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Sample records for nanoparticles densely loaded

  1. Intravaginal gene silencing using biodegradable polymer nanoparticles densely loaded with small-interfering RNA

    NASA Astrophysics Data System (ADS)

    Woodrow, Kim A.; Cu, Yen; Booth, Carmen J.; Saucier-Sawyer, Jennifer K.; Wood, Monica J.; Mark Saltzman, W.

    2009-06-01

    Vaginal instillation of small-interfering RNA (siRNA) using liposomes has led to silencing of endogenous genes in the genital tract and protection against challenge from infectious disease. Although siRNA lipoplexes are easily formulated, several of the most effective transfection agents available commercially may be toxic to the mucosal epithelia and none are able to provide controlled or sustained release. Here, we demonstrate an alternative approach using nanoparticles composed entirely of FDA-approved materials. To render these materials effective for gene silencing, we developed novel approaches to load them with high amounts of siRNA. A single dose of siRNA-loaded nanoparticles to the mouse female reproductive tract caused efficient and sustained gene silencing. Knockdown of gene expression was observed proximal (in the vaginal lumen) and distal (in the uterine horns) to the site of topical delivery. In addition, nanoparticles penetrated deep into the epithelial tissue. This is the first report demonstrating that biodegradable polymer nanoparticles are effective delivery vehicles for siRNA to the vaginal mucosa.

  2. Demagnetization effects in dense nanoparticle assemblies

    NASA Astrophysics Data System (ADS)

    Normile, P. S.; Andersson, M. S.; Mathieu, R.; Lee, S. S.; Singh, G.; De Toro, J. A.

    2016-10-01

    We highlight the relevance of demagnetizing-field corrections in the characterization of dense magnetic nanoparticle assemblies. By an analysis that employs in-plane and out-of-plane magnetometry on cylindrical assemblies, we demonstrate the suitability of a simple analytical formula-based correction method. This allows us to identify artifacts of the demagnetizing field in temperature-dependent susceptibility curves (e.g., shoulder peaks in curves from a disordered assembly of essentially bare magnetic nanoparticles). The same analysis approach is shown to be a straightforward procedure for determining the magnetic nanoparticle packing fraction in dense, disordered assemblies.

  3. Microchannel cross load array with dense parallel input

    DOEpatents

    Swierkowski, Stefan P.

    2004-04-06

    An architecture or layout for microchannel arrays using T or Cross (+) loading for electrophoresis or other injection and separation chemistry that are performed in microfluidic configurations. This architecture enables a very dense layout of arrays of functionally identical shaped channels and it also solves the problem of simultaneously enabling efficient parallel shapes and biasing of the input wells, waste wells, and bias wells at the input end of the separation columns. One T load architecture uses circular holes with common rows, but not columns, which allows the flow paths for each channel to be identical in shape, using multiple mirror image pieces. Another T load architecture enables the access hole array to be formed on a biaxial, collinear grid suitable for EDM micromachining (square holes), with common rows and columns.

  4. A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

    PubMed Central

    Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

    2013-01-01

    Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

  5. Interface interaction induced ultra-dense nanoparticles assemblies.

    PubMed

    Song, Yujun; Wang, Yan; Li, Bin Bin; Fernandes, Carlos; Ruda, Harry E

    2013-08-07

    We demonstrate a simple and clean physical methodology for fabricating such nanoparticle assemblies (dense arrays and/or dendrites) related to the interfacial interaction between the constructed materials and the anodized aluminum oxide (AAO) porous templates. The interfacial interaction can be regulated by the surface tension of the constructed materials and the AAO membrane, and the AAO-template structure, such as pore size, membrane thickness and surface morphologies. Depending on the interfacial interaction between the constructed materials and the AAO templates, NP arrays with mean particle diameters from 3.8 ± 1.0 nm to 12.5 ± 2.9 nm, mean inter-edge spacings from 3.5 ± 1.4 nm to 7.9 ± 3.4 nm and areal densities from 5.6 × 10(11) NPs per cm(2) to 1.5 × 10(12) NPs per cm(2) are fabricated over large areas (currently ~2 cm × 3 cm). The fabrication process includes firstly thermal evaporation of metal layers no more than 10 nm thick on the pre-coated Si wafer by AAO templates with a thickness of less than 150 nm and mean pore sizes no more than 12 nm, and then removal of the AAO templates. The NP arrays can be stable for hours at a temperature slightly below the melting point of the constructed materials (e.g., ~800 °C for Au NPs for 4 hours) with little change in size and inter-particle separation. Using one of them (e.g., 11.8 nm Au NPs) as growth-oriented catalysts, ultra-thin (12.1 ± 2.3 nm) dense nanowires can be conveniently obtained. Furthermore, dendrite superstructures can be generated easily from eutectic alloy NPs with diameters of ~10 nm pre-formed by thermal evaporation of metal layers more than 20 nm thick on surface-patterned thick AAO templates (e.g., 500 nm). The resulting dendrites, dense arrays and other superstructures (i.e., nanorods and nanowires) formed using NP arrays as catalysts, should have broad applications in catalysis, information technology, photovoltaics and biomedical engineering.

  6. Interface interaction induced ultra-dense nanoparticles assemblies

    NASA Astrophysics Data System (ADS)

    Song, Yujun; Wang, Yan; Li, Bin Bin; Fernandes, Carlos; Ruda, Harry E.

    2013-07-01

    We demonstrate a simple and clean physical methodology for fabricating such nanoparticle assemblies (dense arrays and/or dendrites) related to the interfacial interaction between the constructed materials and the anodized aluminum oxide (AAO) porous templates. The interfacial interaction can be regulated by the surface tension of the constructed materials and the AAO membrane, and the AAO-template structure, such as pore size, membrane thickness and surface morphologies. Depending on the interfacial interaction between the constructed materials and the AAO templates, NP arrays with mean particle diameters from 3.8 +/- 1.0 nm to 12.5 +/- 2.9 nm, mean inter-edge spacings from 3.5 +/- 1.4 nm to 7.9 +/- 3.4 nm and areal densities from 5.6 × 1011 NPs per cm2 to 1.5 × 1012 NPs per cm2 are fabricated over large areas (currently ~2 cm × 3 cm). The fabrication process includes firstly thermal evaporation of metal layers no more than 10 nm thick on the pre-coated Si wafer by AAO templates with a thickness of less than 150 nm and mean pore sizes no more than 12 nm, and then removal of the AAO templates. The NP arrays can be stable for hours at a temperature slightly below the melting point of the constructed materials (e.g., ~800 °C for Au NPs for 4 hours) with little change in size and inter-particle separation. Using one of them (e.g., 11.8 nm Au NPs) as growth-oriented catalysts, ultra-thin (12.1 +/- 2.3 nm) dense nanowires can be conveniently obtained. Furthermore, dendrite superstructures can be generated easily from eutectic alloy NPs with diameters of ~10 nm pre-formed by thermal evaporation of metal layers more than 20 nm thick on surface-patterned thick AAO templates (e.g., 500 nm). The resulting dendrites, dense arrays and other superstructures (i.e., nanorods and nanowires) formed using NP arrays as catalysts, should have broad applications in catalysis, information technology, photovoltaics and biomedical engineering.We demonstrate a simple and clean physical

  7. Preparation and characterization of DNA block copolymer assemblies loaded with nanoparticles.

    PubMed

    Chen, Xi-Jun; Hickey, Robert J; Park, So-Jung

    2013-01-01

    We have recently developed a universal procedure to functionalize inorganic nanoparticles with a dense layer of DNA through the self-assembly of DNA block copolymers and nanoparticles. This functionalization strategy allows one to combine the useful physical properties of inorganic nanoparticle with the enhanced DNA binding properties that originate from the high surface DNA density. In particular, the hybrid nanostructures exhibit orders of magnitude higher binding constants than regular DNA strands. This chapter presents a detailed protocol for the preparation and characterization of DNA block copolymer assemblies loaded with nanoparticles.

  8. Targeting Paclitaxel-Loaded Nanoparticles to Ovarian Cancer

    DTIC Science & Technology

    2013-05-01

    Final Targeting Paclitaxel-Loaded Nanoparticles to Ovarian Cancer Stephen B. Howell showell@ucsd.edu University of California, San Diego La Jolla, CA...None provided. 24 3 Targeting paclitaxel-loaded nanoparticles to ovarian cancer W81XWH-09-1-0223 Table of Contents...N/A 4 Title: Targeting Paclitaxel-Loaded Nanoparticles to Ovarian Cancer Grant

  9. Porphyrin-loaded nanoparticles for cancer theranostics

    NASA Astrophysics Data System (ADS)

    Zhou, Yiming; Liang, Xiaolong; Dai, Zhifei

    2016-06-01

    Porphyrins have been used as pioneering theranostic agents not only for the photodynamic therapy, sonodynamic therapy and radiotherapy of cancer, but also for diagnostic fluorescence imaging, magnetic resonance imaging and photoacoustic imaging. A variety of porphyrins have been developed but very few of them have actually been employed in clinical trials due to their poor selectivity to tumorous tissue and high accumulation rates in the skin. In addition, most porphyrin molecules are hydrophobic and form aggregates in aqueous media. Nevertheless, the use of nanoparticles as porphyrin carriers shows great promise to overcome these shortcomings. Encapsulating or attaching porphyrins to nanoparticles makes them more suitable for tissue delivery because we can create materials with a conveniently specific tissue lifetime, specific targeting, immune tolerance, and hydrophilicity as well as other characteristics through rational design. In addition, various functional components (e.g. for targeting, imaging or therapeutic functions) can be easily introduced into a single nanoparticle platform for cancer theranostics. This review presents the current state of knowledge on porphyrin-loaded nanoparticles for the interwined imaging and therapy of cancer. The future trends and limitations of prophyrin-loaded nanoparticles are also outlined.

  10. Polymer-mediated spatial organization of nanoparticles in dense melts: Transferability and an effective one-component approach

    NASA Astrophysics Data System (ADS)

    Chakrabarti, Rajarshi; Schweizer, Kenneth S.

    2010-10-01

    We study two problems in the framework of the integral equation theory of polymer-mediated spatial organization of nanoparticles in dense melts motivated by multiscale simulation and many body physics issues. How nonspherical nanoparticle shape modifies polymer-induced interactions under dilute nanoparticle conditions is investigated over a range of primary particle sizes and interfacial cohesion strengths. Nonuniversal consequences of nonspherical shape are found for the pair-correlation function on local scales and some qualitative differences on larger scales due primarily to intraparticle connectivity constraints. For a large enough nanoparticle site diameter, the potentials of mean force (PMF) for all shapes studied (sphere, rod, disk, compact tetrahedral cluster) exhibit linear scaling with the size ratio of nanoparticle to polymer monomer site diameter and quite good "transferability." The ability of a simple effective one-component approach, based on the dilute nanoparticle PMF as an effective pair-decomposable potential, to describe interparticle structure at nonzero volume fractions is also studied. Although not generally quantitatively accurate due to neglect of many body correlation effects, especially at high nanoparticle loadings and near contact separations, the simple approach captures rather well many aspects of the real space structure. The errors incurred depend systematically on whether interfacial cohesion strength results in contact aggregation, steric stabilization, or bridging. For the filler collective static structure factor, many body effects are weakest for local cage scale correlations and grow significantly at smaller wavevectors under depletion or bridging conditions.

  11. Dead Sea Minerals loaded polymeric nanoparticles.

    PubMed

    Dessy, Alberto; Kubowicz, Stephan; Alderighi, Michele; Bartoli, Cristina; Piras, Anna Maria; Schmid, Ruth; Chiellini, Federica

    2011-10-15

    Therapeutic properties of Dead Sea Water (DSW) in the treatment of skin diseases such as atopic dermatitis, psoriasis and photo aging UV damaged skin have been well established. DSW is in fact rich in minerals such as calcium, magnesium, sodium, potassium, zinc and strontium which are known to exploit anti-inflammatory effects and to promote skin barrier recovery. In order to develop a Dead Sea Minerals (DSM) based drug delivery system for topical therapy of skin diseases, polymeric nanoparticles based on Poly (maleic anhydride-alt-butyl vinyl ether) 5% grafted with monomethoxy poly(ethyleneglycol) 2000 MW (PEG) and 95% grafted with 2-methoxyethanol (VAM41-PEG) loaded with DSM were prepared by means of a combined miniemulsion/solvent evaporation process. The resulting nanoparticles were characterized in terms of dimension, morphology, biocompatibility, salt content and release. Cytocompatible spherical nanoparticles possessing an average diameter of about 300 nm, a time controlled drug release profile and a high formulation yield were obtained.

  12. Polymer nanocomposite films with extremely high nanoparticle loadings via capillary rise infiltration (CaRI)

    NASA Astrophysics Data System (ADS)

    Huang, Yun-Ru; Jiang, Yijie; Hor, Jyo Lyn; Gupta, Rohini; Zhang, Lei; Stebe, Kathleen J.; Feng, Gang; Turner, Kevin T.; Lee, Daeyeon

    2014-12-01

    Polymer nanocomposite films (PNCFs) with extremely high concentrations of nanoparticles are important components in energy storage and conversion devices and also find use as protective coatings in various applications. PNCFs with high loadings of nanoparticles, however, are difficult to prepare because of the poor processability of polymer-nanoparticle mixtures with high concentrations of nanoparticles even at an elevated temperature. This problem is exacerbated when anisotropic nanoparticles are the desired filler materials. Here we report a straightforward method for generating PNCFs with extremely high loadings of nanoparticles. Our method is based on what we call capillary rise infiltration (CaRI) of polymer into a dense packing of nanoparticles. CaRI consists of two simple steps: (1) the preparation of a two-layer film, consisting of a porous layer of nanoparticles and a layer of polymer and (2) annealing of the bilayer structure above the temperature that imparts mobility to the polymer (e.g., glass transition of the polymer). The second step leads to polymer infiltration into the interstices of the nanoparticle layer, reminiscent of the capillary rise of simple fluid into a narrow capillary or a packing of granules. We use in situ spectroscopic ellipsometry and a three-layer Cauchy model to follow the capillary rise of polystyrene into the random network of nanoparticles. The infiltration of polystyrene into a densely packed TiO2 nanoparticle layer is shown to follow the classical Lucas-Washburn type of behaviour. We also demonstrate that PNCFs with densely packed anisotropic TiO2 nanoparticles can be readily generated by spin coating anisotropic TiO2 nanoparticles atop a polystyrene film and subsequently thermally annealing the bilayer film. We show that CaRI leads to PNCFs with modulus, hardness and scratch resistance that are far superior to the properties of films of the component materials. In addition, CaRI fills in cracks that may exist in the

  13. Sustained release Curcumin loaded Solid Lipid Nanoparticles

    PubMed Central

    Jourghanian, Parisa; Ghaffari, Solmaz; Ardjmand, Mehdi; Haghighat, Setareh; Mohammadnejad, Mahdieh

    2016-01-01

    Purpose: curcumin is poorly water soluble drug with low bioavailability. Use of lipid systems in lipophilic substances increases solubility and bioavailability of poorly soluble drugs. The aim of this study was to prepare curcumin loaded Solid Lipid Nanoparticles (SLNs) with high loading efficiency, small particle size and prolonged release profile with enhanced antibacterial efficacy. Methods: to synthesize stable SLNs, freeze- Drying was done using mannitol as cryoprotectant. Cholesterol was used as carrier because of good tolerability and biocompatibility. SLNs were prepared using high pressure homogenization method. Results: optimized SLNs had 112 and 163 nm particle size before and after freeze drying, respectively. The prepared SLNs had 71% loading efficiency. 90% of loaded curcumin was released after 48 hours. Morphologic study for formulation was done by taking SEM pictures of curcumin SLNs. Results show the spherical shape of curcumin SLNs. DSC studies were performed to determine prolonged release mechanism. Antimicrobial studies were done to compare the antimicrobial efficacy of curcumin SLNs with free curcumin. DSC studies showed probability of formation of hydrogen bonds between cholesterol and curcumin which resulted in prolonged release of curcumin. Lipid structure of cholesterol could cause enhanced permeability in studied bacteria to increase antibacterial characteristics of curcumin. Conclusion: the designed curcumin SLNs could be candidate for formulation of different dosage forms or cosmeceutical products. PMID:27123413

  14. Interparticle magnetic correlations in dense Co nanoparticle assemblies

    SciTech Connect

    Kortright, Jeffrey B.; Hellwig, Olav; Sun, Shouheng; Fullerton, Eric E.

    2004-01-16

    Resonant magnetic x-ray scattering from dense self-assemblies of 9-nm diameter epsilon-Co and hcp-Co particles is reported. For lower anisotropy epsilon-Co we find remanent magnetic scattering that is significantly enhanced, indicating preferred inter-particle moment orientations of both antiferromagnetic and ferromagnetic character. This interaction-mediated collective behavior is consistent with dipolar fields and exists well above the isolated particles blocking temperature where thermal activation is operative, suggesting that magnetostatic super-spin waves exist in such systems.

  15. Transient magnetic birefringence for determining magnetic nanoparticle diameters in dense, highly light scattering media

    NASA Astrophysics Data System (ADS)

    Köber, Mariana; Moros, Maria; Grazú, Valeria; de la Fuente, Jesus M.; Luna, Mónica; Briones, Fernando

    2012-04-01

    The increasing use of biofunctionalized magnetic nanoparticles in biomedical applications calls for further development of characterization tools that allow for determining the interactions of the nanoparticles with the biological medium in situ. In cell-incubating conditions, for example, nanoparticles may aggregate and serum proteins adsorb on the particles, altering the nanoparticles’ performance and their interaction with cell membranes. In this work we show that the aggregation of spherical magnetite nanoparticles can be detected with high sensitivity in dense, highly light scattering media by making use of magnetically induced birefringence. Moreover, the hydrodynamic particle diameter distribution of anisometric nanoparticle aggregates can be determined directly in these media by monitoring the relaxation time of the magnetically induced birefringence. As a proof of concept, we performed measurements on nanoparticles included in an agarose gel, which scatters light in a similar way as a more complex biological medium but where particle-matrix interactions are weak. Magnetite nanoparticles were separated by agarose gel electrophoresis and the hydrodynamic diameter distribution was determined in situ. For the different particle functionalizations and agarose concentrations tested, we could show that gel electrophoresis did not yield a complete separation of monomers and small aggregates, and that the electrophoretic mobility of the aggregates decreased linearly with the hydrodynamic diameter. Furthermore, the rotational particle diffusion was not clearly affected by nanoparticle-gel interactions. The possibility to detect nanoparticle aggregates and their hydrodynamic diameters in complex scattering media like cell tissue makes transient magnetic birefringence an interesting technique for biological applications.

  16. Enhanced antiviral activity of acyclovir loaded into nanoparticles.

    PubMed

    Cavalli, Roberta; Donalisio, Manuela; Bisazza, Agnese; Civra, Andrea; Ranucci, Elisabetta; Ferruti, Paolo; Lembo, David

    2012-01-01

    The activity of antivirals can be enhanced by their incorporation in nanoparticulate delivery systems. Peculiar polymeric nanoparticles, based on a β-cyclodextrin-poly(4-acryloylmorpholine) monoconjugate (β-CD-PACM), are proposed as acyclovir carriers. The experimental procedure necessary to obtain the acyclovir-loaded nanoparticles using the solvent displacement preparation method will be described in this chapter. Fluorescent labeled nanoparticles are prepared using the same method for cellular trafficking studies. The biocompatibility assays necessary to obtain safe nanoparticles are reported. Section 4 of this chapter describes the assessment of the antiviral activity of the acyclovir-loaded nanoparticles.

  17. Design of naltrexone-loaded hydrolyzable crosslinked nanoparticles

    PubMed Central

    Yin, Wusheng; Akala, Emmanuel O.; Taylor, Robert E.

    2010-01-01

    A hydrolyzable crosslinker (N,O-dimethacryloylhydroxylamine (MANHOMA)) was synthesized by a modified method and was characterized using 1H-NMR, FTIR, and melting point determination. Naltrexone-loaded nanoparticles were prepared by copolymerization of poly(ethylene glycol)1000 monomethyl ether mono methacrylate (PEO-MA), methyl methacrylate (MMA) and N,O-dimethacryloylhydroxylamine (MANHOMA) in 0.4% poly(vinyl alcohol) aqueous solution. The nanoparticles were characterized by FTIR, particle size determination and transmission electron microscope (TEM). The TEM photomicrographs of the nanoparticles show a crosslinked core surrounded by a ring formed by the polyethylene glycol tail of PEO-MA. The loading efficiency of the nanoparticles and in vitro drug availability from the nanoparticles were investigated. The naltrexone-loaded hydrolyzable crosslinked nanoparticles were able to sustain the release of naltrexone for different periods of time, depending on the monomer feed composition. PMID:12204561

  18. Antioxidative and antiinflammatory activities of quercetin-loaded silica nanoparticles.

    PubMed

    Lee, Ga Hyun; Lee, Sung June; Jeong, Sang Won; Kim, Hyun-Chul; Park, Ga Young; Lee, Se Geun; Choi, Jin Hyun

    2016-07-01

    Utilizing the biological activities of compounds by encapsulating natural components in stable nanoparticles is an important strategy for a variety of biomedical and healthcare applications. In this study, quercetin-loaded silica nanoparticles were synthesized using an oil-in-water microemulsion method, which is a suitable system for producing functional nanoparticles of controlled size and shape. The resulting quercetin-loaded silica nanoparticles were spherical, highly monodispersed, and stable in an aqueous system. Superoxide radical scavenging effects were found for the quercetin-loaded silica nanoparticles as well as free quercetin. The quercetin-loaded silica nanoparticles showed cell viability comparable to that of the controls. The amounts of proinflammatory cytokines produced by macrophages, such as interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha, were reduced significantly for the quercetin-loaded silica nanoparticles. These results suggest that the antioxidative and antiinflammatory activities of quercetin are maintained after encapsulation in silica. Silica nanoparticles can be used for the effective and stable incorporation of biologically active natural components into composite biomaterials.

  19. Convection enhanced delivery of cisplatin-loaded brain penetrating nanoparticles cures malignant glioma in rats.

    PubMed

    Zhang, Clark; Nance, Elizabeth A; Mastorakos, Panagiotis; Chisholm, Jane; Berry, Sneha; Eberhart, Charles; Tyler, Betty; Brem, Henry; Suk, Jung Soo; Hanes, Justin

    2017-03-07

    Glioblastoma multiforme (GBM) is highly invasive and uniformly fatal, with median survival<20months after diagnosis even with the most aggressive treatment that includes surgery, radiation, and systemic chemotherapy. Cisplatin is a particularly potent chemotherapeutic agent, but its use to treat GBM is limited by severe systemic toxicity and inefficient penetration of brain tumor tissue even when it is placed directly in the brain within standard delivery systems. We describe the development of cisplatin-loaded nanoparticles that are small enough (70nm in diameter) to move within the porous extracellular matrix between cells and that possess a dense polyethylene glycol (PEG) corona that prevents them from being trapped by adhesion as they move through the brain tumor parenchyma. As a result, these "brain penetrating nanoparticles" penetrate much deeper into brain tumor tissue compared to nanoparticles without a dense PEG corona following local administration by either manual injection or convection enhanced delivery. The nanoparticles also provide controlled release of cisplatin in effective concentrations to kill the tumor cells that they reach without causing toxicity-related deaths that were observed when cisplatin was infused into the brain without a delivery system. Median survival time of rats bearing orthotopic glioma was significantly enhanced when cisplatin was delivered in brain penetrating nanoparticles (median survival not reached; 80% long-term survivors) compared to cisplatin in conventional un-PEGylated particles (median survival=40days), cisplatin alone (median survival=12days) or saline-treated controls (median survival=28days).

  20. Preparation and Characterization of Nateglinide Loaded Hydrophobic Biocompatible Polymer Nanoparticles

    NASA Astrophysics Data System (ADS)

    Naik, Jitendra; Lokhande, Amolkumar; Mishra, Satyendra; Kulkarni, Ravindra

    2016-09-01

    The aim of the present study was to develop sustained release Nateglinide loaded Ethylcellulose nanoparticles and characterize the properties of recovered nanoparticles. The sustained release nanoparticles were prepared by oil in water single emulsion solvent evaporation method. The developed nanoparticles were characterised for their particle size, morphology, encapsulation efficiency, drug polymer compatibility and in vitro drug release. The drug polymer compatibility was investigated by XRPD. Imaging of particles was performed by field emission scanning electron microscopy. The highest particle size and encapsulation efficiency of recovered nanoparticles were 248.37 nm and 91.16 % respectively. The recovered nanoparticles are spherical in nature and uniform in size. Developed nanoparticles have low crystallinity than the pure Nateglinide. The highest drug-polymer ratio formulation showed drug release 61.1 ± 1.76 % up to 24 h.

  1. Novel Methods of Lipidic Nanoparticle Preparation and Drug Loading

    NASA Astrophysics Data System (ADS)

    Maitani, Y.

    2013-09-01

    In improving cancer chemotherapy, lipidic nanoparticle systems for drug delivery, such as liposomes and emulsions, have received much attention because they are capable of delivering their drug payload selectively to cancer cells and of circulating for a long period in the bloodstream. In addition, lipidic nanoparticles have been examined for use in gene delivery as a non-viral vector. Preparation methods of particles and drug loading methods are crucial for the physicochemical properties of nanoparticles, which are the key aspects for pharmaceutical applications. This review describes new preparation methods for nanoparticles and a loading method for drugs using nanotechnology, including an evaluation of nanoparticles from the point of drug release for applications in cancer therapy and gene delivery.

  2. Complexation-induced phase separation: preparation of composite membranes with a nanometer-thin dense skin loaded with metal ions.

    PubMed

    Villalobos, Luis Francisco; Karunakaran, Madhavan; Peinemann, Klaus-Viktor

    2015-05-13

    We present the development of a facile phase-inversion method for forming asymmetric membranes with a precise high metal ion loading capacity in only the dense layer. The approach combines the use of macromolecule-metal intermolecular complexes to form the dense layer of asymmetric membranes with nonsolvent-induced phase separation to form the porous support. This allows the independent optimization of both the dense layer and porous support while maintaining the simplicity of a phase-inversion process. Moreover, it facilitates control over (i) the thickness of the dense layer throughout several orders of magnitude from less than 15 nm to more than 6 μm, (ii) the type and amount of metal ions loaded in the dense layer, (iii) the morphology of the membrane surface, and (iv) the porosity and structure of the support. This simple and scalable process provides a new platform for building multifunctional membranes with a high loading of well-dispersed metal ions in the dense layer.

  3. Asymmetric Collagen/chitosan Membrane Containing Minocycline-loaded Chitosan Nanoparticles for Guided Bone Regeneration

    PubMed Central

    Ma, Shiqing; Adayi, Aidina; Liu, Zihao; Li, Meng; Wu, Mingyao; Xiao, Linghao; Sun, Yingchun; Cai, Qing; Yang, Xiaoping; Zhang, Xu; Gao, Ping

    2016-01-01

    Infections caused by pathogens colonization at wound sites in the process of bone healing are considered as one of the major reasons for the failure of guided bone regeneration (GBR). The objective of this study was to prepare a novel asymmetric collagen/chitosan GBR membrane containing minocycline-loaded chitosan nanoparticles. The morphologies of the membranes and nanoparticles were observed by SEM and TEM, respectively. The characterization and biocompatibility of the membranes was evaluated. The effect of the membrane on bone regeneration was assessed using the critical-size at cranial defect model. TEM images showed the spherical morphology of the nanoparticles. The results of SEM indicated that the asymmetric membrane contained a dense collagen layer and a loose chitosan layer. An in vitro experiment showed that the membrane can inhibit bacterial growth and promote osteoblasts and fibroblasts growth. The membrane showed the ability to promote angiogenesis and enhance bone regeneration in vivo. An asymmetric collagen/chitosan GBR membrane can be fabricated by loading minocycline encapsulated chitosan nanoparticles, and shows satisfactory biocompatibility and barrier function, which enhances bone regeneration. Therefore, this antibacterial GBR membrane is a promising therapeutic approach to prevent infection and guide bone regeneration. PMID:27546177

  4. Reliability analysis of an RC defense structure loaded by a dense snow avalanche pressure signal

    NASA Astrophysics Data System (ADS)

    Ousset, Isabelle; Bertrand, David; Limam, Ali; Naaïm, Mohamed

    2014-05-01

    To protect humans, roads or houses against snow avalanches, civil engineering structures are widely used. Designing these structures is still a challenge especially due to the uncertainties related to the loading developed by a snow avalanche. The case of the avalanche of Taconnaz (France), which occurred in 1999 and where important parts of the RC defense structure were destroyed, underlines the necessary to consider reliability approaches for the design of such structures. This paper proposes a reliability analysis of an L-shaped reinforced concrete (RC) protective structure subjected to a dense snow avalanche. A deterministic mechanical model, based on the finite element method, has been developed and allows describing the behavior of the structure. Next, a reliable model allows propagating uncertainties through the mechanical model and assessing the failure probability of the structure. The choices of random variables (the inputs) and their distributions, the failure criteria and the reliability methods are presented and discussed. Two criteria are considered: on the one hand, a local criterion defined in term of stress exceedence within concrete and steel, and on the other hand a global criterion defined in term of maximal displacement of the structure. Moreover, Kernel Smoothing and Monte-Carlo methods are used and compared to assess the failure probability and to derive fragility curves. These latter describe the failure probability of the structure according to the loading magnitude.

  5. Intranasal drug delivery of olanzapine-loaded chitosan nanoparticles.

    PubMed

    Baltzley, Sarah; Mohammad, Atiquzzaman; Malkawi, Ahmad H; Al-Ghananeem, Abeer M

    2014-12-01

    The aim of this study was to investigate olanzapine (OZ) systemic absolute bioavailability after intranasal (i.n.) administration in vivo to conscious rabbits. Furthermore, the study investigated the potential use of chitosan nanoparticles as a delivery system to enhance the systemic bioavailability of olanzapine following intranasal administration. Olanzapine-loaded chitosan nanoparticles were prepared through ionotropic gelation of chitosan with tripolyphosphate anions and studied in terms of their size, drug loading, and in vitro release. The OZ nanoparticles were administered i.n. to rabbits, and OZ plasma concentration at predetermined time points was compared to i.n. administration of OZ in solution. The concentrations of OZ in plasma were analyzed by ultra performance liquid chromatography mass spectroscopy (UPLC/MS). OZ-loaded chitosan nanoparticles significantly (p < 0.05) enhanced systemic absorption with 51 ± 11.2% absolute bioavailability as compared to 28 ± 6.7% after i.n. administration of OZ solution. The results of the present study suggest that intranasal administration of OZ-loaded chitosan nanoparticles formulation could be an attractive modality for delivery of OZ systemically.

  6. Drug-Loaded Polymeric Nanoparticles for Cancer Stem Cell Targeting

    PubMed Central

    Li, Binbin; Li, Qinghua; Mo, Jingxin; Dai, Honglian

    2017-01-01

    Cancer stem cells (CSCs) have been reported to play critical roles in tumor initiation, propagation, and regeneration of cancer. Nano-size vehicles are employed to deliver drugs to target the CSCs for cancer therapy. Polymeric nanoparticles have been considered as the most efficient vehicles for drug delivery due to their excellent pharmacokinetic properties. The CSCs specific antibodies or ligands can be conjugated onto the surface or interior of nanoparticles to successfully target and finally eliminate CSCs. In this review, we focus on the approaches of polymeric nanoparticles design for loading drug, and their potential application for CSCs targeting in cancer therapy. PMID:28261093

  7. Processing and properties of magnesium containing a dense uniform dispersion of nanoparticles

    NASA Astrophysics Data System (ADS)

    Chen, Lian-Yi; Xu, Jia-Quan; Choi, Hongseok; Pozuelo, Marta; Ma, Xiaolong; Bhowmick, Sanjit; Yang, Jenn-Ming; Mathaudhu, Suveen; Li, Xiao-Chun

    2015-12-01

    Magnesium is a light metal, with a density two-thirds that of aluminium, is abundant on Earth and is biocompatible; it thus has the potential to improve energy efficiency and system performance in aerospace, automobile, defence, mobile electronics and biomedical applications. However, conventional synthesis and processing methods (alloying and thermomechanical processing) have reached certain limits in further improving the properties of magnesium and other metals. Ceramic particles have been introduced into metal matrices to improve the strength of the metals, but unfortunately, ceramic microparticles severely degrade the plasticity and machinability of metals, and nanoparticles, although they have the potential to improve strength while maintaining or even improving the plasticity of metals, are difficult to disperse uniformly in metal matrices. Here we show that a dense uniform dispersion of silicon carbide nanoparticles (14 per cent by volume) in magnesium can be achieved through a nanoparticle self-stabilization mechanism in molten metal. An enhancement of strength, stiffness, plasticity and high-temperature stability is simultaneously achieved, delivering a higher specific yield strength and higher specific modulus than almost all structural metals.

  8. Processing and properties of magnesium containing a dense uniform dispersion of nanoparticles.

    PubMed

    Chen, Lian-Yi; Xu, Jia-Quan; Choi, Hongseok; Pozuelo, Marta; Ma, Xiaolong; Bhowmick, Sanjit; Yang, Jenn-Ming; Mathaudhu, Suveen; Li, Xiao-Chun

    2015-12-24

    Magnesium is a light metal, with a density two-thirds that of aluminium, is abundant on Earth and is biocompatible; it thus has the potential to improve energy efficiency and system performance in aerospace, automobile, defence, mobile electronics and biomedical applications. However, conventional synthesis and processing methods (alloying and thermomechanical processing) have reached certain limits in further improving the properties of magnesium and other metals. Ceramic particles have been introduced into metal matrices to improve the strength of the metals, but unfortunately, ceramic microparticles severely degrade the plasticity and machinability of metals, and nanoparticles, although they have the potential to improve strength while maintaining or even improving the plasticity of metals, are difficult to disperse uniformly in metal matrices. Here we show that a dense uniform dispersion of silicon carbide nanoparticles (14 per cent by volume) in magnesium can be achieved through a nanoparticle self-stabilization mechanism in molten metal. An enhancement of strength, stiffness, plasticity and high-temperature stability is simultaneously achieved, delivering a higher specific yield strength and higher specific modulus than almost all structural metals.

  9. Resveratrol-loaded Nanoparticles Induce Antioxidant Activity against Oxidative Stress

    PubMed Central

    Kim, Jae-Hwan; Park, Eun-Young; Ha, Ho-Kyung; Jo, Chan-Mi; Lee, Won-Jae; Lee, Sung Sill; Kim, Jin Wook

    2016-01-01

    Resveratrol acts as a free radical scavenger and a potent antioxidant in the inhibition of numerous reactive oxygen species (ROS). The function of resveratrol and resveratrol-loaded nanoparticles in protecting human lung cancer cells (A549) against hydrogen peroxide was investigated in this study. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay was performed to evaluate the antioxidant properties. Resveratrol had substantially high antioxidant capacity (trolox equivalent antioxidant capacity value) compared to trolox and vitamin E since the concentration of resveratrol was more than 50 μM. Nanoparticles prepared from β-lactoglobulin (β-lg) were successfully developed. The β-lg nanoparticle showed 60 to 146 nm diameter in size with negatively charged surface. Non-cytotoxicity was observed in Caco-2 cells treated with β-lg nanoparticles. Fluorescein isothiocynate-conjugated β-lg nanoparticles were identified into the cell membrane of Caco-2 cells, indicating that nanoparticles can be used as a delivery system. Hydrogen peroxide caused accumulation of ROS in a dose- and time-dependent manner. Resveratrol-loaded nanoparticles restored H2O2-induced ROS levels by induction of cellular uptake of resveratrol in A549 cells. Furthermore, resveratrol activated nuclear factor erythroid 2-related factor 2-Kelch ECH associating protein 1 (Nrf2-Keap1) signaling in A549 cells, thereby accumulation of Nrf2 abundance, as demonstrated by western blotting approach. Overall, these results may have implications for improvement of oxidative stress in treatment with nanoparticles as a biodegradable and non-toxic delivery carrier of bioactive compounds. PMID:26732454

  10. Defect-induced loading of Pt nanoparticles on carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Kim, Sung Jin; Park, Yong Jin; Ra, Eun Ju; Kim, Ki Kang; An, Kay Hyeok; Lee, Young Hee; Choi, Jae Young; Park, Chan Ho; Doo, Seok Kwang; Park, Min Ho; Yang, Cheol Woong

    2007-01-01

    Carbon nanotubes-supported Pt nanoparticles were loaded using a microwave oven on the defective carbon nanotubes generated by an additional oxidant during acid treatment. The authors' Raman spectra and x-ray diffraction analysis demonstrated that defects created during oxidation and microwave treatment acted as nucleation seeds for Pt adsorption. The generated Pt nanoparticles had the size distributions of 2-3nm and were uniformly distributed on the defects of carbon nanotubes. The authors' density functional calculations showed that the adsorption of Pt atom on the vacancy of nanotube was significantly stronger by s-p hybridization with carbon atoms near the defect site.

  11. Synthesis and characterization of noscapine loaded magnetic polymeric nanoparticles

    NASA Astrophysics Data System (ADS)

    Abdalla, Mohamed O.; Aneja, Ritu; Dean, Derrick; Rangari, Vijay; Russell, Albert; Jaynes, Jessie; Yates, Clayton; Turner, Timothy

    2010-01-01

    The delivery of noscapine therapies directly to the site of the tumor would ultimately allow higher concentrations of the drug to be delivered, and prolong circulation time in vivo to enhance the therapeutic outcome of this drug. Therefore, we sought to design magnetic based polymeric nanoparticles for the site directed delivery of noscapine to invasive tumors. We synthesized Fe 3O 4 nanoparticles with an average size of 10±2.5 nm. These Fe 3O 4 NPs were used to prepare noscapine loaded magnetic polymeric nanoparticles (NMNP) with an average size of 252±6.3 nm. Fourier transform infrared (FT-IR) spectroscopy showed the encapsulation of noscapine on the surface of the polymer matrix. The encapsulation of the Fe 3O 4 NPs on the surface of the polymer was confirmed by elemental analysis. We studied the drug loading efficiency of polylactide acid (PLLA) and poly (l-lactide acid-co-gylocolide) (PLGA) polymeric systems of various molecular weights. Our findings revealed that the molecular weight of the polymer plays a crucial role in the capacity of the drug loading on the polymer surface. Using a constant amount of polymer and Fe 3O 4 NPs, both PLLA and PLGA at lower molecule weights showed higher loading efficiencies for the drug on their surfaces.

  12. Novel Lutein Loaded Lipid Nanoparticles on Porcine Corneal Distribution

    PubMed Central

    Liu, Chi-Hsien; Chiu, Hao-Che; Wu, Wei-Chi; Sahoo, Soubhagya Laxmi; Hsu, Ching-Yun

    2014-01-01

    Topical delivery has the advantages including being user friendly and cost effective. Development of topical delivery carriers for lutein is becoming an important issue for the ocular drug delivery. Quantification of the partition coefficient of drug in the ocular tissue is the first step for the evaluation of delivery efficacy. The objectives of this study were to evaluate the effects of lipid nanoparticles and cyclodextrin (CD) on the corneal lutein accumulation and to measure the partition coefficients in the porcine cornea. Lipid nanoparticles combined with 2% HPβCD could enhance lutein accumulation up to 209.2 ± 18 (μg/g) which is 4.9-fold higher than that of the nanoparticles. CD combined nanoparticles have 68% of drug loading efficiency and lower cytotoxicity in the bovine cornea cells. From the confocal images, this improvement is due to the increased partitioning of lutein to the corneal epithelium by CD in the lipid nanoparticles. The novel lipid nanoparticles could not only improve the stability and entrapment efficacy of lutein but also enhance the lutein accumulation and partition in the cornea. Additionally the corneal accumulation of lutein was further enhanced by increasing the lutein payload in the vehicles. PMID:25101172

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

    PubMed

    Baharifar, Hadi; Amani, Amir

    2017-01-01

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

  14. Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.

    PubMed

    Nayak, Aditya P; Tiyaboonchai, Waree; Patankar, Swati; Madhusudhan, Basavaraj; Souto, Eliana B

    2010-11-01

    In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level.

  15. In vitro digestion of curcuminoid-loaded lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Noack, Andreas; Oidtmann, Johannes; Kutza, Johannes; Mäder, Karsten

    2012-09-01

    Curcuminoid-loaded lipid nanoparticles were produced by melt homogenization. The used lipid matrices were medium chain triglycerides, trimyristin (TM), and tristearin. The mean particle size of the preparations was between 130 and 180 nm. The incorporated curcuminoids revealed a good stability over a period of 12 months. The curcuminoid-loaded lipid nanoparticles were intended for the oral delivery of curcuminoids. Therefore, the fate of the triglyceride matrix in simulated gastric and simulated intestinal media under the influence of pepsin and pancreatin, respectively, was assessed. The degradation of the triglycerides was monitored by the pH-stat method and with high performance thin layer chromatography in connection with spectrodensitometry to quantify the different lipid fractions. The TM nanoparticles were not degraded in simulated gastric fluid (SGF), but the decomposition of the triglyceride matrix was rapid in the intestinal media. The digestion process was faster in the simulated fed state medium compared to the simulated fasted state medium. Additionally, the stability of the incorporated drug was tested in the respective physiological media. The curcuminoids showed an overall good stability in the different test media. The release of the curcuminoids from the lipid nanoparticles was determined by fluorescence imaging techniques. A slow release of the drug was found in phosphate buffer. In contrast, a more distinct release of the curcuminoids was verifiable in SGF and in simulated intestinal fluids. Overall, it was considered that the transfer of the drug into the outer media was mainly triggered by the lipid degradation and not by drug release.

  16. Lysozyme loading and release from Se doped hydroxyapatite nanoparticles.

    PubMed

    Wang, Yanhua; Hao, Hang; Zhang, Shengmin

    2016-04-01

    Element-substituted hydroxyapatite (HA) based nanocomposites have become a promising therapeutic material for improving bone defect repair. Selenium substituted HA nanoparticles can both induce apoptosis of bone tumor cells and enhance osteointegration. However, the effect of selenite ions on the proteins in combination with the HA nanoparticles remains to be elucidated. Here, we investigated the influence of selenium doping concentration on the loading and release of lysozyme (LSM) as a model protein drug. The selenium substituted HA-LSM composites with different doping concentrations were synthesized and characterized. The subsequent delivery of lysozyme was studied in a phosphate buffer solution (PBS). We found that selenium substituted HA-LSM composites with Se:P=10% showed the highest amount of lysozyme loading (41.7%), whereas the amount of lysozyme loaded in undoped HA nanoparticles was the lowest (34.1%). The doped selenium interacts with lysozyme molecules, which leads to the increase of β-sheet and unordered, and the decrease of self-association, α-helix and β-turns in protein structures. Moreover, selenium addition significantly slows the protein release from HA-LSM composites. The composites with Se:P=10% release lysozyme at the slightly slower rate among the samples with different Se doping concentrations. It also shows that the released lysozyme retains most of its enzymatic activity.

  17. Erythropoietin-loaded oligochitosan nanoparticles for treatment of periventricular leukomalacia.

    PubMed

    Wang, Ting; Hu, Yan; Leach, Michelle K; Zhang, Long; Yang, Wenjing; Jiang, Li; Feng, Zhang-Qi; He, Nongyue

    2012-01-17

    In this study, a single intraperitoneal injection of erythropoietin (EPO) loaded oligochitosan nanoparticles (epo-NPs) (average diameter 266 nm) was investigated as a treatment for periventricular leukomalacia (PVL). Nanoparticles were fabricated using a gelation technology process. PVL rats models were prepared to examine the therapeutic efficacy of epo-NPs and analyze the mechanism by which epo-NPs protect white matter. The metabolization of epo-NPs in the liver was also investigated. The pathology and behavioral data show that this single injection of a low quantity of epo-NPs had an excellent therapeutic effect on the rat model of PVL. The EPO release curve in phosphate buffered saline solution was a good fit with the zero-order kinetics distribution and was maintained at around 25% in 48 h. In vivo experiments demonstrated that 50 IU/kg epo-NPs had the same effect as a 5000 IU/kg direct injection of free EPO. Nanoparticles prolonged the time course of EPO metabolization in the liver and the stable release of EPO from the nanoparticles kept the plasma concentration of EPO at around 100 IU/ml during the 8-12h post-injection. Therefore, we suggest that oligochitosan based nanoparticles are an effective vehicle for drug delivery.

  18. Cargo and Carrier Effects of Rapamycin-Loaded Perfluorocarbon Nanoparticles

    NASA Astrophysics Data System (ADS)

    Bibee, Kristin Page

    Nanoparticle-based drug delivery has been championed as a means to increase local delivery of therapeutics while decreasing systemic drug exposure. By targeting the particles, and therefore the drugs, to diseased cells of interest, healthy cells will be spared and side effects avoided. This delivery mechanism would be particularly useful for drugs that interfere with cell growth and proliferation pathways, as blocking proliferation in normal cells leads to significant patient morbidity. Rapamycin is a macrolide and a known inhibitor of mTORC1, a protein complex that plays a crucial role in protein translation and cell growth. This work demonstrates the effects of rapamycin complexed with a nanoparticle carrier on two distinct pathologies: a new triple negative breast cancer cell line and a conventional mouse model of muscular dystrophy (mdx). Rapamycin is able to alter mitochondrial function and thus metabolism in both free and nanoparticle-delivered form without killing the cells. Although nanoparticles are considered to be a benign carrier, this work shows that perfluorocarbon nanoparticles are able to induce autophagy in vitro. The benefits of autophagy induction in cancer cells is cell and stage specific, but has been reported to be useful for radiosensitization of triple negative breast cancers. Additionally, the particles are shown to induce autophagy in the mdx model of Duchenne Muscular Dystrophy and, when loaded with rapamycin, dramatically improve strength even in older animals with muscular dystrophy. Overall, this work enhances our understanding of the cellular effects of perfluorocarbon nanoparticles in two different disease models and enhances prospects for clinical translation of nanoparticle-based drug delivery.

  19. A simple approach to obtain hybrid Au-loaded polymeric nanoparticles with a tunable metal load

    NASA Astrophysics Data System (ADS)

    Luque-Michel, Edurne; Larrea, Ane; Lahuerta, Celia; Sebastian, Víctor; Imbuluzqueta, Edurne; Arruebo, Manuel; Blanco-Prieto, María J.; Santamaría, Jesús

    2016-03-01

    A new strategy to nanoengineer multi-functional polymer-metal hybrid nanostructures is reported. By using this protocol the hurdles of most of the current developments concerning covalent and non-covalent attachment of polymers to preformed inorganic nanoparticles (NPs) are overcome. The strategy is based on the in situ reduction of metal precursors using the polymeric nanoparticle as a nanoreactor. Gold nanoparticles and poly(dl-lactic-co-glycolic acid), PLGA, are located in the core and shell, respectively. This novel technique enables the production of PLGA NPs smaller than 200 nm that bear either a single encapsulated Au NP or several smaller NPs with tunable sizes and a 100% loading efficiency. In situ reduction of Au ions inside the polymeric NPs was achieved on demand by using heat to activate the reductive effect of citrate ions. In addition, we show that the loading of the resulting Au NPs inside the PLGA NPs is highly dependent on the surfactant used. Electron microscopy, laser irradiation, UV-Vis and fluorescence spectroscopy characterization techniques confirm the location of Au nanoparticles. These promising results indicate that these hybrid nanomaterials could be used in theranostic applications or as contrast agents in dark-field imaging and computed tomography.A new strategy to nanoengineer multi-functional polymer-metal hybrid nanostructures is reported. By using this protocol the hurdles of most of the current developments concerning covalent and non-covalent attachment of polymers to preformed inorganic nanoparticles (NPs) are overcome. The strategy is based on the in situ reduction of metal precursors using the polymeric nanoparticle as a nanoreactor. Gold nanoparticles and poly(dl-lactic-co-glycolic acid), PLGA, are located in the core and shell, respectively. This novel technique enables the production of PLGA NPs smaller than 200 nm that bear either a single encapsulated Au NP or several smaller NPs with tunable sizes and a 100% loading

  20. Assembling metal oxide nanocrystals into dense, hollow, porous nanoparticles for lithium-ion and lithium-oxygen battery application

    NASA Astrophysics Data System (ADS)

    Ming, Jun; Wu, Yingqiang; Park, Jin-Bum; Lee, Joong Kee; Zhao, Fengyu; Sun, Yang-Kook

    2013-10-01

    New dense hollow porous (DHP) metal oxide nanoparticles that are smaller than 100 nm and composed of Co3O4, FeOx, NiO and MnOx were prepared by densely assembling metal oxide nanocrystals based on the hard-template method using a carbon colloid as a sacrificial core. These nanoparticles are quite different from the traditional particles as their hollow interior originates from the stacking of nanocrystals rather than a spherical shell. The DHP nanoparticles preserve the intriguing properties of nanocrystals and possess desirable surface area and pore volume that enhance the active surface, which ultimately benefits applications such as lithium-ion batteries. The DHP Co3O4 nanoparticles demonstrated an enhanced capacity of 1168 mA h g-1 at 100 mA g-1vs. 590 mA h g-1 of powders and stable cycling performance greater than 250 cycles when used as an anode material. Most importantly, the electrochemical performance of DHP Co3O4 nanoparticles in a lithium-O2 battery was also investigated for the first time. A low charge potential of ~4.0 V, a high discharge voltage near 2.74 V and a long cycle ability greater than 100 cycles at a delivered capacity of 2000 mA h g-1 (current density, 200 mA g-1) were observed. The performances were considerably improved compared to recent results of mesoporous Co3O4, Co3O4 nanoparticles and a composite of Co3O4/RGO and Co3O4/Pd. Therefore, it would be promising to investigate such properties of DHP nanoparticles or other hollow metal (oxide) particles for the popular lithium-air battery.New dense hollow porous (DHP) metal oxide nanoparticles that are smaller than 100 nm and composed of Co3O4, FeOx, NiO and MnOx were prepared by densely assembling metal oxide nanocrystals based on the hard-template method using a carbon colloid as a sacrificial core. These nanoparticles are quite different from the traditional particles as their hollow interior originates from the stacking of nanocrystals rather than a spherical shell. The DHP

  1. Formulation and characterization of curcuminoids loaded solid lipid nanoparticles.

    PubMed

    Tiyaboonchai, Waree; Tungpradit, Watcharaphorn; Plianbangchang, Pinyupa

    2007-06-07

    Curcuminoids loaded solid lipid nanoparticles (SLNs) have been successfully developed using a microemulsion technique at approximately 75 degrees C. It was found that variation in the amount of ingredients had profound effects on the curcuminoid loading capacity, the mean particle size, and size distribution. At optimized process conditions, lyophilized curcuminoids loaded SLNs showed spherical particles with a mean particle size of approximately 450nm and a polydispersity index of 0.4. Up to 70% (w/w) curcuminoids incorporation efficacy was achieved. In vitro release studies showed a prolonged release of the curcuminoids from the solid lipid nanoparticles up to 12h following the Higuchi's square root model. After 6-month storage at room temperature in the absence of sunlight, the physical and chemical stabilities of the lyophilized curcuminoids loaded SLNs could be maintained, i.e. the mean particle size and the amount of curcuminoids showed no significant changes (P>0.05) compared to the freshly prepared SLNs. In addition, the chemical stability of curcuminoids incorporated into SLNs was further investigated by dispersing them into a model cream base. The results revealed that after storage in the absence of sunlight for 6 months, the percentages of the remaining curcumin, bisdemethoxycurcumin and demethoxycurcumin were 91, 96 and 88, respectively.

  2. Roxithromycin-loaded lipid nanoparticles for follicular targeting.

    PubMed

    Wosicka-Frąckowiak, Hanna; Cal, Krzysztof; Stefanowska, Justyna; Główka, Eliza; Nowacka, Magdalena; Struck-Lewicka, Wiktoria; Govedarica, Biljana; Pasikowska, Monika; Dębowska, Renata; Jesionowski, Teofil; Srčič, Stane; Markuszewski, Michał Jan

    2015-11-30

    Particulate drug carriers e.g. nanoparticles (NPs) have been shown to penetrate and accumulate preferentially in skin hair follicles creating high local concentration of a drug. In order to develop such a follicle targeting system we obtained and characterized solid lipid nanoparticles (SLN) loaded with roxithromycin (ROX). The mean particle size (172±2 nm), polydisperisty index (0.237±0.007), zeta potential (-31.68±3.10 mV) and incorporation efficiency (82.1±3.0%) were measured. The long term stability of ROX-loaded SLN suspensions was proved up to 26 weeks. In vitro drug release study was performed using apparatus 4 dialysis adapters. Skin irritation test conducted using the EpiDerm™ tissue model demonstrated no irritation potential for ROX-loaded SLN. Ex vivo human skin penetration studies, employing rhodamine B hexyl ester perchlorate (RBHE) as a fluorescent dye to label the particles, revealed fluorescence deep in the skin, specifically around the hair follicles up to over 1mm depth. The comparison of fluorescence intensities after application of RBHE solution and RBHE-labelled ROX-loaded SLN was done. Then cyanoacrylate follicular biopsies were obtained in vivo and analyzed for ROX content, proving the possibility of penetration to human pilosebaceous units and delivering ROX by using SLN with the size below 200 nm.

  3. Assembling metal oxide nanocrystals into dense, hollow, porous nanoparticles for lithium-ion and lithium-oxygen battery application.

    PubMed

    Ming, Jun; Wu, Yingqiang; Park, Jin-Bum; Lee, Joong Kee; Zhao, Fengyu; Sun, Yang-Kook

    2013-11-07

    New dense hollow porous (DHP) metal oxide nanoparticles that are smaller than 100 nm and composed of Co3O4, FeOx, NiO and MnOx were prepared by densely assembling metal oxide nanocrystals based on the hard-template method using a carbon colloid as a sacrificial core. These nanoparticles are quite different from the traditional particles as their hollow interior originates from the stacking of nanocrystals rather than a spherical shell. The DHP nanoparticles preserve the intriguing properties of nanocrystals and possess desirable surface area and pore volume that enhance the active surface, which ultimately benefits applications such as lithium-ion batteries. The DHP Co3O4 nanoparticles demonstrated an enhanced capacity of 1168 mA h g(-1) at 100 mA g(-1)vs. 590 mA h g(-1) of powders and stable cycling performance greater than 250 cycles when used as an anode material. Most importantly, the electrochemical performance of DHP Co3O4 nanoparticles in a lithium-O2 battery was also investigated for the first time. A low charge potential of ∼4.0 V, a high discharge voltage near 2.74 V and a long cycle ability greater than 100 cycles at a delivered capacity of 2000 mA h g(-1) (current density, 200 mA g(-1)) were observed. The performances were considerably improved compared to recent results of mesoporous Co3O4, Co3O4 nanoparticles and a composite of Co3O4/RGO and Co3O4/Pd. Therefore, it would be promising to investigate such properties of DHP nanoparticles or other hollow metal (oxide) particles for the popular lithium-air battery.

  4. Physicochemical characterization of curcuminoid-loaded solid lipid nanoparticles.

    PubMed

    Noack, Andreas; Hause, Gerd; Mäder, Karsten

    2012-02-28

    Curcuminoid-loaded solid lipid nanoparticles (SLN) were produced by melt-homogenization. The used lipid matrices were medium chain triglycerides, trimyristin and tristearin. The resulting nanoparticles had an anisometric shape and a platelet-like structure. Curcuminoid-loaded trimyristin particles did not solidify when stored at room temperature. The supercooled state of trimyristin was studied by DSC and (1)H NMR experiments. A partial recrystallization of the lipid matrix was detected but no change of the mobility of the lipid was noted. Nanoparticles based on tristearin had an α- and β-modification which was subsequently converted into the stable β-phase. Curcuminoids did neither influence the melting behavior nor the crystalline or geometric structure of the particles. The interactions between the curcuminoids and the lipid matrix were investigated by Raman and fluorescence spectroscopy. The shape of the curcuminoid bands in the Raman spectra suggested that the drug was in an amorphous state. The fluorescence spectra showed an effect of the lipid matrix on fluorescence properties of the curcuminoids. It was further demonstrated that the drug was not secluded by the solid lipid matrix, but it was influenced by the surrounding aqueous environment. Fluorescence anisotropy measurements revealed a decreased mobility of the curcuminoids within the nanodispersions. From the results of Raman and fluorescence measurements it was concluded that the drug was mainly located on the surface of the crystalline particles.

  5. Curcumin-Loaded PLA Nanoparticles: Formulation and Physical Evaluation

    PubMed Central

    Rachmawati, Heni; Yanda, Yulia L.; Rahma, Annisa; Mase, Nobuyuki

    2016-01-01

    Curcumin is a polyphenolic compound derived from Curcuma domestica (Zingiberaceae) that possesses diverse pharmacological effects including anti-inflammatory, antioxidant, antimicrobial, and anticarcinogenic activities. Although phase I clinical trials have shown curcumin as a safe drug even at high doses (12 g/day) in humans, poor bioavaibility largely limits its pharmacological activity. Nanoencapsulation in biodegradable polymers is a promising alternative to improve curcumin bioavaibility. In this study, curcumin was encapsulated in biodegradable polymer poly-(lactic acid) (PLA) nanoparticles via the emulsification-solvent evaporation method. Optimization of selected parameters of this method including the type of solvent, surfactant concentration, drug loading, sonication time, and centrifugation speed, were performed to obtain polymeric nano-carriers with optimum characteristics. Dichloromethane was used as the solvent and vitamin E polyethylene glycol succinate (TPGS) was used as the surfactant. Four minutes of sonication time and centrifugation at 10500 rpm were able to produce spherical nanoparticles with average size below 300 nm. The highest encapsulation efficiency was found on PLA nanoparticles containing 5% of curcumin at 89.42 ± 1.04%. The particle size, polydispersity index, zeta potential of 5% curcumin-PLA nanoparticles were 387.50 ± 58.60 nm, 0.289 ± 0.047, and −1.12 mV, respectively. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies showed partial interaction between the drug and polymer. PMID:27110509

  6. 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.

  7. Eugenol-loaded chitosan nanoparticles: II. Application in bio-based plastics for active packaging.

    PubMed

    Woranuch, Sarekha; Yoksan, Rangrong

    2013-07-25

    The aim of the present research was to study the possibility of using eugenol-loaded chitosan nanoparticles as antioxidants for active bio-based packaging material. Eugenol-loaded chitosan nanoparticles were incorporated into thermoplastic flour (TPF) - a model bio-based plastic - through an extrusion process at temperatures above 150°C. The influences of eugenol-loaded chitosan nanoparticles on crystallinity, morphology, thermal properties, radical scavenging activity, reducing power, tensile properties and barrier properties of TPF were investigated. Although the incorporation of 3% (w/w) of eugenol-loaded chitosan nanoparticles significantly reduced the extensibility and the oxygen barrier property of TPF, it provided antioxidant activity and improved the water vapor barrier property. In addition, TPF containing eugenol-loaded chitosan nanoparticles exhibited superior radical scavenging activity and stronger reducing power compared with TPF containing naked eugenol. The results suggest the applicability of TPF containing eugenol-loaded chitosan nanoparticles as an antioxidant active packaging material.

  8. Single-Particle Cryo-EM and 3D Reconstruction of Hybrid Nanoparticles with Electron-Dense Components.

    PubMed

    Yu, Guimei; Yan, Rui; Zhang, Chuan; Mao, Chengde; Jiang, Wen

    2015-10-01

    Single-particle cryo-electron microscopy (cryo-EM), accompanied with 3D reconstruction, is a broadly applicable tool for the structural characterization of macromolecules and nanoparticles. Recently, the cryo-EM field has pushed the limits of this technique to higher resolutions and samples of smaller molecular mass, however, some samples still present hurdles to this technique. Hybrid particles with electron-dense components, which have been studied using single-particle cryo-EM yet with limited success in 3D reconstruction due to the interference caused by electron-dense elements, constitute one group of such challenging samples. To process such hybrid particles, a masking method is developed in this work to adaptively remove pixels arising from electron-dense portions in individual projection images while maintaining maximal biomass signals for subsequent 2D alignment, 3D reconstruction, and iterative refinements. As demonstrated by the success in 3D reconstruction of an octahedron DNA/gold hybrid particle, which has been previously published without a 3D reconstruction, the devised strategy that combines adaptive masking and standard single-particle 3D reconstruction approach has overcome the hurdle of electron-dense elements interference, and is generally applicable to cryo-EM structural characterization of most, if not all, hybrid nanomaterials with electron-dense components.

  9. Magnetic poly(D,L-lactide) nanoparticles loaded with aliskiren: A promising tool for hypertension treatment

    NASA Astrophysics Data System (ADS)

    Antal, Iryna; Kubovcikova, Martina; Zavisova, Vlasta; Koneracka, Martina; Pechanova, Olga; Barta, Andrej; Cebova, Martina; Antal, Vitaliy; Diko, Pavel; Zduriencikova, Martina; Pudlak, Michal; Kopcansky, Peter

    2015-04-01

    In this study anti-hypertensive drug called aliskiren was encapsulated in magnetic poly(D,L-lactide) nanoparticles by the modified nanoprecipitation method. The effect of magnetite and drug concentrations on the size distribution and zeta potential of polymer nanoparticles was investigated. The optimized loadings were as follows: theoretical magnetite loading was 20 mg/100 mg polymer nanoparticles and aliskiren was encapsulated in magnetic poly(D,L-lactide) nanoparticles at theoretical loading 0.6 mg aliskiren/100 mg magnetic polymer nanoparticles. The physicochemical characteristics of nanoparticles were studied, with spherical shape of nanoparticles sized between 58 and 227 nm being one of the observed results. Differential scanning calorimetry and infrared spectroscopy confirmed that aliskiren was successfully identified in the magnetic poly(D,L-lactide) nanoparticles. The in vivo experiments indicated that encapsulated aliskiren decreased blood pressure of the studied male spontaneously hypertensive rat even more significantly than common administered drug.

  10. DEM analyses of the whole failure process of shallow foundation in plate load test on dense sand

    NASA Astrophysics Data System (ADS)

    Li, L.; Jiang, M. J.; Li, T.; Chen, S. L.

    2015-09-01

    Shallow foundations are widely used in civil engineering practice, but the instability mechanism is still unclear yet. Previously, the Finite Element Method (FEM) was commonly used to analyze the failure process of shallow foundations, but it meets difficulty in properly simulating the whole failure process of shallow foundation on the strain-softening material. Hence, the Discrete Element Method (DEM) is employed in this paper to study the instability mechanism of the shallow foundation via numerical plate load test with focus on the microscopic features evolution during vertical loading. In the simulation, an amplified gravity was applied to a dense granular ground to reproduce a gravity stress state at a large scale. Then, a plate was put on the granular ground to simulate the plate load test. Deformation pattern, particle velocity and distribution of void ratio in the ground were examined to illustrate the microscopic features in the whole failure process of the granular ground. The results show that: 1) There are a marked peak value and a settlement softening branch in the stress-settlement relationship. 2) The grids close to the edge of the plate are peculiarly extended and twisted. 3) Four particle motion patterns were observed in the velocity fields and the percentage of each motion pattern changes during loading. 4) The void ratio field varies during loading, and the distinguishing interface tends to be similar to Terzaghi's shear failure surface.

  11. Insulin-loaded alginic acid nanoparticles for sublingual delivery.

    PubMed

    Patil, Nilam H; Devarajan, Padma V

    2016-01-01

    Alginic acid nanoparticles (NPs) containing insulin, with nicotinamide as permeation enhancer were developed for sublingual delivery. The lower concentration of proteolytic enzymes, lower thickness and enhanced retention due to bioadhesive property, were relied on for enhanced insulin absorption. Insulin-loaded NPs were prepared by mild and aqueous based nanoprecipitation process. NPs were negatively charged and had a mean size of ∼200 nm with low dispersity index. Insulin loading capacities of >95% suggested a high association of insulin with alginic acid. Fourier Transform Infra-Red Spectroscopy (FTIR) spectra and DSC (Differential Scanning Calorimetry) thermogram of insulin-loaded NPs revealed the association of insulin with alginic acid. Circular dichroism (CD) spectra confirmed conformational stability, while HPLC analysis confirmed chemical stability of insulin in the NPs. Sublingually delivered NPs with nicotinamide exhibited high pharmacological availability (>100%) and bioavailability (>80%) at a dose of 5 IU/kg. The high absolute pharmacological availability of 20.2% and bioavailability of 24.1% in comparison with subcutaneous injection at 1 IU/kg, in the streptozotocin-induced diabetic rat model, suggest the insulin-loaded alginic acid NPs as a promising sublingual delivery system of insulin.

  12. Spectral and Spatial Characterization of Protein Loaded PLGA Nanoparticles

    PubMed Central

    Zidan, Ahmed S.; Rahman, Ziyaur; Habib, Muhammad J.; Khan, Mansoor A.

    2011-01-01

    The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess drug contents in poly(dl-lactide-co-glycolide) (PLGA) based nanoparticles of a model protein, cyclosporine A (CyA). A 6-factors 12-runs designed set of experiments with Plackett–Burman (PB) screening was applied in order to examine the effects of drug loading (X1), polymer loading (X2), emulsifier concentration (X3), stirring rate (X4), type of organic solvent (X5), and ratio of organic to aqueous phases' volumes (X6), on drug entrapment efficiency (EFF). After omitting the factors with nonsignificant influences on EFF, a reduced mathematical relationship, EFF = 48.34 + 7.3X1 − 29.95X3, was obtained to explain the effect of the significant factors on EFF. Using two different sets for calibration and validation, the developed NIR calibration model was able to assess CyA contents within the 12 PB formulations. NIR spectral imaging was capable of clearly distinguishing the 12 formulations, both qualitatively and quantitatively. A good correlation with a coefficient of 0.9727 was obtained for constructing a quantile-quantile plot for the actual drug loading percentage and the % standard deviation obtained for the drug loading prediction using the hyperspectral images. PMID:19774658

  13. Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment

    PubMed Central

    Zhang, Zhen; Qian, Hanqing; Yang, Mi; Li, Rutian; Hu, Jing; Li, Li; Yu, Lixia; Liu, Baorui; Qian, Xiaoping

    2017-01-01

    Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid) (PLGA) with red blood-cell membrane (RBCm), and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier. PMID:28280328

  14. Next generation radiotherapy biomaterials loaded with high-Z nanoparticles

    NASA Astrophysics Data System (ADS)

    Cifter, Gizem

    This research investigates the dosimetric feasibility of using high-Z nanoparticles as localized radiosensitizers to boost the dose to the residual tumor cells during accelerated partial breast irradiation while minimizing the dose to surrounding healthy tissue. Analytical microdosimetry calculations were carried out to calculate dose enhancement (DEF) in the presence of high-Z nanoparticles. It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. Prototype smart biomaterials were produced by incorporating the GNPs in poly (D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. In vitro release of GNPs was monitored over time by optical/spectroscopy methods as a function of various design parameters. The prototype smart biomaterials displayed sustained customizable release of NPs in-vitro, reaching a burst release profile approximately after 25 days. The results also show that customizable release profiles can be achievable by varying GNP concentrations that are embedded within smart biomaterials, as well as other design parameters. This would potentially allow customizable local dose boost resulting in diverse treatment planning opportunities for individual cases. Considered together, the results provide preliminary data for development of next generation of RT biomaterials, which can be employed at no additional inconvenience to RT patients.

  15. Preparation and characterization of solid lipid nanoparticles loaded with doxorubicin.

    PubMed

    Subedi, Robhash Kusam; Kang, Keon Wook; Choi, Hoo-Kyun

    2009-06-28

    Solid lipid nanoparticles (SLN) loaded with doxorubicin were prepared by solvent emulsification-diffusion method. Glyceryl caprate (Capmul)MCM C10) was used as lipid core, and curdlan as the shell material. Dimethyl sulfoxide (DMSO) was used to dissolve both lipid and drug. Polyethylene glycol 660 hydroxystearate (Solutol)HS15) was employed as surfactant. Major formulation parameters were optimized to obtain high quality nanoparticles. The mean particle size measured by photon correlation spectroscopy (PCS) was 199nm. The entrapment efficiency (EE) and drug loading capacity (DL), determined with fluorescence spectroscopy, were 67.5+/-2.4% and 2.8+/-0.1%, respectively. The drug release behavior was studied by in vitro method. Cell viability assay showed that properties of SLN remain unchanged during the process of freeze-drying. Stability study revealed that lyophilized SLN were equally effective (p<0.05) after 1 year of storage at 4 degrees C. In conclusion, SLN with small particle size, high EE, and relatively high DL for doxorubicin can be obtained by this method.

  16. Microfluidic generation of droplets with a high loading of nanoparticles.

    PubMed

    Wan, Jiandi; Shi, Lei; Benson, Bryan; Bruzek, Matthew J; Anthony, John E; Sinko, Patrick J; Prudhomme, Robert K; Stone, Howard A

    2012-09-18

    Microfluidic approaches for controlled generation of colloidal clusters, for example, via encapsulation of colloidal particles in droplets, have been used for the synthesis of functional materials including drug delivery carriers. Most of the studies, however, use a low concentration of an original colloidal suspension (<10 wt %). Here we demonstrate microfluidic approaches for directly making droplets with moderate (10-25 wt %) and high (>60 wt %) particle concentrations. Three types of microfluidic devices, PDMS flow-focusing, PDMS T-junction, and microcapillary devices, are investigated for direct encapsulation of a high concentration of polystyrene (PS) nanoparticles in droplets. In particular, it is shown that PDMS devices fabricated by soft lithography can generate droplets from a 25 wt % PS suspension, whereas microcapillary devices made from glass capillary tubes are able to produce droplets from a 67 wt % PS nanoparticle suspension. When the PS concentration is between 0.6 and 25 wt %, the size of the droplets is found to change with the oil-to-water flow rate ratio and is independent of the concentration of particles in the initial suspensions. Drop sizes from ~12 to 40 μm are made using flow rate ratios Q(oil)/Q(water) from 20 to 1, respectively, with either of the PDMS devices. However, clogging occurs in PDMS devices at high PS concentrations (>25 wt %) arising from interactions between the PS colloids and the surface of PDMS devices. Glass microcapillary devices, on the other hand, are resistant to clogging and can produce droplets continuously even when the concentration of PS nanoparticles reaches 67 wt %. We believe that our findings indicate useful approaches and guidelines for the controlled generation of emulsions filled with a high loading of nanoparticles, which are useful for drug delivery applications.

