. Process recipe variables affecting drug load and release rate were identified, including pH and molarity of quench buffer. Ion pair formation between AZD2811 and pamoic acid as a model counterion was investigated using solubility enhancement as well as nuclear magnetic resonance spectroscopy to demonstrate solution-state interactions. Further evidence for an ion pairing mechanism of controlled release was provided through the measurement of API and counterion release profiles using high-performance liquid chromatography, which had stoichiometric relationships. Finally, Raman spectra of an AZD2811-pamoate salt compared well with those of the formulated nanoparticles, while single components (AZD2811, pamoic acid) alone did not. A library of AZD2811 batches was created for analytical and preclinical characterization. Dramatically improved preclinical efficacy and tolerability data were generated for the pamoic acid lead formulation, which has been selected for evaluation in a Phase 1 clinical trial (ClinicalTrials.gov Identifier NCT 02579226). This work clearly demonstrates the importance of assessing a wide range of drug release rates during formulation screening as a critical step for new drug product development, and how utilizing hydrophobic ion pairing enabled this promising nanoparticle formulation to proceed into clinical development. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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.

Tunable Semiconducting Polymer Nanoparticles with INDT-Based Conjugated Polymers for Photoacoustic Molecular Imaging.

PubMed

Stahl, Thomas; Bofinger, Robin; Lam, Ivan; Fallon, Kealan J; Johnson, Peter; Ogunlade, Olumide; Vassileva, Vessela; Pedley, R Barbara; Beard, Paul C; Hailes, Helen C; Bronstein, Hugo; Tabor, Alethea B

2017-06-21

Photoacoustic imaging combines both excellent spatial resolution with high contrast and specificity, without the need for patients to be exposed to ionizing radiation. This makes it ideal for the study of physiological changes occurring during tumorigenesis and cardiovascular disease. In order to fully exploit the potential of this technique, new exogenous contrast agents with strong absorbance in the near-infrared range, good stability and biocompatibility, are required. In this paper, we report the formulation and characterization of a novel series of endogenous contrast agents for photoacoustic imaging in vivo. These contrast agents are based on a recently reported series of indigoid π-conjugated organic semiconductors, coformulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, to give semiconducting polymer nanoparticles of about 150 nm diameter. These nanoparticles exhibited excellent absorption in the near-infrared region, with good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients of up to three times higher than those previously reported. The absorption maximum is conveniently located in the spectral region of low absorption of chromophores within human tissue. Using the most promising semiconducting polymer nanoparticle, we have demonstrated wavelength-dependent differential contrast between vasculature and the nanoparticles, which can be used to unambiguously discriminate the presence of the contrast agent in vivo.

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.

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.

Nanocarriers for cancer-targeted drug delivery.

PubMed

Kumari, Preeti; Ghosh, Balaram; Biswas, Swati

2016-01-01

Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.

Uncapped silver nanoparticles synthesized by DC arc thermal plasma technique for conductor paste formulation

NASA Astrophysics Data System (ADS)

Shinde, Manish; Pawar, Amol; Karmakar, Soumen; Seth, Tanay; Raut, Varsha; Rane, Sunit; Bhoraskar, Sudha; Amalnerkar, Dinesh

2009-11-01

Uncapped silver nanoparticles were synthesized by DC arc thermal plasma technique. The synthesized nanoparticles were structurally cubic and showed wide particle size variation (between 20-150 nm). Thick film paste formulated from such uncapped silver nanoparticles was screen-printed on alumina substrates and the resultant `green' films were fired at different firing temperatures. The films fired at 600 °C revealed better microstructure properties and also yielded the lowest value of sheet resistance in comparison to those corresponding to conventional peak firing temperature of 850 °C. Our findings directly support the role of silver nanoparticles in substantially depressing the operative peak firing temperature involved in traditional conductor thick films technology.

Irradiation effect of low-energy ion on polyurethane nanocoating containing metal oxide nanoparticles

NASA Astrophysics Data System (ADS)

Verma, Jaya; Nigam, Subhasha; Sinha, Surbhi; Sikarwar, B. S.; Bhattacharya, Arpita

2017-12-01

Irradiation effect of low-energy ion beam has been investigated on nanocoating developed with silica, titania and silica-titania core-shell nanoparticles embedded in an organic binder for nanopaint application. In this work, we have taken polyurethane as a model organic binder. Silica nanoparticles have been prepared through sol-gel synthesis with a particle size of 85 nm. Titania and core-shell nanoparticles have been prepared through both sol-gel and peptization process. Particle sizes obtained were 107 nm for titania and 240 nm for core-shell nanoparticles prepared through sol-gel process and 75 nm for TiO2 and 144 nm for core-shell nanoparticles prepared through peptization process. The coating formulations were developed with the above nanoparticles individually and nanoparticle concentration was varied from 1 to 6 wt% and the best performance in terms of hydrophobicity was obtained with 4 wt % of the nanoparticles in polyurethane coating formulation. All the coating formulations prepared were applied on a glass substrate and dried at 100°C. The dry film thickness obtained was around 100 µm in each case. These films dried on glass substrate were irradiated by nitrogen and argon ion beam with energy of 26 keV at fluences of 1014 to 1016 ions/cm2. The anti-algal property of the irradiated samples was improved and hydrophobicity was reduced.

Delivery of platinum(IV) drug to subcutaneous tumor and lung metastasis using bradykinin-potentiating peptide-decorated chitosan nanoparticles.

PubMed

Wang, Xin; Yang, Chenchen; Zhang, Yajun; Zhen, Xu; Wu, Wei; Jiang, Xiqun

2014-08-01

Selectively activating tumor vessels to increase drug delivery and reduce interstitial fluid pressure of tumors is actively pursued. Here we developed a vasoactive peptide-decorated chitosan nanoparticles for enhancing drug accumulation and penetration in subcutaneous tumor and lung metastasis. The vasoactive peptide used here is bradykinin-potentiating peptide (BPP) containing 9 amino acid residues and the drug is bioreductively sensitive platinum(IV) compound which becomes cisplatin in intracellular reductive environments. Both peptide and drug are covalently linked with chitosan nanoparticles with a diameter of 120 nm. We demonstrate that BPP-decorated chitosan nanoparticles increase the tumorous vascular permeability and reduce the interstitial fluid pressure of tumor simultaneously, both of which improve the penetration of nanoparticles in tumor tissues. The in vivo biodistribution and tumor inhibition examinations demonstrate that the BPP-decorated nanoparticle formulation has more superior efficacy in enhancing drug accumulation in tumor, restraining tumor growth and prolonging the lifetime of tumor-bearing mice than free drug and non-decorated nanoparticle formulation. Meanwhile, the drug accumulation in the lung with metastasis reaches 17% and 20% injected dose per gram of lung for the chitosan nanoparticles without and with BPP decoration, respectively, which is 10-fold larger than that of free cisplatin. The examination of lung metastasis inhibition further indicates that BPP-decorated chitosan nanoparticle formulations can more effectively inhibit lung metastasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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

Quality by design case study 1: Design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion - Solvent evaporation method.

PubMed

Amasya, Gulin; Badilli, Ulya; Aksu, Buket; Tarimci, Nilufer

2016-03-10

With Quality by Design (QbD), a systematic approach involving design and development of all production processes to achieve the final product with a predetermined quality, you work within a design space that determines the critical formulation and process parameters. Verification of the quality of the final product is no longer necessary. In the current study, the QbD approach was used in the preparation of lipid nanoparticle formulations to improve skin penetration of 5-Fluorouracil, a widely-used compound for treating non-melanoma skin cancer. 5-Fluorouracil-loaded lipid nanoparticles were prepared by the W/O/W double emulsion - solvent evaporation method. Artificial neural network software was used to evaluate the data obtained from the lipid nanoparticle formulations, to establish the design space, and to optimize the formulations. Two different artificial neural network models were developed. The limit values of the design space of the inputs and outputs obtained by both models were found to be within the knowledge space. The optimal formulations recommended by the models were prepared and the critical quality attributes belonging to those formulations were assigned. The experimental results remained within the design space limit values. Consequently, optimal formulations with the critical quality attributes determined to achieve the Quality Target Product Profile were successfully obtained within the design space by following the QbD steps. Copyright © 2016 Elsevier B.V. All rights reserved.

Fabrication of surfactant-free quercetin-loaded PLGA nanoparticles: evaluation of hepatoprotective efficacy by nuclear scintigraphy

NASA Astrophysics Data System (ADS)

Ganguly, Soumya; Gaonkar, Raghuvir H.; Sinha, Samarendu; Gupta, Amit; Chattopadhyay, Dipankar; Chattopadhyay, Sankha; Sachdeva, Satbir S.; Ganguly, Shantanu; Debnath, Mita C.

2016-07-01

The purpose of this study was to develop surfactant-free quercetin-loaded PLGA nanoparticles (Qr-NPs) and investigate the hepatoprotective efficacy of the product non-invasively by nuclear scintigraphy. The nanoparticles were prepared using PLGA by dialysis method and ranged in size between 50 and 250 nm with a narrow range of distribution. They were found to arrive at the fenestra of liver sinusoidal epithelium for accumulation. The sizes of nanoparticles (batch S1) were optimal to reach the target and offer enough protection of the hepatocytes degenerated by CCl4 intoxication as determined by various biochemical and histopathological tests. In vitro studies exhibited the cytotoxic effect of the formulation against HepG2 cell line. The hepatoprotective efficacy of Qr-NPs evaluated non-invasively by nuclear scintigraphic technique using 99mTc-labelled sulphur colloid revealed abnormality in liver at the area of decreased uptake in rats of CCl4-treated group, which disappeared in Qr-NP-treated group. In dynamic studies with 99mTc-mebrofenin, excretion was severely impaired in CCl4-treated group but was moderate in drug-treated group, proving the recovery of animals from damage.

Influence of carbon nanoparticles/epoxy matrix interaction on mechanical, electrical and transport properties of structural advanced materials

NASA Astrophysics Data System (ADS)

Guadagno, Liberata; Naddeo, Carlo; Raimondo, Marialuigia; Barra, Giuseppina; Vertuccio, Luigi; Russo, Salvatore; Lafdi, Khalid; Tucci, Vincenzo; Spinelli, Giovanni; Lamberti, Patrizia

2017-03-01

The focus of this study is to design new nano-modified epoxy formulations using carbon nanofillers, such as carbon nanotubes, carbon nanofibers and graphene-based nanoparticles (CpEG), that reduce the moisture content and provide additional functional performance. The chemical structure of epoxy mixture, using a non-stoichiometric amount of hardener, exhibits unique properties in regard to the water sorption for which the equilibrium concentration of water (C eq) is reduced up to a maximum of 30%. This result, which is very relevant for several industrial applications (aeronautical, shipbuilding industries, wind turbine blades, etc), is due to a strong reduction of the polar groups and/or sites responsible to bond water molecules. All nanofillers are responsible of a second phase at lower glass transition temperature (Tg). Compared with other carbon nanofillers, functionalized graphene-based nanoparticles exhibit the best performance in the multifunctionality. The lowest moisture content, the high performance in the mechanical properties, the low electrical percolation threshold (EPT) have been all ascribed to particular arrangements of the functionalized graphene sheets embedded in the polymeric matrix. Exfoliation degree and edge carboxylated groups are responsible of self-assembled architectures which entrap part of the resin fraction hindering the interaction of water molecules with the polar sites of the resin, also favouring the EPT paths and the attractive/covalent interactions with the matrix.

Influence of carbon nanoparticles/epoxy matrix interaction on mechanical, electrical and transport properties of structural advanced materials.

PubMed

Guadagno, Liberata; Naddeo, Carlo; Raimondo, Marialuigia; Barra, Giuseppina; Vertuccio, Luigi; Russo, Salvatore; Lafdi, Khalid; Tucci, Vincenzo; Spinelli, Giovanni; Lamberti, Patrizia

2017-03-03

The focus of this study is to design new nano-modified epoxy formulations using carbon nanofillers, such as carbon nanotubes, carbon nanofibers and graphene-based nanoparticles (CpEG), that reduce the moisture content and provide additional functional performance. The chemical structure of epoxy mixture, using a non-stoichiometric amount of hardener, exhibits unique properties in regard to the water sorption for which the equilibrium concentration of water (C eq ) is reduced up to a maximum of 30%. This result, which is very relevant for several industrial applications (aeronautical, shipbuilding industries, wind turbine blades, etc), is due to a strong reduction of the polar groups and/or sites responsible to bond water molecules. All nanofillers are responsible of a second phase at lower glass transition temperature (Tg). Compared with other carbon nanofillers, functionalized graphene-based nanoparticles exhibit the best performance in the multifunctionality. The lowest moisture content, the high performance in the mechanical properties, the low electrical percolation threshold (EPT) have been all ascribed to particular arrangements of the functionalized graphene sheets embedded in the polymeric matrix. Exfoliation degree and edge carboxylated groups are responsible of self-assembled architectures which entrap part of the resin fraction hindering the interaction of water molecules with the polar sites of the resin, also favouring the EPT paths and the attractive/covalent interactions with the matrix.

Potential of insulin nanoparticle formulations for oral delivery and diabetes treatment.

PubMed

Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

2017-10-28

Nanoparticles have demonstrated significant advancements in potential oral delivery of insulin. In this publication, we review the current status of polymeric, inorganic and solid-lipid nanoparticles designed for oral administration of insulin. Firstly, the structure and physiological function of insulin are examined. Then, the efficiency and shortcomings of insulin nanoparticle are discussed. These include the susceptibility to digestive enzyme degradation, instability in the acidic pH environment, poor mucus diffusion and inadequate permeation through the gastrointestinal epithelium. In order to optimise the nanocarriers, the following considerations, including polymer nature, surface charge, size, polydispersity index and morphology of nanoparticles, have to be taken into account. Some novel designs such as chitosan-based glucose-responsive nanoparticles, layer by layer technique-based nanoparticles and zwitterion nanoparticles are being adopted to overcome the physiological challenges. The review ends with some future directions and challenges to be addressed for the success of oral delivery of insulin-loaded nanoparticle formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Development and evaluation of sunscreen creams containing morin-encapsulated nanoparticles for enhanced UV radiation protection and antioxidant activity

PubMed Central

Shetty, Pallavi Krishna; Venuvanka, Venkatesh; Jagani, Hitesh Vitthal; Chethan, Gejjalagere Honnappa; Ligade, Virendra S; Musmade, Prashant B; Nayak, Usha Y; Reddy, Meka Sreenivasa; Kalthur, Guruprasad; Udupa, Nayanabhirama; Rao, Chamallamudi Mallikarjuna; Mutalik, Srinivas

2015-01-01

The objective of present work was to develop novel sunscreen creams containing polymeric nanoparticles (NPs) of morin. Polymeric NPs containing morin were prepared and optimized. The creams containing morin NPs were also prepared and evaluated. Optimized NPs exhibited particle size of 90.6 nm and zeta potential of −31 mV. The entrapment efficiency of morin, within the polymeric NPs, was found to be low (12.27%). Fourier transformed infrared spectroscopy and differential scanning calorimetry studies revealed no interaction between morin and excipients. Transmission electron microscopy and atomic force microscopy revealed that the NPs were spherical in shape with approximately 100 nm diameter. Optimized NPs showed excellent in vitro free radical scavenging activity. Skin permeation and deposition of morin from its NPs was higher than its plain form. Different sunscreen creams (SC1–SC8) were formulated by incorporating morin NPs along with nano zinc oxide and nano titanium dioxide. SC5 and SC8 creams showed excellent sun protection factor values (≈40). In vitro and in vivo skin permeation studies of sunscreen creams containing morin NPs indicated excellent deposition of morin within the skin. Morin NPs and optimized cream formulations (SC5 and SC8) did not exhibit cytotoxicity in Vero and HaCaT cells. Optimized sunscreen creams showed excellent dermal safety. SC5 and SC8 creams demonstrated exceptional in vivo antioxidant effect (estimation of catalase, superoxide dismutase, and glutathione) in UV radiation-exposed rats. The optimized sunscreen creams confirmed outstanding UV radiation protection as well as antioxidant properties. PMID:26508854

Novel Methods to Incorporate Photosensitizers Into Nanocarriers for Cancer Treatment by Photodynamic Therapy

PubMed Central

Wang, Shouyan; Fan, Wenzhe; Kim, Gwangseong; Hah, Hoe Jin; Lee, Yong-Eun Koo; Kopelman, Raoul; Ethirajan, Manivannan; Gupta, Anurag; Goswami, Lalit N.; Pera, Paula; Morgan, Janet; Pandey, Ravindra K.

2013-01-01

Objective A hydrophobic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was loaded into nontoxic biodegradable amine functionalized polyacrylamide (AFPAA) nanoparticles using three different methods (encapsulation, conjugation, and post-loading), forming a stable aqueous dispersion. Each formulation was characterized for physicochemical properties as well as for photodynamic performance so as to determine the most effective nanocarrier formulation containing HPPH for photodynamic therapy (PDT). Materials and Methods HPPH or HPPH-linked acrylamide was added into monomer mixture and polymerized in a microemulsion for encapsulation and conjugation, respectively. For post-loading, HPPH was added to an aqueous suspension of pre-formed nanoparticles. Those nanoparticles were tested for optical characteristics, dye loading, dye leaching, particle size, singlet oxygen production, dark toxicity, in vitro photodynamic cell killing, whole body fluorescence imaging and in vivo PDT. Results HPPH was successfully encapsulated, conjugated or post-loaded into the AFPAA nanoparticles. The resultant nanoparticles were spherical with a mean diameter of 29 ± 3 nm. The HPPH remained intact after entrapment and the HPPH leaching out of nanoparticles was negligible for all three formulations. The highest singlet oxygen production was achieved by the post-loaded formulation, which caused the highest phototoxicity in in vitro assays. No dark toxicity was observed. Post-loaded HPPH AFPAA nanoparticles were localized to tumors in a mouse colon carcinoma model, enabling fluorescence imaging, and producing a similar photodynamic tumor response to that of free HPPH in equivalent dose. Conclusions Post-loading is the promising method for loading nanoparticles with hydrophobic photosensitizers to achieve effective in vitro and in vivo PDT. Lasers Surg. Med. 43:686–695, 2011. PMID:22057496

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

PubMed

Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

2016-08-01

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

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

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come.

PubMed

Yingchoncharoen, Phatsapong; Kalinowski, Danuta S; Richardson, Des R

2016-07-01

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current standard treatments for a variety of cancers is suboptimal. First, most cancer treatments lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts. Second, many anticancer agents are highly toxic, and thus, limit their use in treatment. Third, a number of cytotoxic chemotherapeutics are highly hydrophobic, which limits their utility in cancer therapy. Finally, many chemotherapeutic agents exhibit short half-lives that curtail their efficacy. As a result of these deficiencies, many current treatments lead to side effects, noncompliance, and patient inconvenience due to difficulties in administration. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems known commonly as nanoparticles. Among these delivery systems, lipid-based nanoparticles, particularly liposomes, have shown to be quite effective at exhibiting the ability to: 1) improve the selectivity of cancer chemotherapeutic agents; 2) lower the cytotoxicity of anticancer drugs to normal tissues, and thus, reduce their toxic side effects; 3) increase the solubility of hydrophobic drugs; and 4) offer a prolonged and controlled release of agents. This review will discuss the current state of lipid-based nanoparticle research, including the development of liposomes for cancer therapy, different strategies for tumor targeting, liposomal formulation of various anticancer drugs that are commercially available, recent progress in liposome technology for the treatment of cancer, and the next generation of lipid-based nanoparticles. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Chitosan-poly (lactide-co-glycolide) (CS-PLGA) nanoparticles containing metformin HCl: preparation and in vitro evaluation.

PubMed

Gundogdu, Nuran; Cetin, Meltem

2014-11-01

In this study, the preparation and in vitro characterisation of metformin HCl-loaded CS-PLGA nanoparticles (NPs) were aimed. The prepared nanoparticles (blank nanoparticles (C-1), 50 mg of metformin HCl loaded nanoparticles (C-2) and 75 mg of metformin HCl loaded nanoparticles (C-3) ranged in size from 506.67±13.61 to 516.33±16.85 nm and had surface charges of 22.57±1.21 to 32.37±0.57 mV. Low encapsulation efficiency was observed for both nanoparticle formulations due to the leakage of metformin HCl to the external medium during preparation of nanoparticles. Nanoparticle formulations showed highly reproducible drug release profiles. ~20% of metformin HCl was released within 30 minutes and approximately 98% of the loaded metformin HCl was released at 144 hours in a phosphate buffer (PB; pH 6.8). No statistically significant difference was noted between the in vitro release profiles of the nanoparticles (C-2 and C-3) containing metformin HCl. Also, nanoparticles were characterised using FT-IR and DSC.

Formulation/preparation of functionalized nanoparticles for in vivo targeted drug delivery.

PubMed

Gu, Frank; Langer, Robert; Farokhzad, Omid C

2009-01-01

Targeted cancer therapy allows the delivery of therapeutic agents to cancer cells without incurring undesirable side effects on the neighboring healthy tissues. Over the past decade, there has been an increasing interest in the development of advanced cancer therapeutics using targeted nanoparticles. Here we describe the preparation of drug-encapsulated nanoparticles formulated with biocompatible and biodegradable poly(D: ,L: -lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) copolymer and surface functionalized with the A10 2-fluoropyrimidine ribonucleic acid aptamers that recognize the extracellular domain of prostate-specific membrane antigen (PSMA), a well-characterized antigen expressed on the surface of prostate cancer cells. We show that the self-assembled nanoparticles can selectively bind to PSMA-targeted prostate cancer cells in vitro and in vivo. This formulation method may contribute to the development of highly selective and effective cancer therapeutic and diagnostic devices.

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.

Cyclosporine a loaded solid lipid nanoparticles: optimization of formulation, process variable and characterization.

PubMed

Varia, Jigisha K; Dodiya, Shamsunder S; Sawant, Krutika K

2008-01-01

Solid lipid nanoparticles (SLNs) loaded with Cyclosporine A using glyceryl monostearate (GMS) and glyceryl palmitostearate (GPS) as lipid matrices were prepared by melt-homogenization using high-pressure homogenizer. Various process parameters such as homogenization pressure, homogenization cycles and formulation parameters such as ratio of drug: lipid, emulsifier: lipid and emulsifier: co-emulsifier were optimized using particle size and entrapment efficiencies as the dependent variables. The mean particle size of optimized batches of the GMS SLN and GPS SLN were found to be 131 nm and 158 nm and their entrapment efficiencies were 83 +/- 3.08% and 97 +/- 2.59% respectively. To improve the handling processing and stability of the prepared SLNs, the SLN dispersions were spray dried and its effect on size and reconstitution parameters were evaluated. The spray drying of SLNs did not significantly alter the size of SLNs and they exhibited good redispersibility. Solid state studies such as Infra Red Spectroscopy and Differential Scanning Calorimetry indicated absence of any chemical interaction between Cyclosporine A and the lipids. Scanning Electron Microscopy of optimized formulations showed spherical shape with smooth and non porous surface. In vitro release studies revealed that GMS based SLNs released the drug faster (41.12% in 20 hours) than GPS SLNs (7.958% in 20 hours). Release of Cyclosporine A from GMS SLN followed Higuchi equation better than first order while release from GPS SLN followed first order better than Higuchi model.

Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis

PubMed Central

Pinheiro, Marina; Ribeiro, Ricardo; Vieira, Alexandre; Andrade, Fernanda; Reis, Salette

2016-01-01

This work aimed to design, develop, and characterize a lipid nanocarrier system for the selective delivery of rifabutin (RFB) to alveolar macrophages. Lipid nanoparticles, specifically nanostructured lipid carriers (NLC), were synthetized by the high-shear homogenization and ultrasonication techniques. These nanoparticles were designed to exhibit both passive and active targeting strategies to be efficiently internalized by the alveolar macrophages, traffic to the acidified phagosomes and phagolysosomes, and release bactericidal concentrations of the antituberculosis drug intracellularly. NLC that could entrap RFB were prepared, characterized, and further functionalized with mannose. Particles’ diameter, zeta potential, morphology, drug% entrapping efficiency, and drug release kinetics were evaluated. The mannose coating process was confirmed by Fourier transform infrared. Further, the cytotoxicity of the formulations was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay in A549, Calu-3, and Raw 264.7 cells. The diameter of NLC formulations was found to be in the range of 175–213 nm, and drug entrapping efficiency was found to be above 80%. In addition, high storage stability for the formulations was expected since they maintained the initial characteristics for 6 months. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. These results pose a strong argument that the developed nanocarrier can be explored as a promising carrier for safer and more efficient management of tuberculosis by exploiting the pulmonary route of administration. PMID:27536067

An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma

PubMed Central

Reolon, Luciano Antonio; Amaral-Machado, Lucas; Gremião, Maria Palmira Daflon; Guterres, Silvia S.

2018-01-01

Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively. PMID:29385692

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.

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.

Design and evaluation of an intravesical delivery system for superficial bladder cancer: preparation of gemcitabine HCl-loaded chitosan–thioglycolic acid nanoparticles and comparison of chitosan/poloxamer gels as carriers

PubMed Central

Ay Şenyiğit, Zeynep; Karavana, Sinem Yaprak; İlem-Özdemir, Derya; Çalışkan, Çağrı; Waldner, Claudia; Şen, Sait; Bernkop-Schnürch, Andreas; Baloğlu, Esra

2015-01-01

This study aimed to develop an intravesical delivery system of gemcitabine HCl for superficial bladder cancer in order to provide a controlled release profile, to prolong the residence time, and to avoid drug elimination via urination. For this aim, bioadhesive nanoparticles were prepared with thiolated chitosan (chitosan–thioglycolic acid conjugate) and were dispersed in bioadhesive chitosan gel or in an in situ gelling poloxamer formulation in order to improve intravesical residence time. In addition, nanoparticle-loaded gels were diluted with artificial urine to mimic in vivo conditions in the bladder and were characterized regarding changes in gel structure. The obtained results showed that chitosanthioglycolic acid nanoparticles with a mean diameter of 174.5±3.762 nm and zeta potential of 32.100±0.575 mV were successfully developed via ionotropic gelation and that the encapsulation efficiency of gemcitabine HCl was nearly 20%. In vitro/ex vivo characterization studies demonstrated that both nanoparticles and nanoparticle-loaded chitosan and poloxamer gels might be alternative carriers for intravesical administration of gemcitabine HCl, prolonging its residence time in the bladder and hence improving treatment efficacy. However, when the gel formulations were diluted with artificial urine, poloxamer gels lost their in situ gelling properties at body temperature, which is in conflict with the aimed formulation property. Therefore, 2% chitosan gel formulation was found to be a more promising carrier system for intravesical administration of nanoparticles. PMID:26508855

Local delivery of sirolimus nanoparticles for the treatment of in-stent restenosis.

PubMed

Zago, Alexandre C; Raudales, José C; Attizzani, Guilherme; Matte, Bruno S; Yamamoto, German I; Balvedi, Julise A; Nascimento, Ludmila; Kosachenco, Beatriz G; Centeno, Paulo R; Zago, Alcides J

2013-02-01

To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model. Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high. Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment. There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1. PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans. Copyright © 2012 Wiley Periodicals, Inc.

Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles.

PubMed

Chuah, Lay Hong; Roberts, Clive J; Billa, Nashiru; Abdullah, Syahril; Rosli, Rozita

2014-04-01

Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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

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.

Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

PubMed Central

Nair K, Lekha; Jagadeeshan, Sankar; Nair, S Asha; Kumar, GS Vinod

2011-01-01

Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy. PMID:21980233

Synthesis and characterization of folate decorated albumin bio-conjugate nanoparticles loaded with a synthetic curcumin difluorinated analogue.

PubMed

Gawde, Kaustubh A; Kesharwani, Prashant; Sau, Samaresh; Sarkar, Fazlul H; Padhye, Subhash; Kashaw, Sushil K; Iyer, Arun K

2017-06-15

Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF). CDF has demonstrated a 16-fold improvement in stability and remarkable anticancer potency compared to its natural derivative, curcumin. CDF showed marked inhibition of cancer cell growth through down-regulation of multiple miRNAs, up-regulation of phosphatase and tensin homolog (PTEN), and attenuation of histone methyl transferase EZH2. However, CDF is highly hydrophobic and photodegradable with sparing aqueous solubility. In this study, we have formulated albumin nanoparticle using a modified desolvation method, which yielded high CDF loading in a nanoformulation. The physicochemical properties of CDF loaded albumin and folate-decorated albumin nanosuspensions were assessed for particle size, morphology, zeta potential, drug encapsulation efficiency/loading, solubility and drug release. Importantly, the folate ligand decorated albumin nanoparticles were formulated in principle to passively and actively target folate-overexpressing-cancers. In this study, the synthesis and optimization of BSA and folate decorated BSA conjugated CDF nanoparticles are assessed in detail that will be useful for its future clinical translation. Copyright © 2017 Elsevier Inc. All rights reserved.

Physico-chemical separation process of nanoparticles in cosmetic formulations

NASA Astrophysics Data System (ADS)

Retamal Marín, R. R.; Babick, F.; Stintz, M.

2017-06-01

Understanding the world of nanoparticles, especially their interactions with the environment, begins with their correct detection and successive quantification. To achieve this purpose, one needs to perform correctly developed standard operating procedures (SOPs). Furthermore, the study of nanoparticles frequently requires their characterisation in complex media (e.g. in cosmetic formulations). In this study, a set of sample preparation procedures for the detection and extraction of NMs in emulsion-based formulations is proposed and their performance for model and real-life products is discussed. A separation or extraction of lipid phases is achieved by means of organic solvents. The polarity of the lipid phases is decisive for selecting an optimum solvent. The use of the Hansen Solubility Parameters (HSP) may clearly support this decision.

Folate-decorated anticancer drug and magnetic nanoparticles encapsulated polymeric carrier for liver cancer therapeutics.

PubMed

Li, Yu-Ji; Dong, Ming; Kong, Fan-Min; Zhou, Jian-Ping

2015-07-15

Nanoparticulate system with theranostic applications has attracted significant attention in cancer therapeutics. In the present study, we have developed a novel composite PLGA NP co-encapsulated with anticancer drug (sorafenib) and magnetic NP (SPION). We have successfully developed nanosized folate-conjugated PEGylated PLGA nanoparticles (SRF/FA-PEG-PLGA NP) with both anticancer and magnetic resonance property. We have showed that FA-conjugated NP exhibits sustained drug release and enhanced cellular uptake in BEL7402 cancer cells. The targeted NP effectively suppressed the tumor cell proliferation and has improved the anticancer efficacy than that of free drug or non-targeted one. Additionally, enhanced MRI properties demonstrate this formulation has good imaging agent characteristics. Finally, SRF/FA-PEG-PLGA NP effectively inhibited the colony forming ability indicating its superior anticancer effect. Together, these multifunctional nanoparticles would be most ideal to improve the therapeutic response in cancer and holds great potential to be a part of future nanomedicine. Our unique approach could be extended for multiple biomedical applications. Copyright © 2015. Published by Elsevier B.V.

Shape-Dependent Skin Penetration of Silver Nanoparticles: Does It Really Matter?

PubMed Central

Tak, Yu Kyung; Pal, Sukdeb; Naoghare, Pravin K.; Rangasamy, Sabarinathan; Song, Joon Myong

2015-01-01

Advancements in nano-structured materials have facilitated several applications of nanoparticles (NPs). Skin penetration of NPs is a crucial factor for designing suitable topical antibacterial agents with low systemic toxicity. Available reports focus on size-dependent skin penetration of NPs, mainly through follicular pathways. Herein, for the first time, we demonstrate a proof-of-concept study that entails variations in skin permeability and diffusion coefficients, penetration rates and depth-of-penetration of differently shaped silver NPs (AgNPs) via intercellular pathways using both in vitro and in vivo models. The antimicrobial activity of AgNPs is known. Different shapes of AgNPs may exhibit diverse antimicrobial activities and skin penetration capabilities depending upon their active metallic facets. Consideration of the shape dependency of AgNPs in antimicrobial formulations could help developing an ideal topical agent with the highest efficacy and low systemic toxicity. PMID:26584777

Hyaluronic acid grafted PLGA copolymer nanoparticles enhance the targeted delivery of Bromelain in Ehrlich's Ascites Carcinoma.

PubMed

Bhatnagar, Priyanka; Pant, Aditya Bhushan; Shukla, Yogeshwer; Panda, Amulya; Gupta, Kailash Chand

2016-08-01

Rapidly increasing malignant neoplastic disease demands immediate attention. Several dietary compounds have recently emerged as strong anti-cancerous agents. Among, Bromelain (BL), a protease from pineapple plant, was used to enhance its anti-cancerous efficacy using nanotechnology. In lieu of this, hyaluronic acid (HA) grafted PLGA copolymer, having tumor targeting ability, was developed. BL was encapsulated in copolymer to obtain BL-copolymer nanoparticles (NPs) that ranged between 140 to 281nm in size. NPs exhibited higher cellular uptake and cytotoxicity in cells with high CD44 expression as compared with non-targeted NPs. In vivo results on tumor bearing mice showed that NPs were efficient in suppressing the tumor growth. Hence, the formulation could be used as a self-targeting drug delivery cargo for the remission of cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation and Optimization OF Palm-Based Lipid Nanoparticles Loaded with Griseofulvin.

PubMed

Huei Lim, Wen; Jean Tan, Yann; Sin Lee, Choy; Meng Er, Hui; Fung Wong, Shew

2017-01-01

Palm-based lipid nanoparticle formulation loaded with griseofulvin was prepared by solvent-free hot homogenization method. The griseofulvin loaded lipid nanoparticles were prepared via stages of optimisation, by altering the high pressure homogenisation (HPH) parameters, screening on palm-based lipids and Tween series surfactants and selection of lipid to surfactant ratios. A HPLC method has been validated for the drug loading capacity study. The optimum HPH parameter was determined to be 1500 bar with 5 cycles and among the palm-based lipid materials; Lipid C (triglycerides) was selected for the preparation of lipid nanoparticles. Tween 80 was chosen from the Tween series surfactants for its highest saturated solubility of griseofulvin at 53.1 ± 2.16 µg/mL. The optimum formulation of the griseofulvin loaded lipid nanoparticles demonstrated nano-range of particle size (179.8 nm) with intermediate distribution index (PDI) of 0.306, zeta potential of -27.9 mV and drug loading of 0.77%. The formulation was stable upon storage for 1 month at room temperature (25 ° C) and 45 ° C with consistent drug loading capacity.

New Dendrimer-Based Nanoparticles Enhance Curcumin Solubility.

PubMed

Falconieri, Maria Cristina; Adamo, Mauro; Monasterolo, Claudio; Bergonzi, Maria Camilla; Coronnello, Marcella; Bilia, Anna Rita

2017-03-01

Curcumin, the main curcuminoid of the popular Indian spice turmeric, is a potent chemopreventive agent and useful in many different diseases. A major limitation of applicability of curcumin as a health promoting and medicinal agent is its extremely low bioavailability due to efficient first pass metabolism, poor gastrointestinal absorption, rapid elimination, and poor aqueous solubility. In the present study, nanotechnology was selected as a choice approach to enhance the bioavailability of the curcuminis. A new polyamidoamine dendrimer (G0.5) was synthesized, characterized, and tested for cytotoxicity in human breast cancer cells (MCF-7). No cytotoxicity of G0.5 was found in the range between 10 -3 and 3 × 10 -8  M. Consequently, G0.5 was used to prepare spherical nanoparticles of ca. 150 nm, which were loaded with curcumin [molar ratio G0.5/curcumin 1 : 1 (formulation 1) and 1 : 0.5 (formulation 2)]. Remarkably, the occurrence of a single population of nanoparticles having an excellent polydispersity index (< 0.20) was found in both formulations. Formulation 1 was selected to test in vitro drug release because it was superior in terms of encapsulation efficiency (62 %) and loading capacity (32 %). The solubility of curcumin was increased ca. 415 and 150 times with respect to the unformulated drug, respectively, for formulation 1 and formulation 2. The release of curcumin from the nanoparticles showed an interesting prolonged and sustained release profile. Georg Thieme Verlag KG Stuttgart · New York.

Plasma-Functionalized Polytetrafluoroethylene Nanoparticles for Improved Wear in Lubricated Contact

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

Sharma, Vinay; Timmons, Richard; Erdemir, Ali

Plasma-functionalized polytetrafluoroethylene (PTFE) nanoparticles were employed to evaluate their utility in improving the lubrication property of a group III mineral oil with a significantly low amount of zinc dialkyl dithiophosphate (ZDDP). The particles were coated with two consecutive films; the initial coating contained silica to enhance amorphous glassy tribofilm formation, followed by a methacrylate film to protect the silica coating and enhance dispersibility in the oil. The functionalized nanoparticles were evaluated for their tribological performance using a high-frequency reciprocating rig, in a cylinder-on-flat configuration. The oil formulations containing ZDDP (350 ppm phosphorus level) and the functionalized nanoparticles resulted in dramaticmore » reductions in the friction coefficient and overall wear compared to the samples containing nonfunctionalized PTFE nanoparticles, ZDDP (350 ppm P), and samples devoid of nanoparticles but containing ZDDP with a 700 ppm P treat rate. XPS and XANES spectroscopy were employed to characterize the tribological films formed on the test samples. The samples with functionalized particles and ZDDP clearly exhibited tribofilms with Si- and F-doped polyphosphates of Zn coupled with the presence of ZnS at the metal-tribofilm interface. On the other hand, oils without the functionalized nanoparticles have oxides of Fe and to a lesser extent short-chain phosphates of Zn. The overall results suggest that the synergism between plasma-coated PTFE nanoparticles and ZDDP contributed to the development of protective tribofilms even at reduced amount of phosphorus in the oil. This new method of employing nanoparticles to deliver novel antifriction and antiwear chemistries at the tribological interfaces stands out as a promising approach to further reduce P levels in oils without compromising friction and wear performance.« less

The influence of mannitol on morphology and disintegration of spray-dried nano-embedded microparticles.

PubMed

Torge, Afra; Grützmacher, Philipp; Mücklich, Frank; Schneider, Marc

2017-06-15

Nano-embedded microparticles represent a promising approach to deliver nanoparticles to the lungs. Microparticles with an appropriate aerodynamic diameter enable an application by dry powder inhaler and the transport of nanoparticles into the airways. By disintegration after deposition, nanoparticles can be released to exhibit their advantages such as a sustained drug release and delivery of the drug across the mucus barrier. The use of an appropriate matrix excipient to embed the nanoparticles is essential for the necessary disintegration and release of nanoparticles. In this context we investigated the influence of mannitol on the morphology, aerodynamic properties and disintegration behavior of nano-embedded microparticles. PLGA nanoparticles and mannitol were spray dried each as sole component and in combination in three different ratios. An influence of the mannitol content on the morphology was observed. Pure mannitol microparticles were solid and spherical, while the addition of nanoparticles resulted in raisin-shaped hollow particles. The different morphologies can be explained by diffusion processes of the compounds described by the Péclet-number. All powders showed suitable aerodynamic properties. By dispersion of the powders in simulated lung fluid, initial nanoparticle sizes could be recovered for samples containing mannitol. The fraction of redispersed nanoparticles was increased with increasing mannitol content. To evaluate the disintegration under conditions with higher comparability to the in vivo situation, spray-dried powders were exposed to >90% relative humidity. The disintegration behavior was monitored by analyzing roughness values by white light interferometry and supporting SEM imaging. The exposure to high relative humidity was shown to be sufficient for disintegration of the microparticles containing mannitol, releasing morphologically unchanged nanoparticles. With increasing mannitol content, the disintegration occurred faster and to a higher degree. Under these conditions, microparticles only composed of nanoparticles did not disintegrate. By enabling the release of nanoparticles from nano-embedded microparticles, mannitol was shown to be an ideal excipient to convert nanoparticles by spray drying into an inhalable dry power formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

Formulation to target delivery to the ciliary body and choroid via the suprachoroidal space of the eye using microneedles.

PubMed

Kim, Yoo Chun; Oh, Kyung Hee; Edelhauser, Henry F; Prausnitz, Mark R

2015-09-01

In this work, we tested the hypothesis that particles injected into the suprachoroidal space can be localized at the site of injection or broadly distributed throughout the suprachoroidal space by controlling polymeric formulation properties. Single hollow microneedles were inserted into the sclera of New Zealand White rabbits and injected non-biodegradable fluorescently tagged nanoparticles and microparticles suspended in polymeric formulations into the suprachoroidal space of the eye. When formulated in saline, the particles were distributed over 29-42% of the suprachoroidal space immediately after injection. To spread particles over larger areas of the choroidal surface, addition of hyaluronic acid to make moderately non-Newtonian solutions increased particle spread to up to 100% of the suprachoroidal space. To localize particles at the site of injection adjacent to the ciliary body, strongly non-Newtonian polymer solutions localized particles to 8.3-20% of the suprachoroidal space, which exhibited a small increase in area over the course of two months. This study demonstrates targeted particle delivery within the suprachoroidal space using polymer formulations that spread particles over the whole choroidal surface or localized them adjacent to the ciliary body after injection. Copyright © 2015 Elsevier B.V. All rights reserved.

Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil.

PubMed

Yadav, Awesh K; Agarwal, Abhinav; Rai, Gopal; Mishra, Pradeep; Jain, Sanyog; Mishra, Anil K; Agrawal, Himanshu; Agrawal, Govind P

2010-11-01

The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of 99m Tc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA-PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG-PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo.

IgG particle formation during filling pump operation: a case study of heterogeneous nucleation on stainless steel nanoparticles.

PubMed

Tyagi, Anil K; Randolph, Theodore W; Dong, Aichun; Maloney, Kevin M; Hitscherich, Carl; Carpenter, John F

2009-01-01

This study investigated factors associated with vial filling with a positive displacement piston pump leading to formation of protein particles in a formulation of an IgG. We hypothesized that nanoparticles shed from the pump's solution-contact surfaces nucleated protein aggregation and particle formation. Vials of IgG formulation filled at a clinical manufacturing site contained a few visible particles and about 100,000 particles (1.5-3 microm) per mL. In laboratory studies with the same model (National Instruments FUS-10) of pump, pumping of 20 mg/mL IgG formulation resulted in about 300,000 particles (1.5-3 microm) per mL. Pumping of protein-free formulation resulted in 13,000 particles (1.5-15 microm) per mL. More than 99% of the particles were 0.25-0.95 microm in size. Mixing of protein-free pumped solution with an equal volume of 40 mg/mL IgG resulted in 300,000 particles (1.5-15 microm) per mL. Also, mixing IgG formulation with 30,000/mL stainless steel nanoparticles resulted in formation of 30,000 protein microparticles (1.5-15 microm) per mL. Infrared spectroscopy showed that secondary structure of IgG in microparticles formed by pumping or mixing with steel nanoparticles was minimally perturbed. Our results document that nanoparticles of foreign materials shed by pumps can serve as heterogeneous nuclei for formation of protein microparticles. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

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.

