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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. Engineering Tenofovir Loaded Chitosan Nanoparticles

    PubMed Central

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

    2011-01-01

    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 was 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. Drug release from medium (281 nm) and large size (602 nm)-sized NPs fitted the Higuchi (r2=0.991) and first-order release (r2=0.999) models, respectively. These NPs were not cytotoxic to both the vaginal epithelial cell line and Lactobacillus for 48 hours. When the diameter of the NPs decreased from 900 nm to 188 nm, the mucoadhesion increased from 6% to 12%. However, the combinatorial effect of EE% × 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. PMID:21704704

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Nanoparticle-Loaded Multifunctional Block Copolymer Micelles

    NASA Astrophysics Data System (ADS)

    Bae, Jinhye; Lawrence, Jimmy; Miesch, Caroline; Ribbe, Alexander; Li, Weikun; Emrick, Todd; Zhu, Jintao; Hayward, Ryan

    2012-02-01

    We have studied the incorporation of pre-synthesized hydrophobic inorganic nanoparticles within the cores of amphiphilic polystyrene-block-poly(ethylene oxide) (PS-PEO) diblock copolymer micelles formed through solvent-evaporation-induced interfacial instabilities of emulsion droplets. Using iron oxide, gold, and cadmium selenide nanoparticles coated with native alkane ligands, highly uniform encapsulation is obtained for cylindrical micelles, while spherical micelles can be enriched to ˜ 90 % of loaded micelles through simple magnetic or centrifugal purification steps. Multiple different types of nanoparticles can easily be incorporated into each micelle, yielding multi-functional micelles. The ability to encapsulate both spherical and rod-like particles of different core chemistries and sizes ranging from ˜ 1 to 20 nm, without the necessity of coating particles with specially designed ligands, makes this a versatile route to prepare hybrid micelle structures.

  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. Molecular dynamics of spherical nanoparticles in dense polymer melts.

    PubMed

    Patti, Alessandro

    2014-04-03

    By performing molecular dynamics simulations, we investigate the structural and dynamical properties of polymer melts containing probe spherical nanoparticles. Generally speaking, the behavior of these polymer nanocomposites is strongly affected by the interaction strength established between the nanoparticles and the chain monomers and by the nanoparticle sizes. We highlight that this dependence is not always evident and some intriguing properties, such as the heterogeneous dynamics of both polymer chains and nanoparticles and their nonGaussian behavior at short and long timescales, are not particularly influenced by the degree of attraction between nanoparticles and polymer for the range of interactions we study (up to 6 kBT). We find the existence of weakly ordered interdigitated structures with sequential arrangements of particles and polymer chains, which separate each other and hence inhibit the formation of nanoparticle clusters. This is especially evident with big nanoparticles, being less prone to aggregate than small ones, even when their interaction with the polymer chain is as low as 0.5 kBT. Moreover, by integrating the stress-tensor autocorrelation functions, we estimate the shear viscosity and determine its dependence on the strength of the polymer-nanoparticle interactions and on the nanoparticle size. By acting as plasticizers, small nanoparticles decrease the viscosity, especially at low-to-moderate interactions with the polymer. By contrast, big nanoparticles that establish strongly attractive interactions with the polymer chains behave as thickening agents and significantly increase the viscosity. This complex and perhaps still scantily understood balance between the geometry of nanoparticles and their interaction with the polymer is key to predict and fully control the macroscopic response of nanocomposite materials and hence suitably tailor their mechanical properties.

  13. 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

  14. 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

  15. 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.

  16. Characterization of ergocalciferol loaded solid lipid nanoparticles.

    PubMed

    Patel, Mandar R; San Martin-Gonzalez, M Fernanda

    2012-01-01

    The use of solid lipid nanoparticles (SLNs) is a technique that has been widely used in the pharmaceutical industry for the last 2 decades and has become of increasing interest to food scientists due to its potential for encapsulation and controlled release. Ergocalciferol (vitamin D₂) is a bioactive compound whose deficiency may lead to rickets in children and osteomalacia in adults. In this study, ergocalciferol was encapsulated in tripalmitin SLNs stabilized by polysorbate 20 (Tween 20). SLN dispersions (5% w/w) were prepared by hot homogenization technique using a nozzle-type high-pressure homogenizer. Ergocalciferol at 0%, 5%, 10%, 15%, and 20% (w/w of lipid) was dissolved in the molten lipid at 80 °C, mixed with a 5% (w/w) aqueous solution of polysorbate 20 and homogenized at 138 MPa at 80 °C. Particle size, thermal properties, and microstructure were evaluated by dynamic light scattering (DLS), differential scanning calorimetry (DSC), and transmission electron microscopy (TEM) respectively. As the proportion of ergocalciferol in the SLN increased from 0% to 20%, the Z-average values of the particles gradually decreased (P≤ 0.05) from approximately 120 nm to approximately 65 nm. DSC analysis of freeze dried SLN samples showed gradual decrease in enthalpies of fusion and crystallization for stable β-subcell whereas for SLN dispersions, the enthalpy of fusion of unstable α-subcell crystal increased with increased ergocalciferol loading. The TEM images of the ergocalciferol loaded SLN samples showed the presence of spherical as well as rod-shaped nanoparticles. It was also observed that the turbidity of the SLN dispersions reduced noticeably with increased ergocalciferol loading. This finding could be useful in terms of fortification of clear juices with ergocalciferol. Solid lipid nanoparticles (SLNs) were used in this study to encapsulate vitamin D₂, a vitamin important for bone health. It was found that as the concentration of vitamin D₂ increased

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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).

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

    NASA Astrophysics Data System (ADS)

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

    2017-10-01

    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.

  3. 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.

  4. 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.

  5. [Progress of researches on drug-loaded nanoparticles].

    PubMed

    Zhao, Jian; Sheng, Yan; Shan, Xiaoqian; Zhang, Xiaolan; Yuan, Yuan; Liu, Changsheng

    2008-02-01

    The progress of researches on drug-loaded nanoparticles was summarized in this review. The major emphasis was laid on the selection of wall polymers, technology of preparation, surface modification, investigation of release in vitro and biocompatibility evaluation. Additionally, we envisioned a perspective regarding the development in this field. With the development of synthesis of biodegradable polymer, with the appearance of novel equipment, and with the deep-going studies on modification of nanoparticles surface method, on fabrication of nanoparticles art as well as on evaluation of drug release and reaction between drug and organ, further researches in this field will open up the way to applications of drug-loaded nanoparticles in larger field.

  6. Functional polymeric nanoparticles for dexamethasone loading and release.

    PubMed

    Fratoddi, Ilaria; Venditti, Iole; Cametti, Cesare; Palocci, Cleofe; Chronopoulou, Laura; Marino, Maria; Acconcia, Filippo; Russo, Maria V

    2012-05-01

    Poly(phenylacetylene) (PPA) and poly(phenylacetylene-co-acrylic acid) (P(PA-co-AA)), nanoparticles bioconjugated with dexamethasone (DXM) during the synthesis, named PPA@DXM and P(PA-co-AA)@DXM, were prepared by a modified surfactant free emulsion method. The loading was studied as a function of different functionality grades of the copolymer and different amounts of drug, obtaining up to 90% of drug loading for P(PA-co-AA)@DXM with 8/1 PA/AA monomer ratio. The SEM images and DLS measurements showed spheres with average diameters in the range 190-500 nm, depending on the content of acrylic acid monomer units in the copolymer and of DXM loading. ζ-potential and surface charge density of DXM loaded nanoparticles were also investigated and confirm the charge density modulation in the range 0.62-2.68σ (μC/m(2)). The results highlight the enhanced capability of our copolymer of hosting DXM, with the advantage of a control of size, surface functionality, charge and release. Moreover we demonstrate for the first time the ability of P(PA-co-AA) DXM loaded nanoparticles to be used in the apoptosis inhibition of human tumor cells (HeLa). On the basis of the results obtained by comparing the effects elicited in HeLa cells by free DXM versus DXM loaded nanoparticles we confirmed the biological efficacy of our preparation. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. 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.

  8. Proanthocyanidins-Loaded Nanoparticles Enhance Dentin Degradation Resistance.

    PubMed

    Fawzy, A S; Priyadarshini, B M; Selvan, S T; Lu, T B; Neo, J

    2017-07-01

    Previous studies reported that grapeseed extract (GSE), which is rich in proanthocyanidins (PAs), improves the biodegradation resistance of demineralized dentin. This study aimed to investigate the effect of a new GSE delivery strategy to demineralized dentin through loading into biodegradable polymer poly-[lactic-co-glycolic acid] (PLGA) nanoparticles on the biodegradation resistance in terms of structural stability and surface/bulk mechanical and biochemical properties with storage time in collagenase-containing solutions. GSE-loaded nanoparticles were synthetized by nanoprecipitation at PLGA/GSE (w/w) ratios of 100:75, 100:50, and 100:25 and characterized for their morphological/structural features, physicochemical characteristics, and drug loading, entrapment, and release. Nanoparticle suspensions in distilled water (12.5% w/v) were applied (1 min) to demineralized dentin specimens by simulating pulpal pressure. The nanoparticle delivery was investigated by scanning electron microscopy (SEM)/transmission electron microscopy (TEM), and the GSE release from the delivered nanoparticles was further characterized. The variations in surface and bulk mechanical properties were characterized in terms of reduced elastic-modulus, hardness, nanoindentation testing, and apparent elastic-modulus with a storage time up to 3 mo. Hydroxyproline release with exposure to collagenase up to 7 d was estimated. An etch-and-rinse dentin adhesive was applied to investigate the morphology of the resin-dentin interface after nanoparticle delivery. Treatment with the GSE-loaded nanoparticles enhanced the collagen fibril structural resistance, reflected from the TEM investigation, and improved the biomechanical and biochemical stability of demineralized dentin. Nanoparticles having PLGA/GSE of 100:75 (w/w) showed the highest cumulative GSE release and were associated with the best improvement in biodegradation resistance. TEM/SEM showed the ability of the nanoparticles to infiltrate

  9. 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

  10. 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.

  11. 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

  12. Pulmonary targeting with biodegradable salbutamol-loaded nanoparticles.

    PubMed

    Beck-Broichsitter, Moritz; Gauss, Julia; Gessler, Tobias; Seeger, Werner; Kissel, Thomas; Schmehl, Thomas

    2010-02-01

    Aerosol therapy using particulate drug carriers has become an increasingly attractive method to deliver therapeutic or diagnostic compounds to the lung. Polymeric nanoparticles are widely investigated carriers in nanomedicine. The targeted and controlled release of drugs from nanoparticles for pulmonary delivery, however, is a research field that has been so far rather unexploited. Therefore, the objective of this study was to compare the pulmonary absorption and distribution characteristics of salbutamol after aerosolization as solution or entrapped into novel polymeric nanoparticles in an isolated rabbit lung model (IPL). Physicochemical properties, morphology, encapsulation efficiency, in vitro drug release, stability of nanoparticles to nebulization, as well as pulmonary drug absorption and distribution after nebulization in the IPL were investigated. Salbutamol-loaded poly(D,L-lactide-co-glycolide) (PLGA) and poly(vinyl sulfonate-co-vinyl alcohol)-graft-poly(D,L-lactide-co-glycolide) (VS(72)-10) nanoparticles were prepared by a modified solvent displacement technique with a mean particle size of approximately 120 nm and a polydispersity index below 0.150. VS(72)-10 nanoparticles showed a more negative zeta-potential of -54.2 +/- 3.3 mV compared to PLGA nanoparticles (-36.5 +/- 2.6 mV). Salbutamol encapsulation efficiency was 25.2 +/- 4.9% and 63.4 +/- 3.5% for PLGA and VS(72)-10 nanoparticles, respectively. After nebulization utilizing the MicroSprayer physicochemical properties of salbutamol-loaded VS(72)-10 nanoparticles were virtually unchanged, whereas nebulized salbutamol-loaded PLGA nanoparticles showed a significant increase in mean particle size and polydispersity. In vitro release studies demonstrated a sustained release of the encapsulated salbutamol from VS(72)-10 nanoparticles. In parallel, a sustained salbutamol release profile was observed after aerosol delivery of these particles to the IPL as reflected by a lower salbutamol recovery in the

  13. 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.

  14. 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.

  15. 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.

  16. Convection-enhanced delivery of methotrexate-loaded maghemite nanoparticles

    PubMed Central

    Corem-Salkmon, Enav; Ram, Zvi; Daniels, Dianne; Perlstein, Benny; Last, David; Salomon, Sharona; Tamar, Gregory; Shneor, Ran; Guez, David; Margel, Shlomo; Mardor, Yael

    2011-01-01

    Convection-enhanced delivery (CED) is a novel approach for delivering drugs directly into brain tumors by intracranial infusion, enabling the distribution of high drug concentrations over large tissue volumes. This study was designed to present a method for binding methotrexate (MTX) to unique crystalline, highly ordered and superparamagnetic maghemite nanoparticles via human serum albumin (HSA) coating, optimized for CED treatments of gliomas. Naked nanoparticles and HSA- or polyethylene glycol (PEG)-coated nanoparticles with/without MTX were studied. In vitro results showed no toxicity and a similar cell-kill efficacy of the MTX-loaded particles via HSA coating to that of free MTX, while MTX-loaded particles via PEG coating showed low efficacy. In vivo, the PEG-coated nanoparticles provided the largest distributions in normal rat brain and long clearance times, but due to their low efficacy in vitro, were not considered optimal. The naked nanoparticles provided the smallest distributions and shortest clearance times. The HSA-coated nanoparticles (with/without MTX) provided good distributions and long clearance times (nearly 50% of the distribution volume remained in the brain 3 weeks post treatment). No MTX-related toxicity was noted. These results suggest that the formulation in which HSA was bound to our nanoparticles via a unique precipitation method, and MTX was bound covalently to the HSA, could enable efficient and stable drug loading with no apparent toxicity. The cell-kill efficacy of the bound MTX remained similar to that of free MTX, and the nanoparticles presented efficient distribution volumes and slow clearance times in vivo, suggesting that these particles are optimal for CED. PMID:21904449

  17. Development and characterization of voriconazole loaded nanoparticles for parenteral delivery.

    PubMed

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

    2016-08-20

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

  18. Dopamine-loaded chitosan nanoparticles: formulation and analytical characterization.

    PubMed

    De Giglio, Elvira; Trapani, Adriana; Cafagna, Damiana; Sabbatini, Luigia; Cometa, Stefania

    2011-06-01

    The formulation and characterization of dopamine (DA)-loaded chitosan nanoparticles (CSNPs) are described as preliminary steps for the development of potential DA carrier systems intended for Parkinson's disease treatment. For this purpose, CSNPs were firstly produced and, afterwards, they were incubated in a DA aqueous solution to promote neurotransmitter loading. The characterization of the resulting nanoparticles started with Fourier transform infrared spectroscopy analysis to ascertain the presence of DA in the nanocarrier, whereas X-ray photoelectron spectroscopy analysis provided evidence of the localization of DA on the nanoparticle surface. A quartz crystal microbalance with dissipation monitoring (QCM-D) was then exploited to investigate both swelling of CSNPs and interaction of DA with CSNPs. In particular, the QCM-D revealed that this interaction is fast and so this allows a stable nanostructured system to be obtained.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  6. A review of models for the analysis of the injection of densely loaded flows into entrained flow gasifiers

    SciTech Connect

    Edelman, R.; Rizk, M. A.

    1989-11-01

    An analysis of turbulent gas-particle flow has been conducted for which dilute and dense flows were considered. This study showed that, although, there are a variety of models postulated for the analysis of dilute-phase particulate transport, there exists limited information on dense-phase flow. Several derivations of multi-phase flow equations have appeared in the literature. The differences between these equations are in the momentum source terms, the pressure gradient terms and in the convection terms of the dispersed phase momentum equation. In most of the studies on dilute two-phase flow, the effects of the dispersed phase on fluid turbulence have not been considered at all or considered only in an ad hoc fashion. In the few studies where such effects have been incorporated properly, many simplifying assumptions and various empirical constants were introduced. Evaluation of the constants was made via a comparison between model predictions and experimental data. Among these studies the work of Elghobashi and his co-workers, in general, and of Rizk (1985), in particular, provides a foundation for the extension to densely loaded gas/solid flows. Based on this approach, a new mathematical model has been formulated to analyze densely loaded gas/solid flows taking into account particle-particle interactions and gas-particle interactions. 136 refs., 2 figs., 2 tabs.

  7. A review of models for the analysis of the injection of densely loaded flows into entrained flow gasifiers

    NASA Astrophysics Data System (ADS)

    Edelman, R.; Rizk, M. A.

    1989-11-01

    An analysis of turbulent gas-particle flow has been conducted for which dilute and dense flows were considered. This study showed that, although, there are a variety of models postulated for the analysis of dilute-phase particulate transport, there exists limited information on dense-phase flow. Several derivations of multi-phase flow equations have appeared in the literature. The differences between these equations are in the momentum source terms, the pressure gradient terms and in the convection terms of the dispersed phase momentum equation. In most of the studies on dilute two-phase flow, the effects of the dispersed phase on fluid turbulence have not been considered at all or considered only in an ad hoc fashion. In the few studies where such effects have been incorporated properly, many simplifying assumptions and various empirical constants were introduced. Evaluation of the constants was made via a comparison between model predictions and experimental data. Among these studies the work of Elghobashi and his co-workers, in general, and of Rizk (1985), in particular, provides a foundation for the extension to densely loaded gas/solid flows. Based on this approach, a new mathematical model has been formulated to analyze densely loaded gas/solid flows taking into account particle-particle interactions and gas-particle interactions.

  8. 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.

  9. 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.

  10. Tuning of Magnetic Optical Response in a Dielectric Nanoparticle by Ultrafast Photoexcitation of Dense Electron-Hole Plasma.

    PubMed

    Makarov, Sergey; Kudryashov, Sergey; Mukhin, Ivan; Mozharov, Alexey; Milichko, Valentin; Krasnok, Alexander; Belov, Pavel

    2015-09-09

    We propose a novel approach for efficient tuning of optical properties of a high refractive index subwavelength nanoparticle with a magnetic Mie-type resonance by means of femtosecond laser irradiation. This concept is based on ultrafast photoinjection of dense (>10(20) cm(-3)) electron-hole plasma within such nanoparticle, drastically changing its transient dielectric permittivity. This allows manipulation by both electric and magnetic nanoparticle responses, resulting in dramatic changes of its scattering diagram and scattering cross section. We experimentally demonstrate 20% tuning of reflectance of a single silicon nanoparticle by femtosecond laser pulses with wavelength in the vicinity of the magnetic dipole resonance. Such a single-particle nanodevice enables designing of fast and ultracompact optical switchers and modulators.

  11. 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.