  17. Noble Metal Nanoparticle-loaded Mesoporous Oxide Microspheres for Catalysis

    NASA Astrophysics Data System (ADS)

    Jin, Zhao

    Noble metal nanoparticles/nanocrystals have attracted much attention as catalysts due to their unique characteristics, including high surface areas and well-controlled facets, which are not often possessed by their bulk counterparts. To avoid the loss of their catalytic activities brought about by their size and shape changes during catalytic reactions, noble metal nanoparticles/nanocrystals are usually dispersed and supported finely on solid oxide supports to prevent agglomeration, nanoparticle growth, and therefore the decrease in the total surface area. Moreover, metal oxide supports can also play important roles in catalytic reactions through the synergistic interactions with loaded metal nanoparticles/nanocrystals. In this thesis, I use ultrasonic aerosol spray to produce hybrid microspheres that are composed of noble metal nanoparticles/nanocrystals embedded in mesoporous metal oxide matrices. The mesoporous metal oxide structure allows for the fast diffusion of reactants and products as well as confining and supporting noble metal nanoparticles. I will first describe my studies on noble metal-loaded mesoporous oxide microspheres as catalysts. Three types of noble metals (Au, Pt, Pd) and three types of metal oxide substrates (TiO2, ZrO2, Al 2O3) were selected, because they are widely used for practical catalytic applications involved in environmental cleaning, pollution control, petrochemical, and pharmaceutical syntheses. By considering every possible combination of the noble metals and oxide substrates, nine types of catalyst samples were produced. I characterized the structures of these catalysts, including their sizes, morphologies, crystallinity, and porosities, and their catalytic performances by using a representative reduction reaction from nitrobenzene to aminobenzene. Comparison of the catalytic results reveals the effects of the different noble metals, their incorporation amounts, and oxide substrates on the catalytic abilities. For this particular

  18. Polymorphic transformation of dense ZnO nanoparticles: implications for chair/boat-type Peierls distortions of AB semiconductor.

    PubMed

    Chen, Shuei-Yuan; Shen, Pouyan; Jiang, Jianzhong

    2004-12-08

    Peierls distortion path was proved experimentally for dense ZnO nanoparticles prepared by static compression. Electron irradiation caused rock salt (R) to wurtzite (W) transition, following preferential (111)(R)//(0111)(W); [011](R)//[1213](W) and then transformation strain induced (111)(R)//(1011)(W); [011](R)//[0111](W). The two relationships can be rationalized by specified extent of chair- and boat-type Peierls distortions accompanied with band gap opening and intermediate {111}R slip for energetically favorable {111}R/(0111)W match.

  19. Graphene oxide wrapping on squaraine-loaded mesoporous silica nanoparticles for bioimaging.

    PubMed

    Sreejith, Sivaramapanicker; Ma, Xing; Zhao, Yanli

    2012-10-24

    Squaraine dyes were loaded inside mesoporous silica nanoparticles, and the nanoparticle surfaces were then wrapped with ultrathin graphene oxide sheets, leading to the formation of a novel hybrid material. The hybrid exhibits remarkable stability and can efficiently protect the loaded dye from nucleophilic attack. The biocompatible hybrid is noncytotoxic and presents significant potential for application in fluorescence imaging in vitro.

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

    NASA Astrophysics Data System (ADS)

    Subia, B.; Kundu, S. C.

    2013-01-01

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

  1. An Efficient Targeted Drug Delivery through Apotransferrin Loaded Nanoparticles

    PubMed Central

    Kishore, Golla; Kondapi, Anand Kumar

    2009-01-01

    Background Cancerous state is a highly stimulated environment of metabolically active cells. The cells under these conditions over express selective receptors for assimilation of factors essential for growth and transformation. Such receptors would serve as potential targets for the specific ligand mediated transport of pharmaceutically active molecules. The present study demonstrates the specificity and efficacy of protein nanoparticle of apotransferrin for targeted delivery of doxorubicin. Methodology/Principal Findings Apotransferrin nanoparticles were developed by sol-oil chemistry. A comparative analysis of efficiency of drug delivery in conjugated and non-conjugated forms of doxorubicin to apotransferrin nanoparticle is presented. The spherical shaped apotransferrin nanoparticles (nano) have diameters of 25–50 ηm, which increase to 60–80 ηm upon direct loading of drug (direct-nano), and showed further increase in dimension (75–95 ηm) in conjugated nanoparticles (conj-nano). The competitive experiments with the transferrin receptor specific antibody showed the entry of both conj-nano and direct-nano into the cells through transferrin receptor mediated endocytosis. Results of various studies conducted clearly establish the superiority of the direct-nano over conj-nano viz. (a) localization studies showed complete release of drug very early, even as early as 30 min after treatment, with the drug localizing in the target organelle (nucleus) (b) pharmacokinetic studies showed enhanced drug concentrations, in circulation with sustainable half-life (c) the studies also demonstrated efficient drug delivery, and an enhanced inhibition of proliferation in cancer cells. Tissue distribution analysis showed intravenous administration of direct nano lead to higher drug localization in liver, and blood as compared to relatively lesser localization in heart, kidney and spleen. Experiments using rat cancer model confirmed the efficacy of the formulation in regression

  2. Nearly full-dense and fine-grained AZO:Y ceramics sintered from the corresponding nanoparticles

    PubMed Central

    2012-01-01

    Aluminum-doped zinc oxide ceramics with yttria doping (AZO:Y) ranging from 0 to 0.2 wt.% were fabricated by pressureless sintering yttria-modified nanoparticles in air at 1,300°C. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction analysis, a physical property measurement system, and a densimeter were employed to characterize the precursor nanoparticles and the sintered AZO ceramics. It was shown that a small amount of yttria doping can remarkably retard the growth of the as-received precursor nanoparticles, further improve the microstructure, refine the grain size, and enhance the density for the sintered ceramic. Increasing the yttria doping to 0.2 wt.%, the AZO:Y nanoparticles synthetized by a coprecipitation process have a nearly sphere-shaped morphology and a mean particle diameter of 15.1 nm. Using the same amount of yttria, a fully dense AZO ceramic (99.98% of theoretical density) with a grain size of 2.2 μm and a bulk resistivity of 4.6 × 10−3 Ω·cm can be achieved. This kind of AZO:Y ceramic has a potential to be used as a high-quality sputtering target to deposit ZnO-based transparent conductive films with better optical and electrical properties. PMID:22929049

  3. Nearly full-dense and fine-grained AZO:Y ceramics sintered from the corresponding nanoparticles.

    PubMed

    Yang, Ye; Lan, Pinjun; Wang, Muqin; Wei, Tiefeng; Tan, Ruiqin; Song, Weijie

    2012-08-29

    Aluminum-doped zinc oxide ceramics with yttria doping (AZO:Y) ranging from 0 to 0.2 wt.% were fabricated by pressureless sintering yttria-modified nanoparticles in air at 1,300°C. Scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction analysis, a physical property measurement system, and a densimeter were employed to characterize the precursor nanoparticles and the sintered AZO ceramics. It was shown that a small amount of yttria doping can remarkably retard the growth of the as-received precursor nanoparticles, further improve the microstructure, refine the grain size, and enhance the density for the sintered ceramic. Increasing the yttria doping to 0.2 wt.%, the AZO:Y nanoparticles synthetized by a coprecipitation process have a nearly sphere-shaped morphology and a mean particle diameter of 15.1 nm. Using the same amount of yttria, a fully dense AZO ceramic (99.98% of theoretical density) with a grain size of 2.2 μm and a bulk resistivity of 4.6 × 10-3 Ω·cm can be achieved. This kind of AZO:Y ceramic has a potential to be used as a high-quality sputtering target to deposit ZnO-based transparent conductive films with better optical and electrical properties.

  4. Drug loading to lipid-based cationic nanoparticles

    NASA Astrophysics Data System (ADS)

    Cavalcanti, Leide P.; Konovalov, Oleg; Torriani, Iris L.; Haas, Heinrich

    2005-08-01

    Lipid-based cationic nanoparticles are a new promising option for tumor therapy, because they display enhanced binding and uptake at the neo-angiogenic endothelial cells, which a tumor needs for its nutrition and growth. By loading suitable cytotoxic compounds to the cationic carrier, the tumor endothelial and consequently also the tumor itself can be destroyed. For the development of such novel anti-tumor agents, the control of drug loading and drug release from the carrier matrix is essential. We have studied the incorporation of the hydrophobic anti-cancer agent Paclitaxel (PXL) into a variety of lipid matrices by X-Ray reflectivity measurements. Liposome suspensions from cationic and zwitterionic lipids, comprising different molar fractions of Paclitaxel, were deposited on planar glass substrates. After drying at controlled humidity, well ordered, oriented multilayer stacks were obtained, as proven by the presence of bilayer Bragg peaks to several orders in the reflectivity curves. The presence of the drug induced a decrease of the lipid bilayer spacing, and with an excess of drug, also Bragg peaks of drug crystals could be observed. From the results, insight into the solubility of Paclitaxel in the model membranes was obtained and a structural model of the organization of the drug in the membrane was derived. Results from subsequent pressure/area-isotherm and grazing incidence diffraction (GID) measurements performed with drug/lipid Langmuir monolayers were in accordance with these conjectures.

  5. Engineering tenofovir loaded chitosan nanoparticles to maximize microbicide mucoadhesion.

    PubMed

    Meng, Jianing; Sturgis, Timothy F; Youan, Bi-Botti C

    2011-09-18

    The objective of this study was to engineer a model anti-HIV microbicide (tenofovir) loaded chitosan based nanoparticles (NPs). Box-Behnken design allowed to assess the influence of formulation variables on the size of NPs and drug encapsulation efficiency (EE%) that were analyzed by dynamic light scattering and UV spectroscopy, respectively. The effect of the NPs on vaginal epithelial cells and Lactobacillus crispatus viability and their mucoadhesion to porcine vaginal tissue were assessed by cytotoxicity assays and fluorimetry, respectively. In the optimal aqueous conditions, the EE% and NPs size were 5.83% and 207.97nm, respectively. With 50% (v/v) ethanol/water as alternative solvent, these two responses increased to 20% and 602 nm, respectively. Unlike small size (182nm) exhibiting burst release, drug release from medium (281 nm) and large (602 nm)-sized NPs fitted the Higuchi (r(2)=0.991) and first-order release (r(2)=0.999) models, respectively. These NPs were not cytotoxic to both the vaginal epithelial cell line and L. crispatus for 48h. When the diameter of the NPs decreased from 900 to 188 nm, the mucoadhesion increased from 6% to 12%. However, the combinatorial effect of EE% and percent mucoadhesion for larger size NPs was the highest. Overall, large-size, microbicide loaded chitosan NPs appeared to be promising nanomedicines for the prevention of HIV transmission.

  6. Statistical modeling of zaltoprofen loaded biopolymeric nanoparticles: Characterization and anti-inflammatory activity of nanoparticles loaded gel

    PubMed Central

    Shah, Hirva A; Patel, Rakesh P

    2015-01-01

    Objective: The main objective of this study is to formulate polymeric nanoparticles (NPs) loaded with zaltoprofen, an NSAID drug. The optimization, in terms of polymer concentration, stabilizer concentration and pH of the formulation was employed by 3-factor-3-level Box-Behnken experimental design. Materials and Methods: The NPs of zaltoprofen were fabricated using chitosan and alginate as polymers by ionotropic gelation. The ionic interaction between the ionic polymers was studied using Fourier transform infrared and differential scanning calorimetry study. Result: For different formulation the average particle size ranged between 156 ± 1.0 nm and 554 ± 2.8 nm. The drug entrapment ranged between 61.40% ± 3.20% and 90.20% ± 2.47%. The ANOVA results exhibited that all the three factors were significant. The resultant optimized batch was characterized by particle size 156.04 ± 1.4 nm, %entrapment efficacy 88.67% ± 2.0%, zetapotential + 25.3 mV and polydispersity index 0.320. The scanning electron microscopy showed spherical NPs of average size 99.5 nm. The optimized NPs were loaded in carbopol gel, which was subjected to study of drug content, viscosity, spreadability, in vitro drug diffusion and in vivo antiinflammatory test on rats. Conclusion: This study showed that zaltoprofen NPs prepared using the ratio of polymer CS:AG:1:1.8, stabilizer concentration 0.98% and pH 4.73 was found to be of optimized particle size, maximum drug entrapment. The NPs loaded gel showed controlled release for 12 h following Korsmeryer-peppas model of the diffusion profile. The in vivo antiinflammatory study showed prolonged effect of NPs loaded gel for 10 h. PMID:25599029

  7. Dynamic three-dimensional simulations of densely-packed fluid loaded cloth in a complex geometry

    NASA Astrophysics Data System (ADS)

    Akcabay, Deniz T.; Schultz, William W.; Dowling, David R.

    2006-11-01

    This talk presents three-dimensional simulations of the fluid-structure interaction that occurs inside the washtub of a modern clothes washing machine. The results are based on the numerical solution of the incompressible Navier-Stokes equations on a Cartesian grid using Peskin's Immersed Boundary Method for the cloth-fluid coupling, and a weighted domain-mapping method to represent the complicated moving boundaries of the agitator and washtub. Cloth pieces are modeled as impermeable flexible isotropic elastic plates. Results from simple benchmarking studies with theoretical and experimental results for the individual cloth and complex geometry models are presented. A variety of simulation studies involving complicated mixing patterns that result from mechanical excitation from a realistic agitator are shown and analyzed. The effects of cloth size, bending stiffness, and load density on the resulting motion of individual pieces of cloth and on the bulk flow within the machine are analyzed. [Sponsored by Whirlpool Corporation

  8. Ascorbyl palmitate-loaded chitosan nanoparticles: characteristic and polyphenol oxidase inhibitory activity.

    PubMed

    Kim, Mi Kyung; Lee, Ji-Soo; Kim, Kwang Yup; Lee, Hyeon Gyu

    2013-03-01

    The aim of this study was to produce ascorbyl palmitate (AP)-loaded nanoparticles in order to inhibit polyphenol oxidase (PPO) in bananas. AP-loaded chitosan nanoparticles were prepared using acetic acid and citric acid (denoted as CS/AA and CS/CA nanoparticles, respectively). As the initial AP concentration increases, the particle size significantly decreases, and the zeta potential, entrapment and loading efficiency significantly increases. The PPO inhibitory activity of AP was effectively improved when AP was nano-encapsulated by chitosan compared to no encapsulation. These results suggest that chitosan nano-encapsulation can be used to enhance the PPO inhibitory activity of AP.

  9. Effects of ball-milling on PLGA polymer and its implication on lansoprazole-loaded nanoparticles

    PubMed Central

    Shabir, Anjumn; Alhusban, Farhan; Perrie, Yvonne; Mohammed, Afzal R.

    2011-01-01

    PLGA is a biodegradable polymer utilised widely in pharmaceutical research for the encapsulation of a wide range of drugs as nano particulate systems. This study investigates the impact of rotary ball milling on the physical properties of PLGA and its influence on nanoparticle formation prepared using the solvent displacement technique. By applying mechanical stress to the polymer and altering its physical appearance and molecular weight, the loading of lansoprazole within the nanoparticles was increased to 96%, with a reduction in particle size. The results indicate that rotary ball milling significantly reduces particle size, increases lansoprazole loading and improves the release profile for lansoprazole loaded PLGA nanoparticles PMID:24826005

  10. Activation of latent HIV using drug-loaded nanoparticles.

    PubMed

    Kovochich, Michael; Marsden, Matthew D; Zack, Jerome A

    2011-04-05

    Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target and activate primary human CD4+ T-cells and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the HDAC inhibitor sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. Taken together these data demonstrate the ability of nanotechnological approaches to provide improved methods for activating latent HIV and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV therapy.

  11. Preparation and Evaluation of Montelukast Sodium Loaded Solid Lipid Nanoparticles

    PubMed Central

    Priyanka, K; Sathali, A Abdul Hasan

    2012-01-01

    Solid lipid nanoparticles (SLNs) are an alternative carrier system used to load the drug for targeting, to improve the bioavailability by increasing its solubility, and protecting the drug from presystemic metabolism. The avoidance of presystemic metabolism is due to the nano-metric size range, so that the liver cannot uptake the drug from the delivery system and is not metabolized by the liver. Montelukast sodium is an anti-asthmatic drug, because of its poor oral bioavailability, presystemic metabolism, and decreased half-life; it was chosen to formulate as the solid lipid nanoparticle (SLN) system by hot homogenization followed by an ultrasonication method, to overcome the above. Compritol ATO 888, stearic acid, and glyceryl monostearate were used as a lipid matrix and polyvinyl alcohol as a surfactant. The prepared formulations have been evaluated for entrapment efficiency, drug content, in vitro drug release, particle size analysis, scanning electron microscopy, Fourier transform-infrared studies (FT-IR), differential scanning calorimetry (DSC), and stability. Particle size analysis revealed that the SLN prepared from the higher melting point lipid showed a larger particle size and with increased carbon chain length of the fatty acids. Entrapment efficiency (EE) was ranging from 42% to 92%. In vitro release studies showed maximum cumulative drug release was obtained for F 1 (59.1%) containing stearic acid, and the lowest was observed for F 18 (28.1%) containing compritol ATO 888 after 12 h and all the formulations followed first-order release kinetics. FT-IR and DSC studies revealed no interaction between drug and lipids. Studies showed that increase in lipid concentration, increased particle size, EE, and maintained the sustained release of drug. Among all, compritol ATO 888 was chosen as the best lipid for formulating SLN because it had high EE and sustained the drug release. PMID:23112531

  12. 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.

  13. Polymorphic transformation of dense ZnO nanoparticles: Implications for chair/boat-type Peierls distortions of AB semiconductor

    SciTech Connect

    Chen, S.-Y.; Shen Pouyan; Jiang Jianzhong

    2004-12-08

    Peierls distortion path was proved experimentally for dense ZnO nanoparticles prepared by static compression. Electron irradiation caused rock salt (R) to wurtzite (W) transition, following preferential (11-bar1){sub R}//(01-bar11){sub W}; [011]{sub R}//[1-bar21-bar3]{sub W} and then transformation strain induced (111-bar){sub R}//(1-bar011){sub W}; [011]{sub R}//[011-bar1]{sub W}. The two relationships can be rationalized by specified extent of chair- and boat-type Peierls distortions accompanied with band gap opening and intermediate {l_brace}111{r_brace}{sub R} slip for energetically favorable {l_brace}111{r_brace}{sub R}/(01-bar11){sub W} match.

  14. Green synthesis of rifampicin-loaded copper nanoparticles with enhanced antimicrobial activity.

    PubMed

    Woźniak-Budych, Marta J; Przysiecka, Łucja; Langer, Krzysztof; Peplińska, Barbara; Jarek, Marcin; Wiesner, Maciej; Nowaczyk, Grzegorz; Jurga, Stefan

    2017-03-01

    The antimicrobial properties of copper and rifampicin-loaded copper nanoparticles were investigated using four strains: Staphylococcus aureus, Escherichia coli, Bacillus pumilis and Pseudomonas fluorescens. Spherical-shaped copper nanoparticles were synthesized via green reduction method from the peppermint extract. It was found that adsorption of rifampicin on the copper nanosurface enhances its biological activity and prevents the development of resistance. The interactions between rifampicin-copper nanoparticles and bacteria cells were monitored using atomic force microscopy (AFM) and confocal laser scanning microscopy (CLSM). It was proven that loaded with rifampicin copper nanoparticles were able to damage the S. aureus cell membrane and facilitate the bacteria biofilm matrix disintegration. Moreover, the DNA decomposition of S. aureus treated with copper and rifampicin-copper nanoparticles was confirmed by agarose gel electrophoresis. The results obtained indicate that adsorption of rifampicin on the copper nanoparticles surface might provide the reduction of antibiotic dosage and prevent its adverse side effects.

  15. Loading Ag nanoparticles on Cd(II) boron imidazolate framework for photocatalysis

    NASA Astrophysics Data System (ADS)

    Liu, Min; Zhang, De-Xiang; Chen, Shumei; Wen, Tian

    2016-05-01

    An amine-functionalized Cd(II) boron imidazolate framework (BIF-77) with three-dimensional open structure has been successfully synthesized, which can load Ag nanoparticles (NPs) for photocatalytic degradation of methylene blue (MB).

  16. Streptomycin-loaded PLGA-alginate nanoparticles: preparation, characterization, and assessment

    NASA Astrophysics Data System (ADS)

    Asadi, Asadollah

    2013-04-01

    The aim of this study was to formulate and characterize streptomycin-loaded PLGA-alginate nanoparticles for their potential therapeutic use in Salmonella subsp. enterica ATCC 14028 infections. The streptomycin nanoparticle was prepared by solvent diffusion method, and the other properties such as size, zeta potential, loading efficacy, release kinetics, and antimicrobial strength were evaluated. The survey shows that nanoparticles may serve as a carrier of streptomycin and may provide localized antibacterial activity in the treatment of Salmonellosis. Electron microscopy showed spherical particles with indentations. The average size of the nanoparticles was 90 nm. At pH 7.2, the release kinetics of streptomycin from the nanoparticles was successfully illustrated as an initial burst defined by a first order equation that after this stage, it has a drastic tendency to obtain steady state. Nevertheless, nanoparticles showed loading efficacy nearly about 70-75 %. In addition, the tendency of concentration of streptomycin released from nanoparticles to reach antibacterial activity was similar to that of free streptomycin against PLGA-alginate, but it had threefold more antimicrobial strength in comparison with free streptomycin. This work shows the potential use of streptomycin-loaded PLGA-alginate nanoparticles and its capability.

  17. Streptomycin-loaded PLGA-alginate nanoparticles: preparation, characterization, and assessment

    NASA Astrophysics Data System (ADS)

    Asadi, Asadollah

    2014-04-01

    The aim of this study was to formulate and characterize streptomycin-loaded PLGA-alginate nanoparticles for their potential therapeutic use in Salmonella subsp. enterica ATCC 14028 infections. The streptomycin nanoparticle was prepared by solvent diffusion method, and the other properties such as size, zeta potential, loading efficacy, release kinetics, and antimicrobial strength were evaluated. The survey shows that nanoparticles may serve as a carrier of streptomycin and may provide localized antibacterial activity in the treatment of Salmonellosis. Electron microscopy showed spherical particles with indentations. The average size of the nanoparticles was 90 nm. At pH 7.2, the release kinetics of streptomycin from the nanoparticles was successfully illustrated as an initial burst defined by a first order equation that after this stage, it has a drastic tendency to obtain steady state. Nevertheless, nanoparticles showed loading efficacy nearly about 70-75 %. In addition, the tendency of concentration of streptomycin released from nanoparticles to reach antibacterial activity was similar to that of free streptomycin against PLGA-alginate, but it had threefold more antimicrobial strength in comparison with free streptomycin. This work shows the potential use of streptomycin-loaded PLGA-alginate nanoparticles and its capability.

  18. Poly(lactide-co-glycolide)-methoxy-poly(ethylene glycol) nanoparticles: drug loading and release properties.

    PubMed

    Katsikogianni, Georgia; Avgoustakis, Konstantinos

    2006-01-01

    In this work, the drug loading and in vitro release properties of PLGA-mPEG nanoparticles were studied. Three methyl-xanthine derivatives differing significantly in aqueous solubility, i.e., caffeine, theophylline, and theobromine, were employed as model drugs. Two different PLGA-mPEG copolymer compositions, namely PLGA(40)mPEG(5) and PLGA(136)mPEG(5), were included in the study. The nanoparticles were prepared by a double emulsion technique. The drug release properties of the nanoparticles in phosphate buffered saline (PBS) and in human plasma were determined. An increase of the drug proportion in the feed led to increased drug loading. The composition of the PLGA-mPEG copolymer (PLGA/mPEG molar ratio) did not appear to affect drug loading and encapsulation. Caffeine exhibited higher loading in the nanoparticles than theobromine and this exhibited a little higher loading than theophylline. Solid-state solubility of the drug in PLGA-mPEG did not affect drug loading. Drug loading and encapsulation in the PLGA-mPEG nanoparticles appeared to be governed by the partition coefficient of the drug between the organic phase and the external aqueous phase employed in nanoparticle preparation. Relatively low loading and encapsulation values were obtained, suggesting that the physical entrapment of drugs in PLGA-mPEG nanoparticles could only be an option in the development of formulations of potent drugs. Only the release of the least water-soluble theobromine was efficiently sustained by its entrapment in the nanoparticles, indicating that the physical entrapment of drugs provides the means for the development of controlled-release PLGA-mPEG nanoparticulate formulations only in the case of drugs with low aqueous solubility.

  19. Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.

    PubMed

    Deng, Yibin; Mathaes, Roman; Winter, Gerhard; Engert, Julia

    2014-10-15

    Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system.

  20. Activation of Latent HIV Using Drug-loaded Nanoparticles

    NASA Astrophysics Data System (ADS)

    Kovochich, Michael

    Antiretroviral therapy is currently only capable of controlling human immunodeficiency virus (HIV) replication, rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T-cells, which persists even in the presence of highly active antiretroviral therapy (HAART). It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However, no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence, novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target, activate primary human CD4+ T-cells, and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the histone deacetylase inhibitor (HDACi) sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. LNP-Bry was further tested for its in vivo biodistribution in both wild type mice (C57 black 6), as well as humanized mice (SCID-hu Thy/Liv, and bone marrow-liver-thymus [BLT]). LNP-Bry accumulated in the spleen and induced the early activation marker CD69 in wild type mice. Taken together, these data demonstrate the ability of nanotechnological approaches to

  1. Preparation, characterization and luminescent properties of dense nano-silica hybrids loaded with 1,8-naphthalic anhydride.

    PubMed

    Wang, Jinpeng; Sun, Jihong; Li, Yuzhen; Wang, Feng

    2014-03-01

    Novel luminescent dense nano-silica hybrid materials (DNSS) modified with different amounts of (3-aminopropyl)triethoxysilane (APTES) and 1,8-naphthalic anhydride (NA) were successfully synthesized via two steps combined with post-grafting methods. Powder X-ray diffraction (XRD), N2-sorption analysis, Fourier transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), photoluminescence (PL) spectroscopy and elemental analysis, as well as time-resolved decays were employed to characterize the resultant hybrid materials. The results revealed that luminescent organic molecules had been successfully loaded onto the amine-modified surface of nano-silica spheres. In addition, their fluorescence intensity and characteristic peak of emission spectra changed with increasing amount of APTES and NA additive. In particular, the characteristic peak showed a red shift from 390 to 450 nm, however, this was inconsistent with results calculated on the basis of the elemental analysis data, most probably because of the dispersion behaviors of NA molecules from the aggregating to the monolayer state. These observations demonstrated the existence of a quantum confinement effectiveness of NA-DNSS samples, and therefore a possible mechanism was put forward.

  2. Photocatalytic and biocidal activities of novel coating systems of mesoporous and dense TiO₂-anatase containing silver nanoparticles.

    PubMed

    Roldán, María V; de Oña, Paula; Castro, Yolanda; Durán, Alicia; Faccendini, Pablo; Lagier, Claudia; Grau, Roberto; Pellegri, Nora S

    2014-10-01

    Here we describe the development of novel nanostructured coating systems with improved photocatalytic and antibacterial activities. These systems comprise a layer of SiO2 followed by a layer of mesoporous or dense TiO2-anatase, and doping with silver nanoparticles (Ag NPs). The coatings were synthesized via a sol-gel technique by combining colloidal Ag NPs with TiO2 and SiO2 sols. The photocatalytic activity was studied through methyl orange decomposition under UV light. Results showed a great increase of photocatalytic activity by Ag NPs doping. The most active photocatalyst corresponded to the Ag-SiO2/TiO2 mesoporous system, associated with the porosity of the coatings and with the decrease of e-h recombination for the presence of Ag NPs. All the TiO2 coatings showed a strong bactericidal activity against planktonic forms of Gram-negative (enterohemorrhagic Escherichia coli) and Gram-positive (Listeria monocytogenes) pathogens, as well as a strong germicidal effect against deadly spores of human gas gangrene- and anthrax-producing bacteria (Clostridium perfringens and Bacillus anthracis, respectively). The bactericidal and sporocidal activity was improved by doping the coatings with Ag NPs, even more when nanoparticles were in the outer layer of TiO2, because they are more accessible to the environment. The mechanisms responsible for the increase of photocatalytic and bactericidal behaviors related to Ag NP doping were studied by spectroscopic ellipsometry, UV-vis spectroscopy, photoluminescence and anodic stripping voltammetry. It was found that the separation of the electron-hole pair contributed to the enhancement of photocatalysis, whereas the effect of the local electric field reinforcement was probably present. A possible involvement of a decrease of band-gap energy and dispersion by silver nanoparticles is ruled out. bactericidal efficacy was increased by Ag(+) ion release. Overall, the results included in this article show that the architecture of the

  3. Evaluation of self-assembled HCPT-loaded PEG- b-PLA nanoparticles by comparing with HCPT-loaded PLA nanoparticles

    NASA Astrophysics Data System (ADS)

    Yang, Xiangrui; Wu, Shichao; Wang, Yange; Li, Yang; Chang, Di; Luo, Yin; Ye, Shefang; Hou, Zhenqing

    2014-12-01

    We present a dialysis technique to prepare the 10-hydroxycamptothecin (HCPT)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly( d, l-lactide) (PEG- b-PLA) and PLA, respectively. Both HCPT-loaded PEG- b-PLA NPs and HCPT-loaded PLA NPs were characterized by differential scanning calorimetry (DSC), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results showed that the HCPT-loaded PEG- b-PLA NPs and HCPT-loaded PLA NPs presented a hydrodynamic particle size of 120.1 and 226.8 nm, with a polydispersity index of 0.057 and 0.207, a zeta potential of -31.2 and -45.7 mV, drug encapsulation efficiency of 44.52% and 44.94%, and drug-loaded content of 7.42% and 7.49%, respectively. The HCPT-loaded PEG- b-PLA NPs presented faster drug release rate compared to the HCPT-loaded PLA NPs. The HCPT-loaded PEG- b-PLA NPs presented higher cytotoxicity than the HCPT-loaded PLA NPs. These results suggested that the HCPT-loaded PEG- b-PLA NPs presented better characteristics for drug delivery compared to HCPT-loaded PLA NPs.

  4. PLGA nanoparticles from nano-emulsion templating as imaging agents: Versatile technology to obtain nanoparticles loaded with fluorescent dyes.

    PubMed

    Fornaguera, C; Feiner-Gracia, N; Calderó, G; García-Celma, M J; Solans, C

    2016-11-01

    The interest in polymeric nanoparticles as imaging systems for biomedical applications has increased notably in the last decades. In this work, PLGA nanoparticles, prepared from nano-emulsion templating, have been used to prepare novel fluorescent imaging agents. Two model fluorescent dyes were chosen and dissolved in the oil phase of the nano-emulsions together with PLGA. Nano-emulsions were prepared by the phase inversion composition (PIC) low-energy method. Fluorescent dye-loaded nanoparticles were obtained by solvent evaporation of nano-emulsion templates. PLGA nanoparticles loaded with the fluorescent dyes showed hydrodynamic radii lower than 40nm; markedly lower than those reported in previous studies. The small nanoparticle size was attributed to the nano-emulsification strategy used. PLGA nanoparticles showed negative surface charge and enough stability to be used for biomedical imaging purposes. Encapsulation efficiencies were higher than 99%, which was also attributed to the nano-emulsification approach as well as to the low solubility of the dyes in the aqueous component. Release kinetics of both fluorescent dyes from the nanoparticle dispersions was pH-independent and sustained. These results indicate that the dyes could remain encapsulated enough time to reach any organ and that the decrease of the pH produced during cell internalization by the endocytic route would not affect their release. Therefore, it can be assumed that these nanoparticles are appropriate as systemic imaging agents. In addition, in vitro toxicity tests showed that nanoparticles are non-cytotoxic. Consequently, it can be concluded that the preparation of PLGA nanoparticles from nano-emulsion templating represents a very versatile technology that enables obtaining biocompatible, biodegradable and safe imaging agents suitable for biomedical purposes.

  5. Critical material attributes (CMAs) of strip films loaded with poorly water-soluble drug nanoparticles: III. Impact of drug nanoparticle loading.

    PubMed

    Krull, Scott M; Moreno, Jacqueline; Li, Meng; Bilgili, Ecevit; Davé, Rajesh N

    2017-03-16

    Polymer strip films have emerged as a robust platform for poorly water-soluble drug delivery. However, the common conception is that films cannot exceed low drug loadings, mainly due to poor drug stability, slow release, and film brittleness. This study explores the ability to achieve high loadings of poorly water-soluble drug nanoparticles in strip films while retaining good mechanical properties and enhanced dissolution rate. Aqueous suspensions containing up to 30wt% griseofulvin nanoparticles were prepared via wet stirred media milling and incorporated into hydroxypropyl methylcellulose (HPMC) films. Griseofulvin loading in films was adjusted to be between 9 and 49wt% in HPMC-E15 films and 30 and 73wt% in HPMC-E4M films by varying the mixing ratio of HPMC solution-to-griseofulvin suspension. All films exhibited good content uniformity and nanoparticle redispersibility up to 50wt% griseofulvin, while E4M films above 50wt% griseofulvin had slightly worse content uniformity and poor nanoparticle redispersibility. Increasing drug loading in films generally required more time to achieve 100% release during dissolution, although polymer-drug clusters dispersed from E4M films above 50wt% griseofulvin, resulting in similar dissolution profiles. While all films exhibited good tensile strength, a significant decrease in percent elongation was observed above 40-50wt% GF, resulting in brittle films.

  6. In vitro effect of imatinib mesylate loaded on polybutylcyanoacrylate nanoparticles on leukemia cell line K562.

    PubMed

    Hasandoost, Leyla; Akbarzadeh, Azim; Attar, Hossein; Heydarinasab, Amir

    2017-05-01

    The study aimed to prepare imatinib mesylate-loaded polybutylcyanoacrylate (PBCA) nanoparticles and evaluate their efficacy on leukemia cell line K562. The formulation was prepared by miniemulsion polymerization technique. Nanoparticles were characterized by dynamic light scattering (DLS), spectrophotometry, Fourier transform infrared spectroscopy (FTIR), dialysis membrane, and 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) techniques. Nanoscale particles with high encapsulation efficiency (86%) and physical entrapment of drug were observed. In addition, nanoparticles showed suitable drug retention capability and potentiate the cytotoxicity effects of imatinib mesylate. Findings of study suggested PBCA nanoparticles are promising carrier for imatinib mesylate delivery to leukemia cell line K562.

  7. Preparation and characterization of carvacrol loaded polyhydroxybutyrate nanoparticles by nanoprecipitation and dialysis methods.

    PubMed

    Shakeri, Fatemeh; Shakeri, Shahryar; Hojjatoleslami, Mohammad

    2014-04-01

    In this investigation, preparation of carvacrol loaded polyhydroxybutyrate (PHB) nanoparticles was performed by nanoprecipitation and dialysis methods. PHB particles were obtained by nanoprecipitation method without and with low concentration of Tween 80 or pluronic as surfactant. Nano- and micro-sized particles were formed with trimodal distribution and large aggregates. Size and distribution of nanoparticles were decreased when concentration of Tween 80 was increased to 1% (v/v) in water as polar phase. PHB nanoparticles had narrow size (157 nm) with monomodal distribution. Nanoparticles, which were prepared by dialysis method had 140 nm in diameter with monomodal distribution. Carvacrol was used as a lipophilic drug and entrapped in optimized nanoparticles formulation by nanoprecipitation and dialysis methods. Entrapment efficacy was 21% and 11%, respectively. Morphology of PHB nanoparticles was spherical. The results of kinetic release study showed that carvacrol was released for at least 3 days. Release kinetic parameters showed a simple Fickian diffusion behavior for both formulations. Carvacrol loaded PHB nanoparticles had good dispersion into the agar medium and antimicrobial activity against Escherichia coli. This study describes the 1st work on loading of carvacrol into the PHB nanoparticles by nanoprecipitation and dialysis methods.

  8. Nanoparticles Containing High Loads of Paclitaxel Silicate Prodrugs: Formulation, Drug Release, and Anti-cancer Efficacy

    PubMed Central

    Han, Jing; Michel, Andrew R.; Lee, Han Seung; Kalscheuer, Stephen; Wohl, Adam; Hoye, Thomas R.; McCormick, Alon V.; Panyam, Jayanth; Macosko, Christopher W.

    2016-01-01

    We have investigated particle size, interior structure, drug release kinetics, and anticancer efficacy of PEG-b-PLGA-based nanoparticles loaded with a series of paclitaxel (PTX) silicate prodrugs [PTX-Si(OR)3]. Silicate derivatization enabled us to adjust the hydrophobicity and hydrolytic lability of the prodrugs by the choice of the alkyl group (R) in the silicate derivatives. The greater hydrophobicity of these prodrugs allows for the preparation of nanoparticles that are stable in aqueous dispersion even when loaded with up to ca. 75 wt% of the prodrug. The hydrolytic lability of silicates allows for facile conversion of prodrugs back to the parent drug, PTX. A suite of eight PTX-silicate prodrugs was investigated; nanoparticles were made by flash nanoprecipitation (FNP) using a confined impingement jet mixer with a dilution step (CIJ-D). The resulting nanoparticles were 80–150 nm in size with a loading level of 47–74 weight percent (wt%) of a PTX-silicate, which corresponds to 36–59 effective wt % of free PTX. Cryogenic transmission electron microscopy images show that particles are typically spherical with a core-shell structure. Prodrug/drug release profiles were measured. Release tended to be slower for prodrugs having greater hydrophobicity and slower hydrolysis rate. Nanoparticles loaded with PTX-silicate prodrugs that hydrolyze most rapidly showed in vitro cytotoxicity similar to that of the parent PTX. Nanoparticles loaded with more labile silicates also tended to show greater in vivo efficacy. PMID:26505116

  9. Nanoparticles Containing High Loads of Paclitaxel-Silicate Prodrugs: Formulation, Drug Release, and Anticancer Efficacy.

    PubMed

    Han, Jing; Michel, Andrew R; Lee, Han Seung; Kalscheuer, Stephen; Wohl, Adam; Hoye, Thomas R; McCormick, Alon V; Panyam, Jayanth; Macosko, Christopher W

    2015-12-07

    We have investigated particle size, interior structure, drug release kinetics, and anticancer efficacy of PEG-b-PLGA-based nanoparticles loaded with a series of paclitaxel (PTX)-silicate prodrugs [PTX-Si(OR)3]. Silicate derivatization enabled us to adjust the hydrophobicity and hydrolytic lability of the prodrugs by the choice of the alkyl group (R) in the silicate derivatives. The greater hydrophobicity of these prodrugs allows for the preparation of nanoparticles that are stable in aqueous dispersion even when loaded with up to ca. 75 wt % of the prodrug. The hydrolytic lability of silicates allows for facile conversion of prodrugs back to the parent drug, PTX. A suite of eight PTX-silicate prodrugs was investigated; nanoparticles were made by flash nanoprecipitation (FNP) using a confined impingement jet mixer with a dilution step (CIJ-D). The resulting nanoparticles were 80-150 nm in size with a loading level of 47-74 wt % (wt %) of a PTX-silicate, which corresponds to 36-59 effective wt % of free PTX. Cryogenic transmission electron microscopy images show that particles are typically spherical with a core-shell structure. Prodrug/drug release profiles were measured. Release tended to be slower for prodrugs having greater hydrophobicity and slower hydrolysis rate. Nanoparticles loaded with PTX-silicate prodrugs that hydrolyze most rapidly showed in vitro cytotoxicity similar to that of the parent PTX. Nanoparticles loaded with more labile silicates also tended to show greater in vivo efficacy.

  10. Silk sericin loaded alginate nanoparticles: Preparation and anti-inflammatory efficacy.

    PubMed

    Khampieng, Thitikan; Aramwit, Pornanong; Supaphol, Pitt

    2015-09-01

    In this study, silk sericin loaded alginate nanoparticles were prepared by the emulsification method followed by internal crosslinking. The effects of various silk sericin loading concentration on particle size, shape, thermal properties, and release characteristics were investigated. The initial silk sericin loadings of 20, 40, and 80% w/w to polymer were incorporated into these alginate nanoparticles. SEM images showed a spherical shape and small particles of about 71.30-89.50 nm. TGA analysis showed that thermal stability slightly increased with increasing silk sericin loadings. FTIR analysis suggested interactions between alginate and silk sericin in the nanoparticles. The release study was performed in acetate buffer at normal skin conditions (pH 5.5; 32 °C). The release profiles of silk sericin exhibited initial rapid release, consequently with sustained release. These silk sericin loaded alginate nanoparticles were further incorporated into topical hydrogel and their anti-inflammatory properties were studied using carrageenan-induced paw edema assay. The current study confirms the hypothesis that the application of silk sericin loaded alginate nanoparticle gel can inhibit inflammation induced by carrageenan.

  11. Structural control of nonlinear optical absorption and refraction in dense metal nanoparticle arrays.

    PubMed

    Kohlgraf-Owens, Dana C; Kik, Pieter G

    2009-08-17

    The linear and nonlinear optical properties of a composite containing interacting spherical silver nanoparticles embedded in a dielectric host are studied as a function of interparticle separation using three dimensional frequency domain simulations. It is shown that for a fixed amount of metal, the effective third-order nonlinear susceptibility of the composite chi((3))(omega) can be significantly enhanced with respect to the linear optical properties, due to a combination of resonant surface plasmon excitation and local field redistribution. It is shown that this geometry-dependent susceptibility enhancement can lead to an improved figure of merit for nonlinear absorption. Enhancement factors for the nonlinear susceptibility of the composite are calculated, and the complex nature of the enhancement factors is discussed.

  12. X-ray excited luminescence of polystyrene composites loaded with SrF2 nanoparticles

    NASA Astrophysics Data System (ADS)

    Demkiv, T. M.; Halyatkin, O. O.; Vistovskyy, V. V.; Hevyk, V. B.; Yakibchuk, P. M.; Gektin, A. V.; Voloshinovskii, A. S.

    2017-03-01

    The polystyrene film nanocomposites of 0.3 mm thickness with embedded SrF2 nanoparticles up to 40 wt% have been synthesized. The luminescent and kinetic properties of the polystyrene composites with embedded SrF2 nanoparticles upon the pulse X-ray excitation have been investigated. The luminescence intensity of the pure polystyrene scintillator film significantly increases when it is loaded with the inorganic SrF2 nanoparticles. The film nanocomposites show fast (∼2.8 ns) and slow (∼700 ns) luminescence decay components typical for a luminescence of polystyrene activators (p-Terphenyl and POPOP) and SrF2 nanoparticles, respectively. It is revealed that the fast decay luminescence component of the polystyrene composites is caused by the excitation of polystyrene by the photoelectrons escaped from the nanoparticles due to photoeffect, and the slow component is caused by reabsorption of the self-trapped exciton luminescence of SrF2 nanoparticles by polystyrene.

  13. Potent engineered PLGA nanoparticles by virtue of exceptionally high chemotherapeutic loadings.

    PubMed

    Enlow, Elizabeth M; Luft, J Christopher; Napier, Mary E; DeSimone, Joseph M

    2011-02-09

    Herein we report the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT (particle replication in nonwetting templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%. The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere.

  14. Magnetic properties of superparamagnetic nanoparticles loaded into silicon nanotubes

    NASA Astrophysics Data System (ADS)

    Granitzer, Petra; Rumpf, Klemens; Gonzalez, Roberto; Coffer, Jeffery; Reissner, Michael

    2014-08-01

    In this work, the magnetic properties of silicon nanotubes (SiNTs) filled with Fe3O4 nanoparticles (NPs) are investigated. SiNTs with different wall thicknesses of 10 and 70 nm and an inner diameter of approximately 50 nm are prepared and filled with superparamagnetic iron oxide nanoparticles of 4 and 10 nm in diameter. The infiltration process of the NPs into the tubes and dependence on the wall-thickness is described. Furthermore, data from magnetization measurements of the nanocomposite systems are analyzed in terms of iron oxide nanoparticle size dependence. Such biocompatible nanocomposites have potential merit in the field of magnetically guided drug delivery vehicles.

  15. Therapeutic effect of apatinib-loaded nanoparticles on diabetes-induced retinal vascular leakage

    PubMed Central

    Jeong, Ji Hoon; Nguyen, Hong Khanh; Lee, Jung Eun; Suh, Wonhee

    2016-01-01

    Apatinib, a novel and selective inhibitor of vascular endothelial growth factor (VEGF) receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF signaling pathway. Given the importance of VEGF in retinal vascular leakage, the present study was designed to investigate whether apatinib-loaded polymeric nanoparticles inhibit VEGF-mediated retinal vascular hyperpermeability and block diabetes-induced retinal vascular leakage. For the delivery of water-insoluble apatinib, the drug was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro paracellular permeability and transendothelial electric resistance assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles significantly inhibited VEGF-induced endothelial hyperpermeability in human retinal microvascular endothelial cells. In addition, they substantially reduced the VEGF-induced junctional loss and internalization of vascular endothelial-cadherin, a major component of endothelial junction complexes. In vivo intravitreal injection of Apa-HSA-PEG nanoparticles in mice blocked VEGF-induced retinal vascular leakage. These in vitro and in vivo data indicated that Apa-HSA-PEG nanoparticles efficiently blocked VEGF-induced breakdown of the blood–retinal barrier. In vivo experiments with streptozotocin-induced diabetic mice showed that an intravitreal injection of Apa-HSA-PEG nanoparticles substantially inhibited diabetes-induced retinal vascular leakage. These results demonstrated, for the first time, that apatinib-loaded nanoparticles may be a promising therapeutic agent for the prevention and treatment of diabetes-induced retinal vascular disorders. PMID:27462154

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

    NASA Astrophysics Data System (ADS)

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

    2017-03-01

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

  17. Dual drug-loaded paclitaxel-thymoquinone nanoparticles for effective breast cancer therapy

    NASA Astrophysics Data System (ADS)

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan

    2015-01-01

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose.

  18. Degradable polyphosphoester-based silver-loaded nanoparticles as therapeutics for bacterial lung infections

    NASA Astrophysics Data System (ADS)

    Zhang, Fuwu; Smolen, Justin A.; Zhang, Shiyi; Li, Richen; Shah, Parth N.; Cho, Sangho; Wang, Hai; Raymond, Jeffery E.; Cannon, Carolyn L.; Wooley, Karen L.

    2015-01-01

    In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate.In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate. Electronic supplementary information (ESI) available: Materials, experimental details, and characterization. See DOI: 10.1039/c4nr07103d

  19. Improved photodynamic action of nanoparticles loaded with indium (III) phthalocyanine on MCF-7 breast cancer cells

    NASA Astrophysics Data System (ADS)

    Souto, Carlos Augusto Zanoni; Madeira, Klésia Pirola; Rettori, Daniel; Baratti, Mariana Ozello; Rangel, Letícia Batista Azevedo; Razzo, Daniel; da Silva, André Romero

    2013-09-01

    Indium (III) phthalocyanine (InPc) was encapsulated into nanoparticles of PEGylated poly( d, l-lactide-co-glycolide) (PLGA-PEG) to improve the photobiological activity of the photosensitizer. The efficacy of nanoparticles loaded with InPc and their cellular uptake was investigated with MCF-7 breast tumor cells, and compared with the free InPc. The influence of photosensitizer (PS) concentration (1.8-7.5 μmol/L), incubation time (1-2 h), and laser power (10-100 mW) were studied on the photodynamic effect caused by the encapsulated and the free InPc. Nanoparticles with a size distribution ranging from 61 to 243 nm and with InPc entrapment efficiency of 72 ± 6 % were used in the experiments. Only the photodynamic effect of encapsulated InPc was dependent on PS concentration and laser power. The InPc-loaded nanoparticles were more efficient in reducing MCF-7 cell viability than the free PS. For a light dose of 7.5 J/cm2 and laser power of 100 mW, the effectiveness of encapsulated InPc to reduce the viability was 34 ± 3 % while for free InPc was 60 ± 7 %. Confocal microscopy showed that InPc-loaded nanoparticles, as well as free InPc, were found throughout the cytosol. However, the nanoparticle aggregates and the aggregates of free PS were found in the cell periphery and outside of the cell. The nanoparticles aggregates were generated due to the particles concentration used in the experiment because of the small loading of the InPc while the low solubility of InPc caused the formation of aggregates of free PS in the culture medium. The participation of singlet oxygen in the photocytotoxic effect of InPc-loaded nanoparticles was corroborated by electron paramagnetic resonance experiments, and the encapsulation of photosensitizers reduced the photobleaching of InPc.

  20. Magnetic Properties of Polyvinyl Alcohol and Doxorubicine Loaded Iron Oxide Nanoparticles for Anticancer Drug Delivery Applications

    PubMed Central

    Nadeem, Muhammad; Ahmad, Munir; Akhtar, Muhammad Saeed; Shaari, Amiruddin; Riaz, Saira; Naseem, Shahzad; Masood, Misbah; Saeed, M. A.

    2016-01-01

    The current study emphasizes the synthesis of iron oxide nanoparticles (IONPs) and impact of hydrophilic polymer polyvinyl alcohol (PVA) coating concentration as well as anticancer drug doxorubicin (DOX) loading on saturation magnetization for target drug delivery applications. Iron oxide nanoparticles particles were synthesized by a reformed version of the co-precipitation method. The coating of polyvinyl alcohol along with doxorubicin loading was carried out by the physical immobilization method. X-ray diffraction confirmed the magnetite (Fe3O4) structure of particles that remained unchanged before and after polyvinyl alcohol coating and drug loading. Microstructure and morphological analysis was carried out by transmission electron microscopy revealing the formation of nanoparticles with an average size of 10 nm with slight variation after coating and drug loading. Transmission electron microscopy, energy dispersive, and Fourier transform infrared spectra further confirmed the conjugation of polymer and doxorubicin with iron oxide nanoparticles. The room temperature superparamagnetic behavior of polymer-coated and drug-loaded magnetite nanoparticles were studied by vibrating sample magnetometer. The variation in saturation magnetization after coating evaluated that a sufficient amount of polyvinyl alcohol would be 3 wt. % regarding the externally controlled movement of IONPs in blood under the influence of applied magnetic field for in-vivo target drug delivery. PMID:27348436

  1. Microbubbles loaded with nanoparticles: a route to multiple imaging modalities.

    PubMed

    Park, Jai Il; Jagadeesan, Dinesh; Williams, Ross; Oakden, Wendy; Chung, Siyon; Stanisz, Greg J; Kumacheva, Eugenia

    2010-11-23

    We report a single-step approach to producing small and stable bubbles functionalized with nanoparticles. The strategy includes the following events occurring in sequence: (i) a microfluidic generation of bubbles from a mixture of CO(2) and a minute amount of gases with low solubility in water, in an aqueous solution of a protein, a polysaccharide, and anionic nanoparticles; (ii) rapid dissolution of CO(2) leading to the shrinkage of bubbles and an increase in acidity of the medium in the vicinity of the bubbles; and (iii) co-deposition of the biopolymers and nanoparticles at the bubble-liquid interface. The proposed approach yielded microbubbles with a narrow size distribution, long-term stability, and multiple functions originating from the attachment of metal oxide, metal, or semiconductor nanoparticles onto the bubble surface. We show the potential applications of these bubbles in ultrasound and magnetic resonance imaging.

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

    PubMed

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

    2016-10-01

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

  3. Two-dimensional ultrathin gold film composed of steadily linked dense nanoparticle with surface plasmon resonance

    PubMed Central

    2012-01-01

    Background Noble metallic nanoparticles have prominent optical local-field enhancement and light trapping properties in the visible light region resulting from surface plasmon resonances. Results We investigate the optical spectral properties and the surface-enhanced Raman spectroscopy of two-dimensional distinctive continuous ultrathin gold nanofilms. Experimental results show that the one- or two-layer nanofilm obviously increases absorbance in PEDOT:PSS and P3HT:PCBM layers and the gold nanofilm acquires high Raman-enhancing capability. Conclusions The fabricated novel structure of the continuous ultrathin gold nanofilms possesses high surface plasmon resonance properties and boasts a high surface-enhanced Raman scattering (SERS) enhancement factor, which can be a robust and cost-efficient SERS substrate. Interestingly, owing to the distinctive morphology and high light transmittance, the peculiar nanofilm can be used in multilayer photovoltaic devices to trap light without affecting the physical thickness of solar photovoltaic absorber layers and yielding new options for solar cell design. PMID:23259927

  4. Continuous separation of protein loaded nanoparticles by simulated moving bed chromatography.

    PubMed

    Satzer, Peter; Wellhoefer, Martin; Jungbauer, Alois

    2014-07-04

    For scale up and efficient production of protein loaded nanoparticles continuous separation by size exclusion chromatography in simulated moving bed (SMB) mode helps do reduce unbound protein concentration and increase yields for perfectly covered particles. Silica nanoparticles were loaded with an excess of beta casein or bovine serum albumin (BSA) and the loaded particles purified by size exclusion chromatography using Sephacryl300 as stationary phase in a four zone SMB. We determined our working points for the SMB from batch separations and the triangle theory described by Mazzotti et al. with an SMB setup of one Sephacryl300 26/70mm column per zone with switch times of 5min for BSA and 7min for beta casein. In the case of BSA the Raffinate contained loaded nanoparticles of 63% purity with 98% recovery and the extract was essentially particle free (95% purity). We showed that the low purity of the Raffinate was only due to BSA multimers present in the used protein solution. In the case of beta casein where no multimers are present we achieved 89% purity and 90% recovery of loaded nanoparticles in the Raffinate and an extract free of particles (92% purity). Using a tangential flow filtration unit with 5kDa cutoff membrane we proved that the extract can be concentrated for recycling of protein and buffer. The calculated space-time-yield for loaded nanoparticles was 0.25g of loaded nanoparticles per hour and liter of used resin. This proves that the presented process is suitable for large scale production for industrial purposes.

  5. High-performance flexible all-solid-state supercapacitors based on densely-packed graphene/polypyrrole nanoparticle papers

    NASA Astrophysics Data System (ADS)

    Yang, Chao; Zhang, Liling; Hu, Nantao; Yang, Zhi; Wei, Hao; Wang, Yanyan; Zhang, Yafei

    2016-11-01

    Graphene-based all-solid-state supercapacitors (ASSSCs) have received increasing attention. It's a great challenge to fabricate high-performance flexible solid-state supercapacitors with high areal and volumetric energy storage capability, superior electron and ion conductivity, robust mechanical flexibility, as well as long term stability. Herein, we report a facile method to fabricate flexible ASSSCs based on densely-packed reduced graphene oxide (rGO)/polypyrrole nanoparticle (PPy NP) hybrid papers with a sandwich framework, which consists of well-separated and continuously-aligned rGO sheets. The incorporation of PPy NPs not only provides pseudocapacitance but also facilitates the infiltration of gel electrolyte. The assembled ASSSCs possess maximum areal and volumetric specific capacitances of 477 mF/cm2 and 94.9 F/cm3 at 0.5 mA/cm2. They also exhibit little capacitance deviation under different bending states, excellent cycling stability, small leakage current and low self-discharge characteristics. Additionally, the maximum areal and volumetric energy densities of 132.5 μWh/cm2 and 26.4 mWh/cm3 are achieved, which indicate that this hybrid paper is a promising candidate for high-performance flexible energy storage devices.

  6. Preparation and characterization of ketoprofen loaded eudragit RS polymeric nanoparticles for controlled release

    NASA Astrophysics Data System (ADS)

    Anh, Nguyen Tuan; Chi, Nguyen T.; Khai Tran, T.; Tuyen Dao, T. P.; Nhan Le, N. T.; Mau Chien, Dang; Hoai, Nguyen To

    2012-12-01

    Nanospheres containing ketoprofen (Keto) and polymer eudragit RS were prepared using an emulsion solvent evaporation method. The ultrasonic probe (VCX500, vibracell) was used as a tool to disperse oil phase into aqueous phase leading to water/oil emulsion. Nanoparticles were successfully prepared and their morphologies and diameters were confirmed by transmission electron microscope (TEM) and dynamic light scattering (DLS), respectively. The result showed that particles were spherical with submicron size. The particle size was dependent on the RS concentration, emulsification tools and the types of organic solvents. For the encapsulation ability, Keto-loaded RS nanoparticle showed 9.8% of Keto in nanoparticle, which was evaluated by high-performance liquid chromatography (HPLC). Moreover, the drug release behavior of Keto-loaded eudragit RS nanoparticle was also investigated in vitro at pH 7.4 and compared to referential profenid.

  7. Plasmon-Induced Water Splitting Using Metallic-Nanoparticle-Loaded Photocatalysts and Photoelectrodes.

    PubMed

    Ueno, Kosei; Oshikiri, Tomoya; Misawa, Hiroaki

    2016-01-18

    Visible- and near-infrared-light-driven water splitting, which splits water molecules to generate hydrogen and oxygen gases, is a significant subject in artificial photosynthesis with the goal of achieving a low-carbon society. In recent years, considerable attention has been paid to studies on the development of a plasmon-induced water-splitting system responding to visible light. In this review, we categorized water-splitting systems as gold-nanoparticle-loaded semiconductor photocatalytic particles system and metallic-nanoparticles-loaded semiconductor photoelectrode systems, and introduce the latest studies according to these categories. Especially, we describe the studies that optimize a material or a structural design of metallic-nanoparticle-loaded semiconductor photoelectrodes and consider a whole water-splitting system, including a cathode design. Furthermore, we discuss important points when studying plasmon-induced water splitting, and we describe a methodology that enhances plasmon-induced water-splitting efficiency.

  8. Synthesis of methylprednisolone loaded ibuprofen modified inulin based nanoparticles and their application for drug delivery.

    PubMed

    Zhang, Luzhong; Li, Yue; Wang, Caiping; Li, Guicai; Zhao, Yahong; Yang, Yumin

    2014-09-01

    Ibuprofen modified inulin was synthesized through a direct esterification linkage in which the in situ activation of the carboxylic acid with N,N'-carbonyldiimidazole was carried out. The critical aggregation concentration of the ibuprofen modified inulin was determined by using pyrene as the fluorescence probe. Methylprednisolone loaded nanoparticles were prepared by the self-assembly of the ibuprofen modified inulin copolymer and methylprednisolone. In vitro release of the methylprednisolone and the cytotoxicity of the methylprednisolone loaded nanoparticles against RSC-96 cells were evaluated. Since the ibuprofen and methylprednisolone could stimulate a significant neurite growth and diminish the human neurological deficits after the spinal cord injury, the methylprednisolone loaded nanoparticles based on the ibuprofen modified inulin copolymer may have a great potential in the synergetic effect treatment for spinal cord injury.

  9. Prostate-targeted biodegradable nanoparticles loaded with androgen receptor silencing constructs eradicate xenograft tumors in mice

    PubMed Central

    Yang, Jun; Xie, Sheng-Xue; Huang, Yiling; Ling, Min; Liu, Jihong; Ran, Yali; Wang, Yanlin; Thrasher, J Brantley; Berkland, Cory; Li, Benyi

    2012-01-01

    Background Prostate cancer is the major cause of cancer death in men and the androgen receptor (AR) has been shown to play a critical role in the progression of the disease. Our previous reports showed that knocking down the expression of the AR gene using a siRNA-based approach in prostate cancer cells led to apoptotic cell death and xenograft tumor eradication. In this study, we utilized a biodegradable nanoparticle to deliver the therapeutic AR shRNA construct specifically to prostate cancer cells. Materials & methods The biodegradable nanoparticles were fabricated using a poly(dl-lactic-co-glycolic acid) polymer and the AR shRNA constructs were loaded inside the particles. The surface of the nanoparticles were then conjugated with prostate-specific membrane antigen aptamer A10 for prostate cancer cell-specific targeting. Results A10-conjugation largely enhanced cellular uptake of nanoparticles in both cell culture- and xenograft-based models. The efficacy of AR shRNA encapsulated in nanoparticles on AR gene silencing was confirmed in PC-3/AR-derived xenografts in nude mice. The therapeutic property of A10-conjugated AR shRNA-loaded nanoparticles was evaluated in xenograft models with different prostate cancer cell lines: 22RV1, LAPC-4 and LNCaP. Upon two injections of the AR shRNA-loaded nanoparticles, rapid tumor regression was observed over 2 weeks. Consistent with previous reports, A10 aptamer conjugation significantly enhanced xenograft tumor regression compared with nonconjugated nanoparticles. Discussion These data demonstrated that tissue-specific delivery of AR shRNA using a biodegradable nanoparticle approach represents a novel therapy for life-threatening prostate cancers. PMID:22583574

  10. Wettability alteration properties of fluorinated silica nanoparticles in liquid-loaded pores: An atomistic simulation

    NASA Astrophysics Data System (ADS)

    Sepehrinia, Kazem; Mohammadi, Aliasghar

    2016-05-01

    Control over the wettability of reservoir rocks is of crucial importance for enhancing oil and gas recovery. In order to develop chemicals for controlling the wettability of reservoir rocks, we present a study of functionalized silica nanoparticles as candidates for wettability alteration and improved gas recovery applications. In this paper, properties of fluorinated silica nanoparticles were investigated in water or decane-loaded pores of mineral silica using molecular dynamics simulation. Trifluoromethyl groups as water and oil repellents were placed on the nanoparticles. Simulating a pore in the presence of trapped water or decane molecules leads to liquid bridging for both of the liquids. Adsorption of nanoparticles on the pore wall reduces the density of liquid molecules adjacent to the wall. The density of liquid molecules around the nanoparticles decreases significantly with increasing the number of trifluoromethyl groups on the nanoparticles' surfaces. An increased hydrophobicity of the pore wall was observed in the presence of adsorbed fluorinated silica nanoparticles. Also, it is observed that increasing the number of the trifluoromethyl groups results in weakening of liquid bridges. Moreover, the free energy of adsorption on mineral surface was evaluated to be more favorable than that of aggregation of nanoparticles, which suggests nanoparticles adsorb preferably on mineral surface.

  11. Self-assembled silk fibroin nanoparticles loaded with binary drugs in the treatment of breast carcinoma

    PubMed Central

    Li, Hui; Tian, Jian; Wu, Anqing; Wang, Jiamin; Ge, Cuicui; Sun, Ziling

    2016-01-01

    Self-assembled nanoparticles of the natural polymer, silk fibroin (SF), are a very promising candidate in drug delivery due to their biocompatible and biodegradable properties. In this study, SF nanoparticles loaded with 5-fluorouracil (5-FU) and curcumin with size 217±0.4 nm and with a loading efficacy of 45% and 15% for 5-FU and curcumin, respectively, were prepared. The in vitro release effect of 5-FU and curcumin from nanoparticles was evaluated as ~100% and ~5%, respectively. It has been revealed that the application of such a nanodrug can increase the level of reactive oxygen species, which in turn induces apoptosis of cancer cells in vitro. Animal studies have shown that tumors could be noticeably reduced after being injected with the drug-entrapped nanoparticles. More apoptotic cells were found after 7 days of treatment with SF nanoparticles by a hematoxylin–eosin staining assay. These results demonstrate the future potential of nanoparticle-loaded binary drugs in the treatment of breast cancer. PMID:27621628

  12. Self-assembled silk fibroin nanoparticles loaded with binary drugs in the treatment of breast carcinoma.

    PubMed

    Li, Hui; Tian, Jian; Wu, Anqing; Wang, Jiamin; Ge, Cuicui; Sun, Ziling

    Self-assembled nanoparticles of the natural polymer, silk fibroin (SF), are a very promising candidate in drug delivery due to their biocompatible and biodegradable properties. In this study, SF nanoparticles loaded with 5-fluorouracil (5-FU) and curcumin with size 217±0.4 nm and with a loading efficacy of 45% and 15% for 5-FU and curcumin, respectively, were prepared. The in vitro release effect of 5-FU and curcumin from nanoparticles was evaluated as ~100% and ~5%, respectively. It has been revealed that the application of such a nanodrug can increase the level of reactive oxygen species, which in turn induces apoptosis of cancer cells in vitro. Animal studies have shown that tumors could be noticeably reduced after being injected with the drug-entrapped nanoparticles. More apoptotic cells were found after 7 days of treatment with SF nanoparticles by a hematoxylin-eosin staining assay. These results demonstrate the future potential of nanoparticle-loaded binary drugs in the treatment of breast cancer.

  13. Silymarin-loaded solid nanoparticles provide excellent hepatic protection: physicochemical characterization and in vivo evaluation

    PubMed Central

    Yang, Kwan Yeol; Hwang, Du Hyeong; Yousaf, Abid Mehmood; Kim, Dong Wuk; Shin, Young-Jun; Bae, Ok-Nam; Kim, Yong-II; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

    2013-01-01

    Background The purpose of this study was to develop a novel silymarin-loaded solid nanoparticle system with enhanced oral bioavailability and an ability to provide excellent hepatic protection for poorly water-soluble drugs using Shirasu porous glass (SPG) membrane emulsification and a spray-drying technique. Methods A silymarin-loaded liquid nanoemulsion was formulated by applying the SPG membrane emulsification technique. This was further converted into solid state nanosized particles by the spray-drying technique. The physicochemical characteristics of these nanoparticles were determined by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction. Their dissolution, bioavailability, and hepatoprotective activity in rats were assessed by comparison with a commercially available silymarin-loaded product. Results Formulation of a silymarin-loaded nanoemulsion, comprising silymarin, castor oil, polyvinylpyrrolidone, Transcutol HP, Tween 80, and water at a weight ratio of 5/3/3/1.25/1.25/100 was accomplished using an SPG membrane emulsification technique at an agitator speed of 700 rpm, a feed pressure of 15 kPa, and a continuous phase temperature of 25°C. This resulted in generation of comparatively uniform emulsion globules with a narrow size distribution. Moreover, the silymarin-loaded solid nanoparticles, containing silymarin/castor oil/polyvinylpyrrolidone/Transcutol HP/Tween 80 at a weight ratio of 5/3/3/1.25/1.25, improved about 1,300-fold drug solubility and retained a mean size of about 210 nm. Silymarin was located in unaltered crystalline form in the nanoparticles. The drug dissolved rapidly from the nanoparticles, reaching nearly 80% within 15 minutes, indicating three-fold better dissolution than that of the commercial product. Further, the nanoparticles showed a considerably shorter time to peak concentration, a greater area under the concentration-time curve, and a higher maximum concentration of silymarin compared

  14. 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

  15. Photodynamic effects of methylene blue-loaded polymeric nanoparticles on dental plaque bacteria

    PubMed Central

    Klepac-Ceraj, Vanja; Patel, Niraj; Song, Xiaoqing; Holewa, Colleen; Patel, Chitrang; Kent, Ralph; Amiji, Mansoor M.; Soukos, Nikolaos S.

    2011-01-01

    Background and Objectives Photodynamic therapy (PDT) is increasingly being explored for treatment of oral infections. Here, we investigate the effect of PDT on human dental plaque bacteria in vitro using methylene blue (MB)-loaded poly(lactic-co-glycolic) (PLGA) nanoparticles with a positive or negative charge and red light at 665 nm. Study Design/Materials and Methods Subgingival plaque samples were obtained from 14 patients with chronic periodontitis. Suspensions of plaque microorganisms from seven patients were sensitized with anionic, cationic PLGA nanoparticles (50 μg/ml equivalent to MB) or free MB (50 μg/ml) for 20 min followed by exposure to red light for 5 min with a power density of 100 mW/cm2. Polymicrobial oral biofilms, which were developed on blood agar in 96-well plates from dental plaque inocula obtained from seven patients, were also exposed to PDT as above. Following the treatment, survival fractions were calculated by counting the number of colony-forming units. Results The cationic MB-loaded nanoparticles exhibited greater bacterial phototoxicity in both planktonic and biofilm phase compared to anionic MB-loaded nanoparticles and free MB, but results were not significantly different (p>0.05). Conclusion Cationic MB-loaded PLGA nanoparticles have the potential to be used as carriers of MB for PDT systems. PMID:22057487

  16. Characterization and carboplatin loaded chitosan nanoparticles for the chemotherapy against breast cancer in vitro studies.

    PubMed

    Khan, Md Asad; Zafaryab, Md; Mehdi, Syed Hassan; Quadri, Javed; Rizvi, M Moshahid A

    2017-04-01

    Aim of the studies to synthesized chitosan nanoparticles by an ionic interaction procedure. The nanoparticles were characterized by physicochemical methods like, DLS, TEM, Surface potential measurements, FT-IR and DSC. The average particle size of chitosan and carboplatin nanoparticles was found to be 277.25±11.37nm and 289.30±8.15nm and zeta potential was found to be 31±3.14mV and 33±2.15mV respectively with low polydispersity index. The maximum entrapment of carboplatin in nanoparticles was a spherical shape with a positive charge. The maximum encapsulation and loading efficiencies of carboplatin (5mg/ml) were obtained to be 58.43% and 13.27% respectively. The nanocarboplatin was better blood compatibility as compared to chitosan nanoparticles. Finally, the cytotoxic effects of the carboplatin loaded chitosan nanoparticles were tested in-vitro against breast cancer (MCF-7) cell lines. Our studies showed that the chitosan nanoparticles could be used as a promising candidate for drug delivery for the therapeutic treatment of breast cancer.

  17. Preparation and in vitro investigation of antigastric cancer activities of carvacrol-loaded human serum albumin nanoparticles.

    PubMed

    Maryam, Keshavarzi; Shakeri, Shahryar; Kiani, Keyhaneh

    2015-10-01

    In this study, carvacrol-loaded human serum albumin (HSA) nanoparticles were developed and characterised. Nanoparticles were prepared by desolvation and emulsion/desolvation methods. Encapsulation efficiency (EE%) and loading capacity (LC%) of nanoparticles prepared by desolvation method were 48.4 and 45.1%, respectively. Carvacrol-loaded nanoparticles had 132±42 nm in diameter with monomodal distribution. Carvacrol-loaded nanoparticles which is prepared by emulsion/desolvation method had EE% and LC% of 32 and 32.3%, respectively, and 230±38 nm in size. The release of carvacrol from nanoparticles was monitored in phosphate-buffered saline (pH=7.4), 100 rpm at 37°C for 10 days. About 21.4% of carvacrol was released after 3 h from nanoparticles that were prepared by desolvation method. In emulsion/desolvation method, 26.8% of total carvacrol was released during 3 h of incubation. Cytotoxicity effect of loaded carvacrol was assessed by 3-[4, 5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test on gastric cancer cells line (AGS). Cell line was exposed to the free carvacrol, unloaded and carvacrol-loaded nanoparticles for 48 h. The half maximal inhibitory concentration (IC50) for free carvacrol, unloaded and carvacrol-loaded HSA nanoparticles were 30, 1070 and 120 µg/ml, respectively. In conclusion, the results of this study showed applications of HSA nanoparticles for entrapment of carvacrol and antigastric cancer activity. Moreover, loading of carvacrol in combination with chemotherapy agents into the HSA nanoparticles may treat cancer cells better than single drug loaded nanoparticles.

  18. Evaluation of aminoalkylmethacrylate nanoparticles as colloidal drug carrier systems. Part II: characterization of antisense oligonucleotides loaded copolymer nanoparticles.

    PubMed

    Zobel, H P; Stieneker, F; Atmaca-Abdel Aziz, S; Gilbert, M; Werner, D; Noe, C R; Kreuter, J; Zimmer, A

    1999-07-01

    Aminoalkylmethacrylate methylmethacrylate copolymer nanoparticles were evaluated for their use as potential drug carrier systems. Their cytotoxicity, as well as the loading of antisense oligonucleotides that were employed as anionic model drugs depended on the substitution of the basic aminoalkyl copolymer. Toxic influences on the integrity of cell membranes depended on aminoalkyl groups located on the particle surfaces. Toxicity was observed either by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays using African green monkey kidney (AGMK) cells or by a hemolysis test, where the efflux of haemoglobin from disrupted erythrocytes was measured. The cytotoxic effects were increased by the elongation of the N-alkyl chain by four additional methylene groups. Lipophilic polymethylmethacrylate (PMMA) homopolymer nanoparticles showed a negative surface charge and, therefore, were not suitable for the adsorption of anionic drugs. The surface charge was changed to positive values by the incorporation of basic monomers. Consequently, the loading efficacy was increased by raising the basic copolymer portion. Additionally, a pH-dependent loading behaviour of oligonucleotides was observed. Substitution of the amino nitrogen protons by methyl groups led to a decreased oligonucleotide loading and to a reduced cytotoxicity. Nanoparticles with permanent positively charged quarternary ammonium groups showed a high pH-independent loading efficacy, but also possessed a high cytotoxic potential. In this study, cationic copolymer nanoparticles containing 30% (w/w) methylaminoethyl-methacrylate (MMAEMC) were found to be optimal with regard to biocompatibility and carrier properties for hydrophilic anionic antisense oligonucleotides. A significant portion of adsorbed oligonucleotides were protected from enzymatic degradation. The cellular uptake of oligonucleotides into Vero cells was significantly enhanced by this methylaminoethyl-methacrylate derivative.