Design of eudragit RL nanoparticles by nanoemulsion method as carriers for ophthalmic drug delivery of ketotifen fumarate

PubMed Central

Soltani, Saieede; Zakeri-Milani, Parvin; Barzegar-Jalali, Mohammad; Jelvehgari, Mitra

2016-01-01

Objective(s): Ketotifen fumarate (KF) is a selective and noncompetitive histamine antagonist (H1-receptor) that is used topically in the treatment of allergic conditions of rhinitis and conjunctivitis. The aim of this study was to formulate and improve an ophthalmic delivery system of KF. Ocular nanoparticles were prepared with the objective of reducing the frequency of administration and obtaining controlled release to improve the anti-inflammatory drug delivery. Materials and Methods: In the present study, ocular KF loaded Eudragit RL 100 nanoparticles were prepared using O/W solvent diffusion method. The nanoparticles were evaluated for particle size, entrapment efficiency, surface morphology, X-ray diffraction (XRD), Fourier transform spectroscopy (FTIR), and differential scanning calorimetry (DSC). In vitro release and permeation studies were also carried out on nanoparticles. Results: An average size range of 182 to 314.30 nm in diameter was obtained and encapsulation efficiency up to 95.0% was observed for all the formulations. Drug release for all formulations after 24 hr was between 65.51% and 88.82% indicating effective controlled release property of KF. The mechanism of drug release for best formulation was found to be fickian diffusion mechanism. KF nanoparticles containing high polymer concentration (1:15) presented a faster drug release and a higher drug penetration; on the contrary, nanoparticles containing low polymer concentration (1:7.5) were able to give a more sustained release of the drug and thus a slower KF permeation through the cornea. Conclusion: The study revealed that KF NPs were capable of releasing the drug for a prolonged period of time and increasing the ocular bioavailability. PMID:27403262

Delivery of expression constructs of secreted frizzled-related protein 4 and its domains by chitosan-dextran sulfate nanoparticles enhances their expression and anti-cancer effects.

PubMed

Perumal, Vanathi; Arfuso, Frank; Chen, Yan; Fox, Simon; Dharmarajan, Arun M

2018-06-01

In malignant mesothelioma (MM) cells, secreted frizzled-related protein 4 (SFRP4) expression is downregulated by promoter methylation. In this study, we evaluated the effect of encapsulated chitosan-dextran (CS-DS) nanoparticle formulations of SFRP4 and its cysteine-rich domain (CRD) and netrin-like domain (NLD) as means of SFRP4-GFP protein delivery and their effects in JU77 and ONE58 MM cell lines. CS-DS formulations of SFRP4, CRD, and NLD nanoparticles were prepared by a complex coacervation technique, and particle size ranged from 300 nm for empty particles to 337 nm for particles containing the proteins. Measurement of the zeta potential showed that all preparations were around 25 mV or above, suggesting stable formulation and good affinity for the DNA molecules. The CS-DS nanoparticle formulation maintained high integrity and entrapment efficiency. Gene delivery of SFRP4 and its domains showed enhanced biological effects in both JU77 and ONE58 cell lines when compared to the non-liposomal FUGENE ® HD transfection reagent. In comparison to the CRD nanoparticles, both the SFRP4 and NLD nanoparticles significantly reduced the viability of MM cells, with the NLD showing the greatest effect. The CS-DS nanoparticle effects were observed at an earlier time point and with lower DNA concentrations. Morphological changes in MM cells were characterized by the formation of membrane-associated vesicles and green fluorescent protein expression specific to SFRP4 and the NLD. The findings from our proof-of-concept study provide a stepping stone for further investigations using in vivo models.

Enhanced oral bioavailability and in vivo antioxidant activity of chlorogenic acid via liposomal formulation.

PubMed

Feng, Yingshu; Sun, Congyong; Yuan, Yangyang; Zhu, Yuan; Wan, Jinyi; Firempong, Caleb Kesse; Omari-Siaw, Emmanuel; Xu, Yang; Pu, Zunqin; Yu, Jiangnan; Xu, Ximing

2016-03-30

In the present study, a formulation system consisting of cholesterol and phosphatidyl choline was used to prepare an effective chlorogenic acid-loaded liposome (CAL) with an improved oral bioavailability and an increased antioxidant activity. The developed liposomal formulation produced regular, spherical and multilamellar-shaped distribution nanoparticles. The pharmacokinetic analysis of CAL compared with chlorogenic acid (CA), showed a higher value of Cmax(6.42 ± 1.49 min versus 3.97 ± 0.39 min) and a delayed Tmax(15 min versus 10 min), with 1.29-fold increase in relative oral bioavailability. The tissue distribution in mice also demonstrated that CAL predominantly accumulated in the liver which indicated hepatic targeting potential of the drug. The increased activities of antioxidant enzymes (Total Superoxide Dismutase (T-SOD) and Glutathione Peroxidase (GSH-Px)) and total antioxidant capacity (T-AOC), in addition to decreased level of malondialdehyde (MDA) in CCl4-induced hepatotoxicity study further revealed that CAL exhibited significant hepatoprotective and antioxidant effects. Collectively, these findings present a liposomal formulation with significantly improved oral bioavailability and an increased in vivo antioxidant activity of CA. Copyright © 2016 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.

Multifunctional antitumor magnetite/chitosan- l-glutamic acid (core/shell) nanocomposites

NASA Astrophysics Data System (ADS)

Santos, Daniela P.; Ruiz, M. Adolfina; Gallardo, Visitación; Zanoni, Maria Valnice B.; Arias, José L.

2011-09-01

The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan- l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.

Preparation and Characterization of Three Tilmicosin-loaded Lipid Nanoparticles: Physicochemical Properties and in-vitro Antibacterial Activities

PubMed Central

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. PMID:28261309

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.

Multifunctional Cationic Lipid-Based Nanoparticles Facilitate Endosomal Escape and Reduction-Triggered Cytosolic siRNA Release

PubMed Central

Gujrati, Maneesh; Malamas, Anthony; Shin, Tesia; Jin, Erlei; Sun, Lulu; Lu, Zheng-Rong

2015-01-01

Small interfering RNA (siRNA) has garnered much attention in recent years as a promising avenue for cancer gene therapy due to its ability to silence disease-related genes. Effective gene silencing is contingent upon the delivery of siRNA into the cytosol of target cells and requires the implementation of delivery systems possessing multiple functionalities to overcome delivery barriers. The present work explores the multifunctional properties and biological activity of a recently developed cationic lipid carrier, (1-aminoethyl)iminobis[N-(oleicylcysteinyl-1-amino-ethyl)propionamide]) (ECO). The physicochemical properties and biological activity of ECO/siRNA nanoparticles were assessed over a range of N/P ratios to optimize the formulation. Potent and sustained luciferase silencing in a U87 glioblastoma cell line was observed, even in the presence of serum proteins. ECO/siRNA nanoparticles exhibited pH-dependent membrane disruption at pH levels corresponding to various stages of the intracellular trafficking pathway. It was found that disulfide linkages created during nanoparticle formation enhanced the protection of siRNA from degradation and facilitated site-specific siRNA release in the cytosol by glutathione-mediated reduction. Confocal microscopy confirmed that ECO/siRNA nanoparticles readily escaped from late endosomes prior to cytosolic release of the siRNA cargo. These results demonstrate that the rationally designed multifunctionality of ECO/siRNA nanoparticles is critical for intracellular siRNA delivery and the continuing development of safe and effective delivery systems. PMID:25020033

Comparison of different models for the testing of pilocarpine eyedrops using conventional eyedrops and a novel depot formulation (nanoparticles).

PubMed

Diepold, R; Kreuter, J; Himber, J; Gurny, R; Lee, V H; Robinson, J R; Saettone, M F; Schnaudigel, O E

1989-01-01

An objective in the development of ophthalmic formulations is the use of in vitro or animal models that closely resemble the clinical situation. For this reason, experiments with conventional pilocarpine nitrate eyedrops and a depot formulation of pilocarpine nitrate sorbed to poly (butylcyanoacrylate) nanoparticles were carried out. In vitro, the diffusion of pilocarpine through bovine cornea was measured using Edelhauser cells. In vivo, the rabbit aqueous humor concentration of pilocarpine and miosis were determined after application of the above formulations. In addition, intraocular pressure was measured. Since pilocarpine has little influence on intraocular pressure in healthy rabbits, the pressure had to be increased artificially. Three models were employed that are described in the literature, namely, the betamethasone model, the alpha-chymotrypsin model, and the water-loading model. Pilocarpine could be loaded onto nanoparticles by 15% but was rapidly released from the nanoparticles based on the bovine corneal experiment. Nanoparticles only enhanced the aqueous humor concentration at 30 min; this increase, however, led to a considerably extended period of miosis as well as a reduction in intraocular pressure. The duration of the action and the intensity of the response were different among the three models tested. According to the present results, the betamethasone model seems to represent the best correlation to the clinical situation.

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

Enhanced and Extended Anti-Hypertensive Effect of VP5 Nanoparticles

PubMed Central

Yu, Ting; Zhao, Shengnan; Li, Ziqiang; Wang, Yi; Xu, Bei; Fang, Dailong; Wang, Fazhan; Zhang, Zhi; He, Lili; Song, Xiangrong; Yang, Jian

2016-01-01

Hypertension has become a significant global public health concern and is also one of the most common risk factors of cardiovascular disease. Recent studies have shown the promising result of peptides inhibiting angiotensin converting enzyme (ACE) in lowering the blood pressure in both animal models and humans. However, the oral bioavailability and continuous antihypertensive effectiveness require further optimization. Novel nanoparticle-based drug delivery systems are helpful to overcome these barriers. Therefore, a poly-(lactic-co-glycolic) acid nanoparticle (PLGANPs) oral delivery system, of the antihypertensive small peptides Val-Leu-Pro-Val-Pro (VLPVP, VP5) model, was developed in this study and its antihypertensive effect was investigated in spontaneously hypertensive rats (SHRs) for the first time. The obtained VP5 nanoparticles (VP5-NPs) showed a small particle size of 223.7 ± 2.3 nm and high entrapment efficiency (EE%) of 87.37% ± 0.92%. Transmission electronic microscopy (TEM) analysis showed that the nanoparticles were spherical and homogeneous. The optimal preparation of VP5-NPs exhibited sustained release of VP5 in vitro and a 96 h long-term antihypertensive effect with enhanced efficacy in vivo. This study illustrated that PLGANPs might be an optimal formulation for oral delivery of antihypertensive small peptides and VP5-NPs might be worthy of further development and use as a potential therapeutic strategy for hypertension in the future. PMID:27898022

Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design.

PubMed

Emami, J; Mohiti, H; Hamishehkar, H; Varshosaz, J

2015-01-01

Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7(®) software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the application of SLNs in pulmonary delivery system of budesonide.

Formulation and optimization of solid lipid nanoparticle formulation for pulmonary delivery of budesonide using Taguchi and Box-Behnken design

PubMed Central

Emami, J.; Mohiti, H.; Hamishehkar, H.; Varshosaz, J.

2015-01-01

Budesonide is a potent non-halogenated corticosteroid with high anti-inflammatory effects. The lungs are an attractive route for non-invasive drug delivery with advantages for both systemic and local applications. The aim of the present study was to develop, characterize and optimize a solid lipid nanoparticle system to deliver budesonide to the lungs. Budesonide-loaded solid lipid nanoparticles were prepared by the emulsification-solvent diffusion method. The impact of various processing variables including surfactant type and concentration, lipid content organic and aqueous volume, and sonication time were assessed on the particle size, zeta potential, entrapment efficiency, loading percent and mean dissolution time. Taguchi design with 12 formulations along with Box-Behnken design with 17 formulations was developed. The impact of each factor upon the eventual responses was evaluated, and the optimized formulation was finally selected. The size and morphology of the prepared nanoparticles were studied using scanning electron microscope. Based on the optimization made by Design Expert 7® software, a formulation made of glycerol monostearate, 1.2 % polyvinyl alcohol (PVA), weight ratio of lipid/drug of 10 and sonication time of 90 s was selected. Particle size, zeta potential, entrapment efficiency, loading percent, and mean dissolution time of adopted formulation were predicted and confirmed to be 218.2 ± 6.6 nm, -26.7 ± 1.9 mV, 92.5 ± 0.52 %, 5.8 ± 0.3 %, and 10.4 ± 0.29 h, respectively. Since the preparation and evaluation of the selected formulation within the laboratory yielded acceptable results with low error percent, the modeling and optimization was justified. The optimized formulation co-spray dried with lactose (hybrid microparticles) displayed desirable fine particle fraction, mass median aerodynamic diameter (MMAD), and geometric standard deviation of 49.5%, 2.06 μm, and 2.98 μm; respectively. Our results provide fundamental data for the application of SLNs in pulmonary delivery system of budesonide. PMID:26430454

Enhancement of scutellarin oral delivery efficacy by vitamin B12-modified amphiphilic chitosan derivatives to treat type II diabetes induced-retinopathy.

PubMed

Wang, Jingnan; Tan, Jiayun; Luo, Jiahao; Huang, Peilin; Zhou, Wuyi; Chen, Luming; Long, Lingli; Zhang, Li-Ming; Zhu, Banghao; Yang, Liqun; Deng, David Y B

2017-03-01

Diabetic retinopathy is the most common complication in diabetic patients relates to high expression of VEGF and microaneurysms. Scutellarin (Scu) turned out to be effective against diabetes related vascular endothelial cell dysfunction. However, its clinical applications have been limited by its low bioavailability. In this study, we formulated and characterized a novel intestinal target nanoparticle carrier based on amphiphilic chitosan derivatives (Chit-DC-VB12) loaded with scutellarin to enhance its bioavailability and then evaluated its therapeutic effect in experimental diabetic retinopathy model. Chit-DC-VB12 nanoparticles showed low toxicity toward the human colon adenocarcinoma (Caco-2) cells and zebra fish within concentration of 250 μg/ml, owing to good biocompatibility of chitosan. The scutellarin-loaded Chit-DC-VB12 nanoparticles (Chit-DC-VB12-Scu) were then prepared by self-assembly in aqueous solution. Scanning electron microscopy and dynamic light scattering analysis indicated that the Chit-DC-VB12-Scu nanoparticles were spherical particles in the sizes ranging from 150 to 250 nm. The Chit-DC-VB12-Scu nanoparticles exhibited high permeation in Caco-2 cell, indicated it could be beneficial to be absorbed in humans. We also found that Chit-DC-VB12 nanoparticles had a high cellular uptake. Bioavailability studies were performed in Sprague-Dawley rats, which present the area under the curve of scutellarin of Chit-DC-VB12-Scu was two to threefolds greater than that of free scutellarin alone. Further to assess the therapeutic efficacy of diabetic retinopathy, we showed Chit-DC-VB12-Scu down-regulated central retinal artery resistivity index and the expression of angiogenesis proteins (VEGF, VEGFR2, and vWF) of retinas in type II diabetic rats. Chit-DC-VB12 nanoparticles loaded with scutellarin have better bioavailability and cellular uptake efficiency than Scu, while Chit-DC-VB12-Scu nanoparticles alleviated the structural disorder of intraretinal neovessels in the retina induced by diabetes, and it also inhibited the retinal neovascularization via down-regulated the expression of angiogenesis proteins. In conclusion, the Chit-DC-VB12 nanoparticles enhanced scutellarin oral delivery efficacy and exhibited potential as small intestinal target promising nano-carriers for treatment of type II diabetes induced-retinopathy.

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.

Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle

NASA Astrophysics Data System (ADS)

Sau, Samaresh; Agarwalla, Pritha; Mukherjee, Sudip; Bag, Indira; Sreedhar, Bojja; Pal-Bhadra, Manika; Patra, Chitta Ranjan; Banerjee, Rajkumar

2014-05-01

Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied on the delivery of `exogenous' genes invoking gene knockdown or replacement. Practically, there are no instances for the nanoparticle-mediated promoter regulation of `endogenous' genes, more so, as a cancer selective phenomenon. In this regard, we report the development of a simple, easily modifiable GNP-formulation, which promoted/up-regulated the expression of a specific category of `endogenous' genes, the glucocorticoid responsive genes. This genetic up-regulation was induced in only cancer cells by modified GNP-mediated transcriptional activation of its cytoplasmic receptor, glucocorticoid receptor (GR). Normal cells and their GR remained primarily unperturbed by this GNP-formulation. The most potent gene up-regulating GNP-formulation down-regulated a cancer-specific proliferative signal, phospho-Akt in cancer cells, which accompanied retardation of tumor growth in the murine melanoma model. We show that GR-targeted GNPs may find potential use in the targeting and modulation of genetic information in cancer towards developing novel anticancer therapeutics.Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied on the delivery of `exogenous' genes invoking gene knockdown or replacement. Practically, there are no instances for the nanoparticle-mediated promoter regulation of `endogenous' genes, more so, as a cancer selective phenomenon. In this regard, we report the development of a simple, easily modifiable GNP-formulation, which promoted/up-regulated the expression of a specific category of `endogenous' genes, the glucocorticoid responsive genes. This genetic up-regulation was induced in only cancer cells by modified GNP-mediated transcriptional activation of its cytoplasmic receptor, glucocorticoid receptor (GR). Normal cells and their GR remained primarily unperturbed by this GNP-formulation. The most potent gene up-regulating GNP-formulation down-regulated a cancer-specific proliferative signal, phospho-Akt in cancer cells, which accompanied retardation of tumor growth in the murine melanoma model. We show that GR-targeted GNPs may find potential use in the targeting and modulation of genetic information in cancer towards developing novel anticancer therapeutics. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr00974f

Thiolated chitosans: useful excipients for oral drug delivery.

PubMed

Werle, Martin; Bernkop-Schnürch, Andreas

2008-03-01

To improve the bioavailability of orally administered drugs, formulations based on polymers are of great interest for pharmaceutical technologists. Thiolated chitosans are multifunctional polymers that exhibit improved mucoadhesive, cohesive and permeation-enhancing as well as efflux-pump-inhibitory properties. They can be synthesized by derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions. Various data gained in-vitro as well as in-vivo studies clearly demonstrate the potential of thiolated chitosans for oral drug delivery. Within the current review, the synthesis and characterization of thiolated chitosans so far developed is summarized. Features of thiolated chitosans important for oral drug delivery are discussed as well. Moreover, different formulation approaches, such as matrix tablets and micro-/nanoparticles, as well as the applicability of thiolated chitosans for the oral delivery of various substance classes including peptides and efflux pump substrates, are highlighted.

ICP-MS analysis of lanthanide-doped nanoparticles: A quantitative and multiplexing approach to investigate biodistribution, blood clearance, and targeting

NASA Astrophysics Data System (ADS)

Crayton, Samuel

The rapidly progressing field of nanotechnology promises to revolutionize healthcare in the 21st century, with applications in the prevention, diagnosis, and treatment of a wide range of diseases. However, before nanoparticulate agents can be brought into clinical use, they must first be developed, optimized, and evaluated in animal models. In the typical pre-clinical paradigm, almost all of the optimization is done at the in vitro level, with only a few select agents reaching the level of animal studies. Since only one experimental nanoparticle formulation can be investigated in a single animal, and in vivo experiments have relatively higher complexity, cost, and time requirements, it is not feasible to evaluate a very large number of agents at the in vivo stage. A major drawback of this approach, however, is that in vitro assays do not always accurately predict how a nanoparticle will perform in animal studies. Therefore, a method that allows many agents to be evaluated in a single animal subject would allow for much more efficient and predictive optimization of nanoparticles. We have found that by incorporating lanthanide tracer metals into nanoparticle formulations, we are successfully able to use inductively coupled plasma mass spectrometry (ICP-MS) to quantitatively determine a nanoparticle's blood clearance kinetics, biodistribution, and tumor delivery. This approach was applied to evaluate both passive and active tumor targeting, as well as metabolically directed targeting of nanoparticles to low pH tumor microenvironments. Importantly, we found that these in vivo measurements could be made for many nanoparticle formulations simultaneously, in single animals, due to the high-order multiplexing capability of mass spectrometry. This approach allowed for efficient and reproducible comparison of performance between different nanoparticle formulations, by eliminating the effects of subject-to-subject variability. In the future, we envision that this "higher-throughput" evaluation of agents at the in vivo level, using ICP-MS multiplex analysis, will constitute a powerful tool to accelerate pre-clinical evaluation of nanoparticles in animal models.

Preparation of psoralen polymer-lipid hybrid nanoparticles and their reversal of multidrug resistance in MCF-7/ADR cells.

PubMed

Huang, Qingqing; Cai, Tiange; Li, Qianwen; Huang, Yinghong; Liu, Qian; Wang, Bingyue; Xia, Xi; Wang, Qi; Whitney, John C C; Cole, Susan P C; Cai, Yu

2018-11-01

Multidrug resistance (MDR) is the leading cause of failure for breast cancer in the clinic. Thus far, polymer-lipid hybrid nanoparticles (PLN) loaded chemotherapeutic agents has been used to overcome MDR in breast cancer. In this study, we prepared psoralen polymer-lipid hybrid nanoparticles (PSO-PLN) to reverse drug resistant MCF-7/ADR cells in vitro and in vivo. PSO-PLN was prepared by the emulsification evaporation-low temperature solidification method. The formulation, water solubility and bioavailability, particle size, zeta potential and entrapment efficiency, and in vitro release experiments were optimized in order to improve the activity of PSO to reverse MDR. Optimal formulation: soybean phospholipids 50 mg, poly(lactic-co-glycolic) acid (PLGA) 15 mg, PSO 3 mg, and Tween-80 1%. The PSO-PLN possessed a round appearance, uniform size, exhibited no adhesion. The average particle size was 93.59 ± 2.87 nm, the dispersion co-efficient was 0.249 ± 0.06, the zeta potential was 25.47 ± 2.84 mV. In vitro analyses revealed that PSO resistance index was 3.2, and PSO-PLN resistance index was 5.6, indicating that PSO-PLN versus MCF-7/ADR reversal effect was significant. Moreover, PSO-PLN is somewhat targeted to the liver, and has an antitumor effect in the xenograft model of drug-resistant MCF-7/ADR cells. In conclusion, PSO-PLN not only reverses MDR but also improves therapeutic efficiency by enhancing sustained release of PSO.

Development, optimization and characterization of glycyrrhetinic acid-chitosan nanoparticles of atorvastatin for liver targeting.

PubMed

Rohilla, Raman; Garg, Tarun; Bariwal, Jitender; Goyal, Amit K; Rath, Goutam

2016-09-01

Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-targeted carrier for drug delivery. In this study, nanoparticles were prepared by ionic gelation process, and glycyrrhetinic acid act as the targeting ligand. The structure of the product was confirmed by IR and NMR techniques. The main aim of this study was to deliver atorvastatin directly to the liver by using same conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high dose. Characterization of the developed formulation was performed by differential scanning calorimetry, particle size measurements and cellular uptake studies. Release profile, pharmacokinetics studies and organ distribution studies showed that developed formulation shows a relative higher liver uptake. The optimized formulation showed increased plasma concentration than the CTS nanoparticles as well as plain drug and the accumulation in the liver was nearly 2.59 times more than that of obtained with the CTS nanoparticles. Pharmaceutical and pharmacological indicators suggested that the proposed strategy can be successfully utilized for liver targeting of therapeutics.

Disregarded Effect of Biological Fluids in siRNA Delivery: Human Ascites Fluid Severely Restricts Cellular Uptake of Nanoparticles.

PubMed

Dakwar, George R; Braeckmans, Kevin; Demeester, Joseph; Ceelen, Wim; De Smedt, Stefaan C; Remaut, Katrien

2015-11-04

Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the clinic. While numerous successful in vitro siRNA delivery stories exist in reduced-protein conditions, most studies so far overlook the influence of the biological fluids present in the in vivo environment. In this study, we compared the transfection efficiency of liposomal formulations in Opti-MEM (low protein content, routinely used for in vitro screening) and human undiluted ascites fluid obtained from a peritoneal carcinomatosis patient (high protein content, representing the in vivo situation). In Opti-MEM, all formulations are biologically active. In ascites fluid, however, the biological activity of all lipoplexes is lost except for lipofectamine RNAiMAX. The drop in transfection efficiency was not correlated to the physicochemical properties of the nanoparticles, such as premature siRNA release and aggregation of the nanoparticles in the human ascites fluid. Remarkably, however, all of the formulations except for lipofectamine RNAiMAX lost their ability to be taken up by cells following incubation in ascites fluid. To take into account the possible effects of a protein corona formed around the nanoparticles, we recommend always using undiluted biological fluids for the in vitro optimization of nanosized siRNA formulations next to conventional screening in low-protein content media. This should tighten the gap between in vitro and in vivo performance of nanoparticles and ensure the optimal selection of nanoparticles for further in vivo studies.

Synthesis and characterization of multifunctional hybrid-polymeric nanoparticles for drug delivery and multimodal imaging of cancer

PubMed Central

Tng, Danny Jian Hang; Song, Peiyi; Lin, Guimiao; Soehartono, Alana Mauluidy; Yang, Guang; Yang, Chengbin; Yin, Feng; Tan, Cher Heng; Yong, Ken-Tye

2015-01-01

In this study, multifunctional hybrid-polymeric nanoparticles were prepared for the treatment of cultured multicellular tumor spheroids (MCTS) of the PANC-1 and MIA PaCa-2 pancreatic carcinoma cell lines. To synthesize the hybrid-polymeric nanoparticles, the poly lactic-co-glycolic acid core of the particles was loaded with Rhodamine 6G dye and the chemotherapeutic agent, Paclitaxel, was incorporated into the outer phospholipid layer. The surface of the nanoparticles was coated with gadolinium chelates for magnetic resonance imaging applications. This engineered nanoparticle formulation was found to be suitable for use in guided imaging therapy. Specifically, we investigated the size-dependent therapeutic response and the uptake of nanoparticles that were 65 nm, 85 nm, and 110 nm in size in the MCTS of the two pancreatic cancer cell lines used. After 24 hours of treatment, the MCTS of both PANC-1 and MIA PaCa-2 cell lines showed an average increase in the uptake of 18.4% for both 65 nm and 85 nm nanoparticles and 24.8% for 110 nm nanoparticles. Furthermore, the studies on therapeutic effects showed that particle size had a slight influence on the overall effectiveness of the formulation. In the MCTS of the MIA PaCa-2 cell line, 65 nm nanoparticles were found to produce the greatest therapeutic effect, whereas 12.8% of cells were apoptotic of which 11.4% of cells were apoptotic for 85 nm nanoparticles and 9.79% for 110 nm nanoparticles. Finally, the study conducted in vivo revealed the importance of nanoparticle size selection for the effective delivery of drug formulations to the tumors. In agreement with our in vitro results, excellent uptake and retention were found in the tumors of MIA PaCa-2 tumor-bearing mice treated with 110 nm nanoparticles. PMID:26396511

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.

Colloid particle formulations for antimicrobial applications.

PubMed

Halbus, Ahmed F; Horozov, Tommy S; Paunov, Vesselin N

2017-11-01

Colloidal particles are being extensively studied in various antimicrobial applications due to their small size to volume ratio and ability to exhibit a wide spectrum of antibacterial, antifungal, antialgal and antiviral action. The present review focuses on various nanoparticles (NPs) of inorganic, organic and hybrid materials, and discusses some of the methods for their preparation as well as mechanisms of their antimicrobial action. We consider the antimicrobial applications of metal oxide nanoparticles (ZnO, MgO, CuO, Cu 2 O, Al 2 O 3 , TiO 2 , CeO 2 and Y 2 O 3 ), metal nanoparticles (NPs), such as copper, silver and gold, metal hydroxide NPs such as Mg(OH) 2 as well as hybrid NPs made from biodegradable materials, such as chitosan, lignin and dextran, loaded with other antimicrobial agents. Recent developments for targeted delivery of antimicrobials by using colloid antibodies for microbial cell shape and surface recognition are also discussed. We also consider recent advances in the functionalization of nanoparticles and their potential antimicrobial applications as a viable alternative of conventional antibiotics and antiseptic agents which can help to tackle antimicrobial resistance. The review also covers the recently developed environmentally benign NPs (EbNPs) as a "safer-by-design" green chemistry solution of the post use fate of antimicrobial nanomaterials. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel patternable and conducting metal-polymer nanocomposites: a step towards advanced mutlifunctional materials

NASA Astrophysics Data System (ADS)

Rodríguez-Cantó, Pedro J.; Martínez-Marco, Mariluz; Abargues, Rafael; Latorre-Garrido, Victor; Martínez-Pastor, Juan P.

2013-03-01

In this work, we present a novel patternable conducting nanocomposite containing gold nanoparticles. Here, the in-situ polymerization of 3T is carried out using HAuCl4 as oxidizing agent inside PMMA as host matrix. During the bake step, the gold salt is also reduced from Au(III) to Au(0) generating Au nanoparticles in the interpenetrating polymer network (IPN) system. We found that this novel multifunctional resist shows electrical conductivity and plasmonic properties as well as potential patterning capability provided by the host matrix. The resulting nanocomposite has been investigated by TEM and UV-Vis spectroscopy. Electrical characterization was also conducted for different concentration of 3T and Au(III) following a characteristic percolation behaviour. Conductivities values from 10-5 to 10 S/cm were successfully obtained depending on the IPN formulation. Moreover, The Au nanoparticles generated exhibited a localized surface plasmon resonance at around 520 nm. This synthetic approach is of potential application to modify the conductivity of numerous insulating polymers and synthesize Au nanoparticles preserving to some extent their physical and chemical properties. In addition, combination of optical properties (Plasmonics), electrical, and lithographic capability in the same material allows for the design of materials with novel functionalities and provides the basis for next generation devices.

Hyaluronan- and heparin-reduced silver nanoparticles with antimicrobial properties

PubMed Central

Kemp, Melissa M; Kumar, Ashavani; Clement, Dylan; Ajayan, Pulickel; Mousa, Shaker

2009-01-01

Aims Silver nanoparticles exhibit unique antibacterial properties that make these ideal candidates for biological and medical applications. We utilized a clean method involving a single synthetic step to prepare silver nanoparticles that exhibit antimicrobial activity. Materials & methods These nanoparticles were prepared by reducing silver nitrate with diaminopyridinylated heparin (DAPHP) and hyaluronan (HA) polysaccharides and tested for their efficacy in inhibiting microbial growth. Results & discussion The resulting silver nanoparticles exhibit potent antimicrobial activity against Staphylococcus aureus and modest activity against Escherichia coli. Silver–HA showed greater antimicrobial activity than silver–DAPHP, while silver–glucose nanoparticles exhibited very weak antimicrobial activity. Neither HA nor DAPHP showed activity against S. aureus or E. coli. Conclusion These results suggest that DAPHP and HA silver nanoparticles have potential in antimicrobial therapeutic applications. PMID:19505245

SYK as a New Therapeutic Target in B-Cell Precursor Acute Lymphoblastic Leukemia

PubMed Central

Uckun, Fatih M.; Qazi, Sanjive

2014-01-01

The identification of SYK as a master regulator of apoptosis controlling the activation of the PI3-K/AKT, NFκB, and STAT3 pathways—three major anti-apoptotic signaling pathways in B-lineage leukemia/lymphoma cells—prompts the hypothesis that rationally designed inhibitors targeting SYK may overcome the resistance of malignant B-lineage lymphoid cells to apoptosis and thereby provide the foundation for more effective multi-modality treatment regimens for poor prognosis B-precursor acute lymphoblastic leukemia (BPL). In recent preclinical proof-of-concept studies, a liposomal nanoparticle (LNP) formulation of a SYK substrate-binding site inhibitor, known as C61, has been developed as a nanomedicine candidate against poor prognosis and relapsed BPL. This nanoscale formulation of C61 exhibited a uniquely favorable pharmacokinetics and safety profile in mice, induced apoptosis in radiation-resistant primary leukemic cells taken directly from BPL patients as well as in vivo clonogenic BPL xenograft cells, destroyed the leukemic stem cell fraction of BPL blasts, and exhibited potent in vivo anti-leukemic activity in xenograft models of aggressive BPL. Further development of C61-LNP may provide the foundation for new and effective treatment strategies against therapy-refractory BPL. PMID:24851191

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.

Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia.

PubMed

Hamishehkar, Hamed; Ghanbarzadeh, Saeed; Sepehran, Sasan; Javadzadeh, Yousef; Adib, Zahra Mardhiah; Kouhsoltani, Maryam

2016-01-01

Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia. The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia. Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively. The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug. It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia.

Assessing the heterogeneity level in lipid nanoparticles for siRNA delivery: size-based separation, compositional heterogeneity, and impact on bioperformance.

PubMed

Zhang, Jingtao; Pei, Yi; Zhang, Hangchun; Wang, Lei; Arrington, Leticia; Zhang, Ye; Glass, Angela; Leone, Anthony M

2013-01-07

A primary consideration when developing lipid nanoparticle (LNP) based small interfering RNA (siRNA) therapeutics is formulation polydispersity or heterogeneity. The level of heterogeneity of physicochemical properties within a pharmaceutical batch could greatly affect the bioperformance, quality, and ability of a manufacturer to consistently control and reproduce the formulations. This article studied the heterogeneity in the size, composition, and in vitro performance of siRNA containing LNPs, by conducting preparative scale fractionation using a sephacryl S-1000 based size-exclusion chromatography (SEC) method. Eight LNPs with size in the range of 60-190 nm were first evaluated by the SEC method for size polydispersity characterization, and it was found that LNPs in the range of 60-150 nm could be well-resolved. Two LNPs (LNP A and LNP B) with similar bulk properties were fractionated, and fractions were studied in-depth for potential presence of polydispersity in size, composition, and in vitro silencing, as well as cytotoxicity. LNP A was deemed to be monodisperse following results of a semipreparative SEC fractionation that showed similar size, chemical composition, in vitro silencing activity, and cytotoxicity across the fractions. Therefore, LNP A represents a relatively homogeneous formulation and offers less of a challenge in its pharmaceutical development. In contrast, LNP B fractions were shown to be significantly more polydisperse in size distribution. Interestingly, LNP B SEC fractions also exhibited profound compositional variations (e.g., 5 fold difference in N/P ratio and 3 fold difference in lipid composition) along with up to 40 fold differences in the in vitro silencing activity. The impact of LNP size and formulation composition on in vitro performance is also discussed. The present results demonstrate the complexity and potential for presence of heterogeneity in LNP-based siRNA drug products. This underscores the need for tools that yield a detailed characterization of LNP formulations. This capability in tandem with the pursuit of improved formulation and process design can lead to more facile development of LNP-based siRNA pharmaceuticals of higher quality.

Finasteride topical delivery systems for androgenetic alopecia.

PubMed

Khan, Muhammad Zia Ullah; Khan, Shujaat Ali; Ubaid, Muhammad; Shah, Aamna; Kousar, Rozina; Murtaza, Ghulam

2018-01-23

Androgenetic alopecia, generally recognized as male pattern baldness, is a gradually developing medical and physiological change, which is manifested by continuous hair-loss from scalp. Finasteride (4-aza-3-oxosteroid) is a potent anti-baldness compound that selectively and competitively inhibits the 5α-reductase isoenzymes. Prolonged oral use of finasteride leads to the emergence of sexual disorders including decrease in libido, gynecomastia, erectile dysfunction, ejaculation disorder, orgasm disorders and mood disturbances. Since, hair follicles widely home in 5α-reductase, topical formulations of finasteride in comparison to its oral formulations are expected to potentially reduce its systemic adverse effects. The analysis of literature has revealed some delivery systems developed for the enhanced and localized penetration of finasteride into the skin. These finasteride delivery systems include polymersomes, vesicular nanocarriers, vesicular ethosomal carriers, liposomes and niosomes, liquid crystalline nanoparticles, topical solutions and gels. The aim of this review article is to briefly amass all literature on topical delivery of finasteride to elaborate best dosage form, i.e. formulation having maximum permeation rate. This study will serve as a future perspective regarding topical delivery of finasteride. The literature analysis has exhibited that most of the previous investigators have used propylene glycol in their finasteride-loaded topical formulations, while poloxamer P407, monoolein, transcutol P and choline was used in few formulations. Moreover among all drug delivery systems, finasteride liposomal gel system consisting of 2% methyl cellulose and gel system containing poloxamer P407 exhibited the highest flux with a value of 28.4 ± 1.3 µg/cm2h and 23.1 ± 1.4 µg/cm2h, respectively. Several topical drug delivery techniques such as topical microneedles, aerosol foams, nanoemulsions, microsponges, and emulsifier free formulations, fullerenes, ointments, pastes, creams, gel and lotions are still to be worthy regarding finasteride topical delivery in future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Nanoparticle albumin-bound paclitaxel: a novel Cremphor-EL-free formulation of paclitaxel.

PubMed

Stinchcombe, Thomas E

2007-08-01

Standard formulation paclitaxel requires the use of solvents, such as Cremphor-EL, which contribute to some of the toxicities commonly associated with paclitaxel-based therapy. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel solvent-free formulation of paclitaxel. The formulation is prepared by high-pressure homogenization of paclitaxel in the presence of serum albumin into a nanoparticle colloidal suspension. The human albumin-stabilized paclitaxel particles have an average size of 130 nm. Nab-paclitaxel has several practical advantages over Cremphor-EL-paclitaxel, including a shorter infusion time (30 min) and no need for premedications for hypersensitivity reactions. The nab-paclitaxel formulation eliminates the impact of Cremphor-EL on paclitaxel pharmacokinetics and utilizes the endogenous albumin transport mechanisms to concentrate nab-paclitaxel within the tumor. A recent Phase III trial compared nab- and Cremphor-EL-paclitaxel in patients with metastatic breast cancer. Patients treated with nab-paclitaxel experienced a higher response, longer time to tumor progression and, in patients receiving second-line or greater therapy, a longer median survival. Patients treated with nab-paclitaxel had a significantly lower rate of severe neutropenia and a higher rate of sensory neuropathy. The preclinical and clinical data indicate that the nab-paclitaxel formulation has significant advantages over Cremphor-EL-paclitaxel.

Co-localization of fluorescent labeled lipid nanoparticles with specifically tagged subcellular compartments by single particle tracking at low nanoparticle to cell ratios.

PubMed

Tiffany, Matthew; Szoka, Francis C

2016-11-01

We utilized quantitative high-resolution single particle tracking to study the internalization and endosomal sorting of lipid nanoparticles (LNPs) by HeLa cells in vitro to gain a better understanding of how cells process LNPs that are used for siRNA delivery. We compared the trafficking of three formulations that have been demonstrated to deliver siRNA into cells. They were composed of either a tritratable anionic lipid, formulation of cholesterol hemisuccinate (CHEMS), or a titratatable cationic lipid formulation of 1,2-dilinoleyloxy-3-dimethylaminopropane (DLinDMA) or a non-titratable cationic formulation lipid formulation of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). They also contained either a substantial percentage of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) or cholesterol and 5 mole percent 1,2-dimyristoyl-sn-glycerol-[methoxy(polyethylene glycol)-2000 (PEG-DMG). We optically measured the endosomal pH experienced by individual LNPs, observed the internalization pathways used and tracked the particles as they co-localized with fluorescent protein tags on compartment-specific proteins, during endosomal sorting to the lysosome. The data revealed significant differences in the accumulation in subcellular compartments among the three formulations, which help to explain the observed effects LNP composition exerts on in vitro delivery efficiency.

Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.

PubMed

Elsayed, Amani; Al-Remawi, Mayyas; Qinna, Nidal; Farouk, Asim; Al-Sou'od, Khaldoun A; Badwan, Adnan A

2011-09-01

The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.

Interference Lithography for Optical Devices and Coatings

DTIC Science & Technology

2010-01-01

semiconductor quantum dots. J. Chem. Phys. 2004, 121, 7421. 100. Jeon, S.; Braun, P. V., Hydrothermal Synthesis of Er-Doped Luminescent TiO2 Nanoparticles ...Silica Nanoparticle Synthesis .....................................................................23 2.2.2 Polymer Matrix Formulation...41 CHAPTER 3: NANOPARTICLE SYNTHESIS , FUNCTIONALIZATION, AND INCORPORATION INTO

Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities

PubMed Central

Mangal, Sharad; Gao, Wei; Li, Tonglei; Zhou, Qi (Tony)

2017-01-01

Lung cancer is the second most prevalent and the deadliest among all cancer types. Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival. Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects, which are often attributed to the distribution of anticancer drugs to non-targeted sites. In contrast, inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the anti-tumor effect while alleviating systemic adverse effects. Preliminary studies in animals and humans have suggested that most inhaled chemotherapies are tolerable with manageable pulmonary adverse effects, including cough and bronchospasm. Promoting the deposition of anticancer drugs in tumorous cells and minimizing access to healthy lung cells can further augment the efficacy and reduce the risk of local toxicities caused by inhaled chemotherapy. Sustained release and tumor localization characteristics make nanoparticle formulations a promising candidate for the inhaled delivery of chemotherapeutic agents against lung cancers. However, the physiology of respiratory tracts and lung clearance mechanisms present key barriers for the effective deposition and retention of inhaled nanoparticle formulations in the lungs. Recent research has focused on the development of novel formulations to maximize lung deposition and to minimize pulmonary clearance of inhaled nanoparticles. This article systematically reviews the challenges and opportunities for the pulmonary delivery of nanoparticle formulations for the treatment of lung cancers. PMID:28504252

Preparation and in Vitro Analysis of Human Serum Albumin Nanoparticles Loaded with Anthracycline Derivatives.

PubMed

Kimura, Kotaro; Yamasaki, Keishi; Nakamura, Hideaki; Haratake, Mamoru; Taguchi, Kazuaki; Otagiri, Masaki

2018-01-01

Nanoparticles prepared using human serum albumin (HSA) have emerged as versatile carriers for improving the pharmacokinetic profile of drugs. The desolvation of HSA using ethanol followed by stabilization through crosslinking with glutaraldehyde is a common technique for preparing HSA nanoparticles, but our knowledge concerning the characteristics (or functions) of HSA nanoparticles and their efficiency when loaded with drugs is limited. To address this issue in more detail, we prepared anthracycline-loaded HSA nanoparticles. Doxorubicin-loaded HSA nanoparticles with a size similar to doxorubicin-unloaded particles could be prepared by desolvating at a higher pH (8-9), and the size (100-150 nm) was optimum for delivery to tumor tissues. Using this procedure, HSA nanoparticles were loaded with other anthracycline derivatives, and all showed cytotoxicity in cancer cells. However, the efficiency of drug loading and dissolution rate were different among them possibly due to the differences in the type of association of the drugs on nanoparticles (doxorubicin and daunorubicin; covalently bound to nanoparticles, pirarubicin; both covalently bound to and adsorbed on nanoparticles, aclarubicin; adsorbed on nanoparticles). Since the formulation of such drug-loaded HSA nanoparticles should be modified for efficient delivery to tumors, the findings reported herein provide the useful information for optimizing the formulation and the production process for the HSA nanoparticles using a desolvation technique.

Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution.

PubMed

Tran, Nhiem; Bye, Nicole; Moffat, Bradford A; Wright, David K; Cuddihy, Andrew; Hinton, Tracey M; Hawley, Adrian M; Reynolds, Nicholas P; Waddington, Lynne J; Mulet, Xavier; Turnley, Ann M; Morganti-Kossmann, M Cristina; Muir, Benjamin W

2017-02-01

Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapid treatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes and hexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. This is the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magnetic resonance (MR) imaging modalities in cubosomes and hexosomes. High-throughput screening was used to rapidly optimize formulations with desirable nano-architectures and low in vitro cytotoxicity. The dual-modal imaging nanoparticles in vivo biodistribution and organ specific contrast enhancement were then studied. The NIRF in vivo imaging results indicated accumulation of both cubosomes and hexosomes in the liver and spleen of mice up to 20h post-injection. Remarkably, the biodistribution of the nanoparticle formulations was affected by the mesophase (i.e. cubic or hexagonal), a finding of significant importance for the future use of these compounds, with hexosomes showing higher accumulation in the spleen than the liver compared to cubosomes. Furthermore, in vivo MRI data of animals injected with either type of lyotropic liquid crystal nanoparticle displayed enhanced contrast in the liver and spleen. Copyright © 2016 Elsevier B.V. All rights reserved.

Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

PubMed

Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

2016-04-01

The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Dual sustained release delivery system for multiple route therapy of an antiviral drug.

PubMed

Ramyadevi, D; Sandhya, P

2014-06-01

The first successful molecule against herpes infections was Acyclovir, which competes with new generations in the market, with its potential activity. The major physicochemical constraints and pharmacokinetics of Acyclovir such as low solubility, poor permeability, less half-life, high dose has initiated many researchers to develop diverse modified release dosage forms. The objective of this work was to design polymeric nanoparticles of Acyclovir and then incorporate the drug-loaded nanoparticles within an in situ gelling system to provide dual sustained release effect, whereby the duration of action and bioavailability through different routes of administration could be improved. The formulation was designed through 3(2) factorial design, first developing the nanoparticles using Polycaprolactone and Pluronic F127 by Solvent evaporation process, followed by dispersion of the suspended nanoparticles into thermosensitive in situ gelling system of Pluronic F127 with Carbopol. The characterization of the nanoparticles and its sol-gel system performed through zeta sizer, SEM, XRD, TG-DSC, FTIR and rheology helped to optimize the formulation. The drug release could be sustained to 60% and 30% at eight hours, for the nanoparticles and their in situ gel systems, respectively, with non-Fickian diffusion mechanism of drug release. The test for % cell viability with NIH3T3 cell line revealed low level of toxicity for the nanoparticles. The statistical significance obtained for the trail formulations experimentally proved its suitability for this dosage form design to achieve desired level of drug release.

Aerosolized Antimicrobial Agents Based on Degradable Dextran Nanoparticles Loaded with Silver Carbene Complexes

PubMed Central

Ornelas-Megiatto, Cátia; Shah, Parth N.; Wich, Peter R.; Cohen, Jessica L.; Tagaev, Jasur A.; Smolen, Justin A.; Wright, Brian D.; Panzner, Matthew J.; Youngs, Wiley J.; Fréchet, Jean M. J.; Cannon, Carolyn L.

2012-01-01

Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH2Cl2 (organic): PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery. PMID:23025592

Aerosolized antimicrobial agents based on degradable dextran nanoparticles loaded with silver carbene complexes.

PubMed

Ornelas-Megiatto, Cátia; Shah, Parth N; Wich, Peter R; Cohen, Jessica L; Tagaev, Jasur A; Smolen, Justin A; Wright, Brian D; Panzner, Matthew J; Youngs, Wiley J; Fréchet, Jean M J; Cannon, Carolyn L

2012-11-05

Degradable acetalated dextran (Ac-DEX) nanoparticles were prepared and loaded with a hydrophobic silver carbene complex (SCC) by a single-emulsion process. The resulting particles were characterized for morphology and size distribution using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The average particle size and particle size distribution were found to be a function of the ratio of the organic phase to the surfactant containing aqueous phase with a 1:5 volume ratio of Ac-DEX CH(2)Cl(2) (organic):PBS (aqueous) being optimal for the formulation of nanoparticles with an average size of 100 ± 40 nm and a low polydispersity. The SCC loading was found to increase with an increase in the SCC quantity in the initial feed used during particle formulation up to 30% (w/w); however, the encapsulation efficiency was observed to be the best at a feed ratio of 20% (w/w). In vitro efficacy testing of the SCC loaded Ac-DEX nanoparticles demonstrated their activity against both Gram-negative and Gram-positive bacteria; the nanoparticles inhibited the growth of every bacterial species tested. As expected, a higher concentration of drug was required to inhibit bacterial growth when the drug was encapsulated within the nanoparticle formulations compared with the free drug illustrating the desired depot release. Compared with free drug, the Ac-DEX nanoparticles were much more readily suspended in an aqueous phase and subsequently aerosolized, thus providing an effective method of pulmonary drug delivery.

Formulation, Characterization and Pulmonary Deposition of Nebulized Celecoxib Encapsulated Nanostructured Lipid Carriers

PubMed Central

Patlolla, Ram R.; Chougule, Mahavir; Patel, Apurva R.; Jackson, Tanise; Tata, Prasad NV; Singh, Mandip

2010-01-01

The aim of the current study was to encapsulate celecoxib (Cxb) in the Nanostructured Lipid Carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for physical and aerosol properties. In-vitro cytotoxicity studies were performed with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC and Cxb solution (Cxb-Soln) formulations were determined using Inexpose™ system and Pari LC star jet nebulizer. The particle size and entrapment efficiency of Cxb-NLC formulation were 217 ± 20 nm and > 90%, respectively. The Cxb-NLC released the drug in controlled fashion, and in vitro aersolization of Cxb-NLC formulation showed FPF of 75.6 ± 4.6 %, MMAD of 1.6 ±0.13 μm and GSD of 1.2 ± 0.21. Cxb-NLC showed dose and time dependent cytotoxicity against A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUCt/D in lung tissues compared to Cxb-Soln. The systemic clearance of Cxb-NLC was slower (0.93 L/h) compared to Cxb-Soln (20.03 L/h). Cxb encapsulated NLC were found to be stable and aerodynamic properties were within the respirable limits. Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to solution formulation which will potentially lead to better patient compliance with minimal dosing intervals. PMID:20153385

Cryo-electron tomography investigation of serum albumin-camouflaged tobacco mosaic virus nanoparticles.

PubMed

Gulati, Neetu M; Pitek, Andrzej S; Steinmetz, Nicole F; Stewart, Phoebe L

2017-03-09

Nanoparticles offer great potential in drug delivery and imaging, but shielding strategies are necessary to increase circulation time and performance. Structure-function studies are required to define the design rules to achieve effective shielding. With several formulations reaching clinical testing and approval, the ability to assess and detail nanoparticle formulations at the single particle level is becoming increasingly important. To address this need, we use cryo-electron tomography (cryo-ET) to investigate stealth-coated nanoparticles. As a model system, we studied the soft matter nanotubes formed by tobacco mosaic virus (TMV) coated with human serum albumin (SA) stealth proteins. Cryo-ET and subtomogram averaging allow for visualization of individual SA molecules and determination of their orientations relative to the TMV surface, and also for measurement of the surface coverage provided by added stealth proteins. This information fills a critical gap in the understanding of the structural morphology of stealth-coated nanoparticles, and therefore cryo-ET may play an important role in guiding the development of future nanoparticle-based therapeutics.

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.

Improved Poly (D,L-lactide) nanoparticles-based formulation for hair follicle targeting.

PubMed

Fernandes, B; Silva, R; Ribeiro, A; Matamá, T; Gomes, A C; Cavaco-Paulo, A M

2015-06-01

Hair follicles are widely recognized as the preferential target and site of accumulation for nanoparticles after topical application. This feature is of particular importance for hair cosmetics, having the potential to refine the treatment of several hair follicle-related disorders. The aim of this work was to improve the preparation of Poly (D,L-lactide) (PLA) nanoparticles for in vivo follicular target and drug delivery. Envisaging a future industrial scale-up of the process, nanoprecipitation method was used to prepare PLA nanoparticles: the effect of several processing parameters on their properties was examined and the yield of nanoparticles formation determined. Encapsulation efficiencies and in vitro release profiles of lipophilic and hydrophilic model compounds were also assessed. In vitro cytotoxicity and ex vivo penetration studies were performed on a reference skin cell line (NCTC2455, human skin keratinocytes) and porcine skin, respectively. Using acetone : ethanol (50 : 50, v/v) as the solvent phase, 0.6% (w/w) of Pluronic(®) F68 as a surfactant agent and agitation to mix the solvent and non-solvent phases, a monodispersed population of non-cytotoxic spherical nanoparticles of approximately 150 nm was obtained. The yield of nanoparticles for this formulation was roughly 90%. After encapsulation of model compounds, no significant changes were found in the properties of particles and the entrapment efficiencies were above 80%. The release kinetics of dyes from PLA nanoparticles indicate an anomalous transport mechanism (diffusion and polymer degradation) for Nile Red (lipophilic) and a Fickian diffusion of first order for fluorescein 5(6)-isothiocyanate (hydrophilic). Ex vivo skin penetration studies confirmed the presence of nanoparticles along the entire follicular ducts. The optimized method allows the preparation of ideal PLA nanoparticles-based formulations for hair follicle targeting. PLA nanoparticles can effectively transport and release lipophilic and hydrophilic compounds into the hair follicles, and the yields obtained are acceptable for industrial purposes. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

A review of the efficacy and safety of nanoparticle-based oral insulin delivery systems.

PubMed

Card, Jeffrey W; Magnuson, Bernadene A

2011-12-01

Nanotechnology is providing new and innovative means to detect, diagnose, and treat disease. In this regard, numerous nanoparticle-based approaches have been taken in an effort to develop an effective oral insulin therapy for the treatment of diabetes. This review summarizes efficacy data from studies that have evaluated oral insulin therapies in experimental models. Also provided here is an overview of the limited safety data that have been reported in these studies. To date, the most promising approaches for nanoparticle-based oral insulin therapy appear to involve the incorporation of insulin into complex multilayered nanoparticles that are mucoadhesive, biodegradable, biocompatible, and acid protected and into nanoparticles that are designed to take advantage of the vitamin B(12) uptake pathway. It is anticipated that the continued investigation and optimization of nanoparticle-based formulations for oral delivery of insulin will lead to a much sought-after noninvasive treatment for diabetes. Such investigations also may provide insight into the use of nanoparticle-based formulations for peptide- and protein-based oral treatment of other diseases and for various food-related purposes.

An investigation of in vivo wound healing activity of biologically synthesized silver nanoparticles

NASA Astrophysics Data System (ADS)

Kaler, Abhishek; Mittal, Amit Kumar; Katariya, Mahesh; Harde, Harshad; Agrawal, Ashish Kumar; Jain, Sanyog; Banerjee, Uttam Chand

2014-09-01

Therapeutic use of nano-silver is claimed to have reduced side effects and enhanced curative activity as compared to its ionic counterpart (silver ions). The present work aims to screen microbes for the synthesis of silver nanoparticles (AgNPs), to formulate the nano-silver-based Carbopol gel and evaluating its wound healing efficacy on rat model. The goal was to develop the topical formulation based on bio-nano-silver to control the infection and healing the wounds with higher efficacy. Procedure involved the use of Saccharomyces boulardii for the synthesis of silver nanoparticles in the size range of 3-10 nm and these nanoparticles were used for the preparation of Carbopol-based nano-silver gel. Highly stable Carbopol nanogel was developed with good rheological properties. The burn wound healing potential of this nano-silver gel was evaluated on SD rats via visual observation, transepidermal water loss and histology of skin. Excellent wound healing was observed with AgNPs. Biologically synthesized AgNPs-based nano-silver gel showed superior wound healing efficacy as compared to marketed formulations and silver ions.

Formulation Strategies to Improve the Bioavailability of Poorly Absorbed Drugs with Special Emphasis on Self-Emulsifying Systems

PubMed Central

Gupta, Shweta; Kesarla, Rajesh

2013-01-01

Poorly water-soluble drug candidates are becoming more prevalent. It has been estimated that approximately 60–70% of the drug molecules are insufficiently soluble in aqueous media and/or have very low permeability to allow for their adequate and reproducible absorption from the gastrointestinal tract (GIT) following oral administration. Formulation scientists have to adopt various strategies to enhance their absorption. Lipidic formulations are found to be a promising approach to combat the challenges. In this review article, potential advantages and drawbacks of various conventional techniques and the newer approaches specifically the self-emulsifying systems are discussed. Various components of the self-emulsifying systems and their selection criteria are critically reviewed. The attempts of various scientists to transform the liquid self-emulsifying drug delivery systems (SEDDS) to solid-SEDDS by adsorption, spray drying, lyophilization, melt granulation, extrusion, and so forth to formulate various dosage forms like self emulsifying capsules, tablets, controlled release pellets, beads, microspheres, nanoparticles, suppositories, implants, and so forth have also been included. Formulation of SEDDS is a potential strategy to deliver new drug molecules with enhanced bioavailability mostly exhibiting poor aqueous solubility. The self-emulsifying system offers various advantages over other drug delivery systems having potential to solve various problems associated with drugs of all the classes of biopharmaceutical classification system (BCS). PMID:24459591

Scalable organic solvent free supercritical fluid spray drying process for producing dry protein formulations.

PubMed

Nuchuchua, O; Every, H A; Hofland, G W; Jiskoot, W

2014-11-01

In this study, we evaluated the influence of supercritical carbon dioxide (scCO2) spray drying conditions, in the absence of organic solvent, on the ability to produce dry protein/trehalose formulations at 1:10 and 1:4 (w/w) ratios. When using a 4L drying vessel, we found that decreasing the solution flow rate and solution volume, or increasing the scCO2 flow rate resulted in a significant reduction in the residual water content in dried products (Karl Fischer titration). The best conditions were then used to evaluate the ability to scale the scCO2 spray drying process from 4L to 10L chamber. The ratio of scCO2 and solution flow rate was kept constant. The products on both scales exhibited similar residual moisture contents, particle morphologies (SEM), and glass transition temperatures (DSC). After reconstitution, the lysozyme activity (enzymatic assay) and structure (circular dichroism, HP-SEC) were fully preserved, but the sub-visible particle content was slightly increased (flow imaging microscopy, nanoparticle tracking analysis). Furthermore, the drying condition was applicable to other proteins resulting in products of similar quality as the lysozyme formulations. In conclusion, we established scCO2 spray drying processing conditions for protein formulations without an organic solvent that holds promise for the industrial production of dry protein formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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.

Preparation of HCPT-Loaded Nanoneedles with Pointed Ends for Highly Efficient Cancer Chemotherapy

NASA Astrophysics Data System (ADS)

Wu, Shichao; Yang, Xiangrui; Li, Yang; Wu, Hongjie; Huang, Yu; Xie, Liya; Zhang, Ying; Hou, Zhenqing; Liu, Xiangyang

2016-06-01

The high-aspect-ratio nanoparticles were proved to be internalized much more rapidly and efficiently by cancer cells than the nanoparticles with an equal aspect ratio. Herein, a kind of high-aspect ratio, pointed-end nanoneedles (NDs) with a high drug loading (15.04 %) and the prolonged drug release profile were fabricated with an anti-tumor drug—10-hydroxycamptothecin (HCPT)—via an ultrasound-assisted emulsion crystallization technique. It is surprising to see that the cellular internalization of NDs with an average length of 5 μm and an aspect ratio of about 12:1 was even much faster and higher than that of nanorods with the same size and the nanospheres with a much smaller size of 150 nm. The results further validated that cellular internalization of the nanoparticles exhibited a strong shape-dependent effect, and cellular uptake may favor the particles with sharp ends as well as a high-aspect ratio instead of particle size. The NDs with enhanced cytotoxicity would lead to a promising sustained local drug delivery system for highly efficient anticancer therapy. More importantly, the fabrication of NDs opens a door to design new formulations of nanoneedle drug delivery systems for highly efficient cancer.

“Click” Synthesis of Dextran Macrostructures for Combinatorial-Designed Self-Assembled Nanoparticles Encapsulating Diverse Anticancer Therapeutics

PubMed Central

Abeylath, Sampath C.; Amiji, Mansoor

2011-01-01

With the non-specific toxicity of anticancer drugs to healthy tissues upon systemic administration, formulations capable of enhanced selectivity in delivery to the tumor mass and cells are highly desirable. Based on the diversity of the drug payloads, we have investigated a combinatorial-designed strategy where the nano-sized formulations are tailored based on the physicochemical properties of the drug and the delivery needs. Individually functionalized C2 to C12 lipid-, thiol-, and poly(ethylene glycol) (PEG)-modified dextran derivatives were synthesized via “click” chemistry from O-pentynyl dextran and relevant azides. These functionalized dextrans in combination with anticancer drugs form nanoparticles by self-assembling in aqueous medium having PEG surface functionalization and intermolecular disulfide bonds. Using anticancer drugs with logP values ranging from −0.5 to 3.0, the optimized nanoparticles formulations were evaluated for preliminary cellular delivery and cytotoxic effects in SKOV3 human ovarian adenocarcinoma cells. The results show that with the appropriate selection of lipid-modified dextran, one can effectively tailor the self-assembled nano-formulation for intended therapeutic payload. PMID:21978947

Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems--enhancement of oral bioavailability.

PubMed

Hashem, Fahima M; Al-Sawahli, Majid M; Nasr, Mohamed; Ahmed, Osama A A

2015-01-01

Poor water solubility of a drug is a major challenge in drug delivery research and a main cause for limited bioavailability and pharmacokinetic parameters. This work aims to utilize custom fractional factorial design to assess the development of self-nanoemulsifying drug delivery systems (SNEDDS) and solid nanosuspensions (NS) in order to enhance the oral delivery of atorvastatin (ATR). According to the design, 14 experimental runs of ATR SNEDDS were formulated utilizing the highly ATR solubilizing SNEDDS components: oleic acid, Tween 80, and propylene glycol. In addition, 12 runs of NS were formulated by the antisolvent precipitation-ultrasonication method. Optimized formulations of SNEDDS and solid NS, deduced from the design, were characterized. Optimized SNEDDS formula exhibited mean globule size of 73.5 nm, zeta potential magnitude of -24.1 mV, and 13.5 μs/cm of electrical conductivity. Optimized solid NS formula exhibited mean particle size of 260.3 nm, 7.4 mV of zeta potential, and 93.2% of yield percentage. Transmission electron microscopy showed SNEDDS droplets formula as discrete spheres. The solid NS morphology showed flaky nanoparticles with irregular shapes using scanning electron microscopy. The release behavior of the optimized SNEDDS formula showed 56.78% of cumulative ATR release after 10 minutes. Solid NS formula showed lower rate of release in the first 30 minutes. Bioavailability estimation in Wistar albino rats revealed an augmentation in ATR bioavailability, relative to ATR suspension and the commercial tablets, from optimized ATR SNEDDS and NS formulations by 193.81% and 155.31%, respectively. The findings of this work showed that the optimized nanocarriers enhance the oral delivery and pharmacokinetic profile of ATR.

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.

Novel siRNA formulation to effectively knockdown mutant p53 in osteosarcoma.

PubMed

Kundu, Anup K; Iyer, Swathi V; Chandra, Sruti; Adhikari, Amit S; Iwakuma, Tomoo; Mandal, Tarun K

2017-01-01

The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318-1, a murine osteosarcoma cell line. The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP) and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer. A series of studies that include using different nanoparticles, different amount of siRNAs, cell numbers, incubation time, transfection media volume, and storage temperature was performed to optimize the gene silencing efficiency. Replacement of lipids by PLGA or PLGA-PEG decreased the particle size and overall cytotoxicity. Among all lipid-polymer nanoformulations, nanoparticles with 10% PLGA showed highest mutant p53 knockdown efficiency while maintaining higher cell viability when a nanoparticle to siRNA ratio equal to 6.8:0.66 and 75 nM siRNA was used. With long term storage the mutant p53 knockdown efficiency decreased to a greater extent. This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.

Formulation, optimization and characterization of cationic polymeric nanoparticles of mast cell stabilizing agent using the Box-Behnken experimental design.

PubMed

Gajra, Balaram; Patel, Ravi R; Dalwadi, Chintan

2016-01-01

The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. SCG-CSNPs exhibited particle size of 200.4 ± 4.06 nm and %EE of 62.68 ± 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in-vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs.

Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies

PubMed Central

Bhaskar, Kesavan; Anbu, Jayaraman; Ravichandiran, Velayutham; Venkateswarlu, Vobalaboina; Rao, Yamsani Madhusudan

2009-01-01

The aim of the study is to prepare aqueous dispersions of lipid nanoparticles – flurbiprofen solid lipid nanoparticles (FLUSLN) and flurbiprofen nanostructured lipid carriers (FLUNLC) by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1) and NLC gel (B1) for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 ± 2.77 μg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 ± 2.96 μg/ml). The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel PMID:19243632

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.

Rare Earth Oxide Fluoride Nanoparticles And Hydrothermal Method For Forming Nanoparticles

DOEpatents

Fulton, John L.; Hoffmann, Markus M.

2003-12-23

A hydrothermal method for forming nanoparticles of a rare earth element, oxygen and fluorine has been discovered. Nanoparticles comprising a rare earth element, oxygen and fluorine are also described. These nanoparticles can exhibit excellent refractory properties as well as remarkable stability in hydrothermal conditions. The nanoparticles can exhibit excellent properties for numerous applications including fiber reinforcement of ceramic composites, catalyst supports, and corrosion resistant coatings for high-temperature aqueous solutions.

Rare earth oxide fluoride nanoparticles and hydrothermal method for forming nanoparticles

DOEpatents

Fulton, John L [Richland, WA; Hoffmann, Markus M [Richland, WA

2001-11-13

A hydrothermal method for forming nanoparticles of a rare earth element, oxygen and fluorine has been discovered. Nanoparticles comprising a rare earth element, oxygen and fluorine are also described. These nanoparticles can exhibit excellent refractory properties as well as remarkable stability in hydrothermal conditions. The nanoparticles can exhibit excellent properties for numerous applications including fiber reinforcement of ceramic composites, catalyst supports, and corrosion resistant coatings for high-temperature aqueous solutions.

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.

Application of Solid-State NMR Relaxometry for Characterization and Formulation Optimization of Grinding-Induced Drug Nanoparticle.

PubMed

Ueda, Keisuke; Higashi, Kenjirou; Moribe, Kunikazu

2016-03-07

The formation mechanism of drug nanoparticles was investigated using solid-state nuclear magnetic resonance (NMR) techniques for the efficient discovery of an optimized nanoparticle formulation. The cogrinding of nifedipine (NIF) with polymers, including hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), and sodium dodecyl sulfate (SDS) was performed to prepare the NIF nanoparticle formulations. Then, solid-state NMR relaxometry was used for the nanometer-order characterization of NIF in the polymer matrix. Solid-state NMR measurements revealed that the crystal size of NIF was reduced to several tens of nanometers with amorphization of NIF by cogrinding with HPMC and SDS for 100 min. Similarly, the size of the NIF crystal was reduced to less than 90 nm in the 40 min ground mixture of NIF/PVP/SDS. Furthermore, 100 min grinding of NIF/PVP/SDS induced amorphization of almost all the NIF crystals followed by nanosizing. The hydrogen bond between NIF and PVP led to the efficient amorphization of NIF in the NIF/PVP/SDS system compared with NIF/HPMC/SDS system. The efficient nanosizing of the NIF crystal in the solid state, revealed by the solid-state NMR relaxation time measurements, enabled the formation of large amounts of NIF nanoparticles in water followed by the polymer dissolution. In contrast, excess amorphization of the NIF crystals failed to efficiently prepare the NIF nanoparticles. The solid-state characterization of the crystalline NIF revealed good correlation with the NIF nanoparticles formation during aqueous dispersion. Furthermore, the solid-state NMR measurements including relaxometry successfully elucidated the nanometer-order dispersion state of NIF in polymer matrix, leading to the discovery of optimized conditions for the preparation of suitable drug nanoparticles.

The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability.

PubMed

Ma, Yiran; Zhao, Xinyi; Li, Jian; Shen, Qi

2012-01-01

The aim of this research was to increase the oral bioavailability of daidzein by the formulations of poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with daidzein. Amongst the various traditional and novel techniques of preparing daidzein-loaded PLGA nanoparticles, daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were selected. The average drug entrapment efficiency, particle size, and zeta potential of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were 81.9% ± 5%, 309.2 ± 14.0 nm, -32.14 ± 2.53 mV and 83.2% ± 7.2%, 323.2 ± 4.8 nm, -18.73 ± 1.68 mV, respectively. The morphological characterization of nanoparticles was observed with scanning electron microscopy by stereological method and the physicochemical state of nanoparticles was valued by differential scanning calorimetry. The in vitro drug-release profile of both nanoparticle formulations fitted the Weibull dynamic equation. Pharmacokinetic studies demonstrated that after oral administration of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 5.57- and 8.85-fold, respectively, compared to daidzein suspension as control. These results describe an effective strategy for oral delivery of daidzein-loaded PLGA nanoparticles and might provide a fresh approach to enhancing the bioavailability of drugs with poor lipophilic and poor hydrophilic properties.

The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability

PubMed Central

Ma, Yiran; Zhao, Xinyi; Li, Jian; Shen, Qi

2012-01-01

The aim of this research was to increase the oral bioavailability of daidzein by the formulations of poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with daidzein. Amongst the various traditional and novel techniques of preparing daidzein-loaded PLGA nanoparticles, daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were selected. The average drug entrapment efficiency, particle size, and zeta potential of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles were 81.9% ± 5%, 309.2 ± 14.0 nm, −32.14 ± 2.53 mV and 83.2% ± 7.2%, 323.2 ± 4.8 nm, −18.73 ± 1.68 mV, respectively. The morphological characterization of nanoparticles was observed with scanning electron microscopy by stereological method and the physicochemical state of nanoparticles was valued by differential scanning calorimetry. The in vitro drug-release profile of both nanoparticle formulations fitted the Weibull dynamic equation. Pharmacokinetic studies demonstrated that after oral administration of daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion complexes PLGA nanoparticles to rats at a dose of 10 mg/kg, relative bioavailability was enhanced about 5.57- and 8.85-fold, respectively, compared to daidzein suspension as control. These results describe an effective strategy for oral delivery of daidzein-loaded PLGA nanoparticles and might provide a fresh approach to enhancing the bioavailability of drugs with poor lipophilic and poor hydrophilic properties. PMID:22346351

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.

New inhalation-optimized itraconazole nanoparticle-based dry powders for the treatment of invasive pulmonary aspergillosis

PubMed Central

Duret, Christophe; Wauthoz, Nathalie; Sebti, Thami; Vanderbist, Francis; Amighi, Karim

2012-01-01

Purpose Itraconazole (ITZ) dry powders for inhalation (DPI) composed of nanoparticles (NP) embedded in carrier microparticles were prepared and characterized. Methods DPIs were initially produced by reducing the ITZ particle size to the nanometer range using high-pressure homogenization with tocopherol polyethylene 1000 succinate (TPGS, 10% w/w ITZ) as a stabilizer. The optimized nanosuspension and the initial microsuspension were then spray-dried with different proportions of or in the absence of mannitol and/or sodium taurocholate. DPI characterization was performed using scanning electron microscopy for morphology, laser diffraction to evaluate the size-reduction process, and the size of the dried NP when reconstituted in aqueous media, impaction studies using a multistage liquid impactor to determine the aerodynamic performance and fine-particle fraction that is theoretically able to reach the lung, and dissolution studies to determine the solubility of ITZ. Results Scanning electron microscopy micrographs showed that the DPI particles were composed of mannitol microparticles with embedded nano- or micro-ITZ crystals. The formulations prepared from the nanosuspension exhibited good flow properties and better fine-particle fractions, ranging from 46.2% ± 0.5% to 63.2% ± 1.7% compared to the 23.1% ± 0.3% that was observed with the formulation produced from the initial microsuspension. Spray-drying affected the NP size by inducing irreversible aggregation, which was able to be minimized by the addition of mannitol and sodium taurocholate before the drying procedure. The ITZ NP-based DPI considerably increased the ITZ solubility (58 ± 2 increased to 96 ± 1 ng/mL) compared with that of raw ITZ or an ITZ microparticle-based DPI (<10 ng/mL). Conclusion Embedding ITZ NP in inhalable microparticles is a very effective method to produce DPI formulations with optimal aerodynamic properties and enhanced ITZ solubility. These formulations could be applied to other poorly water-soluble drugs and could be a very effective alternative for treating invasive pulmonary aspergillosis. PMID:23093903

Еvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin.

PubMed

Aluani, Denitsa; Tzankova, Virginia; Kondeva-Burdina, Magdalena; Yordanov, Yordan; Nikolova, Elena; Odzhakov, Feodor; Apostolov, Alexandar; Markova, Tzvetanka; Yoncheva, Krassimira

2017-10-01

The present study deals with development and evaluation of the safety profile of chitosan/alginate nanoparticles as a platform for delivery of a natural antioxidant quercetin. The nanoparticles were prepared by varying the ratios between both biopolymers giving different size and charge of the formulations. The biocompatibility was explored in vitro in cells from different origin: cultivated HepG2 cells, isolated primary rat hepatocytes, isolated murine spleen lymphocytes and macrophages. In vivo toxicological evaluation was performed after repeated 14-day oral administration to rats. The study revealed that chitosan/alginate nanoparticles did not change body weight, the relative weight of rat livers, liver histology, hematology and biochemical parameters. The protective effects of quercetin-loaded nanoparticles were investigated in the models of iron/ascorbic acid (Fe 2+ /AA) induced lipid peroxidation in microsomes and tert-butyl hydroperoxide oxidative stress in isolated rat hepatocytes. Interesting finding was that the empty chitosan/alginate nanoparticles possessed protective activity themselves. The antioxidant effects of quercetin loaded into the nanoparticles formulated with higher concentration of chitosan were superior compared to quercetin encapsulated in nanoparticles with higher amount of sodium alginate. In conclusion, chitosan/alginate nanoparticles can be considered appropriate carrier for quercetin, combining safety profile and improved protective activity of the encapsulated antioxidant. Copyright © 2017 Elsevier B.V. All rights reserved.

High-order TRAIL oligomer formation in TRAIL-coated lipid nanoparticles enhances DR5 cross-linking and increases antitumour effect against colon cancer.

PubMed

De Miguel, Diego; Gallego-Lleyda, Ana; Ayuso, José María; Pejenaute-Ochoa, Dolores; Jarauta, Vidal; Marzo, Isabel; Fernández, Luis J; Ochoa, Ignacio; Conde, Blanca; Anel, Alberto; Martinez-Lostao, Luis

2016-12-28

During the last years, a great effort has been invested into developing new TRAIL formulations with increased bioactivity, trying to overcome the resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumours. In our group, we have generated artificial lipid nanoparticles decorated with sTRAIL (LUV-TRAIL), emulating the physiological TRAIL-containing exosomes by which T-cells release TRAIL upon activation. We already demonstrated that LUV-TRAIL has greater cytotoxicity against both chemoresistant haematologic tumour cells and epithelial carcinoma cells compared to a form of sTRAIL similar to that used in clinical trials. In this study we have tested LUV-TRAIL in several human colon cancer cell lines with different sensitivity to sTRAIL. LUV-TRAIL significantly improved sTRAIL cytotoxicity in all colon cancer cell lines tested. Trying to ascertain the molecular mechanism by which LUV-TRAIL exhibited improved cytotoxicity, we demonstrated that TRAIL-coated lipid nanoparticles were able to activate DR5 more efficiently than sTRAIL, and this relied on LUV-TRAIL ability to promote DR5 clustering on the cell surface. Moreover, we show that TRAIL molecules are arranged in higher order oligomers only in LUV-TRAIL, which may explain their enhanced DR5 clustering ability. Finally, LUV-TRAIL showed significantly better antitumour activity than sTRAIL in an in vivo model using HCT-116 xenograft tumours in nude mice, validating its potential clinical application. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Evaluating the Properties of Poly(lactic-co-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach.

PubMed

Kozaki, Masato; Kobayashi, Shin-Ichiro; Goda, Yukihiro; Okuda, Haruhiro; Sakai-Kato, Kumiko

2017-01-01

We applied the Quality by Design (QbD) approach to the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations encapsulating triamcinolone acetonide, and the critical process parameters (CPPs) were identified to clarify the correlations between critical quality attributes and CPPs. Quality risk management was performed by using an Ishikawa diagram and experiments with a fractional factorial design (ANOVA). The CPPs for particle size were PLGA concentration and rotation speed, and the CPP for relative drug loading efficiency was the poor solvent to good solvent volume ratio. By assessing the mutually related factors in the form of ratios, many factors could be efficiently considered in the risk assessment. We found a two-factor interaction between rotation speed and rate of addition of good solvent by using a fractional factorial design with resolution V. The system was then extended by using a central composite design, and the results obtained were visualized by using the response surface method to construct a design space. Our research represents a case study of the application of the QbD approach to pharmaceutical development, including formulation screening, by taking actual production factors into consideration. Our findings support the feasibility of using a similar approach to nanoparticle formulations under development. We could establish an efficient method of analyzing the CPPs of PLGA nanoparticles by using a QbD approach.

Improvement in bone properties by using risedronate adsorbed hydroxyapatite novel nanoparticle based formulation in a rat model of osteoporosis.

PubMed

Sahana, H; Khajuria, Deepak Kumar; Razdan, Rema; Mahapatra, D Roy; Bhat, M R; Suresh, Sarasija; Rao, R Ramachandra; Mariappan, L

2013-02-01

A superior drug formulation capable of achieving efficient osteogenesis is in imperative demand for the treatment of osteoporosis. In the present study we investigated the potential of using novel risedronate-hydroxyapatite (HA) nanoparticle based formulation in an animal model of established osteoporosis. Nanoparticles of HA loaded with risedronate (NHLR) of various sizes (80-130 nm) were generated for bone targeted drug delivery. Three months after ovariectomy, 36 ovariectomized (OVX) rats were divided into 6 equal groups and treated with various doses of NHLR (500, 350 and 250 microg/kg intravenous single dose) and sodium risedronate (500 microg/kg, intravenous single dose). Untreated OVX and sham OVX served as controls. One month after drug administration, the left tibia and femur were tested for bone mechanical properties and histology, respectively. In the right femur, bone density was measured by method based on Archimedes principle and bone porosity analyses were performed using X-ray imaging. NHLR (250 microg/kg) showed a significant increase in bone density and reduced bone porosity when compared with OVX control. Moreover, NHLR (250 microg/kg) significantly increased bone mechanical properties and bone quality when compared with OVX control. The results strongly suggest that the NHLR, which is a novel nanoparticle based formulation, has a therapeutic advantage over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model of postmenopausal osteoporosis.

In vitro anticancer evaluation of 5-fluorouracil lipid nanoparticles using B16F10 melanoma cell lines

NASA Astrophysics Data System (ADS)

Shenoy, Vikram S.; Gude, Rajiv P.; Murthy, Rayasa S. Ramachandra

2013-05-01

The present study is aimed to investigate the formulation and in vitro anticancer activities of solid lipid nanoparticles (SLNs) of 5-fluorouracil (5-FU) prepared using glyceryl monostearate (GMS) and cetyl palmitate (CP) by hot homogenization method. The lipids were selected based on the partition coefficient of 5-FU in lipids. The lipid nanoparticles were optimized for process and formulation parameters. The optimized nanoparticles were characterized for their zeta potential, morphology, release kinetics, and anticancer activity. Higher entrapments were achieved using a combination of emulsifiers. The zeta potential of the optimized CP and GMS SLN formulation were -8.26 and -9.35 mV, respectively. Both the optimized formulations were spherical. The in vitro release studies of SLNs of both the lipid carriers followed Peppas-Korsenmeyer equation when carried out at pH 3.5 and 7.4. The chemosensitivity assay carried out in B16F10 cell lines revealed that CP SLNs had better cytotoxicity than 5-FU solution and GMS SLNs at 48 h of incubation. Subtoxic concentration of 5-FU-loaded CP SLNs (0.12 μg/mL) possessed comparable antimigrational activity, colony inhibition activity, and cytopathic as that of 5-FU solution effects. The results indicated that encapsulating 5-FU in CP would be a promising delivery system for delivering 5-FU.

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.

Engineering safer-by-design, transparent, silica-coated ZnO nanorods with reduced DNA damage potential

PubMed Central

Sotiriou, Georgios A.; Watson, Christa; Murdaugh, Kimberly M.; Darrah, Thomas H.; Pyrgiotakis, Georgios; Elder, Alison; Brain, Joseph D.; Demokritou, Philip

2014-01-01

Zinc oxide (ZnO) nanoparticles absorb UV light efficiently while remaining transparent in the visible light spectrum rendering them attractive in cosmetics and polymer films. Their broad use, however, raises concerns regarding potential environmental health risks and it has been shown that ZnO nanoparticles can induce significant DNA damage and cytotoxicity. Even though research on ZnO nanoparticle synthesis has made great progress, efforts on developing safer ZnO nanoparticles that maintain their inherent optoelectronic properties while exhibiting minimal toxicity are limited. Here, a safer-by-design concept was pursued by hermetically encapsulating ZnO nanorods in a biologically inert, nanothin amorphous SiO2 coating during their gas-phase synthesis. It is demonstrated that the SiO2 nanothin layer hermetically encapsulates the core ZnO nanorods without altering their optoelectronic properties. Furthermore, the effect of SiO2 on the toxicological profile of the core ZnO nanorods was assessed using the Nano-Cometchip assay by monitoring DNA damage at a cellular level using human lymphoblastoid cells (TK6). Results indicate significantly lower DNA damage (>3 times) for the SiO2-coated ZnO nanorods compared to uncoated ones. Such an industry-relevant, scalable, safer-by-design formulation of nanostructured materials can liberate their employment in nano-enabled products and minimize risks to the environment and human health. PMID:24955241

Solid lipid nanoparticles as vesicles for oral delivery of olmesartan medoxomil: formulation, optimization and in vivo evaluation.

PubMed

Nooli, Mounika; Chella, Naveen; Kulhari, Hitesh; Shastri, Nalini R; Sistla, Ramakrishna

2017-04-01

Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability (28%) resulting from poor aqueous solubility, presystemic metabolism and P-glycoprotein mediated efflux. The present investigation studies the role of lipid nanocarriers in enhancing the OLM bioavailability through oral delivery. Solid lipid nanoparticles (SLN) were prepared by solvent emulsion-evaporation method. Statistical tools like regression analysis and Pareto charts were used to detect the important factors effecting the formulations. Formulation and process parameters were then optimized using mean effect plot and contour plots. The formulations were characterized for particle size, size distribution, surface charge, percentage of drug entrapped in nanoparticles, drug-excipients interactions, powder X-ray diffraction analysis and drug release in vitro. The optimized formulation comprised glyceryl monostearate, soya phosphatidylcholine and Tween 80 as lipid, co-emulsifier and surfactant, respectively, with an average particle size of 100 nm, PDI 0.291, zeta potential of -23.4 mV and 78% entrapment efficiency. Pharmacokinetic evaluation in male Sprague Dawley rats revealed 2.32-fold enhancement in relative bioavailability of drug from SLN when compared to that of OLM plain drug on oral administration. In conclusion, SLN show promising approaches as a vehicle for oral delivery of drugs like OLM.

Bio-active nanoemulsions enriched with gold nanoparticle, marigold extracts and lipoic acid: In vitro investigations.

PubMed

Guler, Emine; Barlas, F Baris; Yavuz, Murat; Demir, Bilal; Gumus, Z Pinar; Baspinar, Yucel; Coskunol, Hakan; Timur, Suna

2014-09-01

A novel and efficient approach for the preparation of enriched herbal formulations was described and their potential applications including wound healing and antioxidant activity (cell based and cell free) were investigated via in vitro cell culture studies. Nigella sativa oil was enriched with Calendula officinalis extract and lipoic acid capped gold nanoparticles (AuNP-LA) using nanoemulsion systems. The combination of these bio-active compounds was used to design oil in water (O/W) and water in oil (W/O) emulsions. The resulted emulsions were characterized by particle size measurements. The phenolic content of each nanoemulsion was examined by using both colorimetric assay and chromatographic analyses. Two different methods containing cell free chemical assay (1-diphenyl-2-picrylhydrazyl method) and cell based antioxidant activity test were used to evaluate the antioxidant capacities. In order to investigate the bio-activities of the herbal formulations, in vitro cell culture experiments, including cytotoxicity, scratch assay, antioxidant activity and cell proliferation were carried out using Vero cell line as a model cell line. Furthermore, to monitor localization of the nanoemulsions after application of the cell culture, the cell images were monitored via fluorescence microscope after FITC labeling. All data confirmed that the enriched N. sativa formulations exhibited better antioxidant and wound healing activity than N. sativa emulsion without any enrichment. In conclusion, the incorporation of AuNP-LA and C. officinalis extract into the N. sativa emulsions significantly increased the bio-activities. The present work may support further studies about using the other bio-active agents for the enrichment of herbal preparations to strengthen their activities. Copyright © 2014 Elsevier B.V. All rights reserved.

Activated human neutrophil response to perfluorocarbon nanobubbles: oxygen-dependent and -independent cytotoxic responses.

PubMed

Hwang, Tsong-Long; Fang, Chia-Lang; Al-Suwayeh, Saleh A; Yang, Li-Jia; Fang, Jia-You

2011-06-10

Nanobubbles, a type of nanoparticles with acoustically active properties, are being utilized as diagnostic and therapeutic nanoparticles to better understand, detect, and treat human diseases. The objective of this work was to prepare different nanobubble formulations and investigate their physicochemical characteristics and toxic responses to N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated human neutrophils. The nanobubbles were prepared using perfluoropentane and coconut oil as the respective core and shell, with soybean phosphatidylcholine (SPC) and/or cationic surfactants as the interfacial layers. The cytotoxic effect of the nanobubbles on neutrophils was determined by extracellular O₂(.)⁻ release, intracellular reactive oxygen species (ROS), lactate dehydrogenase (LDH), and elastase release. Particle sizes of the nanobubbles with different percentages of perfluorocarbon, oil, and surfactants in ranged 186-432 nm. The nanobubbles were demonstrated to inhibit the generation of superoxide and intracellular ROS. The cytotoxicity of nanobubbles may be mainly associated with membrane damage, as indicated by the high LDH leakage. Systems with Forestall (FE), a cationic surfactant, or higher SPC contents exhibited the greatest LDH release by 3-fold compared to the control. The further addition of an oil component reduced the cytotoxicity induced by the nanobubbles. Exposure to most of the nanobubble formulations upregulated elastase release by activated neutrophils. Contrary to this result, stearylamine (SA)-containing systems slightly but significantly suppressed elastase release. FE and SA in a free form caused stronger responses by neutrophils than when they were incorporated into nanobubbles. In summary, exposure to nanobubbles resulted in a formulation-dependent toxicity toward human neutrophils that was associated with both oxygen-dependent and -independent pathways. Clinicians should therefore exercise caution when using nanobubbles in patients for diagnostic and drug targeting aims. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Assessing manganese nanostructures based carbon nanotubes composite for the highly sensitive determination of vitamin C in pharmaceutical formulation.