  12. 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

  13. Mucus permeating carriers: formulation and characterization of highly densely charged nanoparticles.

    PubMed

    Pereira de Sousa, Irene; Steiner, Corinna; Schmutzler, Matthias; Wilcox, Matthew D; Veldhuis, Gert J; Pearson, Jeffrey P; Huck, Christian W; Salvenmoser, Willi; Bernkop-Schnürch, Andreas

    2015-11-01

    The GI mucus layer represents a significant block to drug carriers absorption. Taking an example from nature, virus-mimicking nanoparticles (NPs) with highly densely charged surface were designed with the aim to improve their mucus permeation ability. NPs were formulated by combining chitosan with chondroitin sulfate and were characterized by particle size, ζ-potential and hydrophobicity. The interaction occurring between NPs and diluted porcine intestinal mucus was investigated by a new method. Furthermore, the rotating tube technique was exploited to evaluate the NPs permeation ability in fresh undiluted porcine intestinal mucus. NPs (400-500 nm) presenting a slightly positive (4.02 mV) and slightly negative (-3.55 mV) ζ-potential resulted to be hydrophobic and hydrophilic, respectively. On the one hand the hydrophobic NPs undergo physico-chemical changes when incubated with mucus, namely the size increased and the ζ-potential decreased. On the other hand, the hydrophilic NPs did not significantly change size and net charge during incubation with mucus. Both types of NPs showed a 3-fold higher diffusion ability compared to the reference 50/50 DL-lactide/glycolide copolymer NPs (136 nm, -23 mV, hydrophilic). Based on these results, this work gives valuable information for the further design of mucus-penetrating NPs. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. 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

  15. Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles.

    PubMed

    Gauthier, Marianne; Yin, Qian; Cheng, Jianjun; O'Brien, William D

    2015-08-01

    A protocol was designed to produce albumin-coated microbubbles (MBs) loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug delivery studies. Microbubbles resulted from the sonication of 5% bovine serum albumin and 15% dextrose solution. Functionalized NPs were produced by mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates. Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs were produced and compared. Statistical evaluations were based on quantitative analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB fabrication): MB diameter using a circle detection routine based on the Hough transform, MB number density using a hemocytometer, and NP-loading yield based on MB counts from fluorescence and light microscopic images. Loading capacity of the albumin-coated MBs was evaluated by fluorescence. Loaded MB sizes were stable over 6 days after production and were not significantly different from that of time-matched unloaded MBs. Number density evaluation showed that only 1/1 NP/MB volume ratio and unloaded MB number densities were stable over time, and that the 1/1 MB number density evaluated at each time point was not significantly different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had unstable number densities that were significantly different from that of unloaded MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP-loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested that the 1/1 MBs had a loading capacity of 3700 NPs/MB. A protocol was developed to load albumin MBs with functionalized PLA NPs for further drug delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to produce stable loaded MBs with a loading capacity of 3700 NPs/MB. © 2015 by the American Institute of Ultrasound in Medicine.

  16. Design of Albumin-Coated Microbubbles Loaded With Polylactide Nanoparticles

    PubMed Central

    Gauthier, Marianne; Yin, Qian; Cheng, Jianjun; O'Brien, William D.

    2015-01-01

    Objectives A protocol was designed to produce albumin-coated microbubbles (MBs) loaded with functionalized polylactide (PLA) nanoparticles (NPs) for future drug delivery studies. Methods Microbubbles resulted from the sonication of 5% bovine serum albumin and 15% dextrose solution. Functionalized NPs were produced by mixing fluorescent PLA and PLA-polyethylene glycol-carboxylate conjugates. Nanoparticle-loaded MBs resulted from the covalent conjugation of functionalized NPs and MBs. Three NP/MB volume ratios (1/1, 1/10, and 1/100) and unloaded MBs were produced and compared. Statistical evaluations were based on quantitative analysis of 3 parameters at 4 time points (1, 4, 5, and 6 days post MB fabrication): MB diameter using a circle detection routine based on the Hough transform, MB number density using a hemocytometer, and NP-loading yield based on MB counts from fluorescence and light microscopic images. Loading capacity of the albumin-coated MBs was evaluated by fluorescence. Results Loaded MB sizes were stable over 6 days after production and were not significantly different from that of time-matched unloaded MBs. Number density evaluation showed that only 1/1 NP/MB volume ratio and unloaded MB number densities were stable over time, and that the 1/1 MB number density evaluated at each time point was not significantly different from that of unloaded MBs. The 1/10 and 1/100 NP/MB volume ratios had unstable number densities that were significantly different from that of unloaded MBs (P < .05). Fluorescence evaluation suggested that 1/1 MBs had a higher NP-loading yield than 1/10 and 1/100 MBs. Quantitative loading evaluation suggested that the 1/1 MBs had a loading capacity of 3700 NPs/MB. Conclusions A protocol was developed to load albumin MBs with functionalized PLA NPs for further drug delivery studies. The 1/1 NP/MB volume ratio appeared to be the most efficient to produce stable loaded MBs with a loading capacity of 3700 NPs/MB. PMID:26206822

  17. 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.

  18. 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.

  19. 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.

  20. 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.

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

    PubMed

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

    2016-03-28

    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.

  2. 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

  3. 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.

  4. Preparation, characterization and antibacterial properties against E. coli K88 of chitosan nanoparticle loaded copper ions

    NASA Astrophysics Data System (ADS)

    Du, Wen-Li; Xu, Ying-Lei; Xu, Zi-Rong; Fan, Cheng-Li

    2008-02-01

    The present study was conducted to prepare and characterize chitosan nanoparticle loaded copper ions, and evaluate their antibacterial activity. Chitosan nanoparticles were prepared based on ionotropic gelation, and then the copper ions were loaded. The particle size, zeta potential and morphology were determined. Antibacterial activity was evaluated against E. coli K88 by determination of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) in vitro. Results showed that the antibacterial activity was significantly enhanced by the loading of copper ions compared to those of chitosan nanoparticles and copper ions. The MIC and MBC of chitosan nanoparticle loaded copper ions were 21 times and 42 times lower than those of copper ions, respectively. To confirm the antibacterial mechanism, morphological changes of E. coli K88 treated by chitosan nanoparticle loaded copper ions were dynamically observed with an atomic force microscope (AFM). It was found that chitosan nanoparticle loaded copper ions killed E. coli K88 through damage to the cell membrane.

  5. Contrast-Enhanced X-ray Detection of Microcalcifications in Radiographically Dense Mammary Tissue Using Targeted Gold Nanoparticles.

    PubMed

    Cole, Lisa E; Vargo-Gogola, Tracy; Roeder, Ryan K

    2015-09-22

    Breast density reduces the accuracy of mammography, motivating methods to improve sensitivity and specificity for detecting abnormalities within dense breast tissue, but preclinical animal models are lacking. Therefore, the objectives of this study were to investigate a murine model of radiographically dense mammary tissue and contrast-enhanced X-ray detection of microcalcifications in dense mammary tissue by targeted delivery of bisphosphonate-functionalized gold nanoparticles (BP-Au NPs). Mammary glands (MGs) in the mouse mammary tumor virus - polyomavirus middle T antigen (MMTV-PyMT or PyMT) model exhibited greater radiographic density with age and compared with strain- and age-matched wild-type (WT) controls at 6-10 weeks of age. The greater radiographic density of MGs in PyMT mice obscured radiographic detection of microcalcifications that were otherwise detectable in MGs of WT mice. However, BP-Au NPs provided enhanced contrast for the detection of microcalcifications in both radiographically dense (PyMT) and WT mammary tissues as measured by computed tomography after intramammary delivery. BP-Au NPs targeted microcalcifications to enhance X-ray contrast with surrounding mammary tissue, which resulted in improved sensitivity and specificity for detection in radiographically dense mammary tissues.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Nanoparticles loaded with ferrocenyl tamoxifen derivatives for breast cancer treatment.

    PubMed

    Nguyen, Anh; Marsaud, Véronique; Bouclier, Céline; Top, Siden; Vessieres, Anne; Pigeon, Pascal; Gref, Ruxandra; Legrand, Philippe; Jaouen, Gérard; Renoir, Jack-Michel

    2008-01-22

    For the first time, two organometallic triphenylethylene compounds (Fc-diOH and DFO), with strong antiproliferative activity in breast cancer cells, but insoluble in biological fluids, were incorporated in two types of stealth nanoparticles (NP): PEG/PLA nanospheres (NS) and nanocapsules (NC). Their physicochemical parameters were measured (size, zeta potential, encapsulation and loading efficiency), and their biological activity was assessed. In vitro drug release after high dilution of loaded NPs was measured by estradiol binding competition in MELN cells. The influence of the encapsulated drugs on the cell cycle and apoptosis was studied by flow cytometry analyses. Notwithstanding potential drug adsorption at the NP surface, Fc-diOH and DFO were incorporated efficiently in NC and NS, which slowly released both compounds. They arrested the cell cycle in the S-phase and induced apoptosis, whose activity is increased by loaded NS. A decrease in their antiproliferative activity by the antioxidant alpha-tocopherol indicated that reactive oxygen species (ROS) may be involved. Therefore, nanosystems, containing for the first time a high load of anticancer organometallic triphenylethylenes, have been developed. Their small size and delayed drug release, combined with their enhanced apoptotic potential, are compatible with an increased persistence in the blood and a promising antitumour activity.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel.

    PubMed

    Kesarla, Rajesh; Tank, Tanvi; Vora, Pratik Ashwinbhai; Shah, Tanvi; Parmar, Sagar; Omri, Abdelwahab

    2016-09-01

    Conventional ophthalmic solutions often eliminate rapidly after administration and cannot provide and maintain an adequate concentration of drug in the pre-corneal area. Above problem can be overcome by the use of in situ gel forming systems that are instilled as drops in to the eye and undergo a sol-gel transition in the cul-de-sac. An ion sensitive polymer gellan gum was used as gelling agent which formed immediate gel and remained for extended time period. Nanoparticles of moxifloxacin, prepared by solvent evaporation, were separated by freeze drying. The rheological properties and in vitro drug release test of in situ gel loaded with nanoparticles were evaluated and compared with marketed preparation. In vitro release study demonstrated diffusion controlled release for moxifloxacin from formulations over a period of 12 h. The developed formulation was stable and showed enhanced contact time minimizing the frequency of administration. Confocal microscopy showed clear permeation of drug loaded nanoparticles across L/S of cornea. The formulation of moxifloxacin was found liquid at the formulated pH and formed gel in the presence of mono or divalent cations. The gel formed in situ showed sustained drug release over a period of 10-12 h. The formulations were less viscous before instillation and formed strong gel after instilling it into cul-de-sac. It is thus concluded that by adopting a systematic formulation approach, an optimum point can be reached in the shortest time with minimum efforts to achieve desirable rheological and in vitro release property for in situ gel forming system.

  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. Next-Generation Polymer Shells for Inorganic Nanoparticles are Highly Compact, Ultra-Dense, and Long-Lasting Cyclic Brushes.

    PubMed

    Morgese, Giulia; Shirmardi Shaghasemi, Behzad; Causin, Valerio; Zenobi-Wong, Marcy; Ramakrishna, Shivaprakash N; Reimhult, Erik; Benetti, Edmondo M

    2017-04-10

    Cyclic poly-2-ethyl-2-oxazoline (PEOXA) ligands for superparamagnetic Fe3 O4 nanoparticles (NPs) generate ultra-dense and highly compact shells, providing enhanced colloidal stability and bio-inertness in physiological media. When linear brush shells fail in providing colloidal stabilization to NPs, the cyclic ones assure long lasting dispersions. While the thermally induced dehydration of linear PEOXA shells cause irreversible aggregation of the NPs, the collapse and subsequent rehydration of similarly grafted cyclic brushes allow the full recovery of individually dispersed NPs. Although linear ligands are densely grafted onto Fe3 O4 cores, a small plasma protein such as bovine serum albumin (BSA) still physisorbs within their shells. In contrast, the impenetrable entropic shield provided by cyclic brushes efficiently prevents nonspecific interaction with proteins. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. 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

  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. AFM topographies of densely packed nanoparticles: a quick way to determine the lateral size distribution by autocorrelation function analysis

    NASA Astrophysics Data System (ADS)

    Fekete, L.; Kůsová, K.; Petrák, V.; Kratochvílová, I.

    2012-08-01

    The distribution of sizes is one of the basic characteristics of nanoparticles. Here, we propose a novel way to determine the lateral distribution of sizes from AFM topographies. Our algorithm is based on the autocorrelation function and can be applied both on topographies containing spatially separated and densely packed nanoparticles as well as on topographies of polycrystalline films. As no manual treatment is required, this algorithm can be easily automatable for batch processing. The algorithm works in principle with any kind of spatially mapped information (AFM current maps, optical microscope images, etc.), and as such has no size limitations. However, in the case of AFM topographies, the tip/sample convolution effects will be the factor limiting the smallest size to which the algorithm is applicable. Here, we demonstrate the usefulness of this algorithm on objects with sizes ranging between 20 nm and 1.5 μm.

  2. 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

  3. 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

  4. 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.

  5. Formulation and Characterization of Anthocyanins-Loaded Nanoparticles.

    PubMed

    Dupeyrón, Danay; Kawakami, Monique; Rieumont, Jacques; Carvalho, José Carlos

    2017-01-01

    Açaí berry, from the Euterpe oleracea Mart. Palm, has been described as the most important fruit in the Brazilian Amazon. Several studies have reported that anthocyanins (ACNs), one of the components of the açaí, have enormous potential for pharmaceuticals applications. However, the bioavailability of anthocyanins is relatively low compared to that of other flavonoids. Then, in the present work, anthocyanins-loaded nanoparticles have been developed to overcome their poor bioavailability. A two-level factorial design with three factors was considered to evaluate the effect of EUDRAGIT ® L100, polyethylene glycol 2000 (PEG 2000) and polysorbate 80 on encapsulation efficiency (EE) of anthocyanins. Also, major parameters of nanoparticles were assessed by using mainly SEM microscopy and Dynamic light scattering. PEG 2000 was the only individual factor that has statistical significance (95% confidence level). The process yields (PY) were found in between 67% and 92%; the particle size and morphology analysis showed two distribution size, one for NPs and another for the agglomerates. The pH-sensitive polymer together with the hydrophilic polymer showed to be suitable as ACNs delivery system. The delayed release profile of ACNs, observed for all formulations, can enhance their poor bioavailability. Nevertheless, ACNs bioavailability in vivo remains to be studied. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Design of Curcumin loaded Cellulose Nanoparticles for Prostate Cancer

    PubMed Central

    Yallapu, Murali Mohan; Dobberpuhl, Mitch Ray; Maher, Diane Michele; Jaggi, Meena; Chauhan, Subhash Chand

    2013-01-01

    Prostate cancer (PC) is the most frequently diagnosed disease in men in the United States. Curcumin (CUR), a natural polyphenol, has shown potent anti-cancer efficacy in various types of cancers. However, suboptimal pharmacokinetics and poor bioavailability limit its effective use in cancer therapeutics. Several successful CUR nanoformulations have recently been reported which improve upon these features; however there is no personalized safe nanoformulation for prostate cancer. This study contributes two important scientific aspects of prostate cancer therapeutics. The first objective was to investigate the comparative cellular uptake and cytotoxicity evaluation of β-cyclodextrin (CD), hydroxyl propyl methyl cellulose (cellulose), poly(lactic-co-glycolic acid) (PLGA), magnetic nanoparticles (MNP), and dendrimer based CUR nanoformulations in prostate cancer cells. Curcumin loaded cellulose nanoparticles (cellulose-CUR) formulation exhibited the highest cellular uptake and caused maximum ultrastructural changes related to apoptosis (presence of vacuoles) in prostate cancer cells. Secondly, the anti-cancer potential of the optimized cellulose-CUR formulation was evaluated in cell culture models using cell proliferation, colony formation and apoptosis (7-AAD staining) assays. In these assays, the cellulose-CUR formulation showed improved anti-cancer efficacy compared to free curcumin. Our study shows, for the first time, the feasibility of cellulose-CUR formulation and its potential use in prostate cancer therapy. PMID:21892919

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

    SciTech Connect

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

    2016-05-15

    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). - Graphical abstract: An amine-functionalized neutral Cd(II) boron imidazolate framework can load Ag NPs and show excellent photocatalytic degradation behavious for MB. - Highlights: • Amine-functionalization. • Neutral boron imidazolate framework. • Loading Ag nanoparticles (NPs). • Photocatalytic degradation of methylene blue.

  8. Optimal Base Station Density of Dense Network: From the Viewpoint of Interference and Load

    PubMed Central

    Feng, Zhiyong

    2017-01-01

    Network densification is attracting increasing attention recently due to its ability to improve network capacity by spatial reuse and relieve congestion by offloading. However, excessive densification and aggressive offloading can also cause the degradation of network performance due to problems of interference and load. In this paper, with consideration of load issues, we study the optimal base station density that maximizes the throughput of the network. The expected link rate and the utilization ratio of the contention-based channel are derived as the functions of base station density using the Poisson Point Process (PPP) and Markov Chain. They reveal the rules of deployment. Based on these results, we obtain the throughput of the network and indicate the optimal deployment density under different network conditions. Extensive simulations are conducted to validate our analysis and show the substantial performance gain obtained by the proposed deployment scheme. These results can provide guidance for the network densification. PMID:28891997

  9. Emodin-Loaded PLGA-TPGS Nanoparticles Combined with Heparin Sodium-Loaded PLGA-TPGS Nanoparticles to Enhance Chemotherapeutic Efficacy Against Liver Cancer.

    PubMed

    Liu, Hongyan; Xu, Hong; Zhang, Chenghong; Gao, Meng; Gao, Xiaoguang; Ma, Chuchu; Lv, Li; Gao, Dongyan; Deng, Sa; Wang, Changyuan; Tian, Yan

    2016-11-01

    Heparin sodium (HS)-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (HPTNs) were prepared as a sustained and targeting delivery carrier and combined with emodin (EMO)-loaded PLGA-TPGS nanoparticles (EPTNs), which were investigated previously to form a combination therapy system for the treatment of liver cancer. To assess cellular uptake and evaluate the liver-targeting capacity by analyzing the drug concentrations and frozen slices, HS/eosin-loaded PLGA-TPGS nanoparticles, HS/fluorescein- loaded PLGA-TPGS nanoparticles and EMO/C6-loaded PLGA-TPGS nanoparticles, which contained eosin, fluorescein and C6 as fluorescent probes, respectively, were also prepared. All of these nanoparticles were characterized in terms of their size, size distribution, surface charge, drug loading, encapsulation efficiency, in vitro release profile and cellular uptake. The apoptosis of HepG2 cells induced by EPTNs in combination with HPTNs was determined by Annexin V-FITC staining and PI labelling. Transmission electron microscopy indicated that these nanoparticles were stably dispersed spheres with sizes ranging from 100 to 200 nm. The results demonstrated that fluorescent nanoparticles were internalized into HepG2 and HCa-F cells efficiently and had improved liver-targeting properties. The combination of EPTNs and HPTNs effectively inhibited cell growth in vitro and had a remarkable synergistic anticancer effect in vivo. EPTNs combined with HPTNs induced HepG2 cell apoptosis with synergistic effects. The liver H&E slice images of a hepatocarcinogenic mouse model indicated that EPTNs in combination with HPTNs significantly suppressed tumour growth in vivo. The research suggests that the combination therapy system of EPTNs and HPTNs could be a new direction for liver cancer therapy.