  19. Fabrication of magnetic nanoparticles with controllable drug loading and release through a simple assembly approach.

    PubMed

    Fang, Chen; Kievit, Forrest M; Veiseh, Omid; Stephen, Zachary R; Wang, Tingzhong; Lee, Donghoon; Ellenbogen, Richard G; Zhang, Miqin

    2012-08-20

    Nanoparticle-based cancer therapeutics promises to improve drug delivery safety and efficacy. However, fabrication of consistent theranostic nanoparticles with high and controllable drug loading remains a challenge, primarily due to the cumbersome, multi-step synthesis processes conventionally applied. Here, we present a simple and highly controllable method for assembly of theranostic nanoparticles, which may greatly reduce batch-to-batch variation. The major components of this nanoparticle system include a superparamagnetic iron oxide nanoparticle (SPION), a biodegradable and pH-sensitive poly (beta-amino ester) (PBAE) copolymer, a chemotherapeutic agent doxorubicin (DOX). Here the polymer pre-loaded with drug is directly assembled to the surface of SPIONs forming a drug loaded nanoparticle (NP-DOX). NP-DOX demonstrated a high drug loading efficiency of 679 μg DOX per mg iron, sustained stability in cell culture media up to 7 days, and a strong r(2) relaxivity of 146 mM(-1)•s(-1) for magnetic resonance imaging (MRI). The drug release analysis of NP-DOX showed fast DOX release at pH 5.5 and 6.4 (as in endosomal environment) and slow release at pH 7.4 (physiological condition), demonstrating pH-sensitive drug release kinetics. In vitro evaluation of NP-DOX efficacy using drug-resistant C6 glioma cells showed a 300% increase in cellular internalization at 24h post-treatment and 65% reduction of IC50 at 72 h post-treatment when compared to free DOX. These nanoparticles could serve as a foundation for building smart theranostic formulations for sensitive detection through MRI and effective treatment of cancer by controlled drug release.

  20. The Antidepressant Effect of L-Tyrosine-Loaded Nanoparticles: Behavioral Aspects

    PubMed Central

    Alabsi, Abdelrahman; Khoudary, Adel Charbel; Abdelwahed, Wassim

    2016-01-01

    Background Depression has been linked to disruption in the cerebral levels of specific neurotransmitters. L-tyrosine is a precursor of more than one of the neurotransmitters affected by depression. Even though setbacks of monoamines precursors include high doses and low efficiency, many studies have suggested using L-tyrosine as antidepressant. Purpose The purpose of this study was to explore the possible antidepressant effect of L-tyrosine loaded in a nanoparticle-designed formula, using behavioral tests in acute and chronic mild stress (CMS) models of depression in rats. Methods Animals from both models received L-tyrosine-loaded nanoparticles (5 or 10 mg/kg), L-tyrosine solution (10 mg/kg), fluoxetine (10 mg/kg) or placebo daily for 21 days. Rats from the acute stress model of depression were subjected to open field and forced swim tests (FSTs). For the CMS model, sucrose preference test was carried out. Additionally, 3 profiles of the nanoparticles formula were tested in vitro. High dissolution rate and entrapment efficiency were obtained from the in vitro tests. Moreover, L-tyrosine-loaded nanoparticles 10 mg/kg and fluoxetine 10 mg/kg significantly decreased the immobility time in the FST, concomitant with restoration of the basal levels of locomotor activity, distance travelled and rearing counts. Also, an increase of the sucrose consumption was recorded in the sucrose preference test after treatment with L-tyrosine-loaded nanoparticles 10 mg/kg and fluoxetine 10 mg/kg. Results The positive results after treatment with L-tyrosine-loaded nanoparticles, through behavioral tests, are probably attributed to restorating the basal levels of the cerebral noradrenaline. Conclusion The effects of L-tyrosine administration on the cerebral levels of tyrosine hydroxylase and corticotropin-releasing factor should be further investigated. PMID:27647959

  1. 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.

  2. Comparative Evaluation of Nimesulide-Loaded Nanoparticles for Anticancer Activity Against Breast Cancer Cells.

    PubMed

    Sengel-Turk, Ceyda Tuba; Hascicek, Canan; Bakar, Filiz; Simsek, Elif

    2017-02-01

    Recent clinical and epidemiological researches have declared that non-steroidal anti-inflammatory agents may display as antineoplastic agents and indicate pro-apoptotic and antiproliferative effects on cancer cells. The major purpose of this research was to develop a novel poly(ethyleneglycol)-block-poly(ε-caprolactone) (PEG-b-PCL) nano-sized particles encapsulated with nimesulide (NMS), a selective COX-2 inhibitor, and to evaluate its anticancer activity against MCF-7 breast cancer cells. NMS-encapsulated PEG-b-PCL nanoparticles were fabricated using three different production techniques: (i) by emulsion-solvent evaporation using a high shear homogenizer, (ii) by emulsion-solvent evaporation using an ultrasonicator, and (iii) by nanoprecipitation. Nanoparticles were evaluated with respect to the entrapment efficiency, size characteristics, drug release rates, thermal behavior, cell viability assays, and apoptosis. The resulting nanoparticles were found to be spherical shapes with negative surface charges. The average diameter of all nanoparticles ranged between 148.5 and 307.2 nm. In vitro release profiles showed that all nanoparticles exhibited a biphasic release pattern. NMS-loaded PEG-b-PCL nanoparticles demonstrated significant anticancer activity against MCF-7 breast cancer cells in a dose-dependent manner, and the effects of nanoparticles on cell proliferation were significantly affected by the preparation techniques. The nanoparticles developed in this work displayed higher potential for the NMS delivery against breast cancer treatment for the future.

  3. Transistor memory devices with large memory windows, using multi-stacking of densely packed, hydrophobic charge trapping metal nanoparticle array

    NASA Astrophysics Data System (ADS)

    Cho, Ikjun; Kim, Beom Joon; Ryu, Sook Won; Cho, Jeong Ho; Cho, Jinhan

    2014-12-01

    Organic field-effect transistor (OFET) memories have rapidly evolved from low-cost and flexible electronics with relatively low-memory capacities to memory devices that require high-capacity memory such as smart memory cards or solid-state hard drives. Here, we report the high-capacity OFET memories based on the multilayer stacking of densely packed hydrophobic metal NP layers in place of the traditional transistor memory systems based on a single charge trapping layer. We demonstrated that the memory performances of devices could be significantly enhanced by controlling the adsorption isotherm behavior, multilayer stacking structure and hydrophobicity of the metal NPs. For this study, tetraoctylammonium (TOA)-stabilized Au nanoparticles (TOA-AuNPs) were consecutively layer-by-layer (LbL) assembled with an amine-functionalized poly(amidoamine) dendrimer (PAD). The formed (PAD/TOA-AuNP)n films were used as a multilayer stacked charge trapping layer at the interface between the tunneling dielectric layer and the SiO2 gate dielectric layer. For a single AuNP layer (i.e. PAD/TOA-AuNP)1) with a number density of 1.82 × 1012 cm-2, the memory window of the OFET memory device was measured to be approximately 97 V. The multilayer stacked OFET memory devices prepared with four AuNP layers exhibited excellent programmable memory properties (i.e. a large memory window (ΔVth) exceeding 145 V, a fast switching speed (1 μs), a high program/erase (P/E) current ratio (greater than 106) and good electrical reliability) during writing and erasing over a relatively short time scale under an operation voltage of 100 V applied at the gate.

  4. Transistor memory devices with large memory windows, using multi-stacking of densely packed, hydrophobic charge trapping metal nanoparticle array.

    PubMed

    Cho, Ikjun; Kim, Beom Joon; Ryu, Sook Won; Cho, Jeong Ho; Cho, Jinhan

    2014-12-19

    Organic field-effect transistor (OFET) memories have rapidly evolved from low-cost and flexible electronics with relatively low-memory capacities to memory devices that require high-capacity memory such as smart memory cards or solid-state hard drives. Here, we report the high-capacity OFET memories based on the multilayer stacking of densely packed hydrophobic metal NP layers in place of the traditional transistor memory systems based on a single charge trapping layer. We demonstrated that the memory performances of devices could be significantly enhanced by controlling the adsorption isotherm behavior, multilayer stacking structure and hydrophobicity of the metal NPs. For this study, tetraoctylammonium (TOA)-stabilized Au nanoparticles (TOA-Au(NPs)) were consecutively layer-by-layer (LbL) assembled with an amine-functionalized poly(amidoamine) dendrimer (PAD). The formed (PAD/TOA-Au(NP))(n) films were used as a multilayer stacked charge trapping layer at the interface between the tunneling dielectric layer and the SiO2 gate dielectric layer. For a single AuNP layer (i.e. PAD/TOA-Au(NP))1) with a number density of 1.82 × 10(12) cm(-2), the memory window of the OFET memory device was measured to be approximately 97 V. The multilayer stacked OFET memory devices prepared with four Au(NP) layers exhibited excellent programmable memory properties (i.e. a large memory window (ΔV(th)) exceeding 145 V, a fast switching speed (1 μs), a high program/erase (P/E) current ratio (greater than 10(6)) and good electrical reliability) during writing and erasing over a relatively short time scale under an operation voltage of 100 V applied at the gate.

  5. Coupled equilibria of a self-associating drug loaded into polymeric nanoparticles.

    PubMed

    Fan, H Y; Raval, G; Shalviri, A; May, S; Wu, X Y; Heerklotz, H

    2015-04-01

    Doxorubicin (DOX) and other anti-cancer drugs are often formulated using nanoparticles for passive or active targeting and reducing detrimental side effects. Anionic polymers have been shown to effectively facilitate loading of cationic DOX hydrochloride into nanoparticles with high efficiency. One powerful method to study DOX loading into anionic polymeric nanoparticles has been isothermal titration calorimetry (ITC), but the curves are complex and were previously interpreted in a largely qualitative manner only. Here we present detailed quantitative modelling of such ITC data, corroborated by zeta potential measurements and dynamic light scattering. The model takes into account 3 coupled equilibria. First, DOX self-associates in solution to dimers and larger aggregates. This effect is modelled in terms of the stepwise aggregation model. Second, DOX binds with a 1:1 stoichiometry to the carboxylic acids in the polymer at low salt. At about 33% saturation, the nanoparticles collapse in size and the enthalpy of further binding becomes less exothermic. Third, free DOX also stacks onto polymer-bound DOX. This stacking effect is very weak and hardly detected by ITC. It is, however, revealed by a positive zeta potential. The present work demonstrates the power of combining ITC with light scattering and zeta potential measurements for studying the thermodynamics of drug loading into polymeric nanoparticles.

  6. Nanoparticle Drug Loading as a Design Parameter to Improve Docetaxel Pharmacokinetics and Efficacy

    PubMed Central

    Chu, Kevin S.; Schorzman, Allison N.; Finniss, Mathew C.; Bowerman, Charles J.; Peng, Lei; Luft, J. Christopher; Madden, Andrew; Wang, Andrew Z.; Zamboni, William C.; DeSimone, Joseph M.

    2013-01-01

    Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel. PMID:23899444

  7. Targeting Paclitaxel-Loaded Nanoparticles to Ovarian Cancer

    DTIC Science & Technology

    2010-05-01

    Selective Integrin avb3 Antagonists. J Am Chem Soc. 1996;118:7461-72. 11. Jolimaitre P , Poirier C, Richard A, Blanpain A, Delord B, Roux D, et al...Tissue-penetrating delivery of compounds and nanoparticles into tumors. Cancer Cell. 2009;16:510-20. 15. Laakkonen P , Porkka K, Hoffman JA, Ruoslahti...E. A tumor-homing peptide with a targeting specificity related to lymphatic vessels. Nat Med. 2002;8:751-5. 16. Laakkonen P , Akerman ME, Biliran H

  8. Artemisinin loaded chitosan magnetic nanoparticles for theefficient targeting to the breast cancer.

    PubMed

    Natesan, Subramanian; Ponnusamy, Chandrasekar; Sugumaran, Abimanyu; Chelladurai, Senthilkumar; Palaniappan, Sharavanan Shanmugam; Palanichamy, Rajaguru

    2017-03-27

    Artemisinin, a natural anti-malarial agent, also possesses anti-proliferative and anti-angiogenic activity in cancer cells with very low toxicity to normal healthy cells. Drug loaded magnetic nanoparticlesby using external magnetic field could selectively accumulate the drug at the target site and thereby reduce the doses required to achieve therapeutic concentration which may otherwise produce serious side effects on healthy cells. In the present study the artemisinin magnetic nanoparticles were successfully formulated using chitosan by ionic-gelation method. The developed magnetic nanoparticles of artemisinin were smooth and spherical in natureand their size was in the range of 349 to 445nm. The polydispersity index (PDI) and zeta potential of the formulated nanoparticles were in the range of 0.373 to 0.908 and -9.34 to -33.3 respectively. They showed 55% to 62.5% of drug encapsulation efficiency and 20% to 25% drug loading capacity. Around 62% to 78% of artemisinin was released from the artemisinin magnetic nanoparticles over the period of 48h. On application of physiologically acceptable external magnetic field, FITC conjugated artemisinin magnetic nanoparticles showed an enhanced accumulation of nanoparticles in the 4T1 breast tumour tissues of BALB/c mice model.

  9. 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.

  10. Prolonged Prevention of Retinal Degeneration with Retinylamine Loaded Nanoparticles

    PubMed Central

    Puntel, Anthony; Maeda, Akiko; Golczak, Marcin; Gao, Song-Qi; Yu, Guanping; Palczewski, Krzysztof; Lu, Zheng-Rong

    2015-01-01

    Retinal degeneration impairs the vision of millions in all age groups worldwide. Increasing evidence suggests that the etiology of many retinal degenerative diseases is associated with impairment in biochemical reactions involved in the visual cycle, a metabolic pathway responsible for regeneration of the visual chromophore (11-cis-retinal). Inefficient clearance of toxic retinoid metabolites, especially all-trans-retinal, is considered responsible for photoreceptor cytotoxicity. Primary amines, including retinylamine, are effective in lowing the concentration of all-trans-retinal within the retina and thus prevent retina degeneration in mouse models of human retinopathies. Here we achieved prolonged prevention of retinal degeneration by controlled delivery of retinylamine to the eye from polylactic acid nanoparticles in Abca4−/−Rdh8−/− (DKO) mice, an animal model of Stargardt disease/age-related macular degeneration. Subcutaneous administration of the nanoparticles containing retinylamine provided a constant supply of the drug to the eye for about a week and resulted in effective prolonged prevention of light-induced retinal degeneration in DKO mice. Retinylamine nanoparticles hold promise for prolonged prophylactic treatment of human retinal degenerative diseases, including Stargardt disease and age-related macular degeneration. PMID:25617130

  11. Expansion and improvement of the FORMA system for response and load analysis. Volume 2A: Listings, dense FORMA subroutines

    NASA Technical Reports Server (NTRS)

    Wohlen, R. L.

    1976-01-01

    A listing of the source deck of each dense FORMA subroutine is given to remove the 'black-box' aura of the subroutines so that the analyst may better understand the detail operations of each subroutine. The FORTRAN 4 programming language is used throughout.

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

    NASA Astrophysics Data System (ADS)

    Afolabi, Afola we mi

    One way to improve the bioavailability of poorly water-soluble drugs is to reduce particle size of drug crystals down to nanoscale via wet stirred media milling. An increase in total surface area per mass loading of the drug and specific surface area as well as reduced external mass transfer resistance allow a faster dissolution of the poorly-water soluble drug from nanocrystals. To prevent aggregation of nanoparticles, polymers and surfactants are dissolved in water acting as stabilizers via adsorption onto the drug crystals. In the last two decades, ample experimental data were generated in the area of wet stirred media milling for the production of drug nanoparticle suspensions. However, a fundamental scientific/engineering understanding of various aspects of this process is still lacking. These challenges include elucidation of the governing mechanism(s) during nanoparticle formation and physical stabilization of the nanosuspension with the use of polymers and surfactants (formulation parameters), understanding the impact of process parameters in the context of first-principle-based models, and production of truly nanosized drug particles (10-100 nm) with acceptable physical stability and minimal contamination with the media. Recirculation mode of milling operation, where the drug suspension in a holding tank continuously circulates through the stirred media mill, has been commonly used in lab, pilot, and commercial scales. Although the recirculation is continuous, the recirculation operation mode is overall a batch operation, requiring significant number of batches for a large-volume pharmaceutical product. Hence, development and investigation of a truly continuous process should offer significant advantages. To explain the impact of some of the processing parameters, stress intensity and stress number concepts were widely used in literature, which do not account for the effect of suspension viscosity explicitly. The impact of the processing parameters has not

  13. An interdisciplinary computational/experimental approach to evaluate drug-loaded gold nanoparticle tumor cytotoxicity

    PubMed Central

    Curtis, Louis T; England, Christopher G; Wu, Min; Lowengrub, John; Frieboes, Hermann B

    2016-01-01

    Aim: Clinical translation of cancer nanotherapy has largely failed due to the infeasibility of optimizing the complex interaction of nano/drug/tumor/patient parameters. We develop an interdisciplinary approach modeling diffusive transport of drug-loaded gold nanoparticles in heterogeneously-vascularized tumors. Materials & methods: Evaluated lung cancer cytotoxicity to paclitaxel/cisplatin using novel two-layer (hexadecanethiol/phosphatidylcholine) and three-layer (with high-density-lipoprotein) nanoparticles. Computer simulations calibrated to in-vitro data simulated nanotherapy of heterogeneously-vascularized tumors. Results: Evaluation of free-drug cytotoxicity between monolayer/spheroid cultures demonstrates a substantial differential, with increased resistance conferred by diffusive transport. Nanoparticles had significantly higher efficacy than free-drug. Simulations of nanotherapy demonstrate 9.5% (cisplatin) and 41.3% (paclitaxel) tumor radius decrease. Conclusion: Interdisciplinary approach evaluating gold nanoparticle cytotoxicity and diffusive transport may provide insight into cancer nanotherapy. PMID:26829163

  14. Potent Engineered PLGA Nanoparticles by Virtue of Exceptionally High Chemotherapeutic Loadings

    PubMed Central

    Enlow, Elizabeth M.; Luft, J. Christopher; Napier, Mary E.; DeSimone, Joseph M.

    2011-01-01

    Herein we report the fabrication of engineered poly(lactic acid-co-glycolic acid) nanoparticles via the PRINT® (Particle Replication In Non-wetting Templates) process with high and efficient loadings of docetaxel, up to 40% (w/w) with encapsulation efficiencies >90%. The PRINT process enables independent control of particle properties leading to a higher degree of tailorability than traditional methods. Particles with 40% loading display better in vitro efficacy than particles with lower loadings and the clinical formulation of docetaxel, Taxotere®. PMID:21265552

  15. Effect of erythropoietin loading chitosan-tripolyphosphate nanoparticles on an IgA nephropathy rat model

    PubMed Central

    ZHANG, XIAOLI; WU, YIN; SUN, KUN; TAN, JING

    2014-01-01

    The aim of the present study was to investigate the effect of erythropoietin (EPO) loading chitosan-tripolyphosphate (CS-TPP) nanoparticles on an immunoglobulin A nephropathy (IgAN) rat model. CS-TPP nanoparticles were produced from CS and TPP and EPO was loaded by mixing with the nanoparticles. The IgAN rat models were randomly divided into three groups: the CS-TPP-EPO group, CS-TPP group and EPO group. Hemoglobin (Hb), blood urea nitrogen (BUN) and creatinine (Cr) levels were measured in each group using a Biochemical Analyzer (Hitachi, Tokyo, Japan). The average size of nanoparticles was 485±12 nm and the encapsulation efficiency of EPO was 78.45%. The EPO release curve in CS-TPP-EPO nanoparticles exhibited a biphasic distribution in vitro. The levels of BUN and Cr in the CS-TPP-EPO group were significantly lower compared with the control group (P<0.05); however, the level of Hb in the CS-TPP-EPO group was higher compared with the other groups (P<0.05). The changes in Hb, BUN and Cr in the CS-TPP-EPO group were maintained for less than one week following the end of the treatment with CS-TPP-EPO nanoparticles. In conclusion, the CS-TPP-EPO nanoparticles had a lower toxicity compared with EPO and CS-TPP treatment. Furthermore, CS-TPP-EPO may improve the therapeutic effect in the IgAN model. This suggests that CS-TPP-EPO nanoparticles may be a potential therapeutic drug for the treatment of patients with IgAN. PMID:24926362

  16. Super-paramagnetic loaded nanoparticles based on biological macromolecules for in vivo targeted MR imaging.

    PubMed

    Sanjai, Chutimon; Kothan, Suchart; Gonil, Pattarapond; Saesoo, Somsak; Sajomsang, Warayuth

    2016-05-01

    Target-specific MRI contrast agent based on super-paramagnetic iron oxide-chitosan-folic acid (SPIONP-CS-FA) nanoparticles was fabricated by using an ionotropic gelation method, which involved the loading of SPIONPs at various concentrations into CS-FA nanoparticles by electrostatic interaction. The SPIONP-CS-FA nanoparticles were characterized by ATR-FTIR, XRD, TEM, and VSM techniques. This study revealed that the advantages of this system would be green fabrication, low cytotoxicity at iron concentrations ranging from 0.52 mg/L to 4.16 mg/L, and high water stability (pH 6) at 4°C over long periods. Average particle size and positive zeta-potential of the SPIONP-CS-FA nanoparticles was found to be 130 nm with narrow size distribution and 42 mV, respectively. In comparison to SPIONP-0.5-CS nanoparticles, SPIONP-0.5-CS-FA nanoparticles showed higher and specific cellular uptake levels into human cervical adenocarcinoma cells due to the presence of folate receptors, while in vivo results (Wistar rat) indicated that only liver tissue showed significant decreases in MR image intensity on T2 weighted images and T2* weighted images after post-injection, in comparison with other organs. Our results demonstrated that SPIONP-CS-FA nanoparticles can be applied as an either tumor or organ specific MRI contrast agents.

  17. Novel docetaxel-loaded nanoparticles based on PCL-Tween 80 copolymer for cancer treatment

    PubMed Central

    Ma, Yuandong; Zheng, Yi; Zeng, Xiaowei; Jiang, Liqin; Chen, Hongbo; Liu, Ranyi; Huang, Laiqiang; Mei, Lin

    2011-01-01

    Background The formulation of docetaxel available for clinical use (Taxotere®) contains a high concentration of polysorbate 80 (Tween 80). After incorporation of Tween 80 into poly-ɛ-caprolactone (PCL)-Tween 80 copolymer, the relative amount of Tween 80 should be decreased and the advantages of PCL and Tween 80 should be combined. Methods A novel PCL-Tween 80 copolymer was synthesized from ɛ-caprolactone and Tween 80 in the presence of stannous octoate as a catalyst via ring opening polymerization. Two types of nanoparticle formulation were made from commercial PCL and a self-synthesized PCL-Tween 80 copolymer using a modified solvent extraction/evaporation method. Results The nanoparticles were found by field emission scanning electron microscopy to have a spherical shape and be 200 nm in diameter. The copolymers could encapsulate 10% of the drug in the nanoparticles and release 34.9% of the encapsulated drug over 28 days. PCL-Tween 80 nanoparticles could be internalized into the cells and had higher cellular uptake than the PCL nanoparticles. The drug-loaded PCL-Tween 80 nanoparticles showed better in vitro cytotoxicity towards C6 cancer cells than commercial Taxotere at the same drug concentration. Conclusion Nanoparticles using PCL-Tween 80 copolymer as drug delivery vehicles may have a promising outcome for cancer patients. PMID:22114498

  18. Comparative receptor based brain delivery of tramadol-loaded poly(lactic-co-glycolic acid) nanoparticles.

    PubMed

    Lalani, Jigar; Raichandani, Yogesh; Mathur, Rashi; Lalan, Manisha; Chutani, Krishna; Mishra, Anil Kumar; Misra, Ambikanandan

    2012-12-01

    Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf). Nanoparticles of tramadol were prepared using nanoprecipitation technique and surface conjugated with Tf and Lf using epoxy linker. Prepared nanoparticles were characterized for their size, surface charge, drug entrapment, transmission electron microscopy and in vitro drug release. The surface density of Tf and Lf was estimated by protein estimation. The drug distribution in blood, brain and other tissues was studied in mice after intravenous administration. Tf and Lf anchored nanoparticles exhibit enhanced uptake with 2.38 and 3.85 folds higher targeting respectively in the brain when compared with unconjugated nanoparticles. The brain targeting observed for Lf anchored PLGA nanoparticles (Lf-TMD-PLGA-NP) was 1.62 folds that of Tf anchored PLGA nanoparticles (Tf-TMD-PLGA-NP). Hence, the study revealed Tf and specially Lf as promising ligand for enhanced brain deposition of tramadol.

  19. Development of drug-loaded chitosan-vanillin nanoparticles and its cytotoxicity against HT-29 cells.

    PubMed

    Li, Pu-Wang; Wang, Guang; Yang, Zi-Ming; Duan, Wei; Peng, Zheng; Kong, Ling-Xue; Wang, Qing-Huang

    2016-01-01

    Chitosan as a natural polysaccharide derived from chitin of arthropods like shrimp and crab, attracts much interest due to its inherent properties, especially for application in biomedical materials. Presently, biodegradable and biocompatible chitosan nanoparticles are attractive for drug delivery. However, some physicochemical characteristics of chitosan nanoparticles still need to be further improved in practice. In this work, chitosan nanoparticles were produced by crosslinking chitosan with 3-methoxy-4-hydroxybenzaldehyde (vanillin) through a Schiff reaction. Chitosan nanoparticles were 200-250 nm in diameter with smooth surface and were negatively charged with a zeta potential of - 17.4 mV in neutral solution. Efficient drug loading and drug encapsulation were achieved using 5-fluorouracil as a model of hydrophilic drug. Drug release from the nanoparticles was constant and controllable. The in vitro cytotoxicity against HT-29 cells and cellular uptake of the chitosan nanoparticles were evaluated by methyl thiazolyl tetrazolium method, confocal laser scanning microscope and flow cytometer, respectively. The results indicate that the chitosan nanoparticles crosslinked with vanillin are a promising vehicle for the delivery of anticancer drugs.

  20. Photophysical property of a polymeric nanoparticle loaded with an aryl benzyl ester silicon (IV) phthalocyanine

    NASA Astrophysics Data System (ADS)

    Pan, Sujuan; Ma, Dongdong; Chen, Xiuqin; Wang, Yuhua; Yang, Hongqin; Peng, Yiru

    2014-09-01

    Because of their excellent near-infrared (NIR) optical properties, phthalocyanines (Pcs) have been regarded as promising therapy agents for fluorescence image-guided drug delivery and noninvasive treatment of tumors by photodynamic therapy (PDT). Nevertheless, phthalocyanines are substantially limited in clinical applications owing to their poor solubility, aggregation and insufficient selectivity for cancer cells. To address these issues, we have developed a novel dendrimer-based theranostic nanoparticle for tumor-targeted delivery of phthalocyanine. The preparation procedure involved the modification of the silicon (IV) phthalocyanine molecule with a dendritic axially substitution, which significantly enhances their photophysical property. In order to improve biocompatibility and tumor-targeted delivery, the hydrophobic dendritic phthalocyanine was encapsulated by diblock amphiphilic copolymer poly (ethylene glycol)-poly (Epsilon-caprolactone) (MPEG-PCL) to form a polymeric nanoparticle. The polymeric nanoparticle is spherical with a diameter at about 90 nm. The photophysical property of the polymeric nanoparticle was studied by UV/Vis and fluorescence spectroscopic methods. Compared with the free dendritic phthalocyanine, the Q band of the polymeric nanoparticle was red-shifted, and the fluorescence intensity decreased. Furthermore, the polymeric nanoparticle has a relatively high loading amount and encapsulation rate. Therefore, the polymeric nanoparticle would be a promising third-generation photosensitizer (PS) for PDT.

  1. pH-Responsive Isoniazid-Loaded Nanoparticles Markedly Improve Tuberculosis Treatment in Mice.

    PubMed

    Hwang, Angela A; Lee, Bai-Yu; Clemens, Daniel L; Dillon, Barbara Jane; Zink, Jeffrey I; Horwitz, Marcus A

    2015-10-01

    Tuberculosis is a major global health problem for which improved therapeutics are needed to shorten the course of treatment and combat emergence of drug resistance. Mycobacterium tuberculosis, the etiologic agent of tuberculosis, is an intracellular pathogen of mononuclear phagocytes. As such, it is an ideal pathogen for nanotherapeutics because macrophages avidly ingest nanoparticles even without specific targeting molecules. Hence, a nanoparticle drug delivery system has the potential to target and deliver high concentrations of drug directly into M. tuberculosis-infected cells-greatly enhancing efficacy while avoiding off-target toxicities. Stimulus-responsive mesoporous silica nanoparticles of two different sizes, 100 and 50 nm, are developed as carriers for the major anti-tuberculosis drug isoniazid in a prodrug configuration. The drug is captured by the aldehyde-functionalized nanoparticle via hydrazone bond formation and coated with poly(ethylene imine)-poly(ethylene glycol) (PEI-PEG). The drug is released from the nanoparticles in response to acidic pH at levels that naturally occur within acidified endolysosomes. It is demonstrated that isoniazid-loaded PEI-PEG-coated nanoparticles are avidly ingested by M. tuberculosis-infected human macrophages and kill the intracellular bacteria in a dose-dependent manner. It is further demonstrated in a mouse model of pulmonary tuberculosis that the nanoparticles are well tolerated and much more efficacious than an equivalent amount of free drug.

  2. Nanodisco Balls: Control over Surface versus Core Loading of Diagnostically Active Nanocrystals into Polymer Nanoparticles

    PubMed Central

    2015-01-01

    Nanoparticles of complex architectures can have unique properties. Self-assembly of spherical nanocrystals is a high yielding route to such systems. In this study, we report the self-assembly of a polymer and nanocrystals into aggregates, where the location of the nanocrystals can be controlled to be either at the surface or in the core. These nanospheres, when surface decorated with nanocrystals, resemble disco balls, thus the term nanodisco balls. We studied the mechanism of this surface loading phenomenon and found it to be Ca2+ dependent. We also investigated whether excess phospholipids could prevent nanocrystal adherence. We found surface loading to occur with a variety of nanocrystal types including iron oxide nanoparticles, quantum dots, and nanophosphors, as well as sizes (10–30 nm) and shapes. Additionally, surface loading occurred over a range of polymer molecular weights (∼30–3000 kDa) and phospholipid carbon tail length. We also show that nanocrystals remain diagnostically active after loading onto the polymer nanospheres, i.e., providing contrast in the case of magnetic resonance imaging for iron oxide nanoparticles and fluorescence for quantum dots. Last, we demonstrated that a fluorescently labeled protein model drug can be delivered by surface loaded nanospheres. We present a platform for contrast media delivery, with the unusual feature that the payload can be controllably localized to the core or the surface. PMID:25188401

  3. Paclitaxel-loaded nanoparticles of star-shaped cholic acid-core PLA-TPGS copolymer for breast cancer treatment

    PubMed Central

    2013-01-01

    A system of novel nanoparticles of star-shaped cholic acid-core polylactide-d-α-tocopheryl polyethylene glycol 1000 succinate (CA-PLA-TPGS) block copolymer was developed for paclitaxel delivery for breast cancer treatment, which demonstrated superior in vitro and in vivo performance in comparison with paclitaxel-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles and linear PLA-TPGS nanoparticles. The paclitaxel- or couramin 6-loaded nanoparticles were fabricated by a modified nanoprecipitation method and then characterized in terms of size, surface charge, surface morphology, drug encapsulation efficiency, and in vitro drug release. The CA-PLA-TPGS nanoparticles were found to be spherical in shape with an average size of around 120 nm. The nanoparticles were found to be stable, showing no change in the particle size and surface charge during 90-day storage of the aqueous solution. The release profiles of the paclitaxel-loaded nanoparticles exhibited typically biphasic release patterns. The results also showed that the CA-PLA-TPGS nanoparticles have higher antitumor efficacy than the PLA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, such nanoparticles of star-shaped cholic acid-core PLA-TPGS block copolymer could be considered as a potentially promising and effective strategy for breast cancer treatment. PMID:24134303

  4. Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery.

    PubMed

    Kumar, Manoj; Pandey, Ravi Shankar; Patra, Kartik Chandra; Jain, Sunil Kumar; Soni, Muarai Lal; Dangi, Jawahar Singh; Madan, Jitender

    2013-10-01

    Leucine-enkephalin (Leu-Enk) is a neurotransmitter or neuromodulator in pain transmission. Due to non-addictive opioid analgesic activity of this peptide, it might have great potential in pain management. Leu-Enk loaded N-trimethyl chitosan (TMC) nanoparticles were prepared and evaluated as a brain delivery vehicle via nasal route. TMC biopolymer was synthesized and analyzed by (1)H NMR spectroscopy. TMC nanoparticles were prepared by ionic gelation method. Mean peptide encapsulation efficiency and loading capacity were 78.28±3.8% and 14±1.3%, respectively. Mean particle size, polydispersity index and zeta potential were found to be 443±23 nm, 0.317±0.17 and +15±2 mV respectively for optimized formulations. Apparent permeability coefficient (Papp) of Leu-Enk released from nanoparticles across the porcine nasal mucosa was determined to be 7.45±0.30×10(-6) cm s(-1). Permeability of Leu-Enk released from nanoparticles was 35 fold improved from the nasal mucosa as compared to Leu-Enk solution. Fluorescent microscopy of brain sections of mice showed higher accumulation of fluorescent marker NBD-F labelled Leu-Enk, when administered nasally by TMC nanoparticles, while low brain uptake of marker solution was observed. Furthermore, enhancement in brain uptake resulted into significant improvement in the observed antinociceptive effect of Leu-Enk as evidenced by hot plate and acetic acid induced writhing assay.

  5. Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

    NASA Astrophysics Data System (ADS)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

    2013-03-01

    Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide- co-glycolide) (PLGA) microparticles (size 1-4 μm, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

  6. Influence of Parathyroid Hormone-Loaded PLGA Nanoparticles in Porous Scaffolds for Bone Regeneration

    PubMed Central

    Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Pabari, Ritesh; Daly, Jacqueline; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

    2015-01-01

    Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1–34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3–4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. Both in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds. PMID:26343649

  7. In vitro and in vivo performance of biocompatible negatively-charged salbutamol-loaded nanoparticles.

    PubMed

    Rytting, Erik; Bur, Michael; Cartier, Regis; Bouyssou, Thierry; Wang, Xiaoying; Krüger, Michael; Lehr, Claus-Michael; Kissel, Thomas

    2010-01-04

    The development and performance of a novel nanoparticle-based formulation for pulmonary delivery has been characterized chronologically through the particle preparation process, in vitro testing of drug release, biocompatibility, degradation, drug transport in cell culture, and in vivo bronchoprotection studies in anaesthetised guinea pigs. This study demonstrates excellent agreement of the in vitro and in vivo experiments undertaken to prove the feasibility of the design, thereby serving as an example highlighting the importance of in vitro test methods that predict in vivo performance. Nanoparticles were prepared from the newly designed negatively-charged polymer poly(vinyl sulfonate-co-vinyl alcohol)-g-poly(d,l-lactic-co-glycolic acid) loaded with salbutamol free base. Average particle sizes of blank and drug-loaded nanoparticles prepared at the various stages of the investigations were between 91 and 204nm; average zeta potential values were between -50.1 and -25.6mV. Blank nanoparticles showed no significant toxicity, and no inflammatory activity was detected in Calu-3 cells. Sustained release of salbutamol from the nanoparticles was observed for 2.5h in vitro, and a prolonged effect was observed for 120min in vivo. These results demonstrate good agreement between in vitro and in vivo tests and also present a promising foundation for future advancement in nanomedicine strategies for pulmonary drug delivery.

  8. Synthesis of protein-coated biocompatible methotrexate-loaded PLA-PEG-PLA nanoparticles for breast cancer treatment

    PubMed Central

    Massadeh, Salam; Alaamery, Manal; Al-Qatanani, Shatha; Alarifi, Saqer; Bawazeer, Shahad; Alyafee, Yusra

    2016-01-01

    Background PLA-PEG-PLA triblock polymer nanoparticles are promising tools for targeted dug delivery. The main aim in designing polymeric nanoparticles for drug delivery is achieving a controlled and targeted release of a specific drug at the therapeutically optimal rate and choosing a suitable preparation method to encapsulate the drug efficiently, which depends mainly on the nature of the drug (hydrophilic or hydrophobic). In this study, methotrexate (MTX)-loaded nanoparticles were prepared by the double emulsion method. Method Biodegradable polymer polyethylene glycol-polylactide acid tri-block was used with poly(vinyl alcohol) as emulsifier. The resulting methotrexate polymer nanoparticles were coated with bovine serum albumin in order to improve their biocompatibility. This study focused on particle size distribution, zeta potential, encapsulation efficiency, loading capacity, and in vitro drug release at various concentrations of PVA (0.5%, 1%, 2%, and 3%). Results Reduced particle size of methotrexate-loaded nanoparticles was obtained using lower PVA concentrations. Enhanced encapsulation efficiency and loading capacity was obtained using 1% PVA. FT-IR characterization was conducted for the void polymer nanoparticles and for drug-loaded nanoparticles with methotrexate, and the protein-coated nanoparticles in solid state showed the structure of the plain PEG-PLA and the drug-loaded nanoparticles with methotrexate. The methotrexate-loaded PLA-PEG-PLA nanoparticles have been studied in vitro; the drug release, drug loading, and yield are reported. Conclusion The drug release profile was monitored over a period of 168 hours, and was free of burst effect before the protein coating. The results obtained from this work are promising; this work can be taken further to develop MTX based therapies.

  9. Particulate Release From Nanoparticle-Loaded Shape Memory Polymer Foams.

    PubMed

    Nathan, Adam L; Fletcher, Grace K; Monroe, Mary Beth B; Hwang, Wonjun; Herting, Scott M; Hasan, Sayyeda M; Keller, Brandis K; Maitland, Duncan J

    2017-03-01

    Highly porous, open-celled shape memory polymer (SMP) foams are being developed for a number of vascular occlusion devices. Applications include abdominal aortic and neurovascular aneurysm or peripheral vascular occlusion. A major concern with implanting these high surface area materials in the vasculature is the potential to generate unacceptable particulate burden, in terms of number, size, and composition. This study demonstrates that particulate numbers and sizes in SMP foams are in compliance with limits stated by the most relevant standard and guidance documents. Particulates were quantified in SMP foams as made, postreticulation, and after incorporating nanoparticles intended to increase material toughness and improve radiopacity. When concentrated particulate treatments were administered to fibroblasts, they exhibited high cell viability (100%). These results demonstrate that the SMP foams do not induce an unacceptable level of risk to potential vascular occlusion devices due to particulate generation.

  10. Enhanced lateral flow immunoassay using gold nanoparticles loaded with enzymes.

    PubMed

    Parolo, Claudio; de la Escosura-Muñiz, Alfredo; Merkoçi, Arben

    2013-02-15

    The use of gold nanoparticles (AuNPs) as labeling carriers in combination with the enzymatic activity of the horseradish peroxidase (HRP) in order to achieve an improved optical lateral flow immunoassay (LFIA) performance is presented here. Briefly in a LFIA with an immune-sandwich format AuNPs are functionalized with a detection antibody already modified with HRP, obtaining an 'enhanced' label. Two different detection strategies have been tested: the first one following just the red color of the AuNPs and the second one using a substrate for the HRP (3 different substrates are evaluated), which produces a darker color that enhances the intensity of the previous red color of the unmodified AuNPs. In such very simple way it is gaining sensitivity (up to 1 order of magnitude) without losing the simplicity of the LFIA format, opening the way to other LFIA applications including their on-demand performance tuning according to the analytical scenario.

  11. Gene therapy based on interleukin-12 loaded chitosan nanoparticles in a mouse model of fibrosarcoma

    PubMed Central

    Soofiyani, Saiedeh Razi; Hallaj-Nezhadi, Somayeh; Lotfipour, Farzaneh; Hosseini, Akbar Mohammad; Baradaran, Behzad

    2016-01-01

    Objective(s): Interleukin-12 (IL-12) as a cytokine has been proved to have a critical role in stimulating the immune system and has been used as immunotherapeutic agents in cancer gene therapy. Chitosan as a polymer, with high ability of binding to nucleic acids is a good candidate for gene delivery since it is biodegradable, biocompatible and non-allergenic polysaccharide. The objective of the present study was to investigate the effects of cells transfected with IL-12 loaded chitosan nanoparticles on the regression of fibrosarcoma tumor cells (WEHI-164) in vivo. Materials and Methods: WEHI-164 tumor cells were transfected with IL-12 loaded chitosan nanoparticles and then were injected subcutaneously to inoculate tumor in BALB/c mice. Tumor volumes were determined and subsequently extracted after mice sacrifice. The immunohistochemistry staining was performed for analysis of Ki-67 expression (a tumor proliferation marker) in tumor masses. The expression of IL-12 and IFN-γ were studied using real-time polymerase chain reaction and immunoblotting. Results: The group treated with IL-12 loaded chitosan nanoparticles indicated decreasing of tumor mass[r1] volume (P<0.001). The results of western blotting and real-time PCR showed that the IL-12 expression was increased in the group. Immunohistochemistry staining indicated that the Ki-67expression was reduced in the group treated with IL-12 loaded chitosan nanoparticles. Conclusion: IL-12 gene therapy using chitosan nanoparticles has therapeutic effects on the regression of tumor masses in fibrosarcoma mouse model. PMID:27917281

  12. Chitosan-clodronate nanoparticles loaded in poloxamer gel for intra-articular administration.

    PubMed

    Russo, E; Gaglianone, N; Baldassari, S; Parodi, B; Croce, I; Bassi, A M; Vernazza, S; Caviglioli, G

    2016-07-01

    This work was based on the study of an intra-articular delivery system constituted by a poloxamer gel vehiculating clodronate in chitosan nanoparticles. This system has been conceived to obtain a specific and controlled release of clodronate in the joints to reduce the arthritis rheumatoid degenerative effect. Clodronate (CLO) is a first-generation bisphosphonate with anti-inflammatory properties, inhibiting the cytokine and NO secretion from macrophages, therefore causing apoptosis in these cells. This is related to its ability to be metabolized by cells and converted into a cytotoxic intermediate as a non-hydrolysable analogue of ATP. Chitosan (CHI) was used to develop nanosystems, by ionotropic gelation induced by clodronate itself. A fractional factorial experimental design allowed us to obtain nanoparticles, the diameter of which ranged from 200 to 300nm. Glutaraldehyde was used to increase nanoparticle stability and modify the drug release profile. The zeta potential value of crosslinked nanopaparticles was 21.0mV±1.3, while drug loading was 31.0%±5.4 w/w; nanoparticle yield was 18.2%±1.8 w/w, the encapsulation efficiency was 48.8%±9.9 w/w. Nanoparticles were homogenously loaded in a poloxamer sol, and the drug delivery system is produced in-situ after local administration, when sol become gel at physiological temperature. The properties of poloxamer gels containing CHI-CLO nanoparticles, such as viscosity, gelation temperature and drug release properties, were evaluated. In vitro studies were conducted to evaluate the effects of these nanoparticles on a human monocytic cell line (THP1). The results showed that this drug delivery system is more efficient, with respect to the free drug, to counteract the inflammatory process characteristic of several degenerative diseases.

  13. Magnetic loading of graphene-nickel nanoparticle hybrid for electrochemical sensing of carbohydrates.

    PubMed

    Qu, Weidong; Zhang, Luyan; Chen, Gang

    2013-04-15

    Graphene-nickel nanoparticle hybrid was prepared by the one-step far infrared-assisted reduction of graphene oxide and nickel (II) ions using hydrazine. It was loaded on the surface of a magnetic electrode for electrochemical sensing. The feasibility and performance of the novel electrode were demonstrated by measuring carbohydrates using cyclic voltammetry and amperometry. It demonstrated that nickel nanoparticles decorated on graphene sheets exhibited higher electrocatalytic activity toward the oxidation of carbohydrates while graphene improved the electron transduction. The synergistic effect significantly enhanced the current response of carbohydrates.

  14. Imaging of the GI tract by QDs loaded heparin-deoxycholic acid (DOCA) nanoparticles.

    PubMed

    Khatun, Zehedina; Nurunnabi, Md; Cho, Kwang Jae; Lee, Yong-kyu

    2012-11-06

    This study presents an approach to deliver non invasive, near-IR imaging agent using oral delivery system. Low molecular weight heparin (LMWH)-deoxycholic acid (DOCA)/(LHD) nanoparticles formed by a self-assembly method was prepared to evaluate their physicochemical properties and oral absorption in vitro and in vivo. Near-IR QDs were prepared and loaded into LHD nanoparticles for imaging of the gastro-intestinal (GI) tract absorption. Q-LHD nanoparticles were almost spherical in shape with diameters of 194-217 nm. The size and fluorescent intensity of the Q-LHD nanoparticles were stable in 10% FBS solution and retained their fluorescent even after 5 days of incubation. Cell viability of Q-LHD nanoparticles maintained in the range of 80-95% for 24h incubation. No damage was found in tissues or organs during animal experiments. The in vivo oral absorption of Q-LHD was observed in SKH1 mice for 3h under different doses. From the results, we confirmed that Q-LHD was absorbed mostly into the ileum of small intestine containing intestinal bile acid transporter as observed in TEM and molecular imaging system. Our designed nanoparticles could be administered orally for bio-imaging and studying the bio-distribution of drug.

  15. Tamoxifen-loaded poly(L-lactide) nanoparticles: Development, characterization and in vitro evaluation of cytotoxicity.

    PubMed

    Altmeyer, Clescila; Karam, Thaysa Ksiaskiewcz; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2016-03-01

    In this study, poly(L-lactide) (PLA) nanoparticles containing Tamoxifen (Tmx) were developed using an emulsion/solvent evaporation method, observing the influence of surfactants and their concentrations on mean particle size and drug entrapment. Nanoparticles were characterized in terms of size, morphology, polydispersity, interaction drug-polymer and in vitro drug release profile. Cytotoxicity over erythrocytes and tumor cells was assessed. The optimized formulation employed as surfactant 1% polyvinyl alcohol. Mean particle size was 155±4 nm (n=3) and Tmx encapsulation efficiency was 85±8% (n=3). The in vitro release profile revealed a biphasic release pattern diffusion-controlled with approximately 24% of drug released in 24 h followed by a sustained release up to 120 h (30% of Tmx released). PLA nanoparticles containing Tmx presented a very low index of hemolysis (less than 10%), in contrast to free Tmx that was significantly hemolytic. Tmx-loaded PLA nanoparticles showed IC50 value 2-fold higher than free Tmx, but considering the prolonged Tmx release from nanoparticles, cytotoxicity on tumor cells was maintained after nanoencapsulation. Thus, PLA nanoparticles are promising carriers for controlled delivery of Tmx with potential application in cancer treatment.

  16. In vitro release and biological activities of Carum copticum essential oil (CEO) loaded chitosan nanoparticles.

    PubMed

    Esmaeili, Akbar; Asgari, Azadeh

    2015-11-01

    In recent years, the unparalleled and functional properties of essential oils have been extensively reported, but the sensitivity of essential oils to environmental factors and their poor aqueous solubility have limited their applications in industries. Hence, we encapsulated CEO in chitosan nanoparticles by an emulsion-ionic gelation with pantasodium tripolyphosphate (TPP) and sodium hexametaphosphte (HMP), separately, as crosslinkers. The nanoparticles were analyzed by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-vis), differential scanning calorimetry (DSC), scanning electron microscope (SEM) and dynamic light scattering (DLS). The encapsulation efficiency (EE) and loading capacity (LC) of CEO in chitosan nanoparticles increased with the increase of initial CEO amount. The nanoparticles displayed an average size of 30-80nm with a spherical shape and regular distribution. In vitro release profiles exhibited an initial burst release and followed by a sustained CEO release at different pH conditions. The amount of CEO release from chitosan nanoparticles was higher in acidic pH to basic or neutral pH, respectively. The biological properties of CEO, before and after the encapsulation process were evaluated by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and agar disk diffusion method, respectively. The results indicated the encapsulation of CEO in chitosan nanoparticles could be protected the quality.

  17. D, L-Sulforaphane Loaded Fe3O4@ Gold Core Shell Nanoparticles: A Potential Sulforaphane Delivery System

    PubMed Central

    Kheiri Manjili, Hamidreza; Ma’mani, Leila; Tavaddod, Sharareh; Mashhadikhan, Maedeh; Shafiee, Abbas; Naderi-Manesh, Hossein

    2016-01-01

    A novel design of gold-coated iron oxide nanoparticles was fabricated as a potential delivery system to improve the efficiency and stability of d, l-sulforaphane as an anticancer drug. To this purpose, the surface of gold-coated iron oxide nanoparticles was modified for sulforaphane delivery via furnishing its surface with thiolated polyethylene glycol-folic acid and thiolated polyethylene glycol-FITC. The synthesized nanoparticles were characterized by different techniques such as FTIR, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, scanning and transmission electron microscopy. The average diameters of the synthesized nanoparticles before and after sulforaphane loading were obtained ∼ 33 nm and ∼ 38 nm, respectively, when ∼ 2.8 mmol/g of sulforaphane was loaded. The result of cell viability assay which was confirmed by apoptosis assay on the human breast cancer cells (MCF-7 line) as a model of in vitro-cancerous cells, proved that the bare nanoparticles showed little inherent cytotoxicity, whereas the sulforaphane-loaded nanoparticles were cytotoxic. The expression rate of the anti-apoptotic genes (bcl-2 and bcl-xL), and the pro-apoptotic genes (bax and bak) were quantified, and it was found that the expression rate of bcl-2 and bcl-xL genes significantly were decreased when MCF-7 cells were incubated by sulforaphane-loaded nanoparticles. The sulforaphane-loaded into the designed gold-coated iron oxide nanoparticles, acceptably induced apoptosis in MCF-7 cells. PMID:26982588

  18. Near-infrared fluorescent aza-BODIPY dye-loaded biodegradable polymeric nanoparticles for optical cancer imaging

    NASA Astrophysics Data System (ADS)

    Hamon, Casey L.; Dorsey, Christopher L.; Özel, Tuğba; Barnes, Eugenia M.; Hudnall, Todd W.; Betancourt, Tania

    2016-07-01

    Nanoparticles are being readily investigated as carriers for the delivery of imaging and therapeutic agents for the detection, monitoring, and treatment of cancer and other diseases. In the present work, the preparation of biodegradable polymeric nanoparticles loaded with a near-infrared fluorescent aza-boron dipyrromethene (NIR-BODIPY ) derivative, and their use as contrast agents for optical imaging in cancer are described. Nanoparticles were prepared by nanoprecipitation of amphiphilic block copolymers of poly(lactic acid) and poly(ethylene glycol). The size, morphology, dye loading, spectral properties, quantum yield, cytocompatibility, and in vitro NIR imaging potential of the nanoparticles in breast and ovarian cancer cells were evaluated. Spherical nanoparticles of 30-70 nm in diameter were loaded with 0.73 w/w% BODIPY derivative. At this loading, the dye presented a fluorescence quantum yield in the same order of magnitude as in solution. Nanoparticle suspensions at concentrations up to 580 μg/mL were cytocompatible to breast (MDA-MB-231) and ovarian (SKOV-3 and Caov-3) cancer cells after a four-hour incubation period. Fluorescence microscopy images demonstrated the ability of the nanoparticles to act as imaging agents in all three cell lines in as little as 1 hour. The results shown indicate the potential of these NIR-BODIPY-loaded nanoparticles as contrast agents for near-infrared optical imaging in cancer.

  19. Evaluation of in vitro dissolution and in vivo oral absorption of dutasteride-loaded eudragit E nanoparticles.

    PubMed

    Kim, M-S

    2013-06-01

    The present study sought to evaluate the pharmacokinetics of dutasteride-loaded Eudragit E nanoparticle in rats. In addition, the study investigated the effect of increasing drug load on the in vitro solubility and dissolution behavior of dutasteride together with its in vivo oral absorption characteristics. The suspension of dutasteride-loaded Eudragit E nanoparticles prepared by the nanoprecipitation method showed blue opalescence and the particles were uniform in appearance. The entrapment efficiency and the mean particle size of these nanoparticles were in the range of 98.1-99.3% and 120.5-128.4 nm, respectively, and no significant difference in these parameters was observed between the nanoparticles in the sample. Eudragit E nanoparticles containing a drug load of 5% showed an increase in bioavailability by 550% as compared to dutasteride suspension. This finding is attributable to enhanced solubility and dissolution of dutasteride when formulated as nanoparticles. Furthermore, the oral absorption of dutasteride in rats increased as a function of the extent of supersaturation of dutasteride in Eudragit E nanoparticles. Therefore, the preliminary results from our study suggest that dutasteride-loaded Eudragit E nanoparticles may have significant potential for clinical application.

  20. Preparation of nanoparticles by solvent displacement for drug delivery: a shift in the "ouzo region" upon drug loading.

    PubMed

    Beck-Broichsitter, Moritz; Rytting, Erik; Lebhardt, Tobias; Wang, Xiaoying; Kissel, Thomas

    2010-10-09

    As biodegradable nanoparticles meet with increasing interest for drug delivery applications, a series of investigations were carried out to understand the mechanism of the formation of drug-loaded nanoparticles using the solvent displacement method. Although previous explanations referred to Marangoni convection as the driving force for nanoprecipitation, recent publications describing the so-called "ouzo effect" sparked these current studies using a novel negatively charged polymer, poly(vinyl sulfonate-co-vinyl alcohol)-graft-poly(D,L-lactide-co-glycolide) (P(VS-VA)-g-PLGA), and a positively charged model drug, salbutamol. Interfacial tension did not influence the nanoparticle formation as would be expected if governed by Marangoni convection, but ternary phase diagrams outlined the so-called "ouzo regions" defining the polymer and solvent concentrations leading to stable nanoparticle suspensions for both this novel polymer and unmodified poly(D,L-lactide-co-glycolide) (PLGA). Physicochemical properties, morphology and drug loading of the nanoparticles were analyzed, and stable P(VS-VA)-g-PLGA nanoparticles with and without salbutamol ranged in size from 59-191nm. The "ouzo region" phase diagram boundaries shifted considerably upon drug loading, which can be explained by the increased solubility of the polymer-drug complex. This behavior necessitated a substantial adjustment of polymer concentrations required to produce drug-loaded nanoparticles with characteristics comparable to blank nanoparticles. In conclusion, the use of "ouzo diagrams" is a beneficial tool to manufacture nanoparticles with specified physicochemical properties by the solvent displacement method.

  1. Amphiphilic core–shell nanoparticles containing dense polyethyleneimine shells for efficient delivery of microRNA to Kupffer cells

    PubMed Central

    Liu, Zuojin; Niu, Dechao; Zhang, Junyong; Zhang, Wenfeng; Yao, Yuan; Li, Pei; Gong, Jianping

    2016-01-01

    Efficient and targeted delivery approach to transfer exogenous genes into macrophages is still a great challenge. Current gene delivery methods often result in low cellular uptake efficiency in vivo in some types of cells, especially for the Kupffer cells (KCs). In this article, we demonstrate that amphiphilic core–shell nanoparticles (NPs) consisting of well-defined hydrophobic poly(methyl methacrylate) (PMMA) cores and branched polyethyleneimine (PEI) shells (denoted as PEI@PMMA NPs) are efficient nanocarriers to deliver microRNA (miRNA)-loaded plasmid to the KCs. Average hydrodynamic diameter of PEI@ PMMA NPs was 279 nm with a narrow size distribution. The NPs also possessed positive surface charges up to +30 mV in water, thus enabling effective condensation of negatively charged plasmid DNA. Gel electrophoresis assay showed that the resultant PEI@PMMA NPs were able to completely condense miRNA plasmid at a weight ratio of 25:1 (N/P ratio equal to 45:1). The Cell Counting Kit-8 assay and flow cytometry results showed that the PEI@PMMA/miRNA NPs displayed low cytotoxicity and cell apoptosis activity against the KCs. The maximum cell transfection efficiency reached 34.7% after 48 hours, which is much higher than that obtained by using the commercial Lipofectamine™ 2000 (1.7%). Bio-transmission electron microscope observation revealed that the PEI@PMMA NPs were mainly distributed in the cytoplasm of the KCs. Furthermore, when compared to the control groups, the protein expression of target nuclear factor κB P65 was considerably inhibited (P<0.05) both in vitro and in vivo. These results demonstrate that the PEI@PMMA NPs with a unique amphiphilic core–shell nanostructure are promising nanocarriers for delivering miRNA plasmid to KCs. PMID:27366061

  2. Enhanced apoptotic effect of curcumin loaded solid lipid nanoparticles.

    PubMed

    Vandita, Kakkar; Shashi, Bhushan; Santosh, Kumar Guru; Pal, Kaur Indu

    2012-12-03

    Curcumin is reported to show potent in vitro anticancer effects in a surfeit of human cancer cell lines and majorly in the carcinogenesis of GIT, in animals. Its poor pharmacokinetics and stability limit its vivo clinical efficacy for the other systemic cancers. We recently reported on a 32-155 times enhancement in bioavailability of curcumin when incorporated into solid lipid nanoparticles (C-SLNs). Presently we report on a 54-85% reduction in IC 50 values with developed C-SLNs in comparison to free curcumin against a panel of human cancer cell lines (HL-60, A549, and PC3). Results demonstrate mechanisms similar to those claimed for free curcumin, including induction of cellular apoptosis by activation of caspases, release of cyctochrome c, loss of membrane potential, blockade of nuclear factor kappa B (NF-κB) activation, and upregulation of TNF-R for C-SLNs. However, the extent of cell death provided by C-SLNs in all these tests was significantly higher (p < 0.001). This may be attributed to the presentation of curcumin in a dispersible/soluble form which enhanced permeability across the cell surface. The display of significantly better in vitro anticancer effect coupled with high in vivo bioavailability points toward a great potential of using C-SLNs for cancer therapeutics.

  3. [Preparation and stability of β-carotene loaded using mesoporous silica nanoparticles as carriers system].

    PubMed

    Liu, Jing; Ren, Zhi-hui; Wang, Hai-yuan; Jin, Xing-hua

    2015-09-01

    1,3,5-Trimethylbenzene (1,3,5-TMB) was used as the pore-enlarging modifier to expand the pore size of MCM-41 (mobil company of matter) mesoporous silica nanoparticles. The solvent impregnation method was adopted to assemble non-water-soluble β-carotene into the pore channel of MCM-41. The MCM-41 and drug assemblies were characterized by TEM, FT-IR, elemental analysis and N2 adsorption-desorption. The results showed that MCM-41 has good sphericity and regular pore structure. The research also investigated the optimal loading time, the drug loading and the vitro stability of the β-carotene. As a drug carrier, the modified MCM-41 showing a shorter drug loading time, the drug loading as high as 85.58% and the stability of β-carotene in drug assemblies has improved. The study of this new formulation provides a new way for β-carotene application.

  4. A Novel Method for the Preparation of Retinoic Acid-Loaded Nanoparticles

    PubMed Central

    Errico, Cesare; Gazzarri, Matteo; Chiellini, Federica

    2009-01-01

    The goal of present work was to investigate the use of bioerodible polymeric nanoparticles as carriers of retinoic acid (RA), which is known to induce differentiation of several cell lines into neurons. A novel method, named “Colloidal-Coating”, has been developed for the preparation of nanoparticles based on a copolymer of maleic anhydride and butyl vinyl ether (VAM41) loaded with RA. Nanoparticles with an average diameter size of 70 nm and good morphology were prepared. The activity of the encapsulated RA was evaluated on SK-N-SH human neuroblastoma cells, which are known to undergo inhibition of proliferation and neuronal differentiation upon treatment with RA. The activity of RA was not affected by the encapsulation and purification processes. PMID:19564952

  5. Improved insulin loading in poly(lactic-co-glycolic) acid (PLGA) nanoparticles upon self-assembly with lipids.

    PubMed

    García-Díaz, María; Foged, Camilla; Nielsen, Hanne Mørck

    2015-03-30

    Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes.

  6. An antibacterial coating based on a polymer/sol-gel hybrid matrix loaded with silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Rivero, Pedro José; Urrutia, Aitor; Goicoechea, Javier; Zamarreño, Carlos Ruiz; Arregui, Francisco Javier; Matías, Ignacio Raúl

    2011-12-01

    In this work a novel antibacterial surface composed of an organic-inorganic hybrid matrix of tetraorthosilicate and a polyelectrolyte is presented. A precursor solution of tetraethoxysilane (TEOS) and poly(acrylic acid sodium salt) (PAA) was prepared and subsequently thin films were fabricated by the dip-coating technique using glass slides as substrates. This hybrid matrix coating is further loaded with silver nanoparticles using an in situ synthesis route. The morphology and composition of the coatings have been studied using UV-VIS spectroscopy and atomic force microscopy (AFM). Energy dispersive X-ray (EDX) was also used to confirm the presence of the resulting silver nanoparticles within the thin films. Finally the coatings have been tested in bacterial cultures of genus Lactobacillus plantarum to observe their antibacterial properties. It has been experimentally demonstrated that these silver loaded organic-inorganic hybrid films have a very good antimicrobial behavior against this type of bacteria.

  7. Preparation and characterization of n-dodecyl-ferulate-loaded solid lipid nanoparticles (SLN).

    PubMed

    Souto, E B; Anselmi, C; Centini, M; Müller, R H

    2005-05-13

    Solid lipid nanoparticles (SLN) containing a novel potential sunscreen n-dodecyl-ferulate (ester of ferulic acid) were developed. The preparation and stability parameters of n-dodecyl-ferulate-loaded SLN have been investigated concerning particle size, surface electrical charge (zeta potential) and matrix crystallinity. The chemical stability of n-dodecyl-ferulate at high temperatures was also assessed by thermal gravimetry analysis. For the selection of the appropriated lipid matrix, chemically different lipids were melted with 4% (m/m) of active and lipid nanoparticles were prepared by the so-called high pressure homogenization technique. n-Dodecyl-ferulate-loaded SLN prepared with cetyl palmitate showed the lowest mean particle size and polydispersity index, as well as the highest physical stability during storage time of 21 days at 4, 20 and 40 degrees C. These colloidal dispersions containing the sunscreen also exhibited the common melting behaviour of aqueous SLN dispersions.

  8. Facile fabrication of graphene oxide loaded with silver nanoparticles as antifungal materials

    NASA Astrophysics Data System (ADS)

    Cui, Jianghu; Yang, Yunhua; Zheng, Mingtao; Liu, Yingliang; Xiao, Yong; Lei, Bingfu; Chen, Wei

    2014-12-01

    Graphene oxide loaded silver nanoparticles (GO-Ag) were synthesized using a simple method. Our evidence showed that silver nanoparticles (Ag NPs) were successfully loaded on the surface of graphene oxide sheets. The antifungal property of GO-Ag composites was investigated. The results revealed that the obtained GO-Ag composites exhibit enhanced antifungal property in comparison with that of Ag NPs. The toxicity of GO-Ag and Ag NPs were systematically evaluated. The study of cell viability, lactate dehydrogenase, reactive oxygen species, apoptosis/necrosis and hemolysis revealed that GO-Ag composites have lower cytotoxicity and better blood compatibility than Ag NPs. Therefore, these findings provide nanotoxicological information regarding GO-Ag composites which may be alternative antifungal materials in their application of biomedical fields.

  9. Formulation and Evaluation of Morin-Loaded Solid Lipid Nanoparticles.

    PubMed

    Ikeuchi-Takahashi, Yuri; Ishihara, Chizuko; Onishi, Hiraku

    2016-09-01

    In this study, solid lipid nanoparticle (SLN) suspensions were prepared using a base of hard fat with or without ethylcellulose (EC) and polyvinyl alcohols (PVA) and polysorbate (Tween) 60 surfactants. Commercially available PVAs vary in their degree of saponification and polymerization, and the appropriate PVAs to form SLNs from hard fat with or without EC were investigated. A relatively low-saponification-degree PVA was required to reproducibly form SLN suspensions without EC and relatively high-saponification-degree PVAs were suitable for SLNs with EC. The release of morin from SLNs with EC was more sustained than that from SLNs without EC. The maximum plasma concentration (Cmax) of SLNs with and without EC were almost the same, and both were higher than that of a morin suspension. The area under the curve for 0 to 360 min (AUC0-360) of SLNs with EC was increased compared with those of a morin suspension and SLNs without EC. The median diameter of SLNs with EC and a very low-saponification-degree PVA was decreased compared to other formulation, and morin release was more sustained for this formulation. SLNs with EC and a very low-saponification-degree PVA showed higher Cmax and AUC0-360 than SLNs with EC lacking a very low-saponification-degree PVA. The optimized SLNs with EC and a very low-saponification-degree PVA improved bioavailability via increased accessibility to the enterocyte surface by decreased particle size and increased permeation of SLN encapsulated morin through the intestinal membrane by sustained release properties.

  10. Effect of drying and loading methods on the release behavior of ciprofloxacin from starch nanoparticles.

    PubMed

    Shi, Aimin; Li, Dong; Liu, Hongzhi; Adhikari, Benu; Wang, Qiang

    2016-06-01

    Drug loading into and release from starch nanoparticles (StNPs), one kind of novel biological macromolecule, were investigated. Two drying methods (spray and vacuum freeze drying) and drug loading methods (coating and adsorption) were used for evaluation. 40% (w/w) of ciprofloxacin was loaded using coating method while only 7% for adsorption method. Glass transition temperature (Tg) and melting point temperature (Tmp) of ciprofloxacin loaded starch nanoparticles varied from 40°C to 55°C and 125°C to 175°C. Particles using adsorption method had lower loading rate of ciprofloxacin, higher Tg, Tmp and release rate compared to using coating method. Tg and Tmp were not affected by these two drying methods. Release rate of ciprofloxacin was higher from freeze dried particles than from spray dried particles using coating method. For adsorption method, drying methods had not effect on the release rate. A double decay exponential model was able to fit the release data suitably well with coefficient of determination (R(2))>0.97.

  11. Glaucoma therapy by extended release of timolol from nanoparticle loaded silicone-hydrogel contact lenses.

    PubMed

    Jung, Hyun Jung; Abou-Jaoude, Michelle; Carbia, Blanca E; Plummer, Caryn; Chauhan, Anuj

    2013-01-10

    Glaucoma is the second major cause of blindness in the world after cataract. Glaucoma management through eye drops that reduce the intraocular pressure (IOP) has major deficiencies including low patient compliance and low bioavailability. Extended wear contact lenses that deliver glaucoma drugs for extended periods could increase patient compliance, while also increasing the bioavailability. To develop extended wear contact lenses that can also provide extended glaucoma therapy, we disperse nanoparticles of PGT (propoxylated glyceryl triacylate) that contain a glaucoma drug timolol. The particles can also be loaded into prefabricated lenses by soaking the lenses in a solution of particles in ethanol. The particle loaded gels can release timolol in phosphate buffered saline (PBS) for about a month at room temperature. The most likely rate controlling mechanism is hydrolysis of the ester bond that links timolol to the PGT matrix, but other mechanisms such as water and drug diffusion, drug dissolution, drug-polymer chain cleavage, time-dependent drug permeability within the polymeric matrix, etc. may also be important. Nanoparticle incorporation in the silicone hydrogels results in reduction in ion and oxygen permeabilities, and an increase in modulus, and the impact on each of these properties is proportional to the particle loading. A gel with 5% particle loading can deliver timolol at therapeutic doses for about a month at room temperature, with a minimal impact on critical lens properties. Preliminary animal studies in Beagle dogs conducted with lenses in which particles are loaded by soaking the lenses in ethanol show a reduction in IOP.

  12. 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

  13. Rivastigmine-Loaded L-Lactide-Depsipeptide Polymeric Nanoparticles: Decisive Formulation Variable Optimization

    PubMed Central

    Pagar, Kunal; Vavia, Pradeep

    2013-01-01

    The main aim of the investigation was to explore a novel L-lactide-depsipeptide copolymer for the development of rivastigmine-loaded polymeric nanoparticles. L-lactide-depsipeptide synthesis was based on the ring opening polymerization reaction of L-lactide with the cyclodepsipeptide, cyclo(Glc-Leu), using tin 2-ethyl hexanoate as an initiator. Rivastigmine-loaded nanoparticles were prepared by the single emulsion-solvent evaporation technique. The influence of various critical formulation variables like sonication time, amount of polymer, amount of drug, stabilizer concentration, drug-to-polymer ratio, and organic-to-aqueous phase ratio on particle size and entrapment efficiency was studied. The optimized formulation having a particle size of 142.2 ± 21.3 nm with an entrapment efficiency of 60.72 ± 3.72% was obtained. Increased rivastigmine entrapment within the polymer matrix was obtained with a relatively low organic-to-aqueous phase ratio and high drug-to-polymer ratio. A decrease in the average size of the nanoparticles was observed with a decrease in the amount of polymer added and an increase in the sonication time. Prolonged sonication time, however, decreased rivastigmine entrapment. From the different lyoprotectant tested, only trehalose was found to prevent nanoparticle aggregation upon application of the freeze-thaw cycle. Drug incorporation into the polymeric matrix was confirmed by the DSC and XRD study. The spherical nature of the nanoparticles was confirmed by the SEM study. The in vitro drug release study showed the sustained release of more than 90% of the drug up to 72 h. Thus, L-lactide-depsipeptide can be used as an efficient carrier for the nanoparticle preparation of rivastigmine. PMID:24106679

  14. Altered Cell Cycle Arrest by Multifunctional Drug-Loaded Enzymatically-Triggered Nanoparticles.

    PubMed

    Huang, Can; Sun, Ying; Shen, Ming; Zhang, Xiangyu; Gao, Pei; Duan, Yourong

    2016-01-20

    cRGD-targeting matrix metalloproteinase (MMP)-sensitive nanoparticles [PLGA-PEG1K-cRGD/PLGA-peptide-PEG5K (NPs-cRGD)] were successfully developed. Au-Pt(IV) nanoparticles, PTX, and ADR were encapsulated into NPs-RGD separately. The effects of the drug-loaded nanoparticles on the cell cycle were investigated. Here, we showed that higher cytotoxicity of drug-loaded nanoparticles was related to the cell cycle arrest, compared to that of free drugs. The NPs-cRGD studied here did not disrupt cell cycle progression. The cell cycle of Au-Pt(IV)@NPs-cRGD showed a main S phase arrest in all phases of the cell cycle phase, especially in G0/G1 phase. PTX@NPs-cRGD and ADR@NPs-cRGD showed a higher ratio of G2/M and S phase arrest than the free drugs, respectively. Cells in G0/G1 and S phases of the cell cycle had a higher uptake ratio of NPs-cRGD. A nutrient deprivation or an increase in the requirement of nutrients in tumor cells could promote the uptake of nanoparticles from the microenvironments. In vivo, NPs-cRGD could efficiently accumulate at tumor sites. The inhibition of tumor growth coupled with cell cycle arrest is in line with that in vitro. On the basis of our results, we propose that future studies on nanoparticle action mechanism should consider the cell cycle, which could be different from free drugs. Understanding the actions of cell cycle arrest could affect the application of nanomedicine in the clinic.