PubMed

Hameed, Sadaf; Munawar, Anam; Khan, Waheed S; Mujahid, Adnan; Ihsan, Ayesha; Rehman, Asma; Ahmed, Ishaq; Bajwa, Sadia Z

2017-03-15

This work is the first report describing the development of a novel three dimensional manganese nanostructures based carbon nanotubes (CNTs-Mn NPs) composite, for the determination of ascorbic acid (vitamin C) in pharmaceutical formulation. Carbon nanotubes (CNTs) were used as a conductive skeleton to anchor highly electrolytic manganese nanoparticles (Mn NPs), which were prepared by a hydrothermal method. Scanning electron microscopy and atomic force microscopy revealed the presence of Mn Nps of 20-25nm, anchored along the whole length of CNTs, in the form of patches having a diameter of 50-500nm. Fourier transform infrared spectroscopy confirmed the surface modification of CNTs by amine groups, whereas dynamic light scattering established the presence of positive charge on the prepared nanocomposite. The binding events were studied by monitoring cyclic voltammetry signals and the developed nanosensor exhibited highly sensitive response, demonstrating improved electrochemical activity towards ascorbic acid. Linear dependence of the peak current on the square root of scan rates (R 2 =0.9785), demonstrated that the oxidation of ascorbic acid by the designed nanostructures is a diffusion control mechanism. Furthermore, linear range was found to be 0.06-4.0×10 -3 M, and nanosensor displayed an excellent detection limit of 0.1µM (S/N=3). This developed nanosensor was successfully applied for the determination of vitamin C in pharmaceutical formulation. Besides, the results of the present study indicate that such a sensing platform may offer a different pathway to utilize manganese nanoparticles based CNTs composite for the determination of other bio-molecules as well. Copyright © 2016 Elsevier B.V. All rights reserved.

Nanoparticle formulation by Büchi B-90 Nano Spray Dryer for oral mucoadhesion

PubMed Central

Harsha, Sree N; Aldhubiab, Bander E; Nair, Anroop B; Alhaider, Ibrahim Abdulrahman; Attimarad, Mahesh; Venugopala, Katharigatta N; Srinivasan, Saminathan; Gangadhar, Nagesh; Asif, Afzal Haq

2015-01-01

Diabetes is considered one of the main threats to global public health in this era. It is increasing rapidly in every part of the world; the prevalence of the disease will grow to the point where 366 million people will be affected by 2030. The prevalence of diabetes mellitus (DM) in the Saudi population is high, and the majority of patients suffer from type 2 DM. Marketed oral antidiabetic drugs have indicated poor tolerability during chronic treatments, and this contributes to the moderately large proportion of type 2 DM patients that remain inadequately managed. Vildagliptin nanospheres were prepared with aminated gelatin using a spray-drying method; narrow particle-size distribution was seen at 445 nm. The angle of repose was found to be θ <33.5°. The nanospheres appeared to be spherical with a smooth surface. The drug content and percentage yield of the nanospheres were found to be 76.2%±4.6% and 83%±2%, respectively. The nanosphere-swell profile was found to be 165%±7%. The pure drug was 100% dissolved in 30 minutes, and the nanosphere formulation took 12 hours to dissolve (97.5%±2%), and followed a Korsmeyer–Peppas kinetic model with an R2 of 0.9838. The wash-off test of nanospheres found that they exhibited an excellent mucoadhesive property at 86.7% for 8 hours. The stability-study data showed no changes in the physicochemical properties of the nanospheres, and suggested that the nanospheres be stored below room temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours). PMID:25670882

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

L-Cysteine conjugated poly L-lactide nanoparticles containing 5-fluorouracil: formulation, characterization, release and uptake by tissues in vivo.

PubMed

Mishra, Brijeshkunvar J; Kaul, Ankur; Trivedi, Piyush

2015-02-01

Targeted delivery of drugs is still a therapeutic challenge and numerous methods have been reported for the same. In this study, emphasis was placed on developing nanoparticles loaded with 5-fluorouracil (FU) and modifying the surface of the nanoparticles by conjugation with amino acid, to improve the distribution of 5-FU in the lungs. An emulsion solvent evaporation technique was used to formulate nanoparticles of FU using Poly L-lactide and Pluronic F-68. The nanoparticles were conjugated with L-Cysteine using EDC as the activator of COOH group and were evaluated for product yield, particle size, surface morphology, amount of conjugation by Ellman's method and in vitro drug release study. The results indicated 60-65% yield with an average particle size of 242.7 ± 37.11 nm for the cysteine conjugated nanoparticle (CNP) formulation and more than 70% conjugation of cysteine. The cumulative percentage of drug released over a period of 24 h was found to be 58%. An increase in distribution of the delivery system in lungs (11.4% ID after 1 h) in mice was found indicating the role of L-Cysteine in the transport mechanism to the lungs. In vivo kinetic studies in rats revealed higher circulation time of CNP as compared to pure FU solution. The study helps in designing a colloidal delivery system for increased distribution of drugs to the lungs and may be helpful in delivery of drugs in conditions like non-small cell lung carcinomas.

Design of experiments for the development of poly( d, l-lactide- co-glycolide) nanoparticles loaded with Uncaria tomentosa

NASA Astrophysics Data System (ADS)

Ribeiro, Ana Ferreira; Ferreira, Carina Torres Garruth; dos Santos, Juliana Fernandes; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira

2015-02-01

Polymeric nanoparticles have been shown to be effective carriers for natural substances that possess anticancer properties. Incorporation of these natural substances into polymeric nanoparticles increases targeting of these drugs, thus reducing side effects. Uncaria tomentosa (UT) is a Peruvian Amazon plant (existing in the Brazilian Amazon rainforest) that possesses promising anti-tumor activity. This paper describes the development of poly( d, l-lactide- co-glycolide) (PLGA) nanoparticles loaded with UT extract. The emulsion solvent evaporation method was utilized and the initial conditions were determined for the organic phase (OP) and the aqueous phase (AP). The influence of surfactant (type and concentration), PLGA concentration and AP volume on nanoparticle size, polydispersity index (PI), and entrapment efficiency (EE) was determined using a fractional factorial design (FFD). In addition, the formulation was optimized using a Box-Behnken design. After the conditions were optimized, UT nanoparticles were obtained using an OP composed of an ethyl acetate:acetone (3:2) mixture which contained the UT alkaloids and PLGA, and an AP composed of a buffered solution of Poloxamer 188 (pH 7.5). The optimized formulation produced an EE of 64.6 %, a particle size of 107.4 nm and a PI of 0.163. The preliminary experiments provided important information regarding the behavior of the nanoparticulate system and the FFD used in this study greatly facilitated the selection of the most optimal conditions for formulation development.

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.

Nanostructured delivery system for Suberoylanilide hydroxamic acid against lung cancer cells.

PubMed

Sankar, Renu; Karthik, Selvaraju; Subramanian, Natesan; Krishnaswami, Venkateshwaran; Sonnemann, Jürgen; Ravikumar, Vilwanathan

2015-06-01

With the objective to provide a potential approach for the treatment of lung cancer, nanotechnology based Suberoylanilide hydroxamic acid (SAHA)-loaded Poly-d, l-lactide-co glycolide (PLGA) nanoparticles have been formulated using the nanoprecipitation technique. The acquired nanoparticles were characterized by various throughput techniques and the analyses showed the presence of smooth and spherical shaped SAHA-loaded PLGA nanoparticles, with an encapsulation efficiency of 44.8% and a particle size of 208nm. The compatibility between polymer and drug in the formulation was tested using FT-IR, Micro-Raman spectrum and DSC thermogram analyses, revealing a major interaction between the drug and polymer. The in vitro drug release from the SAHA-loaded PLGA nanoparticles was found to be biphasic with an initial burst followed by a sustained release for up to 50h. In experiments using the lung cancer cell line A549, SAHA-loaded PLGA nanoparticles demonstrated a superior antineoplastic activity over free SAHA. In conclusion, SAHA-loaded PLGA nanoparticles may be a useful novel approach for the treatment of lung cancer. Copyright © 2015. Published by Elsevier B.V.

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.

PEGylated PLGA-based nanoparticles targeting M cells for oral vaccination.

PubMed

Garinot, Marie; Fiévez, Virginie; Pourcelle, Vincent; Stoffelbach, François; des Rieux, Anne; Plapied, Laurence; Theate, Ivan; Freichels, Hélène; Jérôme, Christine; Marchand-Brynaert, Jacqueline; Schneider, Yves-Jacques; Préat, Véronique

2007-07-31

To improve the efficiency of orally delivered vaccines, PEGylated PLGA-based nanoparticles displaying RGD molecules at their surface were designed to target human M cells. RGD grafting was performed by an original method called "photografting" which covalently linked RGD peptides mainly on the PEG moiety of the PCL-PEG, included in the formulation. First, three non-targeted formulations with size and zeta potential adapted to M cell uptake and stable in gastro-intestinal fluids, were developed. Their transport by an in vitro model of the human Follicle associated epithelium (co-cultures) was largely increased as compared to mono-cultures (Caco-2 cells). RGD-labelling of nanoparticles significantly increased their transport by co-cultures, due to interactions between the RGD ligand and the beta(1) intregrins detected at the apical surface of co-cultures. In vivo studies demonstrated that RGD-labelled nanoparticles particularly concentrated in M cells. Finally, ovalbumin-loaded nanoparticles were orally administrated to mice and induced an IgG response, attesting antigen ability to elicit an immune response after oral delivery.

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

Fabrication of nanocomposite particles using a two-solution mixing-type spray nozzle for use in an inhaled curcumin formulation.

PubMed

Taki, Moeko; Tagami, Tatsuaki; Fukushige, Kaori; Ozeki, Tetsuya

2016-09-10

A unique two-solution mixing-type spray nozzle is useful for producing nanocomposite particles (microparticles containing drug nanoparticles) in one step. The nanocomposite particles can prevent nanoparticle aggregation. Curcumin has many reported pharmacological effects. Curcumin was entrapped in mannitol microparticles using a spray dryer coupled with a two-solution mixing-type spray nozzle to prepare "curcumin nanocomposite particles" and the application of these particles for inhalation formulations was investigated. Spray drying conditions (flow rate, concentration and inlet temperature) affected the size of both the resulting curcumin nanocomposite particles and the curcumin nanoparticles in the nanocomposite particles. The aerosol performance of the curcumin nanocomposite particles changed depending on the spray drying conditions and several conditions provided better deposition compared with the curcumin original powder. The curcumin nanocomposite particles showed an improved dissolution profile of curcumin compared with the original powder. Furthermore, the curcumin nanocomposite particles showed a higher cytotoxic effect compared with the curcumin original powder towards three cancer cell lines. Curcumin nanocomposite particles containing curcumin nanoparticles show promise as an inhalation formulation for treating lung-related diseases including cancer. Copyright © 2016. Published by Elsevier B.V.

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.

A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses.

PubMed

Klier, John; Fuchs, Sebastian; May, Anna; Schillinger, Ulrike; Plank, Christian; Winter, Gerhard; Coester, Conrad; Gehlen, Heidrun

2012-06-01

In the recent years, nanotechnology has boosted the development of potential drug delivery systems and material engineering on nanoscale basis in order to increase drug specificity and reduce side effects. A potential delivery system for immunostimulating agents such as cytosine-phosphate-guanine-oligodeoxynucleotides (CpG-ODN) needs to be developed to maximize the efficacy of immunotherapy against hypersensitivity. In this study, an aerosol formulation of biodegradable, biocompatible and nontoxic gelatin nanoparticle-bound CpG-ODN 2216 was used to treat equine recurrent airway obstruction in a clinical study. Bronchoalveolar lavage fluid was obtained from healthy and allergic horses to quantify Th1/Th2 cytokine levels before and after inhalation regimen. Full clinical examinations were performed to evaluate the therapeutic potential of this nebulized gelatin nanoparticle-based CpG formulation. Most remarkable was that regulatory anti-inflammatory and anti-allergic cytokine IL-10 expression was significantly triggered by five consecutive inhalations. Thorough assessment of clinical parameters following nanoparticle treatment indicated a partial remission of the allergic condition. Thus this study, for the first time, showed effectiveness of colloidal nanocarrier-mediated immunotherapy in food-producing animals with potential future applicability to other species including humans.

Preparation and Characterization of Nanoparticle β-Cyclodextrin:Geraniol Inclusion Complexes.

PubMed

Hadian, Zahra; Maleki, Majedeh; Abdi, Khosro; Atyabi, Fatemeh; Mohammadi, Abdoreza; Khaksar, Ramin

2018-01-01

The aim of the present study was to formulate β-cyclodextrin (β-CD) nanoparticles loaded with geraniol (GR) essential oil (EO) with appropriate physicochemical properties. Complexation of GR with β-CD was optimized by evaluation of four formulations, using the co-precipitation method, and the encapsulation efficiency (EE), loading, size, particle size distribution (PDI) and zeta potential were investigated. Further characterization was performed with nuclear magnetic resonance spectroscopy ( 1 H NMR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and infra-red (IR) spectroscopy analysis. Results showed that the physicochemical properties of the nanoparticles were affected by GR content in formulations that yielded nanoscale-size particles ranging from 111 to 258 nm. The highest encapsulation efficiency (79.4 ± 5.4%) was obtained when the molar ratio of EO to β-CD was 0.44: 0.13 with negative zeta potential (-21.1 ± 0.5 mV). The 1 H-NMR spectrum confirmed the formation structure of the EO and β-CD nanoparticle complex. Complexation with geraniol resulted in changes of IR profile, NMR chemical shifts, DSC properties, and SEM of β-cyclodextrin. Inclusion complex of essential oil with β-cyclodextrin was considered as promising bioactive materials for designing functional food.

Preparation and Characterization of Nanoparticle β-Cyclodextrin:Geraniol Inclusion Complexes

PubMed Central

Hadian, Zahra; Maleki, Majedeh; Abdi, Khosro; Atyabi, Fatemeh; Mohammadi, Abdoreza; Khaksar, Ramin

2018-01-01

The aim of the present study was to formulate β-cyclodextrin (β-CD) nanoparticles loaded with geraniol (GR) essential oil (EO) with appropriate physicochemical properties. Complexation of GR with β-CD was optimized by evaluation of four formulations, using the co-precipitation method, and the encapsulation efficiency (EE), loading, size, particle size distribution (PDI) and zeta potential were investigated. Further characterization was performed with nuclear magnetic resonance spectroscopy (1H NMR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and infra-red (IR) spectroscopy analysis. Results showed that the physicochemical properties of the nanoparticles were affected by GR content in formulations that yielded nanoscale-size particles ranging from 111 to 258 nm. The highest encapsulation efficiency (79.4 ± 5.4%) was obtained when the molar ratio of EO to β-CD was 0.44: 0.13 with negative zeta potential (-21.1 ± 0.5 mV). The 1H-NMR spectrum confirmed the formation structure of the EO and β-CD nanoparticle complex. Complexation with geraniol resulted in changes of IR profile, NMR chemical shifts, DSC properties, and SEM of β-cyclodextrin. Inclusion complex of essential oil with β-cyclodextrin was considered as promising bioactive materials for designing functional food.

Sub acute toxicity assessment of glipizide engineered polymeric nanoparticles.

PubMed

Lekshmi, U M Dhana; Kishore, Narra; Reddy, P Neelakanta

2011-08-01

To our knowledge, no such polymeric nanoparticle formulation toxicity study has been reported for oral use. The oral route of drug administration is generally preferred because of its versatility, safety and relative patient comfort. Hence, there is an outstanding need of research for polymeric nanoparticles to find whether they are stable for prolonged shelf life, and yet have no toxicity when administered orally. The main objective of this study is to assess the safety of Glipizide (GZ) loaded polymeric nanoparticle systematically and to observe the toxic effects of nanoparticles on the functions of various tissues and organs in rats. The rats were randomly divided into 7 groups (6 in each group); viz. one normal control group (received saline), two groups (1:2 and 1:5 ratio of GZ-Chitosan nanoparticle), two groups (1:2 and 1:5 ratio of GZ-Poly(methyl methacrylate) nanoparticle) and two groups (1:2 and 1:5 ratio of GZ-Ethyl Cellulose nanoparticle). After 30 days of nanoparticle administration, the blood haematology and biochemistry were investigated, along with the histopathological examination. The rats did not show any significant changes in all the parameters studied and the results clearly evidenced its safety. All formulations showed in vitro haemolytic activity less than 5%. Conclusion drawn from the present study is that the polymeric nanoparticles may be a suitable device for safe oral administration. A rigorous safety of these nanoparticles would enable their use in the field of diabetic therapy.

Preparation and in vitro evaluation of hydrophilic fenretinide nanoparticles.

PubMed

Ledet, Grace A; Graves, Richard A; Glotser, Elena Y; Mandal, Tarun K; Bostanian, Levon A

2015-02-20

Fenretinide is an effective anti-cancer drug with high in vitro cytotoxicity and low in vivo systemic toxicity. In clinical trials, fenretinide has shown poor therapeutic efficacy following oral administration - attributed to its low bioavailability and solubility. The long term goal of this project is to develop a formulation for the oral delivery of fenretinide. The purpose of this part of the study was to prepare and characterize hydrophilic nanoparticle formulations of fenretinide. Three different ratios of polyvinyl pyrrolidone (PVP) to fenretinide were used, namely, 3:1, 4:1, and 5:1. Both drug and polymer were dissolved in a mixture of methanol and dichloromethane (2:23 v/v). Rotary evaporation was used to remove the solvents, and, following reconstitution with water, a high pressure homogenizer was used to form nanoparticles. The particle size and polydispersity index were measured before and after lyophilization. The formulations were studied by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). The effectiveness of the formulations was assessed by release studies and Caco-2 cell permeability assays. As the PVP content increased, the recovered particle size following lyophilization became more consistent with the pre-lyophilization particle size, especially for those formulations with less lactose. The DSC scans of the formulations did not show any fenretinide melting endotherms, indicating that the drug was either present in an amorphous form in the formulation or that a solid solution of the drug in PVP had formed. For the release studies, the highest drug release among the formulations was 249.2±35.5ng/mL for the formulation with 4:1 polymer-to-drug. When the permeability of the formulations was evaluated in a Caco-2 cell model, the mean normalized flux for each treatment group was significantly higher (p<0.05) from the fenretinide control. The formulation containing 4:1 polymer-to-drug ratio and 6:5 lactose-to-formulation ratio emerged as the optimal choice for further evaluation as a potential oral delivery formulation for fenretinide. Copyright © 2014 Elsevier B.V. All rights reserved.

Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release

PubMed Central

Ilyinskii, Petr O.; Roy, Christopher J.; O’Neil, Conlin P.; Browning, Erica A.; Pittet, Lynnelle A.; Altreuter, David H.; Alexis, Frank; Tonti, Elena; Shi, Jinjun; Basto, Pamela A.; Iannacone, Matteo; Radovic-Moreno, Aleksandar F.; Langer, Robert S.; Farokhzad, Omid C.; von Andrian, Ulrich H.; Johnston, Lloyd P.M.; Kishimoto, Takashi Kei

2014-01-01

Augmentation of immunogenicity can be achieved by particulate delivery of an antigen and by its co-administration with an adjuvant. However, many adjuvants initiate strong systemic inflammatory reactions in vivo, leading to potential adverse events and safety concerns. We have developed a synthetic vaccine particle (SVP) technology that enables co-encapsulation of antigen with potent adjuvants. We demonstrate that co-delivery of an antigen with a TLR7/8 or TLR9 agonist in synthetic polymer nanoparticles results in a strong augmentation of humoral and cellular immune responses with minimal systemic production of inflammatory cytokines. In contrast, antigen encapsulated into nanoparticles and admixed with free TLR7/8 agonist leads to lower immunogenicity and rapid induction of high levels of inflammatory cytokines in the serum (e.g., TNF-α and IL-6 levels are 50- to 200-fold higher upon injection of free resiquimod (R848) than of nanoparticle-encapsulated R848). Conversely, local immune stimulation as evidenced by cellular infiltration of draining lymph nodes and by intranodal cytokine production was more pronounced and persisted longer when SVP-encapsulated TLR agonists were used. The strong local immune activation achieved using a modular self-assembling nanoparticle platform markedly enhanced immunogenicity and was equally effective whether antigen and adjuvant were co-encapsulated in a single nanoparticle formulation or co-delivered in two separate nanoparticles. Moreover, particle encapsulation enabled the utilization of CpG oligonucleotides with the natural phosphodiester backbone, which are otherwise rapidly hydrolyzed by nucleases in vivo. The use of SVP may enable clinical use of potent TLR agonists as vaccine adjuvants for indications where cellular immunity or robust humoral responses are required. PMID:24593999

Self-assembled amphotericin B-loaded polyglutamic acid nanoparticles: preparation, characterization and in vitro potential against Candida albicans

PubMed Central

Zia, Qamar; Khan, Aijaz Ahmed; Swaleha, Zubair; Owais, Mohammad

2015-01-01

In the present study, we developed a self-assembled biodegradable polyglutamic acid (PGA)-based formulation of amphotericin B (AmB) and evaluated its in vitro antifungal potential against Candida albicans. The AmB-loaded PGA nanoparticles were prepared in-house and had a mean size dimension of around 98±2 nm with a zeta potential of −35.2±7.3 mV. Spectroscopic studies revealed that the drug predominantly acquires an aggregated form inside the formulation with an aggregation ratio above 2. The PGA-based AmB formulation was shown to be highly stable in phosphate-buffered saline as well as in serum (only 10%–20% of the drug was released after 10 days). The AmB–PGA nanoparticles were less toxic to red blood cells (<15% lysis at an AmB concentration of 100 μg/mL after 24 hours) when compared with Fungizone®, a commercial antifungal product. An MTT assay showed that the viability of mammalian cells (KB and RAW 264.7) was negligibly affected at AmB concentrations as high as 200 μg/mL. Histopathological examination of mouse kidney revealed no signs of tissue necrosis. The AmB–PGA formulation showed potent antimicrobial activity similar to that of Fungizone against C. albicans. Interestingly, AmB-bearing PGA nanoparticles were found to inhibit biofilm formation to a considerable extent. In summary, AmB–PGA nanoparticles showed highly attenuated toxicity when compared with Fungizone, while retaining equivalent active antifungal properties. This study indicates that the AmB–PGA preparation could be a promising treatment for various fungal infections. PMID:25784804

Design and formulation of nano-sized spray dried efavirenz-part I: influence of formulation parameters

NASA Astrophysics Data System (ADS)

Katata, Lebogang; Tshweu, Lesego; Naidoo, Saloshnee; Kalombo, Lonji; Swai, Hulda

2012-11-01

Efavirenz (EFV) is one of the first-line antiretroviral drugs recommended by the World Health Organisation for treating HIV. It is a hydrophobic drug that suffers from low aqueous solubility (4 μg/mL), which leads to a limited oral absorption and low bioavailability. In order to improve its oral bioavailability, nano-sized polymeric delivery systems are suggested. Spray dried polycaprolactone-efavirenz (PCL-EFV) nanoparticles were prepared by the double emulsion method. The Taguchi method, a statistical design with an L8 orthogonal array, was implemented to optimise the formulation parameters of PCL-EFV nanoparticles. The types of sugar (lactose or trehalose), surfactant concentration and solvent (dichloromethane and ethyl acetate) were chosen as significant parameters affecting the particle size and polydispersity index (PDI). Small nanoparticles with an average particle size of less than 254 ± 0.95 nm in the case of ethyl acetate as organic solvent were obtained as compared to more than 360 ± 19.96 nm for dichloromethane. In this study, the type of solvent and sugar were the most influencing parameters of the particle size and PDI. Taguchi method proved to be a quick, valuable tool in optimising the particle size and PDI of PCL-EFV nanoparticles. The optimised experimental values for the nanoparticle size and PDI were 217 ± 2.48 nm and 0.093 ± 0.02.

Freeze-drying of HI-6-loaded recombinant human serum albumin nanoparticles for improved storage stability.

PubMed

Dadparvar, Miriam; Wagner, Sylvia; Wien, Sascha; Worek, Franz; von Briesen, Hagen; Kreuter, Jörg

2014-10-01

Severe intoxications with organophosphates require the immediate administration of atropine in combination with acetyl cholinesterase (AChE) reactivators such as HI-6. Although this therapy regimen enables the treatment of peripheral symptoms, the blood-brain barrier (BBB) restricts the access of the hydrophilic antidotes to the central nervous system which could lead to a fatal respiratory arrest. Therefore, HI-6-loaded albumin nanoparticles were previously developed to enhance the transport across this barrier and were able to reactivate organophosphate-(OP)-inhibited AChE in an in vitro BBB model. Since HI-6 is known to be moisture-sensitive, the feasibility of freeze-drying of the HI-6-loaded nanoparticles was investigated in the present study using different cryo- and lyoprotectants at different concentrations. Trehalose and sucrose (3%, w/v)-containing formulations were superior to mannitol concerning the physicochemical parameters of the nanoparticles whereas trehalose-containing samples were subject of a prolonged storage stability study at temperatures between -20°C and +40°C for predetermined time intervals. Shelf-life computations of the freeze-dried HI-6 nanoparticle formulations revealed a shelf-life time of 18 months when stored at -20°C. The formulations' efficacy was proven in vitro by reactivation of OP-inhibited AChE after transport over a porcine brain capillary endothelial cell layer model. Copyright © 2014 Elsevier B.V. All rights reserved.

Chitosan Nanoparticles of Gamma-Oryzanol: Formulation, Optimization, and In vivo Evaluation of Anti-hyperlipidemic Activity.

PubMed

Rawal, Tejal; Mishra, Neha; Jha, Abhishek; Bhatt, Apurva; Tyagi, Rajeev K; Panchal, Shital; Butani, Shital

2018-05-01

The elevated blood levels of cholesterol and low-density lipoproteins result in hyperlipidemia. The available expensive prophylactic treatments are kindred with severe side effects. Therefore, we fabricated the polymeric nanoparticles of gamma-oryzanol to achieving the improved efficacy of drug. The nanoparticles were prepared by ionic gelation method and optimized using 2 3 full factorial design taking drug/polymer ratio (X 1 ), polymer/cross linking agent ratio (X 2 ), and stirring speed (X 3 ) as independent variables. The average particle size, percentage entrapment efficiency, and in vitro drug release at 2, 12, and 24 h were selected as response parameters. The factorial batches were statistically analyzed and optimized. The optimized nanoparticles were characterized with respect to particle size (141 nm) and zeta potential (+ 6.45 mV). Results obtained with the prepared and characterized formulation showed 83% mucoadhesion towards the intestinal mucosa. The in vitro findings were complemented well by in vivo anti-hyperlipidemic activity of developed formulation carried out in Swiss albino mouse model. The in vivo studies showed improved atherogenic index, malondialdehyde, and superoxide dismutase levels in poloxamer-407-induced hyperlipidemic animals when treated with oryzanol and gamma-oryzanol nanoformulation. Based on our findings, we believe that chitosan-mediated delivery of gamma-oryzanol nanoparticles might prove better in terms of anti-hyperlipidemic therapeutics.

Light induced cytosolic drug delivery from liposomes with gold nanoparticles.

PubMed

Lajunen, Tatu; Viitala, Lauri; Kontturi, Leena-Stiina; Laaksonen, Timo; Liang, Huamin; Vuorimaa-Laukkanen, Elina; Viitala, Tapani; Le Guével, Xavier; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

2015-04-10

Externally triggered drug release at defined targets allows site- and time-controlled drug treatment regimens. We have developed liposomal drug carriers with encapsulated gold nanoparticles for triggered drug release. Light energy is converted to heat in the gold nanoparticles and released to the lipid bilayers. Localized temperature increase renders liposomal bilayers to be leaky and triggers drug release. The aim of this study was to develop a drug releasing system capable of releasing its cargo to cell cytosol upon triggering with visible and near infrared light signals. The liposomes were formulated using either heat-sensitive or heat- and pH-sensitive lipid compositions with star or rod shaped gold nanoparticles. Encapsulated fluorescent probe, calcein, was released from the liposomes after exposure to the light. In addition, the pH-sensitive formulations showed a faster drug release in acidic conditions than in neutral conditions. The liposomes were internalized into human retinal pigment epithelial cells (ARPE-19) and human umbilical vein endothelial cells (HUVECs) and did not show any cellular toxicity. The light induced cytosolic delivery of calcein from the gold nanoparticle containing liposomes was shown, whereas no cytosolic release was seen without light induction or without gold nanoparticles in the liposomes. The light activated liposome formulations showed a controlled content release to the cellular cytosol at a specific location and time. Triggering with visual and near infrared light allows good tissue penetration and safety, and the pH-sensitive liposomes may enable selective drug release in the intracellular acidic compartments (endosomes, lysosomes). Thus, light activated liposomes with gold nanoparticles are an attractive option for time- and site-specific drug delivery into the target cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of the Formulation Parameters on the Particle Size and Encapsulation Efficiency of Resveratrol in PLA and PLA-PEG Blend Nanoparticles: A Factorial Design.

PubMed

Lindner, Gabriela da Rocha; Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

2015-12-01

Polymeric nanoparticles are colloidal systems that promote protection and modification of physicochemical characteristics of a drug and that also ensure controlled and extended drug release. This paper reports a 2(3) factorial design study to optimize poly(lactide) (PLA) and poly(lactide)-polyethylene glycol (PLA-PEG) blend nanoparticles containing resveratrol (RVT) for prolonged release. The independent variables analyzed were solvent composition, surfactant concentration and ratio of aqueous to organic phase (two levels each factor). Mean particle size and RVT encapsulation efficiency were set as the dependent variables. The selected optimized parameters were set as organic phase comprised of a mixture of dichloromethane and ethyl acetate, 1% of surfactant polyvinyl alcohol and a 3:1 ratio of aqueous to organic phase, for both PLA and PLA-PEG blend nanoparticles. This formulation originated nanoparticles with size of 228 ± 10 nm and 185 ± 70 nm and RVT encapsulation efficiency of 82 ± 10% and 76 ± 7% for PLA and PLA-PEG blend nanoparticles, respectively. The in vitro release study showed a biphasic pattern with prolonged RVT release and PEG did not influence the RVT release. The in vitro release data were in favor of Higuchi-diffusion kinetics for both nanoformulations and the Kossmeyer-Peppas coefficient indicated that anomalous transport was the main release mechanism of RVT. PLA and PLA-PEG blend nanoparticles produced with single emulsion-solvent evaporation technology were found to be a promising approach for the incorporation of RVT and promoted its controlled release. The factorial design is a tool of great value in choosing formulations with optimized parameters.

Effects of PEG tethering chain length of vitamin E TPGS with a Herceptin-functionalized nanoparticle formulation for targeted delivery of anticancer drugs.

PubMed

Zhao, Jing; Feng, Si-Shen

2014-03-01

Drug formulation by ligand conjugated nanoparticles of biodegradable polymers has become one of the most important strategies in drug targeting. We have developed in our previous work nanoparticles of a mixture of two vitamin E TPGS based copolymers PLA-TPGS and TPGS-TOOH with the latter for Herceptin conjugation for targeted delivery of anticancer drugs such as docetaxel to the cancer cells of human epidermal growth factor receptor 2 (HER2) overexpression. In this research, we investigated the effects of the PEG chain length in TPGS, which is in fact a PEGylated vitamin E, on the cellular uptake and cytotoxicity of the drug formulated in the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend (NPs). Such NPs of PEG1000, PEG2000, PEG3350 and PEG5000, i.e. the PEG of molecule weight 1000, 2000, 3350 and 5000, were prepared by the nanoprecipitation method and characterized for their size and size distribution, drug loading, surface morphology, surface charge and surface chemistry as well as in vitro drug release profile, cellular uptake and cytotoxicity. We found among such nanoparticles, those of PEG1000, i.e. of the shortest PEG tethering chain length, could result in the best therapeutic effects, which are 24.1%, 37.3%, 38.1% more efficient in cellular uptake and 68.1%, 90%, 92.6% lower in IC50 (thus higher in cytotoxicity) than the Herceptin-conjugated nanoparticles of PLA-TPGS/TPGS-COOH blend of PEG2000, PEG3350 and PEG5000 respectively in treatment of SK-BR-3 cancer cells which are of high HER2 overexpression. We provided a theoretical explanation from surface mechanics and thermodynamics for endocytosis of nanoparticles. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies

PubMed Central

Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

2014-01-01

Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around −30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds. PMID:24634584

Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies.

PubMed

Gomes, Maria João; Martins, Susana; Ferreira, Domingos; Segundo, Marcela A; Reis, Salette

2014-01-01

Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds.

Antibacterial and Cytotoxic Efficacy of Extracellular Silver Nanoparticles Biofabricated from Chromium Reducing Novel OS4 Strain of Stenotrophomonas maltophilia

PubMed Central

Oves, Mohammad; Khan, Mohammad Saghir; Zaidi, Almas; Ahmed, Arham S.; Ahmed, Faheem; Ahmad, Ejaz; Sherwani, Asif; Owais, Mohammad; Azam, Ameer

2013-01-01

Biofabricated metal nanoparticles are generally biocompatible, inexpensive, and ecofriendly, therefore, are used preferably in industries, medical and material science research. Considering the importance of biofabricated materials, we isolated, characterized and identified a novel bacterial strain OS4 of Stenotrophomonas maltophilia (GenBank: JN247637.1). At neutral pH, this Gram negative bacterial strain significantly reduced hexavalent chromium, an important heavy metal contaminant found in the tannery effluents and minings. Subsequently, even at room temperature the supernatant of log phase grown culture of strain OS4 also reduced silver nitrate (AgNO3) to generate nanoparticles (AgNPs). These AgNPs were further characterized by UV–visible, Nanophox particle size analyzer, XRD, SEM and FTIR. As evident from the FTIR data, plausibly the protein components of supernatant caused the reduction of AgNO3. The cuboid and homogenous AgNPs showed a characteristic UV-visible peak at 428 nm with average size of ∼93 nm. The XRD spectra exhibited the characteristic Bragg peaks of 111, 200, 220 and 311 facets of the face centred cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. From the nanoparticle release kinetics data, the rapid release of AgNPs was correlated with the particle size and increasing surface area of the nanoparticles. A highly significant antimicrobial activity against medically important bacteria by the biofabricated AgNPs was also revealed as decline in growth of Staphylococcus aureus (91%), Escherichia coli (69%) and Serratia marcescens (66%) substantially. Additionally, different cytotoxic assays showed no toxicity of AgNPs to liver function, RBCs, splenocytes and HeLa cells, hence these particles were safe to use. Therefore, this novel bacterial strain OS4 is likely to provide broad spectrum benefits for curing chromium polluted sites, for biofabrication of AgNPs and ultimately in the nanoparticle based drug formulation for the treatment of infectious diseases. PMID:23555625

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.

Application of rotatable central composite design in the preparation and optimization of poly(lactic-co-glycolic acid) nanoparticles for controlled delivery of paclitaxel.

PubMed

Kollipara, Sivacharan; Bende, Girish; Movva, Snehalatha; Saha, Ranendra

2010-11-01

Polymeric carrier systems of paclitaxel (PCT) offer advantages over only available formulation Taxol® in terms of enhancing therapeutic efficacy and eliminating adverse effects. The objective of the present study was to prepare poly (lactic-co-glycolic acid) nanoparticles containing PCT using emulsion solvent evaporation technique. Critical factors involved in the processing method were identified and optimized by scientific, efficient rotatable central composite design aiming at low mean particle size and high entrapment efficiency. Twenty different experiments were designed and each formulation was evaluated for mean particle size and entrapment efficiency. The optimized formulation was evaluated for in vitro drug release, and absorption characteristics were studied using in situ rat intestinal permeability study. Amount of polymer and duration of ultrasonication were found to have significant effect on mean particle size and entrapment efficiency. First-order interactions of amount of miglyol with amount of polymer were significant in case of mean particle size, whereas second-order interactions of polymer were significant in mean particle size and entrapment efficiency. The developed quadratic model showed high correlation (R(2) > 0.85) between predicted response and studied factors. The optimized formulation had low mean particle size (231.68 nm) and high entrapment efficiency (95.18%) with 4.88% drug content. The optimized formulation showed controlled release of PCT for more than 72 hours. In situ absorption study showed faster and enhanced extent of absorption of PCT from nanoparticles compared to pure drug. The poly (lactic-co-glycolic acid) nanoparticles containing PCT may be of clinical importance in enhancing its oral bioavailability.

Albumin nanoparticle encapsulation of potent cytotoxic therapeutics shows sustained drug release and alleviates cancer drug toxicity.

PubMed

Wang, Hangxiang; Wu, Jiaping; Xu, Li; Xie, Ke; Chen, Chao; Dong, Yuehan

2017-02-23

We here provide the first report on the construction of nanoparticles formulating highly potent cytotoxic therapeutics using albumin. Maytansinoid DM1 can be efficiently integrated into albumin nanoparticles, resulting in remarkable alleviation of in vivo drug toxicity and expanding the repertoire of albumin technology available for cancer therapy.

A novel paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 blend nanoparticle overcoming multidrug resistance for cancer treatment.

PubMed

Zhang, Yangqing; Tang, Lina; Sun, Leilei; Bao, Junbo; Song, Cunxian; Huang, Laiqiang; Liu, Kexin; Tian, Yan; Tian, Ge; Li, Zhen; Sun, Hongfan; Mei, Lin

2010-06-01

Multidrug resistance (MDR) of tumor cells is a major obstacle to the success of cancer chemotherapy. Poloxamers have been used in cancer therapy to overcome MDR. The objective of this research is to test the feasibility of paclitaxel-loaded poly(epsilon-caprolactone)/Poloxamer 188 (PCL/Poloxamer 188) nanoparticles to overcome MDR in a paclitaxel-resistant human breast cancer cell line. Paclitaxel-loaded nanoparticles were prepared by a water-acetone solvent displacement method using commercial PCL and self-synthesized PCL/Poloxamer 188 compound, respectively. PCL/Poloxamer 188 nanoparticles were found to be of spherical shape and tended to have a rough and porous surface. The nanoparticles had an average size of around 220nm, with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a clear biphasic release pattern. There was an increased level of uptake of PCL/Poloxamer 188 nanoparticles (PPNP) in the paclitaxel-resistant human breast cancer cell line MCF-7/TAX, in comparison with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxol in the MCF-7/TAX cell culture, but the differences were not significant. However, the PCL/Poloxamer 188 nanoparticles achieved a significantly higher level of cytotoxicity than both of PCL nanoparticle formulation and Taxol(R), indicating that paclitaxel-loaded PCL/Poloxamer 188 nanoparticles could overcome MDR in human breast cancer cells and therefore could have considerable therapeutic potential for breast cancer. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Assessment of interactions of efavirenz solid drug nanoparticles with human immunological and haematological systems.

PubMed

Liptrott, Neill J; Giardiello, Marco; McDonald, Tom O; Rannard, Steve P; Owen, Andrew

2018-03-15

Recent work has developed solid drug nanoparticles (SDNs) of efavirenz that have been demonstrated, preclinically, improved oral bioavailability and the potential to enable up to a 50% dose reduction, and is currently being studied in a healthy volunteer clinical trial. Other SDN formulations are being studied for parenteral administration, either as intramuscular long-acting formulations, or for direct administration intravenously. The interaction of nanoparticles with the immunological and haematological systems can be a major barrier to successful translation but has been understudied for SDN formulations. Here we have conducted a preclinical evaluation of efavirenz SDN to assess their potential interaction with these systems. Platelet aggregation and activation, plasma coagulation, haemolysis, complement activation, T cell functionality and phenotype, monocyte derived macrophage functionality, and NK cell function were assessed in primary healthy volunteer samples treated with either aqueous efavirenz or efavirenz SDN. Efavirenz SDNs were shown not to interfere with any of the systems studied in terms of immunostimulation nor immunosuppression. Although efavirenz aqueous solution was shown to cause significant haemolysis ex vivo, efavirenz SDNs did not. No other interaction with haematological systems was observed. Efavirenz SDNs have been demonstrated to be immunologically and haematologically inert in the utilised assays. Taken collectively, along with the recent observation that lopinavir SDN formulations did not impact immunological responses, these data indicate that this type of nanoformulation does not elicit immunological consequences seen with other types of nanomaterial. The methodologies presented here provide a framework for pre-emptive preclinical characterisation of nanoparticle safety.

Dorzolamide-loaded PLGA/vitamin E TPGS nanoparticles for glaucoma therapy: Pharmacoscintigraphy study and evaluation of extended ocular hypotensive effect in rabbits.

PubMed

Warsi, Musarrat H; Anwar, Mohammed; Garg, Vaidehi; Jain, Gaurav K; Talegaonkar, Sushama; Ahmad, Farhan J; Khar, Roop K

2014-10-01

Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye. Copyright © 2014 Elsevier B.V. All rights reserved.

Synthesis of polymer nanostructures with conductance switching properties

DOEpatents

Su, Kai; Nuraje, Nurxat; Zhang, Lingzhi; Matsui, Hiroshi; Yang, Nan Loh

2015-03-03

The present invention is directed to crystalline organic polymer nanoparticles comprising a conductive organic polymer; wherein the crystalline organic polymer nanoparticles have a size of from 10 nm to 200 nm and exhibits two current-voltage states: (1) a high resistance current-voltage state, and (2) a low resistance current-voltage state, wherein when a first positive threshold voltage (V.sub.th1) or higher positive voltage, or a second negative threshold voltage (V.sub.th2) or higher negative voltage is applied to the nanoparticle, the nanoparticle exhibits the low-resistance current-voltage state, and when a voltage less positive than the first positive threshold voltage or a voltage less negative than the second negative threshold voltage is applied to the nanoparticle, the nanoparticle exhibits the high-resistance current-voltage state. The present invention is also directed methods of manufacturing the nanoparticles using novel interfacial oxidative polymerization techniques.

Novel theranostic zinc phthalocyanine-phospholipid complex self-assembled nanoparticles for imaging-guided targeted photodynamic treatment with controllable ROS production and shape-assisted enhanced cellular uptake.

PubMed

Ma, Jinyuan; Li, Yang; Liu, Guihua; Li, Ai; Chen, Yilin; Zhou, Xinyi; Chen, Dengyue; Hou, Zhenqing; Zhu, Xuan

2018-02-01

The novel drug delivery system based on self-assembly of zinc phthalocyanine-soybean phosphatidylcholine (ZnPc-SPC) complex was developed by a co-solvent method followed by a nanoprecipitaion technique. DSPE-PEG-methotrexate (DSPE-PEG-MTX) was introduced on the surface of ZnPc-SPC self-assembled nanoparticles (ZS) to endow them with folate receptor-targeting property. NMR, XRD, FTIR, and UV-vis-NIR analysis demonstrated the weak molecular interaction between ZnPc and SPC. The ZS functionalized with DSPE-PEG-MTX (ZSPM) was successfully constructed with an average particle size of ∼170nm, a narrow size distribution, and could remain physiologically stable for at least 7days. In vitro cellular uptake and cytotoxicity studies demonstrated that ZSPM exhibited stronger cellular uptake efficacy and photodynamic cytotoxicity against HeLa and MCF-7 cells than ZS functionalized with DSPE-mPEG (ZSP) and free ZnPc. More importantly, ZSPM showed the enhanced accumulation effect at the tumor region compared with ZSP by the active-plus-passive targeting via enhanced permeability and retention (EPR) effect and folate receptor-mediated endocytosis. Furthermore, in vivo antitumor effect and histological analysis demonstrated the superior tumor growth inhibition effect of ZSPM. In addition, the needle-shape ZSP (ZSPN) exhibited better in vitro cellular uptake and in vivo tumor accumulation compared with ZSP due to the shape-assisted effect. Moreover, the interesting off-on switch effect of reactive oxygen species (ROS) production of ZnPc-SPC complex-based nanoparticles was discovered to achieve photodynamic treatment in a controllable way. These findings suggested that the ZnPc-SPC complex-based self-assembled nanoparticles could serve as a promising and effective formulation to achieve tumor-targeting fluorescence imaging and enhanced photodynamic treatment. Copyright © 2017. Published by Elsevier B.V.