  10. 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.

  11. 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.

  12. 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

  13. Curcumin-loaded polysaccharide nanoparticles: Optimization and anticariogenic activity against Streptococcus mutans.

    PubMed

    Maghsoudi, Amir; Yazdian, Fatemeh; Shahmoradi, Saleheh; Ghaderi, Leila; Hemati, Mehran; Amoabediny, Ghassem

    2017-06-01

    Curcumin was loaded into different polysaccharide nanoparticles chitosan, alginate and starch, using the desolvation method. Curcumin-loaded nanoparticles exhibited enhanced solubility in aqueous solutions comparing with free curcumin. Effects of formulation parameters such as curcumin concentration and different volumes of ethanolic solution were affected the particle size and loading efficiency. Under optimum conditions, curcumin-loaded chitosan, starch and alginate nanoparticles with mean particles sizes of 66.3, 61.1 and 78.8nm, and maximum loading efficiencies of 11.9%, 14.3% and 13.35% were achieved, respectively. Additionally, the minimum inhibitory concentration for chitosan, starch and alginate nanoparticles against the microorganism, Streptococcus mutans, were 0.114, 0.204 and 0.204mg/mL, respectively. Curcumin was observed to release from nanoparticles under physiological pH over a period of 96h. The effect of curcumin-loaded nanoparticles on S. mutans biofilms was assessed on dental models. According to the results, curcumin-loaded chitosan nanoparticles hold promises for being used in dental decay fighting products. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Development and evaluation of a novel topical treatment for acne with azelaic acid-loaded nanoparticles.

    PubMed

    Reis, Catarina Pinto; Gomes, Ana; Rijo, Patrícia; Candeias, Sara; Pinto, Pedro; Baptista, Marina; Martinho, Nuno; Ascensão, Lia

    2013-10-01

    Azelaic acid (AzA) is used in the treatment of acne. However, side effects and low compliance have been associated with several topical treatments with AzA. Nanotechnology presents a strategy that can overcome these problems. Polymeric nanoparticles can control drug release and targeting and reduce local drug toxicity. The aim of this study was to produce and evaluate an innovative topical treatment for acne with AzA-loaded poly-DL-lactide/glycolide copolymer nanoparticles. A soft white powder of nanoparticles was prepared. The mean size of loaded nanoparticles was < 400 nm and zeta potential was negative. Spherical nanoparticles were observed by scanning electron microscopy. Encapsulation efficiency was around 80% and a strong interaction between the polymer and the drug was confirmed by differential scanning calorimetric analysis. In vitro drug release studies suggested a controlled and pulsatile release profile. System efficacy tests suggested similar results between the loaded nanoparticles and the nonencapsulated drug against the most common bacteria associated with acne. Cytotoxicity of AzA-loaded nanoparticles was concentration dependent, although not pronounced. The occluded patch test seemed to indicate that the formulation excipients were safe and thus AzA-loaded nanoparticles appear to be an efficient and safe treatment for acne.

  1. Injection of densely loaded flows into entrained-flow gasifiers. First quarterly progress report, October 1-December 31, 1985

    SciTech Connect

    Rizk, M.A.; Edelman, R.B.

    1986-01-01

    The overall objective of this project is to develop improved understanding of the injection and mixing of densely loaded gas/solid mixtures into gas streams. The ultimate application of the results will be the development of improved injection and mixing configurations for entrained-flow coal gasifiers. In entrained-flow gasification, the injection and dispersion of heavily loaded mixtures of coal and gases is an important factor for overall reactor performance and the uniformity of coal processing. Poor disperison in a reactor has several adverse consequences. These include depressed particle heating rates, which affect critical devolatilization phenomena. Limited mixing also leads to increased reactor residence time requirements and nonuniformity of coal treatment. Information is needed to provide guidance for establishing reactor inlet configurations which will accelerate mixing and to facilitate modeling of such reactors. Data are available for systems which are more dilute than those used for entrained gasifiers, but special considerations lead to the desirability of using a minimum amount of injection flow in a gasifier. 54 refs.

  2. Injection of densely loaded flows into entrained-flow gasifiers. Second quarterly report, January 1-March 31, 1986

    SciTech Connect

    Rizk, M.A.; Edelman, R.B.

    1986-04-01

    The overall objective of this project is to develop improved understanding of the injection and mixing of densely loaded gas/solid mixtures into gas streams. The ultimate application of the results will be the development of improved injection and mixing configurations for entrained-flow gasifiers. In entrained-flow gasification, the injection and dispersion of heavily loaded mixtures of coal and gases is an important factor for overall reactor performance and the uniformity of coal processing. Poor dispersion in a reactor has several adverse consequences. These include depressed particle heating rates, which affect critical devolatilization phenomena. Limited mixing also leads to increased reactor residence time requirements and nonuniformity of coal treatment. Information is needed to provide guidance for establishing reactor inlet configurations which will accelerate mixing and to facilitate modeling of such reactors. Data are available for systems which are more dilute than those used for entrained gasifiers, but special considerations lead to the desirability of using a minimum amount of injection flow in a gasifier. Progress reports are presented for the following tasks: (1) test plan; (2) literature search; (3) theoretical investigation; and (4) experimental investigation. 11 refs., 1 fig.

  3. Tetracycline nanoparticles loaded calcium sulfate composite beads for periodontal management.

    PubMed

    Sindhura Reddy, N; Sowmya, S; Bumgardner, Joel D; Chennazhi, K P; Biswas, Raja; Jayakumar, R

    2014-06-01

    The objective of this study was to fabricate, characterize and evaluate in vitro, an injectable calcium sulfate bone cement beads loaded with an antibiotic nanoformulation, capable of delivering antibiotic locally for the treatment of periodontal disease. Tetracycline nanoparticles (Tet NPs) were prepared using an ionic gelation method and characterized using DLS, SEM, and FTIR to determine size, morphology, stability and chemical interaction of the drug with the polymer. Further, calcium sulfate (CaSO4) control and CaSO4-Tet NP composite beads were prepared and characterized using SEM, FTIR and XRD. The drug release pattern, material properties and antibacterial activity were evaluated. In addition, protein adsorption, cytocompatibility and alkaline phosphatase activity of the CaSO4-Tet NP composite beads in comparison to the CaSO4 control were analyzed. Tet NPs showed a size range of 130±20nm and the entrapment efficiency calculated was 89%. The composite beads showed sustained drug release pattern. Further the drug release data was fitted into various kinetic models wherein the Higuchi model showed higher correlation value (R(2)=0.9279) as compared to other kinetic models. The composite beads showed antibacterial activity against Staphylococcus aureus and Escherichia coli. The presence of Tet NPs in the composite bead didn't alter its cytocompatibility. In addition, the composite beads enhanced the ALP activity of hPDL cells. The antibacterial and cytocompatible CaSO4-Tet NP composite beads could be beneficial in periodontal management to reduce the bacterial load at the infection site. Tet NPs would deliver antibiotic locally at the infection site and the calcium sulfate cement, would itself facilitate tissue regeneration. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. 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.

  5. 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).

  6. [Preparation and physiochemical properties of curcumin-loaded lipid cubic liquid crystalline nanoparticles].

    PubMed

    Su, Xun; He, Xiu-li; Liu, Xiu-ju; Guo, Jing-yan; Zhai, Guang-xi

    2012-02-01

    To prepare curcumin-loaded lipid cubic liquid crystalline nanoparticles and evaluate its physiochemical properties. The nanoparticles were prepared using hot and high-pressure homogenization. The prescription and preparation process were optimized by uniform design with drug loading and entrapment efficiency as indexes. The nanoparticles were spherical under transmission electron microscope (TEM) with average particle size of 176.1 nm, zeta potential of -25.19 mV, average drug loading of (1.5 +/- 0.2)% and entrapment efficiency of (95 +/- 1.8)%. The release equation: In (1-Q) = -0.0251t-0.0075. The cumulative release percentage was 60% at 36 h in vitro. The obtained curcumin-loaded lipid cubic liquid crystalline nanoparticles shows high entrapment efficiency and good sustain release property.

  7. 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.

  8. 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.

  9. 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.

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

    DTIC Science & Technology

    2014-02-01

    Based Enhanced Delivery of Drug-Loaded Targeted Nanoparticles for Breast Cancer Therapy” 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0167 5c... Nanotechnologies in Living Systems”, Moscow Region, Russia, September, 2011. 3. “Ionic nanogels for drug delivery in cancer ”. NanoDDS’12; Atlantic City, New...AD Award Number: W81XWH-11-1-0167 TITLE: Mechanism-Based Enhanced Delivery of Drug-Loaded Targeted Nanoparticles for Breast

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

    DTIC Science & Technology

    2014-02-01

    Enhanced Delivery of Drug-Loaded Targeted Nanoparticles for Breast Cancer Therapy” 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0166 5c... Nanotechnologies in Living Systems”, Moscow Region, Russia, September, 2011. 3. “Ionic nanogels for drug delivery in cancer ”. NanoDDS’12; Atlantic City, New...AD Award Number: W81XWH-11-1-0166 TITLE: Mechanism-Based Enhanced Delivery of Drug-Loaded Targeted Nanoparticles for Breast

  12. 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.

  13. Tamoxifen-loaded thiolated alginate-albumin nanoparticles as antitumoral drug delivery systems.

    PubMed

    Martínez, A; Benito-Miguel, M; Iglesias, I; Teijón, J M; Blanco, M D

    2012-06-01

    Nanoparticles based on disulfide bond reduced bovine serum albumin and thiolated alginate (alginate-cysteine conjugate) have been prepared by coacervation method and have been loaded with tamoxifen (TMX). The TMX load into the nanoparticles was optimized (4-6 μg/mg NP) by freeze-drying the systems before the loading procedure. Maximum TMX release (45-52%) took place between 2 and 25 h. Cytotoxicity of unloaded nanoparticles in MCF-7 and HeLa cells was not observed, although a small decrease in viability took place at very high concentration. Cell uptake of nanoparticles occurred in both cell types and the presence of polysaccharide in the nanoparticle composition allowed a better interaction with cells. The administration of 10 μM TMX by TMX-nanoparticles was effective in both cellular lines, and the effect of the drug-loaded systems on MCF-7 cell cycle showed the efficacy of the TMX-loaded nanoparticles. Copyright © 2012 Wiley Periodicals, Inc.

  14. Suppression of agglomeration of ciprofloxacin-loaded human serum albumin nanoparticles.

    PubMed

    Kumar, P Vijayaraj; Jain, Narendr K

    2007-03-02

    The present study is aimed at developing and exploring the use of pectin in suppression of agglomeration of ciprofloxacin-loaded human serum albumin (HSA) nanoparticles. The HSA-pectin nanoparticles loaded with ciprofloxacin were prepared by the pH-coacervation method, and various physicochemical parameters such as particle size, morphology, zeta-potential, electrolyte-induced flocculation, pH-dependent zeta-potential, drug loading, in vitro drug release, and stability of nanoparticles, were evaluated. The size of the HSA-pectin nanoparticles (F3) was found to be 180 to 290 nm. The HSA nanoparticles were modified with pectin when the critical flocculation concentration of nanoparticles in Na(2)SO(4) solution was increased from 0.3 M to 0.9 M. The isoelectric points of the formed nanoparticles were found to be relatively lower between pH values 3 and 6. Pectin may be used as a pharmaceutical additive for the suppression of particle agglomeration in HSA nanoparticles, and the effect may be attributed to the pectin segments present on the surface of nanoparticles.

  15. 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.

  16. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. 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

  18. Chemiresistive/SERS dual sensor based on densely packed gold nanoparticles.

    PubMed

    Boca, Sanda; Leordean, Cosmin; Astilean, Simion; Farcau, Cosmin

    2015-01-01

    Chemiresistors are a class of sensitive electrical devices capable of detecting (bio)chemicals by simply monitoring electrical resistance. Sensing based on surface enhanced Raman scattering (SERS) represents a radically different approach, in which molecules are optically detected according to their vibrational spectroscopic fingerprint. Despite different concepts are involved, one can find in the literature examples from both categories reporting sensors made of gold nanoparticles. The same building blocks appear because both sensor classes share a common principle: nanometric interparticle gaps are needed, for electron tunneling in chemiresistors, and for enhancing electromagnetic fields by plasmon coupling in SERS-based sensors. By exploiting such nano-gaps in self-assembled films of gold nanoparticles, we demonstrate the proof of concept of a dual electrical/optical sensor, with both chemiresistive and SERS capabilities. The proposed device is realized by self-assembling 15 nm gold nanoparticles into few micrometers-wide strips across commercially available interdigitated electrodes. The dual-mode operation of the device is demonstrated by the detection of a biologically relevant model analyte, 4-mercaptophenyl boronic acid.

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

    PubMed

    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.

  20. 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.

  1. Oleanolic acid-loaded PLGA-TPGS nanoparticles combined with heparin sodium-loaded PLGA-TPGS nanoparticles for enhancing chemotherapy to liver cancer.

    PubMed

    Gao, Meng; Xu, Hong; Bao, Xu; Zhang, Chenghong; Guan, Xin; Liu, Hongyan; Lv, Li; Deng, Sa; Gao, Dongyan; Wang, Changyuan; Tian, Yan

    2016-11-15

    Heparin sodium (HS)-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (HPTNs) were prepared as sustained and targeted delivery carriers and combined with oleanolic acid (OA)-loaded PLGA-TPGS nanoparticles (OPTNs) that had been investigated in our previous work to form a combination therapy system for the treatment of liver cancer. To inspect cellular uptake and evaluate liver-targeting performance by analysing drug concentrations and cryosections, fluorescent probe coumarin-6 and eosin was used in preparations of HS/eosin-loaded, HS/coumarin-6-loaded, and OA/coumarin-6-loaded PLGA-TPGS nanoparticles. All of these NPs were characterized in terms of size, size distribution, surface charge, drug loading, encapsulation efficiency, and in vitro release profile. The apoptosis of HepG2 cells induced by OPTNs combined with HPTNs was determined by Annexin V-FITC staining and PI labelling. Transmission electron microscopy indicated that all of the nanoparticles were stably dispersed spheres with diameters ranging from 100 to 200nm. The results demonstrated that fluorescent nanoparticles were efficiently internalized into HepG2 and HCa-F cells, and that they exhibited enhanced liver targeting. The combination of HPTNs and OPTNs resulted in effective cell inhibition in vitro and a remarkable synergistic anticancer effect in vivo. The cell apoptosis results indicated that OPTNs combined with HPTNs could induce HepG2 cell apoptosis and exert synergistic effects. In vivo pharmacodynamics analysis using a solid tumour-bearing mouse model indicated that OPTNs combined with HPTNs could suppress tumour growth by 67.61%. This research suggests that the combined therapy system of OPTNs and HPTNs could be a new means of hepatoma therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. 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.

  3. 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.

  4. 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.

  5. Formulation of gammaoryzanol-loaded nanoparticles for potential application in fortifying food products.

    PubMed

    Ghaderi, Serveh; Ghanbarzadeh, Saeed; Mohammadhassani, Zahra; Hamishehkar, Hamed

    2014-12-01

    The field of nanoparticle delivery systems for nutrients and nutraceuticals with poor water solubility has attracted a great attention during the last decades. Ethyl cellulose (EC) based GO-loaded nanoparticles were prepared by solvent evaporation method. The effects of formulation parameters on nanoparticle size, encapsulation efficiency (EE%) and loading efficiency (LE%) were investigated. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) techniques were used to investigate the crystalline behavior of GO and EC after the preparation of nanoparticles. Stability of the prepared nanoparticle was investigated during five weeks of storage. Particle sizes of all formulation were in the range of 70-100 nm with narrow size distribution. Increase in the time of sonication from 1 to 5 minutes decreased the particle size. However, the mean particle size was increased when the sonication time increased from 5 to 7 minutes. The results showed that in the same concentration of PVA, increasing the ratio of EC:GO led to an increase in the GO encapsulation efficiency and decrease in loading efficiency. During five weeks, the mean diameter and size distribution indexes (SPAN values) of nanoparticles did not show significant changes. DSC and XRD studies indicated that crystallinity of GO was decreased in nanoparticles. EC based nanoparticles are promising carriers for addition of GO as a water insoluble antioxidant to fortify liquid food products without any change in quality of products.

  6. 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.

  7. 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

    2017-05-15

    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. Copyright © 2017 Elsevier B.V. All rights reserved.

  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. Development of flurbiprofen-loaded nanoparticles with a narrow size distribution using sucrose.

    PubMed

    Oh, Dong Hoon; Yan, Yi-Dong; Kim, Dong Wuk; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

    2014-02-01

    A novel flurbiprofen-loaded nanoemulsion which gave uniform emulsion droplets with a narrow size distribution was previously reported to be prepared using membrane emulsification method. The purpose of this study is to develop a novel flurbiprofen-loaded nanoparticle with a narrow size distribution and improved bioavailability. The nanoparticle was prepared by solidifying nanoemulsion using sucrose as a carrier via spray drying method. Its physicochemical properties were investigated using SEM, DSC and PXRD. Furthermore, dissolution and bioavailability in rats were evaluated compared to a flurbiprofen-loaded commercial product. The flurbiprofen-loaded nanoparticles with flurbiprofen/sucrose/surfactant mixture (1/20/2, weight ratio) gave good solidification and no stickiness. They associated with about 70,000-fold improved drug solubility and had a mean size of about 300 nm with a narrow size distribution. Flurbiprofen was present in a changed amorphous state in these nanoparticles. Moreover, the nanoparticles gave significantly shorter Tmax, and higher AUC and Cmax of the drug compared to the commercial product (p < 0.05). In particular, they showed about nine-fold higher AUC of the drug than did the commercial product. These flurbiprofen-loaded nanoparticles prepared with sucrose by the membrane emulsification and spray drying method would be a potential candidate for orally delivering poorly water-soluble flurbiprofen with enhanced bioavailability.

  11. Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system.

    PubMed

    Amidi, Maryam; Romeijn, Stefan G; Borchard, Gerrit; Junginger, Hans E; Hennink, Wim E; Jiskoot, Wim

    2006-03-10

    In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a carrier system for the nasal delivery of proteins was investigated. TMC nanoparticles were prepared by ionic crosslinking of TMC solution (with or without ovalbumin) with tripolyphosphate, at ambient temperature while stirring. The size, zeta-potential and morphology of the nanoparticles were investigated as a function of the preparation conditions. Protein loading, protein integrity and protein release were studied. The toxicity of the TMC nanoparticles was tested by ciliary beat frequency measurements of chicken embryo trachea and in vitro cytotoxicity assays. The in vivo uptake of FITC-albumin-loaded TMC nanoparticles by nasal epithelia tissue in rats was studied by confocal laser scanning microscopy. The nanoparticles had an average size of about 350 nm and a positive zeta-potential. They showed a loading efficiency up to 95% and a loading capacity up to 50% (w/w). The integrity of the entrapped ovalbumin was preserved. Release studies showed that more than 70% of the protein remained associated with the TMC nanoparticles for at least 3 h on incubation in PBS (pH 7.4) at 37 degrees C. Cytotoxicity tests with Calu-3 cells showed no toxic effects of the nanoparticles, whereas a partially reversible cilio-inhibiting effect on the ciliary beat frequency of chicken trachea was observed. In vivo uptake studies indicated the transport of FITC-albumin-associated TMC nanoparticles across the nasal mucosa. In conclusion, TMC nanoparticles are a potential new delivery system for transport of proteins through the nasal mucosa.