  15. Dirhenium decacarbonyl-loaded PLLA nanoparticles: influence of neutron irradiation and preliminary in vivo administration by the TMT technique.

    PubMed

    Hamoudeh, Misara; Fessi, Hatem; Mehier, Henri; Faraj, Achraf Al; Canet-Soulas, Emmanuelle

    2008-02-04

    In a previous study, we have described the elaboration of PLLA-based nanoparticles loaded with non radioactive dirhenium decacarbonyl [Re(2)(CO)(10)], a novel neutron-activatable radiopharmaceutical dosage form for intra-tumoral radiotherapy. These nanoparticles are designed for a neutron irradiation which can be carried out in a nuclear reactor facility. This new paper describes the neutron irradiation influence on these Re(2)(CO)(10)-loaded PLLA nanoparticles. The loaded nanoparticles with 23% (w/w) of metallic rhenium have shown to remain stable and separated and to keep out their sphericity at the lower neutron flux (1x10(11)n/cm(2)/s for 0.5h) which was used for rhenium content determination (neutron activation analysis, NAA). However, when loaded nanoparticles were irradiated at the higher neutron flux (1.45x10(13)n/cm(2)/s, 1h), they have shown to be partially coagglomerated and some pores appeared at their surface. Furthermore, DSC results showed a decrease in the PLLA melting point and melting enthalpy in both blank and loaded nanoparticles indicating a decrease in polymer crystallinity. In addition, the polymer molecular weights (M(n), M(w)) decreased after irradiation but without largely affecting the polymer polydispersity index (P.I.) which indicated that an irradiation-induced PLLA chain scission had occurred in a random way. The XRD patterns of irradiated PLLA provided another proof of polymer loss of crystallinity. FTIR spectra results have shown that irradiated nanoparticles retained the chemical identity of the used Re(2)(CO)(10) and PLLA despite the reduction in polymer crystallinity and molecular weight. Nanoparticles suspending after irradiation became also more difficult, but it was properly achievable by adding PVA (1%) and ethanol (10%) into the dispersing medium. Moreover, after 24h incubation of different irradiated nanoparticles in two different culture mediums, visual examination did not show bacterial growth indicating that applied

  16. 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.

  17. Synthesis and in vitro studies of gold nanoparticles loaded with docetaxel.

    PubMed

    de Oliveira, Rachel; Zhao, Pengxiang; Li, Na; de Santa Maria, Luiz Claudio; Vergnaud, Juliette; Ruiz, Jaime; Astruc, Didier; Barratt, Gillian

    2013-10-01

    The aim of these studies was to synthesize, characterize and evaluate the efficacy of pegylated gold nanoparticles (AuNPs) that differed in their PEG molecular weight, using PEG 550 and PEG 2000. The synthesis of the gold nanoparticles was carried out by modified Brust method with a diameter of 4-15 nm. The targeting agent folic acid was introduced by the covalent linkage. Finally, the anti-cancer drug docetaxel was encapsulated by the AuNPs by non covalent adsorption. The nanoparticles were characterized by transmission electron microscopy and used for in vitro studies against a hormone-responsive prostate cancer cell line, LnCaP. The loaded nanoparticles reduced the cell viability in more than 50% at concentrations of 6 nM and above after 144 h of treatment. Moreover, observation of prostate cancer cells by optical microscopy showed damage to the cells after exposure to drug-loaded AuNPs while unloaded AuNPs had much less effect.

  18. Hydrophobic Gentamicin-Loaded Nanoparticles Are Effective against Brucella melitensis Infection in Mice

    PubMed Central

    Imbuluzqueta, Edurne; Gamazo, Carlos; Lana, Hugo; Campanero, Miguel Ángel; Salas, David; Gil, Ana Gloria; Elizondo, Elisa; Ventosa, Nora; Veciana, Jaume

    2013-01-01

    The clinical management of human brucellosis is still challenging and demands in vitro active antibiotics capable of targeting the pathogen-harboring intracellular compartments. A sustained release of the antibiotic at the site of infection would make it possible to reduce the number of required doses and thus the treatment-associated toxicity. In this study, a hydrophobically modified gentamicin, gentamicin-AOT [AOT is bis(2-ethylhexyl) sulfosuccinate sodium salt], was either microstructured or encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The efficacy of the formulations developed was studied both in vitro and in vivo. Gentamicin formulations reduced Brucella infection in experimentally infected THP-1 monocytes (>2-log10 unit reduction) when using clinically relevant concentrations (18 mg/liter). Moreover, in vivo studies demonstrated that gentamicin-AOT-loaded nanoparticles efficiently targeted the drug both to the liver and the spleen and maintained an antibiotic therapeutic concentration for up to 4 days in both organs. This resulted in an improved efficacy of the antibiotic in experimentally infected mice. Thus, while 14 doses of free gentamicin did not alter the course of the infection, only 4 doses of gentamicin-AOT-loaded nanoparticles reduced the splenic infection by 3.23 logs and eliminated it from 50% of the infected mice with no evidence of adverse toxic effects. These results strongly suggest that PLGA nanoparticles containing chemically modified hydrophobic gentamicin may be a promising alternative for the treatment of human brucellosis. PMID:23650167

  19. Direct interaction of hydrophilic gold nanoparticles with dexamethasone drug: loading and release study.

    PubMed

    Venditti, Iole; Fontana, Laura; Fratoddi, Ilaria; Battocchio, Chiara; Cametti, Cesare; Sennato, Simona; Mura, Francesco; Sciubba, Fabio; Delfini, Maurizio; Russo, Maria Vittoria

    2014-03-15

    Water-soluble gold nanoparticles functionalized by sodium 3-mercapto-1-propansulfonate (Au-3MPS) were synthesized with different Au/thiol molar ratios for their ability to interact with biomolecules. In particular, a synthetic glucocorticoid steroid, i.e. dexamethasone (DXM) was selected. Herein, the formation of the Au-3MPS/DXM bioconjugate is reported. Au-3MPS nanoparticles show a plasmon resonance at 520 nm, have a spherical morphology and average size of 7-10 nm. The total number of gold atoms was estimated to be about 10600, with a surface component of 8800 atoms and a number of thiol ligands of about 720, roughly one anchored thiol every 10 surface gold atoms. The drug-nanoparticle interaction occurs through the fluorine atom of DXM and Au(I) atoms on the gold nanoparticle surface. The 3MPS ligands closely pack apart each other to leave room for the DXM, that lies at the gold surface in an unusual, almost parallel feature. The loading efficiency of DXM on Au-3MPS was assessed in the range 70-80%, depending on the thiol content. Moreover, our studies confirmed the drug release of about 70% in 5 days. Thanks to their unique properties, i.e. high water solubility, small size and almost monodispersity, Au-3MPS display high potential in biotechnological and biomedical applications, mainly for the loading and release of water insoluble drugs.

  20. Eugenol-loaded chitosan nanoparticles: I. Thermal stability improvement of eugenol through encapsulation.

    PubMed

    Woranuch, Sarekha; Yoksan, Rangrong

    2013-07-25

    The objective of the present work was to improve the thermal stability of eugenol by encapsulating into chitosan nanoparticles via an emulsion-ionic gelation crosslinking method. The influences of the initial eugenol content and tripolyphosphate (TPP) concentration on the loading capacity (LC), encapsulation efficiency (EE), morphology and surface charge of the eugenol-loaded chitosan nanoparticles were also investigated. LC and EE tended to increase with increasing initial eugenol content and decreasing TPP concentration. Particles with LC of 12% and EE of 20% exhibited a spherical shape with an average size of less than 100 nm. Thermal stability of the encapsulated eugenol was verified through its extrusion at 155°C with a model plastic, i.e. thermoplastic flour (TPF). TPF containing encapsulated eugenol showed 8-fold higher remaining eugenol content and 2.7-fold greater radical scavenging activity than that containing naked eugenol. The results suggest the possible use of eugenol-loaded chitosan nanoparticles as antioxidants in bioactive plastics for food packaging.

  1. Doxorubicin-loaded mesoporous silica nanoparticle composite nanofibers for long-term adjustments of tumor apoptosis

    NASA Astrophysics Data System (ADS)

    Yuan, Ziming; Pan, Yue; Cheng, Ruoyu; Sheng, Lulu; Wu, Wei; Pan, Guoqing; Feng, Qiming; Cui, Wenguo

    2016-06-01

    There is a high local recurrence (LR) rate in breast-conserving therapy (BCT) and enhancement of the local treatment is promising as a way to improve this. Thus we propose a drug delivery system using doxorubicin (DOX)-loaded mesoporous silica nanoparticle composite nanofibers which can release anti-tumor drugs in two phases—burst release in the early stage and sustained release at a later stage—to reduce the LR of BCT. In the present study, we designed a novel composite nanofibrous scaffold to realize the efficient release of drugs by loading both DOX and DOX-loaded mesoporous silica nanoparticles into an electrospun PLLA nanofibrous scaffold. In vitro results demonstrated that this kind of nanomaterial can release DOX in two phases, and the results of in vivo experiments showed that this hybrid nanomaterial significantly inhibited the tumor growth in a solid tumor model. Histopathological examination demonstrated that the apoptosis of tumor cells in the treated group over a 10 week period was significant. The anti-cancer effects were also accompanied with decreased expression of Bcl-2 and TNF-α, along with up-regulation of Bax, Fas and the activation of caspase-3 levels. The present study illustrates that the mesoporous silica nanoparticle composite nanofibrous scaffold could have anti-tumor properties and could be further developed as adjuvant therapeutic protocols for the treatment of cancer.

  2. High loading Pt nanoparticles on functionalization of carbon nanotubes for fabricating nonenzyme hydrogen peroxide sensor.

    PubMed

    Li, Xiaoyan; Liu, Xiuhui; Wang, Weiwei; Li, Lin; Lu, Xiaoquan

    2014-09-15

    A very efficient, simple approach was developed to fabricate a high Pt nanoparticles-loading multiwall carbon nanotube (MWCNTs) amperometric sensor for hydrogen peroxide (H2O2) determination. In this strategy, MWCNTs were first functionalized with an anionic surfactant, sodium dodecyl sulfate (SDS); then the Pt nanoparticles (NPs) were loaded on MWCNTs-SDS by electrodepositing. The large amounts of Pt nanoparticles could be well deposited on the surface of the MWCNTs-SDS modified electrode, as revealed by scanning electron microscopy (SEM). In addition, the PtNPs/MWCNTs-SDS composite was also characterized by electrochemical methods including cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The experimental results demonstrated that the constructed electrode exhibited good catalytic activity toward the hydrogen peroxide, and obtained a wide linear range from 5.8×10(-9) to 1.1×10(-3) M with a limit of detection (LOD) of 1.9×10(-9) M, which was superior to that obtained with other H2O2 electrochemical sensors reported previously. Moreover, it can also be applied to real samples analysis. The excellent performance of hydrogen peroxide sensor was ascribed to the MWCNTs-SDS composites being used as effective load matrix for the deposition of PtNPs and the synergistic amplification effect of the two kinds of nanomaterials-PtNPs and MWCNTs.

  3. Double loaded self-decomposable SiO₂ nanoparticles for sustained drug release.

    PubMed

    Zhao, Saisai; Zhang, Silu; Ma, Jiang; Fan, Li; Yin, Chun; Lin, Ge; Li, Quan

    2015-10-21

    Sustained drug release for a long duration is a desired feature of modern drugs. Using double-loaded self-decomposable SiO2 nanoparticles, we demonstrated sustained drug release in a controllable manner. The double loading of the drugs was achieved using two different mechanisms-the first one via a co-growth mechanism, and the second one by absorption. A two-phase sustained drug release was firstly revealed in an in vitro system, and then further demonstrated in mice. After a single intravenous injection, the drug was controllably released from the nanoparticles into blood circulation with a Tmax of about 8 h, afterwards a long lasting release pattern was achieved to maintain drug systemic exposure with a plasma elimination half-life of approximately 28 h. We disclosed that the absorbed drug molecules contributed to the initial fast release for quickly reaching the therapeutic level with relatively higher plasma concentrations, while the "grown-in" drugs were responsible for maintaining the therapeutic level via the later controlled slow and sustained release. The present nanoparticle carrier drug configuration and the loading/maintenance release mechanisms provide a promising platform that ensures a prolonged therapeutic effect by controlling drug concentrations within the therapeutic window-a sustained drug delivery system with a great impact on improving the management of chronic diseases.

  4. Antiretroviral Drugs-Loaded Nanoparticles Fabricated by Dispersion Polymerization with Potential for HIV/AIDS Treatment

    PubMed Central

    Ogunwuyi, Oluwaseun; Kumari, Namita; Smith, Kahli A.; Bolshakov, Oleg; Adesina, Simeon; Gugssa, Ayele; Anderson, Winston A.; Nekhai, Sergei; Akala, Emmanuel O.

    2016-01-01

    Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs. PMID:27013886

  5. Dual drug loaded chitosan nanoparticles-sugar--coated arsenal against pancreatic cancer.

    PubMed

    David, Karolyn Infanta; Jaidev, Leela Raghav; Sethuraman, Swaminathan; Krishnan, Uma Maheswari

    2015-11-01

    Pancreatic cancer is an aggressive form of cancer with poor survival rates. The increased mortality due to pancreatic cancer arises due to many factors such as development of multidrug resistance, presence of cancer stem cells, development of a stromal barrier and a hypoxic environment due to hypo-perfusion. The present study aims to develop a nanocarrier for a combination of drugs that can address these multiple issues. Quercetin and 5-fluorouracil were loaded in chitosan nanoparticles, individually as well as in combination. The nanoparticles were characterized for morphology, size, zeta potential, percentage encapsulation of drugs as well as their release profiles in different media. The dual drug-loaded carrier exhibited good entrapment efficiency (quercetin 95% and 5-fluorouracil 75%) with chitosan: quercetin: 5-fluorouracil in the ratio 3:1:2. The release profiles suggest that 5-fluorouracil preferentially localized in the periphery while quercetin was located towards the core of chitosan nanoparticles. Both drugs exhibited considerable association with the chitosan matrix. The dual drug-loaded carrier system exhibited significant toxicity towards pancreatic cancer cells both in the 2D as well as in the 3D cultures. We believe that the results from these studies can open up interesting options in the treatment of pancreatic cancer.

  6. Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment.

    PubMed

    Zamproni, Laura N; Mundim, Mayara V; Porcionatto, Marimelia A; des Rieux, Anne

    2017-03-15

    Recruiting neural stem cell (NSC) at the lesion site is essential for central nervous system repair. This process could be triggered by the local delivery of the chemokine SDF-1. We compared two PLGA formulations for local brain SDF-1 delivery: SDF-1 loaded microspheres (MS) and SDF-1 loaded nanoparticles (NP). Both formulations were able to encapsulate more than 80% of SDF-1 but presented different release profiles, with 100% of SDF-1 released after 6days for the MS and with 25% of SDF-1 released after 2 weeks for NP. SDF-1 bioactivity was demonstrated by a chemotactic assay. When injected in mouse brain after traumatic brain injury, only SDF-1 nanoparticles induced NSC migration to the damage area. More neuroblasts (DCX+ cells) could be visualized around the lesions treated with NP SDF-1 compared to the other conditions. Rostral migratory stream destabilization with massive migration of DCX+ cell toward the perilesional area was observed 2 weeks after NP SDF-1 injection. Local injection of SDF-1-loaded nanoparticles induces recruitment of NSC and could be promising for brain injury lesion.

  7. Buparvaquone loaded solid lipid nanoparticles for targeted delivery in theleriosis

    PubMed Central

    Soni, Maheshkumar P.; Shelkar, Nilakash; Gaikwad, Rajiv V.; Vanage, Geeta R.; Samad, Abdul; Devarajan, Padma V.

    2014-01-01

    Background: Buparvaquone (BPQ), a hydroxynaphthoquinone derivative, has been investigated for the treatment of many infections and is recommended as the gold standard for the treatment of theileriosis. Theileriosis, an intramacrophage infection is localized mainly in reticuloendotheileial system (RES) organs. The present study investigates development of solid lipid nanoparticles (SLN) of BPQ for targeted delivery to the RES. Materials and Methods: BPQ SLN was prepared using melt method by adding a molten mixture into aqueous Lutrol F68 solution (80°C). Larger batches were prepared up to 6 g of BPQ with GMS: BPQ, 2:1. SLN of designed size were obtained using ultraturrax and high pressure homogenizer. A freeze and thaw study was used to optimize type and concentration of cryoprotectant with Sf: Mean particle size, Si: Initial particle size <1.3. Differential scanning calorimetry (DSC), powder X-ray diffraction (XRD) and scanning electron microscope (SEM) study was performed on optimized formulation. Formulation was investigated for in vitro serum stability, hemolysis and cell uptake study. Pharmacokinetic and biodistribution study was performed in Holtzman rat. Results: Based on solubility in lipid; glyceryl monostearate (GMS) was selected for preparation of BPQ SLN. Batches of BPQ SLN were optimized for average particle size and entrapment efficiency at <100 mg solid content. A combination of Solutol HS-15 and Lutrol F68 at 2% w/v and greater enabled the desired Sf/Si < 1.3. Differential scanning calorimetry and powder X-ray diffraction revealed decrease in crystallinity of BPQ in BPQ SLN while, scanning electron microscope revealed spherical morphology. BPQ SLN revealed good stability at 4°C and 25°C. Low hemolytic potential (<8%) and in vitro serum stability up to 5 h was observed. Cytotoxicity of SLN to the U937 cell was low. The macrophage cell line revealed high (52%) uptake of BPQ SLN in 1 h suggesting the potential to RES uptake. SLN revealed longer

  8. Curcumin-Loaded Chitosan-Coated Nanoparticles as a New Approach for the Local Treatment of Oral Cavity Cancer.

    PubMed

    Mazzarino, Leticia; Loch-Neckel, Gecioni; Bubniak, Lorena Dos Santos; Mazzucco, Suelen; Santos-Silva, Maria Cláudia; Borsali, Redouane; Lemos-Senna, Elenara

    2015-01-01

    Mucoadhesive nanoparticles loaded with curcumin were developed as a new approach to deliver curcumin for the local treatment of oral cancer. PCL nanoparticles coated with chitosan displaying different molar masses were prepared by using the nanoprecipitation technique. The mucoadhesive properties of nanoparticle suspensions were demonstrated by their strong ability to interact with the glycoprotein mucin through electrostatic interactions. Similar permeation profiles of curcumin loaded in uncoated and chitosan-coated nanoparticles across porcine esophageal mucosa were verified. Curcumin concentrations retained in the mucosa suggest the possibility of a local effect of the drug. In vitro studies demonstrated that free curcumin.and curcumin loaded into nanoparticles coated with chitosan caused significant reduction of SCC-9 human oral cancer cell viability in a concentration and time-dependent manner. However, no significant cell death was observed after 24 h of treatment with unloaded nanoparticles coated with chitosan. In addition, curcumin-loaded nanoparticles showed reduced cytotoxicity, when compared with the free drug. Therefore, chitosan-coated PCL nanoparticles may be considered a promising strategy to deliver curcumin directly into the oral cavity for the treatment of oral cancer.

  9. "Smart" drug loaded nanoparticle delivery from a self-healing hydrogel enabled by dynamic magnesium-biopolymer chemistry.

    PubMed

    Shi, Liyang; Han, Yuanyuan; Hilborn, Jöns; Ossipov, Dmitri

    2016-09-25

    We report a strategy to generate a self-healing and pH responsive hydrogel network between drug-loaded nanoparticles and natural polysaccharides via magnesium-bisphosphonate ligand interactions. The injectable drug depot disassembles in a tumor-specific environment, providing localized uptake of the nanoparticles, which is highly appreciated in drug delivery applications and manufacturing of drug-loaded biomaterials using a syringe-based deposition technique.

  10. Preparation, characterisation and antibacterial activity of a florfenicol-loaded solid lipid nanoparticle suspension.

    PubMed

    Wang, Ting; Chen, Xiaojin; Lu, Mengmeng; Li, Xihe; Zhou, WenZhong

    2015-12-01

    A florfenicol-loaded solid lipid nanoparticle (FFC-SLN) suspension was prepared by hot homogenisation and ultrasonic technique. The suspension was characterised for its release profile, stability, toxicity, and the physicochemical properties of the nanoparticles. Antibacterial activity of the suspension was evaluated in vitro and in vivo. The results showed that the mean diameter, polydispersity index and zeta potential of the nanoparticles were 253 ± 3 nm, 0.409 ± 0.022 and 47.5 ± 0.21 mV, respectively. In vitro release profile showed the FFC-SLN suspension had sustained release effect. The minimum inhibition concentration values of the FFC-SLN suspension were 6 and 3 µg/mL against Staphylococcus aureus and Escherichia coli respectively, compared with 3.5 and 2 µg/mL of native florfenicol. The suspension was relatively stable at 4°C and less stable at room temperature during 9 months storage. Although the nanoparticle carriers exhibited cytotoxicity in cell cultures, the LD50 of the lyophilised dry power of the suspension was higher than 5 g/kg body weight. Mortality protection against E. coli lethal infection in mice showed that the nanoparticle suspension had much better efficacy (6/10) than native drug (1/10). These results indicate that FFC-SLN suspension could be a promising formulation in veterinary medicine.

  11. Preparation of Temozolomide-Loaded Nanoparticles for Glioblastoma Multiforme Targeting—Ideal Versus Reality

    PubMed Central

    Lee, Chooi Yeng; Ooi, Ing Hong

    2016-01-01

    Temozolomide (TMZ) is one of the most effective chemotherapeutic agents for glioblastoma multiforme, but the required high administration dose is accompanied by side effects. To overcome this problem and to further improve TMZ’s efficacy, targeted delivery of TMZ by using polymeric nanoparticles has been explored. We synthesised the PLGA-PEG-FOL copolymer and attempted encapsulation of TMZ into PLGA-PEG-FOL nanoparticles using the emulsion solvent evaporation method and the nanoprecipitation method. Conjugation of PEG and FOL to PLGA has been reported to be able to increase the delivery of TMZ to the brain as well as targeting the glioma cells. However, despite making numerous modifications to these methods, the loading of TMZ in the nanoparticles only ranged between 0.2% and 2%, and the nanoparticles were between 400 nm and 600 nm in size after freeze-drying. We proceed with determining the release profile of TMZ in phosphate buffered saline (PBS). Our initial data indicated that TMZ was slowly released from the nanoparticles. The metabolite of TMZ rather than the parent compound was detected in PBS. Our study suggests that while PLGA-PEG-FOL can be used as a polymeric or encapsulation material for central delivery of TMZ, a practical and cost effective formulation method is still far from reach. PMID:27618068

  12. Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance.

    PubMed

    Su, Yongsheng; Hu, Jian; Huang, Zhibin; Huang, Yubin; Peng, Bingsheng; Xie, Ni; Liu, Hui

    2017-01-01

    Malignant melanoma (MM) is the most dangerous type of skin cancer with annually increasing incidence and death rates. However, chemotherapy for MM is restricted by low topical drug concentration and multidrug resistance. In order to surmount the limitation and to enhance the therapeutic effect on MM, a new nanoformulation of paclitaxel (PTX)-loaded cholic acid (CA)-functionalized star-shaped poly(lactide-co-glycolide) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (NPs) (shortly PTX-loaded CA-PLGA-TPGS NPs) was fabricated by a modified method of nanoprecipitation. The particle size, zeta potential, morphology, drug release profile, drug encapsulation efficiency, and loading content of PTX-loaded NPs were detected. As shown by confocal laser scanning, NPs loaded with coumarin-6 were internalized by human melanoma cell line A875. The cellular uptake efficiency of CA-PLGA-TPGS NPs was higher than those of PLGA NPs and PLGA-TPGS NPs. The antitumor effects of PTX-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that star-shaped PTX-loaded CA-PLGA-TPGS NPs were significantly superior to commercial PTX formulation Taxol(®). Such drug delivery nanocarriers are potentially applicable to the improvement of clinical MM therapy.

  13. Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance

    PubMed Central

    Su, Yongsheng; Hu, Jian; Huang, Zhibin; Huang, Yubin; Peng, Bingsheng; Xie, Ni; Liu, Hui

    2017-01-01

    Malignant melanoma (MM) is the most dangerous type of skin cancer with annually increasing incidence and death rates. However, chemotherapy for MM is restricted by low topical drug concentration and multidrug resistance. In order to surmount the limitation and to enhance the therapeutic effect on MM, a new nanoformulation of paclitaxel (PTX)-loaded cholic acid (CA)-functionalized star-shaped poly(lactide-co-glycolide) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (NPs) (shortly PTX-loaded CA-PLGA-TPGS NPs) was fabricated by a modified method of nanoprecipitation. The particle size, zeta potential, morphology, drug release profile, drug encapsulation efficiency, and loading content of PTX-loaded NPs were detected. As shown by confocal laser scanning, NPs loaded with coumarin-6 were internalized by human melanoma cell line A875. The cellular uptake efficiency of CA-PLGA-TPGS NPs was higher than those of PLGA NPs and PLGA-TPGS NPs. The antitumor effects of PTX-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that star-shaped PTX-loaded CA-PLGA-TPGS NPs were significantly superior to commercial PTX formulation Taxol®. Such drug delivery nanocarriers are potentially applicable to the improvement of clinical MM therapy. PMID:28293102

  14. Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl)porphyrin-loaded nanoparticles for photodynamic therapy.

    PubMed

    Konan, Yvette Niamien; Cerny, Radovan; Favet, Joselyne; Berton, Myriam; Gurny, Robert; Allémann, Eric

    2003-01-01

    A photosensitizer, meso-tetra(4-hydroxyphenyl)porphyrin, was incorporated into sub-150 nm nanoparticles using the emulsification-diffusion technique in order to perform sterilization by filtration using 0.22 microm membranes. The three selected polyesters (poly(D,L-lactide-co-glycolide), (50:50 PLGA, 75:25 PLGA) and poly(D,L-lactide (PLA)) for the nanoparticle production were all amorphous in nature and have similar molecular weights but different copolymer molar ratios. The influence of the copolymer molar ratio and the theoretical drug loading was investigated in terms of particle size, drug loading, entrapment efficiency and surface characteristics. With all the polymers used, sub-150 nm nanoparticles were produced with good reproducibility and narrow size distributions irrespective of both the polymer nature and the theoretical drug loading. After purification by cross-flow filtration, the nanoparticle suspensions were sterilized by membrane filtration and freeze-dried in the presence of a lyoprotectant (trehalose). For all types of nanoparticles, complete redispersion in various media could be obtained. All final freeze-dried products were refiltrable on a 0.22 microm membrane and were stable in terms of mean particle size and drug loading over a period up to 6 months. The effective drug loading increased at higher theoretical drug loading, the entrapment efficiency was however decreased. The same trend was observed with the three polyesters. The sterility of the final freeze-dried nanoparticles was confirmed by the results of the sterility testing which showed no bacterial contamination.

  15. Antifungal efficacy of itraconazole-loaded TPGS-b-(PCL-ran-PGA) nanoparticles

    PubMed Central

    Qiu, Lixin; Hu, Bicheng; Chen, Hongbo; Li, Shanshan; Hu, Yuqian; Zheng, Yi; Wu, Xinxing

    2015-01-01

    This research was conducted to formulate biodegradable itraconazole (ITZ)-loaded d-a-tocopheryl polyethylene glycol 1000 succinate-b-poly(e-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA); TPP) nanoparticles (NPs) (designed as ITZ-loaded TPP NPs) to improve antifungal efficacy. ITZ-loaded TPP NPs were prepared by a modified double-emulsion method, and their size distribution, morphology, zeta potential, drug encapsulation efficiency, drug-release profile, and antifungal effects were characterized. The cytotoxicity of ITZ-loaded-TPP NPs on HeLa cells and fibroblasts was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The in vivo antifungal activity of ITZ-loaded-TPP NPs was examined in mice by administrating 5×105 colony forming units of Candida albicans through the tail vein. The survival rate and survival time of the mice was observed. The fungal count and pathology of lung tissue was analyzed. The data showed that ITZ-loaded-TPP NPs have size of 265±5.8 nm, zeta potential of −31±0.5 mV, high encapsulation efficiency (95%), and extended drug-release profile. ITZ-loaded-TPP NPs at a high concentration of 25 mg/mL had no cytotoxicity on HeLa cells and fibroblasts. Furthermore, ITZ-loaded-TPP NPs achieved a higher level of antifungal activity both in vitro and in vivo. The survival rate and duration was higher in mice treated by ITZ-loaded-TPP NPs than in the other groups (P<0.05). In conclusion, ITZ-loaded-TPP NPs significantly improved ITZ bioavailability by increasing its aqueous dispersibility and extending the duration of drug release, thereby improving the antifungal efficacy of the ITZ agent. PMID:25733833

  16. Oleyl-hyaluronan micelles loaded with upconverting nanoparticles for bio-imaging

    NASA Astrophysics Data System (ADS)

    Pospisilova, Martina; Mrazek, Jiri; Matuska, Vit; Kettou, Sofiane; Dusikova, Monika; Svozil, Vit; Nesporova, Kristina; Huerta-Angeles, Gloria; Vagnerova, Hana; Velebny, Vladimir

    2015-09-01

    Hyaluronan (HA) represents an interesting polymer for nanoparticle coating due to its biocompatibility and enhanced cell interaction via CD44 receptor. Here, we describe incorporation of oleate-capped β-NaYF4:Yb3+, Er3+ nanoparticles (UCNP-OA) into amphiphilic HA by microemulsion method. Resulting structures have a spherical, micelle-like appearance with a hydrodynamic diameter of 180 nm. UCNP-OA-loaded HA micelles show a good stability in PBS buffer and cell culture media. The intensity of green emission of UCNP-OA-loaded HA micelles in water is about five times higher than that of ligand-free UCNP, indicating that amphiphilic HA effectively protects UCNP luminescence from quenching by water molecules. We found that UCNP-OA-loaded HA micelles in concentrations up to 50 μg mL-1 increase cell viability of normal human dermal fibroblasts (NHDF), while viability of human breast adenocarcinoma cells MDA-MB-231 is reduced at these concentrations. The utility of UCNP-OA-loaded HA micelles as a bio-imaging probe was demonstrated in vitro by successful labelling of NHDF and MDA-MB-231 cells overexpressing the CD44 receptor.

  17. Methylene blue covalently loaded polyacrylamide nanoparticles for enhanced tumor-targeted photodynamic therapy†

    PubMed Central

    Qin, Ming; Hah, Hoe Jin; Kim, Gwangseong; Nie, Guochao; Lee, Yong-Eun Koo

    2013-01-01

    The use of targeted nanoparticles (NPs) as a platform for loading photosensitizers enables selective accumulation of the photosensitizers in the tumor area, while maintaining their photodynamic therapy (PDT) effectiveness. Here two novel kinds of methylene blue (MB)-conjugated polyacrylamide (PAA) nanoparticles, MBI-PAA NPs and MBII-PAA NPs, based on two separate MB derivatives, are developed for PDT. This covalent conjugation with the NPs (i) improves the loading of MB, (ii) prevents any leaching of MB from the NPs and (iii) protects the MB from the effects of enzymes in the biological environment. The loading of MB into these two kinds of NPs was controlled by the input amount, resulting in concentrations with optimal singlet oxygen production. For each of the MB-NPs, the highest singlet oxygen production was found for an MB loading of around 11 nmol mg−1. After attachment of F3 peptide groups, for targeting, each of these NPs was taken up, selectively, by MDA-MB-435 tumor cells, in vitro. PDT tests demonstrated that both kinds of targeted NPs resulted in effective tumor cell kill, following illumination, while not causing dark toxicity. PMID:21479315

  18. Thermal decomposition behaviors and kinetic properties of 1,8-naphthalic anhydride loaded dense nano-silica hybrids

    NASA Astrophysics Data System (ADS)

    Wang, Jinpeng; Sun, Jihong; Wang, Feng; Ren, Bo

    2013-06-01

    A certain amount of (3-aminopropyl)triethoxysilane (APTES) and various capacity of 1,8-naphthalic anhydride (NA) were employed to modify and then graft onto the surface of the dense nano-silica spheres (DNSS) via a post-grafting method, and thereby, a novel luminescent density nano-silica hybrid materials have been successfully synthesized. Meanwhile, the structures and properties of obtained hybrid DNSS were characterized by XRD, TEM, N2 sorption, FT-IR, and TG analysis. Furthermore, the thermal stability of before and after modification were demonstrated by using both Kissinger methods and Ozawa-Flynn-Wall methods. Particularly, the thermal decomposition behaviors of amino-modified groups and NA-grafted organic molecules were emphasized based on the TG and DTG analysis and then the related mechanism was put forward according to Coats and Redfern methods. Finally, as a comparison, the obtained results and the proposed decomposition mechanism of hybrid DNSS with non-pores were discussed with that of mesopores silicas in details.

  19. Development and evaluation of topotecan loaded solid lipid nanoparticles: A study in cervical cancer cell lines.

    PubMed

    Chen, Zhao-Jie; Zhang, Zhen; Xie, Bei-Bei; Zhang, Hai-Yan

    2016-12-01

    The study aims at statistical development of solid lipid nanoparticles (SLNs) loaded with topotecan hydrochloride for avoiding the drawbacks of conventional drug therapies used in cervical cancer. Twenty SLN batches were prepared using organic solvent evaporation method to provide response surface curves. Thereafter, optimized SLNs were obtained using numeric method based on desirability functions providing maximum drug loading and appropriate particle size. Physical characterization of optimized TPH loaded SLNs was performed in terms of particle size, zeta potential, transmission and scanning electron microscopic evaluation. Cytotoxicity studies were performed against cervical cancer cell lines, including cervical squamous cell carcinoma cell line (HeLa) and human squamous cell carcinoma cell line (SiHa). Also, Swiss mouse embryo fibroblast cells (3T3-L1) and African green monkey kidney epithelial (Vero) cells were used to evaluate biocompatibility in normal cells. As pronounced from the results, optimized SLNs may provide an attractive alternative to conventional cervical cancer drug products.

  20. High precision and high yield fabrication of dense nanoparticle arrays onto DNA origami at statistically independent binding sites

    NASA Astrophysics Data System (ADS)

    Takabayashi, Sadao; Klein, William P.; Onodera, Craig; Rapp, Blake; Flores-Estrada, Juan; Lindau, Elias; Snowball, Lejmarc; Sam, Joseph T.; Padilla, Jennifer E.; Lee, Jeunghoon; Knowlton, William B.; Graugnard, Elton; Yurke, Bernard; Kuang, Wan; Hughes, William L.

    2014-10-01

    High precision, high yield, and high density self-assembly of nanoparticles into arrays is essential for nanophotonics. Spatial deviations as small as a few nanometers can alter the properties of near-field coupled optical nanostructures. Several studies have reported assemblies of few nanoparticle structures with controlled spacing using DNA nanostructures with variable yield. Here, we report multi-tether design strategies and attachment yields for homo- and hetero-nanoparticle arrays templated by DNA origami nanotubes. Nanoparticle attachment yield via DNA hybridization is comparable with streptavidin-biotin binding. Independent of the number of binding sites, >97% site-occupation was achieved with four tethers and 99.2% site-occupation is theoretically possible with five tethers. The interparticle distance was within 2 nm of all design specifications and the nanoparticle spatial deviations decreased with interparticle spacing. Modified geometric, binomial, and trinomial distributions indicate that site-bridging, steric hindrance, and electrostatic repulsion were not dominant barriers to self-assembly and both tethers and binding sites were statistically independent at high particle densities.High precision, high yield, and high density self-assembly of nanoparticles into arrays is essential for nanophotonics. Spatial deviations as small as a few nanometers can alter the properties of near-field coupled optical nanostructures. Several studies have reported assemblies of few nanoparticle structures with controlled spacing using DNA nanostructures with variable yield. Here, we report multi-tether design strategies and attachment yields for homo- and hetero-nanoparticle arrays templated by DNA origami nanotubes. Nanoparticle attachment yield via DNA hybridization is comparable with streptavidin-biotin binding. Independent of the number of binding sites, >97% site-occupation was achieved with four tethers and 99.2% site-occupation is theoretically possible with five

  1. MO-FG-BRA-05: Next Generation Radiotherapy Biomaterials Loaded With Gold Nanoparticles

    SciTech Connect

    Cifter, G; Ngwa, W; Sajo, E; Korideck, H; Cormack, R; Makrigiorgos, G; Kumar, R; Sridhar, S

    2015-06-15

    Purpose: It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. In this work, we developed prototypes of such RT biomaterials and investigated the sustained release of GNPs from the biomaterials as a function of design parameters. Methods: Prototype smart biomaterials were produced by incorporating the GNPs in poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. For comparison, commercially available spacers were also coated with a polymer film loaded with fluorescent GNP. Optical/spectroscopy methods were used to monitor in vitro release of GNPs over time as a function of different design parameters: polymer weighting, type, and initial (loading) GNP concentrations. Inductively coupled plasma mass spectrometry was employed to verify GNP release. Results: Results showed that gold nanoparticles could be successfully loaded in the new RT biomaterial prototypes. Burst release of GNPs could be achieved within 1 to 25 days depending on the preparation approach. Burst release was followed by sustained release profile over time. The amount of released GNP increased with increasing loading concentration as expected. The release profiles could also be customized as a function of polymer weighting, or preparation approaches. Conclusion: Considered together, our results highlight potential for the development of next generation RT biomaterials loaded with GNPs customizable to different RT schedules. Such biomaterials could be employed as needed instead of currently used inert spacers/fiducials at no additional inconvenience to patients, to enhance RT.

  2. Solid Lipid Nanoparticles Loaded with Retinoic Acid and Lauric Acid as an Alternative for Topical Treatment of Acne Vulgaris.

    PubMed

    Silva, Elton Luiz; Carneiro, Guilherme; De Araújo, Lidiane Advíncula; Trindade, Mariana de Jesus Vaz; Yoshida, Maria Irene; Oréfice, Rodrigo Lambert; Farias, Luis de Macêdo; De Carvalho, Maria Auxiliadora Roque; Dos Santos, Simone Gonçalves; Goulart, Gisele Assis Castro; Alves, Ricardo José; Ferreira, Lucas Antônio Miranda

    2015-01-01

    Topical therapy is the first choice for the treatment of mild to moderate acne and all-trans retinoic acid is one of the most used drugs. The combination of retinoids and antimicrobials is an innovative approach for acne therapy. Recently, lauric acid, a saturated fatty acid, has shown strong antimicrobial activity against Propionibacterium acnes. However, topical application of retinoic acid is followed by high incidence of side-effects, including erythema and irritation. Solid lipid nanoparticles represent an alternative to overcome these side-effects. This work aims to develop solid lipid nanoparticles loaded with retinoic acid and lauric acid and evaluate their antibacterial activity. The influence of lipophilic stearylamine on the characteristics of solid lipid nanoparticles was investigated. Solid lipid nanoparticles were characterized for size, zeta potential, encapsulation efficiency, differential scanning calorimetry and X-ray diffraction. The in vitro inhibitory activity of retinoic acid-lauric acid-loaded solid lipid nanoparticles was evaluated against Propionibacterium acnes, Staphylococcus aureus and Staphylococcus epidermidis. High encapsulation efficiency was obtained at initial time (94 ± 7% and 100 ± 4% for retinoic acid and lauric acid, respectively) and it was demonstrated that lauric acid-loaded-solid lipid nanoparticles provided the incorporation of retinoic acid. However, the presence of stearylamine is necessary to ensure stability of encapsulation. Moreover, retinoic acid-lauric acid-loaded solid lipid nanoparticles showed growth inhibitory activity against Staphylococcus epidermidis, Propionibacterium acnes and Staphylococcus aureus, representing an interesting alternative for the topical therapy of acne vulgaris.

  3. Efficient antitumor effect of co-drug-loaded nanoparticles with gelatin hydrogel by local implantation

    PubMed Central

    Zhang, Hao; Tian, Yong; Zhu, Zhenshu; Xu, Huae; Li, Xiaolin; Zheng, Donghui; Sun, Weihao

    2016-01-01

    Tetrandrine (Tet) could enhance the antitumor effect of Paclitaxel (Ptx) by increasing intracellular Reactive Oxygen Species (ROS) levels, which leads to the possibility of co-delivery of both drugs for synergistic antitumor effect. In the current study, we reported an efficient, local therapeutic strategy employing effective Tet and Ptx delivery with a nanoparticle-loaded gelatin system. Tet- and Ptx co-loaded mPEG-PCL nanoparticles (P/T-NPs) were encapsulated into the physically cross-linked gelatin hydrogel and then implanted on the tumor site for continuous drug release. The drug-loaded gelatin hydrogel underwent a phase change when the temperature slowly increased. In vitro study showed that Tet/Ptx-loaded PEG-b-PCL nanoparticles encapsulated within a gelatin hydrogel (P/T-NPs-Gelatin) inhibited the growth and invasive ability of BGC-823 cells more effectively than the combination of free drugs or P/T-NPs. In vivo study validated the therapeutic potential of P/T-NPs-Gelatin. P/T-NPs-Gelatin significantly inhibited the activation of p-Akt and the downstream anti-apoptotic Bcl-2 protein and also inducing the activation of pro-apoptotic Bax protein. Moreover, the molecular-modulating effect of P/T-NPs-Gelatin on related proteins varied slightly under the influence of NAC, which was supported by the observations of the tumor volumes and weights. Based on these findings, local implantation of P/T-NPs-Gelatin may be a promising therapeutic strategy for the treatment of gastric cancer. PMID:27226240

  4. Impact of enzyme loading on the efficacy and recovery of cellulolytic enzymes immobilized on enzymogel nanoparticles.

    PubMed

    Samaratunga, Ashani; Kudina, Olena; Nahar, Nurun; Zakharchenko, Andrey; Minko, Sergiy; Voronov, Andriy; Pryor, Scott W

    2015-03-01

    Cellulase and β-glucosidase were adsorbed on a polyacrylic acid polymer brush grafted on silica nanoparticles to produce enzymogels as a form of enzyme immobilization. Enzyme loading on the enzymogels was increased to a saturation level of approximately 110 μg (protein) mg(-1) (particle) for each enzyme. Enzymogels with varied enzyme loadings were then used to determine the impact on hydrolysis rate and enzyme recovery. Soluble sugar concentrations during the hydrolysis of filter paper and Solka-Floc with the enzymogels were 45 and 53%, respectively, of concentrations when using free cellulase. β-Glucosidase enzymogels showed lower performance; hydrolyzate glucose concentrations were just 38% of those using free enzymes. Increasing enzyme loading on the enzymogels did not reduce net efficacy for cellulase and improved efficacy for β-glucosidase. The use of free cellulases and cellulase enzymogels resulted in hydrolyzates with different proportions of cellobiose and glucose, suggesting differential attachment or efficacy of endoglucanases, exoglucanases, and β-glucosidases present in cellulase mixtures. When loading β-glucosidase individually, higher enzyme loadings on the enzymogels produced higher hydrolyzate glucose concentrations. Approximately 96% of cellulase and 66 % of β-glucosidase were recovered on the enzymogels, while enzyme loading level did not impact recovery for either enzyme.

  5. Antimicrobial Activity of Glass lonomer Cement Incorporated with Chlorhexidine-Loaded Zeolite Nanoparticles.

    PubMed

    Kim, Hyun-Jin; Son, Jun Sik; Kim, Kyo-Han; Kwon, Tae-Yub

    2016-02-01

    A functional dental restorative system with antimicrobial properties was developed using zeolite (ZE) nanoparticles (NPs) as a drug delivery carrier. ZE NPs loaded with chlorhexidine (CHX) were prepared using the ionic immobilization method. The resulting CHX-loaded ZE NPs were then incorporated into commercial dental glass ionomer cement (GIC). The average size of the CHX-loaded ZE NPs was about 100 to 200 nm, and the NPs were dispersed homogeneously in the GIC. The in vitro release profile of encapsulated GIC containing CHX showed an early release burst of approximately 30% of the total CHX by day 7, whereas GIC containing CHX-loaded ZE NPs showed a sustained release of CHX without the early release burst in a 4-week immersion study. The agar diffusion test results showed that the GIC incorporated with CHX-loaded ZE NPs showed a larger growth inhibition zone of Streptococcus mutans than GIC alone, indicating that this innovative delivery platform potently imparted antimicrobial activity to the GIC. Moreover, these findings suggest that a range of antimicrobial drugs that inhibit the growth of oral bacteria can be incorporated efficiently into dental GIC using CHX-loaded ZE NPs.

  6. Formation of enriched black tea extract loaded chitosan nanoparticles via electrospraying

    NASA Astrophysics Data System (ADS)

    Hammond, Samuel James

    Creating nanoparticles of beneficial nutraceuticals and pharmaceuticals has had a large surge of research due to the enhancement of absorption and bioavailability by decreasing their size. One of these ways is by electrohydrodynamic atomization, also known as electrospraying. In general, this novel process is done by forcing a liquid through a capillary nozzle and which is subjected to an electrical field. While there are different ways to create nanoparticles, the novel method of electrospraying can be beneficial over other types of nanoparticle formation. Reasons include high control over particle size and distribution by altering electrospray parameters (voltage, flow rate, distance, and time), higher encapsulation efficiency than other methods, and also it is a one step process without exposure to extreme conditions (Gomez-Estaca et. al. 2012, Jaworek and Sobcyzk 2008). The current study aimed to create a chitosan encapsulated theaflavin-2 enriched black tea extract (BTE) nanoparticles via electrospraying. The first step of this process was to create the smallest chitosan nanoparticles possible by altering the electrospray parameters and the chitosan-acetic acid solution parameters. The solution properties altered include chitosan molecular weight, acetic acid concentration, and chitosan concentration. Specifically, the electrospray parameters such as voltage, flow rate and distance from syringe to collector are the most important in determining particle size. After creating the smallest chitosan particles, the TF-2 enriched black tea extract was added to the chitosan-acetic acid solution to be electrosprayed. The particles were assessed with the following procedures: Atomic force microscopy (AFM) and scanning electron microscopy (SEM) for particle morphology and size, and loading efficiency with ultraviolet--visible spectrophotometer (UV-VIS). Chitosan-BTE nanoparticles were successfully created in a one step process. Diameter of the particles on average

  7. Transport of digoxin-loaded polymeric nanoparticles across BeWo cells, an in vitro model of human placental trophoblast

    PubMed Central

    Albekairi, Norah A; Al-Enazy, Sanaalarab; Ali, Shariq; Rytting, Erik

    2015-01-01

    Background: Fetal arrhythmias can lead to fetal congestive heart failure and hydrops fetalis. Digoxin (the first-line treatment) has low transplacental permeability and high risk of maternal side effects. Biodegradable digoxin-loaded PEGylated poly(lactic-co-glycolic acid) nanoparticles may increase digoxin transport across BeWo b30 cell monolayers (an in vitro model of trophoblast in human placenta) by reducing the drug's interaction with P-gp. Results/methodology: The nanoparticles showed high encapsulation efficiency and sustained release over 48 h. Transport studies revealed significantly increased permeability across BeWo cell layers of digoxin-loaded nanoparticles when compared with free digoxin. P-gp inhibition also increased the permeability of digoxin, but not digoxin-loaded nanoparticles. Conclusion: This represents a novel treatment strategy for fetal cardiovascular disease which may improve maternal and fetal outcomes. PMID:26652279

  8. Enhanced cellular uptake and cytotoxicity of folate decorated doxorubicin loaded PLA-TPGS nanoparticles

    NASA Astrophysics Data System (ADS)

    Nguyen, Hoai Nam; Nhung Hoang, Thi My; Thu Trang Mai, Thi; Quynh Trang Nguyen, Thi; Doan Do, Hai; Hien Pham, Thi; Lap Nguyen, Thi; Thu Ha, Phuong

    2015-01-01

    Doxorubicin (DOX) is one of the most effective anticancer drugs for treating many types of cancer. However, the clinical applications of DOX were hindered because of serious side-effects resulting from the unselective delivery to cancer cell including congestive heart failure, chronic cardiomyopathy and drug resistance. Recently, it has been demonstrated that loading anti-cancer drugs onto drug delivery nanosystems helps to maximize therapeutic efficiency and minimize unwanted side-effects via passive and active targeting mechanisms. In this study we prepared folate decorated DOX loaded PLA-TPGS nanoparticles with the aim of improving the potential as well as reducing the side-effects of DOX. Characteristics of nanoparticles were investigated by field emission scanning electron microscopy (FESEM), dynamic light scattering (DLS) method and Fourier transform infrared spectroscopy (FTIR). Anticancer activity of the nanoparticles was evaluated through cytotoxicity and cellular uptake assays on HeLa and HT29 cancer cell lines. The results showed that prepared drug delivery system had size around 100 nm and exhibited higher cytotoxicity and cellular uptake on both tested HeLa and HT29 cells.

  9. Formulation of curcumin-loaded solid lipid nanoparticles produced by fatty acids coacervation technique.

    PubMed

    Chirio, Daniela; Gallarate, Marina; Peira, Elena; Battaglia, Luigi; Serpe, Loredana; Trotta, Michele

    2011-01-01

    Curcumin (CU) loaded solid lipid nanoparticles (SLNs) of fatty acids (FA) were prepared with a coacervation technique based on FA precipitation from their sodium salt micelles in the presence of polymeric non-ionic surfactants. Myristic, palmitic, stearic, and behenic acids, and different polymers with various molecular weights and hydrolysis grades were employed as lipid matrixes and stabilisers, respectively. Generally, spherical-shaped nanoparticles with mean diameters below 500 nm were obtained, and using only middle-high hydrolysis, grade-polymer SLNs with diameters lower than 300 nm were produced. CU encapsulation efficiency was in the range 28-81% and highly influenced by both FA and polymer type. Chitosan hydrochloride was added to FA SLN formulations to produce bioadhesive, positively charged nanoparticles. A CU-chitosan complex formation could be hypothesised by DSC analysis, UV-vis spectra and chitosan surface tension determination. A preliminary study on HCT-116 colon cancer cells was developed to evaluate the influence of CU-loaded FA SLNs on cell viability.

  10. Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer

    PubMed Central

    Jing, Lijia; shao, shangmin; Wang, Yang; Yang, Yongbo; Yue, Xiuli; Dai, Zhifei

    2016-01-01

    This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect. PMID:26722372

  11. Hyaluronic Acid Modified Hollow Prussian Blue Nanoparticles Loading 10-hydroxycamptothecin for Targeting Thermochemotherapy of Cancer.

    PubMed

    Jing, Lijia; Shao, Shangmin; Wang, Yang; Yang, Yongbo; Yue, Xiuli; Dai, Zhifei

    2016-01-01

    This paper reported the fabrication of a multifunctional nanoplatform by modifying hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene glycol, followed by loading 10-hydroxycamptothecin for tumor-targeted thermochemotherapy. It was found that the surface modification of hollow Prussian blue nanoparticles with hyaluronic acid grafting polyethylene endowed a great colloidal stability, long blood circulation time and the capability for targeting Hela cells over-expressing the CD44 receptor. The obtained nanoagent exhibited efficient photothermal effect and a light triggered and stepwise release behavior of 10-hydroxycamptothecin due to the strong optical absorption in the near-infrared region. The investigations on the body weight change, histological injury and blood biochemical indexes showed that such nanoagent had excellent biocompatibility for medical application. Both in vitro and in vivo experiments proved that the combination of chemotherapy and photothermal therapy through the agent of hyaluronic acid modified Prussian blue nanoparticles loading 10-hydroxycamptothecin could significantly improve the therapeutic efficacy compared with either therapy alone because of a good synergetic effect.

  12. Moxifloxacin loaded gelatin nanoparticles for ocular delivery: Formulation and in-vitro, in-vivo evaluation.

    PubMed

    Mahor, Alok; Prajapati, Sunil Kumar; Verma, Amita; Gupta, Rishikesh; Iyer, Arun K; Kesharwani, Prashant

    2016-12-01

    The current research focuses on developing positively charged gelatin nanoparticles loaded with moxifloxacin for its effective ocular delivery and controlled release in corneal eye layer. We selected type A gelatin because of its biodegradable and non-toxic nature as the polymer of choice for fabricating the nanoparticles by a modified two step desolvation technique. The produced nanoparticles were positively charged (+24±0.12mV) with a narrow particle size of 175±1.11nm as measured by dynamic light scattering (DLS). The in-vitro drug release from the nanoformulations exhibited a burst effect in the first hour followed by a controlled release of the drug for the subsequent 12h. The Korsmeyer-Peppas model showed better linearity and the formulations displayed non-Fickian drug release pattern. The optimized formulation was assessed for its utility as an anti-bacterial agent and its effectiveness was tested on the corneal eye surface of rabbits. The in-vivo tolerance tests revealed that the drug loaded nano-formulations was non-irritant to the ocular tissues indicating its safety. The in-vivo anti-bacterial activity of the nanosuspension was more effective against S. aureus than the commercially market product, MoxiGram®. Microbiological efficacy assessed against B. subtilus using cup-plate method suggested that our fabricated nanosuspension possess better anti-microbial activity as compared to the commercial agent, MoxiGram® revealing promising potentials for the currently developed gelatin based nanoformualtions.

  13. Chitosan Nanolayered Cisplatin-Loaded Lipid Nanoparticles for Enhanced Anticancer Efficacy in Cervical Cancer

    NASA Astrophysics Data System (ADS)

    Wang, Jing-yi; Wang, Yu; Meng, Xia

    2016-11-01

    In this study, cisplatin (CDDP)-loaded chitosan-coated solid lipid nanoparticles (SLN) was successfully formulated to treat HeLa cervical carcinoma. The formulation nanoparticles were nanosized and exhibited a controlled release of drug in physiological conditions. The blank nanoparticles exhibited an excellent biocompatibility profile indicating its suitability for cancer targeting. The incorporation of CDDP in SLN remarkably increased the cancer cell death as evident from the MTT assay. Importantly, CDDP-loaded chitosan-coated SLN (CChSLN) significantly ( P < 0.05) decreased the viability of cancer cells even at low concentration. The higher cytotoxicity potential of CChSLN was attributed to the higher cellular uptake as well as the sustained drug release manner in comparison with CSLN. Consistent with the cytotoxicity assay, CChSLN showed the lowest IC50 value of 0.6125 μg/ml while CSLN presented 1.156 μg/ml. CChSLN showed a significantly higher apoptosis in cancer cells compared to that of CSLN and CDDP, which is attributed to the better internalization of nanocarriers and controlled release of anticancer drugs in the intracellular environment. Our findings suggest that this new formulation could be a promising alternative for the treatment of cervical cancers. These findings are encouraging us to continue our research, with a more extended investigation of cellular response in real time and in animal models.

  14. Polyinosinic:polycytidylic acid loading onto different generations of PAMAM dendrimer-coated magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Khodadust, Rouhollah; Mutlu, Pelin; Yalcın, Serap; Unsoy, Gozde; Gunduz, Ufuk

    2013-08-01

    Poly (I:C), which is a synthetic double-stranded RNA, have significant toxicity on tumor cells. The immobilization of Poly (I:C) onto nanoparticles is important for the fabrication of targeted delivery systems. In this study, different generations of newly synthesized PAMAM dendron-coated magnetic nanoparticles (DcMNP) which can be targeted to the tumor site under magnetic field were efficiently loaded for the first time with Poly (I:C). Different generations of DcMNPs (G2, G3, G4, G5, G6, and G7) were synthesized. Poly (I:C) activation was achieved in the presence of EDC and 1-methylimidazole. Loading of Poly (I:C) onto DcMNPs was followed by agarose gel electrophoresis. Acidic reaction conditions were found as superior to basic and neutral for binding of Poly (I:C). In addition, having more functional groups at the surface, higher generations (G7, G6, and G5) of PAMAM DcMNPs were found more suitable as a delivery system for Poly (I:C). Further in vitro and in vivo analyses of Poly (I:C)/PAMAM magnetic nanoparticles may provide new opportunities for the selective targeting and killing of tumor cells.

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

    NASA Astrophysics Data System (ADS)

    Ambaye, Almaz

    Ag/BSA nanoparticles was found to be in a range of 9-13 nm. X-ray photo electron spectroscopy measurements of argon sputtered Ag/BSA nanoparticles provided evidence that the outer and inner region of nanoparticles are mainly composed of BSA and silver, respectively. Having characterized the nanoparticles, the next phase of the study was to evaluate the antibacterial activity and cytotoxicity level of BSA stabilized silver nanoparticles. The antibacterial efficacy of Ag/BSA nanoparticles against E. coli and S. aureus was evaluated, and minimum lethal concentration was found to be 2ppm and 7ppm, respectively. E. coli showed a higher susceptibility to silver nanoparticles than S. aureus, which could be attributed to the difference in the cell wall structure. We have also investigated the cytotoxicity level of Ag/BSA nanoparticles towards MC3T3-E1 osteoblast cells. The minimum bactericidal concentration found for both strains is lower than the silver nanoparticles concentration that was toxic to the osteoblast cells. Preliminary studies of Ag/BSA nanoparticles loaded collagen immobilized PHBV film showed that the Ag/BSA nanoparticles loaded PHBV film inhibit bacterial growth. The findings of our study can be extremely useful in the design of novel scaffold to address the critical needs of bone tissue engineering community.

  16. High Precision and High Yield Fabrication of Dense Nanoparticle Arrays onto DNA Origami at Statistically Independent Binding Sites †

    PubMed Central

    Takabayashi, Sadao; Klein, William P.; Onodera, Craig; Rapp, Blake; Flores-Estrada, Juan; Lindau, Elias; Snowball, Lejmarc; Sam, Joseph Tyler; Padilla, Jennifer E.; Lee, Jeunghoon; Knowlton, William B.; Graugnard, Elton; Yurke, Bernard; Kuang, Wan; Hughes, William L.

    2015-01-01

    High precision, high yield, and high density self-assembly of nanoparticles into arrays is essential for nanophotonics. Spatial deviations as small as a few nanometers can alter the properties of near-field coupled optical nanostructures. Several studies have reported assemblies of few nanoparticle structures with controlled spacing using DNA nanostructures with variable yield. Here, we report multi-tether design strategies and attachment yields for homo- and hetero-nanoparticle arrays templated by DNA origami nanotubes. Nanoparticle attachment yield via DNA hybridization is comparable with streptavidin-biotin binding. Independent of the number of binding sites, >97% site-occupation was achieved with four tethers and 99.2% site-occupation is theoretically possible with five tethers. The interparticle distance was within 2 nm of all design specifications and the nanoparticle spatial deviations decreased with interparticle spacing. Modified geometric, binomial, and trinomial distributions indicate that site-bridging, steric hindrance, and electrostatic repulsion were not dominant barriers to self-assembly and both tethers and binding sites were statistically independent at high particle densities. PMID:25311051

  17. Loading Erythrocytes with Maghemite Nanoparticles via Osmotic Pressure Induced Cell Membrane Pores

    NASA Astrophysics Data System (ADS)

    Ibrahim, Mounir; Wee, Leonard; Saunders, Martin; Woodward, Robert C.; Pierre, Timothy G. St

    2010-12-01

    Encapsulating magnetic nanoparticles within red blood cells is one strategy for extending the lifetime of magnetic resonance imaging contrast agents in the bloodstream. Human red blood cells were incubated for 12 hours with iron oxide (γ-Fe2O3) nanoparticles with a broad range of particle and aggregate sizes (ranging from 10 to 600 nm) at different osmolarities ranging from 100 to 290 mOsm before being returned to an osmolarity of 300 mOsm. Concentrations of nanoparticles trapped within the cells were measured using transmission electron microscopy and iron-mapping by electron energy loss spectroscopy. An osmolarity of 200 mOsm was found to be the optimal condition for loading of the cells with nanoparticles. At this osmolarity, it was shown that the concentration of particles within the cells relative to the average concentration in the suspension is maximized. At 200 mOsm, the maximum size aggregate of particles that entered the cells was approximately 120 nm.

  18. In-vitro release of acyclovir loaded Eudragit RLPO(®) nanoparticles for sustained drug delivery.

    PubMed

    Gandhi, Arijit; Jana, Sougata; Sen, Kalyan Kumar

    2014-06-01

    In this present study the possibility to develop Eudragit RLPO(®) based nanoparticles of acyclovir was investigated in order to increase its efficacy because acyclovir has oral bioavailability of only 10-20% thus showing erratic absorption and bioavailability behaviour. The nanoparticles were prepared by nanoprecipitation technique. Pluronic F68 was used as stabilizer. The nanoparticles were characterized by particle size, entrapment efficiency, DSC, SEM, FTIR and in-vitro drug release. It was found that as drug:polymer (Acyclovir:Eudragit RLPO(®)) ratio increased from 1:1.5 to 1:2, particle size was increased significantly and drug entrapment also increased but thereafter, further increase in drug: polymer ratio showed reduced or insignificant change in the drug entrapment efficiency. DSC results showed that in the prepared nanoaprticles, the drug was present in the amorphous phase and may have been homogeneously dispersed in the polymer matrix. In vitro drug release study of formulations showed release in 24h in the range 71.62±1.72 to 93.25±1.02%. The release was found to follow Higuchi model with non-Fickian diffusion mechanism for all batches. These preliminary results indicate that acyclovir loaded Eudragit RLPO(®) nanoparticles could be effective in sustaining drug release for a prolonged period.

  19. Ocular disposition and tolerance of ganciclovir-loaded albumin nanoparticles after intravitreal injection in rats.

    PubMed

    Merodio, Marta; Irache, Juan Manuel; Valamanesh, Fatemeh; Mirshahi, Massoud

    2002-04-01

    Cytomegalovirus (CMV) infection mainly affects endothelial cells of ocular vessels, optic nerve and the retina, resulting in direct or autoimmune damages, uveoretinitis and disturbed vision. The use of colloidal carriers for the intravitreal delivery of ganciclovir may prolong its residence in the eye, minimizing the opacification observed for macroscopic implants. The aim of this work was to evaluate the ocular toxicity induced by the prolonged presence of ganciclovir-loaded bovine serum albumin nanoparticles after their intravitreal injection. The intraocular disposition of these carriers was also studied by immunochemistry. Two weeks post-injection, a significant amount of nanoparticles remained in the vitreous cavity, mainly in a thin layer overlying the retina and in the area close to the blood aqueoUs barrier. Their prolonged residence in the eve seemed to be well tolerated and the histological evaluation of the retina, mainly the photoreceptor layer, and adjacent tissues revealed the absence of inflammatory reactions or alterations in the tissue architecture (i.e. cellular infiltrations or vascular inflammation). In addition, nanoparticles neither alter the expression and distribution of arrestin and rhodopsin autoantigens nor the mineralocorticoid receptor. In summary, the vision was not affected by autoimmune phenomena or alterations in the behavior of ophthalmic cells due to the intravitreal injection of these nanoparticles.

  20. Preparation, characterization and in-vitro evaluation of sustained release protein-loaded nanoparticles based on biodegradable polymers

    PubMed Central

    Mukherjee, Biswajit; Santra, Kousik; Pattnaik, Gurudutta; Ghosh, Soma

    2008-01-01

    Controlled drug delivery technology of proteins/peptides from biodegradable nanoparticles has emerged as one of the eminent areas to overcome formulation associated problems of the macromolecules. The purpose of the present investigation was to develop protein-loaded nanoparticles using biodegradable polymer poly l-lactide-co-glycolidic acid (PLGA) with bovine serum albumin (BSA) as a model protein. Despite many studies available with PLGA-based protein-loaded nanoparticles, production know-how, process parameters, protein loading, duration of protein release, narrowing polydispersity of particles have not been investigated enough to scale up manufacturing of protein-loaded nanoparticles in formulations. Different process parameters such as protein/polymer ratio, homogenizing speed during emulsifications, particle surface morphology and surface charges, particle size analysis and in-vitro protein release were investigated. The in-vitro protein release study suggests that release profile of BSA from nanoparticles could be modulated by changing protein-polymer ratios and/or by varying homogenizing speed during multiple-emulsion preparation technique. The formulation prepared with protein-polymer ratio of 1:60 at 17,500 rpm gave maximum protein-loading, minimum polydispersion with maximally sustained protein release pattern, among the prepared formulations. Decreased (10,000 rpm) or enhanced (24,000 rpm) homogenizing speeds resulted in increased polydispersion with larger particles having no better protein-loading and -release profiles in the present study. PMID:19337417

  1. Design and Characterization of Metformin-Loaded Solid Lipid Nanoparticles for Colon Cancer.

    PubMed

    Ngwuluka, Ndidi C; Kotak, Darsheen J; Devarajan, Padma V

    2017-02-01

    Colorectal cancer is a global concern, and its treatment is fraught with non-selective effects including adverse side effects requiring hospital visits and palliative care. A relatively safe drug formulated in a bioavailability enhancing and targeting delivery platform will be of significance. Metformin-loaded solid lipid nanoparticles (SLN) were designed, optimized, and characterized for particle size, zeta potential, drug entrapment, structure, crystallinity, thermal behavior, morphology, and drug release. Optimized SLN were 195.01 ± 6.03 nm in size, -17.08 ± 0.95 mV with regard to surface charge, fibrous in shape, largely amorphous, and release of metformin was controlled. The optimized size, charge, and shape suggest the solid lipid nanoparticles will migrate and accumulate in the colon tumor preventing its proliferation and subsequently leading to tumor shrinkage and cell death.

  2. Budesonide-loaded solid lipid nanoparticles for pulmonary delivery: preparation, optimization, and aerodynamic behavior.

    PubMed

    Esmaeili, Maryam; Aghajani, Mahdi; Abbasalipourkabir, Roghayeh; Amani, Amir

    2016-12-01

    Advantages of lipid nanoparticles for pulmonary applications are possibility of deep lung deposition with prolonged release and low toxicity. This study aimed to evaluate the effects of formulation and processing parameters on particle size of prepared SLNs. Budesonide-loaded solid lipid nanoparticles (BUD-SLNs) were prepared with different values of drug content, ultrasonication amplitude, and homogenization time and the data were modeled using artificial neural networks (ANNs). Optimal conditions for fabrication of small-sized particles of 170-200 nm were found to be low drug content with high-amplitude and high-homogenization time. In vitro aerosolization performance of BUD-SLNs was then compared to that of commercial budesonide which indicated enhancement in fine particle fraction value.

  3. Asymmetric photoelectric property of transparent TiO2 nanotube films loaded with Au nanoparticles

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Liang, Wei; Liu, Yiming; Zhang, Wanggang; Zhou, Diaoyu; Wen, Jing

    2016-11-01

    Semitransparent composite films of Au loaded TiO2 nanotubes (TNT-Au) were prepared by sputtering Au nanoparticles on highly transparent TiO2 nanotubes films, which were fabricated directly on FTO glasses by anodizing the Ti film sputtered on the FTO glasses. Compared with pure TNT films, the prepared TNT-Au films possessed excellent absorption ability and high photocurrent response and improved photocatalytic activity under visible-light irradiation. It could be concluded that Au nanoparticles played important roles in improving the photoelectrochemical performance of TNT-Au films. Moreover, in this work, both sides of TNT-Au films were researched and compared owing to theirs semitransparency. It was firstly found that the photoelectric activity of TNT-Au composite films with back-side illumination was obviously superior to front-side illumination.

  4. Magnetic field-enhanced cellular uptake of doxorubicin loaded magnetic nanoparticles for tumor treatment

    NASA Astrophysics Data System (ADS)

    Venugopal, Indu; Pernal, Sebastian; Duproz, Alexandra; Bentley, Jeromy; Engelhard, Herbert; Linninger, Andreas

    2016-09-01

    Cancer remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. In recent years, several varieties of nanoparticles (NPs) have been synthesized with the intent of being utilized as tumor drug delivery vehicles. We have produced superparamagnetic, gold-coated magnetite (Fe3O4@Au) NPs and loaded them with the chemotherapeutic drug doxorubicin (DOX) for magnetic drug targeting (MDT) of tumors. The synthetic strategy uses the food thickening agent gellan gum (Phytagel) as a negatively charged shell around the Fe3O4@Au NP onto which the positively charged DOX molecules are loaded via electrostatic attraction. The resulting DOX-loaded magnetic nanoparticles (DOX-MNPs) were characterized using transmission electron microscopy, energy dispersive x-ray spectroscopy, superconducting quantum interference device magnetometry, surface area electron diffraction, zeta potential measurements, fourier transform infrared spectroscopy as well as UV/Vis and fluorescence spectroscopy. Cytotoxicity of the DOX-MNPs was demonstrated using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay on C6 glioma cells. Cellular uptake of DOX-MNPs was enhanced with magnetic fields, which was quantitatively determined using flow cytometry. This improved uptake also led to greater tumor cell death, which was measured using MTT assay. These MDT results are promising for a new therapy for cancer.

  5. Effect of PEG biofunctional spacers and TAT peptide on dsRNA loading on gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Sanz, Vanesa; Conde, João; Hernández, Yulán; Baptista, Pedro V.; Ibarra, M. R.; de la Fuente, Jesús M.

    2012-06-01

    The surface chemistry of gold nanoparticles (AuNPs) plays a critical role in the self-assembly of thiolated molecules and in retaining the biological function of the conjugated biomolecules. According to the well-established gold-thiol interaction the undefined ionic species on citrate-reduced gold nanoparticle surface can be replaced with a self-assembled monolayer of certain thiolate derivatives and other biomolecules. Understanding the effect of such derivatives in the functionalization of several types of biomolecules, such as PEGs, peptides or nucleic acids, has become a significant challenge. Here, an approach to attach specific biomolecules to the AuNPs ( 14 nm) surface is presented together with a study of their effect in the functionalization with other specific derivatives. The effect of biofunctional spacers such as thiolated poly(ethylene glycol) (PEG) chains and a positive peptide, TAT, in dsRNA loading on AuNPs is reported. Based on the obtained data, we hypothesize that loading of oligonucleotides onto the AuNP surface may be controlled by ionic and weak interactions positioning the entry of the oligo through the PEG layer. We demonstrate that there is a synergistic effect of the TAT peptide and PEG chains with specific functional groups on the enhancement of dsRNA loading onto AuNPs.