Loteprednol Etabonate Nanoparticles: Optimization via Box-Behnken Design Response Surface Methodology and Physicochemical Characterization.

PubMed

Sah, Abhishek K; Suresh, Preeti K

2017-01-01

Abstract: The objective of the present work was to prepare and optimize the loteprednoletabonate (LE) loaded poly (D,L-lactide co-glycolide) (PLGA) polymer based nanoparticle carrier. The review on recent patents (US9006241, US20130224302A1, US2012/0028947A1) assisted in the selection of drug and polymer for designing nanoparticles for ocular delivery applications. The nanoparticles were prepared by solvent evaporation followed by high speed homogenization. Biodegradable polymer PLGA (50:50) grade was utilized to develop various formulations with different drug:polymer ratio. A Box-Behnken design with 33 factorial design was selected for the present study and 17 runs were carried out in totality. The influence of various process variables (viz., polymer concentration, homogenization speed and sonication time) on the characteristics of nanoparticles including the in vitro drug release profile were studied. The nanoparticulate formulations were evaluated for mean spherical diameter, polydispersity index (PDI), zeta potential, surface morphology, drug entrapment and in-vitro drug release profile. The entrapment efficiency, drug loading and mean particle size were found to be 96.31±1.68 %, 35.46±0.35 % and 167.6±2.1 nm respectively. The investigated process and formulation variables were found to have significant effect on the particle size, drug loading (DL), entrapment efficiency (EE), and in vitro drug release profile. A biphasic in vitro drug release profile was apparent from the optimized nanoparticles (NPs) for 24 hours. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Calcium hydroxide nanoparticles for the conservation of cultural heritage: new formulations for the deacidification of cellulose-based artifacts

NASA Astrophysics Data System (ADS)

Poggi, G.; Toccafondi, N.; Melita, L. N.; Knowles, J. C.; Bozec, L.; Giorgi, R.; Baglioni, P.

2014-03-01

Alkaline earth metal hydroxide nanoparticles dispersions have demonstrated to be efficient for the preservation of cellulose-based artifacts, providing a stable neutral environment and, if in excess, turning into mild alkaline species. New formulations tailored for specific conservation issues have been recently obtained via a solvothermal reaction, starting from bulk metal, and short chain alcohols. Using this synthetic procedure, stable, and high concentrated calcium hydroxide nanoparticles dispersions can be obtained. The characterization of nanoparticles was carried out by dynamic light scattering, transmission electron microscopy and X-ray powder diffraction and showed that the dispersed systems are particularly suitable for the application on porous substrates. In a direct application of this technology, acidic paper and canvas samples were artificially aged after deacidification using calcium hydroxide nanoparticles dispersed in short chain alcohols. Cellulose viscosimetric polymerization degree (DPv), cellulose pyrolysis temperature, and samples' pH were evaluated upon the aging and in terms of protective action arising from the applied treatment. In particular, determinations of DPv clearly showed that the degradation of acidic paper and canvas samples proceeds at higher rates with respect to deacidified samples. These evidences were also confirmed by the thermogravimetric analysis of samples, in which the benefits due to the deacidification treatments are measured in terms of pyrolysis temperature of cellulose. These new formulations of nanoparticles dispersions expand the palette of available tools for the conservation of cellulose-based works of art, such as easel paintings, and manuscripts, potentially opening the way for the intervention on parchment and leather, whose preservation is a particularly challenging task.

Solid lipid nanoparticles as carrier for sunscreens: in vitro release and in vivo skin penetration.

PubMed

Wissing, S A; Müller, R H

2002-06-17

The aim of this study was the comparison of two different formulations (solid lipid nanoparticles (SLN) and conventional o/w emulsion) as carrier systems for the molecular sunscreen oxybenzone. The influence of the carrier on the rate of release was studied in vitro with a membrane-free model. The release rate could be decreased by up to 50% with the SLN formulation. Further in vitro measurements with static Franz diffusion cells were performed. In vivo, penetration of oxybenzone into stratum corneum on the forearm was investigated by the tape stripping method. It was shown that the rate of release is strongly dependent upon the formulation and could be decreased by 30-60% in SLN formulations. In all test models, oxybenzone was released and penetrated into human skin more quickly and to a greater extent from the emulsions. The rate of release also depends upon the total concentration of oxybenzone in the formulation. In vitro-in vivo correlations could be made qualitatively.

Safranal-loaded solid lipid nanoparticles: evaluation of sunscreen and moisturizing potential for topical applications

PubMed Central

Khameneh, Bahman; Halimi, Vahid; Jaafari, Mahmoud Reza; Golmohammadzadeh, Shiva

2015-01-01

Objective(s): In the current study, sunscreen and moisturizing properties of solid lipid nanoparticle (SLN)-safranal formulations were evaluated. Materials and Methods: Series of SLN were prepared using glyceryl monostearate, Tween 80 and different amounts of safranal by high shear homogenization, and ultrasound and high-pressure homogenization (HPH) methods. SLN formulations were characterized for size, zeta potential, morphology, thermal properties, and encapsulation efficacy. The Sun Protection Factor (SPF) of the products was determined in vitro using transpore tape. The moisturizing activity of the products was also evaluated by corneometer. Results: The SPF of SLN-safranal formulations was increased when the amount of safranal increased. Mean particle size for all formulas was approximately 106 nm by probe sonication and 233 nm using HPH method. The encapsulation efficiency of safranal was around 70% for all SLN-safranal formulations. Conclusion: The results conclude that SLN-safranal formulations were found to be effective for topical delivery of safranal and succeeded in providing appropriate sunscreen properties. PMID:25810877

Nanoparticle formulations of cisplatin for cancer therapy

PubMed Central

Duan, Xiaopin; He, Chunbai; Kron, Stephen J.; Lin, Wenbin

2016-01-01

The genotoxic agent cisplatin, used alone or in combination with radiation and/or other chemotherapeutic agents, is an important first-line chemotherapy for a broad range of cancers. The clinical utility of cisplatin is limited both by intrinsic and acquired resistance and dose-limiting normal tissue toxicity. That cisplatin shows little selectivity for tumor versus normal tissue may be a critical factor limiting its value. To overcome the low therapeutic ratio of the free drug, macromolecular, liposomal and nanoparticle drug delivery systems have been explored toward leveraging the enhanced permeability and retention (EPR) effect and promoting delivery of cisplatin to tumors. Here, we survey recent advances in nanoparticle formulations of cisplatin, focusing on agents that show promise in preclinical or clinical settings. PMID:26848041

Thymoquinone-based nanotechnology for cancer therapy: promises and challenges.

PubMed

Ballout, Farah; Habli, Zeina; Rahal, Omar Nasser; Fatfat, Maamoun; Gali-Muhtasib, Hala

2018-05-01

Thymoquinone (TQ), the active ingredient of black seed, is a promising anticancer molecule that inhibits cancer cell growth and progression in vitro and in vivo. Despite the promising anticancer activities of TQ, its translation to the clinic is limited by its poor bioavailability and hydrophobicity. As such, we and others encapsulated TQ in nanoparticles to improve its delivery and limit undesirable cytotoxicity. These TQ-nanoparticle formulations showed improved anticancer and anti-inflammatory activities when compared with free TQ. Here, we provide an overview of the various TQ-nanoparticle formulations, highlight their superior efficacy and discuss up-to-date solutions to further enhance TQ bioavailability and anticancer activity, thus improving potential for clinical translation. Copyright © 2018 Elsevier Ltd. All rights reserved.

A sight on protein-based nanoparticles as drug/gene delivery systems.

PubMed

Salatin, Sara; Jelvehgari, Mitra; Maleki-Dizaj, Solmaz; Adibkia, Khosro

2015-01-01

Polymeric nanomaterials have extensively been applied for the preparation of targeted and controlled release drug/gene delivery systems. However, problems involved in the formulation of synthetic polymers such as using of the toxic solvents and surfactants have limited their desirable applications. In this regard, natural biomolecules including proteins and polysaccharide are suitable alternatives due to their safety. According to literature, protein-based nanoparticles possess many advantages for drug and gene delivery such as biocompatibility, biodegradability and ability to functionalize with targeting ligands. This review provides a general sight on the application of biodegradable protein-based nanoparticles in drug/gene delivery based on their origins. Their unique physicochemical properties that help them to be formulated as pharmaceutical carriers are also discussed.

Readily prepared biodegradable nanoparticles to formulate poorly water soluble drugs improving their pharmacological properties: The example of trabectedin.

PubMed

Capasso Palmiero, Umberto; Morosi, Lavinia; Bello, Ezia; Ponzo, Marianna; Frapolli, Roberta; Matteo, Cristina; Ferrari, Mariella; Zucchetti, Massimo; Minoli, Lucia; De Maglie, Marcella; Romanelli, Pierpaolo; Morbidelli, Massimo; D'Incalci, Maurizio; Moscatelli, Davide

2018-04-28

The improvement of the pharmacological profile of lipophilic drug formulations is one of the main successes achieved using nanoparticles (NPs) in medicine. However, the complex synthesis procedure and numerous post-processing steps hamper the cost-effective use of these formulations. In this work, an approach which requires only a syringe to produce self-assembling biodegradable and biocompatible poly(caprolactone)-based NPs is developed. The effective synthesis of monodisperse NPs has been made possible by the optimization of the block-copolymer synthesized via a combination of ring opening polymerization and reversible addition-fragmentation chain transfer polymerization. These NPs can be used to formulate lipophilic drugs that are barely soluble in water, such as trabectedin, a potent anticancer therapeutic. Its biodistribution and antitumor activity have been compared with the commercially available formulation Yondelis®. The results indicate that this trabectedin NP formulation performs with the same antitumor activity as Yondelis®, but does not have the drawback of severe local vascular toxicity in the injection site. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin.

PubMed

Wu, Bo; Yu, Ping; Cui, Can; Wu, Ming; Zhang, Yang; Liu, Lei; Wang, Cai-Xia; Zhuo, Ren-Xi; Huang, Shi-Wen

2015-04-01

The development and evaluation of folate-targeted and reduction-triggered biodegradable nanoparticles are introduced to the research on targeted delivery of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA) core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16) reduction-sensitive shell, and a folic acid-targeted ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated cancer cell reductive environment. The experiments on the release process in vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from flow cytometry, confocal image and in vitro cytotoxicity assays revealed that FLPNPs further enhanced cell uptake and generated higher cytotoxicity against human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive and targeted redox-insensitive controls. Furthermore, in vivo animal experiments demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations have proved to be a stable, controllable and targeted anticancer drug delivery system.

Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer

PubMed Central

Dai, Dejian; Hou, Yiming

2017-01-01

The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen-1 nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1:1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82.9 nm, +21.8 mV, 85.7% and 35.4%, respectively. Bio-CS exhibited an apparent liver cancer targeting effect in vitro and in vivo, as demonstrated by confocal laser scanning, green fluorescent protein transfection, and in vivo imaging assays. In addition, the Bio-CS/plasmid DNA nanoparticles significantly increased the survival period of the orthotropic liver cancer mouse model compared with the plasmid DNA, with no apparent side effects on the cells. Bio-CS nanomaterials stimulated an immune response in hepatoma cells via increased expression of GM-CSF, IL-21 and Rae-1 markers. The data suggest that Bio-CS increased the inhibition of liver cancer cell proliferation in vitro and the activation of the cellular immunity in vivo. PMID:28938619

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.

Estimating Dermal Transfer of Copper Particles from the ...

EPA Pesticide Factsheets

Lumber pressure-treated with micronized copper was examined for the release of copper and copper micro/nanoparticles using a surface wipe method to simulate dermal transfer. In 2003, the wood industry began replacing CCA treated lumber products for residential use with copper based formulations. Micronized copper (nano to micron sized particles) has become the preferred treatment formulation. There is a lack of information on the release of copper, the fate of the particles during dermal contact, and the copper exposure level to children from hand-to-mouth transfer. For the current study, three treated lumber products, two micronized copper and one ionic copper, were purchased from commercial retailers. The boards were left to weather outdoors for approximately 1 year. Over the year time period, hand wipe samples were collected periodically to determine copper transfer from the wood surfaces. The two micronized formulations and the ionic formulation released similar levels of total copper. The amount of copper released was high initially, but decreased to a constant level (~1.5 mg m-2) after the first month of outdoor exposure. Copper particles were identified on the sampling cloths during the first two months of the experiment, after which the levels of copper were insufficient to collect interpretable data. After 1 month, the particles exhibited minimal changes in shape and size. At the end of 2-months, significant deterioration of the particles was

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.

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.

Spray-dried powders enhance vaginal siRNA delivery by potentially modulating the mucus molecular sieve structure.

PubMed

Wu, Na; Zhang, Xinxin; Li, Feifei; Zhang, Tao; Gan, Yong; Li, Juan

2015-01-01

Vaginal small interfering RNA (siRNA) delivery provides a promising strategy for the prevention and treatment of vaginal diseases. However, the densely cross-linked mucus layer on the vaginal wall severely restricts nanoparticle-mediated siRNA delivery to the vaginal epithelium. In order to overcome this barrier and enhance vaginal mucus penetration, we prepared spray-dried powders containing siRNA-loaded nanoparticles. Powders with Pluronic F127 (F127), hydroxypropyl methyl cellulose (HPMC), and mannitol as carriers were obtained using an ultrasound-assisted spray-drying technique. Highly dispersed dry powders with diameters of 5-15 μm were produced. These powders showed effective siRNA protection and sustained release. The mucus-penetrating properties of the powders differed depending on their compositions. They exhibited different potential of opening mesh size of molecular sieve in simulated vaginal mucus system. A powder formulation with 0.6% F127 and 0.1% HPMC produced the maximum increase in the pore size of the model gel used to simulate vaginal mucus by rapidly extracting water from the gel and interacting with the gel; the resulting modulation of the molecular sieve effect achieved a 17.8-fold improvement of siRNA delivery in vaginal tract and effective siRNA delivery to the epithelium. This study suggests that powder formulations with optimized compositions have the potential to alter the steric barrier posed by mucus and hold promise for effective vaginal siRNA delivery.

Enhanced skin penetration of lidocaine through encapsulation into nanoethosomes and nanostructured lipid carriers: a comparative study.

PubMed

Babaei, S; Ghanbarzadeh, S; Adib, Z M; Kouhsoltani, M; Davaran, S; Hamishehkar, H

2016-05-01

Lipid based nanoparticles have become a major research object in topical drug delivery to enable drugs to pass the stratum corneum and reach the desired skin layer. The present investigation deals with the encapsulation of lidoacine into nanostructured lipid carriers (NLCs) and nanoethosomes for improving its dermal delivery and consequently local anesthetic efficacy. Concurrently these two topical delivery systems were compared. Lidocaine-loaded NLCs and nanoethosomes were characterized by various techniques and used for an in vitro skin penetration study using excised rat skin and Franz diffusion cells. The nanoparticles were tracked in the skin by following the Rhodamine-labled nanocarriers under fluorescent microscopy. Optimized lidocaine-loaded NLCs (size 96 nm, zeta potential -13.7 mV, encapsulation efficiency (EE) % 69.86% and loading capacity (LC) % 10.47%) and nanoethosomes (size 105.4 nm, zeta potential -33.6 mV, EE 40.14% and LC 8.02%) were chosen for a skin drug delivery study. Higher skin drug deposition of NLCs and nanoethosomal formulations compared to lidocaine hydroalcoholic solution represented a better localization of the drug in the skin. NLC formulation showed the lowest entered drug in the receptor phase of Franz diffusion cell in comparison with nanoethosomes and hydroalcoholic solution confirming the highest skin accumulation of drug. Both colloidal systems showed superiority over the drug solution for dermal delivery of lidocaine, however, NLC exhibited more promising characteristics than nanoethosomes regarding drug loading and skin targeted delivery.

Fate of Zinc Oxide Nanoparticles during Anaerobic Digestion of Wastewater and Post-Treatment Processing of Sewage Sludge

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

Lombi, Enzo; Donner, Erica; Tavakkoli, Ehsan

2013-01-14

The rapid development and commercialization of nanomaterials will inevitably result in the release of nanoparticles (NPs) to the environment. As NPs often exhibit physical and chemical properties significantly different from those of their molecular or macrosize analogs, concern has been growing regarding their fate and toxicity in environmental compartments. The wastewater-sewage sludge pathway has been identified as a key release pathway leading to environmental exposure to NPs. In this study, we investigated the chemical transformation of two ZnO-NPs and one hydrophobic ZnO-NP commercial formulation (used in personal care products), during anaerobic digestion of wastewater. Changes in Zn speciation as amore » result of postprocessing of the sewage sludge, mimicking composting/stockpiling, were also assessed. The results indicated that 'native' Zn and Zn added either as a soluble salt or as NPs was rapidly converted to sulfides in all treatments. The hydrophobicity of the commercial formulation retarded the conversion of ZnO-NP. However, at the end of the anaerobic digestion process and after postprocessing of the sewage sludge (which caused a significant change in Zn speciation), the speciation of Zn was similar across all treatments. This indicates that, at least for the material tested, the risk assessment of ZnO-NP through this exposure pathway can rely on the significant knowledge already available in regard to other 'conventional' forms of Zn present in sewage sludge.« less

Highly sensitive and selective determination of methylergometrine maleate using carbon nanofibers/silver nanoparticles composite modified carbon paste electrode.

PubMed

Kalambate, Pramod K; Rawool, Chaitali R; Karna, Shashi P; Srivastava, Ashwini K

2016-12-01

A highly sensitive and selective voltammetric method for determination of Methylergometrine maleate (MM) in pharmaceutical formulations, urine and blood serum samples has been developed based on enhanced electrochemical response of MM at carbon nanofibers and silver nanoparticles modified carbon paste electrode (CNF-AgNP-CPE). The electrode material was characterized by various techniques viz., X-ray diffraction, scanning electron microscopy and energy dispersive X-ray spectroscopy. The electrocatalytic response of MM at CNF-AgNP-CPE was studied by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). Under optimized conditions, the proposed sensor exhibits excellent electrochemical response towards MM. The DPV study shows greatly enhanced electrochemical signal for MM at CNF-AgNP-CPE lending high sensitivity to the proposed sensor for MM detection. The peak (Ip) current for MM is found to be rectilinear in the range 4.0×10(-8)-2.0×10(-5)M with a detection limit of 7.1×10(-9)M using DPV. The feasibility of the proposed sensor in analytical applications was investigated by conducting experiments on commercial pharmaceutical formulations, human urine and blood serum samples, which yielded satisfactory recoveries of MM. The proposed electrochemical sensor offers high sensitivity, selectivity, reproducibility and practical utility. We recommend it as an authentic and productive electrochemical sensor for successful determination of MM. Copyright © 2016. Published by Elsevier B.V.

2’-Behenoyl-Paclitaxel Conjugate Containing Lipid Nanoparticles for the Treatment of Metastatic Breast Cancer

PubMed Central

Ma, Ping; Benhabbour, S. Rahima; Feng, Lan; Mumper, Russell J

2012-01-01

The aim of these studies was to develop a novel 2’-behenoyl-paclitaxel (C22-PX) conjugate nanoparticle (NP) formulation for the treatment of metastatic breast cancer. A lipophilic paclitaxel derivative C22-PX was synthesized and incorporated into lipid-based NPs. Free C22-PX and its NP formulation were evaluated in a series of in-vitro and in-vivo studies. The results demonstrated that C22-PX NPs were much better tolerated and had significantly higher plasma and tumor AUCs compared to Taxol at the maximum tolerated dose (MTD) in a subcutaneous 4T1 mouse mammary carcinoma model. These benefits resulted in significantly improved antitumor efficacy with the NP-based formulation. PMID:22902506

Sustained release and permeation of timolol from surface-modified solid lipid nanoparticles through bioengineered human cornea.

PubMed

Attama, A A; Reichl, S; Müller-Goymann, C C

2009-08-01

The aim of the study was to formulate and evaluate surface-modified solid lipid nanoparticles sustained delivery system of timolol hydrogen maleate, a prototype ocular drug using a human cornea construct. Surface-modified solid lipid nanoparticles containing timolol with and without phospholipid were formulated by melt emulsification with high-pressure homogenization and characterized by particle size, wide-angle X-ray diffraction, encapsulation efficiency, and in vitro drug release. Drug transport studies through cornea bioengineered from human donor cornea cells were carried out using a modified Franz diffusion cell and drug concentration analyzed by high-performance liquid chromatography. Results show that surface-modified solid lipid nanoparticles possessed very small particles (42.9 +/- 0.3 nm, 47.2 +/- 0.3 nm, 42.7 +/- 0.7 nm, and 37.7 +/- 0.3 nm, respectively for SM-SLN 1, SM-SLN 2, SM-SLN 3, and SM-SLN 4) with low polydispersity indices, increased encapsulation efficiency (> 44%), and sustained in vitro release compared with unmodified lipid nanoparticles whose particles were greater than 160 nm. Permeation of timolol hydrogen maleate from the surface-modified lipid nanoparticles across the cornea construct was sustained compared with timolol hydrogen maleate solution in distilled water. Surface-modified solid lipid nanoparticles could provide an efficient way of improving ocular bioavailability of timolol hydrogen maleate.

[Preparation of scopolamine hydrobromide nanoparticles-in-microsphere system].

PubMed

Lü, Wei-ling; Hu, Jin-hong; Zhu, Quan-gang; Li, Feng-qian

2010-07-01

This study is to prepare scopolamine hydrobromide nanoparticles-in-microsphere system (SH-NiMS) and evaluate its drug release characteristics in vitro. SH nanoparticles were prepared by ionic crosslinking method with tripolyphosphate (TPP) as crosslinker and chitosan as carrier. Orthogonal design was used to optimize the formulation of SH nanoparticles, which took the property of encapsulation efficiency and drug loading as evaluation parameters. With HPMC as carrier, adjusted the parameters of spray drying technique and sprayed the SH nanoparticles in microspheres encaposulated by HPMC was formed and which is called nanoparticles-in-microsphere system (NiMS). SH-NiMS appearances were observed by SEM, structure was obsearved by FT-IR and the release characteristics in vitro were evaluated. The optimized formulation of SH nanoparticles was TPP/CS 1:3 (w/w), HPMC 0.3%, SH 0.2%. The solution peristaltic speed of the spray drying technique was adjusted to 15%, and the temperature of inlet was 110 degrees C. The encapsulation product yeild, drug loading and particle sizes of SH-NiMS were 94.2%, 20.4%, and 1256.5 nm, respectively. The appearances and the structure of SH-NiMS were good. The preparation method of SH-NiMS is stable and reliable to use, which provide a new way to develop new dosage form.

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.

Dual drug-loaded nanoparticles on self-integrated scaffold for controlled delivery

PubMed Central

Bennet, Devasier; Marimuthu, Mohana; Kim, Sanghyo; An, Jeongho

2012-01-01

Antioxidant (quercetin) and hypoglycemic (voglibose) drug-loaded poly-D,L-lactideco-glycolide nanoparticles were successfully synthesized using the solvent evaporation method. The dual drug-loaded nanoparticles were incorporated into a scaffold film using a solvent casting method, creating a controlled transdermal drug-delivery system. Key features of the film formulation were achieved utilizing several ratios of excipients, including polyvinyl alcohol, polyethylene glycol, hyaluronic acid, xylitol, and alginate. The scaffold film showed superior encapsulation capability and swelling properties, with various potential applications, eg, the treatment of diabetes-associated complications. Structural and light scattering characterization confirmed a spherical shape and a mean particle size distribution of 41.3 nm for nanoparticles in the scaffold film. Spectroscopy revealed a stable polymer structure before and after encapsulation. The thermoresponsive swelling properties of the film were evaluated according to temperature and pH. Scaffold films incorporating dual drug-loaded nanoparticles showed remarkably high thermoresponsivity, cell compatibility, and ex vivo drug-release behavior. In addition, the hybrid film formulation showed enhanced cell adhesion and proliferation. These dual drug-loaded nanoparticles incorporated into a scaffold film may be promising for development into a transdermal drug-delivery system. PMID:22888222

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.

A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity**

PubMed Central

Chen, Kuan-Ju; Wolahan, Stephanie M.; Wang, Hao; Hsu, Chao-Hsiung; Chang, Hsing-Wei; Durazo, Armando; Hwang, Lian-Pin; Garcia, Mitch A.; Jiang, Ziyue Karen; Wu, Lily

2010-01-01

We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd3+·DOTA-encapsulated supramolecular nanoparticles (Gd3+·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd3+·DOTA⊂SNPs with an r1 of 17.3 s−1mM−1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1-weighted imaging of Gd3+·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd3+·DTPA. A Gd3+·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1-weighted imaging after injecting Gd3+·DOTA⊂SNPs but not after injecting Gd3+·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd3+·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis. PMID:21167594

A sensitive determination of terbutaline in pharmaceuticals and urine samples using a composite electrode based on zirconium oxide nanoparticles.

PubMed

Baytak, Aysegul Kutluay; Teker, Tugce; Duzmen, Sehriban; Aslanoglu, Mehmet

2016-10-01

An accurate and precise determination of terbutaline has been carried out using a glassy carbon electrode (GCE) modified with a composite of multi-walled carbon nanotubes (MWCNTs) and nanoparticles of zirconium oxide (ZrO2NPs). Energy dispersive X-ray and scanning electron microscopic techniques were utilized for the characterization of the composite layer. Terbutaline exhibited a broad oxidation peak at 770mV on a GCE. However, MWCNTs/GCE presented an electrocatalytic effect toward the oxidation of terbutaline with a better anodic peak at 660mV. Furthermore, the electrochemical behavior of terbutaline has greatly been improved at a GCE modified with a composite of MWCNTs and nanoparticles of ZrO2. The ZrO2NPs/MWCNTs/GCE exhibited a sharp anodic wave at 645mV with a large enhancement of the current response for terbutaline. Square wave voltammetry (SWV) was performed for the determination of terbutaline at ZrO2NPs/MWCNTs/GCE. A linear plot was obtained for the current responses of terbutaline against concentrations in the range of 10-160nM yielding a detection limit of 2.25nM (based on 3Sb/m). Improved voltammetric behavior, long-time stability and good reproducibility were obtained for terbutaline at the proposed electrode. A mean recovery of 101.2% with an RSD% of 1.9 was obtained for the analysis of the drug formulation. The accurate and precise quantification of terbutaline makes the ZrO2NPs/MWCNTs/GCE system of great interest for monitoring its therapeutic use. Copyright © 2016 Elsevier B.V. All rights reserved.

Fabrication of doxorubicin nanoparticles by controlled antisolvent precipitation for enhanced intracellular delivery.

PubMed

Tam, Yu Tong; To, Kenneth Kin Wah; Chow, Albert Hee Lum

2016-03-01

Over-expression of ATP-binding cassette transporters is one of the most important mechanisms responsible for multidrug resistance. Here, we aimed to develop a stable polymeric nanoparticle system by flash nanoprecipitation (FNP) for enhanced anticancer drug delivery into drug resistant cancer cells. As an antisolvent precipitation process, FNP works best for highly lipophilic solutes (logP>6). Thus we also aimed to evaluate the applicability of FNP to drugs with relatively low lipophilicity (logP=1-2). To this end, doxorubicin (DOX), an anthracycline anticancer agent and a P-gp substrate with a logP of 1.3, was selected as a model drug for the assessment. DOX was successfully incorporated into the amphiphilic diblock copolymer, polyethylene glycol-b-polylactic acid (PEG-b-PLA), by FNP using a four-stream multi-inlet vortex mixer. Optimization of key processing parameters and co-formulation with the co-stabilizer, polyvinylpyrrolidone, yielded highly stable, roughly spherical DOX-loaded PEG-b-PLA nanoparticles (DOX.NP) with mean particle size below 100nm, drug loading up to 14%, and drug encapsulation efficiency up to 49%. DOX.NP exhibited a pH-dependent drug release profile with higher cumulative release rate at acidic pHs. Surface analysis of DOX.NP by XPS revealed an absence of DOX on the particle surface, indicative of complete drug encapsulation. While there were no significant differences in cytotoxic effect on P-gp over-expressing LCC6/MDR cell line between DOX.NP and free DOX in buffered aqueous media, DOX.NP exhibited a considerably higher cellular uptake and intracellular retention after efflux. The apparent lack of cytotoxicity enhancement with DOX.NP may be attributable to its slow DOX release inside the cells. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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.

Green Synthesis of Formulated Zinc Oxide Nanoparticles for Chemical Protection of Skin Care and Related Applications

NASA Astrophysics Data System (ADS)

Koppolu, Ramya

Nanomaterials have diversified applications based on the unique properties. These nanoparticles and functionalized nanocomposites have been studied in the health care filed. Nanoparticles are mostly used in sunscreens which are a part of human life. These sunscreens consist of titanium dioxide and zinc oxide nanoparticles. Due to the higher band crevices, they help the skin to protect from ultraviolet rays, for instance, ultraviolet B and ultraviolet A. A series of nanostructured zinc oxide nanoparticles were prepared by cost-effective chemical and bioinspired methods and variables were optimized. Highly stable and spherical zinc oxide nanoparticles were formulated by aloe vera ( Aloe barbadensis) plant extract and avocado (Persea americana Mill) fruit extract. The state-of-the-art instrumentation was used to characterize the morphology, elemental composition, and particle size distribution. X-ray diffraction data indicated highly crystalline and ultrafine nanoparticles were obtained from the colloidal methods. The X-ray photoelectron spectroscopy results showed the chemical state of zinc, carbon, and oxygen atoms were well-indexed and are used as fingerprint identification of the elements. Transmission electron microscopy images show the shape of particles were cubic and fiber shape contingent upon the protecting operators and heat treatment conditions. The toxicity studies of zinc oxide nanoparticles were found to cause an increase in nitric oxide, which is protecting against further oxidative stress and appears to be nontoxic.

A Glu-urea-Lys Ligand-conjugated Lipid Nanoparticle/siRNA System Inhibits Androgen Receptor Expression In Vivo

PubMed Central

Lee, Justin B; Zhang, Kaixin; Tam, Yuen Yi C; Quick, Joslyn; Tam, Ying K; Lin, Paulo JC; Chen, Sam; Liu, Yan; Nair, Jayaprakash K; Zlatev, Ivan; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Rennie, Paul S; Cullis, Pieter R

2016-01-01

The androgen receptor plays a critical role in the progression of prostate cancer. Here, we describe targeting the prostate-specific membrane antigen using a lipid nanoparticle formulation containing small interfering RNA designed to silence expression of the messenger RNA encoding the androgen receptor. Specifically, a Glu-urea-Lys PSMA-targeting ligand was incorporated into the lipid nanoparticle system formulated with a long alkyl chain polyethylene glycol-lipid to enhance accumulation at tumor sites and facilitate intracellular uptake into tumor cells following systemic administration. Through these features, and by using a structurally refined cationic lipid and an optimized small interfering RNA payload, a lipid nanoparticle system with improved potency and significant therapeutic potential against prostate cancer and potentially other solid tumors was developed. Decreases in serum prostate-specific antigen, tumor cellular proliferation, and androgen receptor levels were observed in a mouse xenograft model following intravenous injection. These results support the potential clinical utility of a prostate-specific membrane antigen–targeted lipid nanoparticle system to silence the androgen receptor in advanced prostate cancer. PMID:28131285

Considerations and Some Practical Solutions to Overcome Nanoparticle Interference with LAL Assays and to Avoid Endotoxin Contamination in Nanoformulations.

PubMed

Neun, Barry W; Dobrovolskaia, Marina A

2018-01-01

Monitoring endotoxin contamination in drugs and medical devices is required to avoid pyrogenic response and septic shock in patients receiving these products. Endotoxin contamination of engineered nanomaterials and nanotechnology-based medical products represents a significant translational hurdle. Nanoparticles often interfere with an in vitro Limulus Amebocyte Lysate (LAL) assay commonly used in the pharmaceutical industry for the detection and quantification of endotoxin. Such interference challenges the preclinical development of nanotechnology-formulated drugs and medical devices containing engineered nanomaterials. Protocols for analysis of nanoparticles using LAL assays have been reported before. Here, we discuss considerations for selecting an LAL format and describe a few experimental approaches for overcoming nanoparticle interference with the LAL assays to obtain more accurate estimation of endotoxin contamination in nanotechnology-based products. The discussed approaches do not solve all types of nanoparticle interference with the LAL assays but could be used as a starting point to address the problem. This chapter also describes approaches to prevent endotoxin contamination in nanotechnology-formulated products.

The impact of microfluidic mixing of triblock micelleplexes on in vitro / in vivo gene silencing and intracellular trafficking

NASA Astrophysics Data System (ADS)

Feldmann, Daniel P.; Xie, Yuran; Jones, Steven K.; Yu, Dongyue; Moszczynska, Anna; Merkel, Olivia M.

2017-06-01

The triblock copolymer polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG) has been shown to spontaneously assemble into nano-sized particulate carriers capable of complexing with nucleic acids for gene delivery. The objective of this study was to investigate micelleplex characteristics, their in vitro and in vivo fate following microfluidic preparation of siRNA nanoparticles compared to the routinely used batch reactor mixing technique. Herein, PEI-PCL-PEG nanoparticles were prepared with batch reactor or microfluidic mixing techniques and characterized by various biochemical assays and in cell culture. Microfluidic nanoparticles showed a reduction of overall particle size as well as a more uniform size distribution when compared to batch reactor pipette mixing. Confocal microscopy, flow cytometry and qRT-PCR displayed the subcellular delivery of the microfluidic formulation and confirmed the ability to achieve mRNA knockdown. Intratracheal instillation of microfluidic formulation resulted in a significantly more efficient (p < 0.05) knockdown of GAPDH compared to treatment with the batch reactor formulation. The use of microfluidic mixing techniques yields an overall smaller and more uniform PEG-PCL-PEI nanoparticle that is able to more efficiently deliver siRNA in vivo. This preparation method may prove to be useful when a scaled up production of well-defined polyplexes is required.

The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams.

PubMed

Zhao, Yanjun; Brown, Marc B; Jones, Stuart A

2010-01-04

Nanocarriers may act as useful tools to deliver therapeutic agents to the skin. However, balancing the drug-particle interactions; to ensure adequate drug loading, with the drug-vehicle interactions; to allow efficient drug release, presents a significant challenge using traditional semi-solid vehicles. The aim of this study was to determine how the physicochemical properties of nanoparticles influenced minoxidil release pre and post dose application when formulated as a simple aqueous suspension compared to dynamic hydrofluoroalkane (HFA) foams. Minoxidil loaded lipid nanoparticles (LN, 1.4 mg/ml, 50 nm) and polymeric nanoparticles with a lipid core (PN, 0.6 mg/ml, 260 nm) were produced and suspended in water to produce the aqueous suspensions. These aqueous suspensions were emulsified with HFA using pluronic surfactant to generate the foams. Approximately 60% of the minoxidil loaded into the PN and 80% of the minoxidil loaded into the LN was released into the external aqueous phase 24h after production. Drug permeation was superior from the PN, i.e. it was the particle that retained the most drugs, irrespective of the formulation method. Premature drug release, i.e. during storage, resulted in the performance of the topical formulation being dictated by the thermodynamic activity of the solubilised drug not the particle properties.

Wood protection by commercial silver formulations against Eastern subterranean termites

Treesearch

Frederick Green; Rachel Ann Arango

2007-01-01

The scope of this paper is to compare commercial formulations of aqueous products containing silver for their ability to prevent termite damage by Eastern subterranean termites in a no-choice laboratory test. Five commercial products were tested in order to explore a broad range of formulation and silver forms: colloidal, ionic and nanoparticles. Southern pine wood...

Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug—Efavirenz

PubMed Central

Jenita, Josephine Leno; Chocalingam, Vijaya; Wilson, Barnabas

2014-01-01

Purpose of the study: The antiretroviral therapy (ART) has dramatically improved human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treatment, prevention and also has been found to increase the lifespan of HIV/AIDS patients by providing durable control of the HIV replication in patients. Efavirenz is a non-nucleoside reverse transcriptase inhibitor of HIV-1. The purpose of this study is to formulate efavirenz-loaded bovine serum albumin nanoparticles to improve efavirenz delivery into various organs. Materials and Methods: Nanoparticles were prepared by desolvation technique and coated with polysorbate 80. Ethanol, glutaraldehyde, and mannitol were used as desolvating, cross linking agent, and cryoprotectant, respectively. Drug to polymer ratio was chosen at five levels from 1:2, 1:3, 1:4, 1:5, and 1:6 (by weight). The formulated nanoparticles were characterized for Fourier Transform Infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) studies, entrapment efficiency, particle size, surface charge, surface morphology, in vitro drug release, release kinetics, stability studies, and biodistribution studies. Results and Major Conclusion: The particle size of the prepared formulations was found below 250nm with narrow size distribution, spherical in shape and showed good entrapment efficiency (45.62-72.49%). The in vitro drug release indicated biphasic release and its data were fitted to release kinetics models and release pattern was Fickian diffusion controlled release profile. The prepared nanoparticles increased efavirenz delivery into various organs by several fold in comparison with the free drug. PMID:25126528

Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of aromatase inhibitor 7alpha-APTADD to breast cancer cells.

PubMed

Zheng, Yu; Yu, Bo; Weecharangsan, Wanlop; Piao, Longzhu; Darby, Michael; Mao, Yicheng; Koynova, Rumiana; Yang, Xiaojuan; Li, Hong; Xu, Songlin; Lee, L James; Sugimoto, Yasuro; Brueggemeier, Robert W; Lee, Robert J

2010-05-10

Transferrin (Tf)-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles carrying the aromatase inhibitor, 7alpha-(4'-amino)phenylthio-1,4-androstadiene-3,17-dione (7alpha-APTADD), were synthesized by a solvent injection method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug-to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were optimized to obtain nanoparticles with desired sizes and drug loading efficiency. The optimal formulation had a drug loading efficiency of 36.3+/-3.4%, mean diameter of 170.3+/-7.6nm and zeta potential of -18.9+/-1.5mV. The aromatase inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer cells. IC(50) value of the Tf-nanoparticles was ranging from 0.77 to 1.21nM, and IC(50) value of the nanoparticles was ranging from 1.90 to 3.41nM (n=3). The former is significantly lower than the latter (p<0.05). These results suggested that the aromatase inhibition activity of the Tf-nanoparticles was enhanced relative to that of the non-targeted nanoparticles, which was attributable to Tf receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA nanoparticles are potential vehicles for improving the efficiency and specificity of therapeutic delivery of aromatase inhibitors. Copyright 2010 Elsevier B.V. All rights reserved.

Synthesis and characterization of bactericidal silver nanoparticles using cultural filtrate of simulated microgravity grown Klebsiella pneumoniae.

PubMed

Kalpana, Duraisamy; Lee, Yang Soo

2013-03-05

Silver nanoparticles were synthesized by biological method using cultural filtrate of Klebsiella pneumoniae cultured under simulated microgravity and silver nitrate solution as precursor. The nanoparticles exhibited typical plasmon absorption maximum of silver nanoparticles between 405 and 407 nm. Spherical silver nanoparticles were found to have size between 15 and 37 nm by TEM analysis. XRD pattern corresponding to planes (111), (200), (220) (311) revealed the crystalline nature of the biosynthesized silver nanoparticles. FTIR spectrum proposed stabilization of silver nanoparticles by the protein molecules present in the cultural filtrate. The silver nanoparticles exhibited high bactericidal activity against Salmonella enterica, Escherichia coli and moderate bactericidal activity against Streptococcus pyogenes. Copyright © 2012 Elsevier Inc. All rights reserved.

Surface interactions between gold nanoparticles and biochar

USDA-ARS?s Scientific Manuscript database

Engineered nanomaterials are directly applied to agricultural soils as a part of pesticide/fertilize formulations and sludge/manure amendments. Yet, no prior reports are available on the extent and reversibility of gold nanoparticles (nAu) retention by soil components including charcoal black carbo...

Glucocorticoid receptor-mediated delivery of nano gold-withaferin conjugates for reversal of epithelial-to-mesenchymal transition and tumor regression.

PubMed

Agarwalla, Pritha; Mukherjee, Sudip; Sreedhar, Bojja; Banerjee, Rajkumar

2016-10-01

To explore the potential of glucocorticoid receptor-targeted nano-gold formulation as antitumor drug sensitizing agent. Simultaneous conjugation of gold nanoparticle with thiol-modified dexamethasone, a synthetic glucocorticoid and anticancer drug withaferin A afforded stable gold nanoparticle-modifed dexamethasone-withaferin A nanoconjugate. This metallic nanoparticle formulation showed glucocorticoid receptor-dependent cancer cell selective cytotoxicity, inhibited growth of aggressive mouse melanoma tumor, reduced mice mortality, while reversing epithelial-to-mesenchymal transition in tumor cells. Same treatment also leads to near-complete downregulation of ABCG2 drug transporter in tumor-associated cells thus attributing it to its drug sensitizing ability. The presently synthesized nanoconjugate holds a great promise to sensitize cancer cells to chemotherapeutics and induce epithelial-to-mesenchymal transition reversal in tumor cells preventing metastasis.

Evaluation of an oral carrier system in rats: bioavailability and gastrointestinal absorption properties of curcumin encapsulated PBCA nanoparticles

NASA Astrophysics Data System (ADS)

Sun, Min; Zhao, Lixia; Guo, Chenyu; Cao, Fengliang; Chen, Huanlei; Zhao, Liyan; Tan, Qi; Zhu, Xiuqing; Zhu, Fanping; Ding, Tingting; Zhai, Yingjie; Zhai, Guangxi

2012-02-01

A new oral delivery system, polybutylcyanoacrylate nanoparticles (PBCNs), was introduced to improve the oral bioavailability of curcumin (CUR), a poorly soluble drug. The formulation was optimized by orthogonal design and the optimal PBCNs loading CUR exhibited a spherical shape under transmission electron microscopy with a range of 40-400 nm. Physicochemical state of CUR in PBCN was investigated by X-ray diffraction and the possible structure changes occurring in CUR after conjugating with polybutylcyanoacrylate were studied with FTIR. The results indicated that CUR in PBCN was in a non-crystalline state and CUR was encapsulated in PBCN without chemical reaction. The oral pharmacokinetic study was conducted in rats and the relative bioavailability of CUR encapsulated PBCNs to the crude CUR was more than 800%. The in situ absorption experiment in rat intestine indicated the absorption was first order with passive diffusion mechanism. The absorption results in various segments of intestine showed that the main absorption sites were ileum and colon. It can be concluded that PBCNs as an oral carrier can significantly improve the oral absorption of a poorly soluble drug.