  12. 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.

  13. 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.

  14. Catalytic bubble-free hydrogenation reduction of azo dye by porous membranes loaded with palladium nanoparticles.

    PubMed

    Jia, Zhiqian; Sun, Huijie; Du, Zhenxia; Lei, Zhigang

    2014-02-01

    Catalytic bubble-free hydrogenation reduction of azo dye by porous membranes loaded with palladium (Pd) nanoparticles was studied for the first time. The effects of Pd loading, dye concentration and reuse repetitions of membranes were investigated. In reduction, the dye concentration decreased whereas the pH rose gradually. An optimal Pd loading was found. The catalytic membranes were able to be reused more than 3 times.

  15. 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.

  16. The impact of retinol loading and surface charge on the hepatic delivery of lipid nanoparticles.

    PubMed

    Pan, Tai-Long; Wang, Pei-Wen; Hung, Chi-Feng; Aljuffali, Ibrahim A; Dai, You-Shan; Fang, Jia-You

    2016-05-01

    The present work developed lipid nanoparticles to determine whether retinol loading and surface charge influenced liver targeting and biodistribution. Silibinin for treating liver fibrosis was used as the active model. The capability of nanoparticles to suppress hepatic stellate cells (HSCs) was investigated by examining cell viability and α-smooth muscle actin (α-SMA). The biodistribution of the nanocarriers in rats was monitored by real-time and organ bioimaging after an intravenous injection. Silibinin concentration in the organs was detected as well. Anionic nanoparticles showed a mean size of around 260 nm, which was greater than that of cationic nanoparticles (about 170 nm). The encapsulation percentage of silibinin was >98% for both anionic and cationic nanoparticles. All nanoparticles tested were able to be ingested into HSCs, with no difference between the formulations. The positive nanoparticles produced activated HSC apoptosis much more strongly than negative nanoparticles. The α-SMA suppression exhibited a contrary trend. The nanoparticles rapidly accumulated in the liver and spleen. Retinol incorporation in nanoparticles offers an active targeting approach to the liver via retinol binding protein (RBP). The negatively charged formulation containing retinol achieved higher uptake and longer retention in the liver than the other formulations. Silibinin inclusion in nanoparticles significantly decreased lung deposition and increased liver uptake. The lipid nanosystems promoted silibinin distribution to the liver by 2-3-fold compared to the free control. A better liver-specific selectivity was obtained by retinol-loaded anionic nanocarriers. It is important to optimize the formulations of the lipid nanoparticles for maximizing hepatic targeting. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. 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

  18. 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.

  19. Sonoprinting and the importance of microbubble loading for the ultrasound mediated cellular delivery of nanoparticles.

    PubMed

    De Cock, Ine; Lajoinie, Guillaume; Versluis, Michel; De Smedt, Stefaan C; Lentacker, Ine

    2016-03-01

    In the last years, research on ultrasound mediated drug delivery using microbubbles is vastly expanding. While some groups simply mix drugs and microbubbles (co-administration), other researchers have a major interest in the potential of drug-loaded microbubbles. However, today, little is known on the pros and cons of these two strategies. In this study we evaluated the delivery of nanoparticles (polystyrene nanospheres and mRNA-lipoplexes) to cells in vitro, in case the nanoparticles were mixed with unloaded microbubbles versus loaded onto the microbubbles. Flow cytometry experiments demonstrated that unloaded microbubbles did not enhance the cellular delivery of the nanospheres and mRNA-lipoplexes. However, upon loading the nanoparticles onto the microbubbles, their delivery to cells substantially improved. Real-time swept field confocal microscopy imaging of the microbubbles and cells during ultrasound radiation revealed that nanoparticle-loaded microbubbles directly deposited the nanoparticles in patches onto the cell membrane, a process that we termed 'sonoprinting'. This phenomenon resulted in the delivery of large amounts of nanoparticles to the cells and is suggested to be different from the creation of cell membrane pores and enhanced endocytosis, which have been reported before as mechanisms behind the improved delivery of drugs to cells by ultrasound. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. 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.

  1. 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

  2. Curcumin-Loaded Lipid Cubic Liquid Crystalline Nanoparticles: Preparation, Optimization, Physicochemical Properties and Oral Absorption.

    PubMed

    He, Xiuli; Li, Qinghua; Liu, Xiuju; Wu, Guangsheng; Zhai, Guangxi

    2015-08-01

    In order to improve the oral absorption of curcumin, curcumin-loaded lipid cubic liquid crystalline nanoparticles were prepared and evaluated in vitro and in vivo. The hot and high-pressure homogenization method was used to prepare the nanoparticles. The formulation and process were optimized by uniform design with drug loading and entrapment efficiency as index, and physicochemical properties were also investigated. Spherical nanoparticles were observed under transmission electron microscope (TEM), with average particle size of 176.1 nm, zeta potential of -25.19 mV, average drug loading of (1.5 ± 0.2)% and entrapment efficiency of (95 ± 1.8)%. The in vitro release of curcumin from the nanoparticle formulation showed a sustained property, while the pharmacokinetics results after oral administration of curcumin loaded lipid cubic liquid crystalline nanoparticles in rat showed that the oral absorption of curcumin fitted one-compartment model and relative bioavailability was 395.56% when compared to crude curcumin. It can be concluded from these results that the lipid cubic liquid crystalline nanoparticles, as carriers, can markedly improve the oral absorption of curcumin.

  3. 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.

  4. 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.

  5. The effect of high intensity ultrasound on the loading of Au nanoparticles into titanium dioxide.

    PubMed

    Belova, Valentina; Borodina, Tatiana; Möhwald, Helmuth; Shchukin, Dmitry G

    2011-01-01

    Novel metal/semiconductor nanocomposites have been synthesized from pre-formed components by applying high intensity ultrasound irradiation. Positively and negatively charged Au nanoparticles were intercalated into mesoporous TiO(2) by sonication. The synthesized nanocomposites with implanted gold nanoparticles possess a narrow pore-size distribution around 7 nm and a large surface area of about 210 m(2)/g. The intercalation of the Au nanoparticles into the TiO(2) framework depends on the charge of the Au nanoparticles, time and amplitude of ultrasonic treatment. The experiments show that at 20 min of ultrasonic irradiation the volume fraction of the negatively charged Au nanoparticles intercalated into TiO(2) is 15%. By contrast, at the same time, 8.1% of positively charged Au nanoparticles with a diameter of about 6-7 nm enters into the TiO(2) matrix. The characterization of the samples was carried out by X-ray diffraction, transmission electron microscopy, high-resolution transmission electron microscopy, scanning electron microscopy, Fourier transform infrared measurements and BET analysis. The structure of TiO(2) was not considerably affected by the intercalation of the Au nanoparticles. TiO(2) doped with negatively charged Au nanoparticles presented a higher photocatalytic activity (75 wt.%) than TiO(2) loaded with positively charged Au nanoparticles (62 wt.%), because of an enlarged surface area and quantity of Au nanoparticles in titania. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. 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

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

    PubMed

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

    2017-10-01

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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Individual-collective crossover driven by particle size in dense assemblies of superparamagnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Ridier, Karl; Gillon, Béatrice; Chaboussant, Grégory; Catala, Laure; Mazérat, Sandra; Rivière, Eric; Mallah, Talal

    2017-02-01

    Prussian blue analogues (PBA) ferromagnetic nanoparticles CsIxNiII[CrIII(CN)6 ]z·3(H2O) embedded in CTA+ (cetyltrimethylammonium) matrix have been investigated by magnetometry and magnetic small-angle neutron scattering (SANS). Choosing particle sizes (diameter D = 4.8 and 8.6 nm) well below the single-domain radius and comparable volume fraction of particle, we show that the expected superparamagnetic regime for weakly anisotropic isolated magnetic particles is drastically affected due to the interplay of surface/volume anisotropies and dipolar interactions. For the smallest particles (D = 4.8 nm), magnetocrystalline anisotropy is enhanced by surface spins and drives the system into a regime of ferromagnetically correlated clusters characterized by a temperature-dependent magnetic correlation length Lmag which is experimentally accessible using magnetic SANS. For D = 8.6 nm particles, a superparamagnetic regime is recovered in a wide temperature range. We propose a model of interacting single-domain particles with axial anisotropy that accounts quantitatively for the observed behaviors in both magnetic regimes. Supplementary material in the form of one pdf file available from the Journal web page at http://https://doi.org/10.1140/epjb/e2017-70534-9

  13. 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.

  14. 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

  15. 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.

  16. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Tamoxifen citrate loaded solid lipid nanoparticles (SLN): preparation, characterization, in vitro drug release, and pharmacokinetic evaluation.

    PubMed

    Reddy, L Harivardhan; Vivek, K; Bakshi, Nishant; Murthy, R S R

    2006-01-01

    Solid lipid nanoparticles (SLN) were prepared by emulsification and high pressure homogenization technique and characterized by size analysis and differential scanning calorimetry. The influence of experimental factors such as homogenization pressure, time, and surfactant concentration on the nanoparticle size and distribution were investigated to optimize the formulation. Homogenization at 15,000 psi for 3 cycles was found to be optimum and resulted in smaller sized nanoparticles. In case of tristearin SLN (TSSLN), tripalmitin SLN (TPSLN), and glycerol behenate SLN (GBSLN), the relatively smaller sized nanoparticles were obtained with 3% sodium tauroglycocholate. The SLN were loaded with an anticancer agent, tamoxifen citrate (TC). The TC-loaded TSSLN shown lower entrapment efficiency (78.78%) compared to the TPSLN (86.75%) and GBSLN (98.64%). Short term stability studies indicated a significant increase in size of nanoparticles when stored at 500C, compared to those stored at 30 degrees C and 4 degrees C. The particle destabilization upon storage in case of all the types of nanoparticles studied was in the order of day light > artificial light > dark. An ultraviolet (UV) spectrophotometric method of estimation of tamoxifen in rat plasma was developed and validated. The TC-loaded TSSLN was administered to the rats intravenously and the pharmacokinetic parameters in the plasma were determined. The t(1/2) and mean residence time of TC-loaded TSSLN in plasma was about 3.5-fold (p < 0.001) and 3-fold (p < 0.001) higher, respectively, than the free tamoxifen, indicating the potential of TC-loaded TSSLN as a long circulating system in blood. Thus the above mentioned solid lipid nanoparticles can be a beneficial system to deliver tamoxifen to cancer tissues through enhanced permeability and retention (EPR) effect.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Design and Optimization of PLGA-Based Diclofenac Loaded Nanoparticles

    PubMed Central

    Cooper, Dustin L.; Harirforoosh, Sam

    2014-01-01

    Drug based nanoparticle (NP) formulations have gained considerable attention over the past decade for their use in various drug formulations. NPs have been shown to increase bioavailability, decrease side effects of highly toxic drugs, and prolong drug release. Nonsteroidal anti-inflammatory drugs such as diclofenac block cyclooxygenase expression and reduce prostaglandin synthesis, which can lead to several side effects such as gastrointestinal bleeding and renal insufficiency. The aim of this study was to formulate and characterize diclofenac entrapped poly(lactide-co-glycolide) (PLGA) based nanoparticles. Nanoparticles were formulated using an emulsion-diffusion-evaporation technique with varying concentrations of poly vinyl alcohol (PVA) (0.1, 0.25, 0.5, or 1%) or didodecyldimethylammonium bromide (DMAB) (0.1, 0.25, 0.5, 0.75, or 1%) stabilizers centrifuged at 8,800 rpm or 12,000 rpm. The resultant nanoparticles were evaluated based on particle size, zeta potential, and entrapment efficacy. DMAB formulated NPs showed the lowest particle size (108±2.1 nm) and highest zeta potential (−27.71±0.6 mV) at 0.1 and 0.25% respectively, after centrifugation at 12,000 rpm. Results of the PVA based NP formulation showed the smallest particle size (92.4±7.6 nm) and highest zeta potential (−11.14±0.5 mV) at 0.25% and 1% w/v, respectively, after centrifugation at 12,000 rpm. Drug entrapment reached 77.3±3.5% and 80.2±1.2% efficiency with DMAB and PVA formulations, respectively. The results of our study indicate the use of DMAB for increased nanoparticle stability during formulation. Our study supports the effective utilization of PLGA based nanoparticle formulation for diclofenac. PMID:24489896

  7. 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.

  8. 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.

  9. Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy

    PubMed Central

    Maji, Ruma; Dey, Niladri Shekhar; Satapathy, Bhabani Sankar; Mukherjee, Biswajit; Mondal, Subhasish

    2014-01-01

    Background Four formulations of Tamoxifen citrate loaded polylactide-co-glycolide (PLGA) based nanoparticles (TNPs) were developed and characterized. Their internalization by Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated. Methods Nanoparticles were prepared by a multiple emulsion solvent evaporation method. Then the following studies were carried out: drug-excipients interaction using Fourier transform infrared spectroscopy (FTIR), surface morphology by field emission scanning electron microscopy (FESEM), zeta potential and size distribution using a Zetasizer Nano ZS90 and particle size analyzer, and in vitro drug release. In vitro cellular uptake of nanoparticles was assessed by confocal microscopy and their cell viability (%) was studied. Results No chemical interaction was observed between the drug and the selected excipients. TNPs had a smooth surface, and a nanosize range (250–380 nm) with a negative surface charge. Drug loadings of the prepared particles were 1.5%±0.02% weight/weight (w/w), 2.68%±0.5% w/w, 4.09%±0.2% w/w, 27.16%±2.08% w/w for NP1–NP4, respectively. A sustained drug release pattern from the nanoparticles was observed for the entire period of study, ie, up to 60 days. Further, nanoparticles were internalized well by the MCF-7 breast cancer cells on a concentration dependent manner and were present in the cytoplasm. The nucleus was free from nanoparticle entry. Drug loaded nanoparticles were found to be more cytotoxic than the free drug. Conclusion TNPs (NP4) showed the highest drug loading, released the drug in a sustained manner for a prolonged period of time and were taken up well by the MCF-7 breast cancer cell line in vitro. Thus the formulation may be suitable for breast cancer treatment due to the good permeation of the formulation into the breast cancer cells. PMID:25028549

  10. Preparation and characterization of Tamoxifen citrate loaded nanoparticles for breast cancer therapy.

    PubMed

    Maji, Ruma; Dey, Niladri Shekhar; Satapathy, Bhabani Sankar; Mukherjee, Biswajit; Mondal, Subhasish

    2014-01-01

    Four formulations of Tamoxifen citrate loaded polylactide-co-glycolide (PLGA) based nanoparticles (TNPs) were developed and characterized. Their internalization by Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated. Nanoparticles were prepared by a multiple emulsion solvent evaporation method. Then the following studies were carried out: drug-excipients interaction using Fourier transform infrared spectroscopy (FTIR), surface morphology by field emission scanning electron microscopy (FESEM), zeta potential and size distribution using a Zetasizer Nano ZS90 and particle size analyzer, and in vitro drug release. In vitro cellular uptake of nanoparticles was assessed by confocal microscopy and their cell viability (%) was studied. No chemical interaction was observed between the drug and the selected excipients. TNPs had a smooth surface, and a nanosize range (250-380 nm) with a negative surface charge. Drug loadings of the prepared particles were 1.5%±0.02% weight/weight (w/w), 2.68%±0.5% w/w, 4.09%±0.2% w/w, 27.16%±2.08% w/w for NP1-NP4, respectively. A sustained drug release pattern from the nanoparticles was observed for the entire period of study, ie, up to 60 days. Further, nanoparticles were internalized well by the MCF-7 breast cancer cells on a concentration dependent manner and were present in the cytoplasm. The nucleus was free from nanoparticle entry. Drug loaded nanoparticles were found to be more cytotoxic than the free drug. TNPs (NP4) showed the highest drug loading, released the drug in a sustained manner for a prolonged period of time and were taken up well by the MCF-7 breast cancer cell line in vitro. Thus the formulation may be suitable for breast cancer treatment due to the good permeation of the formulation into the breast cancer cells.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Doxorubicin-loaded mesoporous magnetic nanoparticles to induce apoptosis in breast cancer cells.

    PubMed

    Zou, Yan; Liu, Pin; Liu, Chuan-He; Zhi, Xu-Ting

    2015-02-01

    Selective targeting of chemotherapeutic drugs toward the cancer cells overcomes the limitations involved in chemotherapy. Ideally, targeted delivery system holds great potential in cancer therapy due to specific release of drug in the cancer tissues. In this regard, DOX-loaded chitosan coated mesoporous magnetic nanoparticles (DOX-CMMN) were prepared and evaluated for its physicochemical and biological characteristics. Nanosized magnetic nanoparticles were observed with a high loading capacity for DOX. The drug-loaded nanoparticles exhibited a controlled and sustained release of drug without any burst release phenomenon. The DOX-DMMN showed a concentration-dependent cell proliferation inhibitory action against breast cancer cells. The blank nanoparticles showed excellent biocompatibility with cell viability >85% at the maximum tested concentration. Our results showed that chitosan coated magnetic system has high potential for breast cancer targeting under an alternating current magnetic field (ACMF). The present study showed that magnetic nanoparticles can be targeted to tumor cells under the presence of oscillating magnetic field. The combined effect of chemotherapy and thermotherapy can have a promising clinical potential for the treatment of breast cancer. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  17. Nanoparticles based on crocin loaded chitosan-alginate biopolymers: Antioxidant activities, bioavailability and anticancer properties.

    PubMed

    Rahaiee, Somayeh; Hashemi, Maryam; Shojaosadati, Seyed Abbas; Moini, Sohrab; Razavi, Seyed Hadi

    2017-06-01

    Crocin, a water-soluble carotenoid in saffron, is a highly bioactive compound with limited use due to instability to pH variations, heat and oxidative stress, rapid absorption and low bioavailability. In this study, chitosan-alginate nanoparticles, considered as a new vehicle for crocin to improve properties in terms of antioxidant activity, bioavailability and anticancer activity. The swelling of crocin loaded nanoparticles was pH-dependent so that the highest swelling ratio (16g/g) was observed in acidic condition (pH=1.2) after 24h. The antioxidant activity of the crocin loaded nanoparticles was the same effective as pure crocin on DPPH free radical scavenging and ferric reducing ability of plasma (FRAP). In vitro crocin release profile from composite nanoparticles was investigated under simulated physiological conditions during incubation time. The experimental reports collected in this study strongly indicate that nanoparticles loaded with crocin could be the prospective candidates for the future anti-cancer therapeutics that deserve additional investigations. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Hydrogels containing porphyrin-loaded nanoparticles for topical photodynamic applications.