  6. Polydopamine Nanoparticles as a Versatile Molecular Loading Platform to Enable Imaging-guided Cancer Combination Therapy

    PubMed Central

    Dong, Ziliang; Gong, Hua; Gao, Min; Zhu, Wenwen; Sun, Xiaoqi; Feng, Liangzhu; Fu, Tingting; Li, Yonggang; Liu, Zhuang

    2016-01-01

    Cancer combination therapy to treat tumors with different therapeutic approaches can efficiently improve treatment efficacy and reduce side effects. Herein, we develop a theranostic nano-platform based on polydopamine (PDA) nanoparticles, which then are exploited as a versatile carrier to allow simultaneous loading of indocyanine green (ICG), doxorubicin (DOX) and manganese ions (PDA-ICG-PEG/DOX(Mn)), to enable imaging-guided chemo & photothermal cancer therapy. In this system, ICG acts as a photothermal agent, which shows red-shifted near-infrared (NIR) absorbance and enhanced photostability compared with free ICG. DOX, a model chemotherapy drug, is then loaded onto the surface of PDA-ICG-PEG with high efficiency. With Mn2+ ions intrinsically chelated, PDA-ICG-PEG/DOX(Mn) is able to offer contrast under T1-weighted magnetic resonance (MR) imaging. In a mouse tumor model, the MR imaging-guided combined chemo- & photothermal therapy achieves a remarkable synergistic therapeutic effect compared with the respective single treatment modality. This work demonstrates that PDA nanoparticles could serve as a versatile molecular loading platform for MR imaging guided combined chemo- & photothermal therapy with minimal side effects, showing great potential for cancer theranostics. PMID:27217836

  7. Vancomycin loaded superparamagnetic MnFe2O4 nanoparticles coated with PEGylated chitosan to enhance antibacterial activity.

    PubMed

    Esmaeili, Akbar; Ghobadianpour, Sepideh

    2016-03-30

    Increasing prevalence of antibiotic-resistant and failed-treatment make more investigations to deal with these problems. Hence new therapeutic approaches for effective treatment are necessary. Ferrite superparamagnetic nanoparticles have potentially antibacterial activity. In this study we prepared MnFe2O4 superparamagnetic nanoparticles as core by precipitation method and used chitosan crosslinked by glutaraldehyde as shell, then modified with PEG to increase stability of particles against RES. Chitosan coating not only improves the properties of ferrit nanoparticles but also has antibacterial activity. FT-IR confirmed this surface modification; XRD and SEM were developed to demonstrate particle size approximately 25 nm and characteristics of crystal structure of these nanoparticles. Magnetic properties of nanoparticles were evaluated by VSM. Actual drug loading and releasing were examined by UV-vis spectroscopy method. We employed liquid broth dilution method to assessment antibacterial activity of nanoparticles against microorganisms. Significant antibacterial effect against gram negative bacteria was developed.

  8. Corticosteroid-loaded biodegradable nanoparticles for prevention of corneal allograft rejection in rats.

    PubMed

    Pan, Qing; Xu, Qingguo; Boylan, Nicholas J; Lamb, Nicholas W; Emmert, David G; Yang, Jeh-Chang; Tang, Li; Heflin, Tom; Alwadani, Saeed; Eberhart, Charles G; Stark, Walter J; Hanes, Justin

    2015-03-10

    Immunologic graft rejection is one of the main causes of short and long-term graft failure in corneal transplantation. Steroids are the most commonly used immunosuppressive agents for postoperative management and prevention of corneal graft rejection. However, steroids delivered in eye drops are rapidly cleared from the surface of the eye, so the required frequency of dosing for corneal graft rejection management can be as high as once every 2h. Additionally, these eye drops are often prescribed for daily use for 1 year or longer, which can result in poor patient compliance and steroid-related side effects. Here, we report a biodegradable nanoparticle system composed of Generally Regarded as Safe (GRAS) materials that can provide sustained release of corticosteroids to prevent corneal graft rejection following subconjunctival injection provided initially during transplant surgery. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing dexamethasone sodium phosphate (DSP) exhibited a size of 200 nm, 8 wt.% drug loading, and sustained drug release over 15 days in vitro under sink conditions. DSP-loaded nanoparticles provided sustained ocular drug levels for at least 7 days after subconjunctival administration in rats, and prevented corneal allograft rejection over the entire 9-week study when administered weekly. In contrast, control treatment groups that received weekly injections of either placebo nanoparticles, saline, or DSP in solution demonstrated corneal graft rejection accompanied by severe corneal edema, neovascularization and opacity that occurred in ≤ 4 weeks. Local controlled release of corticosteroids may reduce the rate of corneal graft rejection, perhaps especially in the days immediately following surgery when risk of rejection is highest and when typical steroid eye drop administration requirements are particularly onerous.

  9. Docosahexaenoic acid loaded lipid nanoparticles with bactericidal activity against Helicobacter pylori.

    PubMed

    Seabra, Catarina Leal; Nunes, Cláudia; Gomez-Lazaro, Maria; Correia, Marta; Machado, José Carlos; Gonçalves, Inês C; Reis, Celso A; Reis, Salette; Martins, M Cristina L

    2017-03-15

    Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol ATO5(®), Miglyol-812(®)) and a surfactant (Tween 60(®)). Homogeneous NLC with 302±14nm diameter, -28±3mV surface charge (dynamic and electrophoretic light scattering) and containing 66±7% DHA (UV/VIS spectroscopy) were successfully produced. Bacterial growth curves, performed over 24h in the presence of different DHA concentrations (free or loaded into NLC), demonstrated that nanoencapsulation enhanced DHA bactericidal effect, since DHA-loaded NLC were able to inhibit H. pylori growth in a much lower concentrations (25μM) than free DHA (>100μM). Bioimaging studies, using scanning and transmission electron microscopy and also imaging flow cytometry, demonstrated that DHA-loaded NLC interact with H. pylori membrane, increasing their periplasmic space and disrupting membrane and allowing the leakage of cytoplasmic content. Furthermore, the developed nanoparticles are not cytotoxic to human gastric adenocarcinoma cells at bactericidal concentrations. DHA-loaded NLC should, therefore, be envisaged as an alternative to the current treatments for H. pylori infection.

  10. Brain targeting effect of camptothecin-loaded solid lipid nanoparticles in rat after intravenous administration.

    PubMed

    Martins, Susana M; Sarmento, Bruno; Nunes, Cláudia; Lúcio, Marlene; Reis, Salette; Ferreira, Domingos C

    2013-11-01

    This study intended to investigate the ability of solid lipid nanoparticles (SLN) to deliver camptothecin into the brain parenchyma after crossing the blood-brain barrier. For that purpose, camptothecin-loaded SLN with mean size below 200 nm, low polydispersity index (<0.25), negative surface charge (-20 mV), and high camptothecin association efficiency (>94%) were produced. Synchrotron small and wide angle X-ray scattering (SAXS/WAXS) analysis indicates that SLN maintain their physical stability in contact with DMPC membrane, whereas SLN change the lamellar structure of DMPC into a cubic phase, which is associated with efficient release of the incorporated drugs. Cytotoxicity studies against glioma and macrophage human cell lines revealed that camptothecin-loaded SLN induced cell death with the lowest maximal inhibitory concentration (IC50) values, revealing higher antitumour activity of camptothecin-loaded SLN against gliomas. Furthermore, in vivo biodistribution studies of intravenous camptothecin-loaded SLN performed in rats proved the positive role of SLN on the brain targeting since significant higher brain accumulation of camptothecin was observed, compared to non-encapsulated drug. Pharmacokinetic studies further demonstrated lower deposition of camptothecin in peripheral organs, when encapsulated into SLN, with consequent decrease in potential side toxicological effects. These results confirmed the potential of camptothecin-loaded SLN for antitumour brain treatments.

  11. Galantamine-loaded PLGA nanoparticles, from nano-emulsion templating, as novel advanced drug delivery systems to treat neurodegenerative diseases

    NASA Astrophysics Data System (ADS)

    Fornaguera, C.; Feiner-Gracia, N.; Calderó, G.; García-Celma, M. J.; Solans, C.

    2015-07-01

    Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from aqueous and micellar solutions. The enzymatic activity of the drug was maintained at 80% after its encapsulation into nanoparticles that were non-cytotoxic at the required therapeutic concentration. Therefore, novel galantamine-loaded polymeric nanoparticles have been designed for the first time using the nano-emulsification approach and showed the appropriate features to become advanced drug delivery systems to treat neurodegenerative diseases.Polymeric nanoparticles could be promising drug delivery systems to treat neurodegenerative diseases. Among the various methods of nanoparticle preparation, nano-emulsion templating was used in the present study to prepare galantamine-loaded nano-emulsions by a low-energy emulsification method followed by solvent evaporation to obtain galantamine-loaded polymeric nanoparticles. This approach was found to be suitable because biocompatible, biodegradable and safe nanoparticles with appropriate features (hydrodynamic radii around 20 nm, negative surface charge and stability higher than 3 months) for their intravenous administration were obtained. Encapsulation efficiencies higher than 90 wt% were obtained with a sustained drug release profile as compared to that from

  12. Practical protein removal using atmospheric-pressure helium plasma for densely packed gold nanoparticle arrays assembled by ferritin-based encapsulation/transport system

    NASA Astrophysics Data System (ADS)

    Hashimoto, Tatsuya; Zettsu, Nobuyuki; Zheng, Bin; Fukuta, Megumi; Yamashita, Ichiro; Uraoka, Yukiharu; Watanabe, Heiji

    2012-08-01

    We propose using atmospheric-pressure helium (AP He) plasma to efficiently remove the ferritin protein shells surrounding gold nanoparticles (GNPs). The high density GNPs assembled on a substrate by using a ferritin-based encapsulation/transport system were exposed to He radicals with a high internal energy to decompose their outer protein shells. In contrast to the conventional methods, AP-plasma treatment was found to suppress the aggregation of adjacent GNPs and produce densely packed and isolated GNP arrays. Consequently, we obtained an intense and sharp surface plasmon band from the plasma-treated GNP arrays. The clear response of their plasmonic behavior according to a refractive index of the surrounding media demonstrated that the proposed method had a significant advantage when fabricating GNP-based plasmonic devices.

  13. Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors.

    PubMed

    Gao, Pei; Zhang, Xiangyu; Wang, Hongzhi; Zhang, Qinghong; Li, He; Li, Yaogang; Duan, Yourong

    2016-01-19

    Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-α-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average size of the hybrid nanoparticles was approximately 53.2 nm with a negative charge of approximately -16.7 mV, which was confirmed by dynamic light scattering (DLS) measurements. The nanoparticles exhibited excellent stability in serum and could protect siRNA from ribonuclease (RNase) degradation. The cellular internalization of siRNA-loaded nanoparticles was evaluated in SMMC-7721 cells using a laser scanning confocal microscope (CLSM) and flow cytometry. The hybrid nanoparticles could efficiently deliver siRNA to cells compared with free siRNA. Moreover, the in vivo distribution of Cy5-siRNA-loaded hybrid nanoparticles was observed after being injected into tumor-bearing nude mice. The nanoparticles concentrated in the tumor regions through an enhanced permeability and retention (EPR) effect based on the fluorescence intensities of tissue distribution. A safety evaluation of the nanoparticles was performed both in vitro and in vivo demonstrating that the hybrid nanoparticle delivery system had almost no toxicity. These results indicated that the mPEG-PE/CaP hybrid nanoparticles could be a stable, safe and promising siRNA nanocarrier for anticancer therapy.

  14. Biocompatible and colloidally stabilized mPEG-PE/calcium phosphate hybrid nanoparticles loaded with siRNAs targeting tumors

    PubMed Central

    Gao, Pei; Zhang, Xiangyu; Wang, Hongzhi; Zhang, Qinghong

    2016-01-01

    Calcium phosphate nanoparticles are safe and effective delivery vehicles for small interfering RNA (siRNA), as a result of their excellent biocompatibility. In this work, mPEG-PE (polyethylene glycol-L-α-phosphatidylethanolamine) was synthesized and used to prepare nanoparticles composed of mPEG-PE and calcium phosphate for siRNA delivery. Calcium phosphate and mPEG-PE formed the stable hybrid nanoparticles through self-assembly resulting from electrostatic interaction in water. The average size of the hybrid nanoparticles was approximately 53.2 nm with a negative charge of approximately −16.7 mV, which was confirmed by dynamic light scattering (DLS) measurements. The nanoparticles exhibited excellent stability in serum and could protect siRNA from ribonuclease (RNase) degradation. The cellular internalization of siRNA-loaded nanoparticles was evaluated in SMMC-7721 cells using a laser scanning confocal microscope (CLSM) and flow cytometry. The hybrid nanoparticles could efficiently deliver siRNA to cells compared with free siRNA. Moreover, the in vivo distribution of Cy5-siRNA-loaded hybrid nanoparticles was observed after being injected into tumor-bearing nude mice. The nanoparticles concentrated in the tumor regions through an enhanced permeability and retention (EPR) effect based on the fluorescence intensities of tissue distribution. A safety evaluation of the nanoparticles was performed both in vitro and in vivo demonstrating that the hybrid nanoparticle delivery system had almost no toxicity. These results indicated that the mPEG-PE/CaP hybrid nanoparticles could be a stable, safe and promising siRNA nanocarrier for anticancer therapy. PMID:26625203

  15. Microfluidic Synthesis Enables Dense and Uniform Loading of Surfactant-Free PtSn Nanocrystals on Carbon Supports for Enhanced Ethanol Oxidation.

    PubMed

    Wu, Fuxiang; Zhang, Dongtang; Peng, Manhua; Yu, Zhihui; Wang, Xiayan; Guo, Guangsheng; Sun, Yugang

    2016-04-11

    Developing new synthetic methods for carbon supported catalysts with improved performance is of fundamental importance in advancing proton exchange membrane fuel cell (PEMFC) technology. Continuous-flow, microfluidic reactions in capillary tube reactors are described, which are capable of synthesizing surfactant-free, ultrafine PtSn alloyed nanoparticles (NPs) on various carbon supports (for example, commercial carbon black particles, carbon nanotubes, and graphene sheets). The PtSn NPs are highly crystalline with sizes smaller than 2 nm, and they are highly dispersed on the carbon supports with high loadings up to 33 wt%. These characteristics make the as-synthesized carbon-supported PtSn NPs more efficient than state of the art commercial Pt/C catalysts applied to the ethanol oxidation reaction (EOR). Significantly enhanced mass catalytic activity (two-times that of Pt/C) and improved stability are obtained.

  16. Ultrasound-guided delivery of microRNA loaded nanoparticles into cancer.

    PubMed

    Wang, Tzu-Yin; Choe, Jung Woo; Pu, Kanyi; Devulapally, Rammohan; Bachawal, Sunitha; Machtaler, Steven; Chowdhury, Sayan Mullick; Luong, Richard; Tian, Lu; Khuri-Yakub, Butrus; Rao, Jianghong; Paulmurugan, Ramasamy; Willmann, Jürgen K

    2015-04-10

    Ultrasound induced microbubble cavitation can cause enhanced permeability across natural barriers of tumors such as vessel walls or cellular membranes, allowing for enhanced therapeutic delivery into the target tissues. While enhanced delivery of small (<1nm) molecules has been shown at acoustic pressures below 1MPa both in vitro and in vivo, the delivery efficiency of larger (>100nm) therapeutic carriers into cancer remains unclear and may require a higher pressure for sufficient delivery. Enhanced delivery of larger therapeutic carriers such as FDA approved pegylated poly(lactic-co-glycolic acid) nanoparticles (PLGA-PEG-NP) has significant clinical value because these nanoparticles have been shown to protect encapsulated drugs from degradation in the blood circulation and allow for slow and prolonged release of encapsulated drugs at the target location. In this study, various acoustic parameters were investigated to facilitate the successful delivery of two nanocarriers, a fluorescent semiconducting polymer model drug nanoparticle as well as PLGA-PEG-NP into human colon cancer xenografts in mice. We first measured the cavitation dose produced by various acoustic parameters (pressure, pulse length, and pulse repetition frequency) and microbubble concentration in a tissue mimicking phantom. Next, in vivo studies were performed to evaluate the penetration depth of nanocarriers using various acoustic pressures, ranging between 1.7 and 6.9MPa. Finally, a therapeutic microRNA, miR-122, was loaded into PLGA-PEG-NP and the amount of delivered miR-122 was assessed using quantitative RT-PCR. Our results show that acoustic pressures had the strongest effect on cavitation. An increase of the pressure from 0.8 to 6.9MPa resulted in a nearly 50-fold increase in cavitation in phantom experiments. In vivo, as the pressures increased from 1.7 to 6.9MPa, the amount of nanoparticles deposited in cancer xenografts was increased from 4- to 14-fold, and the median penetration depth of

  17. Facile fabrication of high-efficiency near-infrared absorption film with tungsten bronze nanoparticle dense layer

    NASA Astrophysics Data System (ADS)

    Lee, Seong Yun; Kim, Jae Young; Lee, Jun Young; Song, Ho Jun; Lee, Sangkug; Choi, Kyung Ho; Shin, Gyojic

    2014-06-01

    An excellent transparent film with effective absorption property in near-infrared (NIR) region based on cesium-doped tungsten oxide nanoparticles was fabricated using a facile double layer coating method via the theoretical considerations. The optical performance was evaluated; the double layer-coated film exhibited 10% transmittance at 1,000 nm in the NIR region and over 80% transmittance at 550 nm in the visible region. To optimize the selectivity, the optical spectrum of this film was correlated with a theoretical model by combining the contributions of the Mie-Gans absorption-based localized surface plasmon resonance and reflections by the interfaces of the heterogeneous layers and the nanoparticles in the film. Through comparison of the composite and double layer coating method, the difference of the nanoscale distances between nanoparticles in each layer was significantly revealed. It is worth noting that the nanodistance between the nanoparticles decreased in the double layer film, which enhanced the optical properties of the film, yielding a haze value of 1% or less without any additional process. These results are very attractive for the nanocomposite coating process, which would lead to industrial fields of NIR shielding and thermo-medical applications.

  18. Facile fabrication of high-efficiency near-infrared absorption film with tungsten bronze nanoparticle dense layer

    PubMed Central

    2014-01-01

    An excellent transparent film with effective absorption property in near-infrared (NIR) region based on cesium-doped tungsten oxide nanoparticles was fabricated using a facile double layer coating method via the theoretical considerations. The optical performance was evaluated; the double layer-coated film exhibited 10% transmittance at 1,000 nm in the NIR region and over 80% transmittance at 550 nm in the visible region. To optimize the selectivity, the optical spectrum of this film was correlated with a theoretical model by combining the contributions of the Mie-Gans absorption-based localized surface plasmon resonance and reflections by the interfaces of the heterogeneous layers and the nanoparticles in the film. Through comparison of the composite and double layer coating method, the difference of the nanoscale distances between nanoparticles in each layer was significantly revealed. It is worth noting that the nanodistance between the nanoparticles decreased in the double layer film, which enhanced the optical properties of the film, yielding a haze value of 1% or less without any additional process. These results are very attractive for the nanocomposite coating process, which would lead to industrial fields of NIR shielding and thermo-medical applications. PACS 78.67.Sc; 78.67.Bf; 81.15.-z PMID:24982605

  19. Colloidal gold-loaded, biodegradable, polymer-based stavudine nanoparticle uptake by macrophages: an in vitro study

    PubMed Central

    Basu, Sumit; Mukherjee, Biswajit; Chowdhury, Samrat Roy; Paul, Paramita; Choudhury, Rupak; Kumar, Ajeet; Mondal, Laboni; Hossain, Chowdhury Mobaswar; Maji, Ruma

    2012-01-01

    Objective We describe the development, evaluation, and comparison of colloidal gold-loaded, poly(d,l-lactic-co-glycolic acid)-based nanoparticles containing anti-acquired immunodeficiency syndrome drug stavudine and uptake of these nanoparticles by macrophages in vitro. Methods We used the following methods in this study: drug-excipient interaction by Fourier transform infrared spectroscopy, morphology of nanoparticles by field-emission scanning electron microscopy, particle size by a particle size analyzer, and zeta potential and polydispersity index by a zetasizer. Drug loading and in vitro release were evaluated for formulations. The best formulation was incorporated with fluorescein isothiocyanate. Macrophage uptake of fluorescein isothiocyanate nanoparticles was studied in vitro. Results Variations in process parameters, such as speed of homogenization and amount of excipients, affected drug loading and the polydispersity index. We found that the drug was released for a prolonged period (over 63 days) from the nanoparticles, and observed cellular uptake of stavudine nanoparticles by macrophages. Conclusion Experimental nanoparticles represent an interesting carrier system for the transport of stavudine to macrophages, providing reduced required drug dose and improved drug delivery to macrophages over an extended period. The presence of colloidal gold in the particles decreased the drug content and resulted in comparatively faster drug release. PMID:23271908

  20. Developing a Highly Stable PLGA-mPEG Nanoparticle Loaded with Cisplatin for Chemotherapy of Ovarian Cancer

    PubMed Central

    Cheng, Lihua; Jin, Chengmeng; Lv, Wen; Ding, Qiuping; Han, Xu

    2011-01-01

    Background Cisplatin is a potent anticancer drug, but its clinical application has been limited due to its undesirable physicochemical characteristics and severe side effects. Better drug formulations for cisplatin are highly desired. Methodology/Principal Findings Herein, we have developed a nanoparticle formulation for cisplatin with high encapsulation efficiency and reduced toxicity by using cisplatin-crosslinked carboxymethyl cellulose (CMC) core nanoparticles made from poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) copolymers (PLGA-mPEG). The nanoparticles have an average diameter of approximately 80 nm measured by transmission electron microscope (TEM). The encapsulation efficiency of cisplatin in the nanoparticles is up to 72%. Meanwhile, we have also observed a controlled release of cisplatin in a sustained manner and dose-dependent treatment efficacy of cisplatin-loaded nanoparticles against IGROV1-CP cells. Moreover, the median lethal dose (LD50) of the cisplatin-loaded nanoparticles was more than 100 mg/kg by intravenous administration, which was much higher than that of free cisplatin. Conclusion This developed cisplatin-loaded nanoparticle is a promising formulation for the delivery of cisplatin, which will be an effective therapeutic regimen of ovarian cancer without severe side effects and cumulative toxicity. PMID:21966528

  1. Cutaneous biocompatible rutin-loaded gelatin-based nanoparticles increase the SPF of the association of UVA and UVB filters.

    PubMed

    Oliveira, Camila Areias de; Peres, Daniela D'Almeida; Graziola, Fabiana; Chacra, Nádia Araci Bou; Araújo, Gabriel Lima Barros de; Flórido, Ana Catarina; Mota, Joana; Rosado, Catarina; Velasco, Maria Valéria Robles; Rodrigues, Luís Monteiro; Fernandes, Ana Sofia; Baby, André Rolim

    2016-01-01

    The encapsulation of natural ingredients, such as rutin, can offer improvements in sun protection effectiveness. This strategy can provide enhanced flavonoid content and produces an improved bioactive compound with new physical and functional characteristics. As an alternative to common synthetic-based sunscreens, rutin-entrapped gelatin nanoparticles (GNPs) were designed and associated with ethylhexyl dimethyl PABA (EHDP), ethylhexyl methoxycinnamate (EHMC) and methoxydibenzoylmethane (BMDBM) in sunscreen formulations. The purpose of this study was to develop rutin-loaded gelatin nanoparticles and characterize their physicochemical, thermal, functional and safety properties. Rutin-loaded gelatin nanoparticles increased antioxidant activity by 74% relative to free-rutin (FR) solution. Also, this new ingredient upgraded the Sun Protection Factor (SPF) by 48%, indicating its potential as a raw material for bioactive sunscreens. The safety profile indicated that GNPs and glutaraldehyde (GTA) decreased HaCaT cell viability in a concentration/time-dependent manner. However, both blank nanoparticles (B-NC) and rutin-loaded nanoparticles (R-NC) had good performance on skin compatibility tests. These results functionally characterized rutin-loaded nanoparticles as a safe SPF enhancer in sunscreens, especially in association with UV filters.

  2. Development of bicalutamide-loaded PLGA nanoparticles: preparation, characterization and in-vitro evaluation for the treatment of prostate cancer.

    PubMed

    Ray, Sayantan; Ghosh Ray, Suparna; Mandal, Supratim

    2016-06-21

    In this study we report the development and optimization of poly (D, L-lactide-co-glycolide) (PLGA) polymer encapsulated poorly aqueous soluble nonsteroidal antiandrogen drug bicalutamide, to develop a sustained release formulation for the treatment of prostate cancer. The bicalutamide-loaded PLGA nanoparticles were prepared by single emulsion (O/W) solvent evaporation method, and different process parameters like polymer concentration in the organic phase, surfactant concentration in aqueous phase and centrifugation speed for separation of nanoparticles were evaluated to optimize the drug-loaded nanoparticles. The optimum formulation of bicalutamide-loaded PLGA nanoparticles characterized extensively by different analytical techniques like laser light scattering to determine average particle size and size distribution, scanning electron microscopy (SEM) for surface morphology, powder X-ray diffraction (PXRD) for surface chemistry and differential scanning calorimetry (DSC) for thermogram properties. Significant decrease of crystallinity of bicalutamide confirms entrapment of the drug within the PLGA polymer matrix. Further, the drug encapsulation efficiency (EE) and in vitro drug release profile were measured by high-performance liquid chromatography and UV-spectrophotometry. In vitro drug release exhibited biphasic pattern with initial burst release followed by slow and continuous release up to 5 days. Optimum formulation of bicalutamide-loaded PLGA nanoparticles shows significant anti-tumor activity over prostate cancer cell lines (DU 145). The newly developed optimum formulation nanoparticles could be useful for sustained release delivery of bicalutamide.

  3. Utilizing the protein corona around silica nanoparticles for dual drug loading and release

    NASA Astrophysics Data System (ADS)

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-01

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration

  4. Mechanism-Based Enhanced Delivery of Drug-Loaded Targeted Nanoparticles for Breast Cancer Therapy

    DTIC Science & Technology

    2012-02-01

    of the reaction mixtures, against (1) 0.5% aqueous ammonia in the presence of ethylenediaminetetraacetic acid (EDTA), and (2) distilled water. The...organs of the reticuloendothelial system such as the liver and spleen . Such high uptake of nanoparticles in liver and spleen has been reported for...0.4 Liver 147 425 2.9 Spleen 218 1601 7.3 Kidney 75 69 0.9 Lung 222 90 0.4 aAUC ratio = AUC of DOX-loaded nanogels/AUC of free DOX Fig. 4

  5. Calix[4]arene-Functionalised Silver Nanoparticles as Hosts for Pyridinium-Loaded Gold Nanoparticles as Guests.

    PubMed

    Vita, Francesco; Boccia, Alice; Marrani, Andrea G; Zanoni, Robertino; Rossi, Francesca; Arduini, Arturo; Secchi, Andrea

    2015-10-19

    A series of lipophilic gold nanoparticles (AuNPs) circa 5 nm in diameter and having a mixed organic layer consisting of 1-dodecanethiol and 1-(11-mercaptoundecyl) pyridinium bromide was synthesised by reacting tetraoctylammonium bromide stabilised AuNPs in toluene with different mixtures of the two thiolate ligands. A bidentate ω-alkylthiolate calix[4]arene derivative was instead used as a functional protecting layer on AgNPs of approximately 3 nm. The functionalised nanoparticles were characterised by transmission electron microscopy (TEM), and by UV/Vis and X-ray photoelectron spectroscopy (XPS). Recognition of the pyridinium moieties loaded on the AuNPs by the calix[4]arene units immobilised on the AgNPs was demonstrated in solution of weakly polar solvents by UV/Vis titrations and DLS measurements. The extent of Au-AgNPs aggregation, shown through the low-energy shift of their surface plasmon bands (SPB), was strongly dependent on the loading of the pyridinium moieties present in the organic layer of the AuNPs. Extensive aggregation between dodecanethiol-capped AuNPs and the Ag calix[4]arene-functionalised NPs was also promoted by the action of a simple N-octyl pyridinium difunctional supramolecular linker. This linker can interdigitate through its long fatty tail in the organic layer of the dodecanethiol-capped AuNPs, and simultaneously interact through its pyridinium moiety with the calix[4]arene units at the surface of the modified AgNPs.

  6. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

    PubMed

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

  7. Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

    PubMed Central

    Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

    2016-01-01

    Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

  8. Biosorption of lead by filamentous fungal biomass-loaded TiO2 nanoparticles.

    PubMed

    Bakircioglu, Yasemin; Bakircioglu, Dilek; Akman, Suleyman

    2010-06-15

    In this study filamentous fungal biomass-loaded TiO(2) nanoparticles were used for the biosorption of lead(II) ions by flow-injection system coupled to flame atomic absorption spectrometry. The effects of pH, sample volume, loading and elution flow rates, eluent type and volume on the recovery of lead were investigated. Lead ions were sorbed on a biosorbent minicolumn at pH 4.0 followed by an elution step using 288 microL of 1.0 mol/L hydrochloric acid solution. The limit of detection was 0.78 microg/L. The validation of the described procedure was performed by the analysis of certified reference material (NRC-CNRC NASS-5 seawater). Finally, the presented biosorption procedure was applied to the determination of lead in tap water and seawater samples.

  9. Design of smart oligo(ethylene glycol)-based biocompatible hybrid microgels loaded with magnetic nanoparticles.

    PubMed

    Boularas, Mohamed; Gombart, Emilie; Tranchant, Jean-François; Billon, Laurent; Save, Maud

    2015-01-01

    This article reports a rational strategy for preparing smart oligo(ethylene glycol)-based hybrid microgels loaded with high content of homogeneously distributed preformed magnetic nanoparticles (NPs) (up to 33 wt%). The strategy is based on the synthesis of biocompatible multiresponsive microgels by precipitation copolymerization of di(ethylene glycol) methyl ether methacrylate, oligo(ethylene glycol) methyl ether methacrylate, methacrylic acid, and oligo(ethylene glycol)diac-rylate. An aqueous dispersion of preformed magnetic NPs is straightforwardly loaded into the microgels. Robust monodisperse thermoresponsive magnetic microgels are produced, exhibiting a constant value of the volume phase transition temperature whatever the NPs content. The homogeneous microstructure of the initial stimuli-responsive biocompatible microgels plays a crucial role for the design of unique well-defined ethylene glycol-based thermoresponsive hybrid microgels.

  10. Development of CMC hydrogels loaded with silver nano-particles for medical applications.

    PubMed

    Hebeish, Ali; Hashem, M; El-Hady, M M Abd; Sharaf, S

    2013-01-30

    Innovative CMC-based hydrogels with great potentials for usage in medical area were principally synthesized as per two strategies .The first involved reaction of epichlorohydrin in alkaline medium containing silver nitrate to yield silver nano-particles (AgNPs)-loaded CMC hydrogel. While CMC acted as stabilizing for AgNPs, trisodium citrate was added to the reaction medium to assist CMC in establishing reduction of Ag(+) to AgNPs. The second strategy entailed preparation of CMC hydrogel which assists the in situ preparation of AgNPs under the same conditions. In both strategies, factors affecting the characterization of AgNPs-loaded CMC hydrogels were studied. Analysis and characterization of the so obtained hydrogels were performed through monitoring swelling behavior, FTIR spectroscopy, SEM, EDX, UV-vis spectrophotometer and TEM. Antimicrobial activity of the hydrogels was examined and mechanisms involved in their synthesis were reported.

  11. Novel Simvastatin-Loaded Nanoparticles Based on Cholic Acid-Core Star-Shaped PLGA for Breast Cancer Treatment.

    PubMed

    Wu, Yanping; Wang, Zhongyuan; Liu, Gan; Zeng, Xiaowei; Wang, Xusheng; Gao, Yongfeng; Jiang, Lijuan; Shi, Xiaojun; Tao, Wei; Huang, Laiqiang; Mei, Lin

    2015-07-01

    A novel nanocarrier system of cholic acid (CA) core, star-shaped polymer consisting of poly(D,L-lactide-co-glycolide) (PLGA) was developed for sustained and controlled delivery of simvastatin for chemotherapy of breast adenocarcinoma. The star-shaped polymer CA-PLGA with three branch arms was synthesized successfully through the core-first approach. The simvastatin-loaded star-shaped CA-PLGA nanoparticles were prepared through a modified nanoprecipitation method. The data showed that the fluorescence star-shaped CA-PLGA nanoparticles could be internalized into MDA-MB-231 and MDA-MB-468 human breast cancer cells. The simvastatin-loaded star-shaped CA-PLGA nanoparticles achieved significantly higher level of cytotoxicity than pristine simvastatin and simvastatin-loaded linear PLGA nanoparticles. Moreover, the expression of the cell cycle protein cyclin D1 was dramatically inhibited by simvastatin in both cells, with simvastatin-loaded star-shaped CA-PLGA nanoparticles having the greatest effect. MDA-MB-231 xenograft tumor model on BALB/c nude mice showed that simvastatin-loaded star-shaped CA-PLGA nanoformulations could effectively inhibit the growth of tumor over a longer period of time than pristine simvastatin and simvastatin-loaded linear PLGA nanoformulations at the same dose. In agreement with these, the nuclear expression of proliferation marker Ki-67 in simvastatin-loaded star-shaped CA-PLGA nanoparticles group was reduced to a most extent among four groups through tumor frozen section immunohistochemistry. In conclusion, the star-shaped CA-PLGA polymers could serve as a novel polymeric nanocarrier for breast cancer chemotherapy.

  12. Phytochemical-loaded mesoporous silica nanoparticles for nose-to-brain olfactory drug delivery.

    PubMed

    Lungare, Shital; Hallam, Keith; Badhan, Raj K S

    2016-11-20

    Central nervous system (CNS) drug delivery is often hampered due to the insidious nature of the blood-brain barrier (BBB). Nose-to-brain delivery via olfactory pathways have become a target of attention for drug delivery due to bypassing of the BBB. The antioxidant properties of phytochemicals make them promising as CNS active agents but possess poor water solubility and limited BBB penetration. The primary aim of this study was the development of mesoporous silica nanoparticles (MSNs) loaded with the poorly water-soluble phytochemicals curcumin and chrysin which could be utilised for nose-to-brain delivery. We formulated spherical MSNP using a templating approach resulting in ∼220nm particles with a high surface porosity. Curcumin and chrysin were successfully loaded into MSNP and confirmed through Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC approaches with a loading of 11-14% for curcumin and chrysin. Release was pH dependant with curcumin demonstrating increased chemical stability at a lower pH (5.5) with a release of 53.2%±2.2% over 24h and 9.4±0.6% for chrysin. MSNP were demonstrated to be non-toxic to olfactory neuroblastoma cells OBGF400, with chrysin (100μM) demonstrating a decrease in cell viability to 58.2±8.5% and curcumin an IC50 of 33±0.18μM. Furthermore confocal microscopy demonstrated nanoparticles of <500nm were able to accumulate within cells with FITC-loaded MSNP showing membrane localised and cytoplasmic accumulation following a 2h incubation. MSNP are useful carriers for poorly soluble phytochemicals and provide a novel vehicle to target and deliver drugs into the CNS and bypass the BBB through olfactory drug delivery.

  13. Evaluation of drug loading, pharmacokinetic behavior, and toxicity of a cisplatin-containing hydrogel nanoparticle

    PubMed Central

    Kai, Marc P.; Keeler, Amanda W.; Perry, Jillian L.; Reuter, Kevin G.; Luft, J. Christopher; O’Neal, Sara K.; Zamboni, William C.

    2015-01-01

    Cisplatin is a cytotoxic drug used as a first-line therapy for a wide variety of cancers. However, significant renal and neurological toxicities limits it clinical use. It has been documented that drug toxicities can be mitigated through nanoparticle formulation, while simultaneously increasing tumor accumulation through the enhanced permeation and retention effect. Circulation persistence is a key characteristic for exploiting this effect, and to that end we have developed long-circulating, PEGylated, polymeric hydrogels using the Particle Replication In Non-wetting Templates (PRINT®) platform and complexed cisplatin into the particles (PRINT-Platin). Sustained release was demonstrated, and drug loading correlated to surface PEG density. A PEG Mushroom conformation showed the best compromise between particle pharmacokinetic (PK) parameters and drug loading (16 wt %). While the PK profile of PEG Brush was superior, the loading was poor (2 wt %). Conversely, the drug loading in non-PEGylated particles was better (20 wt %), but the PK was not desirable. We also showed comparable cytotoxicity to cisplatin in several cancer cell lines (non-small cell lung, A549; ovarian, SKOV-3; breast, MDA-MB-468) and a higher MTD in mice (10 mg/kg versus 5 mg/kg). The pharmacokinetic profiles of drug in plasma, tumor, and kidney indicate improved exposure in the blood and tumor accumulation, with concurrent renal protection, when cisplatin was formulated in a nanoparticle. PK parameters were markedly improved: a 16.4-times higher area-under-the-curve (AUC), a reduction in clearance (CL) by a factor of 11.2, and a 4.20-times increase in the volume of distribution (Vd). Additionally, non-small cell lung and ovarian tumor AUC was at least twice that of cisplatin in both models. These findings suggest the potential for PRINT-Platin to improve efficacy and reduce toxicity compared to current cisplatin therapies. PMID:25744827

  14. Evaluation of drug loading, pharmacokinetic behavior, and toxicity of a cisplatin-containing hydrogel nanoparticle.

    PubMed

    Kai, Marc P; Keeler, Amanda W; Perry, Jillian L; Reuter, Kevin G; Luft, J Christopher; O'Neal, Sara K; Zamboni, William C; DeSimone, Joseph M

    2015-04-28

    Cisplatin is a cytotoxic drug used as a first-line therapy for a wide variety of cancers. However, significant renal and neurological toxicities limit its clinical use. It has been documented that drug toxicities can be mitigated through nanoparticle formulation, while simultaneously increasing tumor accumulation through the enhanced permeation and retention effect. Circulation persistence is a key characteristic for exploiting this effect, and to that end we have developed long-circulating, PEGylated, polymeric hydrogels using the Particle Replication In Non-wetting Templates (PRINT®) platform and complexed cisplatin into the particles (PRINT-Platin). Sustained release was demonstrated, and drug loading correlated to surface PEG density. A PEG Mushroom conformation showed the best compromise between particle pharmacokinetic (PK) parameters and drug loading (16wt.%). While the PK profile of PEG Brush was superior, the loading was poor (2wt.%). Conversely, the drug loading in non-PEGylated particles was better (20wt.%), but the PK was not desirable. We also showed comparable cytotoxicity to cisplatin in several cancer cell lines (non-small cell lung, A549; ovarian, SKOV-3; breast, MDA-MB-468) and a higher MTD in mice (10mg/kg versus 5mg/kg). The pharmacokinetic profiles of drug in plasma, tumor, and kidney indicate improved exposure in the blood and tumor accumulation, with concurrent renal protection, when cisplatin was formulated in a nanoparticle. PK parameters were markedly improved: a 16.4-times higher area-under-the-curve (AUC), a reduction in clearance (CL) by a factor of 11.2, and a 4.20-times increase in the volume of distribution (Vd). Additionally, non-small cell lung and ovarian tumor AUC was at least twice that of cisplatin in both models. These findings suggest the potential for PRINT-Platin to improve efficacy and reduce toxicity compared to current cisplatin therapies.

  15. 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.

  16. Transient loading of CD34+ hematopoietic progenitor cells with polystyrene nanoparticles

    PubMed Central

    Deville, Sarah; Hadiwikarta, Wahyu Wijaya; Smisdom, Nick; Wathiong, Bart; Ameloot, Marcel; Nelissen, Inge; Hooyberghs, Jef

    2017-01-01

    CD34+ hematopoietic progenitor cells (HPCs) offer great opportunities to develop new treatments for numerous malignant and non-malignant diseases. Nanoparticle (NP)-based strategies can further enhance this potential, and therefore a thorough understanding of the loading behavior of HPCs towards NPs is essential for a successful application. The present study focusses on the interaction kinetics of 40 nm sized carboxylated polystyrene (PS) NPs with HPCs. Interestingly, a transient association of the NPs with HPCs is observed, reaching a maximum within 1 hour and declining afterwards. This behavior is not seen in dendritic cells (CD34-DCs) differentiated from HPCs, which display a monotonic increase in NP load. We demonstrate that this transient interaction requires an energy-dependent cellular process, suggesting active loading and release of NPs by HPCs. This novel observation offers a unique approach to transiently equip HPCs. A simple theoretical approach modeling the kinetics of NP loading and release is presented, contributing to a framework of describing this phenomenon. PMID:28138242

  17. Design and characterization of antimicrobial usnic acid loaded-core/shell magnetic nanoparticles.

    PubMed

    Taresco, Vincenzo; Francolini, Iolanda; Padella, Franco; Bellusci, Mariangela; Boni, Adriano; Innocenti, Claudia; Martinelli, Andrea; D'Ilario, Lucio; Piozzi, Antonella

    2015-01-01

    The application of magnetic nanoparticles (MNPs) in medicine is considered much promising especially because they can be handled and directed to specific body sites by external magnetic fields. MNPs have been investigated in magnetic resonance imaging, hyperthermia and drug targeting. In this study, properly functionalized core/shell MNPs with antimicrobial properties were developed to be used for the prevention and treatment of medical device-related infections. Particularly, surface-engineered manganese iron oxide MNPs, produced by a micro-emulsion method, were coated with two different polymers and loaded with usnic acid (UA), a dibenzofuran natural extract possessing antimicrobial activity. Between the two polymer coatings, the one based on an intrinsically antimicrobial cationic polyacrylamide (pAcDED) resulted to be able to provide MNPs with proper magnetic properties and basic groups for UA loading. Thanks to the establishment of acid-base interactions, pAcDED-coated MNPs were able to load and release significant drug amounts resulting in good antimicrobial properties versus Staphylococcus epidermidis (MIC = 0.1 mg/mL). The use of pAcDED having intrinsic antimicrobial activity as MNP coating in combination with UA likely contributed to obtain an enhanced antimicrobial effect. The developed drug-loaded MNPs could be injected in the patient soon after device implantation to prevent biofilm formation, or, later, in presence of signs of infection to treat the biofilm grown on the device surfaces.

  18. In Situ Loading of Basic Fibroblast Growth Factor Within Porous Silica Nanoparticles for a Prolonged Release

    NASA Astrophysics Data System (ADS)

    Zhang, Jin; Postovit, Lynne-Marie; Wang, Dashan; Gardiner, Richard B.; Harris, Richard; Abdul, Mumin Md; Thomas, Anu Alice

    2009-11-01

    Basic fibroblast growth factor (bFGF), a protein, plays a key role in wound healing and blood vessel regeneration. However, bFGF is easily degraded in biologic systems. Mesoporous silica nanoparticles (MSNs) with well-tailored porous structure have been used for hosting guest molecules for drug delivery. Here, we report an in situ route to load bFGF in MSNs for a prolonged release. The average diameter ( d) of bFGF-loaded MSNs is 57 ± 8 nm produced by a water-in-oil microemulsion method. The in vitro releasing profile of bFGF from MSNs in phosphate buffer saline has been monitored for 20 days through a colorimetric enzyme linked immunosorbent assay. The loading efficiency of bFGF in MSNs is estimated at 72.5 ± 3%. In addition, the cytotoxicity test indicates that the MSNs are not toxic, even at a concentration of 50 μg/mL. It is expected that the in situ loading method makes the MSNs a new delivery system to deliver protein drugs, e.g. growth factors, to help blood vessel regeneration and potentiate greater angiogenesis.

  19. High Loading of Pd Nanoparticles by Interior Functionalization of MOFs for Heterogeneous Catalysis.

    PubMed

    Gole, Bappaditya; Sanyal, Udishnu; Banerjee, Rahul; Mukherjee, Partha Sarathi

    2016-03-07

    In this report, the issue related to nanoparticle (NP) agglomeration upon increasing their loading amount into metal-organic frameworks (MOFs) has been addressed by functionalization of MOFs with alkyne groups. The alkynophilicity of the Pd(2+) (or other noble metals) ions has been utilized successfully for significant loading of Pd NPs into alkyne functionalized MOFs. It has been shown here that the size and loading amount of Pd NPs are highly dependent on the surface area and pore width of the MOFs. The loading amount of Pd NPs was increased monotonically without altering their size distribution on a particular MOF. Importantly, the distinct role of alkyne groups for Pd(2+) stabilization has also been demonstrated by performing a control experiment considering a MOF without an alkyne moiety. The preparation of NPs involved two distinct steps viz. adsorption of metal ions inside MOFs and reduction of metal ions. Both of these steps were monitored by microscopic techniques. This report also demonstrates the applicability of Pd@MOF NPs as extremely efficient heterogeneous catalysts for Heck-coupling and hydrogenation reactions of aryl bromides or iodides and alkenes, respectively.

  20. CD98 siRNA-loaded nanoparticles decrease hepatic steatosis in mice.

    PubMed

    Canup, Brandon S B; Song, Heliang; Le Ngo, Vu; Meng, Xiangxiao; Denning, Timothy L; Garg, Pallavi; Laroui, Hamed

    2017-02-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid hepatic accumulation. Here, we investigated whether a reduction of CD98 expression mediated by CD98 siRNA-loaded nanoparticles (NPs) could attenuate liver disease markers in a mouse model of NAFLD. NPs were generated using a double emulsion/solvent evaporation technique. Mice fed a high fat diet for 8 weeks to induce fatty liver were treated with vein tail injections of CD98 siRNA-loaded NPs. In vitro, HepG2 treated with CD98 siRNA-loaded NPs showed significant downregulation of CD98 leading to a significant decrease of major pro-inflammatory cytokines and markers. In vivo, CD98 siRNA-loaded NPs strongly decreased all markers of NAFLD, including the blood levels of ALT and lipids accumulation, fibrosis evidence and pro-inflammatory cytokines. In conclusion, our results indicate that CD98 appears to function as a key actor/inducer in NAFLD, and that our NPs approach may offer a new targeted therapeutic for this disease.

  1. Targeting Intestinal Inflammation With CD98 siRNA/PEI–loaded Nanoparticles

    PubMed Central

    Laroui, Hamed; Geem, Duke; Xiao, Bo; Viennois, Emilie; Rakhya, Poonam; Denning, Timothy; Merlin, Didier

    2014-01-01

    Intestinal CD98 expression plays a crucial role in controlling homeostatic and innate immune responses in the gut. Modulation of CD98 expression in intestinal cells therefore represents a promising therapeutic strategy for the treatment and prevention of inflammatory intestinal diseases, such as inflammatory bowel disease. Here, the advantages of nanoparticles (NPs) are used, including their ability to easily pass through physiological barriers and evade phagocytosis, high loading concentration, rapid kinetics of mixing and resistance to degradation. Using physical chemistry characterizations techniques, CD98 siRNA/polyethyleneimine (PEI)–loaded NPs was characterized (diameter of ~480 nm and a zeta potential of −5.26 mV). Interestingly, CD98 siRNA can be electrostatically complexed by PEI and thus protected from RNase. In addition, CD98 siRNA/PEI–loaded NPs are nontoxic and biocompatible with intestinal cells. Oral administration of CD98/PEI-loaded NPs encapsulated in a hydrogel reduced CD98 expression in mouse colonic tissues and decreased dextran sodium sulfate–induced colitis in a mouse model. Finally, flow cytometry showed that CD98 was effectively downregulated in the intestinal epithelial cells and intestinal macrophages of treated mice. Finally, the results collectively demonstrated the therapeutic effect of “hierarchical nano-micro particles” with colon-homing capabilities and the ability to directly release “molecularly specific” CD98 siRNA in colonic cells, thereby decreasing colitis. PMID:24025751

  2. Physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) for pulmonary application.

    PubMed

    Paranjpe, M; Finke, J H; Richter, C; Gothsch, T; Kwade, A; Büttgenbach, S; Müller-Goymann, C C

    2014-12-10

    For the development of any colloidal system, thorough characterization is extremely essential. This article discusses the physicochemical characterization of sildenafil-loaded solid lipid nanoparticle dispersions (SLN) including stability analysis over 6 months time period for possible pulmonary administration for the treatment of pulmonary arterial hypertension (PAH). SLN consisting of phospholipid and triglycerides were manufactured using a novel microchannel homogenization method. These sildenafil-loaded SLN were then subjected to physicochemical characterization namely, particle size and distribution over shelf life, differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD) and analysis of nebulization performance of these SLN by the means of next generation impactor (NGI). Additionally, the morphology of nebulized particles was assessed by transmission electron microscopy using negative staining technique. The solubility of sildenafil citrate and base in the lipid matrix was determined and was 0.1% w/w and 1% w/w, respectively. From the particle size measurements, it was observed that SLN without sildenafil demonstrated consistent particle sizes over 6 months. For the sildenafil-loaded SLN, increased particle sizes were found after manufacturing and further increased within weeks. From WAXD studies, after 6 months high intensity reflections corresponding to the stable β modification were observed. From DSC results, the peak minimum temperatures increased upon storage, hinting at a transformation to the stable β modification of triglycerides in the case of sildenafil-loaded SLN. Hence, it can be concluded that even small drug concentration influences particle size and stability.

  3. Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections

    PubMed Central

    Díez-Martínez, Roberto; García-Fernández, Esther; Manzano, Miguel; Martínez, Ángel; Domenech, Mirian; Vallet-Regí, María; García, Pedro

    2016-01-01

    Drug-loaded nanoparticles (NPs) can improve infection treatment by ensuring drug concentration at the right place within the therapeutic window. Poly(lactic-co-glycolic acid) (PLGA) NPs are able to enhance drug localization in target site and to sustainably release the entrapped molecule, reducing the secondary effects caused by systemic antibiotic administration. We have loaded auranofin, a gold compound traditionally used for treatment of rheumatoid arthritis, into PLGA NPs and their efficiency as antibacterial agent against two Gram-positive pathogens, Streptococcus pneumoniae and Streptococcus pyogenes was evaluated. Auranofin-PLGA NPs showed a strong bactericidal effect as cultures of multiresistant pneumococcal strains were practically sterilized after 6 h of treatment with such auranofin-NPs at 0.25 μM. Moreover, this potent bactericidal effect was also observed in S. pneumoniae and S. pyogenes biofilms, where the same concentration of auranofin-NPs was capable of decreasing the bacterial population about 4 logs more than free auranofin. These results were validated using a zebrafish embryo model demonstrating that treatment with auranofin loaded into NPs achieved a noticeable survival against pneumococcal infections. All these approaches displayed a clear superiority of loaded auranofin PLGA nanocarriers compared to free administration of the drug, which supports their potential application for the treatment of streptococcal infections. PMID:26776881

  4. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics.

    PubMed

    Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Ghosh, Siddhartha Sankar

    2014-08-29

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a 'green synthesis' method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

  5. Titantium Dioxide Nanoparticles Assembled by DNA Molecules Hybridization and Loading of DNA Interacting Proteins.

    PubMed

    Wu, Aiguo; Paunesku, Tatjana; Brown, Eric M B; Babbo, Angela; Cruz, Cecille; Aslam, Mohamed; Dravid, Vinayak; Woloschak, Gayle E

    2008-02-01

    This work demonstrates the assembly of TiO(2) nanoparticles with attached DNA oligonucleotides into a 3D mesh structure by allowing base pairing between oligonucleotides. A change of the ratio of DNA oligonucleotide molecules and TiO(2) nanoparticles regulates the size of the mesh as characterized by UV-visible light spectra, transmission electron microscopy and atomic force microscopy images. This type of 3D mesh, based on TiO(2)-DNA oligonucleotide nanoconjugates, can be used for studies of nanoparticle assemblies in material science, energy science related to dye-sensitized solar cells, environmental science as well as characterization of DNA interacting proteins in the field of molecular biology. As an example of one such assembly, proliferating cell nuclear antigen protein (PCNA) was cloned, its activity verified, and the protein was purified, loaded onto double strand DNA oligonucleotide-TiO(2) nanoconjugates, and imaged by atomic force microscopy. This type of approach may be used to sample and perhaps quantify and/or extract specific cellular proteins from complex cellular protein mixtures affinity based on their affinity for chosen DNA segments assembled into the 3D matrix.

  6. Application of Box-Behnken design to prepare gentamicin-loaded calcium carbonate nanoparticles.

    PubMed

    Maleki Dizaj, Solmaz; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad-Hossein; Adibkia, Khosro

    2016-09-01

    The aim of this research was to prepare and optimize calcium carbonate (CaCO3) nanoparticles as carriers for gentamicin sulfate. A chemical precipitation method was used to prepare the gentamicin sulfate-loaded CaCO3 nanoparticles. A 3-factor, 3-level Box-Behnken design was used for the optimization procedure, with the molar ratio of CaCl2: Na2CO3 (X1), the concentration of drug (X2), and the speed of homogenization (X3) as the independent variables. The particle size and entrapment efficiency were considered as response variables. Mathematical equations and response surface plots were used, along with the counter plots, to relate the dependent and independent variables. The results indicated that the speed of homogenization was the main variable contributing to particle size and entrapment efficiency. The combined effect of all three independent variables was also evaluated. Using the response optimization design, the optimized Xl-X3 levels were predicted. An optimized formulation was then prepared according to these levels, resulting in a particle size of 80.23 nm and an entrapment efficiency of 30.80%. It was concluded that the chemical precipitation technique, together with the Box-Behnken experimental design methodology, could be successfully used to optimize the formulation of drug-incorporated calcium carbonate nanoparticles.

  7. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

    NASA Astrophysics Data System (ADS)

    Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Sankar Ghosh, Siddhartha

    2014-08-01

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

  8. Antibacterial performance on plasma polymerized heptylamine films loaded with silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Lin, Yu-Chun; Lin, Chia-Chun; Lin, Chih-Hao; Wang, Meng-Jiy

    2017-01-01

    The antibacterial performance of the plasma-polymerized (pp) heptylamine thin films loaded with silver nanoparticles was evaluated against the colonization of Escherichia coli and Staphylococcus aureus. The properties including the thickness and chemical composition of the as deposited HApp films were modulated by adjusting plasma parameters. The acquired results showed that the film thickness was controlled in the range of 20 to 400 nm by adjusting deposition time. The subsequent immersion of the HApp thin films in silver nitrate solutions result in the formation of amine-metal complexes, in which the silver nanoparticles were reduced directly on the matrices to form Ag@HApp. The reduction reaction of silver was facilitated by applying NaBH4 as a reducing agent. The results of physicochemical analyses including morphological analysis and ellipsometry revealed that the silver nanoparticles were successfully reduced on the HApp films, and the amount of reduced silver was closely associated which the thickness of the plasma-polymerized films, the concentration of applied metal ions solutions, and the time of immobilization. Regarding the antibacterial performance, the Ag@HApp films reduced by NaBH4 showed antibacterial abilities of 70.1 and 68.2% against E. coli and S. aureus, respectively.

  9. Optimization and evaluation of a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles

    PubMed Central

    Lou, Jie; Hu, Wenjing; Tian, Rui; Zhang, Hua; Jia, Yuntao; Zhang, Jingqing; Zhang, Liangke

    2014-01-01

    This study aimed to optimize and evaluate a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles (Cur-BSA-NPs-Gel). Albumin nanoparticles were prepared via a desolvation method, and the gels were prepared via a cold method. The central composite design and response surface method was used to evaluate the effects of varying Pluronic® F127 and Pluronic® F68 concentrations on the sol–gel transition temperature, which is an indicator of optimum formulations. The optimized formulation was a free-flowing liquid below 30.9°C that transformed into a semi-solid gel above 34.2°C after dilution with simulated tear fluid. Results of the in vitro release and erosion behavior study indicated that Cur-BSA-NPs-Gel achieved superior sustained-release effects and that incorporation of albumin nanoparticles exerted minimal effects on the gel structure. In addition, in vivo ophthalmic experiments employing Cur-BSA-NPs-Gel were subsequently performed in rabbits. In vivo eye irritation results showed that Cur-BSA-NPs-Gel might be considered safe for ophthalmic drug delivery. The in vivo study also revealed that the formulation could significantly increase curcumin bioavailability in the aqueous humor. In conclusion, the optimized in situ gel formulation developed in this work has significant potential for ocular application. PMID:24904211

  10. Indocyanine Green-Loaded Nanoparticles for Image-Guided Tumor Surgery

    PubMed Central

    Hill, Tanner K.; Abdulahad, Asem; Kelkar, Sneha S.; Marini, Frank C.; Long, Timothy E.; Provenzale, James M.; Mohs, Aaron M.

    2015-01-01

    Detecting positive tumor margins and local malignant masses during surgery is critical for long-term patient survival. The use of image-guided surgery for tumor removal, particularly with near-infrared fluorescent imaging, is a potential method to facilitate removing all neoplastic tissue at the surgical site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared dye indocyanine green, termed NanoICG, for improved delivery of the dye to tumors. Self-assembly of the nanoparticles was driven by conjugation of one of three hydrophobic moieties: aminopropyl-1-pyrenebutanamide (PBA), aminopropyl-5β-cholanamide (5βCA), or octadecylamine (ODA). Nanoparticle self-assembly, dye loading, and optical properties were characterized. NanoICG exhibited quenched fluorescence that could be activated by disassembly in a mixed solvent. NanoICG was found to be nontoxic at physiologically relevant concentrations and exposure was not found to inhibit cell growth. Using an MDA-MB-231 tumor xenograft model in mice, strong fluorescence enhancement in tumors was observed with NanoICG using a fluorescence image-guided surgery system and a whole-animal imaging system. Tumor contrast with NanoICG was significantly higher than with ICG alone. PMID:25565445

  11. Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: Physicochemical and in vitro studies.

    PubMed

    Gaspar, Diana P; Faria, Vasco; Gonçalves, Lídia M D; Taboada, Pablo; Remuñán-López, Carmen; Almeida, António J

    2016-01-30

    Systemic administration of antitubercular drugs can be complicated by off-target toxicity to cells and tissues that are not infected by Mycobacterium tuberculosis . Delivery of antitubercular drugs via nanoparticles directly to the infected cells has the potential to maximize efficacy and minimize toxicity. The present work demonstrates the potential of solid lipid nanoparticles (SLN) as a delivery platform for rifabutin (RFB). Two different RFB-containing SLN formulations were produced using glyceryl dibehenate or glyceryl tristearate as lipid components. Full characterization was performed in terms of particle size, encapsulation and loading efficiency, morphology by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) studies. Physical stability was evaluated when formulations were stored at 5 ± 3°C and in the freeze-dried form. Formulations were stable throughout lyophilization without significant variations on physicochemical properties and RFB losses. The SLN showed to be able to endure harsh temperature conditions as demonstrated by dynamic light scattering (DLS). Release studies revealed that RFB was almost completely released from SLN. In vitro studies with THP1 cells differentiated in macrophages showing a nanoparticle uptake of 46 ± 3% and 26 ± 9% for glyceryl dibehenate and glyceryl tristearate SLN, respectively. Cell viability studies using relevant lung cell lines (A549 and Calu-3) revealed low cytotoxicity for the SLN, suggesting these could be new potential vehicles for pulmonary delivery of antitubercular drugs.

  12. Stability and antimicrobial effect of amikacin-loaded solid lipid nanoparticles

    PubMed Central

    Ghaffari, Solmaz; Varshosaz, Jaleh; Saadat, Afrooz; Atyabi, Fatemeh

    2011-01-01

    Solid lipid nanoparticles (SLNs) of amikacin were designed in this study for pulmonary delivery to reduce the dose or its administration intervals leading to reduction of its toxicities especially in long term treatment. Nanoparticles of amikacin were prepared from cholesterol by solvent diffusion technique and homogenization. The size, zeta potential, loading efficiency, and release profile of the nanoparticles were studied. The conventional broth macrodilution tube method was used to determine the minimum inhibitory concentration (MIC) and minimum bacteriostatic concentration (MBC) of amikacin SLNs with respect to Pseudomonas aeruginosa in vitro. To guarantee the stability of desired SLNs, they were lyophilized using cryoprotectants. Results showed that considering the release profile of amikacin from the studied nanocarrier, MIC and MBC of amikacin could be about two times less in SLNs of amikacin compared to the free drug. Therefore, fewer doses of amikacin in SLNs can clear the infection with less adverse effects and more safety. Particle size enlargement after lyophilization of desired SLNs after two months storage was limited in comparison with non-lyophilized particles, 996 and 194 nm, respectively. Zeta potential of lyophilized particles was increased to +17 mV from +4 mV before lyophilization. Storage of particles in higher temperature caused accelerated drug release. PMID:21289980

  13. Development and optimization of quercetin-loaded PLGA nanoparticles by experimental design

    PubMed Central

    TEFAS, LUCIA RUXANDRA; TOMUŢĂ, IOAN; ACHIM, MARCELA; VLASE, LAURIAN

    2015-01-01

    Background and aims Quercetin is a flavonoid with good antioxidant activity, and exhibits various important pharmacological effects. The aim of the present work was to study the influence of formulation factors on the physicochemical properties of quercetin-loaded polymeric nanoparticles in order to optimize the formulation. Materials and methods The nanoparticles were prepared by the nanoprecipitation method. A 3-factor, 3-level Box-Behnken design was employed in this study considering poly(D,L-lactic-co-glycolic) acid (PLGA) concentration, polyvinyl alcohol (PVA) concentration and the stirring speed as independent variables. The responses were particle size, polydispersity index, zeta potential and encapsulation efficiency. Results The PLGA concentration seemed to be the most important factor influencing quercetin-nanoparticle characteristics. Increasing PLGA concentration led to an increase in particle size, as well as encapsulation efficiency. On the other hand, it exhibited a negative influence on the polydispersity index and zeta potential. The PVA concentration and the stirring speed had only a slight influence on particle size and polydispersity index. However, PVA concentration had an important negative effect on the encapsulation efficiency. Based on the results obtained, an optimized formulation was prepared, and the experimental values were comparable to the predicted ones. Conclusions The overall results indicated that PLGA concentration was the main factor influencing particle size, while entrapment efficiency was predominantly affected by the PVA concentration. PMID:26528074

  14. Indocyanine green-loaded nanoparticles for image-guided tumor surgery.

    PubMed

    Hill, Tanner K; Abdulahad, Asem; Kelkar, Sneha S; Marini, Frank C; Long, Timothy E; Provenzale, James M; Mohs, Aaron M

    2015-02-18

    Detecting positive tumor margins and local malignant masses during surgery is critical for long-term patient survival. The use of image-guided surgery for tumor removal, particularly with near-infrared fluorescent imaging, is a potential method to facilitate removing all neoplastic tissue at the surgical site. In this study we demonstrate a series of hyaluronic acid (HLA)-derived nanoparticles that entrap the near-infrared dye indocyanine green, termed NanoICG, for improved delivery of the dye to tumors. Self-assembly of the nanoparticles was driven by conjugation of one of three hydrophobic moieties: aminopropyl-1-pyrenebutanamide (PBA), aminopropyl-5β-cholanamide (5βCA), or octadecylamine (ODA). Nanoparticle self-assembly, dye loading, and optical properties were characterized. NanoICG exhibited quenched fluorescence that could be activated by disassembly in a mixed solvent. NanoICG was found to be nontoxic at physiologically relevant concentrations and exposure was not found to inhibit cell growth. Using an MDA-MB-231 tumor xenograft model in mice, strong fluorescence enhancement in tumors was observed with NanoICG using a fluorescence image-guided surgery system and a whole-animal imaging system. Tumor contrast with NanoICG was significantly higher than with ICG alone.

  15. Synthesis of MgO nanoparticle loaded mesoporous Al2O3 and its defluoridation study

    NASA Astrophysics Data System (ADS)

    Dayananda, Desagani; Sarva, Venkateswara R.; Prasad, Sivankutty V.; Arunachalam, Jayaraman; Parameswaran, Padmanabhan; Ghosh, Narendra N.

    2015-02-01

    MgO nanoparticle loaded mesoporous alumina has been synthesized using a simple aqueous solution based cost effective method for removal of fluoride from water. Wide angle powder X-ray diffraction, nitrogen adsorption desorption analysis, transmission electron microscopy techniques and energy dispersive X-ray spectroscopy were used to characterize the synthesized adsorbents. Synthesized adsorbents possess high surface area with mesoporous structure. The adsorbents have been thoroughly investigated for the adsorption of F- using batch adsorption method. MgO nanoparticle loading on mesoporous Al2O3 enhances the F- adsorption capacity of Al2O3 from 56% to 90% (initial F- concentration = 10 mg L-1). Kinetic study revealed that adsorption kinetics follows the pseudo-second order model, suggesting the chemisorption mechanism. The F- adsorption isotherm data was explained by both Langmuir and Freundlich model. The maximum adsorption capacity of 40MgO@Al2O3 was 37.35 mg g-1. It was also observed that, when the solutions having F- concentration of 5 mg L-1 and 10 mg L-1 was treated with 40MgO@Al2O3, the F- concentration in treated water became <1 mg L-1, which is well below the recommendation of WHO.

  16. Enhanced Ehrlich tumor inhibition using DOX-NP™ and gold nanoparticles loaded liposomes

    NASA Astrophysics Data System (ADS)

    Mady, M. M.; Al-Shaikh, F. H.; Al-Farhan, F. F.; Aly, A. A.; Al-Mohanna, M. A.; Ghannam, M. M.

    2016-04-01

    Treatment with doxorubicin (DOX) is a common regime in treating various types of cancer. DOX-NP™ is one of a well established marketed liposomal formulation for DOX. It offers distinct advantages over conventional DOX in reducing the cardiac toxicity and increasing the tolerability and efficacy. Gold nanoparticles (GNPs), a typical biocompatible nanomaterial, have been widely used in biomedical engineering and bioanalytical applications such as biomedical imaging and biosensors. Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, free doxorubicin (DOX) in solution, gold nanoparticles loaded liposomes and commercial liposomal encapsulated doxorubicin (DOX-NP™). The results showed that GNPs loaded liposomes could enhance the antitumor activity of commercial liposomal formulation (DOX-NP™) and displayed significantly decreased systemic toxicity compared with free DOX and commercial liposomal formulation (DOX-NP™) at the equivalent dose. So the combination of GNPs and liposomes is expected to significantly increase the likelihood of cell killing and make it a promising new approach to cancer therapy.

  17. Cyanine-loaded lipid nanoparticles for improved in vivo fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Texier, Isabelle; Goutayer, Mathieu; da Silva, Anabela; Guyon, Laurent; Djaker, Nadia; Josserand, Véronique; Neumann, Emmanuelle; Bibette, Jérôme; Vinet, Françoise

    2009-09-01

    Fluorescence is a very promising radioactive-free technique for functional imaging in small animals and, in the future, in humans. However, most commercial near-infrared dyes display poor optical properties, such as low fluorescence quantum yields and short fluorescence lifetimes. In this paper, we explore whether the encapsulation of infrared cyanine dyes within the core of lipid nanoparticles (LNPs) could improve their optical properties. Lipophilic dialkylcarbocyanines DiD and DiR are loaded very efficiently in 30-35-nm-diam lipid droplets stabilized in water by surfactants. No significant fluorescence autoquenching is observed up to 53 dyes per particle. Encapsulated in LNP, which are stable for more than one year at room temperature in HBS buffer (HEPES 0.02 M, EDTA 0.01 M, pH 5.5), DiD and DiR display far improved fluorescence quantum yields Φ (respectively, 0.38 and 0.25) and longer fluorescence lifetimes τ (respectively, 1.8 and 1.1 ns) in comparison to their hydrophilic counterparts Cy5 (φ=0.28, τ=1.0 ns) and Cy7 (φ=0.13, τ=0.57 ns). Moreover, dye-loaded LNPs are able to accumulate passively in various subcutaneous tumors in mice, thanks to the enhanced permeability and retention effect. These new fluorescent nanoparticles therefore appear as very promising labels for in vivo fluorescence imaging.

  18. Magnetic nanoparticles-loaded PLA/PEG microspheres as drug carriers.

    PubMed

    Frounchi, Masoud; Shamshiri, Soodeh

    2015-05-01

    Surface-modified magnetite (Fe3 O4 ) nanoparticles with an average size of 22 nm were prepared. The nanoparticles had a saturation magnetization of 50.7 emu g(-1) . Then magnetite and drug-loaded microspheres of poly (lactic acid)/poly (ethylene glycol) were prepared at various compositions. The microspheres were spherical in shape and had smooth surface. The diameter size of the microspheres ranged between about 0.2 and 4 μm. Doxorubicin hydrochloride for cancer treatment was the drug that loaded into the microspheres. The prepared microspheres were characterized by FTIR, XRD, VSM, SEM and drug-release measurements. It was found that the drug cumulative release percentage was proportional to (time) (n) where 0.61 < n < 0.75 depending on PEG and Fe3 O4 contents. The drug release was controlled through a combination of diffusion and PLA hydrolysis and obeyed a non-fickian mechanism. The drug release was facilitated by presence of poly (ethylene glycol) as PLA plasticizer and was higher under applied external magnetic field. The obtained magnetic microspheres could be used as drug carriers for targeted drug delivery purposes.

  19. Enhancement of temozolomide stability by loading in chitosan-carboxylated polylactide-based nanoparticles

    NASA Astrophysics Data System (ADS)

    Di Martino, Antonio; Kucharczyk, Pavel; Capakova, Zdenka; Humpolicek, Petr; Sedlarik, Vladimir

    2017-02-01

    In the presented work, amphiphilic nanoparticles based on chitosan and carboxy-enriched polylactic acid have been prepared to improve the stability of the pro-drug temozolomide in physiological media by encapsulation. The carrier, with a diameter in the range of 150-180 nm, was able to accommodate up to 800 μg of temozolomide per mg of polymer. The obtained formulation showed good stability in physiological condition and preparation media up to 1 month. Temozolomide loaded inside the carrier exhibited greater stability than the free drug, in particular in simulated physiological solution at pH 7.4 where the hydrolysis in the inactive metabolite was clearly delayed. CS-SPLA nanoparticles demonstrated a pH-dependent TMZ release kinetics with the opportunity to increase or decrease the rate. Mass spectroscopy, UV-Vis analysis, and in vitro cell tests confirmed the improvement in temozolomide stability and effectiveness when loaded into the polymeric carrier, in comparison with the free drug.

  20. Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy.

    PubMed

    Dilnawaz, Fahima; Singh, Abhalaxmi; Mohanty, Chandana; Sahoo, Sanjeeb K

    2010-05-01

    The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects to the healthy tissues. To overcome this, drug loaded multifunctional magnetic nanoparticles are conceptualized. We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO-MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore, antibody conjugated GMO-MNPs could be used as potential drug carrier for the active therapeutic aspects in cancer therapy.

  1. Utilizing the protein corona around silica nanoparticles for dual drug loading and release.

    PubMed

    Shahabi, Shakiba; Treccani, Laura; Dringen, Ralf; Rezwan, Kurosch

    2015-10-21

    A protein corona forms spontaneously around silica nanoparticles (SNPs) in serum-containing media. To test whether this protein corona can be utilized for the loading and release of anticancer drugs we incorporated the hydrophilic doxorubicin, the hydrophobic meloxicam as well as their combination in the corona around SNPs. The application of corona-covered SNPs to osteosarcoma cells revealed that drug-free particles did not affect the cell viability. In contrast, SNPs carrying a protein corona with doxorubicin or meloxicam lowered the cell proliferation in a concentration-dependent manner. In addition, these particles had an even greater antiproliferative potential than the respective concentrations of free drugs. The best antiproliferative effects were observed for SNPs containing both doxorubicin and meloxicam in their corona. Co-localization studies revealed the presence of doxorubicin fluorescence in the nucleus and lysosomes of cells exposed to doxorubicin-containing coated SNPs, suggesting that endocytotic uptake of the SNPs facilitates the cellular accumulation of the drug. Our data demonstrate that the protein corona, which spontaneously forms around nanoparticles, can be efficiently exploited for loading the particles with multiple drugs for therapeutic purposes. As drugs are efficiently released from such particles they may have a great potential for nanomedical applications.