A modified spontaneous emulsification solvent diffusion method for the preparation of curcumin-loaded PLGA nanoparticles with enhanced in vitro anti-tumor activity

NASA Astrophysics Data System (ADS)

Chen, Cen; Yang, Wei; Wang, Dan-Tong; Chen, Chao-Long; Zhuang, Qing-Ye; Kong, Xiang-Dong

2014-12-01

To improve the anti-tumor activity of hydrophobic drug curcumin, we prepared curcumin-loaded PLGA nanoparticles (PLGA-Cur NPs) through a modified spontaneous emulsification solvent diffusion (modified-SESD) method. The influence of main preparation parameters was investigated, such as the volume ratio of binary organic solvents and the concentration of surfactant. Results indicated that the synthesized regular spherical PLGA NPs with the average diameter of 189.7 nm exhibited relatively higher yield (58.9%), drug loading (11.0% (w/w)) and encapsulation efficiency (33.5%), and also a controllable drug release profile. In order to evaluate the in vitro cytotoxicity of the prepared NPs, MTT assay was conducted, and results showed that the NPs could effectively inhibit HL60 and HepG2 cells with lower IC50 values compared with free curcumin. Furthermore, confocal microscopy together with flow cytometry analysis proved the enhanced apoptosis-inducing ability of PLGA-Cur NPs. Polymeric NP formulations are potential to be used for hydrophobic drug delivery systems in cancer therapy.

Friction and Wear of Nanoadditive-Based Biolubricants in Steel-Steel Sliding Contacts: A Comparative Study

NASA Astrophysics Data System (ADS)

Gupta, Rajeev Nayan; Harsha, A. P.

2018-02-01

The present work deals with the study of tribo-pair interaction in lubricated sliding contacts. By considering the environmental issues, the sunflower oil was extracted from the sunflower seeds and used as a base lubricant. The two types of the nanoadditives, i.e., CuO and CeO2, varying concentrations from 0.10 to 0.50% w/v were used to formulate the nanolubricants. The compatibility/synergism of the nanoadditives was examined from antifriction and antiwear behavior study with four-ball tester. Also, sunflower oil was modified by the chemical method to improve its fatty acid structure. A comparative tribological and compatibility study was also done in modified oil at similar concentration levels with both types of nanoparticles. The tribological test result exhibits 0.10% w/v concentration of the nanoadditive as optimum due to lowest wear scar and coefficient of friction. Higher concentration of the nanoparticles impaired the base oil performance. Different analytical tools were used to characterize the oil modification and worn surfaces. Moreover, the role of subsurface of the contacting material with the tribological performance has been reported.

Mechanically Robust, Ultraelastic Hierarchical Foam with Tunable Properties via 3D Printing

DOE PAGES

Chen, Qiyi; Cao, Peng-Fei; Advincula, Rigoberto C.

2018-04-11

We present a mechanically robust, ultraelastic foam with controlled multiscale architectures and tunable mechanical/conductive performance is fabricated via 3D printing. Hierarchical porosity, including both macro- and microscaled pores, are produced by the combination of direct ink writing (DIW), acid etching, and phase inversion. The thixotropic inks in DIW are formulated by a simple one-pot process to disperse duo nanoparticles (nanoclay and silica nanoparticles) in a polyurethane suspension. The resulting lightweight foam exhibits tailorable mechanical strength, unprecedented elasticity (standing over 1000 compression cycles), and remarkable robustness (rapidly and fully recover after a load more than 20 000 times of its ownmore » weight). Surface coating of carbon nanotubes yields a conductive elastic foam that can be used as piezoresistivity sensor with high sensitivity. For the first time, this strategy achieves 3D printing of elastic foam with controlled multilevel 3D structures and mechanical/conductive properties. In conclusion, the facile ink preparation method can be utilized to fabricate foams of various materials with desirable performance via 3D printing.« 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

Mechanically Robust, Ultraelastic Hierarchical Foam with Tunable Properties via 3D Printing

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

Chen, Qiyi; Cao, Peng-Fei; Advincula, Rigoberto C.

We present a mechanically robust, ultraelastic foam with controlled multiscale architectures and tunable mechanical/conductive performance is fabricated via 3D printing. Hierarchical porosity, including both macro- and microscaled pores, are produced by the combination of direct ink writing (DIW), acid etching, and phase inversion. The thixotropic inks in DIW are formulated by a simple one-pot process to disperse duo nanoparticles (nanoclay and silica nanoparticles) in a polyurethane suspension. The resulting lightweight foam exhibits tailorable mechanical strength, unprecedented elasticity (standing over 1000 compression cycles), and remarkable robustness (rapidly and fully recover after a load more than 20 000 times of its ownmore » weight). Surface coating of carbon nanotubes yields a conductive elastic foam that can be used as piezoresistivity sensor with high sensitivity. For the first time, this strategy achieves 3D printing of elastic foam with controlled multilevel 3D structures and mechanical/conductive properties. In conclusion, the facile ink preparation method can be utilized to fabricate foams of various materials with desirable performance via 3D printing.« less

Multifunctional Nanoplatforms for Fluorescence Imaging and Photodynamic Therapy Developed by Post-loading Photosensitizer and Fluorophore to Polyacrylamide Nanoparticles

PubMed Central

Gupta, Anurag; Wang, Shouyan; Pera, Paula; Rao, K.V.R.; Patel, Nayan; Ohulchanskyy, Tymish Y.; Missert, Joseph; Morgan, Janet; Koo-Lee, Yong-Eun; Kopelman, Raoul; Pandey, Ravindra K.

2011-01-01

We report a novel post-loading approach for constructing a multifunctional biodegradable polyacrylamide (PAA) nanoplatform for tumor-imaging (fluorescence) and photodynamic therapy (PDT). This approach provides an opportunity to post-load the imaging and therapeutic agents at desired concentrations. Among the PAA nanoparticles, a formulation containing the photosensitizer, HPPH [3-(1’-hexyloxyethyl)pyropheophorbide-a], and the cyanine dye in a ratio of 2:1 minimized the undesirable quenching of the HPPH electronic excitation energy due to energy migration within the nanoparticles and/or Förster (fluorescence) resonance energy transfer (FRET) between HPPH and cyanine dye. An excellent tumor-imaging (NIR fluorescence) and phototherapeutic efficacy of the nanoconstruct formulation is demonstrated. Under similar treatment parameters the HPPH in 1% Tween 80/5% aqueous dextrose formulation was less effective than the nanoconstruct containing HPPH and cyanine dye in a ratio of 2 to 1. This is the first example showing the utility of the post-loading approach in developing a nanoconstructs for tumor-imaging and therapy. PMID:22115602

Lipid nanocarriers: influence of lipids on product development and pharmacokinetics.

PubMed

Pathak, Kamla; Keshri, Lav; Shah, Mayank

2011-01-01

Lipid nanocarriers are on the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery. Owing to their size-dependent properties, lipid nanoparticles offer the possibility for development of new therapeutics and an alternative system to other colloidal counterparts for drug administration. An important point to be considered in the selection of a lipid for the carrier system is its effect on the properties of the nanocarrier and also its intended use, as different types of lipids differ in their nature. Researchers around the globe have tapped the potential of solid lipid nanoparticles (SLNs) in developing formulation(s) that can be administered by various routes such as oral, ocular, parenteral, topical, and pulmonary. Since the start of this millennium, a new generation of lipid nanoparticles, namely nanostructured lipid carriers (NLCs), lipid drug conjugates (LDCs), and pharmacosomes, has evolved that have the potential to overcome the limitations of SLNs. The current review article presents broad considerations on the influence of various types of lipids on the diverse characteristics of nanocarriers, encompassing their physicochemical, formulation, pharmacokinetic, and cytotoxic aspects.

Nanoparticle-Based Manipulation of Antigen-Presenting Cells for Cancer Immunotherapy.

PubMed

Fang, Ronnie H; Kroll, Ashley V; Zhang, Liangfang

2015-11-04

Immunotherapeutic approaches for treating cancer overall have been receiving a considerable amount of interest due to the recent approval of several clinical formulations. Among the different modalities, anticancer vaccination acts by training the body to endogenously generate a response against tumor cells. However, despite the large amount of work that has gone into the development of such vaccines, the near absence of clinically approved formulations highlights the many challenges facing those working in the field. The generation of potent endogenous anticancer responses poses unique challenges due to the similarity between cancer cells and normal, healthy cells. As researchers continue to tackle the limited efficacy of vaccine formulations, fresh and novel approaches are being sought after to address many of the underlying problems. Here the application of nanoparticle technology towards the development of anticancer vaccines is discussed. Specifically, there is a focus on the benefits of using such strategies to manipulate antigen presenting cells (APCs), which are essential to the vaccination process, and how nanoparticle-based platforms can be rationally engineered to elicit appropriate downstream immune responses. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation and characterization of solid lipid nanoparticles-a review.

PubMed

Parhi, Rabinarayan; Suresh, Padilama

2012-03-01

In the present scenario, most of the developed and new discovered drugs are posing real challenge to the formulation scientists due to their poor aqueous solubility which in turn is responsible for poor bioavailability. One of the approach to overcome above problem is the packaging of the drug in to particulate carrier system. Among various carriers, lipid emerged as very attractive candidate because of its unique property of enhancing the bioavailability of poorly water soluble drugs. Solid lipid, one of the physical forms of lipid, is used to formulate nanoparticles, popularly known as Solid lipid nanoparticles (SLNs), as an alternative carrier system to emulsions, liposomes and polymeric micro- and nano-particles. SLNs combine advantages of the traditional systems but avoid some of their major disadvantages. This paper reviews numerous production techniques for SLNs along with their advantages and disadvantages. Special attention is paid to the characterization of the SLNs by using various analytical tools. It also emphasizes on physical state of lipid (supercooled melts, different lipid modifications).

Solid Lipid Nanoparticle-Based Calix[n]arenes and Calix-Resorcinarenes as Building Blocks: Synthesis, Formulation and Characterization

PubMed Central

Montasser, Imed; Shahgaldian, Patrick; Perret, Florent; Coleman, Anthony W.

2013-01-01

Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. This paper presents an overview about the use of calix[n]arenes and calix-resorcinarenes in the formulation of SLNs. Because of their specific inclusion capability both in the intraparticle spaces and in the host cavities as well as their capacity for functionalization, these colloidal nanostructures represent excellent tools for the encapsulation of different active pharmaceutical ingredients (APIs) in the area of drug targeting, cosmetic additives, contrast agents, etc. Various synthetic routes to the supramolecular structures will be given. These various routes lead to the formulation of the corresponding SLNs. Characterization, properties, toxicological considerations as well as numerous corresponding experimental studies and analytical methods will be also exposed and discussed. PMID:24196356

Silica Coating of Nonsilicate Nanoparticles for Resin-Based Composite Materials

PubMed Central

Kaizer, M.R.; Almeida, J.R.; Gonçalves, A.P.R.; Zhang, Y.; Cava, S.S.; Moraes, R.R.

2016-01-01

This study was designed to develop and characterize a silica-coating method for crystalline nonsilicate ceramic nanoparticles (Al2O3, TiO2, and ZrO2). The hypothesis was that the coated nonsilicate nanoparticles would stably reinforce a polymeric matrix due to effective silanation. Silica coating was applied via a sol-gel method, with tetraethyl orthosilicate as a silica precursor, followed by heat treatment. The chemical and microstructural characteristics of the nanopowders were evaluated before and after silica coating through x-ray diffraction, BET (Brunauer-Emmett-Teller), energy-dispersive x-ray spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy analyses. Coated and noncoated nanoparticles were silanated before preparation of hybrid composites, which contained glass microparticles in addition to the nanoparticles. The composites were mechanically tested in 4-point bending mode after aging (10,000 thermal cycles). Results of all chemical and microstructural analyses confirmed the successful obtaining of silica-coated nanoparticles. Two distinct aspects were observed depending on the type of nanoparticle tested: 1) formation of a silica shell on the surface of the particles and 2) nanoparticle clusters embedded into a silica matrix. The aged hybrid composites formulated with the coated nanoparticles showed improved flexural strength (10% to 30% higher) and work of fracture (35% to 40% higher) as compared with composites formulated with noncoated nanoparticles. The tested hypothesis was confirmed: silanated silica-coated nonsilicate nanoparticles yielded stable reinforcement of dimethacrylate polymeric matrix due to effective silanation. The silica-coating method presented here is a versatile and promising novel strategy for the use of crystalline nonsilicate ceramics as a reinforcing phase of polymeric composite biomaterials. PMID:27470069

Evaluation of damage progression and mechanical behavior under compression of bone cements containing core-shell nanoparticles by using acoustic emission technique.

PubMed

Pacheco-Salazar, O F; Wakayama, Shuichi; Sakai, Takenobu; Cauich-Rodríguez, J V; Ríos-Soberanis, C R; Cervantes-Uc, J M

2015-06-01

In this work, the effect of the incorporation of core-shell particles on the fracture mechanisms of the acrylic bone cements by using acoustic emission (AE) technique during the quasi-static compression mechanical test was investigated. Core-shell particles were composed of a poly(butyl acrylate) (PBA) rubbery core and a methyl methacrylate/styrene copolymer (P(MMA-co-St)) outer glassy shell. Nanoparticles were prepared with different core-shell ratio (20/80, 30/70, 40/60 and 50/50) and were incorporated into the solid phase of bone cement at several percentages (5, 10 and 15 wt%). It was observed that the particles exhibited a spherical morphology averaging ca. 125 nm in diameter, and the dynamic mechanical analysis (DMA) thermograms revealed the desired structuring pattern of phases associated with core-shell structures. A fracture mechanism was proposed taking into account the detected AE signals and the scanning electron microscopy (SEM) micrographs. In this regard, core-shell nanoparticles can act as both additional nucleation sites for microcracks (and crazes) and to hinder the microcrack propagation acting as a barrier to its growth; this behavior was presented by all formulations. Cement samples containing 15 wt% of core-shell nanoparticles, either 40/60 or 50/50, were fractured at 40% deformation. This fact seems related to the coalescence of microcracks after they surround the agglomerates of core-shell nanoparticles to continue growing up. This work also demonstrated the potential of the AE technique to be used as an accurate and reliable detection tool for quasi-static compression test in acrylic bone cements. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anticancer activity of galactoxyloglucan polysaccharide-conjugated doxorubicin nanoparticles: Mechanistic insights and interactome analysis.

PubMed

Joseph, Manu M; Aravind, S R; George, Suraj K; Raveendran Pillai, K; Mini, S; Sreelekha, T T

2015-06-01

Toxicity associated with chemotherapeutic drugs such as doxorubicin (Dox), is one of the major obstacles that is currently affecting patients. PST-Dox (Galactoxyloglucan, PST001-conjugated Dox) nanoparticles were synthesized by encapsulating Dox with polysaccharide PST001, isolated from Tamarindus indica (Ti) by ionic gelation with tripolyphosphate (TPP). Herein, we demonstrate a detailed mechanistic and interactome network analysis that is specific to PST-Dox action in cancer cells and normal lymphocytes. Our results show that PST-Dox is superior to its parental counterparts, exhibiting a greater cytotoxicity by the induction of apoptosis against a wide variety of cancers by enhanced cellular uptake of Dox from the nanoparticle conjugates. Also, PST-Dox nanoparticles were non-toxic to normal lymphocytes with limited immunostimulatory effects up to certain doses. Elucidation of molecular mechanism by whole genome microarray in cancer cells and lymphocytes revealed that a large number of genes were dysregulated specifically in cancer cells. Specifically, a unique target gene EGR1, contextually determined translational activation of P53 in the cancerous and non-cancerous cells. Most of the key downregulated genes were tyrosine kinases, indicating the potential inhibitory action of PST-Dox on tyrosine kinase oncogenic pathways. Western blotting of proteins corresponding to the genes that were altered at the genomic level was very well correlated in the majority of them, except in a few that demonstrated post-transcriptional modifications. The important findings and highly disciplined approaches highlighted in the present study will speed up the therapeutic potential of this augmented nanoparticle formulation for more robust clinical studies and testing in several cancers. Copyright © 2015 Elsevier B.V. All rights reserved.

When Anatase Nanoparticles Become Bulklike: Properties of Realistic TiO2 Nanoparticles in the 1-6 nm Size Range from All Electron Relativistic Density Functional Theory Based Calculations.

PubMed

Lamiel-Garcia, Oriol; Ko, Kyoung Chul; Lee, Jin Yong; Bromley, Stefan T; Illas, Francesc

2017-04-11

All electron relativistic density functional theory (DFT) based calculations using numerical atom-centered orbitals have been carried out to explore the relative stability, atomic, and electronic structure of a series of stoichiometric TiO 2 anatase nanoparticles explicitly containing up to 1365 atoms as a function of size and morphology. The nanoparticles under scrutiny exhibit octahedral or truncated octahedral structures and span the 1-6 nm diameter size range. Initial structures were obtained using the Wulff construction, thus exhibiting the most stable (101) and (001) anatase surfaces. Final structures were obtained from geometry optimization with full relaxation of all structural parameters using both generalized gradient approximation (GGA) and hybrid density functionals. Results show that, for nanoparticles of a similar size, octahedral and truncated octahedral morphologies have comparable energetic stabilities. The electronic structure properties exhibit a clear trend converging to the bulk values as the size of the nanoparticles increases but with a marked influence of the density functional employed. Our results suggest that electronic structure properties, and hence reactivity, for the largest anatase nanoparticles considered in this study will be similar to those exhibited by even larger mesoscale particles or by bulk systems. Finally, we present compelling evidence that anatase nanoparticles become effectively bulklike when reaching a size of ∼20 nm diameter.

Effects of Nanoparticle Size on Cellular Uptake and Liver MRI with PVP-Coated Iron Oxide Nanoparticles

PubMed Central

Huang, Jing; Bu, Lihong; Xie, Jin; Chen, Kai; Cheng, Zhen; Li, Xingguo; Chen, Xiaoyuan

2010-01-01

The effect of nanoparticle size (30–120 nm) on magnetic resonance imaging (MRI) of hepatic lesions in vivo has been systematically examined using polyvinylpyrrolidone (PVP)-coated iron oxide nanoparticles (PVP-IOs). Such biocompatible PVP-IOs with different sizes were synthesized by a simple one-pot pyrolysis method. These PVP-IOs exhibited good crystallinity and high T2 relaxivities, and the relaxivity increased with the size of the magnetic nanoparticles. It was found that cellular uptake changed with both size and surface physiochemical properties, and that PVP-IO-37 with a core size of 37 nm and hydrodynamic particle size of 100 nm exhibited higher cellular uptake rate and greater distribution than other PVP-IOs and Feridex. We systematically investigated the effect of nanoparticle size on MRI of normal liver and hepatic lesions in vivo. The physical and chemical properties of the nanoparticles influenced their pharmacokinetic behavior, which ultimately determined their ability to accumulate in the liver. The contrast enhancement of PVP-IOs within the liver was highly dependent on the overall size of the nanoparticles, and the 100 nm PVP-IO-37 nanoparticles exhibited the greatest enhancement. These results will have implications in designing engineered nanoparticles that are optimized as MR contrast agents or for use in therapeutics. PMID:21043459

Diclofenac sodium delivery to the eye: in vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct.

PubMed

Attama, Anthony A; Reichl, Stephan; Müller-Goymann, Christel C

2008-05-01

Solid lipid nanoparticles (SLNs) were prepared with a combination of homolipid from goat (goat fat) and phospholipid, and evaluated for diclofenac sodium (DNa) delivery to the eye using bio-engineered human cornea, produced from immortalized human corneal endothelial cells (HENC), stromal fibroblasts and epithelial cells CEPI 17 CL 4. Encapsulation efficiency was high and sustained release of DNa and high permeation through the bio-engineered cornea were achieved. Results obtained in this work showed that permeation of DNa through the cornea construct was improved by formulation as SLN modified with phospholipid.

Production of nanoparticle drug delivery systems with microfluidics tools.

PubMed

Khan, Ikram Ullah; Serra, Christophe A; Anton, Nicolas; Vandamme, Thierry F

2015-04-01

Nowadays the development of composite nano- and microparticles is an extensively studied area of research. This interest is growing because of the potential use of such particles in drug delivery systems. Indeed they can be used in various medical disciplines depending upon their sizes and their size distribution, which determine their final biomedical applications. Amongst the different techniques to produce nanoparticles, microfluidic techniques allow preparing particles having a specific size, a narrow size distribution and high encapsulation efficiency with ease. This review covers the general description of microfluidics, its techniques, advantages and disadvantages with focus on the encapsulation of active principles in polymeric nanoparticles as well as on pure drug nanoparticles. Polymeric nanoparticles constitute the majority of the examples reported; however lipid nanoparticulate systems (DNA, SiRNA nanocarriers) are very comparable and their formulation processes are in most cases exactly similar. Accordingly this review focuses also on active ingredient nanoparticles formulated by nanoprecipitation processes in microfluidic devices in general. It also provides detailed description of the different geometries of most common microfluidic devices and the crucial parameters involved in techniques designed to obtain the desired properties. Although the classical fabrication of nanoparticles drug delivery systems in batch is extremely well-described and developed, their production with microfluidic tools arises today as an emerging field with much more potential. In this review we present and discuss these new possibilities for biomedical applications through the current emerging developments.

Fluoride loaded polymeric nanoparticles for dental delivery.

PubMed

Nguyen, Sanko; Escudero, Carlos; Sediqi, Nadia; Smistad, Gro; Hiorth, Marianne

2017-06-15

The overall aim of the present paper was to develop fluoride loaded nanoparticles based on the biopolymers chitosan, pectin, and alginate, for use in dental delivery. First, the preparation of nanoparticles in the presence of sodium fluoride (NaF) as the active ingredient by ionic gelation was investigated followed by an evaluation of their drug entrapment and release properties. Chitosan formed stable, spherical, and monodisperse nanoparticles in the presence of NaF and tripolyphoshate as the crosslinker, whereas alginate and pectin were not able to form any definite nanostructures in similar conditions. The fluoride loading capacity was found to be 33-113ppm, and the entrapment efficiency 3.6-6.2% for chitosan nanoparticles prepared in 0.2-0.4% (w/w) NaF, respectively. A steady increase in the fluoride release was observed for chitosan nanoparticles prepared in 0.2% NaF both in pH5 and 7 until it reached a maximum at time point 4h and maintained at this level for at least 24h. Similar profiles were observed for formulations prepared in 0.4% NaF; however the fluoride was released at a higher level at pH5. The low concentration, but continuous delivery of fluoride from the chitosan nanoparticles, with possible expedited release in acidic environment, makes these formulations highly promising as dental delivery systems in the protection against caries development. Copyright © 2017 Elsevier B.V. All rights reserved.

Surface modification of PLGA nanoparticles by carbopol to enhance mucoadhesion and cell internalization.

PubMed

Surassmo, Suvimol; Saengkrit, Nattika; Ruktanonchai, Uracha Rungsardthong; Suktham, Kunat; Woramongkolchai, Noppawan; Wutikhun, Tuksadon; Puttipipatkhachorn, Satit

2015-06-01

Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90 nm), and strong negative surface charge (-25.70 mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer. Copyright © 2015 Elsevier B.V. All rights reserved.

Green synthesis of gold and silver nanoparticles using gallic acid: catalytic activity and conversion yield toward the 4-nitrophenol reduction reaction

NASA Astrophysics Data System (ADS)

Park, Jisu; Cha, Song-Hyun; Cho, Seonho; Park, Youmie

2016-06-01

In the present report, gallic acid was used as both a reducing and stabilizing agent to synthesize gold and silver nanoparticles. The synthesized gold and silver nanoparticles exhibited characteristic surface plasmon resonance bands at 536 and 392 nm, respectively. Nanoparticles that were approximately spherical in shape were observed in high-resolution transmission electron microscopy and atomic force microscopy images. The hydrodynamic radius was determined to be 54.4 nm for gold nanoparticles and 33.7 nm for silver nanoparticles in aqueous medium. X-ray diffraction analyses confirmed that the synthesized nanoparticles possessed a face-centered cubic structure. FT-IR spectra demonstrated that the carboxylic acid functional groups of gallic acid contributed to the electrostatic binding onto the surface of the nanoparticles. Zeta potential values of -41.98 mV for the gold nanoparticles and -53.47 mV for the silver nanoparticles indicated that the synthesized nanoparticles possess excellent stability. On-the-shelf stability for 4 weeks also confirmed that the synthesized nanoparticles were quite stable without significant changes in their UV-visible spectra. The synthesized nanoparticles exhibited catalytic activity toward the reduction reaction of 4-nitrophenol to 4-aminophenol in the presence of sodium borohydride. The rate constant of the silver nanoparticles was higher than that of the gold nanoparticles in the catalytic reaction. Furthermore, the conversion yield (%) of 4-nitrophenol to 4-aminophenol was determined using reversed-phase high-performance liquid chromatography with UV detection at 254 nm. The silver nanoparticles exhibited an excellent conversion yield (96.7-99.9 %), suggesting that the synthesized silver nanoparticles are highly efficient catalysts for the 4-nitrophenol reduction reaction.

Indentation Size Effect on Ag Nanoparticle-Modified Graphene/Sn-Ag-Cu Solders

NASA Astrophysics Data System (ADS)

Xu, L. Y.; Zhang, S. T.; Jing, H. Y.; Wang, L. X.; Wei, J.; Kong, X. C.; Han, Y. D.

2018-01-01

This paper presents the results for the indentation size effect (ISE) on the creep stress exponent and hardness of 0.03 wt.% Ag-modified graphene nanosheet Sn-Ag-Cu solder alloys, using constant loading/holding and multi-cycle (CMC) loading methods, respectively. At each maximum load, with increasing indentation depth, the creep exponent first decreased and then increased. At the same strain rate, the stress exponent also showed the same tendency, increasing as the indentation depth (peak load) increased and then decreased. The hardness was measured continuously with increasing indentation depth by the CMC loading method. The hardness did not exhibit a decrease as the indentation depth increased, which differs from the classical description of the ISE. After an initial decrease, the hardness then increased and finally decreased as the indentation depth increased. This study reviews the existing theories and formulations describing ISE with hardening effects. The experimental results fit well with the empirical formulation. The phenomenon of ISE accompanied by hardening effects has been explained physically via the interaction between geometrically necessary dislocations and grain boundaries.

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.

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.

Synergistic combination of antioxidants, silver nanoparticles and chitosan in a nanoparticle based formulation: Characterization and cytotoxic effect on MCF-7 breast cancer cell lines.

PubMed

Nayak, Debasis; Minz, Aliva Prity; Ashe, Sarbani; Rauta, Pradipta Ranjan; Kumari, Manisha; Chopra, Pankaj; Nayak, Bismita

2016-05-15

Chitosan (Cs) is a biocompatible, biodegradable cationic polymer having the ability of targeted drug delivery. Vitamin E and C are not synthesized in our body thus, when encapsulated within a carrier system these vitamins in combination with/alone can be utilized for their anti-cancer potentials. The present investigation was conducted to develop a stable nanoparticle based formulation encapsulating antioxidants (Vitamin E, catechol) and silver nanoparticles synthesized from Hibiscus rosa-sinensis (HRS) petal extracts within a chitosan matrix. The prepared nanoformulations were characterized using Field emission scanning electron microscopy (Fe-SEM), X-ray diffraction (XRD) and Attenuated Total Reflection Fourier Transform Infrared spectroscopy (ATR-FTIR). They were further tested for their antioxidant potentials using DPPH assay, hydrogen peroxide scavenging assay, nitric oxide scavenging assay and ferrous antioxidant reducing potential assay. The nanoformulations were found to be highly hemocompatible and showed high encapsulation efficiency up to 76%. They also showed higher antioxidant activity than their base materials. Further, their anti-cancer efficacy was observed against MCF-7 breast cancer cells having IC50 values of 53.36±0.36μg/mL (chitosan-ascorbic acid-glucose), 55.28±0.85μg/mL (chitosan-Vitamin E), 63.72±0.27μg/mL (Chitosan-catechol) and 58.53±0.55μg/mL (chitosan-silver nanoparticles). Thus, the prepared formulations can be therapeutically applied for effective and targeted delivery in breast cancer treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Preparation and characterization of oxybenzone-loaded solid lipid nanoparticles (SLNs) with enhanced safety and sunscreening efficacy: SPF and UVA-PF.

PubMed

Sanad, R A; Abdel Malak, N S; El-Bayoomy, T S; Badawi, A A

2010-12-01

The objective of the current study was to formulate solid lipid nanoparticles of oxybenzone to enhance its sunscreening efficacy while reducing its side effects. Solid lipid nanoparticles (SLNs) of oxybenzone were prepared by the solvent diffusion method. A complete 2(4) factorial design was used to optimize preparations. The study design involves the investigation of four independent variables, namely lipid type (Glyceryl monostearate, GMS; and Witepsol E85, WE85), lipid concentration (5 and 10%), polyvinyl alcohol (PVA) concentration (1 and 2%), and ethanol/acetone ratios (1:1 and 3:1, v/v), in terms of their effect on the particle size and entrapment efficiency. GMS was found to significantly increase the p.s. and EE%. SLNs prepared using 10% lipid had slower drug release compared to those prepared using 5%. The candidate oxybenzone-loaded SLN formula (SLN2) consisting of 0.5% oxybenzone, 10% GMS, 1% PVA, and ethanol/acetone (1:1, v/v) was then formulated into a gel and compared to the corresponding free oxybenzone nanosuspension and placebo SLN. The formulations were evaluated for skin irritation, in vitro sun protection factor, and ultraviolet A protection factors. The incorporation of oxybenzone into solid lipid nanoparticles greatly increased the SPF and UVA protection factor of oxybenzone more than five-fold while providing the advantage of overcoming skin irritancy problems.

Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels - A Strategy for Brain Cancer Treatments.

PubMed

Fisusi, Funmilola A; Siew, Adeline; Chooi, Kar Wai; Okubanjo, Omotunde; Garrett, Natalie; Lalatsa, Katerina; Serrano, Dolores; Summers, Ian; Moger, Julian; Stapleton, Paul; Satchi-Fainaro, Ronit; Schätzlein, Andreas G; Uchegbu, Ijeoma F

2016-05-01

The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression. Mice were dosed with either intravenous lomustine Molecular Envelope Technology (MET) nanoparticles (13 mg kg(-1)) or ethanolic lomustine (6.5 mg kg(-1)) and tissues analysed. Efficacy was assessed in an orthotopic U-87 MG glioblastoma model, following intravenous MET lomustine (daily 13 mg kg(-1)) or ethanolic lomustine (daily 1.2 mg kg(-1) - the highest repeated dose possible). Myelosuppression and MET particle macrophage uptake were also investigated. The MET formulation resulted in modest brain targeting (brain/ bone AUC0-4h ratios for MET and ethanolic lomustine = 0.90 and 0.53 respectively and brain/ liver AUC0-4h ratios for MET and ethanolic lomustine = 0.24 and 0.15 respectively). The MET formulation significantly increased mice (U-87 MG tumours) survival times; with MET lomustine, ethanolic lomustine and untreated mean survival times of 33.2, 22.5 and 21.3 days respectively and there were no material treatment-related differences in blood and femoral cell counts. Macrophage uptake is slower for MET nanoparticles than for liposomes. Particulate drug formulations improved brain tumour therapy without major bone marrow toxicity.

Application of hydroxyapatite nanoparticles in development of an enhanced formulation for delivering sustained release of triamcinolone acetonide

PubMed Central

Koocheki, Saeid; Madaeni, Sayed Siavash; Niroomandi, Parisa

2011-01-01

We report an analysis of in vitro and in vivo drug release from an in situ formulation consisting of triamcinolone acetonide (TR) and poly(d,l-lactide-co-glycolide) (PLGA) and the additives glycofurol (GL) and hydroxyapatite nanoparticles (HA). We found that these additives enhanced drug release rate. We used the Taguchi method to predict optimum formulation variables to minimize the initial burst. This method decreased the burst rate from 8% to 1.3%. PLGA-HA acted as a strong buffer, thereby preventing tissue inflammation at the injection site caused by the acidic degradation products of PLGA. Characterization of the optimized formulation by a variety of techniques, including scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, and Fourier transform near infrared spectroscopy, revealed that the crystalline structure of TR was converted to an amorphous form. Therefore, this hydrophobic agent can serve as an additive to modify drug release rates. Data generated by in vitro and in vivo experiments were in good agreement. PMID:21589650

Design of a Small-Scale Multi-Inlet Vortex Mixer for Scalable Nanoparticle Production and Application to the Encapsulation of Biologics by Inverse Flash NanoPrecipitation.

PubMed

Markwalter, Chester E; Prud'homme, Robert K

2018-05-14

Flash NanoPrecipitation (FNP) is a scalable approach to generate polymeric nanoparticles using rapid micromixing in specially-designed geometries such as a confined impinging jets (CIJ) mixer or a Multi-Inlet Vortex Mixer (MIVM). A major limitation of formulation screening using the MIVM is that a single run requires tens of milligrams of the therapeutic. To overcome this, we have developed a scaled-down version of the MIVM, requiring as little as 0.2 mg of therapeutic, for formulation screening. The redesigned mixer can then be attached to pumps for scale-up of the identified formulation. It was shown that Reynolds Number allowed accurate scaling between the two MIVM designs. The utility of the small-scale MIVM for formulation development was demonstrated through the encapsulation of a number of hydrophilic macromolecules using inverse Flash NanoPrecipitation with target loadings as high as 50% by mass. Copyright © 2018. Published by Elsevier Inc.

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.

In vitro, ex vivo and in vivo characterization of PLGA nanoparticles loading pranoprofen for ocular administration.

PubMed

Cañadas, Cristina; Alvarado, Helen; Calpena, Ana C; Silva, Amélia M; Souto, Eliana B; García, Maria L; Abrego, Guadalupe

2016-09-25

Pranoprofen (PF) is a NSAID considered as a safe anti-inflammatory treatment for strabismus and/or cataract surgery. The drug has been formulated in poly (lactic/glycolic) acid (PLGA) nanoparticles (PF-F1NPs with cPF 1.5mg/mL, PF-F2NPs with cPF 1mg/mL) produced by solvent displacement technique and tested the in vitro cytotoxicity, ex vivo corneal permeation, in vivo ocular tolerance and in vivo anti-inflammatory efficacy of PF-F1NPs, PF-F2NPs, in comparison to eye drops conventional dosage form (Oftalar(®), PF 1mg/mL) and free drug solution (PF dissolved in PBS, 1.5mg/mL). The mean particle size of both formulations was around 350nm, with polydispersity index below 0.1, and a net negative charge of -7.41mV and -8.5mV for PF-F1NPs and PF-F2NPs, respectively. Y-79 human retinoblastoma cell line was used to evaluate the cytotoxicity of PF-F1NPs and PF-F2NPs, which were compared to blank NPs and free drug solution (PF dissolved in PBS, 1.5mg/mL). Concentrations up to 75μg/mL exhibited no toxicity to Y-79 cells, whereas at 150μg/mL a decrease of about 80% on the cell viability was observed after exposing the cells to PF-F1NPs. When treating the Y-79 cells with concentrations of PF-F2NPs between 1μg/mL to 100μg/mL, the cell viability was similar to control values after 24h and 48h of exposure. An ex vivo corneal permeation study was carried out in New Zealand rabbits. A very similar profile has been observed for the permeation of PF through the cornea when administered as eye drops and as free drug solution, which was kept much lower in comparison to PF-NPs formulations. The permeated amount of PF from the PF-F1NPs was slightly smaller than from PF-F2NPs, attributed to the increase of viscosity of the formulations with the increase of cPVA concentration. New Zealand white rabbits were also used to evaluate the irritancy of PF-F1NPs and PF-F2NPs, which demonstrated to be well-tolerated to the eye (i.e. the mean total score (MTS) was 0). PF-F2NPs exhibited the highest QP (amounts of PF permeated in the cornea) and significantly reduced the ocular edema compared to the tested formulations. The QR (amounts of PF retained in the cornea) of the PF-F1NPs was greater than that obtained for PF-F2NPs. Copyright © 2016 Elsevier B.V. All rights reserved.

Gold core@silver semishell Janus nanoparticles prepared by interfacial etching

NASA Astrophysics Data System (ADS)

Chen, Limei; Deming, Christopher P.; Peng, Yi; Hu, Peiguang; Stofan, Jake; Chen, Shaowei

2016-07-01

Gold core@silver semishell Janus nanoparticles were prepared by chemical etching of Au@Ag core-shell nanoparticles at the air/water interface. Au@Ag core-shell nanoparticles were synthesized by chemical deposition of a silver shell onto gold seed colloids followed by the self-assembly of 1-dodecanethiol onto the nanoparticle surface. The nanoparticles then formed a monolayer on the water surface of a Langmuir-Blodgett trough, and part of the silver shell was selectively etched away by the mixture of hydrogen peroxide and ammonia in the water subphase, where the etching was limited to the side of the nanoparticles that was in direct contact with water. The resulting Janus nanoparticles exhibited an asymmetrical distribution of silver on the surface of the gold cores, as manifested in transmission electron microscopy, UV-vis absorption, and X-ray photoelectron spectroscopy measurements. Interestingly, the Au@Ag semishell Janus nanoparticles exhibited enhanced electrocatalytic activity in oxygen reduction reactions, as compared to their Au@Ag and Ag@Au core-shell counterparts, likely due to a synergistic effect between the gold cores and silver semishells that optimized oxygen binding to the nanoparticle surface.Gold core@silver semishell Janus nanoparticles were prepared by chemical etching of Au@Ag core-shell nanoparticles at the air/water interface. Au@Ag core-shell nanoparticles were synthesized by chemical deposition of a silver shell onto gold seed colloids followed by the self-assembly of 1-dodecanethiol onto the nanoparticle surface. The nanoparticles then formed a monolayer on the water surface of a Langmuir-Blodgett trough, and part of the silver shell was selectively etched away by the mixture of hydrogen peroxide and ammonia in the water subphase, where the etching was limited to the side of the nanoparticles that was in direct contact with water. The resulting Janus nanoparticles exhibited an asymmetrical distribution of silver on the surface of the gold cores, as manifested in transmission electron microscopy, UV-vis absorption, and X-ray photoelectron spectroscopy measurements. Interestingly, the Au@Ag semishell Janus nanoparticles exhibited enhanced electrocatalytic activity in oxygen reduction reactions, as compared to their Au@Ag and Ag@Au core-shell counterparts, likely due to a synergistic effect between the gold cores and silver semishells that optimized oxygen binding to the nanoparticle surface. Electronic supplementary information (ESI) available: Additional TEM, UV-vis, XPS, and electrochemical data. See DOI: 10.1039/c6nr03368g

Biogenic silver and gold nanoparticles synthesized using red ginseng root extract, and their applications.

PubMed

Singh, Priyanka; Kim, Yeon Ju; Wang, Chao; Mathiyalagan, Ramya; El-Agamy Farh, Mohamed; Yang, Deok Chun

2016-05-01

In the present study, we report a green methodology for the synthesis of silver and gold nanoparticles, using the root extract of the herbal medicinal plant Korean red ginseng. The silver and gold nanoparticles were synthesized within 1 h and 10 min respectively. The nanoparticles generated were not aggregated, and remained stable for a long time, which suggests the nature of nanoparticles. The phytochemicals and ginsenosides present in the root extract assist in reducing and stabilizing the synthesized nanoparticles. The red ginseng root extract-generated silver nanoparticles exhibit antimicrobial activity against pathogenic microorganisms including Vibrio parahaemolyticus, Staphylococcus aureus, Bacillus cereus, and Candida albicans. In addition, the silver nanoparticles exhibit biofilm degrading activity against S. aureus and Pseudomonas aeruginosa. Thus, the present study opens up a new possibility of synthesizing silver and gold nanoparticles in a green and rapid manner using Korean red ginseng root extract, and explores their biomedical applications.

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

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...

Structural, Optical, and Electrical Properties of Cobalt-Doped CdS Quantum Dots

NASA Astrophysics Data System (ADS)

Thambidurai, M.; Muthukumarasamy, N.; Velauthapillai, Dhayalan; Agilan, S.; Balasundaraprabhu, R.

2012-04-01

In the present work, a systematic study has been carried out to understand the influence of cobalt (Co) doping on various properties of CdS nanoparticles. CdS and Co-doped CdS quantum dots have been prepared at room temperature using a chemical precipitation method without using catalysts, capping agents, or surfactants. X-ray diffraction reveals that both undoped and Co-doped CdS nanoparticles exhibit hexagonal structure without any impurity phase, and the lattice constants of CdS nanoparticles are observed to decrease slightly with increasing cobalt concentration. High-resolution transmission electron microscopy (HRTEM) shows that the particle size of CdS and 5.02% Co-doped CdS nanoparticles is in the range of 2 nm to 4 nm. The Raman spectra of Co-doped CdS nanoparticles exhibit a red-shift compared with that of bulk CdS, which may be attributed to optical phonon confinement. The optical absorption spectra of Co-doped CdS nanoparticles also exhibit a red-shift with respect to that of CdS nanoparticles. The electrical conductivity of CdS and Co-doped CdS nanoparticles is found to increase with increasing temperature and cobalt concentration.

Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms

PubMed Central

Ong, Teik Hwa; Chitra, Ebenezer; Ramamurthy, Srinivasan; Siddalingam, Rajinikanth Paruvathanahalli; Yuen, Kah Hay; Ambu, Stephen Periathamby

2017-01-01

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections. PMID:28362873

Surface chemistry and serum type both determine the nanoparticle-protein corona.

PubMed

Pozzi, Daniela; Caracciolo, Giulio; Capriotti, Anna Laura; Cavaliere, Chiara; La Barbera, Giorgia; Anchordoquy, Thomas J; Laganà, Aldo

2015-04-24

The protein corona that forms around nanoparticles in vivo is a critical factor that affects their physiological response. The potential to manipulate nanoparticle characteristics such that either proteins advantageous for delivery are recruited and/or detrimental proteins are avoided offers exciting possibilities for improving drug delivery. In this work, we used nanoliquid chromatography tandem mass spectrometry to characterize the corona of five lipid formulations after incubation in mouse and human plasma with the hope of providing data that may contribute to a better understanding of the role played by both the nanoparticle properties and the physiological environment in recruiting specific proteins to the corona. Notably, we showed that minor changes in the lipid composition might critically affect the protein corona composition demonstrating that the surface chemistry and arrangement of lipid functional groups are key players that regulate the liposome-protein interactions. Notably, we provided evidence that the protein corona that forms around liposomes is strongly affected by the physiological environment, i.e., the serum type. These results are likely to suggest that the translation of novel pharmaceutical formulations from animal models to the clinic must be evaluated on a case-by-case basis. In the present work nanoliquid chromatography tandem mass spectrometry was used to characterize the protein corona of five different liposome formulations after exposure to mouse and human plasma. The modern proteomic methods employed have clarified that the arrangement of lipid functional groups is a key player that regulates the liposome-protein interactions. We also clarified that the protein corona enrichment and complexity depend on the serum type. Our results suggest that the translational of novel pharmaceutical formulations from animal models to the clinic must be evaluated on a case-by-case basis. Copyright © 2015. Published by Elsevier B.V.

Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design.