    PubMed

    González-Delgado, José A; Castro, Pedro M; Machado, Alexandra; Araújo, Francisca; Rodrigues, Francisca; Korsak, Bárbara; Ferreira, Marta; Tomé, João P C; Sarmento, Bruno

    2016-08-20

    5,10,15,20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra-iodide (TMPyP), a potent water-soluble photosensitizer (PS) used in antimicrobial applications, was encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TMPyP-PLGA) for topical delivery purposes. Nanoparticles resulted in a mean particle size around 130nm, narrow polydispersity index (PdI), spherical morphology and association efficiency up to 93%. Free TMPyP and TMPyP-PLGA nanoparticles were incorporated into Carbopol(®) hydrogels, resulting in controlled TMPyP release of about 60% and 20% after 4.5h, respectively. Critical properties such as appearance, clarity, viscosity and pH were maintained over time, as hydrogels were stable during 6 months at 4°C, 25°C/60% RH and 40°C/75% RH. For photodynamic applications, the photoproduction of singlet oxygen from these hydrogels was quite efficient being both formulations very photostable after 20min. No TMPyP permeation through pig ear skin was observed after 24h, and histological assays did not show relevant damages in surrounding tissues. All these excellent characteristics make them promising platforms for photodynamic applications through topical clinical use. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. 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

  6. Preparation, characterization and immunological evaluation: canine parvovirus synthetic peptide loaded PLGA nanoparticles.

    PubMed

    Derman, Serap; Mustafaeva, Zeynep Akdeste; Abamor, Emrah Sefik; Bagirova, Melahat; Allahverdiyev, Adil

    2015-10-20

    Canine parvovirus 2 (CPV-2) remains a significant worldwide canine pathogen and the most common cause of viral enteritis in dogs. The 1 L15 and 7 L15 peptides overlap each other with QPDGGQPAV residues (7-15 of VP2 capsid protein of CPV) is shown to produce high immune response. PLGA nanoparticles were demonstrated to have special properties such as; controlled antigen release, protection from degradation, elimination of booster-dose and enhancing the cellular uptake by antigen presenting cells. Nevertheless, there is no study available in literature, about developing vaccine based on PLGA nanoparticles with adjuvant properties against CPV. Thus, the aim of the present study was to synthesize and characterize high immunogenic W-1 L19 peptide (from the VP2 capsid protein of CPV) loaded PLGA nanoparticle and to evaluate their in vitro immunogenic activity. PLGA nanoparticles were produced with 5.26 ± 0.05 % loading capacity and high encapsulation efficiency with 81.2 ± 3.1 %. Additionally, it was evaluated that free NPs and W-1 L19 peptide encapsulated PLGA nanoparticles have Z-ave of 183.9 ± 12.1 nm, 221.7 ± 15.8 nm and polydispersity index of 0.107 ± 0.08, 0.135 ± 0.12 respectively. It was determined that peptide loaded PLGA nanoparticles were successfully phagocytized by macrophage cells and increased NO production at 2-folds (*P < 0.05) in contrast to free peptide, and 3-folds (*P < 0.01) in contrast to control. In conclusion, for the first time, W-1 L19 peptide loaded PLGA nanoparticles were successfully synthesized and immunogenic properties evaluated. Obtained results showed that PLGA nanoparticles enhanced the capacity of W-1 L19 peptide to induce nitric oxide production in vitro due to its adjuvant properties. Depend on the obtained results, these nanoparticles can be accepted as potential vaccine candidate against Canine Parvovirus. Studies targeting PLGA nanoparticles based delivery system must be maintained in near

  7. 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

  8. 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

  9. 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.

  10. Doxorubicin loaded iron oxide nanoparticles overcome multidrug resistance in cancer in vitro.

    PubMed

    Kievit, Forrest M; Wang, Freddy Y; Fang, Chen; Mok, Hyejung; Wang, Kui; Silber, John R; Ellenbogen, Richard G; Zhang, Miqin

    2011-05-30

    Multidrug resistance (MDR) is characterized by the overexpression of ATP-binding cassette (ABC) transporters that actively pump a broad class of hydrophobic chemotherapeutic drugs out of cancer cells. MDR is a major mechanism of treatment resistance in a variety of human tumors, and clinically applicable strategies to circumvent MDR remain to be characterized. Here we describe the fabrication and characterization of a drug-loaded iron oxide nanoparticle designed to circumvent MDR. Doxorubicin (DOX), an anthracycline antibiotic commonly used in cancer chemotherapy and substrate for ABC-mediated drug efflux, was covalently bound to polyethylenimine via a pH sensitive hydrazone linkage and conjugated to an iron oxide nanoparticle coated with amine terminated polyethylene glycol. Drug loading, physiochemical properties and pH lability of the DOX-hydrazone linkage were evaluated in vitro. Nanoparticle uptake, retention, and dose-dependent effects on viability were compared in wild-type and DOX-resistant ABC transporter over-expressing rat glioma C6 cells. We found that DOX release from nanoparticles was greatest at acidic pH, indicative of cleavage of the hydrazone linkage. DOX-conjugated nanoparticles were readily taken up by wild-type and drug-resistant cells. In contrast to free drug, DOX-conjugated nanoparticles persisted in drug-resistant cells, indicating that they were not subject to drug efflux. Greater retention of DOX-conjugated nanoparticles was accompanied by reduction of viability relative to cells treated with free drug. Our results suggest that DOX-conjugated nanoparticles could improve the efficacy of chemotherapy by circumventing MDR. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. 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

  12. 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.

  13. Preparation, physicochemical characterization and antioxidant activity of diphenyl diselenide-loaded poly(lactic acid) nanoparticles.

    PubMed

    Dos Reis Antunes Junior, Osmar; Antônio, Emilli; Mainardes, Rubiana Mara; Khalil, Najeh Maissar

    2017-01-01

    In this study, we developed, characterized and evaluated the antioxidant activity of poly (lactic acid) nanoparticles containing diphenyl diselenide (PhSe)2. Nanoparticles were characterized in terms of mean particle size, polydispersity index, zeta potential, encapsulation efficiency, in vitro release profile, physical stability, polymer-drug interactions and thermal properties. Also, the antioxidant activity of nanoparticles on hypochlorous acid (HOCl) was assessed. Nanoparticles presented a mean size of 210nm, had low polydispersity, zeta potential of -24mV, and an encapsulation efficiency over 90%. Differential scanning calorimetry and X-ray diffraction results showed (PhSe)2 is dispersed in PLA matrix in an amorphous state. Lyophilized nanoparticles maintained physical stability over three months, while nanoparticles dispersed in water did not present stability over 7days. In vitro release assay was characterized by a biphasic release pattern with burst effect in 8h followed by a sustained release diffusion governed over 192h. Nanoencapsulation did not alter the antioxidant activity of (PhSe)2 on HOCl. The study concludes these properties of (PhSe)2-loaded nanoparticles can be useful to extend the biological effects of (PhSe)2. Copyright © 2016 Elsevier GmbH. All rights reserved.

  14. 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.

  15. 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

  16. 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.

  17. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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

  20. The Role Radius of Curvature Plays in Thiolated Oligonucleotide Loading on Gold Nanoparticles

    PubMed Central

    Hill, Haley D.; Millstone, Jill E.; Banholzer, Matthew J.; Mirkin, Chad A.

    2011-01-01

    We show that by correlating the radius of curvature of spherical gold nanoparticles of varying sizes with their respective thiol terminated oligonucleotide loading densities that a mathematical relationship can be derived for predicting the loading of oligonucleotides on anisotropic gold nanomaterials. This mathematical relationship was tested with gold nanorods (radius 17.5 nm, length 475 nm) where the measured number of oligonucleotides per rod (3330 ±110) was within experimental error of the predicted loading of 3244 oligonucleotides from the derivation. Additionally, we show that once gold nanoparticles reach a diameter of approximately 60 nm (and certainly 100 nm) the local surface experienced by the oligonucleotide is highly similar to that of a planar surface. PMID:19236080

  1. Bovine serum albumin nanoparticles loaded with Photosens photosensitizer for effective photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Khanadeev, Vitaly; Khlebtsov, Boris; Packirisamy, Gopinath; Khlebtsov, Nikolai

    2017-03-01

    Polymeric nanoparticles (NPs) are widely used for drug delivery applications due to high biodegradability, low toxicity and high loading capacity. The focus of this study is the development of photosensitizer Photosens (PS) loaded albumin NPs for efficient photodynamic therapy (PDT). To fabricate PS-loaded bovine serum albumin nanoparticles (BSA-PS NPs), we used a coacervation method with glutaraldehyde followed by passive loading of PS. Successful loading of PS was confirmed by appearance of characteristic peak in absorption spectrum which allows to determine the PS loading in BSA NPs. The synthesized BSA-PS NPs demonstrated low toxicity to HeLa cells at therapeutic concentrations of loaded PS. Compared to free PS solution, the synthesized BSA-PS NPs generated the singlet oxygen more effectively under laser irradiation at 660 nm. In addition, due to presence of various chemical groups on the surface of BSA-PS NPs, they are capable to adsorb on cell surface and accumulate in cells due to cellular uptake mechanisms. Owing to combination of PD and cell uptake advantages, BSA-PS NPs demonstrated higher efficacy of photodynamic damage to cancer cells as compared to free PS at equivalent concentrations. These results suggest that non-targeted BSA-PS NPs with high PD activity and low-fabrication costs of are promising candidates for transfer to PD clinic treatments.

  2. 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

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

    PubMed

    Tang, Xiaolong; Cai, Shuyu; Zhang, Rongbo; Liu, Peng; Chen, Hongbo; Zheng, Yi; Sun, Leilei

    2013-10-17

    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.

  4. A Novel Docetaxel-Loaded Poly (ɛ-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

    NASA Astrophysics Data System (ADS)

    Mei, Lin; Zhang, Yangqing; Zheng, Yi; Tian, Ge; Song, Cunxian; Yang, Dongye; Chen, Hongli; Sun, Hongfan; Tian, Yan; Liu, Kexin; Li, Zhen; Huang, Laiqiang

    2009-12-01

    Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ɛ-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere® in the MCF-7 TAX30 cell culture, but the differences were not significant ( p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere® ( p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer.

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

    NASA Astrophysics Data System (ADS)

    Tang, Xiaolong; Cai, Shuyu; Zhang, Rongbo; Liu, Peng; Chen, Hongbo; Zheng, Yi; Sun, Leilei

    2013-10-01

    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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Repetitive heterocoagulation of oppositely charged particles for enhancement of magnetic nanoparticle loading into monodisperse silica particles.

    PubMed

    Matsumoto, Hideki; Nagao, Daisuke; Konno, Mikio

    2010-03-16

    Oppositely charged particles were repetitively heterocoagulated to fabricate highly monodisperse magnetic silica particles with high loading of magnetic nanoparticles. Positively charged magnetic nanoparticles prepared by surface modification with N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride (TSA) were used to heterocoagulate with silica particles under basic conditions to give rise to negative silica surface charge and prevent the oxidation of the magnetic nanoparticles. The resultant particles of silica core homogeneously coated with the magnetic nanoparticles were further coated with thin silica layer with sodium silicate in order to enhance colloidal stability and avoid desorption of the magnetic nanoparticles from the silica cores. Five repetitions of the heterocoagulation and the silica coating could increase saturation magnetization of the magnetic silica particles to 27.7 emu/g, keeping the coefficient of variation of particle sizes (C(V)) less than 6.5%. Highly homogeneous loading of the magnetic component was confirmed by measuring Fe-to-Si atomic ratios of individual particles with energy dispersive X-ray spectroscopy.

  11. Evaluation of ciprofloxacin-loaded Eudragit RS100 or RL100/PLGA nanoparticles.

    PubMed

    Dillen, Kathleen; Vandervoort, Jo; Van den Mooter, Guy; Ludwig, Annick

    2006-05-11

    The objective of present study was to prepare positively charged ciprofloxacin-loaded nanoparticles providing a controlled release formulation. The particles were prepared by water-in-oil-in-water (w/o/w) emulsification and solvent evaporation, followed by high-pressure homogenisation. Two non-biodegradable positively charged polymers, Eudragit RS100 and RL100, and the biodegradable polymer poly(lactic-co-glycolic acid) or PLGA were used alone or in combination, with varying ratios. The formulations were evaluated in terms of particle size and zeta potential. Differential scanning calorimetry measurements were carried out on the nanoparticles and on the pure polymers Eudragit and PLGA. Drug loading and release properties of the nanoparticles were examined. The antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus was determined. During solvent evaporation, the size and zeta potential of the nanoparticles did not change significantly. The mean diameter was dependent on the presence of Eudragit and on the viscosity of the organic phase. The zeta potential of all Eudragit containing nanoparticles was positive in ultrapure water (around +21/+25 mV). No burst effect but a prolonged drug release was observed from all formulations. The particles' activity against P. aeruginosa and S. aureus was comparable with an equally concentrated ciprofloxacin solution.

  12. 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.

  13. Development of gatifloxacin-loaded cationic polymeric nanoparticles for ocular drug delivery.

    PubMed

    Duxfield, Linda; Sultana, Rubab; Wang, Ruokai; Englebretsen, Vanessa; Deo, Samantha; Swift, Simon; Rupenthal, Ilva; Al-Kassas, Raida

    2016-03-01

    The present investigation aimed at improving the ocular bioavailability of gatifloxacin by prolonging its residence time in the eye and reducing problems associated with the drug re-crystallization after application through incorporation into cationic polymeric nanoparticles. Gatifloxacin-loaded nanoparticles were prepared via the nanoprecipitation and double emulsion techniques. A 50:50 Eudragit® RL and RS mixture was used as cationic polymer with other formulation parameters varied. Prepared nanoparticles were evaluated for size, zeta potential, and drug loading. An optimized formulation was selected and further characterized for in vitro drug release, cytotoxicity, and antimicrobial activity. The double emulsion method produced larger nanoparticles than the nanoprecipitation method (410 nm and 68 nm, respectively). Surfactant choice also affected particle size and zeta potential with Tween 80 producing smaller-sized particles with higher zeta potential than PVA. However, the zeta potential was positive at all experimental conditions investigated. The optimal formulation produced by double emulsion technique and has achieved 46% drug loading. This formulation had optimal physicochemical properties with acceptable cytotoxicity results, and very prolonged release rate. The particles antimicrobial activities of the selected formulation have been tested against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and showed prolonged antimicrobial effect for gatifloxacin.

  14. Synthesis, characterization, release kinetics and toxicity profile of drug-loaded starch nanoparticles.

    PubMed

    El-Naggar, Mehrez E; El-Rafie, M H; El-sheikh, M A; El-Feky, Gina S; Hebeish, A

    2015-11-01

    The current research work focuses on the medical application of the cost-effective cross-linked starch nanoparticles, for the transdermal delivery using Diclofenac sodium (DS) as a model drug. The prepared DS-cross-linked starch nanoparticles were synthesized using nanoprecipitation technique at different concentrations of sodium tripolyphosphate (STPP) in the presence of Tween 80 as a surfactant. The resultant cross-linked starch nanoparticles loaded with DS were characterized using world-class facilities such as TEM, DLS, FT-IR, XRD, and DSc. The efficiency of DS loading was also evaluated via entrapment efficiency as well as in vitro release and histopathological study on rat skin. The optimum nanoparticles formulation selected by the JMP(®) software was the formula that composed of 5% maize starch, 57.7mg DS and 0.5% STPP and 0.4% Tween 80, with particle diameter of about 21.04nm, polydispersity index of 0.2 and zeta potential of -35.3mV. It is also worth noting that this selected formula shows an average entrapment efficiency of 95.01 and sustained DS release up to 6h. The histophathological studies using the best formula on rat skin advocate the use of designed transdermal DS loaded cross-linked starch nanoparticles as it is safe and non-irritant to rat skin. The overall results indicate that, the starch nanoparticles could be considered as a good carrier for DS drug regarding the enhancement in its controlled release and successful permeation, thus, offering a promising nanoparticulate system for the transdermal delivery non-steroidal anti-inflammatory drug (NSAID). Copyright © 2015 Elsevier B.V. All rights reserved.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. [Preparation and antibacterial capacity of artificial skin loaded with nanoparticles silver using bacterial cellulose].

    PubMed

    Sun, Dongping; Yang, Jiazhi; Li, Jun; Zhou, Lingli; Yu, Junwei

    2009-10-01

    In the present paper, in-situ preparation of silver nanoparticles have been conducted in 3D network structure of BC membrane through liquid phase chemical deoxidization method. The characterization of products was investigated using scanning electron microscopy (SEM), infrared spectroscopy (IR), energy dispersion spectrometry (SEM-EDS). The absorbing water capacity and preserving water capacity of substitutes and the antibacterial capacities of antibacterial agent-loaded artificial skin were tested. The results showed the silver nanoparticles were approximately spherical particles with an average diameter of 45nm, and were noted to have excellent sterilizing efficacy the efficiency of against Escherichia coli, yeast and Candida albicans.

  20. Indocyanine green-loaded hollow mesoporous silica nanoparticles as an activatable theranostic agent

    NASA Astrophysics Data System (ADS)

    Hong, Suk ho; Kim, Hyunjin; Choi, Yongdoo

    2017-05-01

    Here we report indocyanine green (ICG)-loaded hollow mesoporous silica nanoparticles (ICG@HMSNP) as an activatable theranostic platform. Near-infrared fluorescence and singlet oxygen generation of ICG@HMSNP was effectively quenched (i.e. turned off) in its native state because of the fluorescence resonance energy transfer between ICG molecules. Therefore, ICG@HMSNP was nonfluorescent and nonphototoxic in the extracellular region. After the nanoparticles entered the cancer cells via endocytosis, they became highly fluorescent and phototoxic. In addition, intracellular uptake of ICG@HMSNP was 2.75 times higher than that of free ICG, resulting in an enhanced phototherapy of cancer.

  1. Indocyanine green-loaded hollow mesoporous silica nanoparticles as an activatable theranostic agent.

    PubMed

    Hong, Suk Ho; Kim, Hyunjin; Choi, Yongdoo

    2017-05-05

    Here we report indocyanine green (ICG)-loaded hollow mesoporous silica nanoparticles (ICG@HMSNP) as an activatable theranostic platform. Near-infrared fluorescence and singlet oxygen generation of ICG@HMSNP was effectively quenched (i.e. turned off) in its native state because of the fluorescence resonance energy transfer between ICG molecules. Therefore, ICG@HMSNP was nonfluorescent and nonphototoxic in the extracellular region. After the nanoparticles entered the cancer cells via endocytosis, they became highly fluorescent and phototoxic. In addition, intracellular uptake of ICG@HMSNP was 2.75 times higher than that of free ICG, resulting in an enhanced phototherapy of cancer.

  2. 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.