  2. Photosensitizer-Loaded Branched Polyethylenimine-PEGylated Ceria Nanoparticles for Imaging-Guided Synchronous Photochemotherapy.

    PubMed

    Yang, Zhang-You; Li, Hong; Zeng, Yi-Ping; Hao, Yu-Hui; Liu, Cong; Liu, Jing; Wang, Wei-Dong; Li, Rong

    2015-11-04

    A multifunctional theranostic platform based on photosensitizer (chlorin e6, Ce6)-loaded branched polyethylenimine-PEGylated ceria nanoparticles (PPCNPs-Ce6) was created for the development of effective cancer treatments involving the use of imaging-guided synchronous photochemotherapy. PPCNPs-Ce6 with high Ce6 photosensitizer loading (Ce6: cerium ∼40 wt %) significantly enhanced the delivery of Ce6 into cells and its accumulation in lysosomes, remarkably improving photodynamic therapeutic (PDT) efficacy levels compared to those in the administration of free Ce6 at ultralow drug doses (∼200 nM). Interestingly, PPCNPs-Ce6 efficiently induced HeLa cell death even at low concentrations (∼10 μM) without the use of laser irradiation and exhibit chemocytotoxicity. Inductively coupled plasma mass spectrometry (ICP-MS) and biology transmission electron microscopy (Bio-TEM) analyses demonstrated that ceria nanoparticles enter cells abundantly and accumulate in lysosomes or large vesicles. We then evaluated the effects of the different materials on lysosomal integrity and function, which revealed that PPCNPs-Ce6 catastrophically impaired lysosomal function compared to results with PPCNPs and Ce6. Studies of apoptosis revealed greater induction of apoptosis by PPCNPs-Ce6 treatment. This multifunctional nanocarrier also exhibited a high degree of solubility and stability in aqueous solutions, suggesting its applicability for extensive biomedical application.

  3. Facile preparation of paclitaxel loaded silk fibroin nanoparticles for enhanced antitumor efficacy by locoregional drug delivery.

    PubMed

    Wu, Puyuan; Liu, Qin; Li, Rutian; Wang, Jing; Zhen, Xu; Yue, Guofeng; Wang, Huiyu; Cui, Fangbo; Wu, Fenglei; Yang, Mi; Qian, Xiaoping; Yu, Lixia; Jiang, Xiqun; Liu, Baorui

    2013-12-11

    Non-toxic, safe materials and preparation methods are among the most important factors when designing nanoparticles (NPs) for future clinical application. Here we report a novel and facile method encapsulating anticancer drug paclitaxel (PTX) into silk fibroin (SF), a biocompatible and biodegradable natural polymer, without adding any toxic organic solvents, surfactants or other toxic agents. The paclitaxel loaded silk fibroin nanoparticles (PTX-SF-NPs) with a diameter of 130 nm were formed in an aqueous solution at room temperature by self-assembling of SF protein, which demonstrated mainly silk I conformation in the NPs. In cellular uptake experiments, coumarin-6 loaded SF NPs were taken up efficiently by two human gastric cancer cell lines BGC-823 and SGC-7901. In vitro cytotoxicity studies demonstrated that PTX kept its pharmacological activity when incorporating into PTX-SF-NPs, while SF showed no cytotoxicity to cells. The in vivo antitumor effects of PTX-SF-NPs were evaluated on gastric cancer nude mice exnograft model. We found that locoregional delivery of PTX-SF-NPs demonstrated superior antitumor efficacy by delaying tumor growth and reducing tumor weights compared with systemic administration. Furthermore, the organs of mice in NP treated groups didn't show obvious toxicity, indicating the in vivo safety of SF NPs. These results suggest that SF NPs are promising drug delivery carriers, and locoregional delivery of SF NPs could be a potential future clinical cancer treatment regimen.

  4. Amsacrine analog-loaded solid lipid nanoparticle to resolve insolubility for injection delivery: characterization and pharmacokinetics

    PubMed Central

    Fang, Yi-Ping; Chuang, Chih-Hung; Wu, Pao-Chu; Huang, Yaw-Bin; Tzeng, Cherng-Chyi; Chen, Yeh-Long; Liu, Ya-Ting; Tsai, Yi-Hung; Tsai, Ming-Jun

    2016-01-01

    Amsacrine analog is a novel chemotherapeutic agent that provides potentially broad antitumor activity when compared to traditional amsacrine. However, the major limitation of amsacrine analog is that it is highly lipophilic, making it nonconductive to intravenous administration. The aim of this study was to utilize solid lipid nanoparticles (SLN) to resolve the delivery problem and to investigate the biodistribution of amsacrine analog-loaded SLN. Physicochemical characterizations of SLN, including particle size, zeta potential, entrapment efficiency, and stability, were evaluated. In vitro release behavior was also measured by the dialysis method. In vivo pharmacokinetics and biodistribution behavior of amsacrine analog were investigated and incorporated with a non invasion in vivo imaging system to confirm the localization of SLN. The results showed that amsacrine analog-loaded SLN was 36.7 nm in particle size, 0.37 in polydispersity index, and 34.5±0.047 mV in zeta potential. More than 99% of amsacrine analog was successfully entrapped in the SLN. There were no significant differences in the physicochemical properties after storage at room temperature (25°C) for 1 month. Amsacrine analog-loaded SLN maintained good stability. An in vitro release study showed that amsacrine analog-loaded SLN sustained a release pattern and followed the zero equation. An in vivo pharmacokinetics study showed that amsacrine analog was rapidly distributed from the central compartment to the tissue compartments after intravenous delivery of amsacrine analog-loaded SLN. The biodistribution behavior demonstrated that amsacrine analog mainly accumulated in the lungs. Noninvasion in vivo imaging system images also confirmed that the drug distribution was predominantly localized in the lungs when IR-780-loaded SLN was used. PMID:27019595

  5. A Room Temperature H2 Sensor Fabricated Using High Performance Pt-Loaded SnO2 Nanoparticles

    PubMed Central

    Wang, Sheng-Chang; Shaikh, Muhammad Omar

    2015-01-01

    Highly sensitive H2 gas sensors were prepared using pure and Pt-loaded SnO2 nanoparticles. Thick film sensors (~35 μm) were fabricated that showed a highly porous interconnected structure made of high density small grained nanoparticles. Using Pt as catalyst improved sensor response and reduced the operating temperature for achieving high sensitivity because of the negative temperature coefficient observed in Pt-loaded SnO2. The highest sensor response to 1000 ppm H2 was 10,500 at room temperature with a response time of 20 s. The morphology of the SnO2 nanoparticles, the surface loading concentration and dispersion of the Pt catalyst and the microstructure of the sensing layer all play a key role in the development of an effective gas sensing device. PMID:26091394

  6. Loading of anthocyanins on chitosan nanoparticles influences anthocyanin degradation in gastrointestinal fluids and stability in a beverage.

    PubMed

    He, Bo; Ge, Jiao; Yue, Pengxiang; Yue, XueYang; Fu, Ruiyan; Liang, Jin; Gao, Xueling

    2017-04-15

    The optimal preparation parameters to create anthocyanin-loaded chitosan nanoparticles was predicted using response surface methodology (RSM). A Box-Behnken design was used to determine the preparation parameters that would achieve the preferred particle size and high encapsulation efficiency. The result suggested that the optimized conditions were 2.86mg/mL carboxymethyl chitosan (CMC), 0.98mg/mL chitosan hydrochloride (CHC) and 5.97mg anthocyanins. Using the predicted amounts, the experimentally prepared particles averaged 219.53nm with 63.15% encapsulation efficiency. The result was less than 5% different than the predicted result of 214.83nm particle size and 61.80% encapsulation efficiency. Compared with the free anthocyanin solution, the anthocyanin-loaded chitosan nanoparticles showed a slowed degradation in simulated gastrointestinal fluid. Compared with the free anthocyanin solutions in a model beverage system, the stability of the anthocyanins was increased in the anthocyanin-loaded chitosan nanoparticles.

  7. Formulation and Physicochemical Characterization of Lycopene-Loaded Solid Lipid Nanoparticles

    PubMed Central

    Nazemiyeh, Elham; Eskandani, Morteza; Sheikhloie, Hossein; Nazemiyeh, Hossein

    2016-01-01

    Purpose: Lycopene belongs to the carotenoids that shows good pharmacological properties including antioxidant, anti-inflammatory and anticancer. However, as a result of very low aqueous solubility, it has a limited systemic absorption, following oral administration. Methods: Here, we prepared a stable lycopene-loaded solid lipid nanoparticles using Precirol® ATO5, Compritol 888 ATO and myristic acid by hot homogenization method with some modification. The size and morphological characteristics of nanoparticles were evaluated using Scanning Electron Microscopy (SEM). Moreover, zeta potential and dispersity index (DI) were measured using zeta sizer. In addition, encapsulation efficiency (EE%), drug loading (DL) and cumulative drug release were quantified. Results: The results showed that the size and DI of particles was generally smaller in the case of SLNs prepared with precirol when compared to SLNs prepared with compritol. Scanning electron microscopy (SEM) and particle size analyses showed spherical SLNs (125 ± 3.89 nm), monodispersed distribution, and zeta potential of −10.06 ± 0.08 mV. High EE (98.4 ± 0.5 %) and DL (44.8 ± 0.46 mg/g) were achieved in the case of nanoparticles prepared by precirol. The stability study of the lycopene-SLNs in aqueous medium (4 °C) was showed that after 2 months there is no significant differences seen in size and DI compared with the fresh formulation. Conclusion: Conclusively, in this investigation we prepared a stable lycopene-SLNs with good physicochemical characteristic which candidate it for the future in vivo trials in nutraceutical industries. PMID:27478786

  8. Synergetic effects of doxycycline-loaded chitosan nanoparticles for improving drug delivery and efficacy

    PubMed Central

    Cover, Natasha F; Lai-Yuen, Susana; Parsons, Anna K; Kumar, Arun

    2012-01-01

    Introduction Doxycycline, a broad-spectrum antibiotic, is the most commonly prescribed antibiotic worldwide for treating infectious diseases. It may be delivered orally or intravenously but can lead to gastrointestinal irritation and local inflammation. For treatment of uterine infections, transcervical administration of doxycycline encapsulated in nanoparticles made of biodegradable chitosan may improve sustained delivery of the drug, thereby minimizing adverse effects and improving drug efficacy. Methods and materials As a first step toward assessing this potential, we used an ionic gelation method to synthesize blank and doxycycline-loaded chitosan nanoparticles (DCNPs), which we then characterized in terms of several properties relevant to clinical efficacy: particle size, shape, encapsulation efficiency, antibacterial activity, and in vitro cytotoxicity. Two particle formulations were examined, with one (named DCNP6) containing approximately 1.5 times the crosslinker concentration of the other (DCNP4). Results The two formulations produced spherically shaped drug-loaded nanoparticles. The spheres ranged in size from 30 to 220 nm diameter for DCNP4 and 200 to 320 nm diameter for DCNP6. Average encapsulation yield was 53% for DCNP4 and 56% for DCNP6. In terms of drug release, both formulations showed a burst effect within the first 4 to 5 hours, followed by a slow, sustained release for the remainder of the 24-hour monitoring period. The in vitro antibacterial activity against Escherichia coli was high, with both formulations achieving more than 90% inhibition of 4-hour bacterial growth. Cytotoxic effects of the DCNPs on normal human ovarian surface epithelial cells were significantly lower than those of unencapsulated doxycycline. After 5 days, cultures exposed to the unencapsulated antibiotic showed a 61% decrease in cell viability, while cultures exposed to the DCNPs exhibited less than a 10% decrease. Conclusion These laboratory results suggest that DCNPs

  9. Preparation and in vitro/in vivo evaluation of resveratrol-loaded carboxymethyl chitosan nanoparticles.

    PubMed

    Zu, Yuangang; Zhang, Yin; Wang, Weiguo; Zhao, Xiuhua; Han, Xue; Wang, Kunlun; Ge, Yunlong

    2016-01-01

    Resveratrol (RES) is natural polyphenol with a strong biological activity, but its disadvantages, such as poor water solubility, susceptibility to oxidative decomposition and rapid metabolism in the body, which substantially restricts in vivo bioavailability, need to be resolved. This study used carboxymethyl chitosan (CMCS) as a drug carrier and utilized emulsion cross-linking to prepare RES-loaded CMCS nanoparticles (RES-CMCSNPs). A single-factor experiment was performed to optimize the preparation of these particles; in vitro and in vivo characteristics were evaluated. Spherical RES-CMCSNPs were prepared under optimal conditions, in which average particle size, potential, drug loading and encapsulation efficiency were (155.3 ± 15.2) nm, (-10.28 ± 6.4) mV, (5.1 ± 0.8)% and (44.5 ± 2.2)%, respectively. FTIR, DSC and XRD showed that RES molecules were wrapped in the nanoparticles. In vitro DPPH radical scavenging abilities showed RES-CMCSNPs were better than RES raw powder. The nanoparticles improved the solubility of RES, thereby greatly improving the antioxidant activity of the drug. In vitro release experiments of RES and RES-CMCSNPs by simulating the human gastrointestinal tract were performed, in which RES-CMCSNPs rendered better releasing effects than raw RES. Raw RES and RES-CMCSNPs results were in line with those obtained for the single-chamber model for pharmacokinetic studies in rats. Compared with the bulk drugs, the RES-CMCSNPs exhibited increased in vivo absorption, prolonged duration of action and increased relative bioavailability by 3.516 times more than those of the raw RES. In addition, the residual chloroform is less than the ICH limit for class 2 solvents.

  10. Synergistic Effect of Cold Atmospheric Plasma and Drug Loaded Core-shell Nanoparticles on Inhibiting Breast Cancer Cell Growth

    PubMed Central

    Zhu, Wei; Lee, Se-Jun; Castro, Nathan J.; Yan, Dayun; Keidar, Michael; Zhang, Lijie Grace

    2016-01-01

    Nano-based drug delivery devices allowing for effective and sustained targeted delivery of therapeutic agents to solid tumors have revolutionized cancer treatment. As an emerging biomedical technique, cold atmospheric plasma (CAP), an ionized non-thermal gas mixture composed of various reactive oxygen species, reactive nitrogen species, and UV photons, shows great potential for cancer treatment. Here we seek to develop a new dual cancer therapeutic method by integrating promising CAP and novel drug loaded core-shell nanoparticles and evaluate its underlying mechanism for targeted breast cancer treatment. For this purpose, core-shell nanoparticles were synthesized via co-axial electrospraying. Biocompatible poly (lactic-co-glycolic acid) was selected as the polymer shell to encapsulate anti-cancer therapeutics. Results demonstrated uniform size distribution and high drug encapsulation efficacy of the electrosprayed nanoparticles. Cell studies demonstrated the effectiveness of drug loaded nanoparticles and CAP for synergistic inhibition of breast cancer cell growth when compared to each treatment separately. Importantly, we found CAP induced down-regulation of metastasis related gene expression (VEGF, MTDH, MMP9, and MMP2) as well as facilitated drug loaded nanoparticle uptake which may aid in minimizing drug resistance-a major problem in chemotherapy. Thus, the integration of CAP and drug encapsulated nanoparticles provides a promising tool for the development of a new cancer treatment strategy. PMID:26917087

  11. Synergistic Effect of Cold Atmospheric Plasma and Drug Loaded Core-shell Nanoparticles on Inhibiting Breast Cancer Cell Growth.

    PubMed

    Zhu, Wei; Lee, Se-Jun; Castro, Nathan J; Yan, Dayun; Keidar, Michael; Zhang, Lijie Grace

    2016-02-26

    Nano-based drug delivery devices allowing for effective and sustained targeted delivery of therapeutic agents to solid tumors have revolutionized cancer treatment. As an emerging biomedical technique, cold atmospheric plasma (CAP), an ionized non-thermal gas mixture composed of various reactive oxygen species, reactive nitrogen species, and UV photons, shows great potential for cancer treatment. Here we seek to develop a new dual cancer therapeutic method by integrating promising CAP and novel drug loaded core-shell nanoparticles and evaluate its underlying mechanism for targeted breast cancer treatment. For this purpose, core-shell nanoparticles were synthesized via co-axial electrospraying. Biocompatible poly (lactic-co-glycolic acid) was selected as the polymer shell to encapsulate anti-cancer therapeutics. Results demonstrated uniform size distribution and high drug encapsulation efficacy of the electrosprayed nanoparticles. Cell studies demonstrated the effectiveness of drug loaded nanoparticles and CAP for synergistic inhibition of breast cancer cell growth when compared to each treatment separately. Importantly, we found CAP induced down-regulation of metastasis related gene expression (VEGF, MTDH, MMP9, and MMP2) as well as facilitated drug loaded nanoparticle uptake which may aid in minimizing drug resistance-a major problem in chemotherapy. Thus, the integration of CAP and drug encapsulated nanoparticles provides a promising tool for the development of a new cancer treatment strategy.

  12. Synthesis, photophysical characterization, and photoinduced antibacterial activity of methylene blue-loaded amino- and mannose-targeted mesoporous silica nanoparticles.

    PubMed

    Planas, Oriol; Bresolí-Obach, Roger; Nos, Jaume; Gallavardin, Thibault; Ruiz-González, Rubén; Agut, Montserrat; Nonell, Santi

    2015-04-09

    Over the last 20 years, the number of pathogenic multi-resistant microorganisms has grown steadily, which has stimulated the search for new strategies to combat antimicrobial resistance. Antimicrobial photodynamic therapy (aPDT), also called photodynamic inactivation, is emerging as a promising alternative to treatments based on conventional antibiotics. We have explored the effectiveness of methylene blue-loaded targeted mesoporous silica nanoparticles (MSNP) in the photodynamic inactivation of two Gram negative bacteria, namely Escherichia coli and Pseudomonas aeruginosa. For E. coli, nanoparticle association clearly reduced the dark toxicity of MB while preserving its photoinactivation activity. For P. aeruginosa, a remarkable difference was observed between amino- and mannose-decorated nanoparticles. The details of singlet oxygen production in the nanoparticles have been characterized, revealing the presence of two populations of this cytotoxic species. Strong quenching of singlet oxygen within the nanoparticles is observed.

  13. Ciprofloxacin HCl-loaded calcium carbonate nanoparticles: preparation, solid state characterization, and evaluation of antimicrobial effect against Staphylococcus aureus.

    PubMed

    Maleki Dizaj, Solmaz; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad-Hossein; Adibkia, Khosro

    2017-05-01

    Ciprofloxacin HCl-loaded calcium carbonate (CaCO3) nanoparticles were prepared via a w/o microemulsion method and characterized by dynamic light scattering, scanning electron microscopy, X-ray powder diffraction (XRPD) analysis, differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). The in vitro drug release profiles as well as antimicrobial effect against Staphylococcus aureus (S. aureus) were also evaluated. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration (MIC) of the nanoparticles and was confirmed by streak cultures. The mean particle size, drug loading and entrapment efficiency were calculated to be 116.09 nm, 20.49% and 44.05%, respectively. PXRD and FTIR studies confirmed that both vaterite and calcite polymorphs of CaCO3 were formed during the preparation process. In vitro release profiles of the nanoparticles showed slow release pattern for 12 h. The drug-loaded nanoparticles showed similar MICs against S. aureus compared to untreated drug. However, a preserved antimicrobial effect was observed for drug-loaded nanoparticles compared to untreated drug after 2 days of incubation.

  14. New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

    NASA Astrophysics Data System (ADS)

    Hou, Zhenqing; Wei, Heng; Wang, Qian; Sun, Qian; Zhou, Chunxiao; Zhan, Chuanming; Tang, Xiaolong; Zhang, Qiqing

    2009-07-01

    The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC-SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC-PLA particles prepared by classical method were used as comparison. The formulated MMC-SPC-PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA-MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA-MMC-SPC nanoparticles, and 74.1% for PLA-MMC particles. The IR analysis of MMC-SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.

  15. Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

    PubMed

    Hazzah, Heba A; Farid, Ragwa M; Nasra, Maha M A; El-Massik, Magda A; Abdallah, Ossama Y

    2015-08-15

    This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity.

  16. Poly(lactic acid) nanoparticles loaded with ursolic acid: Characterization and in vitro evaluation of radical scavenging activity and cytotoxicity.

    PubMed

    Antônio, Emilli; Antunes, Osmar Dos Reis; de Araújo, Isis Souza; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2017-02-01

    The purpose of this study was to develop poly(lactic acid) (PLA) nanoparticles containing ursolic acid (UA) by an emulsification-solvent evaporation technique and evaluate the radical scavenging activity over hypochlorous acid (HOCl) and cytotoxicity over erythrocytes and tumor cells. Nanoparticles were successfully obtained and presented mean size of 246nm with spherical or slightly oval morphology, negative zeta potential and 96% of UA encapsulation efficiency. Analyses of FTIR, XRD and DSC-DTG suggest interaction/complexation of UA with PLA matrix and drug amorphization promoted by nanoencapsulation process. Stability study showed that room temperature was the best condition for nanoparticles storage. The in vitro release study showed UA was released from the polymeric matrix over two constants (α, β), suggesting a second order kinetics. After 120h of assay, 60% of UA were released by diffusion. In the HOCl scavenging activity, after 72h of assay UA-loaded nanoparticles presented the same efficacy of free drug. In cytotoxicity test over red blood cells, UA-loaded nanoparticles showed less toxicity on cells than free drug. The cytotoxicity assay over melanoma cells line (B16-F10) showed after 72h that nanoparticles were able to reduce the cell viability in 70%. PLA nanoparticles showed be potential carriers for UA maintaining the antioxidant and antitumor activity of the UA and decreasing its cytotoxicity over normal cells.

  17. Densely-packed graphene/conducting polymer nanoparticle papers for high-volumetric-performance flexible all-solid-state supercapacitors

    NASA Astrophysics Data System (ADS)

    Yang, Chao; Zhang, Liling; Hu, Nantao; Yang, Zhi; Wei, Hao; Xu, Zhichuan J.; Wang, Yanyan; Zhang, Yafei

    2016-08-01

    Graphene-based all-solid-state supercapacitors (ASSSCs) are one of the most ideal candidates for high-performance flexible power sources. The achievement of high volumetric energy density is highly desired for practical application of this type of ASSSCs. Here, we present a facile method to boost volumetric performances of graphene-based flexible ASSSCs through incorporation of ultrafine polyaniline-poly(4-styrenesulfonate) (PANI-PSS) nanoparticles in reduced graphene oxide (rGO) papers. A compact structure is obtained via intimate contact and π-π interaction between PANI-PSS nanoparticles and rGO sheets. The hybrid paper electrode with the film thickness of 13.5 μm, shows an extremely high volumetric specific capacitance of 272 F/cm3 (0.37 A/cm3 in a three-electrode cell). The assembled ASSSCs show a large volumetric specific capacitance of 217 F/cm3 (0.37 A/cm3 in a two-electrode cell), high volumetric energy and power density, excellent capacitance stability, small leakage current as well as low self-discharge characteristics, revealing the usefulness of this robust hybrid paper for high-performance flexible energy storage devices.

  18. Vincristine and ɛ-viniferine-loaded PLGA-b-PEG nanoparticles: pharmaceutical characteristics, cellular uptake and cytotoxicity.

    PubMed

    Öğünç, Yüksel; Demirel, Müzeyyen; Yakar, Arzu; İncesu, Zerrin

    2017-02-02

    The objective of this study was to prepare the ɛ-viniferine and vincristine-loaded PLGA-b-PEG nanoparticle and to investigate advantages of these formulations on the cytotoxicity of HepG2 cells. Prepared nanoparticle has shown a homogeneous distribution with 113 ± 0.43 nm particle size and 0.323 ± 0.01 polydispersity index. Zeta potential was determined as -35.03 ± 1.0 mV. The drug-loading percentages were 6.01 ± 0.23 and 2.01 ± 0.07 for ɛ-viniferine and vincristine, respectively. The cellular uptake efficiency of coumarin-6-loaded nanoparticles was increased up to 87.8% after 4 h. Nanoparticles loaded with high concentrations of both drugs showed a cytotoxic effect on HepG2 cells, having the percentage of cell viability of between 43.23% and 47.37%. Unfortunately, the percentage of apoptotic cells after treated with drugs-loaded nanaoparticles (10.93%) was similar to free forms of drugs (12.1%) that might be due to low ɛ-viniferine release in biological pH at 24 h.

  19. Optimization, in vitro-in vivo evaluation, and short-term tolerability of novel levofloxacin-loaded PLGA nanoparticle formulation.

    PubMed

    Kumar, Gaurav; Sharma, Sadhna; Shafiq, Nusrat; Khuller, Gopal Krishan; Malhotra, Samir

    2012-06-01

    A novel poly(lactic-co-glycolic acid) (PLGA)-based nanoformulation of levofloxacin was developed for multidrug-resistant tuberculosis with the purpose of achieving sustained release in plasma. After lyophilization of levofloxacin-loaded nanoparticles, the average size, charge, and polydispersity index were 268 ± 18 nm, -10.2 ± 1.5 mV, and 0.15 ± 0.03, respectively. The maximum drug encapsulation efficiency and loading capacity were 36.9 ± 6.1% (w/w) and 7.2 ± 1.2 mg/100 mg nanopowder, respectively. Biphasic extended-release profile was produced in vitro. Scanning electron microscopy and Fourier transform infrared studies showed spherical shape of drug-loaded nanoparticles and no drug-polymer interactions were observed. After single oral administration in mice, levofloxacin-loaded PLGA nanoparticles produced sustained release of levofloxacin for 4 days in plasma against 24 h for free levofloxacin. Levofloxacin was detected in organs (lung, liver, and spleen) for up to 4-6 days in case of levofloxacin-loaded nanoparticles, whereas free levofloxacin was cleared within 24 h. This novel formulation did not show any significant adverse effects on body weight and clinical signs in mice. No treatment-related changes were found in hematological and biochemical parameters and on histopathological evaluation. These results indicate the feasibility of development of an orally efficacious safe formulation of levofloxacin with sustained-release properties.

  20. Preparation and in vitro characterization of gallic acid-loaded human serum albumin nanoparticles

    NASA Astrophysics Data System (ADS)

    Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas; Morshedi, Dina; Arpanaei, Ayyoob; Marvian, Amir Tayaranian

    2015-04-01

    Gallic acid (GA), as an antioxidant and antiparkinson agent, was loaded onto cationic human serum albumin nanoparticles (HSA NPs). Polyethylenimine (PEI)-coated HSA (PEI-HSA) NPs were prepared using three different methods: (I) coating negatively charged HSA NPs with positively charged PEI through attractive electrostatic interactions, (II) coating HSA NPs with PEI via covalent amide bond formation using N-(3-dimethylaminopropyl)- N-ethylcarbodiimide hydrochloride, and (III) coating HSA NPs with PEI via covalent bonding using glutaraldehyde for linking amine groups of PEI and amine groups of albumin NPs. Method II was selected since it resulted in a higher shift in the zeta potential value (mV) and less zeta potential value deviation, and also less size polydispersity. GA was loaded by adsorption onto the surface of PEI-HSA NPs of two different sizes: 117 ± 2.9 nm (PEI-P1) and 180 ± 3.1 nm (PEI-P2) NPs. Both GA-entrapment and GA-loading efficiencies increased slightly with the increasing size of NPs, and were affected intensely by the mass ratio of GA to PEI-HSA NPs. Free radical scavenging of GA was quantified based on the 2,2-diphenyl-1-picrylhydrazyl method. The obtained results showed that GA remains active during the preparation of GA-loaded PEI-HSA NPs. The cytotoxicities of HSA, PEI-HSA, and GA-loaded PEI-HSA NPs on the PC-12 cells, as the neuroendocrine cell line, were measured. Our results indicate that positively charged PEI-HSA NPs are good candidates for efficient and safe delivery of GA to the brain.

  1. Cell death induced by the application of alternating magnetic fields to nanoparticle-loaded dendritic cells

    NASA Astrophysics Data System (ADS)

    Marcos-Campos, I.; Asín, L.; Torres, T. E.; Marquina, C.; Tres, A.; Ibarra, M. R.; Goya, G. F.

    2011-05-01

    In this work, the capability of primary, monocyte-derived dendritic cells (DCs) to uptake iron oxide magnetic nanoparticles (MNPs) is assessed and a strategy to induce selective cell death in these MNP-loaded DCs using external alternating magnetic fields (AMFs) is reported. No significant decrease in the cell viability of MNP-loaded DCs, compared to the control samples, was observed after five days of culture. The number of MNPs incorporated into the cytoplasm was measured by magnetometry, which confirmed that 1-5 pg of the particles were uploaded per cell. The intracellular distribution of these MNPs, assessed by transmission electron microscopy, was found to be primarily inside the endosomic structures. These cells were then subjected to an AMF for 30 min and the viability of the blank DCs (i.e. without MNPs), which were used as control samples, remained essentially unaffected. However, a remarkable decrease of viability from approximately 90% to 2-5% of DCs previously loaded with MNPs was observed after the same 30 min exposure to an AMF. The same results were obtained using MNPs having either positive (NH2 + ) or negative (COOH - ) surface functional groups. In spite of the massive cell death induced by application of AMF to MNP-loaded DCs, the number of incorporated magnetic particles did not raise the temperature of the cell culture. Clear morphological changes at the cell structure after magnetic field application were observed using scanning electron microscopy. Therefore, local damage produced by the MNPs could be the main mechanism for the selective cell death of MNP-loaded DCs under an AMF. Based on the ability of these cells to evade the reticuloendothelial system, these complexes combined with an AMF should be considered as a potentially powerful tool for tumour therapy.

  2. Precise engineering of dapivirine-loaded nanoparticles for the development of anti-HIV vaginal microbicides.

    PubMed

    das Neves, José; Sarmento, Bruno

    2015-05-01

    Polymeric nanoparticles (NPs) have the potential to provide effective and safe delivery of antiretroviral drugs in the context of prophylactic anti-HIV vaginal microbicides. Dapivirine-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) NPs were produced by an emulsion-solvent evaporation method, optimized for colloidal properties using a 3-factor, 3-level Box-Behnken experimental design, and characterized for drug loading, production yield, morphology, thermal behavior, drug release, in vitro cellular uptake, cytotoxicity and pro-inflammatory potential. Also, drug permeability/membrane retention in well-established HEC-1-A and CaSki cell monolayer models as mediated by NPs was assessed in the absence or presence of mucin. Box-Behnken design allowed optimizing monodisperse 170nm drug-loaded NPs. Drug release experiments showed an initial burst effect up to 4h, followed by sustained 24h release at pH 4.2 and 7.4. NPs were readily taken up by different genital and macrophage cell lines as assessed by fluorescence microscopy. Drug-loaded NPs presented lower or at least similar cytotoxicity as compared to the free drug, with up to around one-log increase in half-maximal cytotoxic concentration values. In all cases, no relevant changes in cell pro-inflammatory cytokine/chemokine production were observed. Dapivirine transport across cell monolayers was significantly decreased when mucin was present at the donor side with either NPs or the free drug, thus evidencing the influence of this natural glycoprotein in membrane permeability. Moreover, drug retention in cell monolayers was significantly higher for NPs in comparison with the free drug. Overall, obtained dapivirine-loaded PLGA NPs possess interesting technological and biological features that may contribute to their use as novel safe and effective vaginal microbicides.

  3. Investigating the ability of nanoparticle-loaded hydroxypropyl methylcellulose and xanthan gum gels to enhance drug penetration into the skin.

    PubMed

    Cai, X J; Mesquida, P; Jones, S A

    2016-11-20

    Nanoparticle-loaded topical formulations can disrupt drug aggregation through controlled drug-nanoparticle interactions to enhance topical drug delivery. However, the complex relationship between the drug, nanoparticle and formulation vehicle requires further understanding. The aim of this study was to use nanoparticle-loaded hydroxypropyl methylcellulose (HPMC) and xanthan gum gels to probe how the drug, nanoparticle and formulation vehicle interactions influenced the delivery of an aggregated drug into the skin. Tetracaine was chosen as a model drug. It was loaded into HPMC and xanthan gum gels, and it was presented to porcine skin using infinite and finite dosing protocols. Gel infinite doses showed no important differences in tetracaine skin permeation rate, but HPMC gel finite doses delivered the drug more efficiently (46.99±7.96μg/cm(2)/h) compared to the xanthan gum (1.16±0.14μg/cm(2)/h). Finite doses of the nanoparticle-loaded HPMC gel generated a 10-fold increase in drug flux (109.95±28.63μg/cm(2)/h) compared to the equivalent xanthan gum system (14.19±2.27μg/cm(2)/h). Rheology measurements suggested that the differences in the gels ability to administer the drug into the skin were not a consequence of gel-nanoparticle interactions rather, they were a consequence of the dehydration mediated diffusional restriction imparted on the drug by xanthan gum compared to the viscosity independent interactions of HPMC with the drug.

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

    NASA Astrophysics Data System (ADS)

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

    2014-03-01

    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.

  5. 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.

  6. Development of oral sustained release rifampicin loaded chitosan nanoparticles by design of experiment.

    PubMed

    Patel, Bhavin K; Parikh, Rajesh H; Aboti, Pooja S

    2013-01-01

    Objective. The main objective of the present investigation was to develop and optimize oral sustained release Chitosan nanoparticles (CNs) of rifampicin by design of experiment (DOE). Methodology. CNs were prepared by modified emulsion ionic gelation technique. Here, inclusion of hydrophobic drug moiety in the hydrophilic matrix of polymer is applied for rifampicin delivery using CN. The 2(3) full-factorial design was employed by selecting the independent variables such as Chitosan concentration (X 1), concentration of tripolyphosphate (X 2), and homogenization speed (X 3) in order to achieve desired particle size with maximum percent entrapment efficiency and drug loading. The design was validated by checkpoint analysis, and formulation was optimized using the desirability function. Results. Particle size, drug entrapment efficiency, and drug loading for the optimized batch were found to be 221.9 nm, 44.17 ± 1.98% W/W, and 42.96 ± 2.91% W/W, respectively. In vitro release data of optimized formulation showed an initial burst followed by slow sustained drug release. Kinetic drug release from CNs was best fitted to Higuchi model. Conclusion. Design of Experiment is an important tool for obtaining desired characteristics of rifampicin loaded CNs. In vitro study suggests that oral sustained release CNs might be an effective drug delivery system for tuberculosis.

  7. α-Tocopherol succinate improves encapsulation and anticancer activity of doxorubicin loaded in solid lipid nanoparticles.

    PubMed

    Oliveira, Mariana S; Mussi, Samuel V; Gomes, Dawidson A; Yoshida, Maria Irene; Frezard, Frederic; Carregal, Virgínia M; Ferreira, Lucas A M

    2016-04-01

    This work aimed to develop solid lipid nanoparticles (SLN) co-loaded with doxorubicin and α-tocopheryl succinate (TS), a succinic acid ester of α-tocopherol that exhibits anticancer actions, evaluating the influence of TS on drug encapsulation efficiency. The SLN were characterized for size, zeta potential, entrapment efficiency (EE), and drug release. Studies of in vitro anticancer activity were also conducted. The EE was significantly improved from 30 ± 1% to 96 ± 2% for SLN without and with TS at 0.4%, respectively. In contrast, a reduction in particle size from 298 ± 1 to 79 ± 1 nm was observed for SLN without and with TS respectively. The doxorubicin release data show that SLN provide a controlled drug release. The in vitro studies showed higher cytotoxicity for doxorubicin-TS-loaded SLN than for free doxorubicin in breast cancer cells. These findings suggest that TS-doxorubicin-loaded SLN is a promising alternative for the treatment of cancer.

  8. Development, Optimization, and Evaluation of Carvedilol-Loaded Solid Lipid Nanoparticles for Intranasal Drug Delivery.

    PubMed

    Aboud, Heba M; El Komy, Mohammed H; Ali, Adel A; El Menshawe, Shahira F; Abd Elbary, Ahmed

    2016-12-01

    Carvedilol, a beta-adrenergic blocker, suffers from poor systemic availability (25%) due to first-pass metabolism. The aim of this work was to improve carvedilol bioavailability through developing carvedilol-loaded solid lipid nanoparticles (SLNs) for nasal administration. SLNs were prepared by emulsion/solvent evaporation method. A 2(3) factorial design was employed with lipid type (Compritol or Precirol), surfactant (1 or 2% w/v poloxamer 188), and co-surfactant (0.25 or 0.5% w/v lecithin) concentrations as independent variables, while entrapment efficiency (EE%), particle size, and amount of carvedilol permeated/unit area in 24 h (Q 24) were the dependent variables. Regression analysis was performed to identify the optimum formulation conditions. The in vivo behavior was evaluated in rabbits comparing the bioavailability of carvedilol after intravenous, nasal, and oral administration. The results revealed high drug EE% ranging from 68 to 87.62%. Carvedilol-loaded SLNs showed a spherical shape with an enriched core drug loading pattern having a particle size in the range of 66 to 352 nm. The developed SLNs exhibited significant high amounts of carvedilol permeated through the nasal mucosa as confirmed by confocal laser scanning microscopy. The in vivo pharmacokinetic study revealed that the absolute bioavailability of the optimized intranasal SLNs (50.63%) was significantly higher than oral carvedilol formulation (24.11%). Hence, we conclude that our developed SLNs represent a promising carrier for the nasal delivery of carvedilol.

  9. siRNA-loaded PEGylated porous silicon nanoparticles for lung cancer therapy

    NASA Astrophysics Data System (ADS)

    Chen, Shaomu; Ni, Bin; Huang, Haitao; Chen, Xiaochun; Ma, Haitao

    2014-10-01

    Biocompatible and biodegradable porous silicon nanoparticles (pSiNPs) with tunable pore size have been used as vehicles for drug delivery. Our pSiNPs have a mean size of 110 nm with an average pore size of 26 nm. Approximately 16.3 µg of siRNA can be loaded per mg of pSiNPs followed by polyethylene glycol (PEG) surface coating. siRNA-loaded PEGylated pSiNPs (P-pSiNPs) can be uptaken by A549 cells, and target pyruvate kinase isozyme type M2 (PKM2) mRNA and protein expression were effectively downregulated to 6.3 and 26.8 %, respectively. Cell viability decreased to 37.6 %; meanwhile, cell apoptosis upregulated to 17.3 %. The results prove that the siRNA-loaded pSiNPs coated with PEG can effectively deliver siRNA into cancer cells, and the efficiency is comparable to that of lipofectamine.

  10. Docetaxel-loaded polylactic acid-co-glycolic acid nanoparticles: formulation, physicochemical characterization and cytotoxicity studies.

    PubMed

    Pradhan, Roshan; Poudel, Bijay Kumar; Ramasamy, Thiruganesh; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-08-01

    In the present study, we developed novel docetaxel (DTX)-loaded polylactic acid-co-glycolic acid (PLGA) nanoparticles (NPs) using the combination of sodium lauryl sulfate (SLS) and poloxamer 407, the anionic and non-ionic surfactants respectively for stabilization. The NPs were prepared by emulsification/solvent evaporation method. The combination of these surfactants at weight ratio of 1:0.5 was able to produce uniformly distributed small sized NPs and demonstrated the better stability of NP dispersion with high encapsulation efficiency (85.9 +/- 0.6%). The drug/polymer ratio and phase ratio were 2:10 and 1:10, respectively. The optimized formulation of DTX-loaded PLGA NPs had a particle size and polydispersity index of 104.2 +/- 1.5 nm and 0.152 +/- 0.006, respectively, which was further supported by TEM image. In vitro release study was carried out with dialysis membrane and showed 32% drug release in 192 h. When in vitro release data were fitted to Korsmeyer-Peppas model, the n value was 0.481, which suggested the drug was released by anomalous or non-Fickian diffusion. In addition, DTX-loaded PLGA NPs in 72 h, displayed approximately 75% cell viability reduction at 10 microg/ml DTX concentration, in MCF-7 cell lines, indicating sustained release from NPs. Therefore, our results demonstrated that incorporation of DTX into PLGA NPs could provide a novel effective nanocarrier for the treatment of cancer.

  11. Hydrophilic coating of mitotane-loaded lipid nanoparticles: preliminary studies for mucosal adhesion.

    PubMed

    Severino, Patrícia; Souto, Eliana B; Pinho, Samantha C; Santana, Maria H A

    2013-01-01

    The aim of the present work was to load mitotane, an effective drug for adrenocortical carcinoma treatment, in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The SLN and NLC were successfully prepared by high shear homogenization followed by hot high pressure homogenization. Formulations were composed of cetyl palmitate as the solid lipid for SLN, whereas for NLC PEGylated stearic acid was selected as solid lipid and medium chain triacylglycerols as the liquid lipid. Tween® 80 and Span® 85 were used as surfactants for all formulations. The particle size, zeta potential, polydispersity index (PI), encapsulation efficiency (EE), and loading capacity (LC) were evaluated. The SLN showed a mean particle size of 150 nm, PI of 0.20, and surface charge -10 mV, and the EE and LC could reach up to 92.26% and 0.92%, respectively. The NLC were obtained with a mean particle size of 250 nm, PI of 0.30, zeta potential -15 mV and 84.50% EE, and 0.84% LC, respectively. Hydrophilic coating of SLN with chitosan or benzalkonium chloride was effective in changing zeta potential from negative to positive values. The results suggest that mitotane was efficiently loaded in SLN and in NLC, being potential delivery systems for improving mitotane LC and controlled drug release.

  12. Preparation and characterizations of naproxen-loaded magnetic nanoparticles coated with PLA- g-chitosan copolymer

    NASA Astrophysics Data System (ADS)

    Thammawong, C.; Sreearunothai, P.; Petchsuk, A.; Tangboriboonrat, P.; Pimpha, N.; Opaprakasit, P.

    2012-08-01

    Naproxen (NPX) drug-loaded magnetic nanoparticles (MNPs) have been prepared in a one-step process utilizing a biocompatible polylactide-grafted-chitosan copolymer. The copolymer serves both as a NPX drug carrier as well as a polymeric surfactant for the synthesis of MNPs without the use of any additional surfactant. Highly stable MNPs with high magnetization in the form of maghemite (γ-Fe2O3) are prepared in aqueous media. Effects of preparation conditions on structures and properties of the copolymer-coated and drug-loaded MNPs are investigated by employing particle size and zeta potential measurements, transmission electron microscopy, vibrating sample magnetometer, X-ray diffraction, Fourier-transform infrared, nuclear magnetic resonance, and confocal Raman spectroscopy. The results show that average particle size (150-300 nm), coating efficiency, and coating structures of the resulting MNPs materials are strongly dependent on MNP/copolymer and MNP/NPX ratios in feed. It is also observed that NPX acts as co-surfactant in the drug-loading process, resulting in different encapsulating structures with the variation in the MNP/copolymer and MNP/NPX ratios. Properties of the MNPs materials can be further optimized for use in specific biomedical applications.

  13. Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model

    PubMed Central

    Ali, Hazem; Kalashnikova, Irina; White, Mark Andrew; Sherman, Michael; Rytting, Erik

    2013-01-01

    The purpose of this study was to prepare dexamethasone-loaded polymeric nanoparticles and evaluate their potential for transport across human placenta. Statistical modeling and factorial design was applied to investigate the influence of process parameters on the following nanoparticle characteristics: particle size, polydispersity index, zeta potential, and drug encapsulation efficiency. Dexamethasone and nanoparticle transport was subsequently investigated using the BeWo b30 cell line, an in vitro model of human placental trophoblast cells, which represent the rate-limiting barrier for maternal-fetal transfer. Encapsulation efficiency and drug transport were determined using a validated high performance liquid chromatography method. Nanoparticle morphology and drug encapsulation were further characterized by cryo-transmission electron microscopy and X-ray diffraction, respectively. Nanoparticles prepared from poly(lactic-co-glycolic acid) were spherical, with particle sizes ranging from 140–298 nm, and encapsulation efficiency ranging from 52–89%. Nanoencapsulation enhanced the apparent permeability of dexamethasone from the maternal compartment to the fetal compartment more than 10-fold in this model. Particle size was shown to be inversely correlated with drug and nanoparticle permeability, as confirmed with fluorescently-labeled nanoparticles. These results highlight the feasibility of designing nanoparticles capable of delivering medication to the fetus, in particular, potential dexamethasone therapy for the prenatal treatment of congenital adrenal hyperplasia. PMID:23850397

  14. Enhanced apoptotic and anticancer potential of paclitaxel loaded biodegradable nanoparticles based on chitosan.

    PubMed

    Gupta, Umesh; Sharma, Saurabh; Khan, Iliyas; Gothwal, Avinash; Sharma, Ashok K; Singh, Yuvraj; Chourasia, Manish K; Kumar, Vipin

    2017-05-01

    Taxanes have established and proven effectivity against different types of cancers; in particular breast cancers. However, the high hemolytic toxicity and hydrophobic nature of paclitaxel and docetaxel have always posed challenges to achieve safe and effective delivery. Use of bio-degradable materials with an added advantage of nanotechnology could possibly improve the condition so as to achieve better and safe delivery. In the present study paclitaxel loaded chitosan nanoparticles were formulated and optimized using simple w/o nanoemulsion technique. The observed average size, pdi, zeta potential, entrapment efficiency and drug loading for the optimized paclitaxel loaded chitosan nanoparticle formulation (PTX-CS-NP-10) was 226.7±0.70nm, 0.345±0.039, 37.4±0.77mV, 79.24±2.95% and 11.57±0.81%; respectively. Nanoparticles were characterized further for size by Transmission Electron Microscopy (TEM). In vitro release studies exhibited sustained release pattern and more than 60% release was observed within 24h. Enhanced in vitro anticancer activity was observed as a result of MTT assay against triple negative MDA-MB-231 breast cancer cell lines. The observed IC50 values obtained for PTX-CS-NP-10 was 9.36±1.13μM and was almost 1.6 folds (p<0.05) less than the pure drug. Similarly, PTX-CS-NP-10 were extremely biocompatible and safe as observed for haemolytic toxicity which was almost 4 folds less (p<0.05) than the naïve drug. Anticancer activity was further evaluated using flow cytometry for apoptosis. Cell apoptosis study revealed that PTX-CS-NP-10 treatment resulted into enhanced (almost double) late cell apoptosis than naïve paclitaxel. Hence the developed nanoparticulate formulation not only reduced the overall toxicity but also resulted into improved anticancer efficacy of paclitaxel. It can be concluded that a robust, stable and comparatively safe nanoformulation of paclitaxel was developed, characterized and evaluated.

  15. Controlled hierarchical assembly of gold nanoparticles in macroscopic films: from densely packed monolayers to networks of micropores and nanobundles.

    PubMed

    Gravelsins, Steven; Hasham, Minhal; Lin, Yi; Yu, Kevin; Tie, Monique; Goh, Cynthia; Dhirani, Al-Amin

    2017-03-29

    The present study demonstrates the ability of excess, weakly amphiphilic n-alkanethiols (n = 4, 12, 18) and solvent composition to tune through a wide range of large-scale, macroscopic architectures formed by alkanethiol-capped Au nanoparticles (NPs). Both the alkanethiols and NPs are significantly hydrophobic species and compete for surface area at an air-water interface. When solutions of the two species are spread on a large (50 cm(2)) water surface in a Teflon well, a thin film forms and exhibits co-existing macroscopic regions with various distinct NP self-assembled architectures, namely a close packed monolayer, a network phase characterized by micron-sized pores (micropores) surrounded by quasi-linear bundles of nanoparticles, and finally aggregates. We hypothesize that the co-existence of various NP architectures results from fast, non-uniform evaporation across the large water surface. When solutions are instead deposited on a smaller (5 cm(2)) water surface contained within a Teflon ring to control the water surface curvature and the evaporation rate is slowed, we show for the first time that NPs form macroscopically uniform self-assemblies whose architectures can be tuned from monolayers → monolayers with micropores → extended micropore/NP bundle networks by varying excess alkanethiol concentration and solvent composition. We propose that competition between NPs and excess alkanethiols for water surface area, and alkanethiol self-assembly as well as solvent dewetting play important roles in the formation of the network phase, and discuss a potential mechanism for its formation.

  16. Dense Breasts

    MedlinePlus

    ... fatty tissue. On a mammogram, fatty tissue appears dark (radio-lucent) and the glandular and connective tissues ... white on mammography) and non-dense fatty tissue (dark on mammography) using a visual scale and assign ...

  17. Effects of crystallinity and surface modification of calcium phosphate nanoparticles on the loading and release of tetracycline hydro-chloride

    NASA Astrophysics Data System (ADS)

    Zhang, Huaizhi; Yan, Dong; Menike Korale Gedara, Sriyani; Dingiri Marakkalage, Sajith Sudeepa Fernando; Gamage Kasun Methlal, Jothirathna; Han, YingChao; Dai, HongLian

    2017-03-01

    The influences of crystallinity and surface modification of calcium phosphate nanoparticles (nCaP) on their drug loading capacity and drug release profile were studied in the present investigation. The CaP nanoparticles with different crystallinity were prepared by precipitation method under different temperatures. CaP nanoparticles with lower crystallinity exhibited higher drug loading capacity. The samples were characterized by XRD, FT-IR, SEM, TEM and BET surface area analyzer respectively. The drug loading capacity of nCaP was evaluated to tetracycline hydro-chloride (TCH). The internalization of TCH loaded nCaP in cancer cell was observed by florescence microscope. nCaP could be stabilized and dispersed in aqueous solution by poly(acrylic acid) surface modification agent, leading to enhanced drug loading capacity. The drug release was conducted in different pH environment and the experimental data proved that nCaP were pH sensitive drug carrier, suggesting that nCaP could achieve the controlled drug release in intracellular acidic environment. Furthermore, nCaP with higher crystallinity showed lower drug release rate than that of lower crystallinity, indicating that the drug release profile could be adjusted by crystallinity of nCaP. nCaP with adjustable drug loading and release properties are promising candidate as drug carrier for disease treatment.

  18. Colonic gene silencing using siRNA-loaded calcium phosphate/PLGA nanoparticles ameliorates intestinal inflammation in vivo.

    PubMed

    Frede, Annika; Neuhaus, Bernhard; Klopfleisch, Robert; Walker, Catherine; Buer, Jan; Müller, Werner; Epple, Matthias; Westendorf, Astrid M

    2016-01-28

    Cytokines and chemokines are predominant players in the progression of inflammatory bowel diseases. While systemic neutralization of these players with antibodies works well in some patients, serious contraindications and side effects have been reported. Therefore, the local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach. In this study, we produced multi-shell nanoparticles consisting of a calcium phosphate (CaP) core coated with siRNA directed against pro-inflammatory mediators, encapsulated into poly(d,l-lactide-co-glycolide acid) (PLGA), and coated with a final outer layer of polyethyleneimine (PEI), for the local therapeutic treatment of colonic inflammation. In cell culture, siRNA-loaded CaP/PLGA nanoparticles exhibited a rapid cellular uptake, almost no toxicity, and an excellent in vitro gene silencing efficiency. Importantly, intrarectal application of these nanoparticles loaded with siRNA directed against TNF-α, KC or IP-10 to mice suffering from dextran sulfate sodium (DSS)-induced colonic inflammation led to a significant decrease of the target genes in colonic biopsies and mesenteric lymph nodes which was accompanied with a distinct amelioration of intestinal inflammation. Thus, this study provides evidence that the specific and local modulation of the inflammatory response by CaP/PLGA nanoparticle-mediated siRNA delivery could be a promising approach for the treatment of intestinal inflammation.

  19. 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

    2017-02-14

    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.

  20. Intrinsic Ultrahigh Drug/miRNA Loading Capacity of Biodegradable Bioactive Glass Nanoparticles toward Highly Efficient Pharmaceutical Delivery.

    PubMed

    Yu, Meng; Xue, Yumeng; Ma, Peter X; Mao, Cong; Lei, Bo

    2017-03-03

    The lack of safe and efficient drug and gene delivery vectors has become a major obstacle for the clinical applications of drug and nonviral gene therapy. To date, for nonviral gene vectors, most studies are focused on cationic polymers, liposomes, and modified inorganic nanoparticles which have shown high cellular toxicity, low transfection efficiency, or nondegradation. Additionally, few biodegradable biomaterials demonstrate intrinsic high binding abilities to both drug and gene. Bioactive glasses (BGs) have achieved successful applications in bone regeneration due to their high biocompatibility and biodegradation. Here, for the first time, we demonstrate the intrinsic ultrahigh drug and miRNA binding ability of bioactive glass nanoparticles (BGNs) without any cationic polymer modification. BGNs demonstrate an over 45-fold improvement in hydrophilic drug loading (diclofenac sodium) and 7-fold enhancement in miRNA binding over their corresponding silica nanoparticles. The hydrophilic drug loading ability of BGNs (>45 wt % loading) is also higher than that of most other reported inorganic nanoparticles, including mesoporous silica nanoparticles. BGNs show significantly lower cytotoxicity and higher cellular uptake and miRNA transfection efficiency compared to those of commercial transfection reagents polyethylenimine and lipofectamine 3000. Our results demonstrate that BGNs may become a new competitive vehicle for drug and gene delivery applications. This study may also provide a new strategy to develop novel biomaterials with intrinsic drug and gene binding ability for disease therapy.

  1. Mechanism of heat generation from loading gaseous hydrogen isotopes into palladium nanoparticles

    NASA Astrophysics Data System (ADS)

    Dmitriyeva, Olga

    I have carried out the study of hydrogen isotope reactions in the presence of palladium nanoparticles impregnated into oxide powder. My goal was to explain the mechanisms of heat generation in those systems as a result of exposure to deuterium gas. Some researchers have associated this heating with a nuclear reaction in the Pd lattice. While some earlier experiments showed a correlation between the generation of excess heat and helium production as possible evidence of a nuclear reaction, the results of that research have not been replicated by the other groups and the search for radiation was unsuccessful. Therefore, the unknown origin of the excess heat produced by these systems is of great interest. I synthesized different types of Pd and Pt-impregnated oxide samples similar to those used by other research groups. I used different characterization techniques to confirm that the fabrication method I used is capable of producing Pd nanoparticles on the surface of alumina support. I used a custom built gas-loading system to pressurize the material with hydrogen and deuterium gas while measuring heat output as a result of these pressurizations. My initial study confirmed the excess heat generation in the presence of deuterium. However, the in-situ radiometry and alpha-particle measurements did not show any abnormal increase in counts above the background level. In the absence of nuclear reaction products, I decided to look for a conventional chemical process that could account for the excess heat generation. It was earlier suggested that Pd in its nanoparticle form catalyzes hydrogen/deuterium (H/D) exchange reactions in the material. To prove the chemical nature of the observed phenomena I demonstrated that the reaction can be either exo- or endothermic based on the water isotope trapped in the material and the type of gas provided to the system. The H/D exchange was confirmed by RGA, NMR and FTIR analysis. I quantified the amount of energy that can be released due

  2. Synthesis of drug loaded magnetic nanoparticles and their uptake into immune cells

    NASA Astrophysics Data System (ADS)

    Prinz, Eva-Marie; Eggers, Ruth; Lee, Hyeck-Hee; Steinfeld, Ute; Hempelmann, Rolf

    2010-01-01

    Ferrite nanoparticles (Mn0,8Zn0,2Fe2O4) are synthesized by the co-precipitation method and characterized by X-ray diffraction, transmission electron microscopy and dynamic light scattering. The particles are functionalized with dextran which is activated via amino or carboxymethyl groups. The chemotherapeutic drug doxorubicin (DOX) is attached to these dextran derivates in different ways. One method is based on the attachment of DOX to amino dextran by its keto group; the other is a bond to the primary amino group of DOX. The characterization of drug loaded dextran derivates is performed by Raman, FT-IR-, UV/VIS-and fluorescence spectroscopy. The biofunctionalized particles are intended for use in adoptive cancer immunotherapy as a new approach, where immune cells (T lymphocytes) will be used as new autonomous highly target specific drug delivery systems. The uptake efficiency of these particles into T lymphocytes is investigated by fluorescence and convocal microscopy.

  3. Liposomes loaded with hydrophilic magnetite nanoparticles: Preparation and application as contrast agents for magnetic resonance imaging.

    PubMed

    German, S V; Navolokin, N A; Kuznetsova, N R; Zuev, V V; Inozemtseva, O A; Anis'kov, A A; Volkova, E K; Bucharskaya, A B; Maslyakova, G N; Fakhrullin, R F; Terentyuk, G S; Vodovozova, E L; Gorin, D A

    2015-11-01

    Magnetic fluid-loaded liposomes (MFLs) were fabricated using magnetite nanoparticles (MNPs) and natural phospholipids via the thin film hydration method followed by extrusion. The size distribution and composition of MFLs were studied using dynamic light scattering and spectrophotometry. The effective ranges of magnetite concentration in MNPs hydrosol and MFLs for contrasting at both T2 and T1 relaxation were determined. On T2 weighted images, the MFLs effectively increased the contrast if compared with MNPs hydrosol, while on T1 weighted images, MNPs hydrosol contrasting was more efficient than that of MFLs. In vivo magnetic resonance imaging (MRI) contrasting properties of MFLs and their effects on tumor and normal tissues morphology, were investigated in rats with transplanted renal cell carcinoma upon intratumoral administration of MFLs. No significant morphological changes in rat internal organs upon intratumoral injection of MFLs were detected, suggesting that the liposomes are relatively safe and can be used as the potential contrasting agents for MRI.

  4. Formulation and optimization of raloxifene-loaded solid lipid nanoparticles to enhance oral bioavailability.

    PubMed

    Tran, Tuan Hiep; Ramasamy, Thiruganesh; Cho, Hyuk Jun; Kim, Yong Il; Poudel, Bijay Kumar; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2014-07-01

    The main aim of this study was to improve the oral bioavailability of raloxifene (RXF), a selective estrogen receptor modulator, by incorporation into solid lipid nanoparticles (SLN). RXF-loaded SLN was prepared by homogenization-sonication technique and characterized through physicochemical, pharmacokinetic, and cytotoxicity studies. The optimized SLN formulation exhibited a spherical shape with average size around 140 nm, easing its transport across the lymphatic system. Augmentation in the profiles of C(max) (308%) and AUC (270%) indicated a significant enhancement in the rate and extent of bioavailability by SLN formulations compared to free drug. In vitro cytotoxicity study performed in NIH-3T3 cells revealed that RXF-SLN was cytocompatible, and SLN remained unchanged during the freeze-drying process. Furthermore, the optimized formulation was quite stable at room temperature for more than two months, exemplifying its superior performance. In conclusion, SLN provides a promising platform for the pronounced enhancement of RXF bioavailability.

  5. Hollow silica nanoparticles loaded with hydrophobic phthalocyanine for near-infrared photodynamic and photothermal combination therapy.

    PubMed

    Peng, Juanjuan; Zhao, Lingzhi; Zhu, Xingjun; Sun, Yun; Feng, Wei; Gao, Yanhong; Wang, Liya; Li, Fuyou

    2013-10-01

    Owing to the convenience and minimal invasiveness, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful technique for cancer treatment. To date, however, few examples of combination PDT and PTT have been reported. Phthalocyanine (Pc) is a class of traditional photosensitizer for PDT, but its bioapplication is limited by high hydrophobicity. In this present study, hollow silica nanospheres (HSNs) were employed to endow the hydrophobic phthalocyanine with water-dispersity, and the as-prepared hollow silica nanoparticles loaded with hydrophobic phthalocyanine (Pc@HSNs) exhibits highly efficient dual PDT and PTT effects. In vitro and in vivo experimental results clearly indicated that the dual phototherapeutic effect of Pc@HSNs can kill cancer cells or eradicate tumor tissues. This multifunctional nanomedicine may be useful for PTT/PDT treatment of cancer.

  6. 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.

  7. Characterization and evaluation of metformin-loaded solid lipid nanoparticles for celluar and mitochondrial uptake.

    PubMed

    Xu, Qiang; Zhu, Tao; Yi, Chaoli; Shen, Qi

    2016-05-01

    Considered a popular drug for diabetes in recent years, metformin was determined to have a moderate anti-tumor effect, particularly in breast cancer. In this study, the anticancer mechanism of metformin was verified by preparing solid lipid nanoparticles (SLNs) and chitosan-modified solid lipid nanoparticles (CSLNs) containing metformin and then estimating the potential of these SLNs for uptake in cells and mitochondria. Metformin-SLNs were prepared using an emulsification and low-temperature solidification method. The mean particle size, zeta potential, entrapment efficiency, and loading efficiency of metformin-SLNs and metformin chitosan-modified SLNs were 102.3 ± 4.16 and 200.1 ± 17.69 nm, -21.25 ± 4.89 and 50.6 ± 4.09 mv, 26.25 ± 2.59% and 33.6 ± 2.21%, and 1.74 ± 0.16% and 1.46 ± 0.10%, respectively. TEM images showed that both the nanoparticles had spherical morphologies with no aggregation. Results of cellular and mitochondrial uptake showed that the metformin-SLNs were easier to uptake in cells and mitochondria than the pure drug group (that was the control group without SLN structure modification). The findings of this research provide a basis for conducting further studies on the anticancer mechanism of metformin.

  8. 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

  9. Installing multifunctionality on titanium with RGD-decorated polyurethane-polyurea roxithromycin loaded nanoparticles: toward new osseointegrative therapies.

    PubMed

    Rocas, Pau; Hoyos-Nogués, Mireia; Rocas, Josep; Manero, José M; Gil, Javier; Albericio, Fernando; Mas-Moruno, Carlos

    2015-09-16

    A novel class of polyurethane-polyurea nanoparticles (PUUa NPs) to install multifunctionality on biomaterials is presented. Biofunctionalization of titanium with roxithromycin loaded RGD-decorated PUUa NPs results in an outstanding improvement of osteoblast adhesion and strong suppression of bacterial attachment. This strategy represents a powerful approach to enhance the osseointegration of implant materials.

  10. Novel multifunctional pH-sensitive nanoparticles loaded into microbubbles as drug delivery vehicles for enhanced tumor targeting

    PubMed Central

    Lv, Yongjiu; Hao, Lan; Hu, Wenjing; Ran, Ya; Bai, Yan; Zhang, Liangke

    2016-01-01

    This study fabricated novel multifunctional pH-sensitive nanoparticles loaded into microbubbles (PNP-MB) with the combined advantages of two excellent drug delivery vehicles, namely, pH-sensitive nanoparticles and microbubbles. As an antitumor drug, resveratrol (RES) was loaded into acetylated β-cyclodextrin nanoparticles (RES-PNP). The drug-loaded nanoparticles were then encapsulated into the internal space of the microbubbles. The characterization and morphology of this vehicle were investigated through dynamic light scattering and confocal laser scanning microscopy, respectively. In vitro drug release was performed to investigate the pH sensitivity of RES-PNP. The antitumor property of RES-loaded PNP-MB (RES-PNP-MB) was also analyzed in vivo to evaluate the antitumor effect of RES-PNP-MB. Results suggested that PNP exhibited pH sensitivity, and was successfully encapsulated into the microbubbles. RES-PNP-MB exhibit effective tumor growth suppressing in vivo. Therefore, such drug delivery vehicle should be of great attention in tumor therapy. PMID:27378018

  11. Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T₂ Contrast Agents for MRI.

    PubMed

    Martínez-González, Raquel; Estelrich, Joan; Busquets, Maria Antònia

    2016-07-27

    There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T₂ relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r₂, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA.

  12. Development and performance evaluation of novel nanoparticles of a grafted copolymer loaded with curcumin.

    PubMed

    Mutalik, Srinivas; Suthar, Neelam A; Managuli, Renuka S; Shetty, Pallavi K; Avadhani, Kiran; Kalthur, Guruprasad; Kulkarni, Raghavendra V; Thomas, Ranjeny

    2016-05-01

    Inflammatory bowel disease (IBD) is an inflammatory condition with mucosal ulceration, edema and hemorrhage of gastrointestinal tract. Curcumin has been shown to mitigate colitis in animal models. However, its usefulness is reduced due to poor pharmacokinetic behavior and low oral bioavailability. To address this, novel pH-sensitive hydrolyzed polyacrylamide-grafted-xanthan gum (PAAm-g-XG) nanoparticles (NPs) loaded with curcumin were prepared for colonic delivery. Optimized nanoparticles (CN20) were spherical, with an average size of 425 nm. A negligible amount of curcumin (≈8%) was released from CN20 NPs in pH 1.2 and 4.5 solutions. When the pH was increased to 7.2, curcumin release was comparatively faster than that observed with pH 1.2 and 4.5 collectively. In pH 6.8 solution, excellent release of curcumin was observed. Highest curcumin release was observed when rat caecal contents were incorporated in pH 6.8 solution, indicating microflora-dependent drug release property of NPs. In acetic acid-induced IBD in rats, curcumin NPs reduced myeloperoxidase and nitrite levels, prevented weight loss and attenuated colonic inflammation. Curcumin was better absorbed systemically in nanoparticulate form with increased Cmax (∼3 fold) and AUC (∼2.5 fold) than when delivered as free curcumin. We demonstrate successful development of grafted co-polymeric NPs containing drug suitable for colon targeting.

  13. Formulation, Characterization and Evaluation of Paclitaxel loaded Solid Lipid Nanoparticles Prepared by Temperature Modulated Solidification Technique

    NASA Astrophysics Data System (ADS)

    Deshpande, Ameya Abhay

    The aim of this research was to formulate, characterize, and evaluate the paclitaxel loaded solid lipid nanoparticles (SLNs) prepared by a temperature modulated solidification technique developed and optimized in our laboratory. The particle size analysis through dynamic light scattering (DLS) and transmission electron microscopy (TEM) revealed and confirmed the spherical shape and nanometer size range of the formulated nanoparticles. Zeta potential measurements confirmed the physical stability of the SLNs with a negative surface charge. Atomic force microscopy (AFM) studies were done to study the surface topography and particle size and shape. AFM data showed minimal aggregation and more or less spherical SLNs. Differential scanning calorimetry (DSC), powder X-ray diffraction (P-XRD) and Fourier transform infrared spectroscopy (ATR-FTIR) confirmed the conversion of bulk lipid into SLNs and high entrapment of paclitaxel into the lipid matrix. The optimized formulation had an entrapment efficiency of approximately 62%. The in-vitro drug release depicted a sustained release of paclitaxel from the SLNs over duration of one week. The drug release data was found to best fit and hence followed the Higuchi drug-release model.

  14. A Novel Preparation Method for Camptothecin (CPT) Loaded Folic Acid Conjugated Dextran Tumor-Targeted Nanoparticles

    PubMed Central

    Zu, Yuangang; Wang, Dan; Zhao, Xiuhua; Jiang, Ru; Zhang, Qi; Zhao, Dongmei; Li, Yong; Zu, Baishi; Sun, Zhiqiang

    2011-01-01

    In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy. PMID:21845075

  15. Stable and efficient loading of silver nanoparticles in spherical polyelectrolyte brushes and the antibacterial effects.

    PubMed

    Liu, Xiaochi; Xu, Yisheng; Wang, Xiaohan; Shao, Mingfei; Xu, Jun; Wang, Jie; Li, Li; Zhang, Rui; Guo, Xuhong

    2015-03-01

    A more efficient and convenient strategy was demonstrated to immobilize silver nanoparticles (NPs) with a crystalline structure into the spherical polyelectrolyte brushes (SPB) as an antibacterial material. The SPB used for surface coating (Ag immobilized PVK-PAA SPB) consists of a poly(N-vinylcarbazole) (PVK) core and poly(acrylic acid) (PAA) chain layers which are anchored onto the surface of PVK core at one end. Well-dispersed silver nanoparticles (diameter∼3.5 nm) then formed and were electrostatically confined in the brush layer. Ag content is controlled by a repeated loading process. Thin film coatings were then constructed by layer-by-layer depositions of positive charged poly(diallyldimethylammonium chloride) (PDDA) and SPB. The multilayer composites display excellent stability as well as antibacterial performance but not for simple PVK-PAA coated surface. The results show that almost complete bacteria growth including both dispersed bacterial cells and biofilms was inhibited over a period of 24 h. This approach opens a novel strategy for stable and efficient immobilization of Ag NPs in fabrication of antibacterial materials.

  16. Percutaneous absorption of benzophenone-3 loaded lipid nanoparticles and polymeric nanocapsules: A comparative study.

    PubMed

    Gilbert, E; Roussel, L; Serre, C; Sandouk, R; Salmon, D; Kirilov, P; Haftek, M; Falson, F; Pirot, F

    2016-05-17

    For the last years, the increase of the number of skin cancer cases led to a growing awareness of the need of skin protection against ultraviolet (UV) radiations. Chemical UV filters are widely used into sunscreen formulations as benzophenone-3 (BP-3), a usually used broad spectrum chemical UV filter that has been shown to exercise undesirable effects after topical application. Innovative sunscreen formulations are thus necessary to provide more safety to users. Lipid carriers seem to be a good alternative to formulate chemical UV filters reducing their skin penetration while maintaining good photo-protective abilities. The aim of this work was to compare percutaneous absorption and cutaneous bioavailability of BP-3 loaded into solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), nanostructured polymeric lipid carriers (NPLC) and nanocapsules (NC). Particle size, zeta potential and in vitro sun protection factor (SPF) of nanoparticle suspensions were also investigated. Results showed that polymeric lipid carriers, comprising NPLC and NC, significantly reduced BP-3 skin permeation while exhibiting the highest SPF. This study confirms the interesting potential of NPLC and NC to formulate chemical UV filters.

  17. Quercetin loading CdSe/ZnS nanoparticles as efficient antibacterial and anticancer materials.

    PubMed

    Yang, Xiaofang; Zhang, Weiwei; Zhao, Zhiwei; Li, Nuan; Mou, Zhipeng; Sun, Dongdong; Cai, Yongping; Wang, Weiyun; Lin, Yi

    2017-02-01

    Quercetin (Qe) plays an important role in inflammation, antibacterial, anticancer, and aging. However, Qe has extremely low water solubility, which is a major challenge in drug absorption. In this study, we described a simple method for synthesis of Qe/CdSe/ZnS nanoparticles (QCZ NPs). The QCZ NPs had an average diameter of 10nm and prominent yellow emission under UV irradiation. We investigated the antibacterial activity of QCZ NPs against drug-resistant Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) in vitro. Results showed that QCZ NPs had considerably more effective antibacterial activities than Qe or CdSe nanoparticles (CdSe NPs). Antibacterial experiment results showed that QCZ NPs acted against E. coli and B. subtilis by disrupting the bacterial cell wall and membrane. In vivo study, the QCZ NPs could cure inflammation and lesion which caused by E. coli. In anticancer assays, the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cell proliferation assays exhibited the cytotoxicity of QCZ NPs increased approximately 2-6 fold compared to raw Qe and CdSe NPs. Moreover, by using RT-CES (real-time cell electronic sensing) studies, we had demonstrated QCZ NPs have also an effect on migration and proliferation of BGC-823 cells. CdSe NPs loaded with Qe, these QCZ NPs exhibited excellent antibacterial (E. coli and B. subtilis) and anticancer (BGC-823) activities.

  18. Preparation of Fucoxanthin-Loaded Nanoparticles Composed of Casein and Chitosan with Improved Fucoxanthin Bioavailability.