PubMed

Wang, Fengzhen; Chen, Li; Jiang, Sunmin; He, Jun; Zhang, Xiumei; Peng, Jin; Xu, Qunwei; Li, Rui

2014-09-01

The purpose of the present study was to optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) which were used as topical eye drops by evaluating the relationship between design factors and experimental data. A three factor, three-level Box-Behnken design (BBD) was used for the optimization procedure, choosing the amount of GMS, the amount of phospholipid, the concentration of surfactant as the independent variables. The chosen dependent variables were entrapment efficiency, dosage loading, and particle size. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 100 mg GMS, 150 mg phospholipid, and 1% Tween80 and PEG 400 (1:1, w/v). A new formulation was prepared according to these levels. The observed responses were close to the predicted values of the optimized formulation. The particle size was 197.8 ± 4.9 nm. The polydispersity index of particle size was 0.239 ± 0.01 and the zeta potential was 32.7 ± 2.6 mV. The entrapment efficiency and dosage loading were about 68.39% and 2.49%, respectively. Fourier transform infrared spectroscopy (FT-IR) study indicated that the drug was entrapped in nanoparticles. The optimized formulation showed a sustained release followed the Peppas model. MTZ-SLNs showed significant prolonged decreasing intraocular pressure effect comparing with MTZ solution in vivo pharmacodynamics studies. The results of acute eye irritation study indicated that MTZ-SLNs and AZOPT both had no eye irritation. Furthermore, the MTZ-SLNs were suitable to be stored at low temperature (4 °C).

Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

PubMed

Ong, Teik Hwa; Chitra, Ebenezer; Ramamurthy, Srinivasan; Siddalingam, Rajinikanth Paruvathanahalli; Yuen, Kah Hay; Ambu, Stephen Periathamby; Davamani, Fabian

2017-01-01

Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

Nanoparticle-mediated hyperthermia in cancer therapy

PubMed Central

Chatterjee, Dev Kumar; Diagaradjane, Parmeswaran; Krishnan, Sunil

2011-01-01

A small rise in tumor temperature (hyperthermia) makes cancer cells more susceptible to radiation and chemotherapy. The means of achieving this is not trivial, and traditional methods have certain drawbacks. Loading tumors with systematically asministered energy-transducing nanoparticles can circumvent several of the obstacles to achieve tumor hyperthermia. However, nanoparticles also face unique challenges prior to clinical implementation. This article summarizes the state-of-the-art current technology and discusses the advantages and challenges of the three major nanoparticle formulations in focus: gold nanoshells and nanorods, superparamagnetic iron oxide particles and carbon nanotubes. PMID:22506095

Chemiluminescent Diagnostics of Free-Radical Processes in an Abiotic System and in Liver Cells in the Presence of Nanoparticles Based on Rare-Earth Elements nReVO4:Eu3+ (Re = Gd, Y, La) and CeO2

NASA Astrophysics Data System (ADS)

Averchenko, E. A.; Kavok, N. S.; Klochkov, V. K.; Malyukin, Yu. V.

2014-11-01

We have used luminol-dependent chemiluminescence with Fenton's reagent to study the effect of nanoparticles based on rare-earth elements of different sizes and shapes on free-radical processes in abiotic and biotic cell-free systems, and also in isolated cells in vitro. We have estimated the effects of rare-earth orthovanadate nanoparticles of spherical (GdYVO4:Eu3+, 1-2 nm), spindle-shaped (GdVO4:Eu3+, 25 ×8 nm), and rod-shaped (LaVO4:Eu3+, 57 × (6-8) nm) nanoparticles and spherical CeO2 nanoparticles (sizes 1-2 nm and 8-10 nm). We have shown that in contrast to the abiotic system, in which all types of nanoparticles exhibit antiradical activity, in the presence of biological material, extra-small spherical (1-2 nm) nanoparticles of both types exhibit pro-oxidant activity, and also enhance pro-oxidant induced oxidative stress (for the pro-oxidants hydrogen peroxide and tert-butyl hydroperoxide). The effect of rare-earth orthovanadate spindle and rod shaped nanoparticles in this system was neutral; a moderate antioxidant effect was exhibited by 8-10 nm CeO2 nanoparticles.

Nanoparticles formulation of Cuscuta chinensis prevents acetaminophen-induced hepatotoxicity in rats.

PubMed

Yen, Feng-Lin; Wu, Tzu-Hui; Lin, Liang-Tzung; Cham, Thau-Ming; Lin, Chun-Ching

2008-05-01

Cuscuta chinensis is a commonly used traditional Chinese medicine to nourish the liver and kidney. Due to the poor water solubility of its major constituents such as flavonoids and lignans, its absorption upon oral administration could be limited. The purpose of the present study was to use the nanosuspension method to prepare C. chinensis nanoparticles (CN), and to compare the hepatoprotective and antioxidant effects of C. chinensis ethanolic extract (CE) and CN on acetaminophen-induced hepatotoxicity in rats. An oral dose of CE at 125 and 250 mg/kg and CN at 25 and 50mg/kg showed a significant hepatoprotective effect relatively to the same extent (P<0.05) by reducing levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. These biochemical assessments were supported by rat hepatic biopsy examinations. In addition, the antioxidant activities of CE and CN both significantly increased superoxide dismutase, catalase, glutathione peroxidase, and reduced malondialdehyde (P<0.05). Moreover, the results also indicated that the hepatoprotective and antioxidant effects of 50 mg/kg CN was effectively better than 125 mg/kg CE (P<0.05), and an oral dose of CN that is five times as less as CE could exhibit similar levels of outcomes. In conclusion, we suggest that the nanoparticles system can be applied to overcome other water poorly soluble herbal medicines and furthermore to decrease the treatment dosage.

Drug Synergy of Tenofovir and Nanoparticle-Based Antiretrovirals for HIV Prophylaxis

PubMed Central

Chaowanachan, Thanyanan; Krogstad, Emily; Ball, Cameron; Woodrow, Kim A.

2013-01-01

Background The use of drug combinations has revolutionized the treatment of HIV but there is no equivalent combination product that exists for prevention, particularly for topical HIV prevention. Strategies to combine chemically incompatible agents may facilitate the discovery of unique drug-drug activities, particularly unexplored combination drug synergy. We fabricated two types of nanoparticles, each loaded with a single antiretroviral (ARV) that acts on a specific step of the viral replication cycle. Here we show unique combination drug activities mediated by our polymeric delivery systems when combined with free tenofovir (TFV). Methodology/Principal Findings Biodegradable poly(lactide-co-glycolide) nanoparticles loaded with efavirenz (NP-EFV) or saquinavir (NP-SQV) were individually prepared by emulsion or nanoprecipitation techniques. Nanoparticles had reproducible size (d ∼200 nm) and zeta potential (-25 mV). The drug loading of the nanoparticles was approximately 7% (w/w). NP-EFV and NP-SQV were nontoxic to TZM-bl cells and ectocervical explants. Both NP-EFV and NP-SQV exhibited potent protection against HIV-1 BaL infection in vitro. The HIV inhibitory effect of nanoparticle formulated ARVs showed up to a 50-fold reduction in the 50% inhibitory concentration (IC50) compared to free drug. To quantify the activity arising from delivery of drug combinations, we calculated combination indices (CI) according to the median-effect principle. NP-EFV combined with free TFV demonstrated strong synergistic effects (CI50 = 0.07) at a 1∶50 ratio of IC50 values and additive effects (CI50 = 1.05) at a 1∶1 ratio of IC50 values. TFV combined with NP-SQV at a 1∶1 ratio of IC50 values also showed strong synergy (CI50 = 0.07). Conclusions ARVs with different physicochemical properties can be encapsulated individually into nanoparticles to potently inhibit HIV. Our findings demonstrate for the first time that combining TFV with either NP-EFV or NP-SQV results in pronounced combination drug effects, and emphasize the potential of nanoparticles for the realization of unique drug-drug activities. PMID:23630586

Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

PubMed Central

Vasconcelos, Aimee; Vega, Estefania; Pérez, Yolanda; Gómara, María J; García, María Luisa; Haro, Isabel

2015-01-01

In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery. PMID:25670897

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.

Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

PubMed Central

Wang, Yonglu; Li, Xueming; Wang, Liyao; Xu, Yuanlong; Cheng, Xiaodan; Wei, Ping

2011-01-01

Paclitaxel is a diterpenoid isolated from Taxus brevifolia. It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor® EL (BASF, Ludwigshafen, Germany), which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was formulated as a nanosuspension by high-pressure homogenization. The nanosuspension was lyophilized to obtain the dry paclitaxel nanoparticles (average size, 214.4 ± 15.03 nm), which enhanced both the physical and chemical stability of paclitaxel nanoparticles. Paclitaxel dissolution was also enhanced by the nanosuspension. Differential scanning calorimetry showed that the crystallinity of paclitaxel was preserved during the high-pressure homogenization process. The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection. In rat plasma, paclitaxel nanosuspension exhibited a significantly (P < 0.01) reduced area under the concentration curve (AUC)0–∞ (20.343 ± 9.119 μg · h · mL−1 vs 5.196 ± 1.426 μg · h · mL−1), greater clearance (2.050 ± 0.616 L · kg−1 · h−1 vs 0.556 ± 0.190 L · kg−1 · h−1), and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours) compared with the paclitaxel solution. In contrast, the paclitaxel nanosuspension resulted in a significantly greater AUC0–∞ in liver, lung, and spleen (all P < 0.01), but not in heart or kidney. PMID:21796250

Utilizing the Power of Nanostructures to Their Fullest Capability in Energetic Formulations

DTIC Science & Technology

2016-02-01

aluminum-cyclopentadienyl clusters. J Phys Chem A. 2011;115(48):14100– 14109. Zeng Q, Jiang X, Yu A, Lu G. Growth mechanisms of silver nanoparticles : a...assemblies of gas generators containing nanoscale Al (conventional Al nanoparticles and Al nanoclusters) to overcome the sintering and/or oxide-formation...issues. Experimentally, a previously published hypothesis for the mechanism leading to enhanced energy release from Al nanoparticles in the presence of

Vegetable Oil-Loaded Nanocapsules: Innovative Alternative for Incorporating Drugs for Parenteral Administration.

PubMed

Venturinil, C G; Bruinsmann, A; Oliveira, C P; Contri, R V; Pohlmann, A R; Guterres, S S

2016-02-01

An innovative nanocapsule formulation for parenteral administration using selected vegetable oils (mango, jojoba, pequi, oat, annatto, calendula, and chamomile) was developed that has the potential to encapsulate various drugs. The vegetable oil-loaded nanocapsules were prepared by interfacial deposition and compared with capric/caprylic triglyceride-loaded lipid core nanocapsules. The major objective was to investigate the effect of vegetable oils on particle size distribution and physical stability and to determine the hemolytic potential of the nanocapsules, considering their applicability for intravenous administration. Taking into account the importance of accurately determining particle size for the selected route of administration, different size characterization techniques were employed, such as Laser Diffraction, Dynamic Light Scattering, Multiple Light Scattering, Nanoparticle Tracking Analysis, and Transmission Electronic Microscopy. Laser diffraction studies indicated that the mean particle size of all nanocapsules was below 300 nm. For smaller particles, the laser diffraction and multiple light scattering data were in agreement (D[3,2]-130 nm). Dynamic light scattering and nanoparticle tracking analysis, two powerful techniques that complement each other, exhibited size values between 180 and 259 nm for all nanoparticles. Stability studies demonstrated a tendency of particle creaming for jojoba-nanocapsules and sedimentation for the other nanoparticles; however, no size variation occurred over 30 days. The hemolysis test proved the hemocompatibility of all nanosystems, irrespective of the type of oil. Although all developed nanocapsules presented the potential for parenteral administration, jojoba oil-loaded nanocapsules were selected as the most promising nanoformulation due to their low average size and high particle size homogeneity.

Triple combination MPT vaginal microbicide using curcumin and efavirenz loaded lactoferrin nanoparticles.

PubMed

Lakshmi, Yeruva Samrajya; Kumar, Prashant; Kishore, Golla; Bhaskar, C; Kondapi, Anand K

2016-05-06

We report that a combination of anti-HIV-1 drug efavirenz (EFV), anti-microbial-spermicidal curcumin (Cur) and lactoferrin nanoparticles (ECNPs) act as MPT formulation. These nanoparticles are of well dispersed spherical shape with 40-70 nm size, with encapsulation efficiency of 63 ± 1.9% of Cur &61.5% ± 1.6 of EFV, significantly higher than that of single drug nanoparticles (Cur, 59 ± 1.34%; EFV: 58.4 ± 1.79). ECNPs were found to be sensitive at pH 5 and 6 and have not effected viability of vaginal micro-flora, Lactobacillus. Studies in rats showed that ECNPs delivers 88-124% more drugs in vaginal lavage as compared to its soluble form, either as single or combination of EFV and Cur. The ECNPs also shows 1.39-4.73 fold lower concentration of absorption in vaginal tissue and plasma compared to soluble EFV + Cur. Furthermore, ECNPs show significant reduction in inflammatory responses by 1.6-3.0 fold in terms of IL-6 and TNF-α in vaginal tissue and plasma compared to soluble EFV + Cur. ECNPs showed improved pharmacokinetics profiles in vaginal lavage with more than 50% of enhancement in AUC, AUMC, Cmax and t1/2 suggesting longer exposure of Cur and EFV in vaginal lavage compared to soluble EFV + Cur. Histopathological analysis of vaginal tissue shows remarkably lower toxicity of ECNPs compared to soluble EFV + Cur. In conclusion, ECNPs are significantly safe and exhibit higher bioavailability thus constitute an effective MPT against HIV.

Development, optimization, and in vitro characterization of dasatinib-loaded PEG functionalized chitosan capped gold nanoparticles using Box-Behnken experimental design.

PubMed

Adena, Sandeep Kumar Reddy; Upadhyay, Mansi; Vardhan, Harsh; Mishra, Brahmeshwar

2018-03-01

The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs). Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) were employed to optimize the process parameters. Polynomial equations, contour, and 3D response surface plots were generated to relate the factors and responses. The optimized DSB-PEG-Ch-GNPs were characterized by FTIR, XRD, HR-SEM, EDX, TEM, SAED, AFM, DLS, and ZP. The results of the optimized DSB-PEG-Ch-GNPs showed particle size (PS) of 24.39 ± 1.82 nm, apparent drug content (ADC) of 72.06 ± 0.86%, and zeta potential (ZP) of -13.91 ± 1.21 mV. The responses observed and the predicted values of the optimized process were found to be close. The shape and surface morphology studies showed that the resulting DSB-PEG-Ch-GNPs were spherical and smooth. The stability and in vitro drug release studies confirmed that the optimized formulation was stable at different conditions of storage and exhibited a sustained drug release of the drug of up to 76% in 48 h and followed Korsmeyer-Peppas release kinetic model. A process for preparing gold nanoparticles using chitosan, anchoring PEG to the particle surface, and entrapping dasatinib in the chitosan-PEG surface corona was optimized.

A magnetic, reversible pH-responsive nanogated ensemble based on Fe3O4 nanoparticles-capped mesoporous silica.

PubMed

Gan, Qi; Lu, Xunyu; Yuan, Yuan; Qian, Jiangchao; Zhou, Huanjun; Lu, Xun; Shi, Jianlin; Liu, Changsheng

2011-03-01

Stimuli-sensitive mesoporous silica nanoparticles (MSNs)-based hybrid "gate-like" ensembles capable of performing specific programmed release mode represent a new generation delivery system in recent years. In this paper, a magnetic and reversible pH-responsive, MSNs-based nanogated ensemble was fabricated by anchoring superparamagnetic Fe(3)O(4) nanoparticles on the pore outlet of MSNs via a reversible boronate esters linker. To achieve this, MSNs and Fe(3)O(4) nanoparticles were first synthesized and functionalized by polyalcohol derivative and boronic acid, respectively. The successful incorporation of Fe(3)O(4) nanoparticles onto the MSNs was confirmed by the results of XRD, TEM, XPS and N(2) adsorption-desorption method. The pH-driven "gate-like" effect was studied by in vitro release of an entrapped model dexamethasone from the pore voids into the bulk solution at different pH values. The results indicated that at pH 5-8, the pores of the MSNs were effectively capped with Fe(3)O(4) nanoparticles and the drug release was strongly inhibited. While at pH 2-4, the hydrolysis of the boroester bond took place and thus resulted in a rapid release of the entrapped drug. And by alternately changing the pH from 3 to 7, these Fe(3)O(4) cap gate could be switched "on" and "off" and thereby released the entrapped drug in a pulsinate manner (in small portions). Additionally, this nanogated release system exhibited good magnetic property, high cell biocompatibility and cellular uptake for MC3T3-E1 cells. The present data suggest that it is possible to obtain simple and very effective pH-driven pulsinate release using these Fe(3)O(4)-capped-MSNs, and this new platform represents a promising candidate in the formulation of in vivo targeted delivery of therapeutic agents to low pH tissues, such as tumors and inflammatory sites. Copyright © 2010 Elsevier Ltd. All rights reserved.

Aloe-emodin (AE) nanoparticles suppresses proliferation and induces apoptosis in human lung squamous carcinoma via ROS generation in vitro and in vivo.

PubMed

Wu, Yuan-Yuan; Zhang, Jing-Hua; Gao, Jing-Hua; Li, Yong-Sheng

2017-08-26

Human lung squamous cell carcinoma is a deadly cancer for which present therapeutic strategies are inadequate. And traditional chemotherapy results in severe systemic toxicity. Compounds from living organisms often exert a biological activity, triggering several targets, which may be useful for the improvement of novel pharmaceuticals. Aloe-emodin (AE), a well-known natural compound, is a primary component of anthraquinones in Aloe vera and exhibits anti-proliferative and apoptotic effects on various tumor cells. However, the translational and clinical use of AE has been limited owing to its rapid degradation and poor bioavailability. To improve its efficacy, a poly (lactic-co-glycolic acid) based AE nanoparticle formulation (NanoAE) was prepared. Our study indicated that compared to the free AE, nanoAE significantly suppressed cancer cell proliferation, induced cell cycle arrest and apoptosis, evidenced by high cleavage of Caspase-3, poly (ADP-ribose) polymerase (PARP), Caspase-8 and Caspase-9. NanoAE enhanced reactive oxygen species (ROS) production, along with Mitogen-activated protein kinases (MAPKs) activation and PI3K/AKT inactivation. Cell proliferation, apoptosis and MAPKs and PI3K/AKT were dependent on ROS production in nanoAE-treated groups. In vivo, nanoAE exhibited inhibitory effects on the tumor growth with little toxicity. Together, our results indicated that nanoAE might be an effective treatment for human lung squamous cell carcinoma. Copyright © 2017. Published by Elsevier Inc.

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.

Ion Structure Near a Core-Shell Dielectric Nanoparticle

NASA Astrophysics Data System (ADS)

Ma, Manman; Gan, Zecheng; Xu, Zhenli

2017-02-01

A generalized image charge formulation is proposed for the Green's function of a core-shell dielectric nanoparticle for which theoretical and simulation investigations are rarely reported due to the difficulty of resolving the dielectric heterogeneity. Based on the formulation, an efficient and accurate algorithm is developed for calculating electrostatic polarization charges of mobile ions, allowing us to study related physical systems using the Monte Carlo algorithm. The computer simulations show that a fine-tuning of the shell thickness or the ion-interface correlation strength can greatly alter electric double-layer structures and capacitances, owing to the complicated interplay between dielectric boundary effects and ion-interface correlations.

Design of Novel Ophthalmic Formulation Containing Drug Nanoparticles and Its Usefulness as Anti-glaucoma Drugs.

PubMed

Nagai, Noriaki

2016-01-01

The ophthalmic application of drugs is the primary route of administration for the therapy of glaucoma; however, in traditional formulations, only small amounts of the administered drug penetrate the cornea to reach the desired intraocular tissue due to corneal barriers. Recently, nanoparticulate drug delivery is expected as a technology to overcome the difficulties in delivering drugs across biological barriers (improvement of bioavailability). In this study, we attempted to establish a new method for preparing solid drug nanoparticles by using a bead mill and various additives, and succeeded in preparing a high quality dispersion containing drug nanoparticles. For a more concrete example, a mean particle size of disulfiram (DSF) treated with bead mill is 183 nm. The corneal penetration and corneal residence time of DSF from the ophthalmic dispersion containing DSF nanoparticles were significantly higher than those from a 2-hydroxypropyl-β-cyclodextrin solution containing DSF (DSF solution). It is known that the administration of DSF has intraocular pressure (IOP)-reducing effects. The IOP-reducing effects of the ophthalmic dispersion containing DSF nanoparticles were significantly greater than those of the DSF solution in rabbits (the IOP was enhanced by placing the rabbits in a dark room for 5 h). In addition, the ophthalmic dispersion containing DSF nanoparticles is better tolerated by corneal epithelial cells than DSF solution. It is possible that dispersions containing DSF nanoparticles provide new possibilities for effectively treating glaucoma, and that ocular drug delivery systems using drug nanoparticles may expand their usage for therapy in the ophthalmologic field.

Enhanced singlet oxygen generation from PLGA loaded with verteporfin and gold nanoparticles

NASA Astrophysics Data System (ADS)

Deng, Wei; Kautzka, Zofia; Goldys, Ewa M.

2016-12-01

In this study, poly(lactic-co-glycolic acid) (PLGA) nanocomposites were developed by incorporating a photosensitizer, verteporfin and gold nanoparticles into this polymeric matrix and utilised for enhanced photoynamic therapy. Both enhanced fluorescence and singlet oxygen generation from verteporfin were observed in this new formulation under both 425nm LED and 405nm laser illumination. A maximum enhancement factor of 2.5 for fluorescence and 1.84 for 1O2 generation was obtained when the molar ratio of gold:VP was 5:1 and excited at 425 nm, compared with PLGA doped with verteporfin only. The experiment results could be explained by the local electric field enhancement of gold nanoparticles. Furthermore, in vitro cell-killing effect on human pancreatic cancer cells was also demonstrated by using this new formulation following light exposure, indicating the utility of these nanocomposites for enhanced photodynamic therapy.

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.

Preclinical evaluation of injectable sirolimus formulated with polymeric nanoparticle for cancer therapy

PubMed Central

Woo, Ha Na; Chung, Hye Kyung; Ju, Eun Jin; Jung, Joohee; Kang, Hye-Won; Lee, Sa-Won; Seo, Min-Hyo; Lee, Jin Seong; Lee, Jung Shin; Park, Heon Joo; Song, Si Yeol; Jeong, Seong-Yun; Choi, Eun Kyung

2012-01-01

Nanoparticles are useful delivery vehicles for promising drug candidates that face obstacles for clinical applicability. Sirolimus, an inhibitor of mammalian target of rapamycin has gained attention for targeted anticancer therapy, but its clinical application has been limited by its poor solubility. This study was designed to enhance the feasibility of sirolimus for human cancer treatment. Polymeric nanoparticle (PNP)–sirolimus was developed as an injectable formulation and has been characterized by transmission electron microscopy and dynamic light scattering. Pharmacokinetic analysis revealed that PNP–sirolimus has prolonged circulation in the blood. In addition, PNP–sirolimus preserved the in vitro killing effect of free sirolimus against cancer cells, and intravenous administration displayed its potent in vivo anticancer efficacy in xenograft tumor mice. In addition, PNP–sirolimus enhanced the radiotherapeutic efficacy of sirolimus both in vitro and in vivo. Clinical application of PNP–sirolimus is a promising strategy for human cancer treatment. PMID:22619555

Development and characterization of polymeric nanoparticulate delivery system for hydrophillic drug: Gemcitabine

NASA Astrophysics Data System (ADS)

Khurana, Jatin

Gemcitabine is a nucleoside analogue, used in various carcinomas such as non small cell lung cancer, pancreatic cancer, ovarian cancer and breast cancer. The major setbacks to the conventional therapy with gemcitabine include its short half-life and highly hydrophilic nature. The objectives of this investigation were to develop and evaluate the physiochemical properties, drug loading and entrapment efficiency, in vitro release, cytotoxicity, and cellular uptake of polymeric nano-particulate formulations containing gemcitabine hydrochloride. The study also entailed development and validation of a high performance liquid chromatography (HPLC) method for the analysis of gemcitabine hydrochloride. A reverse phase HPLC method using a C18 Luna column was developed and validated. Alginate and Poly lactide co glycolide/Poly-epsilon-caprolactone (PLGA:PCL 80:20) nanoparticles were prepared by multiple emulsion-solvent evaporation methodology. An aqueous solution of low viscosity alginate containing gemcitabine was emulsified into 10% solution of dioctyl-sulfosuccinate in dichloro methane (DCM) by sonication. The primary emulsion was then emulsified in 0.5% (w/v) aqueous solution of polyvinyl alcohol (PVA). Calcium chloride solution (60% w/v) was used to cause cross linking of the polymer. For PLGA:PCL system, the polymer mix was dissolved in dichloromethane (DCM) and an aqueous gemcitabine (with and without sodium chloride) was emulsified under ultrasonic conditions (12-watts; 1-min). This primary emulsion was further emulsified in 2% (w/v) PVA under ultrasonic conditions (24-watts; 3-min) to prepare a multiple-emulsion (w/o/w). In both cases DCM, the organic solvent was evaporated (20- hours, magnetic-stirrer) prior to ultracentrifugation (10000-rpm for PLGA:PCL; 25000-rpm for alginate). The pellet obtained was washed thrice with de-ionized water to remove PVA and any free drug and re-centrifuged. The particles were re-suspended in de-ionized water and then lyophilized to obtain the dried powdered delivery formulation. Particle size and surface charge of the nano-particles were measured using zeta-sizer. The surface morphology and microstructure were evaluated by scanning electron microscopy The drug loading and entrapment efficiencies were evaluated by a HPLC method (Luna C18 column (4.6 X 250 mm), 95/5 (v/v) 0.04M ammonium acetate/acetonitrile mobile phase (pH 5.5), 1.0 ml/min flow rate and 268 nm UV detection). Differential scanning calorimetry (DSC) was used to determine the physical state of gemcitabine in the nanoparticles. The cytotoxicity in pancreatic cancer cells (BxPC-3) was evaluated by MTT assay. The cellular uptake of gemcitabine solution and gemcitabine loaded alginate nano-particle suspension in BxPC-3 cells was determined for 15, 30 and 60 minutes. The particle-size and surface-charge was 564.7+/-56.5nm and -25.65+/-1.94mV for PLGA:PCL and 210.6+/-6.90nm and -33.21+/-1.63mV for alginate. Both the nano-particles were distinctly spherical and non-porous. The drug load was 5.14% for PLGA:PCL and 6.87% for alginate-particles, and the practical entrapment efficiency was found to be 54.1 % and 22.4% respectively. However, in case of PLGA:PCL particles, a two-fold increase in the entrapment efficiency was observed with the addition of sodium-chloride. The absence of endothermic melting peak of the drug in the DSC thermogram was an indication of the non-crystalline state of gemcitabine in the nanoparticles. In addition, there was no cytotoxicity associated with nanoparticle concentrations at-or-below 5 mg/mL. The uptake of nano-particles was around 4 times higher than the solution with treatment for 15 minutes and increased to almost 7 times following treatment for 60 minutes. Gemcitabine hydrochloride could be successfully formulated into a sustained release nano-particulate formulation using calcium cross-linked alginate and dioctyl sulfo succinate system. The nano-particulate delivery system exhibited better cytotoxic activity and also significantly enhanced the accumulation of the drug in BxPC-3 cell monolayers.

Optimization of chitosan nanoparticles for colon tumors using experimental design methodology.

PubMed

Jain, Anekant; Jain, Sanjay K

2016-12-01

Purpose Colon-specific drug delivery systems (CDDS) can improve the bio-availability of drugs through the oral route. A novel formulation for oral administration using ligand coupled chitosan nanoparticles bearing 5-Flurouracil (5FU) encapsulated in enteric coated pellets has been investigated for CDDS. Method The effect of polymer concentration, drug concentration, stirring time and stirring speed on the encapsulation efficiency, and size of nanoparticles were evaluated. The best (or optimum) formulation was obtained by response surface methodology. Using the experimental data, analysis of variance has been carried out to evolve linear empirical models. Using a new methodology, polynomial models have been evolved and the parametric analysis has been carried out. In order to target nanoparticles to the hyaluronic acid (HA) receptors present on colon tumors, HA coupled nanoparticles were tested for their efficacy in vivo. The HA coupled nanoparticles were encapsulated in pellets and were enteric coated to release the drug in the colon. Results Drug release studies under conditions of mimicking stomach to colon transit have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine. The relatively high local drug concentration with prolonged exposure time provides a potential to enhance anti-tumor efficacy with low systemic toxicity for the treatment of colon cancer. Conclusions Conclusively, HA coupled nanoparticles can be considered as the potential candidate for targeted drug delivery and are anticipated to be promising in the treatment of colorectal cancer.

In vivo evidence of oral vaccination with PLGA nanoparticles containing the immunostimulant monophosphoryl lipid A.

PubMed

Sarti, Federica; Perera, Glen; Hintzen, Fabian; Kotti, Katerina; Karageorgiou, Vassilis; Kammona, Olga; Kiparissides, Costas; Bernkop-Schnürch, Andreas

2011-06-01

Although oral vaccination has numerous advantages over the commonly used parenteral route, degradation of vaccine and its low uptake in the lymphoid tissue of the gastrointestinal (GI) tract still impede their development. In this study, the model antigen ovalbumin (OVA) and the immunostimulant monophosphoryl lipid A (MPLA) were incorporated in polymeric nanoparticles based on poly(D,L-lactide-co-glycolide) (PLGA). These polymeric carriers were orally administered to BALB/c mice (Bagg albino, inbred strain of mouse) and the resulting time-dependent systemic and mucosal immune responses towards OVA were assessed by measuring the OVA-specific IgG and IgA titers using an enzyme-linked immunosorbent assay (ELISA). PLGA nanoparticles were spherical in shape, around 320 nm in size, negatively charged (around -20 mV) and had an OVA and MPLA payload of 9.6% and 0.86%, respectively. A single immunization with formulation containing (OVA + MPLA) incorporated in PLGA nanoparticles induced a stronger IgG immune response than that induced by OVA in PBS solution or OVA incorporated into PLGA nanoparticles. Moreover, significantly higher IgA titers were generated by administration of (OVA + MPLA)/PLGA nanoparticles compared to IgA stimulated by control formulations, proving the capability of inducing a mucosal immunity. These findings demonstrate that co-delivery of OVA and MPLA in PLGA nanoparticles promotes both systemic and mucosal immune responses and represents therefore a suitable strategy for oral vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model.

PubMed

Singh, Amit; Xu, Jing; Mattheolabakis, George; Amiji, Mansoor

2016-04-01

In this study, we have formulated redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a targeted vector for systemic delivery of gemcitabine therapy in pancreatic cancer. The gelatin nanoparticles were formed by ethanol-induced desolvation process to encapsulate the bound drug. The surface of the nanoparticles was decorated either with poly(ethylene glycol) (PEG) chains to impart enhanced circulation time or with EGFR targeting peptide to confer target specificity. Our in vitro studies in Panc-1 human pancreatic ductal adenocarcinoma cells confirm that gemcitabine encapsulated in EGFR-targeted gelatin nanoparticles, released through disulfide bond cleavage, had a significantly improved cytotoxic profile. Further, the in vivo anticancer activity was evaluated in an orthotopic pancreatic adenocarcinoma tumor bearing SCID beige mice, which confirmed that EGFR-targeted gelatin nanoparticles could efficiently deliver gemcitabine to the tumor leading to higher therapeutic benefit as compared to the drug in solution. The treatment of pancreatic cancer remains unsatisfactory, with an average 5-year survival of less than 5%. New treatment modalities are thus urgently needed. In this study, the authors presented their formulation of redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a carrier for gemcitabine. In-vitro and in-vivo experiments showed encouraging results. It is hoped that the findings would provide a novel and alternative drug delivery platform for the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Combination of PLGA nanoparticles with mucoadhesive guar-gum films for buccal delivery of antihypertensive peptide.

PubMed

Castro, Pedro M; Baptista, Patrícia; Madureira, Ana Raquel; Sarmento, Bruno; Pintado, Manuela E

2018-05-22

Oral administration of proteins and peptides still is a challenging task to overcome due to low permeability through absorptive epithelia, degradation and metabolism that lead to poor bioavailability. Attempting to overcome such limitations, an antihypertensive peptide derived from whey protein, with KGYGGVSLPEW sequence, was incorporated for the first time into polymeric nanoparticles. An experimental design was followed in order to optimize drug-loading, association efficiency, mean particle size, zeta-potential and polydispersity index of a formulation of poly(lactic-co-glycolic acid) (PLGA) nanoparticles as carriers for bioactive peptides. In sequence, peptide-loaded PLGA nanoparticles were incorporated in a guar-gum film matrix, resulting in a combined delivery system aiming to promote slow release and permeation across buccal epithelium. Neither PLGA nanoparticles, guar-gum films nor the conjugation of PLGA nanoparticles and guar-gum films (GfNp) significantly compromised in vitro TR146 human buccal carcinoma cell line viability after 12 h contact, as assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide reduction assay (MTT). In vitro release assay for developed formulations allowed to conclude that the combination of orodispersible film and nanoparticles granted a slower release of AhP when compared with PLGA or guar-gum films alone or with control. GfNp offered more effective, synergistic, in vitro permeation of TR146 cell multilayer in comparison with guar-gum films or PLGA nanoparticles alone. The combination of PLGA nanoparticles with guar-gum films represent a suitable alternative to conventional per os delivery systems, leading to an increased buccal permeability of carried antihypertensive peptide. Copyright © 2018 Elsevier B.V. All rights reserved.

Potential phototoxicity of aged Al(OH)3-coated Ti02 nanoparticles in retinal pigment epithelial cells

EPA Science Inventory

Titanium dioxide (TiO2) nanoparticles (NPs) exposed to UVA radiation generate reactive oxygen species (ROS). As a component of sunscreen formulations, TiO2 NPs may be coated with Al(OH)3 to prevent ROS from causing oxidative damage to tissues. Simulated swimming pool water (SSPW)...

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.

Lawsonia inermis-mediated synthesis of silver nanoparticles: activity against human pathogenic fungi and bacteria with special reference to formulation of an antimicrobial nanogel.

PubMed

Gupta, Arpita; Bonde, Shital R; Gaikwad, Swapnil; Ingle, Avinash; Gade, Aniket K; Rai, Mahendra

2014-09-01

Lawsonia inermis mediated synthesis of silver nanoparticles (Ag-NPs) and its efficacy against Candida albicans, Microsporum canis, Propioniabacterium acne and Trichophyton mentagrophytes is reported. A two-step mechanism has been proposed for bioreduction and formation of an intermediate complex leading to the synthesis of capped nanoparticles was developed. In addition, antimicrobial gel for M. canis and T. mentagrophytes was also formulated. Ag-NPs were synthesized by challenging the leaft extract of L. inermis with 1 mM AgNO₃. The Ag-NPs were characterized by Ultraviolet-Visible (UV-Vis) spectrophotometer and Fourier transform infrared spectroscopy (FTIR). Transmission electron microscopy (TEM), nanoparticle tracking and analysis sytem (NTA) and zeta potential was measured to detect the size of Ag-NPs. The antimicrobial activity of Ag-NPs was evaluated by disc diffusion method against the test organisms. Thus these Ag-NPs may prove as a better candidate drug due to their biogenic nature. Moreover, Ag-NPs may be an answer to the drug-resistant microorganisms.

The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation.

PubMed

Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

2017-12-01

Therapeutic peptides are conventionally administered via subcutaneous injection. Chitosan-based nanoparticles are gaining increased attention for their ability to serve as a carrier for oral delivery of peptides and vaccination. They offered superior biocompatibiltiy, controlled drug release profile and facilitated gastrointestinal (GI) absorption. The encapsulated peptides can withstand enzymatic degradation and various pH. Chitosan-based nanoparticles can also be modified by ligand conjugation to the surface of nanoparticle for transcellular absorption and specific-targeted delivery of macromolecules to the tissue of interest. Current research suggests that chitosan-based nanoparticles can deliver therapeutic peptide for the treatment of several medical conditions such as diabetes, bacterial infection and cancer. This review summarises the role of chitosan in oral nanoparticle delivery and identifies the clinical application of peptide-loaded chitosan-based nanoparticles.

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.

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.

Surface functionalization of PLGA nanoparticles by non-covalent insertion of a homo-bifunctional spacer for active targeting in cancer therapy.

PubMed

Thamake, S I; Raut, S L; Ranjan, A P; Gryczynski, Z; Vishwanatha, J K

2011-01-21

This work reports the surface functionalization of polymeric PLGA nanoparticles by non-covalent insertion of a homo-bifunctional chemical crosslinker, bis(sulfosuccinimidyl) suberate (BS3) for targeted cancer therapy. We dissolved BS3 in aqueous solution of PVA during formulation of nanoparticles by a modified solid/oil/water emulsion solvent evaporation method. The non-covalent insertion of BS3 was confirmed by Fourier transform infrared (FTIR) spectroscopy. Curcumin and annexin A2 were used as a model drug and a cell specific target, respectively. Nanoparticles were characterized for particle size, zeta potential and surface morphology. The qualitative assessment of antibody attachment was performed by transmission electron microscopy (TEM) as well as confocal microscopy. The optimized formulation showed antibody attachment of 86%. However, antibody attachment was abolished upon blocking the functional groups of BS3. The availability of functional antibodies was evaluated by the presence of a light chain fraction after gel electrophoresis. We further evaluated the in vitro release kinetics of curcumin from antibody coated and uncoated nanoparticles. The release of curcumin is enhanced upon antibody attachment and followed an anomalous release pattern. We also observed that the cellular uptake of nanoparticles was significantly higher in annexin A2 positive cells than in negative cells. Therefore, these results demonstrate the potential use of this method for functionalization as well as to deliver chemotherapeutic agents for treating cancer.

Surface functionalization of PLGA nanoparticles by non-covalent insertion of a homo-bifunctional spacer for active targeting in cancer therapy

NASA Astrophysics Data System (ADS)

Thamake, S. I.; Raut, S. L.; Ranjan, A. P.; Gryczynski, Z.; Vishwanatha, J. K.

2011-01-01

This work reports the surface functionalization of polymeric PLGA nanoparticles by non-covalent insertion of a homo-bifunctional chemical crosslinker, bis(sulfosuccinimidyl) suberate (BS3) for targeted cancer therapy. We dissolved BS3 in aqueous solution of PVA during formulation of nanoparticles by a modified solid/oil/water emulsion solvent evaporation method. The non-covalent insertion of BS3 was confirmed by Fourier transform infrared (FTIR) spectroscopy. Curcumin and annexin A2 were used as a model drug and a cell specific target, respectively. Nanoparticles were characterized for particle size, zeta potential and surface morphology. The qualitative assessment of antibody attachment was performed by transmission electron microscopy (TEM) as well as confocal microscopy. The optimized formulation showed antibody attachment of 86%. However, antibody attachment was abolished upon blocking the functional groups of BS3. The availability of functional antibodies was evaluated by the presence of a light chain fraction after gel electrophoresis. We further evaluated the in vitro release kinetics of curcumin from antibody coated and uncoated nanoparticles. The release of curcumin is enhanced upon antibody attachment and followed an anomalous release pattern. We also observed that the cellular uptake of nanoparticles was significantly higher in annexin A2 positive cells than in negative cells. Therefore, these results demonstrate the potential use of this method for functionalization as well as to deliver chemotherapeutic agents for treating cancer.

Cytocompatible antifungal acrylic resin containing silver nanoparticles for dentures

PubMed Central

Acosta-Torres, Laura Susana; Mendieta, Irasema; Nuñez-Anita, Rosa Elvira; Cajero-Juárez, Marcos; Castaño, Víctor M

2012-01-01

Background Inhibition of Candida albicans on denture resins could play a significant role in preventing the development of denture stomatitis. The safety of a new dental material with antifungal properties was analyzed in this work. Methods Poly(methyl methacrylate) [PMMA] discs and PMMA-silver nanoparticle discs were formulated, with the commercial acrylic resin, Nature-CrylTM, used as a control. Silver nanoparticles were synthesized and characterized by ultraviolet-visible spectroscopy, dispersive Raman spectroscopy, and transmission electron microscopy. The antifungal effect was assessed using a luminescent microbial cell viability assay. Biocompatibility tests were carried out using NIH-3T3 mouse embryonic fibroblasts and a Jurkat human lymphocyte cell line. Cells were cultured for 24 or 72 hours in the presence or absence of the polymer formulations and analyzed using three different tests, ie, cellular viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation by enzyme-linked immunosorbent assay BrdU, and genomic DNA damage (Comet assay). Finally, the samples were evaluated mechanically, and the polymer-bearing silver nanoparticles were analyzed microscopically to evaluate dispersion of the nanoparticles. Results The results show that PMMA-silver nanoparticle discs significantly reduce adherence of C. albicans and do not affect metabolism or proliferation. They also appear not to cause genotoxic damage to cells. Conclusion The present work has developed a new biocompatible antifungal PMMA denture base material. PMID:22969297

A Nanoparticle Based Sp17 Peptide Vaccine Exposes New Immuno-Dominant and Species Cross-reactive B Cell Epitopes

PubMed Central

Xiang, Sue D.; Gao, Qian; Wilson, Kirsty L.; Heyerick, Arne; Plebanski, Magdalena

2015-01-01

Sperm protein antigen 17 (Sp17), expressed in primary as well as in metastatic lesions in >83% of patients with ovarian cancer, is a promising ovarian cancer vaccine candidate. Herein we describe the formulation of nanoparticle based vaccines based on human Sp17 (hSp17) sequence derived peptides, and map the immuno-dominant T cell and antibody epitopes induced using such formulations. The primary T and B cell immuno-dominant region within Sp17 was found to be the same when using biocompatible nanoparticle carriers or the conventional “mix-in” pro-inflammatory adjuvant CpG, both mapping to amino acids (aa) 111–142. However, delivery of hSp17111–142 as a nanoparticle conjugate promoted a number of new properties, changing the dominant antibody isotype induced from IgG2a to IgG1 and the fine specificity of the B cell epitopes within hSp17111–142, from an immuno-dominant region 134–142 aa for CpG, to region 121–138 aa for nanoparticles. Associated with this change in specificity was a substantial increase in antibody cross-reactivity between mouse and human Sp17. These results indicate conjugation of antigen to nanoparticles can have major effects on fine antigen specificity, which surprisingly could be beneficially used to increase the cross-reactivity of antibody responses. PMID:26529027

New Updates Pertaining to Drug Delivery of Local Anesthetics in Particular Bupivacaine Using Lipid Nanoparticles

NASA Astrophysics Data System (ADS)

Beiranvand, Siavash; Eatemadi, Ali; Karimi, Arash

2016-06-01

Lipid nanoparticles (liposomes) were first described in 1965, and several work have led to development of important technical advances like triggered release liposomes and drug-loaded liposomes. These advances have led to numerous clinical trials in such diverse areas such as the delivery of anti-cancer, antifungal, and antibiotic drugs; the delivery of gene medicines; and most importantly the delivery of anesthesia drugs. Quite a number of liposomes are on the market, and many more are still in developmental stage. Lipid nanoparticles are the first nano-medicine delivery system to be advanced from laboratory concept to clinical application with high considerable clinical acceptance. Drug delivery systems for local anesthetics (LAs) have caught the interest of many researchers because there are many biomedical advantages connected to their application. There have been several formulation techniques to systemically deliver LA that include encapsulation in liposomes and complexation in cyclodextrins, nanoparticles, and to a little extent gold nanoparticles. The proposed formulations help to decrease the LA concentration utilized, increase its permeability, and most importantly increase the localization of the LA for a long period of time thereby leading to increase in the duration of the LA effect and finally to reduce any local and systemic toxicity. In this review, we will highlight on new updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles.