  3. VitD3-loaded solid lipid nanoparticles: stability, cytotoxicity and cytokine levels.

    PubMed

    Demirbilek, Murat; Laçin Türkoglu, Nelisa; Aktürk, Selçuk; Akça, Cem

    2017-08-01

    Vitamin D3 (VitD3) has several beneficial effects on many metabolic pathways such as immunity system, bone development. The aim of the study, encapsulation of VitD3 with solid lipids, determine encapsulation efficiency and biocompatibility of nanoparticles. Therefore, VitD3-loaded solid lipid nanoparticles (SLNPs) were developed by optimising ratios of VitD3, stearic acid, beeswax and sodium dodecyl sulphate (SDS). Thermal stability, degradation profile, crystallinity rate, encapsulation efficiency and release profile of SLNPs were determined. Cytotoxicity of SLNPs on HaCaT, L929 and HUVEC cells were investigated. Negatively charged and VitD3-loaded nanoparticles with diameters between 30 and 60 nm were obtained. SLNPs containing up to 5.1 mg VitD3 per 10 mg powder samples were obtained. Cell proliferations were stimulated after exposure with VitD3-loaded SLNPs. Besides, inflammatory response after exposure to VitD3-loaded SLNPs was evaluated via determining IL10 and TNF-alpha levels on THP-1 cells. According to the results, no inflammatory response was observed.

  4. Microfluidic synthesis of dye-loaded polycaprolactone-block-poly(ethylene oxide) nanoparticles: Insights into flow-directed loading and in vitro release for drug delivery.

    PubMed

    Bains, Aman; Wulff, Jeremy E; Moffitt, Matthew G

    2016-08-01

    Using the fluorescent probe dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) as a surrogate for hydrophobic drugs, we investigate the effects of water content and on-chip flow rate on the multiscale structure, loading and release properties of DiI-loaded poly(ε-caprolactone)-block-poly(ethylene oxide) (PCL-b-PEO) nanoparticles produced in a gas-liquid segmented microfluidic device. We find a linear increase in PCL crystallinity within the nanoparticle cores with increasing flow rate, while mean nanoparticle sizes first decrease and then increase with flow rate coincident with the disappearance and reappearance of long filament nanoparticles. Loading efficiencies at the lower water content (cwc+10wt%) are generally higher (up to 94%) compared to loading efficiencies (up to 53%) at the higher water content (cwc+75wt%). In vitro release times range between ∼2 and 4days for nanoparticles produced at cwc+10wt% and >15days for nanoparticles produced at cwc+75wt%. At the lower water content, slower release of DiI is found for nanoparticles produced at higher flow rate, while at high water content, release times first decrease and then increase with flow rate. Finally, we investigate the effects of the chemical and physical characteristics of the release medium on the kinetics of in vitro DiI release and nanoparticle degradation. This work demonstrates the general utility of dye-loaded nanoparticles as model systems for screening chemical and flow conditions for producing drug delivery formulations within microfluidic devices. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Enhanced photodynamic therapy efficacy of methylene blue-loaded calcium phosphate nanoparticles.

    PubMed

    Seong, Da-Young; Kim, Young-Jin

    2015-05-01

    Although methylene blue (MB) is the most inexpensive photosensitizer with promising applications in the photodynamic therapy (PDT) for its high quantum yield of singlet oxygen generation, the clinical use of MB has been limited by its rapid enzymatic reduction in the biological environment. To enhance PDT efficacy of MB by preventing the enzymatic reduction, we have developed a new mineralization method to produce highly biocompatible MB-loaded calcium phosphate (CaP-MB) nanoparticles in the presence of polymer templates. The resulting CaP-MB nanoparticles exhibited spherical shape with a size of under 50 nm. Fourier transform infrared (FT-IR) and zeta-potential analyses confirmed the insertion of MB into the CaP-MB nanoparticles. The encapsulation of MB in CaP nanoparticles could effectively protect MB from the enzymatic reduction. In addition, the CaP-MB nanoparticles exhibited a good biocompatibility in the dark condition and significantly enhanced PDT efficacy due to apoptotic cell death against human breast cancer cells as compared with free MB, implying that CaP-MB nanoparticle system might be potentially applicable in PDT. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. 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.

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

    PubMed

    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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Strain features and condition assessment of orthotropic steel deck cable-supported bridges subjected to vehicle loads by using dense FBG strain sensors

    NASA Astrophysics Data System (ADS)

    Wei, Shiyin; Zhang, Zhaohui; Li, Shunlong; Li, Hui

    2017-10-01

    Strain is a direct indicator of structural safety. Therefore, strain sensors have been used in most structural health monitoring systems for bridges. However, until now, the investigation of strain response has been insufficient. This paper conducts a comprehensive study of the strain features of the U ribs and transverse diaphragm on an orthotropic steel deck and proposes a statistical paradigm for crack detection based on the features of vehicle-induced strain response by using the densely distributed optic fibre Bragg grating (FBG) strain sensors. The local feature of strain under vehicle load is highlighted, which enables the use of measurement data to determine the vehicle loading event and to make a decision regarding the health status of a girder near the strain sensors via technical elimination of the load information. Time-frequency analysis shows that the strain contains three features: the long-term trend item, the short-term trend item, and the instantaneous vehicle-induced item (IVII). The IVII is the wheel-induced strain with a remarkable local feature, and the measured wheel-induced strain is only influenced by the vehicle near the FBG sensor, while other vehicles slightly farther away have no effect on the wheel-induced strain. This causes the local strain series, among the FBG strain sensors in the same transverse locations of different cross-sections, to present similarities in shape to some extent and presents a time delay in successive order along the driving direction. Therefore, the strain series induced by an identical vehicle can be easily tracked and compared by extracting the amplitude and calculating the mutual ratio to eliminate vehicle loading information, leaving the girder information alone. The statistical paradigm for crack detection is finally proposed, and the detection accuracy is then validated by using dense FBG strain sensors on a long-span suspension bridge in China.

  14. 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

  15. Antimicrobial potential of consolidation polymers loaded with biological copper nanoparticles.

    PubMed

    Essa, Ashraf M M; Khallaf, Mohamed K

    2016-07-11

    Biodeterioration of historic monuments and stone works by microorganisms takes place as a result of biofilm production and secretion of organic compounds that negatively affect on the stone matrix. Copper nanoparticles (CuNPs) were prepared biologically using the headspace gases generated by the bacterial culture Escherichia coli Z1. The antimicrobial activity of CuNPs was evaluated against the bacterial strains Bacillus subtilis, Micrococcus luteus, Streptomyces parvulus, Escherichia coli, Pseudomonas aeruginosa as well as some fungal strains Aspergillus niger, Aspergillus flavus, Penicillium chrysogenum, Fusarium solani and Alternaria solani. Biological CuNPs demonstrated antibacterial and antifungal activities higher than those of the untreated copper sulfate. At the same time, limestone and sandstone blocks treated with consolidation polymers functionalized with CuNPs recorded apparent antimicrobial activity against E. coli, S. parvulus and B. subtilis in addition to an improvement in the physical and mechanical characters of the treated stones. Furthermore, the elemental composition of CuNPs was elucidated using electron dispersive x-ray system connected with the scanning electron microscope. Consolidation polymers impregnated with CuNPs could be used to restrain microbial deterioration in addition to the refinement of physico-mechanical behavior of the historic stones.

  16. Biodistribution of arctigenin-loaded nanoparticles designed for multimodal imaging.

    PubMed

    Cui, Qingxin; Hou, Yuanyuan; Wang, Yanan; Li, Xu; Liu, Yang; Ma, Xiaoyao; Wang, Zengyong; Wang, Weiya; Tao, Jin; Wang, Qian; Jiang, Min; Chen, Dongyan; Feng, Xizeng; Bai, Gang

    2017-04-07

    Tracking targets of natural products is one of the most challenging issues in fields ranging from pharmacognosy to biomedicine. It is widely recognized that the biocompatible nanoparticle (NP) could function as a "key" that opens the target "lock". We report a functionalized poly-lysine NP technique that can monitor the target protein of arctigenin (ATG) in vivo non-invasively. The NPs were synthesized, and their morphologies and surface chemical properties were characterized by transmission electron microscopy (TEM), laser particle size analysis and atomic force microscopy (AFM). In addition, we studied the localization of ATG at the level of the cell and the whole animal (zebrafish and mice). We demonstrated that fluorescent NPs could be ideal carriers in the development of a feasible method for target identification. The distributions of the target proteins were found to be consistent with the pharmacological action of ATG at the cellular and whole-organism levels. The results indicated that functionalized poly-lysine NPs could be valuable in the multimodal imaging of arctigenin.

  17. 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.

  18. Loading of curcumin into macrophages using lipid-based nanoparticles.

    PubMed

    Sou, Keitaro; Inenaga, Shunsuke; Takeoka, Shinji; Tsuchida, Eishun

    2008-03-20

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, Cm) is a natural compound which possesses antioxidant, anti-inflammatory and anti-tumor ability. Here, phospholipid vesicles or lipid-nanospheres embedding Cm (CmVe or CmLn) were formulated to deliver Cm into tissue macrophages through intravenous injection. Cm could be solubilized in hydrophobic regions of these particles to form nanoparticle dispersions, and these formulations showed ability to scavenge reactive oxygen species as antioxidants in dispersions. At 6h after intravenous injection in rats via the tail vein (2mg Cm/kg bw), confocal microscopic observations of tissue sections showed that Cm was massively distributed in cells assumed as macrophages into the bone marrow and spleen. Taken together, these results indicate that the lipid-based nanoparticulates provide improved intravenous delivery of Cm to tissues macrophages, specifically bone marrow and splenic macrophages in present formulation, which has therapeutic potential as an antioxidant and anti-inflammatory.

  19. 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

  20. 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.

  1. [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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Silver Nanoparticles With High Loading Capacity Of Amphotericin B: Characterization, Bactericidal And Antifungal Effects.

    PubMed

    Leonhard, Victoria; Alasino, Roxana Valeria; Muñoz, Adrián; Beltramo, Dante Miguel

    2017-09-18

    The purpose of this study was to evaluate the most appropriate conditions to generate silver nanoparticles (AgNPs) loaded with a potent antimycotic drug like amphotericin B (AmB), characterize the physicochemical properties, and also evaluate the cytotoxic effect and biological activity of these new nanostructures as a potential nanocarrier for hydrophobic drugs. It was determined that the optimal molar ratio between Ag and AmB is 1/1 given the uniformity of size around 1750 nm of the nanoparticles generated as well as their strongly negative ζ potential of -27 mV, a condition that favors repulsions between AgNPs and inhibiting their aggregation. In this condition, only 0.8 mg.mL-1 of Ag is needed to solubilize 5 mg.mL-1 of AmB, a concentration currently used in commercial formulations. It is important to emphasize that the loading capacity (w/w) of this nanostructure is much higher than that of micellar and liposomal formulations. These AgNP-AmB nanoparticles retain both the bactericidal effect of silver and the cytotoxic and antifungal effect of AmB. However, it was shown that these nanoparticles are spontaneously associated with plasma lipoproteins (LDL and HDL), inhibiting their cytotoxic effects on red blood cells and on at least two cell lines, Vero and H1299 and slightly reducing its bactericidal effect on P. aeruginosa. In contrast, the antifungal effect of the formulation is maintained and is even higher than that when the nanoparticle is not associated with lipoproteins, indicating that this association is of the reversible type. The characterization of these nanoparticles is discussed as a potential new model formulation able to improve the antifungal therapeutic efficiency of AmB. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. 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.

  10. 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.

  11. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Microbubbles Loaded with Nickel Nanoparticles: A Perspective for Carbon Sequestration.

    PubMed

    Seo, Seokju; Nguyen, Minh; Mastiani, Mohammad; Navarrete, Gabriel; Kim, Myeongsub

    2017-09-25

    This work reports a microfluidic study investigating the feasibility of accelerating gaseous carbon dioxide (CO2) dissolution into a continuous aqueous phase with the use of metallic nickel (Ni) nanoparticles (NPs) under conditions specific to carbon sequestration in saline aquifers. The dissolution of CO2 bubbles at different pH levels and salinities was studied to understand the effects that the intrinsic characteristics of brine in real reservoir conditions would have on CO2 solubility. Results showed that an increased shrinkage of CO2 bubbles occurred with higher basicity, while an increased expansion of CO2 bubbles was observed with a proportional increase in salinity. To achieve acceleration of CO2 dissolution in acidic brine containing high salinity content, the catalytic effect of Ni NPs was investigated by monitoring change in CO2 bubble size at various Ni NPs concentrations. The optimal concentration for the Ni NPs suspension was determined to be 30 mg L(-1); increasing the concentration up to 30 mg L(-1) showed a significant increase in the dissolution of CO2 bubbles, but increasing from 30 to 50 mg L(-1) displayed a decrease in catalytic potential, due to the decreased translational diffusion coefficient that occurs at higher concentrations. The optimal additive concentration of Ni NPs was tested with variations of solution at acidic and basic conditions and different levels of salinity to reveal how effectively the Ni NPs behave under real reservoir conditions. At the acidic level, Ni NPs proved to be more effective in catalyzing CO2 dissolution and can sufficiently alleviate the negative impact of salinity in brine.

  13. 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.

  14. Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting.

    PubMed

    Aji Alex, M R; Chacko, A J; Jose, S; Souto, E B

    2011-01-18

    The poor orally available lopinavir was successfully encapsulated in glyceryl behenate based solid lipid nanoparticles (Lo-SLN) for its ultimate use to target intestinal lymphatic vessels in combined chemotherapy-the so-called Highly Active Anti-Retroviral Therapy (HAART). SLN with mean particle size of 230 nm (polydispersity index, PDI<0.27) and surface electrical charge of approx. -27mV, were produced by hot homogenization process followed by ultrasonication. Particles were characterized using differential scanning calorimetry (DSC), wide angle X-ray scattering (WAXS) and atomic force microscopy (AFM) to confirm their solid character and the homogeneous distribution of drug within the lipid matrix. In vitro release studies at pH 6.8 phosphate buffer (PBS) and at pH 1.2 HCl 0.1N showed a slow release in both media. From the intestinal lymphatic transport study it became evident that SLN increased the cumulative percentage dose of lopinavir secreted into the lymph, which was 4.91-fold higher when compared with a conventional drug solution in methyl cellulose 0.5% (w/v) as suspending agent (Lo-MC). The percentage bioavailability was significantly enhanced. The AUC for the Lo-SLN was 2.13-fold higher than that obtained for the Lo-MC of similar concentration. The accelerated stability studies showed that there was no significant change in the mean particle size and PDI after storage at 25±2°C/60±5% RH. The shelf life of optimized formulation was assessed based on the remained drug content in the stabilized formulation and was shown to be 21.46 months. Copyright © 2010 Elsevier B.V. All rights reserved.

  15. In vitro evaluation of paclitaxel loaded amorphous chitin nanoparticles for colon cancer drug delivery.

    PubMed

    Smitha, K T; Anitha, A; Furuike, T; Tamura, H; Nair, Shantikumar V; Jayakumar, R

    2013-04-01

    Chitin and its derivatives have been widely used in drug delivery applications due to its biocompatible, biodegradable and non-toxic nature. In this study, we have developed amorphous chitin nanoparticles (150±50 nm) and evaluated its potential as a drug delivery system. Paclitaxel (PTX), a major chemotherapeutic agent was loaded into amorphous chitin nanoparticles (AC NPs) through ionic cross-linking reaction using TPP. The prepared PTX loaded AC NPs had an average diameter of 200±50 nm. Physico-chemical characterization of the prepared nanoparticles was carried out. These nanoparticles were proven to be hemocompatible and in vitro drug release studies showed a sustained release of PTX. Cellular internalization of the NPs was confirmed by fluorescent microscopy as well as by flow cytometry. Anticancer activity studies proved the toxicity of PTX-AC NPs toward colon cancer cells. These preliminary results indicate the potential of PTX-AC NPs in colon cancer drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Local delivery of siRNA-loaded calcium phosphate nanoparticles abates pulmonary inflammation.

    PubMed

    Frede, Annika; Neuhaus, Bernhard; Knuschke, Torben; Wadwa, Munisch; Kollenda, Sebastian; Klopfleisch, Robert; Hansen, Wiebke; Buer, Jan; Bruder, Dunja; Epple, Matthias; Westendorf, Astrid M

    2017-08-08

    The local interference of cytokine signaling mediated by siRNA-loaded nanoparticles might be a promising new therapeutic approach to dampen inflammation during pulmonary diseases. For the local therapeutic treatment of pulmonary inflammation, we produced multi-shell nanoparticles consisting of a calcium phosphate core, coated with siRNAs directed against pro-inflammatory mediators, encapsulated into poly(lactic-co-glycolic acid), and coated with a final outer layer of polyethylenimine. Nasal instillation of nanoparticles loaded with a mixture of siRNAs directed against different cytokines to mice suffering from TH1 cell-mediated lung inflammation, or of siRNA directed against NS-1 in an influenza infection model led to a significant reduction of target gene expression which was accompanied by distinct amelioration of lung inflammation in both models. Thus, this study provides strong 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 inflammatory disorders of the lung. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Preparation and evaluation of ofloxacin-loaded palmitic acid solid lipid nanoparticles

    PubMed Central

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

    2011-01-01

    The purpose of this study was to use solid lipid nanoparticles (SLN) to improve the pharmacological activity of ofloxacin. Ofloxacin-loaded SLN were prepared using palmitic acid as lipid matrix and poly vinyl alcohol (PVA) as emulsifier by a hot homogenization and ultrasonication method. The physicochemical characteristics of SLN were investigated by optical microscope, scanning electron microscopy, and photon correlation spectroscopy. Pharmacokinetics was studied after oral administration in mice. In vitro antibacterial activity and in vivo antibacterial efficacy of the SLN were investigated using minimal inhibitory concentrations (MIC) and a mouse protection model. The results demonstrated that the encapsulation efficiency, loading capacity, diameter, polydispersivity index, and zeta potential of the nanoparticles were 41.36% ± 1.50%, 4.40% ± 0.16%, 156.33 ± 7.51 nm, 0.26 ± 0.04, and −22.70 ± 1.40 mv, respectively. The SLN showed sustained release and enhanced antibacterial activity in vitro. Pharmacokinetic results demonstrated that SLN increased the bioavailability of ofloxacin by 2.27-fold, and extended the mean residence time of the drug from 10.50 to 43.44 hours. Single oral administrations of ofloxacin-loaded nanoparticles at 3 drug doses, 5 mg/kg, 10 mg/kg, and 20 mg/kg, all produced higher survival rates of lethal infected mice compared with native ofloxacin. These results indicate that SLN might be a promising delivery system to enhance the pharmacological activity of ofloxacin. PMID:21468357

  2. 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.

  3. 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

  4. 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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. 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.

  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. Development of hydroxyapatite nanoparticles loaded with folic acid to induce osteoblastic differentiation.