    PubMed

    Koo, Song Yi; Mok, Il-Kyoon; Pan, Cheol-Ho; Kim, Sang Min

    2016-12-14

    To facilitate the utilization of fucoxanthin (FX), a valuable marine carotenoid, in the food industry, FX-loaded casein nanoparticles (FX-CN) and chitosan-coated FX-CN (FX-CS-CN) were developed using the FX-enriched fraction from Phaeodactylum tricornutum. Two nanoscale particles (237 ± 13 nm for FX-CN and 277 ± 26 nm for FX-CN-CN) with spherical and smooth surfaces showed over 71% encapsulation efficiency and polydispersity index (PDI) value of 0.31-0.39 in water. Owing to the chitosan coating, FX-CS-CN showed a positive zeta potential (24.00 mV), whereas that of FX-CN was negative (-12.87 mV). In vitro simulated digestion demonstrated better FX bioaccessibility from the nanoparticles versus P. tricornutum powder (Pt-powder) and from FX-CN versus FX-CS-CN. However, in C57BL/6 mice, fucoxanthinol absorption to the blood circulation was two times higher for FX-CS-CN versus FX-CN, possibly due to increased retention or adsorption to mucin by the cationic biopolymer in the chitosan-coated particles. These results demonstrate that FX-CS-CN can enable the application of FX, with improved bioavailability and water dispersibility, in the food industry.

  19. Silica cross-linked micelles loading with silicon nanoparticles: preparation and characterization.

    PubMed

    Pan, Guo-Hui; Barras, Alexandre; Boussekey, Luc; Boukherroub, Rabah

    2013-08-14

    A new family of luminescent and stable silicon-based nanoparticles (NPs), silica cross-linked pluronic F127 (PF127) micelles loaded with decyl capped silicon nanoparticles (decyl-SiNPs), were synthesized in aqueous media. The decyl-SiNPs were prepared by first liberating hydride terminated SiNPs (H-SiNPs) from a porous silicon matrix followed by their functionalization via hydrosilylation with 1-decene under photochemical activation. The silicon-based NPs exhibit bright photoluminescence (PL) with a quantum yield of ∼3.8% and peaking at ∼2.0 eV, which lies within the transmission window that is useful for biological imaging. They display a hydrodynamic size of ∼25 nm with exterior polyethylene oxide (PEO) blocks stretching out in aqueous media. Chloroform was found to quench the excitation at energy above 4.9 eV by shielding the incident light or relaxing the charge carriers, which highlights that caution against solvent interference should be taken when performing the studies on PL origin and luminescence efficiency of SiNPs. For PF127, the blocks of hydrophilic PEO participate in the PL quenching, while poly(propylene oxide) (PPO) does not. The colloidal solution displays excellent PL stability against salt (NaCl) and temperature but is susceptible to basic solution at pH above 9.

  20. Preparation and evaluation of amoxicillin loaded dual molecularly imprinted nanoparticles for anti-Helicobacter pylori therapy.

    PubMed

    Wu, Zhihui; Hou, Jiapeng; Wang, Yuyan; Chai, Miaolin; Xiong, Yan; Lu, Weiyue; Pan, Jun

    2015-12-30

    This paper reports studies on preparation and evaluation of amoxicillin loaded dual molecularly imprinted nanoparticles (Amo/Dual-MIPs) designed for anti-H. pylori therapy. Both MNQA and AmoNa were chosen as templates to prepare Dual-MIPs using inverse microemulsion polymerization method. NQA was modified with myristic acid (MNQA) to become amphiphilic and assist in leaving NQA cavities on the surface of Dual-MIPs for H. pylori adhesion. AmoNa was applied to produce imprinting sites in Dual-MIPs for rebinding AmoNa to exert its anti-H. pylori effect. Batch rebinding test demonstrated a preferential rebinding effect of NQA toward the Dual-MIPs. In vivofluorescence imaging showed the prolonged residence time of Dual-MIPs in H. pylori infected mice stomachs after intragastric administration of nanoparticles.In vivo H. pylori clearance tests indicated Amo/Dual-MIPs had a better aniti-H. pylori effect than amoxicillin powder did. In conclusion, Amo/Dual-MIPs may provide an alternative drug delivery strategy for anti-H. pylori therapy.

  1. In Vitro Activity of Paclitaxel-Loaded Polymeric Expansile Nanoparticles in Breast Cancer Cells

    PubMed Central

    Zubris, Kimberly Ann V.; Liu, Rong; Colby, Aaron; Schulz, Morgan D.; Colson, Yolonda L.; Grinstaff, Mark W.

    2013-01-01

    Through a series of in vitro studies, the essential steps for intracellular drug delivery of paclitaxel using a pH-responsive nanoparticle system have been investigated in breast cancer cells. We successfully encapsulated paclitaxel within polymeric expansile nanoparticles (Pax-eNPs) at 5% loading via a miniemulsion polymerization procedure. Fluorescently tagged eNPs were readily taken up by MDA-MB-231 breast cancer cells grown in culture as confirmed by confocal microscopy and flow cytometry. The ability of the encapsulated paclitaxel to reach the cytoplasm was also observed using confocal microscopy and fluorescently labeled paclitaxel. Pax-eNPs were shown to be efficacious against three in vitro human breast adenocarcinoma cell lines (MDA-MB-231, MCF-7 and SK-BR-3) as well as cells isolated from the pleural effusions of two different breast cancer patients. Lastly, macropinocytosis was identified as the major cellular pathway responsible for eNP uptake, as confirmed using temperature-sensitive metabolic reduction, pharmacologic inhibitors, and fluid-phase marker co-localization. PMID:23617223

  2. Non-invasive Photoacoustic and Fluorescence Sentinel Lymph Node Identification using Dye-loaded Perfluorocarbon Nanoparticles

    PubMed Central

    Akers, Walter J.; Kim, Chulhong; Berezin, Mikhail; Guo, Kevin; Fuhrhop, Ralph; Lanza, Gregory M.; Fischer, Georg M.; Daltrozzo, Ewald; Zumbusch, Andreas; Cai, Xin; Wang, Lihong V.; Achilefu, Samuel

    2010-01-01

    The contrast mechanisms used for photoacoustic tomography (PAT) and fluorescence imaging differ in subtle but significant ways. Design of contrast agents for each or both modalities requires an understanding of the spectral characteristics as well as intra- and intermolecular interactions that occur during formulation. We found that fluorescence quenching that occurs in the formulation of near infrared (NIR) fluorescent dyes in nanoparticles results in enhanced contrast for PAT. The ability of the new PAT method to utilize strongly absorbing chromophores for signal generation allowed us to convert a highly fluorescent dye into an exceptionally high PA contrast material. Spectroscopic characterization of the developed NIR dye-loaded perfluorocarbon-based nanoparticles for combined fluorescence and PA imaging revealed distinct dye-dependent photophysical behavior. We demonstrate that the enhanced contrast allows detection of regional lymph nodes of rats in vivo with time-domain optical and photoacoustic imaging methods. The results further show that the use of fluorescence lifetime (FLT) imaging, which is less dependent on fluorescence intensity, provides a strategic approach to bridge the disparate contrast reporting mechanisms of fluorescence and PA imaging methods. PMID:21171567

  3. Liposomes Loaded with Hydrophobic Iron Oxide Nanoparticles: Suitable T2 Contrast Agents for MRI

    PubMed Central

    Martínez-González, Raquel; Estelrich, Joan; Busquets, Maria Antònia

    2016-01-01

    There has been a recent surge of interest in the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents (CAs) for magnetic resonance imaging (MRI), due to their tunable properties and their low toxicity compared with other CAs such as gadolinium. SPIONs exert a strong influence on spin-spin T2 relaxation times by decreasing the MR signal in the regions to which they are delivered, consequently yielding darker images or negative contrast. Given the potential of these nanoparticles to enhance detection of alterations in soft tissues, we studied the MRI response of hydrophobic or hydrophilic SPIONs loaded into liposomes (magnetoliposomes) of different lipid composition obtained by sonication. These hybrid nanostructures were characterized by measuring several parameters such as size and polydispersity, and number of SPIONs encapsulated or embedded into the lipid systems. We then studied the influence of acyl chain length as well as its unsaturation, charge, and presence of cholesterol in the lipid bilayer at high field strength (7 T) to mimic the conditions used in preclinical assays. Our results showed a high variability depending on the nature of the magnetic particles. Focusing on the hydrophobic SPIONs, the cholesterol-containing samples showed a slight reduction in r2, while unsaturation of the lipid acyl chain and inclusion of a negatively charged lipid into the bilayer appeared to yield a marked increase in negative contrast, thus rendering these magnetoliposomes suitable candidates as CAs, especially as a liver CA. PMID:27472319

  4. Antioxidant activity of idebenone-loaded neutral and cationic solid-lipid nanoparticles.

    PubMed

    Leonardi, Antonio; Crasci', Lucia; Panico, Annamaria; Pignatello, Rosario

    2015-01-01

    Idebenone (IDE) is a lipophilic benzoquinone electron carrier synthetic analogue of coenzyme Q10, which behaves as an antioxidant and free radical scavenging molecule. Recently, the therapeutic application of IDE in Leber's hereditary optic neuropathy has been discussed. This work was aimed at evaluating the encapsulation of IDE in solid-lipid nanoparticles (SLN). In particular, we tested the possibility of adapting the quasi-emulsion solvent diffusion technique, already proposed to produce polymeric nanoparticles, to prepare positively charged SLN with different compositions. Such a charge, due to the addition of a cationic lipid, would facilitate the interaction with the negatively charged eye surface epithelium, with a consequent longer pre-corneal residence time of the colloidal systems. In a preliminary evaluation of the produced IDE-loaded SLN, the antioxidant activity of the drug was demonstrated using an oxygen radical absorbance capacity assay. Encapsulation of the drug in the nanocarrier systems seems able to protect IDE from degradation and prolong its antioxidant potential.

  5. Optimized Preparation of Levofloxacin-loaded Chitosan Nanoparticles by Ionotropic Gelation

    NASA Astrophysics Data System (ADS)

    Guan, J.; Cheng, P.; Huang, S. J.; Wu, J. M.; Li, Z. H.; You, X. D.; Hao, L. M.; Guo, Y.; Li, R. X.; Zhang, H.

    The present work investigates the feasibility of fabricating chitosan (CS)-levofloxacin (LOF) nanoparticles by ionotropic gelation technology. An orthogonal experiment was designed to optimize its preparing parameters and multi-index comprehensive weighed score analysis method was used to study the effects of various factors including concentration of CS, concentration of tripolyphosphate (TPP), mass ratio of CS to TPP, and mass ratio of CS to LOF on the properties of nanoparticles. The particles prepared under optimal condition of 2 mg/ml CS concentration, 2 mg/ml TPP concentration, 0.5:1 mass ratio of oil to water and 4:1 mass ratio of CS to TPP had 140 nm diameter, 0.95 span, 6.13% loading capacity (LC) and 24.91% encapsulation efficiency (EE). In vitro release profile showed that LOF released fast initially and then slowly with T90 occurring at 76.5 h. Future studies should focus on antibacterial and biocompatible properties in order to evaluate its potential as sustainable delivery system.

  6. Sumatriptan succinate loaded chitosan solid lipid nanoparticles for enhanced anti-migraine potential.

    PubMed

    Hansraj, Girotra Priti; Singh, Shailendra Kumar; Kumar, Pawan

    2015-11-01

    The objective of the present investigation was to prepare chitosan solid lipid nanoparticles (SLN), containing sumatriptan succinate using solvent injection method and to optimize the formulations for brain targeting potential. The formulation optimization was performed using three factor two level full factorial design so as to minimize the particle size and zeta potential, maximize the entrapment efficiency as well as maximize the concentration of drug in brain with maximized brain/plasma ratio of the drug. The particle size, zeta potential and entrapment efficiency for all the batches were in the range of 192-301.4nm, 30.2-51.4mV and 76.3-91.1% respectively. The optimized formulation showed a 4.54-fold increase in brain/blood ratio of drug after 2h of drug administration in male Wistar rats. The optimized nanoparticles were characterized by FT-IR spectroscopy, DSC, TGA, powder X-ray diffraction study and TEM analysis. It could be elucidated from the experimental in vivo and behavioral studies that the formulations successfully crossed the blood brain barrier and significantly exhibited its anti-migraine activity. Present investigation indicated that the hydrophilic drug sumatriptan succinate, loaded in chitosan SLN, can be successfully targeted to brain via oral delivery and thus present an effective approach for the therapeutic management of migraine.

  7. Candesartan cilexetil loaded solid lipid nanoparticles for oral delivery: characterization, pharmacokinetic and pharmacodynamic evaluation.

    PubMed

    Dudhipala, Narendar; Veerabrahma, Kishan

    2016-01-01

    Candesartan cilexetil (CC) is used in the treatment of hypertension and heart failure. It has poor aqueous solubility and low oral bioavailability. In this work, CC loaded solid lipid nanoparticles (CC-SLNs) were developed to improve the oral bioavailability. Components of the SLNs include either of trimyristin/tripalmitin/tristearin, and surfactants (Poloxamer 188 and egg lecithin E80). The CC loaded nanoparticles were prepared by hot homogenization followed by ultrasonication method. The physicochemical properties, morphology of CC-SLNs were characterized, the pharmacokinetic and pharmacodynamic behaviour of CC-SLNs were evaluated in rats. Stable CC-SLNs having a mean particle size of 180-220 nm with entrapment efficiency varying in between 91-96% were developed. The physical stability of optimized formulation was studied at refrigerated and room temperature for 3 months. Further, freeze drying was tried for improving the physical stability. DSC and XRD analyses indicated that the drug incorporated into SLN was in amorphous form but not in crystalline state. The SLN-morphology was found to be nearly spherical by electron microscopic studies. Pharmacokinetic results indicated that the oral bioavailability of CC was improved over 2.75-fold after incorporation into SLNs. Pharmacodynamic study of SLNs in hypertensive rats showed a decrease in systolic blood pressure for 48 h, while suspension showed a decrease in systolic blood pressure for only 2 h. Taken together, these effects are due to enhanced bioavailability coupled with sustained action of CC in SLN formulation. Thus, the results conclusively demonstrated the role of CC-SLNs for a significant enhancement in oral bioavailability along with improved pharmacodynamic effect.

  8. Development and characterization of sorafenib-loaded PLGA nanoparticles for the systemic treatment of liver fibrosis.

    PubMed

    Lin, Ts-Ting; Gao, Dong-Yu; Liu, Ya-Chi; Sung, Yun-Chieh; Wan, Dehui; Liu, Jia-Yu; Chiang, Tsaiyu; Wang, Liying; Chen, Yunching

    2016-01-10

    Sorafenib is a tyrosine kinase inhibitor that has recently been shown to be a potential antifibrotic agent. However, a narrow therapeutic window limits the clinical use and therapeutic efficacy of sorafenib. Herein, we have developed and optimized nanoparticle (NP) formulations prepared from a mixture of poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-PLGA) copolymers with poly(lactic-co-glycolic acid) (PLGA) for the systemic delivery of sorafenib into the fibrotic livers of CCl4-induced fibrosis mouse models. We characterized and compared the pharmaceutical and biological properties of two different PLGA nanoparticles (NPs)--PEG-PLGA NPs (PEG-PLGA/PLGA=10/0) and PEG-PLGA/PLGA NPs (PEG-PLGA/PLGA=5/5). Increasing the PLGA content in the PEG-PLGA/PLGA mixture led to increases in the particle size and drug encapsulation efficacy and a decrease in the drug release rate. Both PEG-PLGA and PEG-PLGA/PLGA NPs significantly prolonged the blood circulation of the cargo and increased the uptake by the fibrotic livers. The systemic administration of PEG-PLGA or PEG-PLGA/PLGA NPs containing sorafenib twice per week for a period of 4 weeks efficiently ameliorated liver fibrosis, as indicated by decreased α-smooth muscle actin (α-SMA) content and collagen production in the livers of CCl4-treated mice. Furthermore, sorafenib-loaded PLGA NPs significantly shrank the abnormal blood vessels and decreased microvascular density (MVD), leading to vessel normalization in the fibrotic livers. In conclusion, our results reflect the clinical potential of sorafenib-loaded PLGA NPs for the prevention and treatment of liver fibrosis.

  9. Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy

    NASA Astrophysics Data System (ADS)

    Aravind, Athulya; Nair, Remya; Raveendran, Sreejith; Veeranarayanan, Srivani; Nagaoka, Yutaka; Fukuda, Takahiro; Hasumura, Takahashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

    2013-10-01

    Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions.

  10. The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load.

    PubMed

    Willcox, D Craig; Willcox, Bradley J; Todoriki, Hidemi; Suzuki, Makoto

    2009-08-01

    Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled "functional foods" and, indeed, are currently being explored for their potential health-enhancing properties.

  11. On the accessibility of surface-bound drugs on magnetic nanoparticles. Encapsulation of drugs loaded on modified dextran-coated superparamagnetic iron oxide by β-cyclodextrin.

    PubMed

    Sudha, Natesan; Yousuf, Sameena; Israel, Enoch V M V; Paulraj, Mosae Selvakumar; Dhanaraj, Premnath

    2016-05-01

    We report the loading of drugs on aminoethylaminodextran-coated iron oxide nanoparticles, their superparamagnetic behavior, loading of drugs on them, and the β-cyclodextrin-complex formation of the drugs on the surface of the nanoparticles. The magnetic behavior is studied using vibrating sample magnetometry and X-ray photoelectron spectroscopy is used to analyze the elemental composition of drug-loaded nanoparticles. Scanning electron microscopy shows ordered structures of drug-loaded nanoparticles. UV-visible absorption and fluorescence spectroscopy are used to study the binding of the surface-loaded drugs to β-cyclodextrin. All of the drugs form 1:1 host-guest complexes. The iodide ion quenching of fluorescence of free- and iron oxide-attached drugs are compared. The binding strengths of the iron oxide surface-loaded drugs-β-cyclodextrin binding are smaller than those of the free drugs.

  12. Loading of atorvastatin and linezolid in β-cyclodextrin-conjugated cadmium selenide/silica nanoparticles: A spectroscopic study.

    PubMed

    Antony, Eva Janet; Shibu, Abhishek; Ramasamy, Sivaraj; Paulraj, Mosae Selvakumar; Enoch, Israel V M V

    2016-08-01

    The preparation of β-cyclodextrin-conjugated cadmium selenide-silica nanoparticles, the loading of two drugs viz., Atorvastatin and linezolid in the cyclodextrin cavity, and the fluorescence energy transfer between CdSe/SiO2 nanoparticles and the drugs encapsulated in the cyclodextrin cavity are reported in this paper. IR spectroscopy, X-ray diffractometry, transmission electron microscopy, and particle size analysis by light-scattering experiment were used as the tools of characterizing the size and the crystal system of the nanoparticles. The nanoparticles fall under hexagonal system. The silica-shell containing CdSe nanoparticles were functionalized by reaction with aminoethylamino-β-cyclodextrin. Fluorescence spectra of the nanoparticles in their free and drug-encapsulated forms were studied. The FÖrster distances between the encapsulated drugs and the CdSe nanoparticles are below 3nm. The change in the FÖrster resonance energy parameters under physiological conditions may aid in tracking the release of drugs from the cavity of the cyclodextrin.

  13. Preparation and evaluation of raloxifene-loaded solid dispersion nanoparticle by spray-drying technique without an organic solvent.

    PubMed

    Tran, Tuan Hiep; Poudel, Bijay K; Marasini, Nirmal; Chi, Sang-Cheol; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-02-25

    The aim of this study was to improve the physicochemical properties and bioavailability of a poorly water-soluble drug, raloxifene by solid dispersion (SD) nanoparticles using the spray-drying technique. These spray-dried SD nanoparticles were prepared with raloxifene (RXF), polyvinylpyrrolidone (PVP) and Tween 20 in water. Reconstitution of optimized RXF-loaded SD nanoparticles in pH 1.2 medium showed a mean particle size of approximately 180 nm. X-ray diffraction and differential scanning calorimetry indicated that RXF existed in an amorphous form within spray-dried nanoparticles. The optimized formulation showed an enhanced dissolution rate of RXF at pH 1.2, 4.0, 6.8 and distilled water as compared to pure RXF powder. The improved dissolution of raloxifene from spray-dried SD nanoparticles appeared to be well correlated with enhanced oral bioavailability of raloxifene in rats. Furthermore, the pharmacokinetic parameters of the spray-dried SD nanoparticles showed increased AUC(0-∞) and C(max) of RXF by approximately 3.3-fold and 2.3-fold, respectively. These results suggest that the preparation of RXF-SD nanoparticles using the spray drying technique without organic solvents might be a promising approach for improving the oral bioavailability of RXF.

  14. Diclofenac sodium-loaded solid lipid nanoparticles prepared by emulsion/solvent evaporation method

    NASA Astrophysics Data System (ADS)

    Liu, Dongfei; Jiang, Sunmin; Shen, Hong; Qin, Shan; Liu, Juanjuan; Zhang, Qing; Li, Rui; Xu, Qunwei

    2011-06-01

    The preparation of solid lipid nanoparticles (SLNs) suffers from the drawback of poor incorporation of water-soluble drugs. The aim of this study was therefore to assess various formulation and process parameters to enhance the incorporation of a water-soluble drug (diclofenac sodium, DS) into SLNs prepared by the emulsion/solvent evaporation method. Results showed that the entrapment efficiency (EE) of DS was increased to approximately 100% by lowering the pH of dispersed phase. The EE of DS-loaded SLNs (DS-SLNs) had been improved by the existence of cosurfactants and increment of PVA concentration. Stabilizers and their combination with PEG 400 in the dispersed phase also resulted in higher EE and drug loading (DL). EE increased and DL decreased as the phospholipid/DS ratio became greater, while the amount of DS had an opposite effect. Ethanol turned out to be the ideal solvent making DS-SLNs. EE and DL of DS-SLNs were not affected by either the stirring speed or the viscosity of aqueous and dispersed phase. According to the investigations, drug solubility in dispersion medium played the most important role in improving EE.

  15. Antitumor properties of platinum(iv) prodrug-loaded silk fibroin nanoparticles.

    PubMed

    Lozano-Pérez, A Abel; Gil, Ana L; Pérez, Sergio A; Cutillas, Natalia; Meyer, Hajo; Pedreño, Mónica; D Aznar-Cervantes, Salvador; Janiak, Christoph; Cenis, Jose Luis; Ruiz, José

    2015-08-14

    Platinum(iv) complexes take advantage of the exclusive conditions that occur within the tumor to carry out their cytotoxic activity. On the other hand, silk fibroin has natural properties which make it very interesting as a biomaterial: high biocompatibility, biodegradability, low immunogenicity, high cellular penetration capacity and high reactive surface. Herein we report the preparation of silk fibroin nanoparticles (SFNs) loaded with the hydrophobic Pt(iv) complex cis,cis,trans-[Pt(NH(3))(2)Cl(2)(O(2)CC(6)H(5))(2)] (PtBz). Only a small fraction of the loaded PtBz is released (less than 10% after 48 h). PtBz-SFNs trigger strong cytotoxic effects against human ovarian carcinoma A2780 cells and their cisplatin-resistant variant A2780cisR cells. Interestingly, PtBz-SFNs are very cytotoxic (nanomolar IC(50) values) toward the triple negative breast tumor cell line MDA-MB-231, and also toward SK-BR-3 and MCF-7, while maintaining an excellent selectivity index.

  16. Cupreous Complex-Loaded Chitosan Nanoparticles for Photothermal Therapy and Chemotherapy of Oral Epithelial Carcinoma.

    PubMed

    Lin, Min; Wang, Dandan; Liu, Shuwei; Huang, Tingting; Sun, Bin; Cui, Yan; Zhang, Daqi; Sun, Hongchen; Zhang, Hao; Sun, Hui; Yang, Bai

    2015-09-23

    Electron transition materials on the basis of transition metal ions usually possess higher photothermal transduction efficiency but lower extinction ability, which have not been considered as efficient photothermal agents for therapeutic applications. In this work, we demonstrate a facile and feasible approach for enhancing 808 nm photothermal conversion effect of d orbits transition Cu(II) ions by forming Cu-carboxylate complexes. The coordination with carboxylate groups greatly enlarges the splitting energy gap of Cu(II) and the capability of electron transition, thus enhancing the extinction ability in near-infrared region. The cupreous complexes are further loaded in biocompatible and biodegradable polymer nanoparticles (NPs) of chitosan to temporarily lower the toxicity, which allows the photothermal therapy of human oral epithelial carcinoma (KB) cells in vitro and KB tumors in vivo. Animal experiments indicate the photothermal tumor inhibition rate of 100%. In addition, the gradual degradation of chitosan NPs leads to the release of cupreous complexes, thus exhibiting additional chemotherapeutic behavior in KB tumor treatment. Onefold chemotherapy experiments indicate the tumor inhibition rate of 93.1%. The combination of photothermal therapy and chemotherapy of cupreous complex-loaded chitosan NPs indicates the possibility of inhibiting tumor recurrence.

  17. Poly(lactic-co-glycolic) Acid-Chitosan Dual Loaded Nanoparticles for Antiretroviral Nanoformulations

    PubMed Central

    Makita-Chingombe, Faithful; Kutscher, Hilliard L.; DiTursi, Sara L.; Morse, Gene D.; Maponga, Charles C.

    2016-01-01

    Poly(lactic-co-glycolic acid) (PLGA) chitosan (CS) coated nanoparticles (NPs) were loaded with two antiretrovirals (ARVs) either lamivudine (LMV) which is hydrophilic or nevirapine (NVP) which is hydrophobic or both LMV and NVP. These ARVs are of importance in resource-limited settings, where they are commonly used in human immunodeficiency virus (HIV-1) treatment due to affordability and accessibility. NPs prepared by a water-oil-water emulsion and reduced pressure solvent evaporation technique were determined to have a positive zeta potential, a capsule-like morphology, and an average hydrodynamic diameter of 240 nm. Entrapment of NVP as a single ARV had a notable increase in NP size compared to LMV alone or in combination with LMV. NPs stored at room temperature in distilled water maintained size, polydispersity (PDI), and zeta potential for one year. No changes in size, PDI, and zeta potential were observed for NPs in 10% sucrose in lyophilized or nonlyophilized states stored at 4°C and −20°C, respectively. Freezing NPs in the absence of sucrose increased NP size. Drug loading, encapsulation efficiency, and kinetic release profiles were quantified by high performance liquid chromatography (HPLC). Our novel nanoformulations have the potential to improve patient outcomes and expand drug access in resource-limited countries for the treatment of HIV-1. PMID:27190651

  18. Vitamin B12-loaded solid lipid nanoparticles as a drug carrier in cancer therapy.

    PubMed

    Genç, Lütfi; Kutlu, H Mehtap; Güney, Gamze

    2015-05-01

    Nanostructure-mediated drug delivery, a key technology for the realization of nanomedicine, has the potential to improve drug bioavailability, ameliorate release deviation of drug molecules and enable precision drug targeting. Due to their multifunctional properties, solid lipid nanoparticles (SLNs) have received great attention of scientists to find a solution to cancer. Vitamin supplements may contribute to a reduction in the risk of cancer. Vitamin B12 has several characteristics that make it an attractive entity for cancer treatment and possible therapeutic applications. The aim of this study was to produce B12-loaded SLNs (B12-SLNs) and determine the cytotoxic effects of B12-SLNs on H-Ras 5RP7 and NIH/3T3 control cell line. Results obtained by MTT assay, transmission electron and confocal microscopy showed that B12-loaded SLNs are more effective than free vitamin B12 on cancer cells. In addition, characterization studies indicate that while the average diameter of the B12 was about 650 nm, B12-SLNs were about 200 nm and the drug release efficiency of vit. B12 by means of SLNs increased up to 3 h. These observations point to the fact that B12-SLNs could be used as carrier systems due to the therapeutic effects on cancer.

  19. Preparation, characterization, and oral delivery of insulin loaded carboxylated chitosan grafted poly(methyl methacrylate) nanoparticles.

    PubMed

    Cui, Fuying; Qian, Feng; Zhao, Ziming; Yin, Lichen; Tang, Cui; Yin, Chunhua

    2009-05-11

    To improve the efficiency of insulin via oral administration, pH-sensitive carboxylated chitosan grafted poly(methyl methacrylate) nanoparticles (CCGN) were prepared. CCGN were characterized by (1)H NMR, dynamic light scattering, zeta potential, and transmission electron microscopy, and the hypoglycemic effect of insulin loaded CCGN via the oral route was evaluated in normal and diabetic rats. CCGN exhibited a homogeneous morphology and a spherical shape with core-shell structure. They were aggregated in simulated gastric fluid while separated in simulated intestinal fluid. Insulin was mainly located in the shell of the CCGN via hydrogen bonding, electrostatic interaction, and Van der Waals force. Insulin release from the CCGN exhibited a pH-sensitive property in that it had a slow release rate at pH 2.0 and a fast release rate at pH 6.8 and 7.4. The pharmacological bioavailability after oral administration of insulin loaded CCGN at a dose of 25 IU/kg was found to be 9.7%. Besides, CCGN showed desirable tissue and blood compatibility. Therefore, the CCGN would be a promising delivery carrier for protein drugs via the oral route.

  20. Comparative studies of salinomycin-loaded nanoparticles prepared by nanoprecipitation and single emulsion method

    NASA Astrophysics Data System (ADS)

    Wang, Qin; Wu, Puyuan; Ren, Wei; Xin, Kai; Yang, Yang; Xie, Chen; Yang, Chenchen; Liu, Qin; Yu, Lixia; Jiang, Xiqun; Liu, Baorui; Li, Rutain; Wang, Lifeng

    2014-07-01

    To establish a satisfactory delivery system for the delivery of salinomycin (Sal), a novel, selective cancer stem cell inhibitor with prominent toxicity, gelatinase-responsive core-shell nanoparticles (NPs), were prepared by nanoprecipitation method (NR-NPs) and single emulsion method (SE-NPs). The gelatinase-responsive copolymer was prepared by carboxylation and double amination method. We studied the stability of NPs prepared by nanoprecipitation method with different proportions of F68 in aqueous phase to determine the best proportion used in our study. Then, the NPs were prepared by nanoprecipitation method with the best proportion of F68 and single emulsion method, and their physiochemical traits including morphology, particle size, zeta potential, drug loading content, stability, and in vitro release profiles were studied. The SE-NPs showed significant differences in particle size, drug loading content, stability, and in vitro release profiles compared to NR-NPs. The SE-NPs presented higher drug entrapment efficiency and superior stability than the NR-NPs. The drug release rate of SE-NPs was more sustainable than that of the NR-NPs, and in vivo experiment indicated that NPs could prominently reduce the toxicity of Sal. Our study demonstrates that the SE-NPs could be a satisfactory method for the preparation of gelatinase-responsive NPs for intelligent delivery of Sal.

  1. Development of silver nanoparticle loaded antibacterial polymer mesh using plasma polymerization process.

    PubMed

    Kumar, Virendra; Jolivalt, Claude; Pulpytel, Jerome; Jafari, Reza; Arefi-Khonsari, Farzaneh

    2013-04-01

    Plasma polymerized polyacrylic acid (PPAA) was deposited on a polymer substrate, namely polyethylene terephthalate (PET) mesh, for entrapment of silver nanoparticle (Ag-NP) in order to achieve antibacterial property to the material. Carboxylic groups of PPAA act as anchor as well as capping and stabilizing agents for Ag-NPs synthesized by chemical reduction method using NaBH(4) as a reducing agent. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy (XPS), and water contact angle analysis were used to characterize the PPAA coatings. The Ag-NPs loaded polymer samples were characterized by UV-visible spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray, and XPS techniques. XPS analysis showed ~1.0 at.% loading of Ag-NPs on to the PPAA-PET-mesh, which was composed of 79% zero-valent (Ag°) and 21% oxidized nano-Ag (Ag(+) ). The plasma processed PET meshes samples were tested for antibacterial activity against two bacterial strains, namely Staphylococcus aureus (Gram positive) and Escherichia coli (Gram negative). Qualitative and quantitative tests showed that silver containing PPAA-PET meshes exhibit excellent antibacterial property against the tested bacteria with percent reduction of bacterial concentration >99%, compared to the untreated PET mesh.

  2. Comparative studies of salinomycin-loaded nanoparticles prepared by nanoprecipitation and single emulsion method

    PubMed Central

    2014-01-01

    To establish a satisfactory delivery system for the delivery of salinomycin (Sal), a novel, selective cancer stem cell inhibitor with prominent toxicity, gelatinase-responsive core-shell nanoparticles (NPs), were prepared by nanoprecipitation method (NR-NPs) and single emulsion method (SE-NPs). The gelatinase-responsive copolymer was prepared by carboxylation and double amination method. We studied the stability of NPs prepared by nanoprecipitation method with different proportions of F68 in aqueous phase to determine the best proportion used in our study. Then, the NPs were prepared by nanoprecipitation method with the best proportion of F68 and single emulsion method, and their physiochemical traits including morphology, particle size, zeta potential, drug loading content, stability, and in vitro release profiles were studied. The SE-NPs showed significant differences in particle size, drug loading content, stability, and in vitro release profiles compared to NR-NPs. The SE-NPs presented higher drug entrapment efficiency and superior stability than the NR-NPs. The drug release rate of SE-NPs was more sustainable than that of the NR-NPs, and in vivo experiment indicated that NPs could prominently reduce the toxicity of Sal. Our study demonstrates that the SE-NPs could be a satisfactory method for the preparation of gelatinase-responsive NPs for intelligent delivery of Sal. PMID:25147486

  3. Crystalline metallic Au nanoparticle-loaded α-Bi2O3 microrods for improved photocatalysis.

    PubMed

    Jiang, Hai-Ying; Cheng, Kun; Lin, Jun

    2012-09-21

    Crystalline metallic Au nanoparticles were loaded on α-Bi(2)O(3) microrods (Au/α-Bi(2)O(3)) using an Au deposition-precipitation method. The prepared samples were characterized by scanning electron and transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and UV-vis diffuse reflectance spectroscopy. Upon visible light irradiation, the Au/α-Bi(2)O(3) exhibits much higher photocatalytic activities than the pure α-Bi(2)O(3) for the degradation of Rhodamine B and 2,4-dichlorophenol in aqueous solution. The role of the Au and the paths of electron transport in the photocatalysis of the Au/α-Bi(2)O(3) were investigated and discussed in detail based on the analysis of the photo-generated hydroxyl radicals (˙OH) and hydrogen peroxide (H(2)O(2)) in the visible light irradiated suspension of pure α-Bi(2)O(3) and Au/α-Bi(2)O(3). The result reveals that the Au loaded on α-Bi(2)O(3) plays a critical role in the separation of the electron and hole pairs by accumulating the electrons from the excited α-Bi(2)O(3), which is responsible for the enhanced photocatalytic activity.

  4. Near-infrared fluorescence imaging platform for quantifying in vivo nanoparticle diffusion from drug loaded implants

    PubMed Central

    Markovic, Stacey; Belz, Jodi; Kumar, Rajiv; Cormack, Robert A; Sridhar, Srinivas; Niedre, Mark

    2016-01-01

    Drug loaded implants are a new, versatile technology platform to deliver a localized payload of drugs for various disease models. One example is the implantable nanoplatform for chemo-radiation therapy where inert brachytherapy spacers are replaced by spacers doped with nanoparticles (NPs) loaded with chemotherapeutics and placed directly at the disease site for long-term localized drug delivery. However, it is difficult to directly validate and optimize the diffusion of these doped NPs in in vivo systems. To better study this drug release and diffusion, we developed a custom macroscopic fluorescence imaging system to visualize and quantify fluorescent NP diffusion from spacers in vivo. To validate the platform, we studied the release of free fluorophores, and 30 nm and 200 nm NPs conjugated with the same fluorophores as a model drug, in agar gel phantoms in vitro and in mice in vivo. Our data verified that the diffusion volume was NP size-dependent in all cases. Our near-infrared imaging system provides a method by which NP diffusion from implantable nanoplatform for chemo-radiation therapy spacers can be systematically optimized (eg, particle size or charge) thereby improving treatment efficacy of the platform. PMID:27069363

  5. Improved antifungal activity of amphotericin B-loaded TPGS-b-(PCL-ran-PGA) nanoparticles

    PubMed Central

    Tang, Xiaolong; Jiao, Ronghong; Xie, Chunmei; Xu, Lifa; Huo, Zhen; Dai, Jingjing; Qian, Yunyun; Xu, Weiwen; Hou, Wei; Wang, Jiang; Liang, Yong

    2015-01-01

    To develop amphotericin B-loaded biodegradable TPGS-b-(PCL-ran-PGA) nanoparticles (PLGA-TPGS-AMB NPs) for fungal infection treatment, PLGA-TPGS NPs and PLGA NPs were synthesized by a modified double emulsion method and characterized in terms of size and size distribution, morphology and zeta potential. Drug encapsulation efficiency, in vitro drug release, and in vitro/vivo tests against Candida glabrata were completed. The data showed that both of the two AMB-loaded NPs (PLGA-AMB NPs, PLGA-TPGS-AMB NPs) achieved significantly higher level of antifungal effects than water suspended AMB. In comparison with PLGA-AMB NPs, PLGA-TPGS-AMB NPs had a stronger protective effect against candidiasis and gained an advantage of prolonged antifungal efficacy. In conclusion, PLGA-TPGS-AMB NPs system significantly improves AMB bioavailability by increasing the aqueous dispersibility and improving the antifungal activity. And this would be an excellent choice for the antifungal treatment of the entrapped drug because of its low toxicity and higher effectiveness. PMID:26131089

  6. Halobetasol propionate-loaded solid lipid nanoparticles (SLN) for skin targeting by topical delivery.

    PubMed

    Bikkad, Mahesh L; Nathani, Ajaz H; Mandlik, Satish K; Shrotriya, Shilpa N; Ranpise, Nisharani S

    2014-06-01

    The clinical use of halobetasol propionate (HP) is related to some adverse effects like irritation, pruritus and stinging. The purpose of this work was to construct HP-loaded solid lipid nanoparticles (HP-SLN) formulation with skin targeting to minimizing the adverse side effects and providing a controlled release. HP-SLN were prepared by solvent injection method and formula was optimized by the application of 3(2) factorial design. The nanoparticulate dispersion was evaluated for particle size and entrapment efficiency (EE). Optimized batch was characterized for differential scanning calorimetry (DSC), scanning electron microscopy, X-ray diffraction study and finally incorporated into polymeric gels of carbopol for convenient application. The nanoparticulate gels were evaluated comparatively with the commercial product with respect to ex-vivo skin permeation and deposition study on human cadaver skins and finally skin irritation study. HP-SLN showed average size between 200 nm and 84-94% EE. DSC studies revealed no drug-excipient incompatibility and amorphous dispersed of HP in SLN. Ex vivo study of HP-SLN loaded gel exhibited prolonged drug release up to 12 h where as in vitro drug deposition and skin irritation studies showed that HP-SLN formulation can avoid the systemic uptake, better accumulative uptake of the drug and nonirritant to the skin compared to marketed formulation. These results indicate that the studied HP-SLN formulation represent a promising carrier for topical delivery of HP, having controlled drug release, and potential of skin targeting with no skin irritation.

  7. Electrospinning of silver nanoparticles loaded highly porous cellulose acetate nanofibrous membrane for treatment of dye wastewater

    NASA Astrophysics Data System (ADS)

    Wang, Ke; Ma, Qian; Wang, Shu-Dong; Liu, Hua; Zhang, Sheng-Zhong; Bao, Wei; Zhang, Ke-Qin; Ling, Liang-Zhong

    2016-01-01

    In this paper, silver nanoparticles (NPs) were reduced form silver nitrate. Morphology and distribution of the synthesized silver NPs were characterized. In order to obtain cellulose acetate (CA), nanofibrous membrane with high effective adsorption performance to carry silver NPs for treatment of dye wastewater, different solvent systems were used to fabricate CA nanofibrous membranes with different morphologies and porous structures via electrospinning. Morphologies and structures of the obtained CA nanofibrous membranes were compared by scanning electron microscopy (SEM), which showed that CA nanofibrous membrane obtained from acetone/dichloromethane (1/2, v/v) was with the highly porous structure. SEM, energy-dispersive spectrometry and Fourier transform infrared spectrometry showed that the silver NPs were effectively incorporated in the CA nanofibrous membrane and the addition of silver NPs did not damage the porous structure of the CA nanofibrous membrane. Adsorption of dye solution (rhodamine B aqueous solution) revealed that the highly porous CA nanofibrous membrane exhibited effective adsorption performance and the addition of silver NPs did not affect the adsorption of the dye. Antibacterial property of the CA nanofibrous membrane showed that the silver-loaded highly porous CA nanofibrous membrane had remarkable antibacterial property when compared to the CA nanofibrous membrane without silver NPs. The silver-loaded highly porous CA nanofibrous membrane could be considered as an ideal candidate for treatment of the dye wastewater.

  8. Paclitaxel-loaded KMnF3 nanoparticles for cancer imaging and therapy in vivo

    NASA Astrophysics Data System (ADS)

    Song, Xiao-xia; Wan, Hong-ping; Zhang, Jin-sheng; Tang, Qun

    2014-11-01

    Biocompatible nanoparticles (NPs) responding to the light, thermal, or magnetic excitation are attracting more attention for diagnosis and therapy of cancer. Design of an effective multifunctional complex based on those NPs is a key issue to be addressed, for example, integration of anti-tumor agents with nanoprobes has been considered as one of the successful strategies for combined cancer diagnosis and therapy. In this paper, we develop paclitaxel (PTX)-loaded PEGylation KMnF3 NP, with the size ranged from 18 to 23 nm, as MRI contrast agents for cancer imaging and drug delivery for chemotherapy. Preliminary cell tests demonstrated that PTX@PEG-KMnF3 NP is highly biocompatible. The NP has high loading capacity of PTX (0.7 mg PTX/mg Mn ions), enhanced solubility of PTX (0.16 mg PTX/ml vs 0.02 mg PTX/ml), and high releasing ratio (90 %) in the weak acid solution. As it was applied for in vivo imaging and therapy, the NP enhanced contrast of tumor's MR images and PTX's anti-tumor effect profoundly. The signal noise ratio of the cancer image increased 170 % as comparison to pre-injection with the injection dose of 1.15 mg Mn/kg. The drug delivery's efficacy was also substantially improved, as the tumor growth inhibition effects reached 50 %, meanwhile only 30 % for pristine PTX. Our studies suggest that PTX-loaded KMnF3 NP might be useful as MR image-guided drug delivery for tumor treatment.

  9. Preparation, characterization, and cellular studies of photosensitizer-loaded lipid nanoparticles for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Navarro, Fabrice P.; Bechet, Denise; Delmas, Thomas; Couleaud, Pierre; Frochot, Céline; Verhille, Marc; Kamarulzaman, Ezatul; Vanderesse, Régis; Boisseau, Patrick; Texier, Isabelle; Gravier, Julien; Vinet, Françoise; Barberi-Heyob, Muriel; Couffin, Anne Claude

    2011-02-01

    PhotoDynamic Therapy (PDT) has been established as a potent and less invasive treatment for different kinds of cancer. Among various attempts to enhance the therapeutics efficacy of PDT, the specific delivery of the PhotoSensitizer (PS) in the tumor is expected to increase its clinical applications, since unwanted accumulation, especially in the skin, impairs the patients' quality of life (prolonged cutaneous photosensitivity). The aim of this study was to engineer Lipid Nanoparticles (LNP) with different sizes and various PS contents, using simple, solvent-free and easily scale up manufacturing processes. Meso-tetra (hydroxyphenyl) chlorin (mTHPC) is one of the most potent photoactive compounds for clinical use and it has been successfully applied in the treatment of various indications, such as the head and neck, prostate and pancreatic cancers. Here, a derivative of mTHPC was efficiently incorporated into the lipid core of LNP, leading to a large range of stable and reproducible mTHPC-loaded LNP with narrow size distribution. The photophysical and photochemical properties of mTHPC-loaded LNP were studied by measuring absorbance and fluorescence spectra, colloidal stability, particle size and zeta potential, as well as singlet oxygen luminescence. The photocytotoxicity of three selected mTHPC-loaded LNP (25 nm, 45 nm and 95 nm of diameter, respectively) was evaluated on MCF-7 cells, in comparison to free mTHPC, under irradiation at 652 nm with a range of light fluence from 1 to 5 J/cm2. All the physico-chemical, photophysical and biological measurements allow us to conclude that LNP is a promising nano-drug delivery system for PDT.

  10. Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

    PubMed Central

    2013-01-01

    Background and the aim of the study The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology. Method A Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses. Results The NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation with a desirability factor of 0.9 was selected and characterized. This formulation demonstrated the particle size of 270 nm, EE of 55%, DL of 3.9% and cumulative drug release of 79% after 12 hrs. In vitro release studies showed a burst release at the initial stage followed by a sustained release of sildenafil from NPs up to 12 hrs. The release kinetic of the optimized formulation was fitted to Higuchi model. Conclusions Sildenafil citrate NPs with small particle size, lipophilic feature, high entrapment efficiency and good loading capacity is produced by this method. Characterization of optimum formulation, provided by an evaluation of experimental data, showed no significant difference between calculated and measured data. PMID:24355133

  11. Improved tumor targeting and antitumor activity of camptothecin loaded solid lipid nanoparticles by preinjection of blank solid lipid nanoparticles.

    PubMed

    Jang, Dong-Jin; Moon, Cheol; Oh, Euichaul

    2016-05-01

    This study aimed to enhance the in vivo antitumor effects of camptothecin (CPT), a strong antitumor agent whose delivery is limited by poor aqueous solubility and instability of the active lactone form. CPT was loaded into sterically stabilized, solid lipid nanoparticles (CPT-SLNs) formulated for intravenous administration. The influence of preinjected blank SLNs on the tumor targeting, pharmacokinetics and antitumor activity of CPT-SLNs was investigated. The CPT-SLNs composed of trilaurin-based lipid matrix containing poloxamer188 and pegylated phospholipid as stabilizers were prepared by hot homogenization method and evaluated for in vitro characteristics and in vivo performance. The CPT-SLNs showed an in vitro long-term sustained release pattern and effectively protected the CPT lactone form from hydrolysis under physiological conditions. Notable tumor targeting and tumor growth inhibition were observed after intravenous administration of CPT-SLNs to mice with subcutaneous transplants of CT26 carcinoma cells. In pharmacokinetic studies in rats, CPT-SLNs markedly elevated plasma CPT level and prolonged blood circulation compared to free CPT. Nonetheless, high uptake of CPT-SLNs by reticuloendothelial system (RES)-rich tissues resulted in limited tumor targeting of CPT-SLNs and plasma CPT levels. Preinjection of blank SLNs before administration of CPT-SLNs to tumor-bearing mice substantially reduced the accumulation of CPT-SLNs in RES organs. This led to significantly enhanced tumor targeting, improved pharmacokinetic parameters and increased antitumor efficacy of CPT-SLNs. These results suggested that the in vivo antitumor effects of CPT-SLNs could be further enhanced by preinjection of blank SLNs. Therefore, CPT-SLNs with preinjected blank SLNs could be a potential approach for stable and effective CPT-based cancer therapy.

  12. Development of silane grafted ZnO core shell nanoparticles loaded diglycidyl epoxy nanocomposites film for antimicrobial applications.

    PubMed

    Suresh, S; Saravanan, P; Jayamoorthy, K; Ananda Kumar, S; Karthikeyan, S

    2016-07-01

    In this article a series of epoxy nanocomposites film were developed using amine functionalized (ZnO-APTES) core shell nanoparticles as the dispersed phase and a commercially available epoxy resin as the matrix phase. The functional group of the samples was characterized using FT-IR spectra. The most prominent peaks of epoxy resin were found in bare epoxy and in all the functionalized ZnO dispersed epoxy nanocomposites (ZnO-APTES-DGEBA). The XRD analysis of all the samples exhibits considerable shift in 2θ, intensity and d-spacing values but the best and optimum concentration is found to be 3% ZnO-APTES core shell nanoparticles loaded epoxy nanocomposites supported by FT-IR results. From TGA measurements, 100wt% residue is obtained in bare ZnO nanoparticles whereas in ZnO core shell nanoparticles grafted DGEBA residue percentages are 37, 41, 45, 46 and 52% for 0, 1, 3, 5 and 7% ZnO-APTES-DGEBA respectively, which is confirmed with ICP-OES analysis. From antimicrobial activity test, it was notable that antimicrobial activity of 7% ZnO-APTES core shell nanoparticles loaded epoxy nanocomposite film has best inhibition zone effect against all pathogens under study.

  13. Factorial design based preparation, optimization, characterization and in vitro drug release studies of olanzapine loaded PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-12-01

    The objective of the present work was to develop and optimize olanzapine loaded polymeric nanoparticles using a factorial design. The presented work developed and optimized olanzapine loaded polymeric nanoparticles by using a 33 factorial design. The 33 factorial design was used for studying the effect of the main preparation variables on particle size and percent drug entrapment efficiency of the nanoparticles. A modified nanoprecipitation method was used to prepare nanoparticles successfully by using the biodegradable polymer poly(lactic-co-glycolic)acid (PLGA), and they were characterized for various parameters such as particle size, shape, zeta potential, percent drug entrapment efficiency, percent process yield and in vitro drug release behavior. Examination of the interaction between the excipients used as well as investigation of the nature of the drug, the formulation and the nature of the drug in the formulations was carried out by FTIR studies. Different kinetic models were used to analyze the in vitro drug release data. The preferred formulation showed a particle size of 127.6 ± 1.9 nm, PDI of 0.239 ± 0.013, zeta potential of -29.2 mV, entrapment efficiency of 72.46 ± 3.8% and process yield of 89.65 ± 1.3%. TEM results showed that these nanoparticles were spherical in shape and follow the Korsmeyer-Peppas model with different release exponent values.

  14. Superior catalytic performances of platinum nanoparticles loaded nitrogen-doped graphene toward methanol oxidation and hydrogen evolution reaction.

    PubMed

    Liu, Dong; Li, Libo; You, Tianyan

    2017-02-01

    The catalysts with excellent catalytic properties and low-cost are still highly desirable in many fields, such as fuel cells. In respect of this challenge, we have synthesized high-quality platinum nanoparticles loaded nitrogen-doped graphene (Pt/NG) by using formic acid as reduction agent and commercial-available nitrogen-doped graphene (N-graphene) as supporting materials. The morphology and component characterization demonstrate that high-loading Pt nanoparticles with a mean diameter of 2.5nm were uniformly dispersed on nitrogen-doped graphene. The resulting Pt/NG exhibit higher catalytic activity toward methanol oxidation and hydrogen evolution reaction compared with commercial Pt/C or self-synthesized platinum nanoparticles-loaded graphene. The superior catalytic performance of Pt/NG are discussed, and ascribed to the well-dispersed Pt nanoparticles and abundant edge plane sites on N-graphene. The resultant Pt/NG with high catalytic properties and cost-effective may emerge as a promising high-performance catalyst for fuel cells.

  15. Fabrication and optimization of camptothecin loaded Eudragit S 100 nanoparticles by Taguchi L4 orthogonal array design

    PubMed Central

    Mahalingam, Manikandan; Krishnamoorthy, Kannan

    2015-01-01

    Introduction: The objective of this investigation was to design and optimize the experimental conditions for the fabrication of camptothecin (CPT) loaded Eudragit S 100. Nanoparticles, and to understand the effect of various process parameters on the average particles size, particle size uniformity and surface area of the prepared polymeric nanoparticles using Taguchi design. Materials and Methods: CPT loaded Eudragit S 100 nanoparticles were prepared by nanoprecipitation method and characterized by particles size analyzer. Taguchi orthogonal array design was implemented to study the influence of seven independent variables on three dependent variables. Eight experimental trials involving seven independent variables at higher and lower levels were generated by design expert. Results: Factorial design result has shown that (a) except, β-cyclodextrin concentration all other parameters do not significantly influenced the average particle size (R1); (b) except, sonication duration and aqueous phase volume, all other process parameters significantly influence the particle size uniformity; (c) all the process parameters does not significantly influence the surface area. Conclusion: The R1, particle size uniformity and surface area of the prepared drug-loaded polymeric nanoparticles were found to be 120 nm, 0.237 and 55.7 m2 /g and the results were good correlated with the data generated by the Taguchi design method. PMID:26258056

  16. Comparison of three different conjugation strategies in the construction of herceptin-bearing paclitaxel-loaded nanoparticles.

    PubMed

    Yu, Kongtong; Zhou, Yulin; Li, Yuhuan; Sun, Xiangshi; Sun, Fengying; Wang, Xinmei; Mu, Hongyan; Li, Jie; Liu, Xiaoyue; Teng, Lesheng; Li, Youxin

    2016-08-19

    Research on quantitatively controlling the ligand density on the surface of nanocarriers is in the frontier and becomes a technical difficulty for targeted delivery system designing. In this study, we developed an improved pre-conjugation (Imp) strategy, in which herceptin as a ligand was pre-conjugated with DSPE-PEG2000-Mal via chemical cross-linking, followed by conjugation onto the surface of pre-prepared paclitaxel-loaded PLGA/DODMA nanoparticles (PDNs) through hydrophobic interaction and electrostatic attraction for paclitaxel delivery. Compared with the post-conjugation (Pos) strategy, in which the ligand was conjugated onto the nanoparticle surface after the preparation of the nanoparticles, it realized a precise control targeting effect via adjustment of the herceptin density on the surface of the nanoparticles. Within the range of 0-20% of DSPE-PEG2000-herceptin in the blend, it showed a linear relation with the ligand density on the surface of the nanoparticles. The Imp strategy protected the bioactivity of the ligand during the preparation of nanoparticles. At the same time it avoided the waste of an excess amount of herceptin to drive the conjugation reaction in comparison with the post-conjugation (Pos) strategy. The nanoparticles from the Imp strategy showed much better cytotoxicity (p < 0.001), tumor targeting and cellular uptake efficiency (p < 0.001) than that of the other strategies in BT474 cells, in which BT474 cells were HER2 receptor over-expression breast cancer cell lines. A significant reduction in cellular uptake of the nanoparticles from the Imp strategy was observed in the presence of sucrose and cytochalasin D, indicating that clathrin-mediated and caveolae-dependent endocytosis was as a primary mechanism of cellular entry for these antibody-modified nanoparticles.

  17. The anti-tumor effect of p53 gene-loaded hydroxyapatite nanoparticles in vitro and in vivo

    NASA Astrophysics Data System (ADS)

    Zhao, Ruibo; Yang, Xinyan; Chen, Cen; Chen, Kan; Wang, Shibing; Xie, Chungang; Ren, Xiaoyuan; Kong, Xiangdong

    2014-04-01

    This research focused on anti-tumor effect of pEGFP-C1-p53 (p53) gene-loaded hydroxyapatite (HAp) nanoparticles in vitro and in vivo. Four kinds of HAp nanoparticles, spherical HAp nanoparticles (S-HAp, diameter: 50 nm), needle-like HAp nanoparticles (N-HAp, average length: 110 nm and width: 30 nm), rod-like HAp nanoparticles (R-HAp, average length: 100 nm and width: 30 nm), and short-rod-like HAp nanoparticles (SR-HAp, average length: 40 nm and width: 30 nm), were prepared initially. The HAp nanoparticles with or without being modified by PEI (named HAp and HAp-PEI, respectively) have excellent biocompatibility as shown by MTT assay and crystal violet staining tests. Then, the subsequent MTT, Hocehst staining tests, and Western blot showed that the killing effect of p53-loaded HAp-PEI (HAp-PEI-p53) was effective with fair selectivity toward Hep-3B and HuH-7 cells' cell lines. Moreover, HAp-PEI-p53 could inhibit the tumor growth in vivo, and the mechanism of tumor growth inhibition was verified by the hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, P53 protein immunohistochemistry, and transmission electron microscope of the tumor cell in vivo. We found that HAp-PEI-p53 has good anti-cancer effect in vitro and in vivo, especially for the S-HAp-PEI-p53. Tumor metastasis could be suppressed significantly by the S-HAp-PEI-p53 and N-HAp-PEI-p53 treatments by the in vivo imaging system. All these results lead to the conclusion that the particle sizes of HAp ranging from 100 to 200 nm are appropriate for cancer gene therapy and may be widely used in anti-cancer investigation.

  18. 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

  19. Leaching and antimicrobial properties of silver nanoparticles loaded onto natural zeolite clinoptilolite by ion exchange and wet impregnation.

    PubMed

    Missengue, Roland N M; Musyoka, Nicholas M; Madzivire, Godfrey; Babajide, Omotola; Fatoba, Ojo O; Tuffin, Marla; Petrik, Leslie F

    2016-01-28

    This study aimed to compare the leaching and antimicrobial properties of silver that was loaded onto the natural zeolite clinoptilolite by ion exchange and wet impregnation. Silver ions were reduced using sodium borohydride (NaBH4). The leaching of silver from the prepared silver-clinoptilolite (Ag-EHC) nanocomposite samples and their antimicrobial activity on Escherichia coli Epi 300 were investigated. It was observed that the percentage of silver loaded onto EHC depended on the loading procedure and the concentration of silver precursor used. Up to 87% of silver was loaded onto EHC by wet impregnation. The size of synthesized silver nanoparticles varied between 8.71-72.67 nm and 7.93-73.91 nm when silver was loaded by ion exchange and wet impregnation, respectively. The antimicrobial activity of the prepared nanocomposite samples was related to the concentration of silver precursor used, the leaching rate and the size of silver nanoparticles obtained after reduction. However, only in the case of the nanocomposite sample (Ag-WEHC) obtained after loading 43.80 ± 1.90 µg of Ag per gram zeolite through wet impregnation was the leaching rate lower than 0.1 mg L(-1) limit recommended by WHO, with an acceptable microbial killing effect.

  20. Surface enhanced fluorescence of anti-tumoral drug emodin adsorbed on silver nanoparticles and loaded on porous silicon

    NASA Astrophysics Data System (ADS)

    Hernandez, Margarita; Recio, Gonzalo; Martin-Palma, Raul J.; Garcia-Ramos, Jose V.; Domingo, Concepcion; Sevilla, Paz

    2012-07-01

    Fluorescence spectra of anti-tumoral drug emodin loaded on nanostructured porous silicon have been recorded. The use of colloidal nanoparticles allowed embedding of the drug without previous porous silicon functionalization and leads to the observation of an enhancement of fluorescence of the drug. Mean pore size of porous silicon matrices was 60 nm, while silver nanoparticles mean diameter was 50 nm. Atmospheric and vacuum conditions at room temperature were used to infiltrate emodin-silver nanoparticles complexes into porous silicon matrices. The drug was loaded after adsorption on metal surface, alone, and bound to bovine serum albumin. Methanol and water were used as solvents. Spectra with 1 μm spatial resolution of cross-section of porous silicon layers were recorded to observe the penetration of the drug. A maximum fluorescence enhancement factor of 24 was obtained when protein was loaded bound to albumin, and atmospheric conditions of inclusion were used. A better penetration was obtained using methanol as solvent when comparing with water. Complexes of emodin remain loaded for 30 days after preparation without an apparent degradation of the drug, although a decrease in the enhancement factor is observed. The study reported here constitutes the basis for designing a new drug delivery system with future applications in medicine and pharmacy.

  1. Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe Vera in glioma cells.

    PubMed

    K S, Joshy; Sharma, Chandra P; Kalarikkal, Nandakumar; Sandeep, K; Thomas, Sabu; Pothen, Laly A

    2016-09-01

    Zidovudine loaded solid lipid nanoparticles of stearic acid modified with Aloe Vera (AV) have been prepared via simple emulsion solvent evaporation method which showed excellent stability at room temperature and refrigerated condition. The nanoparticles were examined by Fourier transform infrared spectroscopy (FT-IR), which revealed the overlap of the AV absorption peak with the absorption peak of modified stearic acid nanoparticles. The inclusion of AV to stearic acid decreased the crystallinity and improved the hydrophilicity of lipid nanoparticles and thereby improved the drug loading efficacy of lipid nanoparticles. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) imaging revealed that, the average particle size of unmodified (bare) nanoparticles was 45.66±12.22nm and modified solid lipid nanoparticles showed an average size of 265.61±80.44nm. Solid lipid nanoparticles with well-defined morphology were tested in vitro for their possible application in drug delivery. Cell culture studies using C6 glioma cells on the nanoparticles showed enhanced growth and proliferation of cells without exhibiting any toxicity. In addition, normal cell morphology and improved uptake were observed by fluorescence microscopy images of rhodamine labeled modified solid lipid nanoparticles compared with unmodified nanoparticles. The cellular uptake study suggested that these nanoparticles could be a promising drug delivery system to enhance the uptake of antiviral drug by brain cells and it could be a suitable drug carrier system for the treatment of HIV.

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

    PubMed Central

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

    2015-01-01

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

  3. Antifungal activity of Zataria multiflora essential oil-loaded solid lipid nanoparticles in-vitro condition

    PubMed Central

    Nasseri, Mahboobeh; Golmohammadzadeh, Shiva; Arouiee, Hossein; Jaafari, Mahmoud Reza; Neamati, Hossein

    2016-01-01

    Objective(s): The aim of the present study was to prepare, characterize, and evaluate solid lipid nanoparticles (SLNs) containing Zataria multiflora essential oil (ZEO). Materials and Methods: In this study, Z. multiflora essential oil-loaded solid lipid nanoparticles (ZE-SLNs) were prepared to improve its efficiency in controlling some fungal pathogens. SLNs containing Z. multiflora essential oil were prepared by high shear homogenization and ultra sound technique. ZEO-SLNs contained 0.03% ZEO in 5% of lipid phase (Glyceryl monostearate-GMS and Precirol® ATO 5). Tween 80 and Poloxamer 188 (2.5% w/v) were used as surfactant in the aqueous phase. The antifungal efficacy of ZE-SLNs and ZEO was compared under in vitro conditions. Results: The particle size of ZE-SLNs was around 255.5±3 nm with PDI of 0.369±0.05 and zeta potential was about -37.8±0.8 mV. Encapsulation efficacy of ZE-SLNs in crystalline form was 84±0.92%. The results showed that the ZEO and ZE-SLNs had 54 and 79% inhibition on the growth of fungal pathogens, respectively. The minimum inhibitory concentration (MIC) under in vitro conditions for the ZEO on the fungal pathogens of Aspergillus ochraceus, Aspergillus niger, Aspergillus flavus, Alternaria solani, Rhizoctonia solani, and Rhizopus stolonifer was 300, 200, 300, 200, 200 and 200 ppm, respectively, for ZE-SLNs, it was 200, 200, 200, 100, 50 and 50 ppm. The antifungal efficacy of ZE-SLNs was significantly more than ZEO. Conclusion: Our results showed that the SLNs were suitable carriers for Z. multiflora essential oil in controlling the fungal pathogens and merits further investigation. PMID:27917280

  4. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile

    PubMed Central

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug’s pharmacokinetics related to the conventional formulation. Poly(lactide-co-glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs’ long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA–PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel’s pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs. PMID:28184163

  5. Nimesulide-loaded nanoparticles for the potential coadjuvant treatment of prostate cancer.

    PubMed

    Huerta, Concepción; Aberturas, María del Rosario; Molpeceres, Jesús

    2015-09-30

    Nimesulide (NS)-loaded nanoparticles (NPNS) were prepared from polylactide-co-glycolide (PLGA) and eventually coated with chitosan (NPNSCS). Nanoparticles (NP) were spherical with sizes 379 ± 59 nm for NPNS and 393 ± 66 nm for NPNSCS and zeta potentials of -15 ± 3 mV for NPNS to 10 ± 4 mV for NPNSCS, suggesting an efficient coating. Drug encapsulation rate was high (88 ± 5% and 83 ± 7% of added drug) for NPNS and NPNSCS, respectively. After NP washing and re-suspension, 98 ± 2% and 99 ± 1% of the drug initially entrapped remained associated to NP. NS was dispersed in amorphous state within the polymeric matrix. Two-fold dilution of NP with pH 7.4 PBS provoked no drug release. However, 30-40% NS was released after a 1/10 dilution. NPNSCS and NPNS diluted 1/100 reduced the encapsulated drug to around 30% and 70%, respectively. In contrast, 100% NS was released from NP under sink conditions in less than 2h. The permeability of free-NS (1-1.5 × 10(-5)cm/s) was compared with NPNS (NPNS = 6.4-8.1 × 10(-6)cm/s and NPNSCS = 5.5-7.0 × 10(-6)cm/s) using the PAMPA assay. The cytotoxicity of free-NS and NS in NP on model prostate cancer cells PC-3 and DU-145 showed the highest cytotoxic effect with NPNSCS on PC-3 cells (IC50 = 89 μM).

  6. Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance: performance and mechanism

    NASA Astrophysics Data System (ADS)

    Shen, Jianan; He, Qianjun; Gao, Yu; Shi, Jianlin; Li, Yaping

    2011-10-01

    Multidrug resistance (MDR) is one of the major obstacles for successful chemotherapy in cancer. One of the effective approaches to overcome MDR is to use nanoparticle-mediated drug delivery to increase drug accumulation in drug resistant cancer cells. In this work, we first report that the performance and mechanism of an inorganic engineered delivery system based on mesoporous silica nanoparticles (MSNs) loading doxorubicin (DMNs) to overcome the MDR of MCF-7/ADR (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The experimental results showed that DMNs could enhance the cellular uptake of doxorubicin (DOX) and increase the cell proliferation suppression effect of DOX against MCF-7/ADR cells. The IC50 of DMNs against MCF-7/ADR cells was 8-fold lower than that of free DOX. However, an improved effect of DOX in DMNs against MCF-7 cells (a DOX-sensitive cancer cell line) was not found. The increased cellular uptake and nuclear accumulation of DOX delivered by DMNs in MCF-7/ADR cells was confirmed by confocal laser scanning microscopy, and could result from the down-regulation of P-gp and bypassing the efflux action by MSNs themselves. The cellular uptake mechanism of DMNs indicated that the macropinocytosis was one of the pathways for the uptake of DMNs by MCF-7/ADR cells. The in vivo biodistribution showed that DMNs induced a higher accumulation of DOX in drug resistant tumors than free DOX. These results suggested that MSNs could be an effective delivery system to overcome multidrug resistance.

  7. Porosity and semipermeability of hemoglobin-loaded polymeric nanoparticles as potential blood substitutes.

    PubMed

    Sheng, Yan; Liu, Changsheng; Yuan, Yuan; Zhang, Xiaolan; Shan, Xiaoqian; Xu, Feng

    2009-11-01

    Porosity and semipermeability, allowing life-sustaining small molecules to penetrate, but hemoglobin (Hb) and other enzymes to cut off, predominantly affect the functionalities of the Hb-loaded polymeric nanoparticles (HbPNPs) as blood substitutes. In this article, HbPNPs formulated in the size range of 110-122 nm were prepared by a modified double-emulsion method with poly(lactic acid) (PLA)-based polymers. The influences of the main preparation conditions, including solvent composition, stirring speed, Hb concentration and polymer matrix, on the porosity were investigated in details. To evaluate the porosity of HbPNPs, a novel nondestructive testing method based on molecular weight cut-off (MWCO) was developed, and an effusion approach was applied to investigate the pore size in the particle shells with poly(ethylene glycol)s (PEGs) of different molecular weights (PEG200, PEG400, PEG600) as probes. Moreover, in vitro diffusion behaviors of ascorbic acid and reduced glutathione from HbPNPs fabricated with various polymer matrices were studied. The MWCO of HbPNPs by changing solvent composition, stirring speed, Hb concentration, and polymer composition varied from 200 to 600, especially the PEGylation of the polymer, which exhibited obvious influence on the MWCO of HbPNPs. Ascorbic acid with molecular weight 176.1 could diffuse into PEGylated nanoparticles with mPEG content of 5-30 wt % freely, while reduced glutathione with molecular weight 307.3 could not penetrate when mPEG content reached 30 wt %. These results suggest that the HbPNPs optimized with MWCO between 400 and 600 can facilitate the transport of all those life-sustaining small molecules.

  8. The effect of mechanical properties of iron oxide nanoparticle-loaded functional nano-carrier on tumor targeting and imaging.

    PubMed

    Choi, Won Il; Kim, Ja-Young; Heo, Seon U; Jeong, Yong Yeon; Kim, Young Ha; Tae, Giyoong

    2012-09-10

    To achieve a sufficient targeting efficiency and prolonged half-life in-vivo, the physicochemical parameters including size and surface chemistry of therapeutic and imaging agents should be controlled. In this study, we prepared an iron oxide nanoparticle (IONP)-loaded, functional nano-carrier with different loading contents to modulate the mechanical properties of the system, and compared the characteristics of tumor targeting and imaging in terms of loading contents of IONP. As a functional nano-carrier, chitosan-conjugated, Pluronic-based nano-carrier with useful properties such as long blood circulation, good tumor targeting, and easy loading of macromolecules was used. IONPs were efficiently encapsulated into the nano-carrier (high loading efficiency over 95%) and the mechanical properties of the IONP-loaded nano-carrier were controlled by varying the loading amount of IONP. The IONP-loaded nano-carrier with the higher loading content of IONP (40 wt.%) was significantly more rigid (over 2×) than those with lower loading contents of IONP (5 and 15 wt.%). Although the nano-carrier with the higher loading content of IONP showed more enhanced MR contrast effect with higher T(2) relaxivity and higher intracellular uptake in vitro, characteristics of in-vivo tumor targeting and MR cancer imaging were not good compared to that of the nano-carrrier with the lower loading contents of IONP. Since different loading contents did not affect other characteristics of the system (size, surface chemistry, and surface charge), the present result suggests that the mechanical properties (strength/flexibility) of nano-systems are also important factors to be controlled for targeted delivery and imaging.

  9. Comparison of pharmacokinetic profiles of PM02734 loaded lipid nanoparticles and cyclodextrins: in vitro and in vivo characterization.

    PubMed

    Estella-Hermoso de Mendoza, A; Calvo, P; Bishop, A; Avilés, P; Blanco-Prieto, M J

    2012-08-01

    PM02734 is a chemically synthesized depsipeptide derived from the marine kahalalides family with a broad spectrum of activity against solid tumors in vitro and in vivo, but presenting low bioavailability. In this work, solid lipid nanoparticles made of Precirol ATO 5 have been developed using a hot homogenization method followed by high shear homogenization and ultrasonication. These solid lipid nanoparticles show suitable size (around 150 nm) and encapsulation efficiency (nearly 70%) for the oral administration of the compound PM02734. A physical-chemical stability study was performed after 6 months of storage at different thermical conditions, concluding that solid lipid nanoparticles stored at 4 degrees C were more stable than solid lipid nanoparticles stored at 25 degrees C. The pharmacokinetic profile of drug-loaded solid lipid nanoparticles was also evaluated in Beagle dogs and compared with that of a cyclodextrin-based delivery system by means of AUC, C(max) and T(max) parameter estimation. Solid lipid nanoparticle based formulation provided a sustained release of the drug for a longer period of time than the cyclodextrins.

  10. On the mucoadhesive properties of chitosan-coated polycaprolactone nanoparticles loaded with curcumin using quartz crystal microbalance with dissipation monitoring.