New Updates Pertaining to Drug Delivery of Local Anesthetics in Particular Bupivacaine Using Lipid Nanoparticles.

PubMed

Beiranvand, Siavash; Eatemadi, Ali; Karimi, Arash

2016-12-01

Lipid nanoparticles (liposomes) were first described in 1965, and several work have led to development of important technical advances like triggered release liposomes and drug-loaded liposomes. These advances have led to numerous clinical trials in such diverse areas such as the delivery of anti-cancer, antifungal, and antibiotic drugs; the delivery of gene medicines; and most importantly the delivery of anesthesia drugs. Quite a number of liposomes are on the market, and many more are still in developmental stage. Lipid nanoparticles are the first nano-medicine delivery system to be advanced from laboratory concept to clinical application with high considerable clinical acceptance. Drug delivery systems for local anesthetics (LAs) have caught the interest of many researchers because there are many biomedical advantages connected to their application. There have been several formulation techniques to systemically deliver LA that include encapsulation in liposomes and complexation in cyclodextrins, nanoparticles, and to a little extent gold nanoparticles. The proposed formulations help to decrease the LA concentration utilized, increase its permeability, and most importantly increase the localization of the LA for a long period of time thereby leading to increase in the duration of the LA effect and finally to reduce any local and systemic toxicity. In this review, we will highlight on new updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles.

Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

PubMed

Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

2012-04-02

This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

Development, characterization, and in vitro evaluation of phosphatidylcholine-sodium cholate-based nanoparticles for siRNA delivery to MCF-7 human breast cancer cells

NASA Astrophysics Data System (ADS)

Pérez, Sebastián Ezequiel; Gándola, Yamila; Carlucci, Adriana Mónica; González, Lorena

2015-03-01

Phosphatidylcholine-sodium cholate (SC)-based nanoparticles were designed, characterized, and evaluated as plausible oligonucleotides delivery systems. For this purpose, formulation of the systems was optimized to obtain low cytotoxic vehicles with high siRNA-loading capacity and acceptable transfection ability. Mixtures of soybean phosphatidylcholine (SPC) and SC were prepared at different molar ratios with 2 % w/v total concentration; distilled water and two different buffers were used as dispersion medium. Nanoparticles below 150 nm were observed showing spherical shape which turned smaller in diameter as the SC molar proportion increased, accounting for small unilamellar vesicles when low proportions of SC were present in the formulation, but clear mixed micellar solutions at higher SC percentages. Macroscopic characteristics along with physico-chemical parameters values supported the presence of these types of structures. SYBR green displacement assays demonstrated an important oligonucleotide binding that increased as bile salt relative content got higher. Within the same molar ratio, nanoparticles showed the following binding efficiency order: pH 7.4 > pH 5.0 > distilled water. siRNA-loading capacity assays confirmed the higher siRNA binding by the mixed micelles containing higher SC proportion; moreover, the complexes formed were smaller as the SC:SPC ratio increased. Considering cytotoxicity and siRNA-loading capacity, 1:2 and 1:4 SPC:SC formulations were selected for further biological assays. Nanoparticles prepared in any of the three media were able to induce dsRNA uptake and efficiently transfect RNA for gene silencing, for the compositions prepared in buffer pH 5.0 being the most versatile.

Impact of the emulsification-diffusion method on the development of pharmaceutical nanoparticles.

PubMed

Quintanar-Guerrero, David; Zambrano-Zaragoza, María de la Luz; Gutierrez-Cortez, Elsa; Mendoza-Munoz, Nestor

2012-12-01

Nanotechnology is having a profound impact in many scientific fields and it has become one of the most important and exciting discipline. Like all technological advances, nanotechnology has its own scientific basis with a broad interdisciplinary effect. Perhaps, we are witnessing an exponential growth of nanotechnology, reflection of this is the important increase in the number of patents, scientific papers and specialized "nano" meetings and journals. The impact in the pharmaceutical area is related to the use of colloidal drug delivery systems as carriers for bioactive agents, in particular, the nanoparticle technology. The term nanoparticles designates solid submicronic particles formed of acceptable materials (e.g. polymers, lipids, etc.) containing an active substance. It includes both nanospheres (matricial systems) and nanocapsules (membrane systems). The knowledge of the nanoparticle preparation methods is a key issue for the formulator involved with drug-delivery research and development. In general, the methods based on preformed polymers, in particular biodegradable polymers, are preferred due to their easy implementation and lower potential toxicity. One of the most widely used methods to prepare polymeric nanoparticles is emulsification-diffusion. This method has been discussed in some reviews that compile research works but has a small number of patents. In this review, the emulsification-diffusion method is discussed from a technological point of view in order to show the operating conditions and formulation variables from data extracted of recent patents and experimental works. The main idea is to provide the reader with a general guide for formulators to make decisions about the usefulness of this method to develop specific nanoparticulate systems. The first part of this review provides an overview of the emulsification-diffusion method to prepare polymeric nanoparticles, while the second part evaluates the influence of preparative variables on the properties of the obtained particles relating the events to the formation mechanism. Novel innovations and applications of the method have also been compiled.

Mucoadhesive buccal tablets containing silymarin Eudragit-loaded nanoparticles: formulation, characterisation and ex vivo permeation.

PubMed

El-Nahas, Amira E; Allam, Ahmed N; El-Kamel, Amal H

2017-08-01

Eudragit-loaded silymarin nanoparticles (SNPs) and their formulation into buccal mucoadhesive tablets were investigated to improve the low bioavailability of silymarin through buccal delivery. Characterisation of SNPs and silymarin buccal tablets (SBTs) containing the optimised NPs were performed. Ex vivo permeability of nominated SBTs were assessed using chicken pouch mucosa compared to SNPs and drug suspension followed by histopathological examination. Selected SNPs had a small size (<150 nm), encapsulation effciency (>77%) with drug release of about 90% after 6 h. For STBs, all physicochemical parameters were satisfactory for different polymers used. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state. Ex vivo permeation significantly emphasised the great enhancement of silymarin permeation after NPs formation and much more increase after formulating into BTs relative to the corresponding drug dispersion with confirmed membrane integrity. Incorporation of SNPs into BTs could be an efficient vehicle for delivery of silymarin.

Evidence does not support absorption of intact solid lipid nanoparticles via oral delivery

NASA Astrophysics Data System (ADS)

Hu, Xiongwei; Fan, Wufa; Yu, Zhou; Lu, Yi; Qi, Jianping; Zhang, Jian; Dong, Xiaochun; Zhao, Weili; Wu, Wei

2016-03-01

Whether and to what extent solid lipid nanoparticles (SLNs) can be absorbed integrally via oral delivery should be clarified because it is the basis for elucidation of absorption mechanisms. To address this topic, the in vivo fate of SLNs as well as their interaction with biomembranes is investigated using water-quenching fluorescent probes that can signal structural variations of lipid-based nanocarriers. Live imaging indicates prolonged retention of SLNs in the stomach, whereas in the intestine, SLNs can be digested quickly. No translocation of intact SLNs to other organs or tissues can be observed. The in situ perfusion study shows bioadhesion of both SLNs and simulated mixed micelles (SMMs) to intestinal mucus, but no evidence of penetration of integral nanocarriers. Both SLNs and SMMs exhibit significant cellular uptake, but fail to penetrate cell monolayers. Confocal laser scanning microscopy reveals that nanocarriers mainly concentrate on the surface of the monolayers, and no evidence of penetration of intact vehicles can be obtained. The mucous layer acts as a barrier to the penetration of both SLNs and SMMs. Both bile salt-decoration and SMM formulation help to strengthen the interaction with biomembranes. It is concluded that evidence does not support absorption of intact SLNs via oral delivery.Whether and to what extent solid lipid nanoparticles (SLNs) can be absorbed integrally via oral delivery should be clarified because it is the basis for elucidation of absorption mechanisms. To address this topic, the in vivo fate of SLNs as well as their interaction with biomembranes is investigated using water-quenching fluorescent probes that can signal structural variations of lipid-based nanocarriers. Live imaging indicates prolonged retention of SLNs in the stomach, whereas in the intestine, SLNs can be digested quickly. No translocation of intact SLNs to other organs or tissues can be observed. The in situ perfusion study shows bioadhesion of both SLNs and simulated mixed micelles (SMMs) to intestinal mucus, but no evidence of penetration of integral nanocarriers. Both SLNs and SMMs exhibit significant cellular uptake, but fail to penetrate cell monolayers. Confocal laser scanning microscopy reveals that nanocarriers mainly concentrate on the surface of the monolayers, and no evidence of penetration of intact vehicles can be obtained. The mucous layer acts as a barrier to the penetration of both SLNs and SMMs. Both bile salt-decoration and SMM formulation help to strengthen the interaction with biomembranes. It is concluded that evidence does not support absorption of intact SLNs via oral delivery. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07474f

Purely aqueous PLGA nanoparticulate formulations of curcumin exhibit enhanced anticancer activity with dependence on the combination of the carrier.

PubMed

Nair, K Lekha; Thulasidasan, Arun Kumar T; Deepa, G; Anto, Ruby John; Kumar, G S Vinod

2012-04-04

Curcumin, a yellow pigment present in turmeric, possess potential anti-proliferative and anti-inflammatory activities but poor aqueous solubility limits its applications. In this study we report a novel comparative study of the formulation and characterization of curcumin nanoparticles (nanocurcumin) using two poly (lactide-co-glycolide) (PLGA) combinations, 50:50 and 75:25 having different lactide to glycolide ratios. Nanocurcumin 50:50 showed smaller size with higher encapsulation efficiency. Thermal evaluation suggested the presence of curcumin in molecular dispersion form which supported its sustained release up to a week where nanocurcumin 50:50 showed faster release. Cellular uptake studies in human epithelial cervical cancer cells (HeLa) exhibited enhanced intracellular fluorescence with nanocurcumin when compared to free curcumin, when both given in purely aqueous media. Antiproliferative studies using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, Annexin V/propidium iodide staining, poly (ADP-ribose) polymerase (PARP) cleavage and downregulation of clonogenic potential of HeLa cells proved the better antitumor activity of nanocurcumin 50:50 administered in aqueous media. Superior efficacy of nanocurcumin 50:50 in comparison to free curcumin was further demonstrated by electrophoretic mobility shift assay and immunocytochemical analysis. In conclusion, the enhanced aqueous solubility and higher anticancer efficacy of nanocurcumin administered in aqueous media clearly demonstrates its potential against cancer chemotherapy, with dependence on the combination of PLGA. Copyright © 2012. Published by Elsevier B.V.

Study of Antimicrobial Effects of Clarithromycin Loaded PLGA Nanoparticles against Clinical Strains of Helicobacter pylori.

PubMed

Lotfipour, F; Valizadeh, H; Milani, M; Bahrami, N; Ghotaslou, R

2016-01-01

Clarithromycin (CLR) formulation was prepared as PLGA nanoparticles in order to enhance the therapeutic effects using the distinctive features of a nanoparticulate delivery system. CLR loaded PLGA nanoparticles were prepared by Quasi Emulsion Solvent Diffusion (QESD) method using Poly lactic-co-Glycolic Acid (PLGA) as a biodegradable polymer. Antibacterial activity of the prepared formulations was evaluated against clinical strains of Helicobacter pylori, isolated from gastric biopsies of patients with gastritis, duodenal ulcer, peptic ulcer, and gastroesophageal reflux disease undergoing endoscopy, by using agar dilution method.Spherical nanoparticles with relatively narrow size distribution (between 200 and 800 nm) in the size range of 305 ± 138, 344 ± 148 and 362 ± 110 nm were achieved for F22, F23 and F23 respectively. CLR encapsulation percentages were measured to be 57.4 ± 4.3 to 80.2 ± 4.0%. CLR loaded PLGA nanoparticles showed equal or enhanced eradication effect against H. pylori strains according to the declined MIC values in comparison with the untreated CLR.In conclusion, the prepared CLR nanoformulation showed appropriate physicochemical properties and improved activity against H. pylori that could be a suitable candidate for oral preparations. © Georg Thieme Verlag KG Stuttgart · New York.

In Vitro and In Vivo Characterization of Drug Nanoparticles Prepared Using PureNano™ Continuous Crystallizer to Improve the Bioavailability of Poorly Water Soluble Drugs.

PubMed

Tahara, Kohei; Nishikawa, Masahiro; Matsui, Ko; Hisazumi, Koji; Onodera, Risako; Tozuka, Yuichi; Takeuchi, Hirofumi

2016-09-01

The aim of this study was to enhance the dissolution and oral absorption of poorly water-soluble active pharmaceutical ingredients (APIs) using nanoparticle suspensions prepared with a PureNano™ continuous crystallizer (PCC). Nanoparticle suspensions were prepared with a PCC, which is based on microfluidics reaction technology and solvent-antisolvent crystallization. Phenytoin, bezafibrate, flurbiprofen, and miconazole were used as model APIs. These APIs were dissolved in ethanol and precipitated by the addition of water and polyvinyl alcohol. Batch crystallization (BC) using a beaker was also performed to prepare the suspensions. Both PCC and BC formulations were freeze-dried before being characterized in vitro and in vivo. The particle sizes of the nanoparticle suspensions prepared with the PCC were smaller than those prepared by BC. The dissolution rate of each API in vitro significantly increased after crystallization. Reducing the particle size of either the BC or PCC formulation led to increased API flux across Caco-2 cell monolayers. PCC preparations showed higher plasma concentrations after oral administration, demonstrating the advantages of a fast dissolution rate and increased interaction with the gastrointestinal tract owing to the smaller particle size. PCC can continuously produce nanoparticle APIs and is an efficient approach for improving their oral bioavailability.

Nanoformulation of D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) diblock copolymer for breast cancer therapy.

PubMed

Huang, Laiqiang; Chen, Hongbo; Zheng, Yi; Song, Xiaosong; Liu, Ranyi; Liu, Kexin; Zeng, Xiaowei; Mei, Lin

2011-10-01

The purpose of this research was to develop formulation of docetaxel-loaded biodegradable TPGS-b-(PCL-ran-PGA) nanoparticles for breast cancer chemotherapy. A novel diblock copolymer, d-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) [TPGS-b-(PCL-ran-PGA)], was synthesized from ε-caprolactone, glycolide and d-α-tocopheryl polyethylene glycol 1000 succinate by ring-opening polymerization using stannous octoate as catalyst. The obtained copolymers were characterized by (1)H NMR, GPC and TGA. The docetaxel-loaded TPGS-b-(PCL-ran-PGA) nanoparticles were prepared and characterized. The data showed that the fluorescence TPGS-b-(PCL-ran-PGA) nanoparticles could be internalized by MCF-7 cells. The TPGS-b-(PCL-ran-PGA) nanoparticles achieved significantly higher level of cytotoxicity than commercial Taxotere®. MCF-7 xenograft tumor model on SCID mice showed that docetaxel formulated in the TPGS-b-(PCL-ran-PGA) nanoparticles could effectively inhibit the growth of tumor over a longer period of time than Taxotere® at the same dose. In conclusion, the TPGS-b-(PCL-ran-PGA) copolymer could be acted as a novel and potential biologically active polymeric material for nanoformulation in breast cancer chemotherapy. This journal is © The Royal Society of Chemistry 2011

Lipid-drug-conjugate (LDC) solid lipid nanoparticles (SLN) for the delivery of nicotine to the oral cavity - optimization of nicotine loading efficiency.

PubMed

Ding, Yuan; Nielsen, Kent A; Nielsen, Bruno P; Bøje, Niels W; Müller, Rainer H; Pyo, Sung Min

2018-03-12

Nicotine, obtained from tobacco leaves, has been used to promote the cessation of smoking and reduce the risk of COPD and lung cancer. Incorporating the active in lipid nanoparticles is an effective tool to minimize its irritation potential and to use the particles as intermediate to produce final products. However, as a hydrophilic active, it is a challenge to prepare nicotine loaded lipid nanoparticles with high drug loading. In this study, lipid-drug-conjugates (LDC) were formed by nicotine and different fatty acids to enable the production of sufficiently loaded nicotine lipid nanoparticles. The encapsulation efficiency of nicotine in LDC-containing SLN was about 50%, which increased at least fourfold compared to the non-LDC formulations (around 10%) due to the increased lipophilicity of nicotine by strong interactions between positively charged nicotine and negatively charged fatty acids (formation of LDCs). The z-average of all formulations (150 to 350 nm) proved to be in the required submicron size range with a narrow size distribution. In summary, nicotine loaded LDC lipid nanoparticles with high drug loading were successfully developed with Kolliwax® S and stearic acid as counter-ion forming the LDC and hydrogenated sunflower oil (HSO) as lipid particle matrix. Copyright © 2018. Published by Elsevier B.V.

Drug transport mechanism of oral antidiabetic nanomedicines.

PubMed

Gundogdu, Evren; Yurdasiper, Aysu

2014-01-01

Over the last few decades, extensive efforts have been made worldwide to develop nanomedicine delivery systems, especially via oral route for antidiabetic drugs. Absorption of insulin is hindered by epithelial cells of gastrointestinal tract, acidic gastric pH and digestive enzymes. Recent reports have identified and explained the beneficial role of several structural molecules like mucoadhesive polymers (polyacrylic acid, sodium alginate, chitosan) and other copolymers for the efficient transport and release of insulin to its receptors. Insulin nanomedicines based on alginate-dextran sulfate core with a chitosan-polyethylene glycol-albumin shell reduced glycaemia in a dose dependent manner. Orally available exendin-4 formulations exerted their effects in a time dependent manner. Insulin nanoparticles formed by using alginate and dextran sulfate nucleating around calcium and binding to poloxamer, stabilized by chitosan, and subsequently coated with albumin showed a threefold increase of the hypoglycemic effect in comparison to free insulin in animal models. Solid lipid nanoparticles showed an enhancement of the bioavailability of repaglinide (RG) within optimized solid lipid nanoparticle formulations when compared with RG alone. Nanoparticles represent multiparticulate delivery systems designed to obtain prolonged or controlled drug delivery and to improve bioavailability as well as stability. Nanoparticles can also offer advantages like limiting fluctuations within therapeutic range, reducing side effects, protecting drugs from degradation, decreasing dosing frequency, and improving patient compliance and convenience.

Combination of hyperthermia and photodynamic therapy on mesenchymal stem cell line treated with chloroaluminum phthalocyanine magnetic-nanoemulsion

NASA Astrophysics Data System (ADS)

de Paula, Leonardo B.; Primo, Fernando L.; Pinto, Marcelo R.; Morais, Paulo C.; Tedesco, Antonio C.

2015-04-01

The present study reports on the preparation and the cell viability assay of two nanoemulsions loaded with magnetic nanoparticle and chloroaluminum phthalocyanine. The preparations contain equal amount of chloroaluminum phthalocyanine (0.05 mg/mL) but different contents of magnetic nanoparticle (0.15×1013 or 1.50×1013 particle/mL). The human bone marrow mesenchymal stem cell line was used as the model to assess the cell viability and this type of cell can be used as a model to mimic cancer stem cells. The cell viability assays were performed in isolated as well as under combined magnetic hyperthermia and photodynamic therapy treatments. We found from the cell viability assay that under the hyperthermia treatment (1 MHz and 40 Oe magnetic field amplitude) the cell viability reduction was about 10%, regardless the magnetic nanoparticle content within the magnetic nanoparticle/chloroaluminum phthalocyanine formulation. However, cell viability reduction of about 50% and 60% were found while applying the photodynamic therapy treatment using the magnetic nanoparticle/chloroaluminum phthalocyanine formulation containing 0.15×1013 or 1.50×1013 magnetic particle/mL, respectively. Finally, an average reduction in cell viability of about 66% was found while combining the hyperthermia and photodynamic therapy treatments.

Novel formulations for antimicrobial peptides.

PubMed

Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

2014-10-09

Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

Novel Formulations for Antimicrobial Peptides

PubMed Central

Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

2014-01-01

Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

Innovative formulation of nystatin particulate systems in toothpaste for candidiasis treatment.

PubMed

Pinto Reis, Catarina; Vasques Roque, Luís; Baptista, Marina; Rijo, Patrícia

2016-01-01

Oral candidiasis is a mycosis on the mucous membranes of the mouth but not limited to the mouth. Nystatin is one of the most frequently employed antifungal agents to treat infections and may be safely given orally as well as applied topically but its absorption through mucocutaneous membranes such as the gut and the skin is minimal. The purpose of this study is to enhance the effectiveness of nystatin using particulate system such as beads, micro- and nanoparticles of alginate incorporated into toothpaste. Those particulate systems of nystatin were prepared by extrusion/external gelation for beads and emulsification/internal gelation for micro- and nanoparticles and characterized. Small, anionic charged and monodispersed particles were successfully produced. The type of particulate system influenced all previous parameters, being microparticles the most suitable particulate system of nystatin showing the slowest release, the highest inhibitory effect of Candida albicans over a period of one year. Those results allowed the conclusion that alginate exhibits properties that enable the in vitro functionality of encapsulated nystatin and thus may provide the basis for new successful approaches for the treatment of oral antifungal infections such as oral candidiasis.

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.

Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(butylcyanoacrylate) nanoparticles

PubMed Central

Melguizo, Consolación; Cabeza, Laura; Prados, Jose; Ortiz, Raúl; Caba, Octavio; Rama, Ana R; Delgado, Ángel V; Arias, José L

2015-01-01

Doxorubicin (Dox) is widely used for the combined chemotherapy of solid tumors. However, the use of these drug associations in lung cancer has low antitumor efficacy. To improve its efficacious delivery and activity in lung adenocarcinoma cells, we developed a biodegradable and noncytotoxic nanoplatform based on biodegradable poly(butylcyanoacrylate) (PBCA). The reproducible formulation method was based on an anionic polymerization process of the PBCA monomer, with the antitumor drug being entrapped within the nanoparticle (NP) matrix during its formation. Improved drug-entrapment efficiencies and sustained (biphasic) drug-release properties were made possible by taking advantage of the synthesis conditions (drug, monomer, and surfactant-agent concentrations). Dox-loaded NPs significantly enhanced cellular uptake of the drug in the A549 and LL/2 lung cancer cell lines, leading to a significant improvement of the drug’s antitumoral activity. In vivo studies demonstrated that Dox-loaded NPs clearly reduced tumor volumes and increased mouse-survival rates compared to the free drug. These results demonstrated that PBCA NPs may be used to optimize the antitumor activity of Dox, thus exhibiting a potential application in chemotherapy against lung adenocarcinoma. PMID:26715840

Improved i.p. drug delivery with bioadhesive nanoparticles

PubMed Central

Deng, Yang; Yang, Fan; Cocco, Emiliano; Song, Eric; Zhang, Junwei; Cui, Jiajia; Mohideen, Muneeb; Bellone, Stefania; Santin, Alessandro D.; Saltzman, W. Mark

2016-01-01

The i.p. administration of chemotherapy in ovarian and uterine serous carcinoma patients by biodegradable nanoparticles may represent a highly effective way to suppress peritoneal carcinomatosis. However, the efficacy of nanoparticles loaded with chemotherapeutic agents is currently hampered by their fast clearance by lymphatic drainage. Here, we show that a unique formulation of bioadhesive nanoparticles (BNPs) can interact with mesothelial cells in the abdominal cavity and significantly extend the retention of the nanoparticles in the peritoneal space. BNPs loaded with a potent chemotherapeutic agent [epothilone B (EB)] showed significantly lower systemic toxicity and higher therapeutic efficacy against i.p. chemotherapy-resistant uterine serous carcinoma-derived xenografts compared with free EB and non-BNPs loaded with EB. PMID:27663731

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.

Image-guided thermal therapy with a dual-contrast magnetic nanoparticle formulation: A feasibility study

PubMed Central

Attaluri, Anilchandra; Seshadri, Madhav; Mirpour, Sahar; Wabler, Michele; Marinho, Thomas; Furqan, Muhammad; Zhou, Haoming; De Paoli, Silvia; Gruettner, Cordula; Gilson, Wesley; DeWeese, Theodore; Garcia, Monica; Ivkov, Robert; Liapi, Eleni

2016-01-01

Purpose/objective The aim of this study was to develop and investigate the properties of a magnetic iron oxide nanoparticle–ethiodised oil formulation for image-guided thermal therapy of liver cancer. Materials and methods The formulation comprises bionised nano-ferrite (BNF) nanoparticles suspended in ethiodised oil, emulsified with polysorbate 20 (BNF-lip). Nanoparticle size was measured via photon correlation spectroscopy and transmission electron microscopy. In vivo thermal therapy capability was tested in two groups of male Foxn1nu mice bearing subcutaneous HepG2 xenograft tumours. Group I (n =12) was used to screen conditions for group II (n =48). In group II, mice received one of BNF-lip (n =18), BNF alone (n =16), or PBS (n =14), followed by alternating magnetic field (AMF) hyperthermia, with either varied duration (15 or 20 min) or amplitude (0, 16, 20, or 24 kA/m). Image-guided fluoroscopic intra-arterial injection of BNF-lip was tested in New Zealand white rabbits (n =10), bearing liver VX2 tumours. The animals were subsequently imaged with CT and 3 T MRI, up to 7 days post-injection. The tumours were histopathologically evaluated for distribution of BNF-lip. Results The BNF showed larger aggregate diameters when suspended in BNF-lip, compared to clear solution. The BNF-lip formulation produced maximum tumour temperatures with AMF >20 kA/m and showed positive X-ray visibility and substantial shortening of T1 and T2 relaxation time, with sustained intratumoural retention up to 7 days post-injection. On pathology, intratumoural BNF-lip distribution correlated well with CT imaging of intratumoural BNF-lip distribution. Conclusion The BNF-lip formulation has favourable thermal and dual imaging capabilities for image-guided thermal therapy of liver cancer, suggesting further exploration for clinical applications. PMID:27151045

Photocatalytic Nanocomposites for the Protection of European Architectural Heritage.

PubMed

Gherardi, Francesca; Roveri, Marco; Goidanich, Sara; Toniolo, Lucia

2018-01-03

In the field of stone protection, the introduction of inorganic nanoparticles, such as TiO₂, ZnO, and Ag in polymeric blends can enhance the protective action of pristine treatments, as well as confer additional properties (photocatalytic, antifouling, and antibacterial). In the framework of the "Nano-Cathedral" European project, nanostructured photocatalytic protective treatments were formulated by using different TiO₂ nanoparticles, solvents, and silane/siloxane systems in the blends. The results about the characterization and application of two promising nano-TiO₂ based products applied on Apuan marble and Ajarte limestone are here reported, aiming at investigating the complex system "treatment/stone-substrate". The nanocomposites show better performances when compared to a commercial reference siloxane based protective treatment, resulting in different performances once applied on different carbonatic substrates, with very low and high open porosity, confirming the necessity of correlating precisely the characteristics of the stone material to those of the protective formulations. In particular, the TiO₂ photocatalytic behavior is strictly linked to the amount of available nanoparticles and to the active surface area. The alkyl silane oligomers of the water-based formulation have a good penetration into the microstructure of Ajarte limestone, whereas the solvent-based and small size monomeric formulation shows better results for Apuan marble, granting a good coverage of the pores. The encouraging results obtained so far in lab will be confirmed by monitoring tests aiming at assessing the effectiveness of the treatments applied in pilot sites of historical Gothic Cathedrals.

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.

Photocatalytic Nanocomposites for the Protection of European Architectural Heritage

PubMed Central

Roveri, Marco; Goidanich, Sara; Toniolo, Lucia

2018-01-01

In the field of stone protection, the introduction of inorganic nanoparticles, such as TiO2, ZnO, and Ag in polymeric blends can enhance the protective action of pristine treatments, as well as confer additional properties (photocatalytic, antifouling, and antibacterial). In the framework of the “Nano-Cathedral” European project, nanostructured photocatalytic protective treatments were formulated by using different TiO2 nanoparticles, solvents, and silane/siloxane systems in the blends. The results about the characterization and application of two promising nano-TiO2 based products applied on Apuan marble and Ajarte limestone are here reported, aiming at investigating the complex system “treatment/stone-substrate”. The nanocomposites show better performances when compared to a commercial reference siloxane based protective treatment, resulting in different performances once applied on different carbonatic substrates, with very low and high open porosity, confirming the necessity of correlating precisely the characteristics of the stone material to those of the protective formulations. In particular, the TiO2 photocatalytic behavior is strictly linked to the amount of available nanoparticles and to the active surface area. The alkyl silane oligomers of the water-based formulation have a good penetration into the microstructure of Ajarte limestone, whereas the solvent-based and small size monomeric formulation shows better results for Apuan marble, granting a good coverage of the pores. The encouraging results obtained so far in lab will be confirmed by monitoring tests aiming at assessing the effectiveness of the treatments applied in pilot sites of historical Gothic Cathedrals. PMID:29301338

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.

``The Princess and the Pea'' at the Nanoscale: Wrinkling and Delamination of Graphene on Nanoparticles

NASA Astrophysics Data System (ADS)

Yamamoto, Mahito; Pierre-Louis, Olivier; Huang, Jia; Fuhrer, Michael S.; Einstein, Theodore L.; Cullen, William G.

2012-10-01

Thin membranes exhibit complex responses to external forces or geometrical constraints. A familiar example is the wrinkling, exhibited by human skin, plant leaves, and fabrics, that results from the relative ease of bending versus stretching. Here, we study the wrinkling of graphene, the thinnest and stiffest known membrane, deposited on a silica substrate decorated with silica nanoparticles. At small nanoparticle density, monolayer graphene adheres to the substrate, detached only in small regions around the nanoparticles. With increasing nanoparticle density, we observe the formation of wrinkles which connect nanoparticles. Above a critical nanoparticle density, the wrinkles form a percolating network through the sample. As the graphene membrane is made thicker, global delamination from the substrate is observed. The observations can be well understood within a continuum-elastic model and have important implications for strain-engineering the electronic properties of graphene.

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.

Gold core@silver semishell Janus nanoparticles prepared by interfacial etching.

PubMed

Chen, Limei; Deming, Christopher P; Peng, Yi; Hu, Peiguang; Stofan, Jake; Chen, Shaowei

2016-08-14

Gold core@silver semishell Janus nanoparticles were prepared by chemical etching of Au@Ag core-shell nanoparticles at the air/water interface. Au@Ag core-shell nanoparticles were synthesized by chemical deposition of a silver shell onto gold seed colloids followed by the self-assembly of 1-dodecanethiol onto the nanoparticle surface. The nanoparticles then formed a monolayer on the water surface of a Langmuir-Blodgett trough, and part of the silver shell was selectively etched away by the mixture of hydrogen peroxide and ammonia in the water subphase, where the etching was limited to the side of the nanoparticles that was in direct contact with water. The resulting Janus nanoparticles exhibited an asymmetrical distribution of silver on the surface of the gold cores, as manifested in transmission electron microscopy, UV-vis absorption, and X-ray photoelectron spectroscopy measurements. Interestingly, the Au@Ag semishell Janus nanoparticles exhibited enhanced electrocatalytic activity in oxygen reduction reactions, as compared to their Au@Ag and Ag@Au core-shell counterparts, likely due to a synergistic effect between the gold cores and silver semishells that optimized oxygen binding to the nanoparticle surface.

Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

NASA Astrophysics Data System (ADS)

Patel, Meghavi

Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core with a well-defined shell and the particle size was in agreement with the particle size analysis data obtained by DLS. DSC thermograms of the lyophilized SLNs indicate a reduction in the crystallinity order of GMS particles. The drug encapsulation efficiency was found to be approximately 30%. In vitro drug release studies from redispersed lyophilized SLNs showed that 17 % of the encapsulated drug was released within 2 h. The SLNs prepared in our lab demonstrated characteristics that can potentially be utilized in an anticancer drug delivery system. Future in vitro cell culture and in vivo animal model studies will delineate compatibility and utility of these formulations in biological systems.

Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma.

PubMed

Bredlau, Amy Lee; Dixit, Suraj; Chen, Chao; Broome, Ann-Marie

2017-01-01

Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as delivery techniques that address the difficulty in crossing the blood brain barrier (BBB) are developed. Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanoparticle delivery system for treatment of the uniformly fatal pediatric disease of DIPG.

Memory effects in nanoparticle dynamics and transport

NASA Astrophysics Data System (ADS)

Sanghi, Tarun; Bhadauria, Ravi; Aluru, N. R.

2016-10-01

In this work, we use the generalized Langevin equation (GLE) to characterize and understand memory effects in nanoparticle dynamics and transport. Using the GLE formulation, we compute the memory function and investigate its scaling with the mass, shape, and size of the nanoparticle. It is observed that changing the mass of the nanoparticle leads to a rescaling of the memory function with the reduced mass of the system. Further, we show that for different mass nanoparticles it is the initial value of the memory function and not its relaxation time that determines the "memory" or "memoryless" dynamics. The size and the shape of the nanoparticle are found to influence both the functional-form and the initial value of the memory function. For a fixed mass nanoparticle, increasing its size enhances the memory effects. Using GLE simulations we also investigate and highlight the role of memory in nanoparticle dynamics and transport.

Nanotechnology Applications for Diffuse Intrinsic Pontine Glioma

PubMed Central

Bredlau, Amy Lee; Dixit, Suraj; Chen, Chao; Broome, Ann-Marie

2017-01-01

Diffuse intrinsic pontine gliomas (DIPGs) are invariably fatal tumors found in the pons of elementary school aged children. These tumors are grade II-IV gliomas, with a median survival of less than 1 year from diagnosis when treated with standard of care (SOC) therapy. Nanotechnology may offer therapeutic options for the treatment of DIPGs. Multiple nanoparticle formulations are currently being investigated for the treatment of DIPGs. Nanoparticles based upon stable elements, polymer nanoparticles, and organic nanoparticles are under development for the treatment of brain tumors, including DIPGs. Targeting of nanoparticles is now possible as delivery techniques that address the difficulty in crossing the blood brain barrier (BBB) are developed. Theranostic nanoparticles, a combination of therapeutics and diagnostic nanoparticles, improve imaging of the cancerous tissue while delivering therapy to the local region. However, additional time and attention should be directed to developing a nanoparticle delivery system for treatment of the uniformly fatal pediatric disease of DIPG. PMID:26903150

Nanoparticles in the clinic

PubMed Central

Anselmo, Aaron C.

2016-01-01

Abstract Nanoparticle/microparticle‐based drug delivery systems for systemic (i.e., intravenous) applications have significant advantages over their nonformulated and free drug counterparts. For example, nanoparticle systems are capable of delivering therapeutics and treating areas of the body that other delivery systems cannot reach. As such, nanoparticle drug delivery and imaging systems are one of the most investigated systems in preclinical and clinical settings. Here, we will highlight the diversity of nanoparticle types, the key advantages these systems have over their free drug counterparts, and discuss their overall potential in influencing clinical care. In particular, we will focus on current clinical trials for nanoparticle formulations that have yet to be clinically approved. Additional emphasis will be on clinically approved nanoparticle systems, both for their currently approved indications and their use in active clinical trials. Finally, we will discuss many of the often overlooked biological, technological, and study design challenges that impact the clinical success of nanoparticle delivery systems. PMID:29313004

Morphology-Controlled Synthesis and Metalation of Porphyrin Nanoparticles with Enhanced Photocatalytic Performance

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

Wang, Jiefei; Zhong, Yong; Wang, Liang

The design and engineering of the size, shape, and chemistry of photoactive building blocks enables the fabrication of functional nanoparticles for applications in light harvesting, photocatalytic synthesis, water splitting, phototherapy, and photodegradation. Here, we report the synthesis of such nanoparticles through a surfactant-assisted interfacial self-assembly process using optically active porphyrin as a functional building block. The self-assembly process relies on specific interactions such as π–π stacking and metalation (metal atoms and ligand coordination) between individual porphyrin building blocks. Depending on the kinetic conditions and type of surfactants, resulting structures exhibit well-defined one- to three-dimensional morphologies such as nanowires, nanooctahedra, andmore » hierarchically ordered internal architectures. Specifically, electron microscopy and X-ray diffraction results indicate that these nanoparticles exhibit stable single-crystalline and nanoporous frameworks. In conclusion, due to the hierarchical ordering of the porphyrins, the nanoparticles exhibit collective optical properties resulted from coupling of molecular porphyrins and photocatalytic activities such as photodegradation of methyl orange (MO) pollutants and hydrogen production.« less

Morphology-Controlled Synthesis and Metalation of Porphyrin Nanoparticles with Enhanced Photocatalytic Performance

DOE PAGES

Wang, Jiefei; Zhong, Yong; Wang, Liang; ...

2016-09-12

The design and engineering of the size, shape, and chemistry of photoactive building blocks enables the fabrication of functional nanoparticles for applications in light harvesting, photocatalytic synthesis, water splitting, phototherapy, and photodegradation. Here, we report the synthesis of such nanoparticles through a surfactant-assisted interfacial self-assembly process using optically active porphyrin as a functional building block. The self-assembly process relies on specific interactions such as π–π stacking and metalation (metal atoms and ligand coordination) between individual porphyrin building blocks. Depending on the kinetic conditions and type of surfactants, resulting structures exhibit well-defined one- to three-dimensional morphologies such as nanowires, nanooctahedra, andmore » hierarchically ordered internal architectures. Specifically, electron microscopy and X-ray diffraction results indicate that these nanoparticles exhibit stable single-crystalline and nanoporous frameworks. In conclusion, due to the hierarchical ordering of the porphyrins, the nanoparticles exhibit collective optical properties resulted from coupling of molecular porphyrins and photocatalytic activities such as photodegradation of methyl orange (MO) pollutants and hydrogen production.« less

Mussel-inspired superhydrophobic surfaces with enhanced corrosion resistance and dual-action antibacterial properties.

PubMed

Qian, Hongchang; Li, Minglu; Li, Zhong; Lou, Yuntian; Huang, Luyao; Zhang, Dawei; Xu, Dake; Du, Cuiwei; Lu, Lin; Gao, Jin

2017-11-01

In this study, a multilayer antibacterial film was assembled onto 316L stainless steel via mussel-inspired depositions of polydopamine (PDA) and silver (Ag) nanoparticles followed by post-modification with 1H, 1H, 2H, 2H-perfluorodecanethiol. The resulting surface exhibited excellent superhydrophobicity with hierarchical micro/nanostructures that were constructed by both PDA and Ag nanoparticles. The crystal structure and chemical composition of these surfaces were investigated using X-ray photoelectron spectroscopy (XPS) analysis. Potentiodynamic polarization measurements revealed that the corrosion resistance of the as-prepared surfaces were sequentially increased after each step of the fabrication process. Compared with the surface covered with only Ag nanoparticles, the superhydrophobic surfaces exhibited substantially enhanced antibacterial activity against the Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus, resulting from the synergistic antibacterial actions of the superhydrophobic surface and Ag nanoparticles. The superhydrophobic surface exhibited lower cytotoxicity, compared to the surface covered with Ag nanoparticles. Copyright © 2017 Elsevier B.V. All rights reserved.

Green synthesis and characterization of zinc oxide nanoparticle using insulin plant (Costus pictus D. Don) and investigation of its antimicrobial as well as anticancer activities

NASA Astrophysics Data System (ADS)

Suresh, Joghee; Pradheesh, Ganeshan; Alexramani, Vincent; Sundrarajan, Mahalingam; Hong, Sun Ig

2018-03-01

In this work we aim to synthesize biocompatible ZnO nanoparticles from the zinc nitrate via green process using leaf extracts of the Costus pictus D. Don medicinal plant. FTIR studies confirm the presence of biomolecules and metal oxides. X-ray diffraction (XRD) structural analysis reveals the formation of pure hexagonal phase structures of ZnO nanoparticles. The surface morphologies of ZnO nanoparticles observed under a scanning electron microscope (SEM) suggest that most ZnO crystallites are hexagonal. EDX analysis confirms the presence of primarily zinc and oxygen. TEM images show that biosynthesized zinc oxide nanoparticles are hexagonal and spherical. The plausible formation mechanisms of zinc oxide nanoparticles are also predicted. The biosynthesized zinc oxide nanoparticles exhibit strong antimicrobial behavior against bacterial and fungal species when employing the agar diffusion method. Synthesized ZnO nanoparticles exhibit anticancer activity against Daltons lymphoma ascites (DLA) cells as well as antimicrobial activity against some bacterial and fungal strains.

Facile solid-state synthesis of oxidation-resistant metal nanoparticles at ambient conditions

NASA Astrophysics Data System (ADS)

Lee, Kyu Hyung; Jung, Hyuk Joon; Lee, Ju Hee; Kim, Kyungtae; Lee, Byeongno; Nam, Dohyun; Kim, Chung Man; Jung, Myung-Hwa; Hur, Nam Hwi

2018-05-01

A simple and scalable method for the synthesis of metal nanoparticles in the solid-state was developed, which can produce nanoparticles in the absence of solvents. Nanoparticles of coinage metals were synthesized by grinding solid hydrazine and the metal precursors in their acetates and oxides at 25 °C. The silver and gold acetates converted completely within 6 min into Ag and Au nanoparticles, respectively, while complete conversion of the copper acetate to the Cu sub-micrometer particles took about 2 h. Metal oxide precursors were also converted into metal nanoparticles by grinding alone. The resulting particles exhibit distinctive crystalline lattice fringes, indicating the formation of highly crystalline phases. The Cu sub-micrometer particles are better resistant to oxidation and exhibit higher conductivity compared to conventional Cu nanoparticles. This solid-state method was also applied for the synthesis of platinum group metals and intermetallic Cu3Au, which can be further extended to synthesize other metal nanoparticles.

The effect of the processing and formulation parameters on the size of nanoparticles based on block copolymers of poly(ethylene glycol) and poly(N-isopropylacrylamide) with and without hydrolytically sensitive groups.

PubMed

Neradovic, D; Soga, O; Van Nostrum, C F; Hennink, W E

2004-05-01

Block copolymers of poly(ethylene glycol) (PEG) as a hydrophilic block and N-isopropylacrylamide (PNIPAAm) or poly (NIPAAm-co-N-(2-hydroxypropyl) methacrylamide-dilactate) (poly(NIPAAm-co-HPMAm-dilactate)) as a thermosensitive block, are able to self-assemble in water into nanoparticles above the cloud point (CP) of the thermosensitive block. The influence of processing and the formulation parameters on the size of the nanoparticles was studied using dynamic light scattering. PNIPAAm-b-PEG 2000 polymers were not suitable for the formation of small and stable particles. Block copolymers with PEG 5000 and 10000 formed relatively small and stable particles in aqueous solutions at temperatures above the CP of the thermosensitive block. Their size decreased with increasing molecular weight of the thermosensitive block, decreasing polymer concentration and using water instead of phosphate buffered saline as solvent. Extrusion and ultrasonication were inefficient methods to size down the polymeric nanoparticles. The heating rate of the polymer solutions was a dominant factor for the size of the nanoparticles. When an aqueous polymer solution was slowly heated through the CP, rather large particles (> or = 200 nm) were formed. Regardless the polymer composition, small nanoparticles (50-70 nm) with a narrow size distribution were formed, when a small volume of an aqueous polymer solution below the CP was added to a large volume of heated water. In this way the thermosensitive block copolymers rapidly pass their CP ('heat shock' procedure), resulting in small and stable nanoparticles.