    PubMed

    Santos, Catarina; Gomes, Pedro; Duarte, José A; Almeida, Margarida M; Costa, Maria E V; Fernandes, Maria H

    2017-01-10

    Recently it has been shown that folic acid can have an important role in bone regeneration. For this reason, combining a classic bone regeneration system as, hydroxyapatite, loaded with folic acid, may be an important issue to be developed. To address this issue, hydroxyapatite nanoparticles loaded with folic acid were designed as an effective bone regenerative system, to induce osteoblast differentiation and improve the bone regeneration. HapNP were prepared by a hydrothermal method that used citric acid as a tailoring agent of particles morphology and, simultaneously, had the particularly to let carboxylic pendant groups in the particle surface, which provided a platform for the immobilization of folic acid (FA), producing HapNP-FA. A comparative study among hydroxyapatite nanoparticles loaded and unloaded with folic acid in presence of human mesenchymal stem cells was performed. The results demonstrate, that nanoparticles were able to be internalized by human mesenchymal stem cells. In addition, cell proliferation and viability were not affected in a wide concentration range. Both particles induced the expression of Runx2 and the expression and activity of alkaline phosphatase. However, HapNP-FA caused a significantly higher overexpression of Runx2. The osteoblastic differentiation confirms the potential applicability of HapNP-FA in the local bone regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. 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.

  9. Intranasal delivery of tapentadol hydrochloride-loaded chitosan nanoparticles: formulation, characterisation and its in vivo evaluation.

    PubMed

    Javia, Ankit; Thakkar, Hetal

    2017-09-18

    The aim of the present investigation was to formulate tapentadol hydrochloride-loaded chitosan nanoparticles (CS-NPs) for nose to brain delivery. Chitosan nanoparticles were prepared using ionotropic gelation technique. Optimisation of the formulation and process parameters was done using Box-Behnken Design. The entrapment efficiency, drug loading, Z-average size and zeta potential of the optimised batch were 63.49 ± 1.61%, 17.25 ± 1.38%w/w, 201.2 ± 1.5 nm and +49.3 mV, respectively. In-vitro release study showed 84.04 ± 1.53% drug release after 28 h, while ex vivo studies indicated higher permeation of CS-NPs through nasal mucosa. The nanoparticles exhibited good mucoadhesiveness, haemocompatibility and safety as evidenced by histopathology. The results of the pharmacodynamic study revealed prolongation of the analgesic activity. The intranasal instillation of CS-NPs resulted in the higher concentrations in brain compared to the drug solution and intravenous administration of CS-NPs. In a nutshell, intranasal administration of tapentadol hydrochloride-loaded CS-NPs is a promising approach for effective pain management.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. "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.

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

    PubMed

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

    2017-08-01

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

  16. Solvent effect in the synthesis of hydrophobic drug-loaded polymer nanoparticles.

    PubMed

    Pal, Sandip; Saha, Chabita

    2017-06-01

    Quercetin is an abundant flavonoid in fruits, vegetables such as onion, tea leaves, cranberry, radish leaves etc. with numerous biological activities and widely used as an effective antioxidant. Its low solubility in water and chemical decomposition in intestinal environment are predicaments in delivery through dietary or oral intake. Noble polymeric nanoparticles are of particular interest today because of their applications in many areas. Polymer nanoparticles have attracted the interest of many research groups and have been utilised in an increasing number of fields such as site targeted drug delivery in cancer research during the last decades. Various techniques can be used to produce polymer nanoparticles, such as solvent evaporation, salting-out, dialysis, supercritical fluid technology etc. The choice of method depends on a number of factors, such as, particle size, particle size distribution, area of application, etc. In the present study, single emulsion-solvent evaporation technique has been utilised with two different organic solvents: acetone and chloroform/methanol to prepare quercetin loaded poly(D,L-lactide-co-glycolide) nanoparticles. According to the authors' observations acetone is a better solvent for encapsulating quercetin in polymer nanoparticles owing to its physical and chemical properties.

  17. 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.

  18. 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

  19. Preparation of Drug-Loaded PLGA-PEG Nanoparticles by Membrane-Assisted Nanoprecipitation.

    PubMed

    Albisa, Airama; Piacentini, Emma; Sebastian, Victor; Arruebo, Manuel; Santamaria, Jesus; Giorno, Lidietta

    2017-06-01

    The aim of this work is to develop a scalable continuous system suitable for the formulation of polymeric nanoparticles using membrane-assisted nanoprecipitation. One of the hurdles to overcome in the use of nanostructured materials as drug delivery vectors is their availability at industrial scale. Innovation in process technology is required to translate laboratory production into mass production while preserving their desired nanoscale characteristics. Membrane-assisted nanoprecipitation has been used for the production of Poly[(D,L lactide-co-glycolide)-co-poly ethylene glycol] diblock) (PLGA-PEG) nanoparticles using a pulsed back-and-forward flow arrangement. Tubular Shirasu porous glass membranes (SPG) with pore diameters of 1 and 0.2 μm were used to control the mixing process during the nanoprecipitation reaction. The size of the resulting PLGA-PEG nanoparticles could be readily tuned in the range from 250 to 400 nm with high homogeneity (PDI lower than 0.2) by controlling the dispersed phase volume/continuous phase volume ratio. Dexamethasone was successfully encapsulated in a continuous process, achieving an encapsulation efficiency and drug loading efficiency of 50% and 5%, respectively. The dexamethasone was released from the nanoparticles following Fickian kinetics. The method allowed to produce polymeric nanoparticles for drug delivery with a high productivity, reproducibility and easy scalability.

  20. Calcium-silicate mesoporous nanoparticles loaded with chlorhexidine for both anti- Enterococcus faecalis and mineralization properties.

    PubMed

    Fan, Wei; Li, Yanyun; Sun, Qing; Ma, Tengjiao; Fan, Bing

    2016-10-21

    In infected periapical tissues, Enterococcus faecalis is one of the most common dominant bacteria. Chlorhexidine has been proved to show strong antibacterial ability against E. faecalis but is ineffective in promoting mineralization for tissues around root apex. Mesoporous calcium-silicate nanoparticles are newly synthesized biomaterials with excellent ability to promote mineralization and carry-release bioactive molecules in a controlled manner. In this study, mesoporous calcium-silicate nanoparticles were functionalized with chlorhexidine and their releasing profile, antibacterial ability, effect on cell proliferation and in vitro mineralization property were evaluated. The chlorhexidine was successfully incorporated into mesoporous calcium-silicate nanoparticles by a mixing-coupling method. The new material could release chlorhexidine as well as Ca(2+) and SiO3(2-) in a sustained manner with an alkaline pH value under different conditions. The antimicrobial ability against planktonic E. faecalis was dramatically improved after chlorhexidine incorporation. The nanoparticles with chlorhexidine showed no negative effect on cell proliferation with low concentrations. On dentin slices, the new synthesized material demonstrated a similar inhibitory effect on E. faecalis as the chlorhexidine. After being immersed in SBF for 9 days, numerous apatite crystals could be observed on surfaces of the material tablets. Mesoporous calcium-silicate nanoparticles loaded with chlorhexidine exhibited release of ions and chlorhexidine, low cytotoxicity, excellent antibacterial ability and in vitro mineralization. This material could be developed into a new effective intra-canal medication in dentistry or a new bone defect filling material for infected bone defects.

  1. 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.

  2. Comparative evaluation of in vitro parameters of tamoxifen citrate loaded poly(lactide-co-glycolide), poly(epsilon-caprolactone) and chitosan nanoparticles.

    PubMed

    Cirpanli, Y; Yerlikaya, F; Ozturk, K; Erdogar, N; Launay, M; Gegu, C; Leturgez, T; Bilensoy, E; Calis, S; Capan, Y

    2010-12-01

    Tamoxifen (TAM), the clinical choice for the antiestrogen treatment of advanced or metastatic breast cancer, was formulated in nanoparticulate carrier systems in the form of poly(lactide-co-glycolide) (PLGA), poly-epsilon-caprolactone (PCL) and chitosan (CS) nanoparticles. The PLGA and PCL nanoparticles were prepared by a nanoprecipitation technique whereas the CS nanoparticles were prepared by the ionic gelation method. Mean particle sizes were under 260 nm for PLGA and PCL nanoparticles and around 400 nm for CS nanoparticles. Polydispersity indices were less than 0.4 for all formulations. Zeta potential values were positive for TAM loaded nanoparticles because of the positive charge of the drug. Drug loading values were significantly higher for PCL nanoparticles when compared to PLGA and CS nanoparticles. All nanoparticle formulations exhibited controlled release properties. These results indicate that TAM loaded PLGA, PCL and CS nanoparticles may provide promising carrier systems for tumor targeting.

  3. Tamoxifen citrate loaded amphiphilic beta-cyclodextrin nanoparticles: in vitro characterization and cytotoxicity.

    PubMed

    Memisoglu-Bilensoy, Erem; Vural, Imran; Bochot, Amélie; Renoir, Jack Michel; Duchene, Dominique; Hincal, A Atilla

    2005-06-02

    Nanospheres and nanocapsules of beta-CDC6, amphiphilic beta-cyclodextrin modified on the secondary face with 6C aliphatic esters, were prepared with nanoprecipitation technique directly from inclusion complexes of tamoxifen citrate and beta-CDC6 (1:1 molar ratio). Blank and loaded nanospheres and nanocapsules were characterized by particle size distribution, zeta potential, drug loading and in vitro drug release. Particle sizes were between 250 and 300 nm for different formulations of nanospheres and nanocapsules. Zeta potential which was around -18 mV for blank particles was reported to be between +12 and +15 mV for tamoxifen-loaded particles. Average entrapped drug quantity was found to be around 150 mug/mL for particles prepared from inclusion complexes and this is double the loading value for conventionally prepared particles. Pre-loaded formulations showed a significantly slower release profile extended up to 6 h while formulations loaded conventionally displayed rapid and complete release within an hour. Cytotoxic efficacy of tamoxifen citrate loaded nanospheres and nanocapsules was determined against MCF-7 cells and tamoxifen citrate incorporated in amphiphilic beta-cyclodextrin nanoparticles was found to be cytotoxic and effective against this cell line.

  4. 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

  5. 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.

  6. Superparamagnetic iron oxide nanoparticles-loaded chitosan-linoleic acid nanoparticles as an effective hepatocyte-targeted gene delivery system.

    PubMed

    Cheong, Su-Jin; Lee, Chang-Moon; Kim, Se-Lim; Jeong, Hwan-Jeong; Kim, Eun-Mi; Park, Eun-Hye; Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee

    2009-05-08

    The goal of this study was to develop a gene delivery imaging system that targets hepatocytes to help diagnose and treat various liver diseases. To this end, we prepared superparamagnetic iron oxide nanoparticles (SPIO)-loaded with water-soluble chitosan (WSC)-linoleic acid (LA) nanoparticles (SCLNs) that formed gene complexes capable of localizing specifically to hepatocytes. We confirmed that (99m)Tc-labeled SCLNs delivered into mice via intravenous injection accumulated mainly in the liver using nuclear and magnetic resonance imaging. SCLN/enhanced green fluorescence protein (pEGFP) complexes were also successfully formed and were characterized with a gel retardation assay. SCLN/pEGFP complexes were transfected into primary hepatocytes, where GFP expression was observed in the cytoplasm. In addition, the injection of the gene complexes into mice resulted in significantly increased expression of GFP in hepatocytes in vivo. Furthermore, gene silencing was effectively achieved by administration of gene complexes loaded with specific siRNAs. In conclusion, our results indicate that the SCLNs have the potential to be useful for hepatocyte-targeted imaging and effective gene delivery into hepatocytes.

  7. Paclitaxel-loaded nanoparticles decorated with anti-CD133 antibody: a targeted therapy for liver cancer stem cells

    NASA Astrophysics Data System (ADS)

    Jin, Cheng; Yang, Zhaoxu; Yang, Jingyue; Li, Haimin; He, Yong; An, Jiaze; Bai, Ling; Dou, Kefeng

    2014-01-01

    Recent studies have revealed the existence of liver cancer stem cells (CSCs). Therefore, there is an urgent need for new and effective treatment strategies specific to liver CSCs. In this work, the poly( d, l-lactide-coglycolide) nanoparticles containing paclitaxel were prepared by emulsification-solvent evaporation method. The nanoparticles decorated with anti-CD133 antibody, termed targeted nanoparticles, were prepared by carbodiimide chemistry for liver CSCs. The physicochemical characteristics of the nanoparticles (i.e., encapsulation efficiency, particle size distribution, morphology, and in vitro release) were investigated. Cellular uptake and accumulation in tumor tissue of nanoparticles were observed. To assess anti-tumor activity of nanoparticles in vitro and in vivo, cell survival assay and tumor regression study were carried out using liver cancer cell lines (Huh7 and HepG2) and their xenografts. Particle size of targeted nanoparticles was 429.26 ± 41.53 nm with zeta potential of -11.2 mV. Targeted nanoparticles possessed spherical morphology and high encapsulation efficiency (87.53 ± 5.9 %). The accumulation of targeted nanoparticles depends on dual effects of passive and active targeting. Drug-loaded nanoparticles showed cytotoxicity on the tumor cells in vitro and in vivo. Targeted nanoparticles resulted in significant improvement in therapeutic response through selectively eliminating CD133 positive subpopulation. These results suggested that the novel nanoparticles could be a promising candidate with excellent therapeutic efficacy for targeting liver CSCs.

  8. 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

  9. 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.

  10. Development of iron/ethylcellulose (core/shell) nanoparticles loaded with diclofenac sodium for arthritis treatment.

    PubMed

    Arias, José L; López-Viota, Margarita; López-Viota, Julián; Delgado, Angel V

    2009-12-01

    Diclofenac sodium is a non-steroidal anti-inflammatory drug of choice to treat arthritis because of its potential anti-inflammatory and analgesic activity. Because of its shorter biological half-life, it is needed to be given frequently and at high doses to elicit the required therapeutic activity, simultaneously leading to severe side effects. We hypothesized that the efficient delivery of diclofenac sodium to inflammation using a magnetic colloid could reduce the dose required to bring out sufficient therapeutic response. Hence, we have developed a diclofenac sodium-loaded magnetic nanomedicine, consisting of a magnetic core (iron) and a biocompatible polymeric shell (ethylcellulose) for parenteral administration. These core/shell nanoparticles were synthesized by an emulsion solvent evaporation process. Two drug loading methods were analyzed: the first one being drug addition prior to the emulsion solvent evaporation process (leading to drug entrapment into the polymeric network), and the second method based on diclofenac sodium surface adsorption onto the preformed nanoparticles. Compared to drug adsorption, the entrapment of this active agent into the polymeric matrix yielded a higher drug loading and a slower drug release profile. Such nanocomposites possessed very important characteristics such as unusually high drug loading, enhanced magnetic susceptibility and prolonged drug release, indicating their potential use as nanocarriers for efficient delivery of diclofenac sodium to inflammation sites.

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

    PubMed

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

    2011-05-01

    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.

  12. 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

  13. Development and evaluation of Desvenlafaxine loaded PLGA-chitosan nanoparticles for brain delivery.

    PubMed

    Tong, Gui-Feng; Qin, Nan; Sun, Li-Wei

    2017-09-01

    Depression is a debilitating psychiatric condition that remains the second most common cause of disability worldwide. Currently, depression affects more than 4 per cent of the world's population. Most of the drugs intended for clinical management of depression augment the availability of neurotransmitters at the synapse by inhibiting their neuronal reuptake. However, the therapeutic efficacy of antidepressants is often compromised as they are unable to reach brain by the conventional routes of administration. The purpose of the present study was to reconnoiter the potential of mucoadhesive PLGA-chitosan nanoparticles for the delivery of encapsulated Desvenlafaxine to the brain by nose to brain delivery route for superior pharmacokinetic and pharmacodynamic profile of Desvenlafaxine. Desvenlafaxine loaded PLGA-chitosan nanoparticles were prepared by solvent emulsion evaporation technique and optimized for various physiochemical characteristics. The antidepressant efficacy of optimized Desvenlafaxine was evaluated in various rodent depression models together with the biochemical estimation of monoamines in their brain. Further, the levels of Desvenlafaxine in brain and blood plasma were determined at various time intervals for calculation of different pharmacokinetic parameters. The optimized Desvenlafaxine loaded PLGA-chitosan nanoparticles (∼172 nm/+35 mV) on intranasal administration significantly reduced the symptoms of depression and enhanced the level of monoamines in the brain in comparison with orally administered Desvenlafaxine. Nose to brain delivery of Desvenlafaxine PLGA-chitosan nanoparticles also enhanced the pharmacokinetic profile of Desvenlafaxine in brain together with their brain/blood ratio at different time points. Thus, intranasal mucoadhesive Desvenlafaxine PLGA-chitosan nanoparticles could be potentially used for the treatment of depression.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Effects of chemical and processing variables on paclitaxel-loaded polymer nanoparticles prepared using microfluidics.

    PubMed

    Bains, Aman; Moffitt, Matthew G

    2017-12-15

    For paclitaxel (PAX)-loaded polymeric nanoparticles PNPs prepared in a two-phase gas-liquid microfluidic reactor, the effects of microfluidic flow rate on the multiscale structure, loading efficiency and release rate are determined for three different copolymer compositions and two orders of magnitude variation in the PAX loading ratio. All experiments are carried out in the limit of low drug-to-polymer loading ratios (r≤0.01, w/w). In this range of r, PCL crystallinity, loading efficiency and release rate are not significantly affected by the amount of PAX dissolved in the core. These results are in sharp contrast to microfluidic PNPs prepared in a range of high loading ratios (r≥0.1), where the amount of added PAX has a strong influence on the multiscale structure and properties of drug delivery PNPs. For the case of r=0.01, we show that flow rate strongly affects PNP morphologies for all three block copolymer compositions. For the shortest and longest PCL block lengths, the relative number of cylindrical morphologies increases and then decreases with increasing flow rate, whereas for the intermediate PCL block length, the number of cylinders steadily increases as the flow rate increases. Internal PCL crystallinities and PAX loading efficiencies show similar trends, both parameters increasing and decreasing with increasing flow rate for the extreme PCL block lengths and steadily increasing for the intermediate PCL block length. PAX release profiles indicate a marked slowing of PAX release as either the PCL block length or the microfluidic flow rate increase. Working in the limit of low loading ratio, this work provides clarity on separating the relative effects of copolymer composition and processing along with perturbations caused by the molecular cargo on the structure and function of drug delivery PNPs. These critical insights thus inform controlled microfluidic preparation of more medically-relevant PNPs at higher therapeutic loading levels. Copyright

  20. 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.

  1. SN-38 loading capacity of hydrophobic polymer blend nanoparticles: formulation, optimization and efficacy evaluation.

    PubMed

    Dimchevska, Simona; Geskovski, Nikola; Petruševski, Gjorgji; Chacorovska, Marina; Popeski-Dimovski, Riste; Ugarkovic, Sonja; Goracinova, Katerina

    2017-03-01

    One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle (NP) core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to NPs prepared using individual polymers. D-optimal design was applied to optimize PLGA/PCL ratio in the polymer blend and the mode of addition of the amphiphilic copolymer Lutrol(®)F127 in order to maximize SN-38 loading and obtain NPs with acceptable size for passive tumor targeting. Drug/polymer and polymer/polymer interaction analysis pointed to high degree of compatibility and miscibility among both hydrophobic polymers, providing core configuration with higher drug loading capacity. Toxicity studies outlined the biocompatibility of the blank NPs. Increased in vitro efficacy of drug-loaded NPs compared to the free drug was confirmed by growth inhibition studies using SW-480 cell line. Additionally, the optimized NP formulation showed very promising blood circulation profile with elimination half-time of 7.4 h.