    PubMed

    Mazzarino, Letícia; Coche-Guérente, Liliane; Labbé, Pierre; Lemos-Senna, Elenara; Borsali, Redouane

    2014-05-01

    Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) was used to investigate the mucoadhesive properties of nanoparticles decorated with low, medium and high molar mass chitosan (CS). Uncoated and chitosan-coated polycaprolactone (PCL) nanoparticles loaded with curcumin were prepared by nanoprecipitation method and characterized in terms of size, surface charge and drug content. The interactions between nanoparticles and mucin layer were monitored after the treatment of SAM-functionalized gold-coated quartz crystals with bovine submaxillary gland mucin (BSM). The results show that all investigated chitosan-coated nanoparticles adsorb onto the BSM layer, and the mass uptake was found to be independent of the chitosan molar mass. Uncoated nanoparticles showed, however, no affinity with BSM layer, confirming that the adsorption of colloidal systems occurs due to their decoration with chitosan. The adhesion is mainly attributed to electrostatic interactions between protonated amino groups of mucoadhesive chitosan and negatively charged groups of mucin. The results suggest that chitosan-coated nanoparticles are promising carriers for hydrophobic drugs delivery in the buccal mucosa.

  11. Drug co-loading and pH-sensitive release core-shell nanoparticles via layer-by-layer assembly.

    PubMed

    Tian, Liang; Yang, Jing; Ji, Feng; Liu, Yuxi; Yao, Fanglian

    2014-01-01

    Multifunctional core-shell nanoparticles are widely used for biomedical and catalytic applications. In this work, bilayers of chitosan (Cs) and phosphorylated polyvinyl alcohol (PPVA) were sequentially deposited on 3-Aminopropyltri-ethoxysilane-modified SiO2 nanoparticles via layer-by-layer electrostatic self-assembly. The good spherical shape and size distribution were observed by DLS and transmission electron microscope analysis. 7-Hydroxycoumarin (7-HC) and rhodamine B (RhB) as model drugs were loaded in the core and shell of the nanoparticles separately. Confocal laser scanning microscopy shows the core-shell structure of HC-SiO2(PPVA/Cs)n-RhB nanoparticles and the embedded location of 7-HC and RhB. The pH-sensitive release investigation of RhB indicates that the release profiles of RhB from HC-SiO2(PPVA/Cs)3PPVA-RhB core-shell nanoparticles are totally different at pH values of 2.0, 7.4, and 9.2. These results predict that the multifunctional nanoparticle SiO2(PPVA/Cs)n has a great potential for drug delivery.

  12. Fragility in dense suspensions

    NASA Astrophysics Data System (ADS)

    Mari, Romain; Cates, Mike

    Dense suspensions can jam under shear when the volume fraction of solid material is large enough. In this work we investigate the mechanical properties of shear jammed suspensions with numerical simulations. In particular, we address the issue of the fragility of these systems, i.e., the type of mechanical response (elastic or plastic) they show when subject to a mechanical load differing from the one applied during their preparation history.

  13. Development of Dorzolamide Loaded 6-O-Carboxymethyl Chitosan Nanoparticles for Open Angle Glaucoma

    PubMed Central

    Ahmed, Mohammed Hadi

    2013-01-01

    Chitosan (CS) is a biodegradable, biocompatible, and mucoadhesive natural polymer soluble in acidic pH only and can be irritating to the eye. Objective of the study was to synthesize water soluble 6-O-carboxymethyl (OCM-CS) derivative of CS, and to develop CS and OCM-CS nanoparticles (NPs) loaded with dorzolamide hydrochloride (DRZ). CS was reacted with monochloroacetic acid (MCA) for OCM-CS synthesis and was characterized by FT-IR, DSC, and 13C NMR. CS and OCM-CS NPs were prepared by ionic gelation method. Ocular irritation potential were evaluated and therapeutic efficacy was measured by reduction in intraocular pressure (IOP) in normotensive rabbits. Maximum yield was obtained when the ratio of water/isopropyl alcohol was 1/4 at 55°C. The FT-IR, DSC and 13C NMR confirmed the formation of an ether linkage between hydroxyl groups of CS and MCA. The particle size and zeta potential of optimised CSNPs was 250.3 ± 2.62 nm and +33.47 ± 0.723 mV, whereas those for OCM-CSNPs were 187.1 ± 2.72 nm and 30.87 ± 0.86 mV. The entrapment efficiency was significantly improved for OCM-CSNPs, compared to CSNPs. OCM-CSNPs had tailored drug release and improved bioavailability with reduction in pulse entry as compared to CSNPs. Hence, it can be concluded that DRZ loaded OCM-CSNPs would be better alternative option to available eye drops for glaucoma treatment. PMID:24222858

  14. Aloe-emodin loaded solid lipid nanoparticles: formulation design and in vitro anti-cancer study.

    PubMed

    Chen, Ruie; Wang, Shengpeng; Zhang, Jinming; Chen, Meiwan; Wang, Yitao

    2015-01-01

    Aloe-emodin (AE) is a promising anti-tumor candidate for its significant activity against various tumors such as lung cancer, hepatic cancer, breast cancer and so on. Nevertheless, AE is clinically limited due to its poor water solubility and low bioavailability. This study was designed to prepare AE-loaded solid lipid nanoparticles (AE-SLNs) in an attempt to improve the anti-cancer efficacy of AE. The AE-SLNs were prepared with optimized prescription using high pressure homogenization (HPH) technique. Ultimately, the AE-SLNs showed stable particle size at 88.9 ± 5.2 nm, ideal drug entrapment efficiency (EE) of 97.71 ± 0.5% and good stability with regard to zeta-potential as high as -42.8 mV. The in vitro release profiles revealed that AE achieved sustained release by loading into SLNs. Moreover, AE-SLNs showed significantly higher in vitro cytotoxicity against human breast cancer MCF-7 cells and human hepatoma HepG2 cells as compared to the AE solution, while they showed no significant toxicity on human mammary epithelial MCF-10A cells. Hoechst 33342 staining and Annexin V/PI double staining indicated that AE-SLNs induced higher apoptotic rates in MCF-7 cells. Further study elucidated that the improved anti-cancer efficacy may be attributed to the increased cellular uptake of AE. Based on these findings, we believe that the development of AE-SLNs is an effective way for improving the anti-cancer efficacy of AE.

  15. Development and analytical characterization of vitamin(s)-loaded chitosan nanoparticles for potential food packaging applications

    NASA Astrophysics Data System (ADS)

    Aresta, Antonella; Calvano, Cosima Damiana; Trapani, Adriana; Cellamare, Saverio; Zambonin, Carlo Giorgio; De Giglio, Elvira

    2013-04-01

    Most vitamins are well-known natural antioxidant agents which can be usefully employed for foods preservation to increase their shelf life. In the present study, we aimed to investigate the potential of vitamin-based chitosan nanoparticles (CSNPs) for novel food packaging application. In particular, Vitamin C- and/or E-loaded CSNPs were formulated following the ionic gelation technique and using sulfobutylether-β-cyclodextrin as cross-linking agent. The obtained CSNPs were characterized in terms of size and zeta potential measurements, leading to size range of 375-503 nm and zeta range values from +16.0 to +33.8 mV. At the solid-state, the same particles were subjected to X-ray photoelectron spectroscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy. Then, the antioxidant potential of the produced vitamin(s) nanoparticulate formulations has been evaluated through 1,1-diphenyl-2-picrylhydrazyl test, a rapid spectrophotometric assay. The standardized procedure was used on vitamin(s)-modified CSNPs systems to determine both the amount of active vitamin(s) loaded in CSNPs and their release performances by in vitro release studies. Of all, high vitamins association efficiency along with an improvement of their shelf life (also under light exposure up to 7 days) were achieved. Altogether, the results suggest that Vitamin E is available in a hydrophilic delivery system able to replace organic solvents usually used for the solubilization of this antioxidant agent. In conclusion, these nanocarriers represent a promising strategy for the co-administration of Vitamin E and Vitamin C in packaging materials intended for a better storage of hydrophilic and/or lipophilic food.

  16. A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles.

    PubMed

    Zariwala, M Gulrez; Elsaid, Naba; Jackson, Timothy L; Corral López, Francisco; Farnaud, Sebastien; Somavarapu, Satyanarayana; Renshaw, Derek

    2013-11-18

    Iron (Fe) loaded solid lipid nanoparticles (SLN's) were formulated using stearic acid and iron absorption was evaluated in vitro using the cell line Caco-2 with intracellular ferritin formation as a marker of iron absorption. Iron loading was optimised at 1% Fe (w/w) lipid since an inverse relation was observed between initial iron concentration and SLN iron incorporation efficiency. Chitosan (Chi) was included to prepare chitosan coated SLN's. Particle size analysis revealed a sub-micron size range (300.3±31.75 nm to 495.1±80.42 nm), with chitosan containing particles having the largest dimensions. As expected, chitosan (0.1%, 0.2% and 0.4% w/v) conferred a net positive charge on the particle surface in a concentration dependent manner. For iron absorption experiments equal doses of Fe (20 μM) from selected formulations (SLN-FeA and SLN-Fe-ChiB) were added to Caco-2 cells and intracellular ferritin protein concentrations determined. Caco-2 iron absorption from SLN-FeA (583.98±40.83 ng/mg cell protein) and chitosan containing SLN-Fe-ChiB (642.77±29.37 ng/mg cell protein) were 13.42% and 24.9% greater than that from ferrous sulphate (FeSO4) reference (514.66±20.43 ng/mg cell protein) (p≤0.05). We demonstrate for the first time preparation, characterisation and superior iron absorption in vitro from SLN's, suggesting the potential of these formulations as a novel system for oral iron delivery.

  17. Fabrication and Evaluation of Curcumin-loaded Nanoparticles Based on Solid Lipid as a New Type of Colloidal Drug Delivery System.

    PubMed

    Chen, J; Dai, W T; He, Z M; Gao, L; Huang, X; Gong, J M; Xing, H Y; Chen, W D

    2013-03-01

    Curcumin has very broad spectrum of biological activities; however, photodegradation, short half-life and low bioavailability have limited its clinical application. Curcumin-loaded solid lipid nanoparticles were studied to overcome these problems. The aim of this study was to optimize the best formulation on curcumin-loaded solid lipid nanoparticles. Emulsion-evaporation and low temperature-solidification technique was applied with monostearin as lipid carriers. The single factor analysis and orthogonal design were used to optimize formulation and various parameters were investigate. By the optimisation of a single factor analysis and orthogonal test, the particles size, polydispersity index, zeta potential, encapsulation efficiency and drug loading capacity of the optimised formulation were 99.99 nm, 0.158, -19.9 mV, 97.86%, and 4.35%, respectively. The differential scanning calorimetry and X-ray diffraction analysis results demonstrated new structure was formed in nanoparticles. The release kinetics in vitro demonstrated curcumin-loaded solid lipid nanoparticles can control drug release. These studies confirmed that curcumin-loaded solid lipid nanoparticles could be prepared successfully with high drug entrapment efficiency and loading capacity. Curcumin-loaded solid lipid nanoparticles may be a promising drug delivery system to control drug release and improve bioavailability.

  18. pACC1 peptide loaded chitosan nanoparticles induces apoptosis via reduced fatty acid synthesis in MDA-MB-231 cells

    NASA Astrophysics Data System (ADS)

    Kaliaperumal, Jagatheesh; Hari, Natarajan; Pavankumar, Padarthi; Elangovan, Namasivayam

    2016-06-01

    The development of formulations with therapeutic peptides has been restricted to poor cell penetration and in this attempt; we developed pACC1 peptide loaded chitosan nanoparticles. The prepared nanoparticles were characterized with FT-IR, XRD, SEM and TEM. In addition, the suitable formulation was evaluated for hemocompatibility, plasma stability and embryo toxicity using Danio rerio embryo model. The results showed that pACC1 peptide loaded chitosan nanoparticles were compatible with plasma. They possess sustained release pattern and also found to be safe up to 300 mg/L in embryo toxicity tests. Cytotoxicity assays with MDA-MB-231 cell lines suggested that, pACC1 peptide loaded chitosan nanoparticles were capable of enhanced cellular penetration and reduced palmitic acid content, which was confirmed by H1 NMR. Hence, these nanoparticles could be employed as excellent adjuvant therapeutics while treating solid tumors with multi-drug resistance.

  19. Characterization and anticancer potential of ferulic acid-loaded chitosan nanoparticles against ME-180 human cervical cancer cell lines

    NASA Astrophysics Data System (ADS)

    Panwar, Richa; Sharma, Asvene K.; Kaloti, Mandeep; Dutt, Dharm; Pruthi, Vikas

    2016-08-01

    Ferulic acid (FA) is a widely distributed hydroxycinnamic acid found in various cereals and fruits exhibiting potent antioxidant and anticancer activities. However, due to low solubility and permeability, its availability to biological systems is limited. Non-toxic chitosan-tripolyphosphate pentasodium (CS-TPP) nanoparticles (NPs) are used to load sparingly soluble molecules and drugs, increasing their bioavailability. In the present work, we have encapsulated FA into the CS-TPP NPs to increase its potential as a therapeutic agent. Different concentrations of FA were tested to obtain optimum sized FA-loaded CS-TPP nanoparticles (FA/CS-TPP NPs) by ionic gelation method. Nanoparticles were characterized by scanning electron microscopy, Fourier transformation infrared spectroscopy (FTIR), thermogravimetric analyses and evaluated for their anticancer activity against ME-180 human cervical cancer cell lines. The FTIR spectra confirmed the encapsulation of FA and thermal analysis depicted its degradation profile. A concentration-dependent relationship between FA encapsulation efficiency and FA/CS-TPP NPs diameter was observed. Smooth and spherical FA-loaded cytocompatible nanoparticles with an average diameter of 125 nm were obtained at 40 µM FA conc. The cytotoxicity of 40 µM FA/CS-TPP NPs against ME-180 cervical cancer cell lines was found to be higher as compared to 40 µM native FA. Apoptotic morphological changes as cytoplasmic remnants and damaged wrinkled cells in ME-180 cells were visualized using scanning electron microscopic and fluorescent microscopic techniques. Data concluded that chitosan enveloped FA nanoparticles could be exploited as an excellent therapeutic drug against cancer cells proliferation.

  20. Towards better modelling of drug-loading in solid lipid nanoparticles: Molecular dynamics, docking experiments and Gaussian Processes machine learning.

    PubMed

    Hathout, Rania M; Metwally, Abdelkader A

    2016-11-01

    This study represents one of the series applying computer-oriented processes and tools in digging for information, analysing data and finally extracting correlations and meaningful outcomes. In this context, binding energies could be used to model and predict the mass of loaded drugs in solid lipid nanoparticles after molecular docking of literature-gathered drugs using MOE® software package on molecularly simulated tripalmitin matrices using GROMACS®. Consequently, Gaussian processes as a supervised machine learning artificial intelligence technique were used to correlate the drugs' descriptors (e.g. M.W., xLogP, TPSA and fragment complexity) with their molecular docking binding energies. Lower percentage bias was obtained compared to previous studies which allows the accurate estimation of the loaded mass of any drug in the investigated solid lipid nanoparticles by just projecting its chemical structure to its main features (descriptors).

  1. Influence of surface passivation of 2-Methoxyestradiol loaded PLGA nanoparticles on cellular interactions, pharmacokinetics and tumour accumulation.

    PubMed

    Pillai, Gopikrishna J; Paul-Prasanth, Bindhu; Nair, Shantikumar V; Menon, Deepthy

    2017-02-01

    In the present work, 2-Methoxyestradiol [2ME2] loaded PLGA nanoparticles [NPs] were stabilized with Casein or poly(ethylene glycol) [PEG] and evaluated for its cellular interactions, pharmacokinetics and tumour accumulation. Surface stabilized PLGA nanoparticles prepared through a modified emulsion route possessed similar size, surface charge, drug loading and release characteristics. Particle-cell interactions as well as the anti-angiogenesis activity were similar for both nanoformulations in vitro. However, in vivo pharmacokinetics and tumour accumulation of the drug were substantially improved for the PEGylated nanoformulation. Reduced protein binding was observed for PEG stabilized PLGA NPs. Thus, it was demonstrated that nanoencapsulation of 2-ME2 within PEGylated PLGA nanocarrier could improve its half-life and plasma concentration and thereby increase the tumour accumulation.

  2. Influence of selected variables on fabrication of Triamcinolone acetonide loaded solid lipid nanoparticles for topical treatment of dermal disorders.

    PubMed

    Pradhan, Madhulika; Singh, Deependra; Singh, Manju Rawat

    2016-01-01

    Aim of the study was to develop solid lipid nanoparticles (SLN) of triamcinolone acetonide (TA) and to study the effect of various process variables in order to optimize the formulation for effective delivery. Drug loaded SLNs were successfully prepared and characterized by TEM, XRD and DSC study. Process variables like surfactant concentration, drug concentration, lipid concentration etc. showed significant effect on the particle size and entrapment efficiency. SLNs exhibited prolonged drug release following Higuchi release kinetics (R(2) = 0.9909). In vitro skin distribution study demonstrated systemic escape of drug from TA loaded SLNs which might eliminate side effects associated with systemic exposure.

  3. Formulation and comparative in vitro evaluation of various dexamethasone-loaded pH-sensitive polymeric nanoparticles intended for dermal applications.

    PubMed

    Sahle, Fitsum Feleke; Gerecke, Christian; Kleuser, Burkhard; Bodmeier, Roland

    2017-01-10

    pH-sensitive nanoparticles have a great potential for dermal and transfollicular drug delivery. In this study, pH-sensitive, dexamethasone-loaded Eudragit(®) L 100, Eudragit(®) L 100-55, Eudragit(®) S 100, HPMCP-50, HPMCP-55 and cellulose acetate phthalate nanoparticles were prepared by nanoprecipitation and characterized. The pH-dependent swelling, erosion, dissolution and drug release kinetics were investigated in vitro using dynamic light scattering and Franz diffusion cells, respectively. Their toxicity potential was assessed by the ROS and MTT assays. 100-700nm nanoparticles with high drug loading and entrapment efficiency were obtained. The nanoparticles bear no toxicity potential. Cellulose phthalates nanoparticles were more sensitive to pH than acrylates nanoparticles. They dissolved in 10mM pH 7.5 buffer and released>80% of the drug within 7h. The acrylate nanoparticles dissolved in 40mM pH 7.5 buffer and released 65-70% of the drug within 7h. The nanoparticles remained intact in 10 and 40mM pH 6.0 buffers (HPMCP nanoparticles dissolved in 40mM pH 6.0 buffer) and released slowly. The nanoparticles properties could be modulated by blending the different polymers. In conclusion, various pH-sensitive nanoparticles that could release differently on the skin surface and dissolve and release in the hair follicles were obtained.

  4. Insight into the impact of ZnO nanoparticles on aerobic granular sludge under shock loading.

    PubMed

    He, Qiulai; Yuan, Zhe; Zhang, Jing; Zhang, Shilu; Zhang, Wei; Zou, Zhuocheng; Wang, Hongyu

    2017-04-01

    The increasing use of zinc oxide nanoparticles (ZnO NPs) has raised concerns about the environmental threats to the wastewater treatment systems. Shock loading of 10, 50 and 100 mg/L ZnO NPs was conducted to evaluate impacts on reactor performance, microbial activities and extracellular polymeric substances (EPS) in parent aerobic/oxic/anoxic (A/O/A) granular sequencing batch reactors (SBRs). The results showed that ZnO NPs caused inhibition to nitrogen transformations due to acute toxicity to nitrification and denitrification. However, phosphorus removal remained unaffected by the exposure to ZnO NPs. Besides, ZnO NPs significantly enhanced the oxygen respiration rate and caused acute toxicity to ammonia oxidizing rate (10.40-35.21%), phosphorus release rate (37.79-19.80%), aerobic phosphorus uptake rate (36.95-20.69%) and total phosphorus uptake rate (32.77-16.91%) of aerobic granules. ZnO NPs stimulated the secretion of EPS, especially the content of protein (PN), which could relieve the toxicity of ZnO NPs.

  5. Near-infrared dye-loaded magnetic nanoparticles as photoacoustic contrast agent for enhanced tumor imaging

    PubMed Central

    Gao, Chuang; Deng, Zi-Jian; Peng, Dong; Jin, Yu-Shen; Ma, Yan; Li, Yan-Yan; Zhu, Yu-Kun; Xi, Jian-Zhong; Tian, Jie; Dai, Zhi-Fei; Li, Chang-Hui; Liang, Xiao-Long

    2016-01-01

    Objective: Photoacoustic (PA) tomography (PAT) has attracted extensive interest because of its optical absorption contrast and ultrasonic detection. This study aims to develop a biocompatible and biodegradable PA contrast agent particularly promising for clinical applications in human body. Methods: In this study, we presented a PA contrast agent: 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine- N-[methoxy (polyethylene glycol)] (DSPE-PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles (NPs) loaded with indocyanine green (ICG). We used ICG and SPIO NPs because both drugs are approved by the U.S. Food and Drug Administration. Given the strong absorption of near-infrared laser pulses, SPIO@DSPE-PEG/ICG NPs with a uniform diameter of ~28 nm could significantly enhance PA signals. Results: We demonstrated the contrast enhancement of these NPs in phantom and animal experiments, in which the in vivo circulation time of SPIO@DSPE-PEG/ICG NPs was considerably longer than that of free ICG. These novel NPs also displayed a high efficiency of tumor targeting. Conclusions: SPIO@DSPE-PEG/ICG NPs are promising PAT contrast agents for clinical applications. PMID:27807502

  6. Preparation, characterization, and anti-tumor property of podophyllotoxin-loaded solid lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Zhu, R. R.; Qin, L. L.; Wang, M.; Wu, S. M.; Wang, S. L.; Zhang, R.; Liu, Z. X.; Sun, X. Y.; Yao, S. D.

    2009-02-01

    In an effort to develop an alternative formulation of podophyllotoxin suitable for drug release and delivery, podophyllotoxin-loaded solid lipid nanoparticles (PPT-SLNs) were constructed, characterized and examined for in vitro cytotoxicity and tumor inhibition. The SLNs were prepared by using a solvent emulsification-evaporation method, and their size was around 50 nm. TEM detection showed that the SLNs were homogeneous and spherical in shape, and differential scanning calorimetry (DSC) measurement revealed a new conformation of PPT-SLNs. An in vitro drug release study showed that PPT was released from the SLNs in a slow but time-dependent manner. Furthermore, the treatment of 293T and HeLa cells with PPT-SLNs demonstrated that PPT-SLNs were less toxic to normal cells and more effective in anti-tumor potency compared with unconjugated PPT. A colony forming efficiency assay showed an effective long-term cancer growth suppression of PPT-SLNs; in addition, they can also enhance the apoptotic and cellular uptake processes on tumor cells compared with PPT. These results collectively demonstrated that this SLN formulation has a potential application as an alternative delivery system for anti-tumor drugs.

  7. Ag nanoparticles loaded on porous graphitic carbon nitride with enhanced photocatalytic activity for degradation of phenol

    NASA Astrophysics Data System (ADS)

    Han, Zhenwei; Wang, Nan; Fan, Hai; Ai, Shiyun

    2017-03-01

    Highly efficient photocatalyst of visible-light-driven Ag nanoparticles loaded on porous graphitic carbon nitride (g-C3N4) was prepared by the reduction of Ag ions on porous g-C3N4. The obtained Ag/porous g-C3N4 composite products were characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM), UV-vis diffuse reflection spectra (DRS), thermal gravimetric analysis (TGA). The results demonstrated that a homogeneous distribution of Ag NPs of 10 nm was attached onto the surface of the porous g-C3N4. The prepared Ag/porous g-C3N4 samples were applied for catalyzing the degradation of phenol in water under visible light irradiation. Porous g-C3N4 demonstrated an excellent support for the formation and dispersion of small uniform Ag NPs. When the weight percentage of Ag reaches 5%, the nanohybrid exhibits superior photocatalytic activities compared to bulk g-C3N4, porous g-C3N4, and 2% Ag/porous g-C3N4 hybrids. The enhanced photocatalytic performance is due to the synergic effect between Ag and porous g-C3N4, which suppressed the recombination of photogenerated electron-hole pairs.

  8. Comparative biophysical properties of tenofovir-loaded, thiolated and nonthiolated chitosan nanoparticles intended for HIV prevention

    PubMed Central

    Meng, Jianing; Zhang, Tao; Agrahari, Vivek; Ezoulin, Miezan J; Youan, Bi-Botti C

    2014-01-01

    Aim This study is designed to test the hypothesis that tenofovir-loaded (an anti-HIV microbicide) chitosan–thioglycolic acid-conjugated (CS–TGA) nanoparticles (NPs) exhibit superior biophysical properties for mucoadhesion compared with those of native CS NPs. Materials & methods The NPs are prepared by ionotropic gelation. The particle mean diameter, encapsulation efficiency and release profile are analyzed by dynamic light scattering and UV spectroscopy, respectively. The cytotoxicity, cellular uptake and uptake mechanism are assessed on VK2/E6E7 and End1/E6E7 cell lines by colorimetry/fluorimetry, and percentage mucoadhesion is assessed using porcine vaginal tissue. Results The mean diameter of the optimal NP formulations ranges from 240 to 252 nm, with a maximal encapsulation efficiency of 22.60%. Tenofovir release from CS and CS–TGA NPs follows first-order and Higuchi models, respectively. Both NPs are noncytotoxic in 48 h. The cellular uptake, which is time dependent, mainly occurs via the caveolin-mediated pathway. The percentage of mucoadhesion of CS–TGA NPs is fivefold higher than that of CS NPs, and reached up to 65% after 2 h. Conclusion Collectively, CS–TGA NPs exhibit superior biophysical properties and can potentially maximize the retention time of a topical microbicide, such as tenofovir, intended for the prevention of HIV transmission. PMID:24405490

  9. Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers

    PubMed Central

    GUO, JUN; WU, SHU-HONG; REN, WEI-GUO; WANG, XIN-LI; YANG, AI-QING

    2015-01-01

    Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in men in western and most developing countries. Bicalutamide (BLT) is an antineoplastic hormonal agent primarily used in the treatment of locally advanced and metastatic prostate cancers. In the present study, the aim was to develop a nanotechnology-based delivery system to target prostate cancer cells. This involved the development of a BLT-loaded poly(D,L-lactide-co-glycolide) PLGA (PLGA-BLT) nanoparticulate system in an attempt to improve the therapeutic efficacy of BLT in prostate cancer and to mitigate its toxicity. Nanosized particles with a uniform size distribution and spherical shape were developed. PLGA-BLT showed a pronounced cytotoxic effect on LNCaP and C4-2 cancer cells. The superior cell-killing effect of the nanoparticles may be attributable to their sustained drug-release characteristics and high cellular internalization. PLGA-BLT was also found to significantly inhibit colony formation in the two cell lines. Furthermore, the caspase-3 activity of PLGA-BLT treated cancer cells was enhanced, indicating the cell apoptosis-inducing potential of PLGA-BLT. Overall, these results suggest that nanotechnology-based formulations of BLT exhibit superior anticancer activity and have enormous potential in the treatment of prostate cancers. PMID:26668633

  10. Sesamol-loaded solid lipid nanoparticles for treatment of skin cancer.

    PubMed

    Geetha, T; Kapila, Meenakshi; Prakash, Om; Deol, Parneet Kaur; Kakkar, Vandita; Kaur, Indu Pal

    2015-02-01

    Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN.

  11. Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers.

    PubMed

    Guo, Jun; Wu, Shu-Hong; Ren, Wei-Guo; Wang, Xin-Li; Yang, Ai-Qing

    2015-12-01

    Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in men in western and most developing countries. Bicalutamide (BLT) is an antineoplastic hormonal agent primarily used in the treatment of locally advanced and metastatic prostate cancers. In the present study, the aim was to develop a nanotechnology-based delivery system to target prostate cancer cells. This involved the development of a BLT-loaded poly(D,L-lactide-co-glycolide) PLGA (PLGA-BLT) nanoparticulate system in an attempt to improve the therapeutic efficacy of BLT in prostate cancer and to mitigate its toxicity. Nanosized particles with a uniform size distribution and spherical shape were developed. PLGA-BLT showed a pronounced cytotoxic effect on LNCaP and C4-2 cancer cells. The superior cell-killing effect of the nanoparticles may be attributable to their sustained drug-release characteristics and high cellular internalization. PLGA-BLT was also found to significantly inhibit colony formation in the two cell lines. Furthermore, the caspase-3 activity of PLGA-BLT treated cancer cells was enhanced, indicating the cell apoptosis-inducing potential of PLGA-BLT. Overall, these results suggest that nanotechnology-based formulations of BLT exhibit superior anticancer activity and have enormous potential in the treatment of prostate cancers.

  12. Long Circulating Lectin Conjugated Paclitaxel Loaded Magnetic Nanoparticles: A New Theranostic Avenue for Leukemia Therapy

    PubMed Central

    Singh, Abhalaxmi; Dilnawaz, Fahima; Sahoo, Sanjeeb Kumar

    2011-01-01

    Amongst all leukemias, Bcr-Abl positive chronic myelogenous leukemia (CML) confers resistance to native drug due to multi drug resistance and also resistance to p53 and fas ligand pathways. In the present study, we have investigated the efficacy of microtubule stabilizing paclitaxel loaded magnetic nanoparticles (pac-MNPs) to ascertain its cytotoxic effect on Bcr-Abl positive K562 cells. For active targeted therapy, pac-MNPs were functionalized with lectin glycoprotein which resulted in higher cellular uptake and lower IC50 value suggesting the efficacy of targeted delivery of paclitaxel. Both pac-MNPs and lectin conjugated pac-MNPs have a prolonged circulation time in serum suggesting increased bioavailability and therapeutics index of paclitaxel in vivo. Further, the molecular mechanism pertaining to pac-induced cytotoxicity was analyzed by studying the involvement of different apoptotic pathway proteins by immunoblotting and quantitative PCR. Our study revealed simultaneous activation of JNK pathway leading to Bcr-Abl instability and the extrinsic apoptotic pathway after pac-MNPs treatment in two Bcr-Abl positive cell lines. In addition, the MRI data suggested the potential application of MNPs as imaging agent. Thus our in vitro and in vivo results strongly suggested the pac-MNPs as a future prospective theranostic tool for leukemia therapy. PMID:22110595

  13. Development of abamectin loaded plant virus nanoparticles for efficacious plant parasitic nematode control.

    PubMed

    Cao, Jing; Guenther, Richard H; Sit, Tim L; Lommel, Steven A; Opperman, Charles H; Willoughby, Julie A

    2015-05-13

    Plant parasitic nematodes are one of the world's major agricultural pests, causing in excess of $157 billion in worldwide crop damage annually. Abamectin (Abm) is a biological pesticide with a strong activity against a wide variety of plant parasitic nematodes. However, Abm's poor mobility in the soil compromises its nematicide performance because of the limited zone of protection surrounding the growing root system of the plant. In this study, we manipulated Abm's soil physical chemistry by encapsulating Abm within the Red clover necrotic mosaic virus (RCNMV) to produce a plant virus nanoparticle (PVN) delivery system for Abm. The transmission electron microscopic and dynamic light scattering characterization of Abm-loaded PVN (PVN(Abm)) indicated the resultant viral capsid integrity and morphology comparable to native RCNMV. In addition, the PVN(Abm) significantly increased Abm's soil mobility while enabling a controlled release strategy for Abm's bioavailability to nematodes. As a result, PVN(Abm) enlarged the zone of protection from Meloidogyne hapla root knot nematodes in the soil as compared to treating with free Abm molecules. Tomato seedlings treated with PVN(Abm) had healthier root growth and a reduction in root galling demonstrating the success of this delivery system for the increased efficacy of Abm to control nematode damage in crops.

  14. Molybdenum-Loaded Anatase TiO2 Nanoparticles With Enhanced Optoelectronics Properties

    NASA Astrophysics Data System (ADS)

    Bargougui, R.; Bouazizi, N.; Ammar, S.; Azzouz, A.

    2017-01-01

    The structural, optical and electrical properties of molybdenum nanoparticles (Mo-NPs)-loaded anatase TiO2 were investigated using x-ray diffraction, UV-Vis diffuse reflectance, and Fourier transform infrared and complex impedance spectroscopy. x-ray diffraction showed that Mo-NPs incorporation induced a decrease in particle size from 30 nm to 21 nm of TiO2 and TiO2-Mo, respectively, producing a slight structure expansion. Mo-NPs dispersion resulted in a slight decrease in the optical band gap energy from 3.85 eV to 3.51 eV. Slight shifts towards higher wavelengths were attributed to the change in the acceptor capacity level induced by Mo-NPs. In addition, the ac impedance studies show the effect of Mo-NPs incorporation that appeared to be responsible for conductance of enhancement. The conduction mechanism is based on space charge-limited current via deep levels with different energy positions in the band gap. The temperature dependence of electrical properties showed that both capacitance and conductance of TiO2-Mo samples increased with increasing temperature. At low frequency, the relaxation phenomenon is related to the surface effect. The results will be beneficial to further developing titanium dioxide photo-catalysts.

  15. In vivo evaluation of curcumin-loaded nanoparticles in a A549 xenograft mice model.

    PubMed

    Yin, Hai-Tao; Zhang, De-Geng; Wu, Xiao-Li; Huang, Xin-En; Chen, Gang

    2013-01-01

    Curcumin (Cum) has been reported to have potential chemo-preventive and chemotherapeutic activity through influencing various processes, inducing cell cycle arrest, differentiation and apoptosis in a series of cancers. However, the poor solubility of Cum limits its further applications in the treatment of cancer. We have previously reported Cum-loaded nanoparticles (Cum-NPs) prepared with amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers. The current study demonstrated superior antitumor efficacy of Cum-NPs over free Cum in the treatment of lung cancer. In vivo evaluation further demonstrated superior anticancer effects of Cum-NPs by delaying tumor growth compared to free Cum in an established A549 transplanted mice model. Moreover, Cum-NPs showed little toxicity to normal tissues including bone marrow, liver and kidney at a therapeutic dose. These results suggest that Cum-NPs are effective to inhibit the growth of human lung cancer with little toxicity to normal tissues, and could provide a clinically useful therapeutic regimen. They thus merit more research to evaluate the feasibility of clinical application.

  16. Development of sulfadiazine-decorated PLGA nanoparticles loaded with 5-fluorouracil and cell viability.

    PubMed

    Guimarães, Pedro Pires Goulart; Oliveira, Sheila Rodrigues; de Castro Rodrigues, Gabrielle; Gontijo, Savio Morato Lacerda; Lula, Ivana Silva; Cortés, Maria Esperanza; Denadai, Ângelo Márcio Leite; Sinisterra, Rubén Dario

    2015-01-08

    The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide) (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR, elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized using transmission and scanning electron microscopy and dynamic light scattering. Additionally, the zeta potential, drug content, and in vitro 5-FU release were evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = -32.1 mV and the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU-PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs were found to both cancer cell lines when compared to normal cell lines, demonstrating that the presence of SUL could significantly enhance the cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the 5-FU antitumor formulation in the future.

  17. Preparation, characterization, and anticancer efficacy of evodiamine-loaded PLGA nanoparticles.

    PubMed

    Zou, Lidi; Chen, Fengqian; Bao, Jiaolin; Wang, Shengpeng; Wang, Lu; Chen, Meiwan; He, Chengwei; Wang, Yitao

    2016-01-01

    Evodiamine (EVO) is a plant-derived indolequinazoline alkaloid with potential anticancer activity. However, low bioavailability caused by its poor water solubility limits it anticancer efficacy in clinic. To enhance the solubility and improve the bioavailability of EVO, a delivery system based on poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with EVO (EVO-PLGA NPs) for treating breast cancer was prepared in this study. The physicochemical characterization and in vitro antitumor evaluation of EVO-PLGA NPs were determined. EVO-PLGA NPs could persistently control the release of EVO for 180 h. 3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl tetrazolium bromide (MTT) assessment and colony formation assay showed that EVO-PLGA NPs could enhance the toxicity and the proliferation inhibition effect of EVO on MCF-7 breast cancer cells. EVO-PLGA NPs did not strengthen G2/M arrest effect of EVO-treated cells after 24h incubation. Meanwhile, EVO-PLGA NPs could increase the expression of cyclin B1 and decrease the expression of β-actin. Taken together, these results suggested that -PLGA NPs is promising for improving anticancer efficacy of EVO in breast cancer therapy.

  18. Formulation and In vitro Interaction of Rhodamine-B Loaded PLGA Nanoparticles with Cardiac Myocytes

    PubMed Central

    Jonderian, Antranik; Maalouf, Rita

    2016-01-01

    This study aims to characterize rhodamine B (Rh B) loaded poly(D,L-lactide-co-glycolide; PLGA) nanoparticles (NPs) and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized NPs were about 184 nm, 0.19, 40% and -21.7 mV, respectively. In vitro release showed that 29% of the Rh B was released within the first 8 h. Scanning electron microscopy measurements performed on the optimized NPs showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on cardiac myocytes after 24 and 48 h of exposure with concentrations up to 200 μg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the 1st hours. Interestingly, our data show an increase in the NPs’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes. PMID:27999542

  19. NiCu Alloy Nanoparticle-Loaded Carbon Nanofibers for Phenolic Biosensor Applications.

    PubMed

    Li, Dawei; Lv, Pengfei; Zhu, Jiadeng; Lu, Yao; Chen, Chen; Zhang, Xiangwu; Wei, Qufu

    2015-11-20

    NiCu alloy nanoparticle-loaded carbon nanofibers (NiCuCNFs) were fabricated by a combination of electrospinning and carbonization methods. A series of characterizations, including SEM, TEM and XRD, were employed to study the NiCuCNFs. The as-prepared NiCuCNFs were then mixed with laccase (Lac) and Nafion to form a novel biosensor. NiCuCNFs successfully achieved the direct electron transfer of Lac. Cyclic voltammetry and linear sweep voltammetry were used to study the electrochemical properties of the biosensor. The finally prepared biosensor showed favorable electrocatalytic effects toward hydroquinone. The detection limit was 90 nM (S/N = 3), the sensitivity was 1.5 µA µM(-1), the detection linear range was 4 × 10(-7)-2.37 × 10(-6) M. In addition, this biosensor exhibited satisfactory repeatability, reproducibility, anti-interference properties and stability. Besides, the sensor achieved the detection of hydroquinone in lake water.

  20. Bevacizumab loaded solid lipid nanoparticles prepared by the coacervation technique: preliminary in vitro studies

    NASA Astrophysics Data System (ADS)

    Battaglia, Luigi; Gallarate, Marina; Peira, Elena; Chirio, Daniela; Solazzi, Ilaria; Giordano, Susanna Marzia Adele; Gigliotti, Casimiro Luca; Riganti, Chiara; Dianzani, Chiara

    2015-06-01

    Glioblastoma, the most common primary brain tumor in adults, has an inauspicious prognosis, given that overcoming the blood-brain barrier is the major obstacle to the pharmacological treatment of brain tumors. As neoangiogenesis plays a key role in glioblastoma growth, the US Food and Drug Administration approved bevacizumab (BVZ), an antivascular endothelial growth factor antibody for the treatment of recurrent glioblastoma in patients whose the initial therapy has failed. In this experimental work, BVZ was entrapped in solid lipid nanoparticles (SLNs) prepared by the fatty-acid coacervation technique, thanks to the formation of a hydrophobic ion pair. BVZ activity, which was evaluated by means of four different in vitro tests on HUVEC cells, increased by 100- to 200-fold when delivered in SLNs. Moreover, SLNs can enhance the permeation of fluorescently labelled BVZ through an hCMEC/D3 cell monolayer—an in vitro model of the blood brain barrier. These results are promising, even if further in vivo studies are required to evaluate the effective potential of BVZ-loaded SLNs in glioblastoma treatment.

  1. Long-term stability, biocompatibility and oral delivery potential of risperidone-loaded solid lipid nanoparticles.

    PubMed

    Silva, A C; Kumar, A; Wild, W; Ferreira, D; Santos, D; Forbes, B

    2012-10-15

    A solid lipid nanoparticles (SLN) formulation to improve the oral delivery of risperidone (RISP), a poorly water-soluble drug, was designed and tested. Initially, lipid-RISP solubility was screened to select the best lipid for SLN preparation. Compritol(®)-based formulations were chosen and their long-term stability was assessed over two years of storage (at 25 °C and 4 °C) by means of particle size, polydispersity index (PI), zeta potential (ZP) and encapsulation efficiency (EE) measurements. SLN shape was observed by transmission electron microscopy (TEM) at the beginning and end of the study. The oxidative potential (OP) of the SLN was measured and their biocompatibility with Caco-2 cells was evaluated using the (4,5-dimethylthiazol-2-yl)2,5-dyphenyl-tetrazolium bromide (MTT) assay. In vitro drug release and transport studies were performed to predict the in vivo release profile and to evaluate the drug delivery potential of the SLN formulations, respectively. The RISP-loaded SLN systems were stable and had high EE and similar shape to the placebo formulations before and after storage. Classical Fickian diffusion was identified as the release mechanism for RISP from the SLN formulation. Biocompatibility and dose-dependent RISP transport across Caco-2 cells were observed for the prepared SLN formulations. The viability of SLN as formulations for oral delivery of poorly water-soluble drugs such as RISP was illustrated.

  2. Cadmium telluride nanoparticles loaded on activated carbon as adsorbent for removal of sunset yellow.

    PubMed

    Ghaedi, M; Hekmati Jah, A; Khodadoust, S; Sahraei, R; Daneshfar, A; Mihandoost, A; Purkait, M K

    2012-05-01

    Adsorption is a promising technique for decolorization of effluents of textile dyeing industries but its application is limited due to requirement of high amounts of adsorbent required. The objective of this study was to assess the potential of cadmium telluride nanoparticles loaded onto activated carbon (CdTN-AC) for the removal of sunset yellow (SY) dye from aqueous solution. Adsorption studies were conducted in a batch mode varying solution pH, contact time, initial dye concentration, CdTN-AC dose, and temperature. In order to investigate the efficiency of SY adsorption on CdTN-AC, pseudo-first-order, pseudo-second-order, Elovich, and intra-particle diffusion kinetic models were studied. It was observed that the pseudo-second-order kinetic model fits better than other kinetic models with good correlation coefficient. Equilibrium data were fitted to the Langmuir model. Thermodynamic parameters such as enthalpy, entropy, activation energy, and sticking probability were also calculated. It was found that the sorption of SY onto CdTN-AC was spontaneous and endothermic in nature. The proposed adsorbent is applicable for SY removal from waste of real effluents including pea-shooter, orange drink and jelly banana with efficiency more than 97%.

  3. Spontaneous arrangement of a tumor targeting hyaluronic acid shell on irinotecan loaded PLGA nanoparticles.

    PubMed

    Giarra, Simona; Serri, Carla; Russo, Luisa; Zeppetelli, Stefania; De Rosa, Giuseppe; Borzacchiello, Assunta; Biondi, Marco; Ambrosio, Luigi; Mayol, Laura

    2016-04-20

    The arrangement of tumor targeting hyaluronic acid (HA) moieties on irinotecan (IRIN)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) has been directed by means of a gradient of lipophilicity between the oil and water phases of the emulsion used to produce the NPs. PLGA constitutes the NP bulk while HA is superficially exposed, with amphiphilic poloxamers acting as a bridge between PLGA and HA. Differential scanning calorimetry, zeta potential analyses and ELISA tests were employed to support the hypothesis of polymer assembly in NP formulations. The presence of flexible HA chains on NP surface enhances NP size stability over time due to an increased electrostatic repulsion between NPs and a higher degree of hydration of the device surface. IRIN in vitro release kinetics can be sustained up to 7-13 days. In vitro biologic studies indicated that HA-containing NPs were more toxic than bare PLGA NPs against CD44-overexpressing breast carcinoma cells (HS578T), therefore indicating their ability to target CD44 receptor.

  4. Cadmium telluride nanoparticles loaded on activated carbon as adsorbent for removal of sunset yellow

    NASA Astrophysics Data System (ADS)

    Ghaedi, M.; Hekmati Jah, A.; Khodadoust, S.; Sahraei, R.; Daneshfar, A.; Mihandoost, A.; Purkait, M. K.

    2012-05-01

    Adsorption is a promising technique for decolorization of effluents of textile dyeing industries but its application is limited due to requirement of high amounts of adsorbent required. The objective of this study was to assess the potential of cadmium telluride nanoparticles loaded onto activated carbon (CdTN-AC) for the removal of sunset yellow (SY) dye from aqueous solution. Adsorption studies were conducted in a batch mode varying solution pH, contact time, initial dye concentration, CdTN-AC dose, and temperature. In order to investigate the efficiency of SY adsorption on CdTN-AC, pseudo-first-order, pseudo-second-order, Elovich, and intra-particle diffusion kinetic models were studied. It was observed that the pseudo-second-order kinetic model fits better than other kinetic models with good correlation coefficient. Equilibrium data were fitted to the Langmuir model. Thermodynamic parameters such as enthalpy, entropy, activation energy, and sticking probability were also calculated. It was found that the sorption of SY onto CdTN-AC was spontaneous and endothermic in nature. The proposed adsorbent is applicable for SY removal from waste of real effluents including pea-shooter, orange drink and jelly banana with efficiency more than 97%.

  5. Mesoporous Silica Nanoparticles Loaded with Cisplatin and Phthalocyanine for Combination Chemotherapy and Photodynamic Therapy in vitro

    PubMed Central

    Vivero-Escoto, Juan L.; Elnagheeb, Maram

    2015-01-01

    Mesoporous silica nanoparticles (MSNs) have been synthesized and loaded with both aluminum chloride phthalocyanine (AlClPc) and cisplatin as combinatorial therapeutics for treating cancer. The structural and photophysical properties of the MSN materials were characterized by different spectroscopic and microscopic techniques. Intracellular uptake and cytotoxicity were evaluated in human cervical cancer (HeLa) cells by confocal laser scanning microscopy (CLSM) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays, respectively. The CLSM experiments showed that the MSN materials can be readily internalized in HeLa cells. The cytotoxic experiments demonstrated that, after light exposure, the combination of both AlClPc and cisplatin compounds in the same MSN platform potentiate the toxic effect against HeLa cells in comparison to the control AlClPc-MSN and cisplatin-MSN materials. These results show the potential of using MSN platforms as nanocarriers for combination photodynamic and chemotherapies to treat cancer. PMID:28347122

  6. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    NASA Astrophysics Data System (ADS)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun

    2016-01-01

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly ( d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion-solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet-Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100-150 nm. We compared the antibacterial effects of PQTs against Escherichia coli ( E. coli) and Micrococcus tetragenus ( M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application.

  7. Development and optimization of N-Acetylcysteine-loaded poly (lactic-co-glycolic acid) nanoparticles by electrospray.

    PubMed

    Karimi Zarchi, Ali Akbar; Abbasi, Shayan; Faramarzi, Mohammad Ali; Gilani, Kambiz; Ghazi-Khansari, Mahmoud; Amani, Amir

    2015-01-01

    N-Acetylcysteine (NAC) loaded PLGA nanoparticles were prepared by electrospray method. The influence of independent parameters such as concentration, flow rate and nozzle to collector distance was studied on particle size and size distribution of generated nanoparticles using a Box-Behnken experimental design. Smallest size was found to be obtained at minimum value for both flow rate and concentration of polymer, regardless of collecting distance value in the ranges studied. Additionally, the minimum value of size distribution was observed at lowest values of both concentration of polymer and collecting distance, regardless of flow rate value. In total, a sample with minimum size and polydispersity was predicted to have flow rate, polymer concentration and collecting distance values of 0.06(ml/h), 0.5(%w/w) and 9.28(cm), respectively. The experimentally prepared nanoparticles with lowest size and size distribution values, had a size of 122(nm) and size distribution of 24. Zeta potential, drug loading and encapsulation efficiency of optimized nanoparticles were -6.58, 5% and 54.5%, respectively.

  8. Galantamine-loaded solid-lipid nanoparticles for enhanced brain delivery: preparation, characterization, in vitro and in vivo evaluations.

    PubMed

    Misra, Shubham; Chopra, Kanwaljit; Sinha, V R; Medhi, Bikash

    2016-05-01

    Galantamine hydrobromide, a promising acetylcholinesterase inhibitor is reported to be associated with cholinergic side effects. Its poor brain penetration results in lower bioavailability to the target site. With an aim to overcome these limitations, solid-lipid nanoparticulate formulation of galantamine hydrobromide was developed employing biodegradable and biocompatible components. The selected galantamine hydrobromide-loaded solid-lipid nanoparticles offered nanocolloidal with size lower than 100 nm and maximum drug entrapment 83.42 ± 0.63%. In vitro drug release from these spherical drug-loaded nanoparticles was observed to be greater than 90% for a period of 24 h in controlled manner. In vivo evaluations demonstrated significant memory restoration capability in cognitive deficit rats in comparison with naive drug. The developed carriers offered approximately twice bioavailability to that of plain drug. Hence, the galantamine hydrobromide-loaded solid-lipid nanoparticles can be a promising vehicle for safe and effective delivery especially in disease like Alzheimer's.

  9. Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug-Loaded Magnetic Solid Lipid Nanoparticles.

    PubMed

    Grillone, Agostina; Riva, Eugenio Redolfi; Mondini, Alessio; Forte, Claudia; Calucci, Lucia; Innocenti, Claudia; de Julian Fernandez, Cesar; Cappello, Valentina; Gemmi, Mauro; Moscato, Stefania; Ronca, Francesca; Sacco, Rodolfo; Mattoli, Virgilio; Ciofani, Gianni

    2015-08-05

    Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its severe toxic side effects. The aim of this study is to develop sorafenib-loaded magnetic nanovectors able to enhance the drug delivery to the disease site with the help of a remote magnetic field, thus enabling cancer treatment while limiting negative effects on healthy tissues. Sorafenib and superparamagnetic iron oxide nanoparticles are encapsulated in solid lipid nanoparticles by a hot homogenization technique using cetyl palmitate as lipid matrix. The obtained nanoparticles (Sor-Mag-SLNs) have a sorafenib loading efficiency of about 90% and are found to be very stable in an aqueous environment. Plain Mag-SLNs exhibit good cytocompatibility, whereas an antiproliferative effect against tumor cells (human hepatocarcinoma HepG2) is observed for drug-loaded Sor-Mag-SLNs. The obtained results show that it is possible to prepare stable Sor-Mag-SLNs able to inhibit cancer cell proliferation through the sorafenib cytotoxic action, and to enhance/localize this effect in a desired area thanks to a magnetically driven accumulation of the drug. Moreover, the relaxivity properties observed in water suspensions hold promise for Sor-Mag-SLN tracking through clinical magnetic resonance imaging.

  10. Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization.

    PubMed

    Harsha, Sree

    2013-01-01

    Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology--the Büchi Nano Spray Dryer B-90 - and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm(3). In vitro drug release of formulations was best fitted by first-order and Peppas models with R (2) of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25 °C ± 2 °C and 60% ± 5% relative humidity.

  11. Preparation and characterization of gold nanoparticles and nanowires loaded into rod-shaped silica by a one-step procedure

    NASA Astrophysics Data System (ADS)

    Mnasri, Najib; Nyalosaso, Jeff L.; Kachbouri, Sana; Zajac, Jerzy; Elaloui, Elimame; Charnay, Clarence

    2017-01-01

    Rod-shaped mesoporous silica nanoparticles (RMSN) with built-in gold nanoparticles or thin gold nanowires in the pore channels were in situ synthesized via a one-step procedure. The insertion of a hydrophobic gold precursor into the mesopores of RMSN was reached through a micellar solubilization mechanism and gold nanoparticles were achieved through a thermal reduction. The resulting RMSN and Au-RMSN samples were characterized by using X-ray diffraction, transmission and scanning microscopies (TEM and SEM), X-ray photoelectron spectroscopy (XPS), nitrogen physisorption and solid-state Nuclear Magnetic Resonance (NMR). The interaction of Au precursor (a carbene complex) with the thiol group at the silica surface was identified and found to play a crucial role in the dispersion of the uniform metal nanoparticles at the internal surface of RMSN. Moreover, TEM micrographs revealed the absence of large gold particles outside the mesopore network. The shape of Au nanoparticles and their loading amount in the mesoporous silica could be easily tuned by altering the concentration of gold precursor.

  12. 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.

  13. Pharmaceutical suspension containing both immediate/sustained-release amoxicillin-loaded gelatin nanoparticles: preparation and in vitro characterization

    PubMed Central

    Harsha, Sree

    2013-01-01

    Pharmaceutical suspension containing oral dosage forms delivering both immediate-release and sustained-release amoxicillin was developed as a new dosage form to eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able to bind with the mucosal membrane after delivery to the stomach and could escalate the effectiveness of a drug, providing dual release. The objective of this study was to develop amoxicillin nanoparticles using innovative new technology – the Büchi Nano Spray Dryer B-90 – and investigate such features as drug content, particle morphology, yield, in vitro release, flow properties, and stability. The nanoparticles had an average particle size of 571 nm. The drug content and percentage yield was 89.2% ± 0.5% and 93.3% ± 0.6%, respectively. Angle of repose of nanoparticle suspension was 26.3° and bulk density was 0.59 g/cm3. In vitro drug release of formulations was best fitted by first-order and Peppas models with R2 of 0.9841 and 0.9837 respectively; release profile was 15.9%, while; for the original drug, amoxicillin, under the same conditions, 90% was released in the first 30 minutes. The nanoparticles used in this study enabled sustained release of amoxicillin over an extended period of time, up to 12 hours, and were stable for 12 months under accelerated storage conditions of 25°C ± 2°C and 60% ± 5% relative humidity. PMID:24101859

  14. Nanotechnology in oncology: Characterization and in vitro release kinetics of cisplatin-loaded albumin nanoparticles: Implications in anticancer drug delivery

    PubMed Central

    Das, Saikat; Jagan, Lavanya; Isiah, Rajesh; Rajesh, B.; Backianathan, Selvamani; Subhashini, J.

    2011-01-01

    Context: Nanotechnology is an empowering technology that holds promise in cancer therapeutics by increasing the ratio of tumor control probability to normal tissue complication probability. It can increase the bioavailability of the drug at the target site, reduce the frequency of administration and reach otherwise lesser-accessible sites. The present study shows the feasibility of the cisplatin-loaded albumin nanoparticle as a sustained delivery system. Aims: Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of malignant disorders. Conventional cisplatin formulation given as intravenous infusion has low bioavailability to the target organ in addition to significant side-effects, like ototoxicity and nephrotoxicity. The aim of this study was to develop a protein-based nanoparticulate system for sustained release of cisplatin. Materials and Methods: Nanoparticles were prepared by the coacervaton method of microcapsulation and chemical cross-linking with glutaraldehyde. Particle size was characterized by dynamic light scattering and transmission electron microscopy. Results and Conclusions: Using the coacervation method, nanoparticles of less than 70 nm diameter were produced. Drug encapsulation measured by ultraviolet spectroscopy varied from 30% to 80% for different ratios of cisplatin and protein. In vitro release kinetics shows that the nanoparticle-based formulation has biphasic release kinetics and is capable of sustained release compared with the free drug (80% release in 45 h). The study proves the feasibility of the albumin-based cisplatin nanoparticle formulation as a sustained release vehicle of cisplatin. PMID:21844995

  15. 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.

  16. Polylactide-based Paclitaxel-loaded Nanoparticles Fabricated by Dispersion Polymerization: Characterization, Evaluation in Cancer Cell Lines, and Preliminary Biodistribution Studies

    PubMed Central

    Adesina, Simeon K.; Holly, Alesia; Kramer-Marek, Gabriela; Capala, Jacek; Akala, Emmanuel O.

    2015-01-01

    The macromonomer method was used to prepare crosslinked, paclitaxel-loaded polylactide-polyethylene glycol (stealth) nanoparticles using free-radical dispersion polymerization. The method can facilitate the attachment of other molecules to the nanoparticle surface to make it multifunctional. Proton NMR and FT-IR spectra confirm the synthesis of polylactide macromonomer and crosslinking agent. Formation of stealth nanoparticles was confirmed by scanning and transmission electron microscopy. The drug release isotherm of paclitaxel-loaded nanoparticles shows that the encapsulated drug is released over 7 days. In vitro cytotoxicity assay in selected breast and ovarian cancer cell lines reveal that the blank nanoparticle is biocompatible compared to medium-only treated controls. In addition, the paclitaxel-loaded nanoparticles exhibit similar cytotoxicity compared to paclitaxel in solution. Confocal microscopy reveals that the nanoparticles are internalized by MCF-7 breast cancer cells within one hour. Preliminary biodistribution studies also show nanoparticle accumulation in tumour xenograft model. The nanoparticles are suitable for the controlled delivery of bioactive agents. PMID:24961596

  17. Genistein-loaded nanoparticles of star-shaped diblock copolymer mannitol-core PLGA-TPGS for the treatment of liver cancer.

    PubMed

    Wu, Binquan; Liang, Yong; Tan, Yi; Xie, Chunmei; Shen, Jin; Zhang, Mei; Liu, Xinkuang; Yang, Lixin; Zhang, Fujian; Liu, Liang; Cai, Shuyu; Huai, De; Zheng, Donghui; Zhang, Rongbo; Zhang, Chao; Chen, Ke; Tang, Xiaolong; Sui, Xuemei

    2016-02-01

    The purpose of this research is to develop nanoparticles (NPs) of star-shaped copolymer mannitol-functionalized PLGA-TPGS for Genistein delivery for liver cancer treatment, and evaluate their therapeutic effects in liver cancer cell line and hepatoma-tumor-bearing nude mice in comparison with the linear PLGA nanoparticles and PLGA-TPGS nanoparticles. The Genistein-loaded M-PLGA-TPGS nanoparticles (MPTN), prepared by a modified nanoprecipitation method, were observed by FESEM and TEM to be near-spherical shape with narrow size distribution. The nanoparticles were further characterized in terms of their size, size distribution, surface charge, drug-loading content, encapsulation efficiency and in vitro drug release profiles. The data showed that the M-PLGA-TPGS nanoparticles were found to be stable, showing almost no change in particle size and surface charge during 3-month storage of their aqueous solution. In vitro Genistein release from the nanoparticles exhibited biphasic pattern with burst release at the initial 4days and sustained release afterwards. The cellular uptake efficiency of fluorescent M-PLGA-TPGS nanoparticles was 1.25-, 1.22-, and 1.29-fold higher than that of the PLGA-TPGS nanoparticles at the nanoparticle concentrations of 100, 250, and 500μg/mL, respectively. In the MPTN group, the ratio of apoptotic cells increased with the drug dose increased, which exhibited dose-dependent effect and a significant difference compared with Genistein solution group (p<0.05). The data also showed that the Genistein-loaded M-PLGA-TPGS nanoparticles have higher antitumor efficacy than that of linear PLGA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, the star-shaped copolymer M-PLGA-TPGS could be used as a potential and promising bioactive material for nanomedicine development for liver cancer treatment.

  18. Preparation and in vitro/in vivo characterization of enteric-coated nanoparticles loaded with the antihypertensive peptide VLPVPR.

    PubMed

    Sun, Haiyan; Liu, Dong; Li, Yan; Tang, Xuwei; Cong, Yanli

    2014-01-01

    Our previous study revealed that the peptide Val-Leu-Pro-Val-Pro-Arg (VLPVPR), which was prepared using deoxyribonucleic acid recombinant technology, effectively decreased the blood pressure of spontaneous hypertensive rats; however, the effect only lasts 6 hours, likely due to its low absorption in the gastrointestinal tract. To overcome this problem, the purpose of this study was to characterize (methoxy-polyethylene glycol)-b-poly(D,L-lactide-co-glycolide)-b-poly(L-lysine) nanoparticles as in vitro and in vivo carriers for the effective delivery of VLPVPR. In our study, the VLPVPR nanoparticles were prepared using a double emulsion method, coated with Eudragit S100, and freeze-dried to produce enteric-coated nanoparticles. The optimized parameters from the double emulsion method was obtained from orthogonal experiments, including drug loading (DL) and encapsulated ratio (ER) at 6.12% and 86.94%, respectively, and the average particle size was below 100 nm. The release experiment demonstrated that the nanoparticles were sensitive to pH: almost completely released at pH 7.4 after 8 hours, but demonstrated much less release at pH 4.5 or pH 1.0 in the same amount of time. Therefore, the nanoparticles are suitable for enteric release. In vivo compared with the untreated group, the medium and high doses of orally administered VLPVPR nanoparticles reduced blood pressure for more than 30 hours, demonstrating that these nanoparticles have long-lasting and significant antihypertensive effects in spontaneously hypertensive rats.

  19. Diphtheria toxoid loaded poly-(epsilon-caprolactone) nanoparticles as mucosal vaccine delivery systems.

    PubMed

    Singh, Jasvinder; Pandit, Sreenivas; Bramwell, Vincent W; Alpar, H Oya

    2006-02-01

    Poly-(epsilon-caprolactone) (PCL), a poly(lactide-co-glycolide) (PLGA)-PCL blend and co-polymer nanoparticles encapsulating diphtheria toxoid (DT) were investigated for their potential as a mucosal vaccine delivery system. The nanoparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method, demonstrated release profiles which were dependent on the properties of the polymers. An in vitro experiment using Caco-2 cells showed significantly higher uptake of PCL nanoparticles in comparison to polymeric PLGA, the PLGA-PCL blend and co-polymer nanoparticles. The highest uptake mediated by the most hydrophobic nanoparticles using Caco-2 cells was mirrored in the in vivo studies following nasal administration. PCL nanoparticles induced DT serum specific IgG antibody responses significantly higher than PLGA. A significant positive correlation between hydrophobicity of the nanoparticles and the immune response was observed following intramuscular administration. The positive correlation between hydrophobicity of the nanoparticles and serum DT specific IgG antibody response was also observed after intranasal administration of the nanoparticles. The cytokine assays showed that the serum IgG antibody response induced is different according to the route of administration, indicated by the differential levels of IL-6 and IFN-gamma. The nanoparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-6 and IFN-gamma.

  20. Novel curcumin-loaded human serum albumin nanoparticles surface functionalized with folate: characterization and in vitro/vivo evaluation

    PubMed Central

    Song, Zhiwang; Lu, Yonglin; Zhang, Xia; Wang, Haiping; Han, Junyi; Dong, Chunyan

    2016-01-01

    Folate-conjugated, curcumin-loaded human serum albumin nanoparticles (F-CM-HSANPs) were obtained by the chemical conjugation of folate to the surface of the curcumin (CM)-loaded human serum albumin nanoparticles (NPs). The NPs were characterized by various parameters, including size, polydispersity, zeta potential, morphology, encapsulation efficiency, and drug release profile. The mean particle size of F-CM-HSANPs was 165.6±15.7 nm (polydispersity index <0.28), and the average encapsulation efficiency percentage and drug loading percentage of the F-CM-HSANPs were 88.7%±4.8% and 7.9%±0.4%, respectively. Applied in vitro, the CM NPs, after conjugation with folate, maintained sustained release, and a faster release of CM was more visibly observed than the unconjugated NPs. F-CM-HSANPs can prolong the retention time of CM significantly in vivo. However, after intravenous injection of F-CM-HSANPs, the pharmacokinetic parameters of CM were not significantly different from those of CM-loaded human serum albumin NPs. The improved antitumor activity of F-CM-HSANPs may be attributable to the protection of drug from enzymatic deactivation followed by the selective localization at the desired site. These results suggest that the intravenous injection of F-CM-HSANPs is likely to have an advantage in the current clinical CM formulation, because it does not require the use of a solubilization agent and it is better able to target the tumor tissue. PMID:27574403

  1. Cyclosporine-loaded solid lipid nanoparticles (SLN): drug-lipid physicochemical interactions and characterization of drug incorporation.

    PubMed

    Müller, R H; Runge, S A; Ravelli, V; Thünemann, A F; Mehnert, W; Souto, E B

    2008-03-01

    Solid lipid nanoparticles (SLN) were produced loaded with cyclosporine A in order to develop an improved oral formulation. In this study, the particles were characterized with regard to the structure of the lipid particle matrix, being a determining factor for mode of drug incorporation and drug release. Differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS) measurements were employed for the analysis of the polymorphic modifications and mode of drug incorporation. Particles were produced using Imwitor 900 as lipid matrix (the suspension consisted of 10% particles, 8% Imwitor 900, 2% cyclosporine A), 2.5% Tagat S, 0.5% sodium cholate and 87% water. DSC and WAXS were used to analyse bulk lipid, bulk drug, drug incorporated in the bulk and unloaded and drug-loaded SLN dispersions. The processing of the bulk lipid into nanoparticles was accompanied by a polymorphic transformation from the beta to the alpha-modification. After production, the drug-free SLN dispersions converted back to beta-modification, while the drug-loaded SLN stayed primarily in alpha-modification. After incorporation of cyclosporine A into SLN, the peptide lost its crystalline character. Based on WAXS data, it could be concluded that cyclosporine is molecularly dispersed in between the fatty acid chains of the liquid-crystalline alpha-modification fraction of the loaded SLN.

  2. In vivo pharmacokinetics and biodistribution of resveratrol-loaded solid lipid nanoparticles for brain delivery.

    PubMed

    Jose, S; Anju, S S; Cinu, T A; Aleykutty, N A; Thomas, S; Souto, E B

    2014-10-20

    Resveratrol is a potent anticancer. However, because of its low half-life (<0.25 h) the molecule is difficult to achieve the therapeutic concentration at the site of action. The aim of this work was to check the brain targeting ability of glyceryl behenate-based solid lipid nanoparticles (SLN) for resveratrol. SLN were prepared by solvent evaporation technique employing high speed homogenization followed by ultrasonication. SLN were designed at varying drug-lipid ratios (1:5, 1:9, 1:10, 1:11, 1:12 and 1:15) using Tween 80 or a combination of Tween 80 and polyvinyl alcohol (PVA) as surfactants. The mean particle size and zeta potential of the optimized formulation (drug-lipid ratio of 1:10) were 248.30 ± 3.80nm and -25.49 ± 0.49mV, respectively. The particle size and the encapsulation efficiency (EE) increased when varying the drug-lipid ratio from 1:5 to 1:15. Scanning electron microscopic (SEM) analysis showed that SLN were spherical in shape and had a smooth surface. The X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses revealed that the matrix of drug-loaded SLN was in disordered crystalline phase. The in vitro release study in phosphate buffer pH 7.4 followed a sustained release pattern. The drug release data was found to fit best into Higuchi kinetic model suggesting the diffusion controlled mechanism of drug release. The cytotoxicity assay (MAT) showed that SLN were equally effective (P<0.5) as free resveratrol, as an anti-tumor agent. The in vivo biodistribution study using Wistar rats demonstrated that SLN could significantly (P<0.001) increase the brain concentration of resveratrol (17.28 ± 0.6344 μg/g) as compared to free resveratrol (3.45 ± 0.3961 μg/g). The results showed that our resveratrol-loaded SLN serve as promising therapeutic systems to treat neoplastic diseases located in the brain tissue.

  3. Near-infrared imaging loaded polymeric nanoparticles: in vitro and in vivo studies

    NASA Astrophysics Data System (ADS)

    Lei, Tingjun; Manchanda, Romila; Huang, Yen-Chih; Fernandez-Fernandez, Alicia; Bunetska, Karina; Milera, Andrew; Sarmiento, Azael; McGoron, Anthony J.

    2013-02-01

    Introduction: Recent research has focused on developing new biomaterials for delivery of imaging agents and drugs. In our study, we report a new biocompatible and biodegradable polymer, termed poly(glycerol-co-malic-dodecanoate) (PGMD), which was then used for synthesis of nanoparticles (NPs) and loading of NIR dyes. Methods: The PGMD polymer was synthesized via thermal condensation method and was characterized by FTIR. The NPs were synthesized via o/w single emulsion technique. IR820 was chosen as the NIR dye. The loading efficiency of IR820 in PGMD NPs was measured by spectrophotometer. The release of IR820 was estimated with a spectrofluorometer in different pH phosphate buffered saline. The cytotoxicity of NPs was estimated through a Sulforhodamine B colorimetric assay. A biodistribution and pharmacokinetics study of the NPs versus free IR820 was performed in a murine model (n=12) after i.v. injection. Plasma samples were collected at time points 15-30-60 minutes and 24 hours. Organ samples were also collected and measured at the 24-hour time point. Results and Discussion: Void PGMD NPs and IR820-PGMD NPs had mean sizes around 90 nm and 110 nm, respectively. FTIR showed that polyester bonds were forming in the PGMD polymer. The release of IR820 was increased in acidic buffer (pH=5.0) as compared to neutral buffer (pH=7.4), indicating that the release of IR820 is controllable. Cellular uptake studies showed comparable fluorescence of IR820-PGMD NPs to free IR820 (5 μM) after 24-hour exposure. IR820-PGMD NPs induced significant cancer cell killing after laser exposure due to the photothermal effect of the dye. In vivo studies showed that the IR820 in NPs formulation has a longer plasma half-life than free IR820, providing longer imaging collection times for cancer diagnostics, and potentially widening the window for hyperthermia applications. Conclusion: We expect that ease of synthesis and good

  4. Characterization, pharmacokinetics, and hypoglycemic effect of berberine loaded solid lipid nanoparticles.

    PubMed

    Xue, Mei; Yang, Ming-xing; Zhang, Wei; Li, Xiu-min; Gao, De-hong; Ou, Zhi-min; Li, Zhi-peng; Liu, Su-huan; Li, Xue-jun; Yang, Shu-yu

    2013-01-01

    The high aqueous solubility, poor permeability, and absorption of berberine (BBR) result in its low plasma level after oral administration, which greatly limits its clinical application. BBR solid lipid nanoparticles (SLNs) were prepared to achieve improved bioavailability and prolonged effect. Developed SLNs showed homogeneous spherical shapes, small size (76.8 nm), zeta potential (7.87 mV), encapsulation efficiency (58%), and drug loading (4.2%). The power of X-ray diffraction combined with (1)H nuclear magnetic resonance spectroscopy was employed to analyze chemical functional groups and the microstructure of BBR-SLNs, and indicated that the drug was wrapped in a lipid carrier. Single dose (50 mg/kg) oral pharmacokinetic studies in rats showed significant improvement (P<0.05) in the peak plasma concentration, area under the curve, and variance of mean residence time of BBR-SLNs when compared to BBR alone (P<0.05), suggesting improved bioavailability. Furthermore, oral administration of both BBR and BBR-SLNs significantly suppressed body weight gain, fasting blood glucose levels, and homeostasis assessment of insulin resistance, and ameliorated impaired glucose tolerance and insulin tolerance in db/db diabetic mice. BBR-SLNs at high dose (100 mg/kg) showed more potent effects when compared to an equivalent dose of BBR. Morphologic analysis demonstrated that BBR-SLNs potentially promoted islet function and protected the islet from regeneration. In conclusion, our study demonstrates that by entrapping BBR into SLNs the absorption of BBR and its anti-diabetic action were effectively enhanced.

  5. Multivariate Optimization of Rizatriptan Benzoate-Loaded Solid Lipid Nanoparticles for Brain Targeting and Migraine Management.

    PubMed

    Girotra, Priti; Singh, Shailendra Kumar

    2017-02-01

    The present investigation aimed at development of brain-targeted rizatriptan benzoate-loaded solid lipid nanoparticles (RB-SLNs) by design of experiment, for improvement of its anti-migraine potential. Several formulation variables affecting the fabrication of RB-SLNs were screened using the Plackett-Burman design (PBD). The PBD results demonstrated lipid (Precirol® ATO 5) concentration, co-surfactant (Phospholipon® 90 H) concentration and temperature of lipid