  2. 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.

  3. 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

  4. Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment.

    PubMed

    Katiyar, Sameer S; Muntimadugu, Eameema; Rafeeqi, Towseef Amin; Domb, Abraham J; Khan, Wahid

    2016-09-01

    P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when using anticancer drugs, moreover, poor bioavailability of few drugs is also due to P-gp efflux in the gut. Rapamycin (RPM) is in the clinical trials for breast cancer treatment, but its P-gp substrate property leads to poor oral bioavailability and efficacy. The objective of this study is to formulate and evaluate nanoparticles of RPM, along with a chemosensitizer (piperine, PIP) for improved oral bioavailability and efficacy. Poly(d,l-lactide-co-glycolide) (PLGA) was selected as polymer as it has moderate MDR reversal activity, which may provide additional benefits. The nanoprecipitation method was used to prepare PLGA nanoparticles with particle size below 150 nm, loaded with both drugs (RPM and PIP). Prepared nanoparticles showed sustained in vitro drug release for weeks, with initial release kinetics of zero order with non-Fickian transport, subsequently followed by Higuchi kinetics with Fickian diffusion. An everted gut sac method was used to study the effect of P-gp efflux on drug transport. This reveals that the uptake of the RPM (P-gp substrate) has been increased in the presence of chemosensitizer. Pharmacokinetic studies showed better absorption profile of RPM from polymeric nanoparticles compared to its suspension counterpart and improved bioavailability of 4.8-folds in combination with a chemosensitizer. An in vitro cell line study indicates higher efficacy of nanoparticles compared to free drug solution. Results suggest that the use of a combination of PIP with RPM nanoparticles would be a promising approach in the treatment of breast cancer.

  5. 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

  6. 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

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

    PubMed

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

    2015-01-01

    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. This represents a novel treatment strategy for fetal cardiovascular disease which may improve maternal and fetal outcomes.

  8. 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.

  9. 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.

  10. Combining magnetic nanoparticles with cell derived microvesicles for drug loading and targeting.

    PubMed

    Silva, Amanda K A; Luciani, Nathalie; Gazeau, Florence; Aubertin, Kelly; Bonneau, Stéphanie; Chauvierre, Cédric; Letourneur, Didier; Wilhelm, Claire

    2015-04-01

    Inspired by microvesicle-mediated intercellular communication, we propose a hybrid vector for magnetic drug delivery. It consists of macrophage-derived microvesicles engineered to enclose different therapeutic agents together with iron oxide nanoparticles. Here, we investigated in vitro how magnetic nanoparticles may influence the vector effectiveness in terms of drug uptake and targeting. Human macrophages were loaded with iron oxide nanoparticles and different therapeutic agents: a chemotherapeutic agent (doxorubicin), tissue-plasminogen activator (t-PA) and two photosensitizers (disulfonated tetraphenyl chlorin-TPCS2a and 5,10,15,20-tetra(m-hydroxyphenyl)chlorin-mTHPC). The hybrid cell microvesicles were magnetically responsive, readily manipulated by magnetic forces and MRI-detectable. Using photosensitizer-loaded vesicles, we showed that the uptake of microvesicles by cancer cells could be kinetically modulated and spatially controlled under magnetic field and that cancer cell death was enhanced by the magnetic targeting. From the clinical editor: In this article, the authors devised a biogenic method using macrophages to produce microvesicles containing both iron oxide and chemotherapeutic agents. They showed that the microvesicles could be manipulated by magnetic force for targeting and subsequent delivery of the drug payload against cancer cells. This smart method could provide a novel way for future fight against cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Sonochemical synthesis of iron oxide nanoparticles loaded with folate and cisplatin: effect of ultrasonic frequency.

    PubMed

    Dolores, Reyman; Raquel, Serrano; Adianez, Garcia-Leis

    2015-03-01

    Simple preparative methods were used to sonosynthesize different magnetic iron oxide nanoparticles (FeNPs) via co-precipitation of aqueous solutions of ferrous salts in a basic aqueous solution of ethylene glycol (EG). Sonosynthesis was achieved using different frequencies of ultrasound: 581, 861, and 1141 kHz under the same acoustic power. The hydroxyl radicals generated by cavitational collapse, induced by the ultrasonic field, led to the oxidation of Fe(2+) to Fe(3+). The rate of sonochemical Fe(3+) production decreased linearly with the frequency. Three different systems of FeNPs were synthesized, all with the same core but a different shell: FeNPs capped with EG (EG/FeNPs), FeNPs capped with EG and folate (Fol/EG/FeNPs), and FeNPs capped with EG, folate and cisplatin (Pt/EG/FeNPs). The nanoparticles were characterized by transmission electron microscopy, fluorescence and Raman microspectroscopy, total-reflection X-ray fluorescence, and elemental analysis (C, N, and H). The magnetization hysteresis loops of these samples were also measured. The obtained values of saturation magnetization were within the interval between 60 and 93 Am(2)kg(-1). From the analysis of these results, it was found that the ultrasonic frequency did not affect the nanoparticle size (diameter of 21-31 nm). In contrast, the frequency affected the amount of drug loaded, as cisplatin loading increased proportionately with ultrasound frequency. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. G-CSF loaded nanofiber/nanoparticle composite coated with collagen promotes wound healing in vivo.

    PubMed

    Tanha, Shima; Rafiee-Tehrani, Morteza; Abdollahi, Mohamad; Vakilian, Saeid; Esmaili, Zahra; Naraghi, Zahra Safaei; Seyedjafari, Ehsan; Javar, Hamid Akbari

    2017-10-01

    Sustained release of functional growth factors can be considered as a beneficial methodology for wound healing. In this study, recombinant human granulocyte colony-stimulating factor (G-CSF)-loaded chitosan nanoparticles were incorporated in Poly(ε-caprolactone) (PCL) nanofibers, followed by surface coating with collagen type I. Physical and mechanical properties of the PCL nanofibers containing G-CSF loaded chitosan nanoparticles PCL/NP(G-CSF) and in vivo performance for wound healing were investigated. G-CSF structural stability was evaluated through SDS_PAGE, reversed phase (RP) HPLC and size-exclusion chromatography, as well as circular dichroism. Nanofiber/nanoparticle composite scaffold was demonstrated to have appropriate mechanical properties as a wound dresser and a sustained release of functional G-CSF. The PCL/NP(G-CSF) scaffold showed a suitable proliferation and well-adherent morphology of stem cells. In vivo study and histopathological evaluation outcome revealed that skin regeneration was dramatically accelerated under PCL/NP(G-CSF) as compared with control groups. Superior fibroblast maturation, enhanced collagen deposition and minimum inflammatory cells were also the beneficial properties of PCL/NP(G-CSF) over the commercial dressing. The synergistic effect of extracellular matrix-mimicking nanofibrous membrane and G-CSF could develop a suitable supportive substrate in order to extensive utilization for the healing of skin wounds. © 2017 Wiley Periodicals Inc. J Biomed Mater Res Part A: 105A: 2830-2842, 2017. © 2017 Wiley Periodicals, Inc.

  13. 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

  14. 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.

  15. Preparation and characterization of DOX loaded keratin nanoparticles for pH/GSH dual responsive release.

    PubMed

    Li, Yanmei; Zhi, Xuelian; Lin, Jiantao; You, Xin; Yuan, Jiang

    2017-04-01

    Smart drug carriers are the current need of the hour in controlled drug delivery applications. In this work, pH and redox dual responsive keratin based drug-loaded nanoparticles (KDNPs) were fabricated through two-step strategies. Keratin nanoparticles were first prepared by desolvation method and chemical crosslinking, followed by electrostatic adsorbing doxorubicin (DOX) to afford drug loaded keratin nanoparticles (KDNPs). The size, size distribution, and morphology of the KDNPs were characterized with dynamic light scattering (DLS) and Scan electronic microscope (SEM). Drug delivery profiles showed that KDNPs exhibited pH and glutathione (GSH) dual-responsive characters. Under tumor tissue/cell microenvironments (more acidic and high GSH level), KDNPs tended to accumulate at the tumor region through a potential enhanced permeability and retention (EPR) effect and perform surface negative-to-positive charge conversion. Hemolysis assay indicated that KDNPs had good blood compatibility. Cellular uptake assay demonstrated that KDNPs could be internalized by A 549 cells through endocytosis. Intriguingly, KDNPs were capable of promoting nitric oxide (NO) release from endogenous donor of S-nitrosoglutathione in the presence of GSH. All of these results demonstrated that keratin based drug carriers had potential for drug/NO delivery and cancer therapy in clinical medicine. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. 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.

  17. [Effect of borneol/mentholum eutectic mixture on nasal-brain delivery of neurotoxin loaded nanoparticles].

    PubMed

    Chai, Guobao; Pan, Yuefang; Li, Fanzhu

    2009-03-01

    To investigate the absorption enhancen effect of borneol/mentholum eutectic mixture (BO/ME) on nasal-brain delivery of neurotoxin loaded nanoparticles. Using microdialysis sampling technique in awake freely-moving rats, the counter per minute (cpm) of dialysates in right PAG of NT-loaded nanoparticles with the BO/ME (BO/ME-NT-NP), radiolabeled with sodium 125I-Iodide, were measured in a gamma-counter for radioactivity. After converting cpm into corresponding concentrations of NT byin vivorecovery of microdialysis probes, the pharmacokinetic parameters were calculated. The BO/ME-NT-NP could be absorbed into the brain, much better to NT-NP and the nanoparticles with borneol or menthdlum only, and the pharmacokinetics accorded with the two-compartment model. The parameters tmax, cmax, AUC, t 1/2(beta) were 0.68 h, 27.32 ng x mL(-1), 132.68 ng x h x mL(-1), 3.1076 h. With adding BO/ME as absorption enhancer, NT could be significantly increased in the brain with the help of nanopartilces as carriers, and the time to maximal concentration was short, the elimination process was prolonged.

  18. 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.

  19. 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.

  20. 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.

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

    PubMed Central

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

    2007-01-01

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

  2. 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.

  3. Preparation of astaxanthin-loaded DNA/chitosan nanoparticles for improved cellular uptake and antioxidation capability.

    PubMed

    Wang, Qian; Zhao, Yingyuan; Guan, Lei; Zhang, Yaping; Dang, Qifeng; Dong, Ping; Li, Jing; Liang, Xingguo

    2017-07-15

    DNA/chitosan co-assemblies were initially used as nanocarriers for efficient astaxanthin encapsulation and delivery. The obtained astaxanthin-loaded DNA/chitosan (ADC) colloidal system was transparent and homogenous, with astaxanthin content up to 65μg/ml. Compared to free astaxanthin, ADC nanoparticles with an astaxanthin concentration as low as 3.35nM still showed a more powerful cytoprotective effect on H2O2-induced oxidative cell damage, and improved cell viability from 49.9% to 61.9%. The ROS scavenging efficiency of ADC nanoparticles was as high as 54.3%, which was 2-fold higher than that of free astaxanthin. Besides this, ADC nanoparticles were easily engulfed by Caco-2 cells in a short time, indicating that the encapsulated astaxanthin could be absorbed through endocytosis by intestinal epithelial cells. The improved antioxidation capability and facilitated cellular uptake enabled the ADC nanoparticles to be good candidates for efficient delivery and absorption of astaxanthin. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Antinociceptive properties of nasal delivery of neurotoxin-loaded nanoparticles coated with polysorbate-80.

    PubMed

    Ruan, Yeping; Yao, Li; Zhang, Bingbing; Zhang, Shuijuan; Guo, Jianyou

    2011-07-01

    Neurotoxin-1 (NT) is an analgesic peptide which is endowed an exceptional specificity of action that blocks transmission of the nerve impulse. The aim of this study was to evaluate the potential application of nanoparticles technology as drug carrier system for the nasal delivery of NT. Mice were administered intranasally (i.n.) with NT (NT-P-NP), free NT solution (F-NT) and intravenously (i.v.) with NT (IV-NT) respectively. The NT levels in animal brain and antinociceptive activity of NT were analyzed. The result on brain transport showed that nanoparticles could exert enhanced delivery of NT into the brain significantly after i.n. administration. The results of antinociceptive activity showed that NT-P-NP increased immobility in the open-field test, both phases of formalin test were significantly inhibited by the NT-P-NP and NT-P-NP significantly inhibited the reaction time to thermal stimuli at 60 and 90 min. Both NT-P-NP and IV-NT were able to inhibit constrictions in acetic acid-induced writhing reaction. These data suggest that NT-loaded nanoparticles coated with polysorbate-80 could generate a significant improvement of drug levels in the brain. Intranasal administration of Neurotoxin-1 entrapped in nanoparticles coated with polysorbate-80 is an attractive alternative to intravenous administration. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Purification of Drug Loaded PLGA Nanoparticles Prepared by Emulsification Solvent Evaporation Using Stirred Cell Ultrafiltration Technique.

    PubMed

    Paswan, Suresh K; Saini, T R

    2017-09-18

    The emulsifiers in an exceedingly higher level are used in the preparation of drug loaded polymeric nanoparticles prepared by emulsification solvent evaporation method. This creates great problem to the formulator due to their serious toxicities when it is to be administered by parenteral route. The final product is therefore required to be freed from the used surfactants by the conventional purification techniques which is a cumbersome job. The solvent resistant stirred cell ultrafiltration unit (Millipore) was used in this study using polyethersulfone ultrafiltration membrane (Biomax®) having pore size of NMWL 300 KDa as the membrane filter. The purification efficiency of this technique was compared with the conventional centrifugation technique. The flow rate of ultrafiltration was optimized for removal of surfactant (polyvinyl alcohol) impurities to the acceptable levels in 1-3.5 h from the nanoparticle dispersion of tamoxifen prepared by emulsification solvent evaporation method. The present investigations demonstrate the application of solvent resistant stirred cell ultrafiltration technique for removal of toxic impurities of surfactant (PVA) from the polymeric drug nanoparticles (tamoxifen) prepared by emulsification solvent evaporation method. This technique offers added benefit of producing more concentrated nanoparticles dispersion without causing significant particle size growth which is observed in other purification techniques, e.g., centrifugation and ultracentrifugation.

  7. 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

  8. 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

  9. Visible-light active photocatalytic WO3 films loaded with Pt nanoparticles deposited by sputtering.

    PubMed

    Murata, Akiyo; Oka, Nobuto; Nakamura, Shinichi; Shigesato, Yuzo

    2012-06-01

    Visible-Light active photocatalytic tungsten trioxide (WO3) films were deposited at a substrate temperature of 800 degrees C by dc reactive magnetron sputtering using a W metal target. In addition, Platinum (Pt) was deposited on the WO3 film surfaces at room temperature, also by sputtering. In the early stages of Pt growth, formation of Pt nanoparticles could be expected because of the island structure observed in Volmer-Weber-type growth mode. The surface coverage of Pt on the WO3 films was estimated quantitatively by X-ray photoelectron spectroscopy and was found to be approximately 60% after 7 s deposition. High resolution electron microscopy (HREM) demonstrated that Pt nanoparticles with a diameter of about 2.5 nm were generated and dispersed uniformly on the entire surface area of the columnar polycrystalline WO3 films. These Pt-loaded films exhibited high photocatalytic activity in the decomposition of acetaldehyde (CH3CHO) under visible light irradiation.

  10. Synergistic bactericidal activity of chlorhexidine-loaded, silver-decorated mesoporous silica nanoparticles.

    PubMed

    Lu, Meng-Meng; Wang, Qiu-Jing; Chang, Zhi-Min; Wang, Zheng; Zheng, Xiao; Shao, Dan; Dong, Wen-Fei; Zhou, Yan-Min

    2017-01-01

    Combination of chlorhexidine (CHX) and silver ions could engender synergistic bactericidal effect and improve the bactericidal efficacy. It is highly desired to develop an efficient carrier for the antiseptics codelivery targeting infection foci with acidic microenvironment. In this work, monodisperse mesoporous silica nanoparticle (MSN) nanospheres were successfully developed as an ideal carrier for CHX and nanosilver codelivery through a facile and environmentally friendly method. The CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) exhibited a pH-responsive release manner of CHX and silver ions simultaneously, leading to synergistically antibacterial effect against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. Moreover, the effective antibacterial concentration of Ag-MSNs@CHX showed less cytotoxicity on normal cells. Given their synergistically bactericidal ability and good biocompatibility, these nanoantiseptics might have effective and broad clinical applications for bacterial infections.

  11. Synergistic bactericidal activity of chlorhexidine-loaded, silver-decorated mesoporous silica nanoparticles

    PubMed Central

    Lu, Meng-meng; Wang, Qiu-jing; Chang, Zhi-min; Wang, Zheng; Zheng, Xiao; Shao, Dan; Dong, Wen-fei; Zhou, Yan-min

    2017-01-01

    Combination of chlorhexidine (CHX) and silver ions could engender synergistic bactericidal effect and improve the bactericidal efficacy. It is highly desired to develop an efficient carrier for the antiseptics codelivery targeting infection foci with acidic microenvironment. In this work, monodisperse mesoporous silica nanoparticle (MSN) nanospheres were successfully developed as an ideal carrier for CHX and nanosilver codelivery through a facile and environmentally friendly method. The CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) exhibited a pH-responsive release manner of CHX and silver ions simultaneously, leading to synergistically antibacterial effect against both gram-positive Staphylococcus aureus and gram-negative Escherichia coli. Moreover, the effective antibacterial concentration of Ag-MSNs@CHX showed less cytotoxicity on normal cells. Given their synergistically bactericidal ability and good biocompatibility, these nanoantiseptics might have effective and broad clinical applications for bacterial infections. PMID:28533681

  12. 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.

  13. 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.

  14. Doxorubicin Hydrochloride Loaded Zymosan-Polyethylenimine Biopolymeric Nanoparticles for Dual 'Chemoimmunotherapeutic' Intervention in Breast Cancer.

    PubMed

    Pawar, Vivek K; Singh, Yuvraj; Sharma, Komal; Shrivastav, Arpita; Sharma, Abhisheak; Singh, Akhilesh; Meher, Jaya Gopal; Singh, Pankaj; Raval, Kavit; Bora, Himangshu K; Datta, Dipak; Lal, Jawahar; Chourasia, Manish K

    2017-09-01

    To utilize nanoparticles produced by condensation of zymosan (an immunotherapeutic polysaccharide) with pegylated polyethylenimine (PEG-PEI) for dual intervention in breast cancer by modulating tumor microenvironment and direct chemotherapy. Positively charged PEG-PEI and negatively charged sulphated zymosan were utilized for electrostatic complexation of chemoimmunotherapeutic nanoparticles (ChiNPs). ChiNPs were loaded with doxorubicin hydrochloride (DOX) for improved delivery at tumor site and were tested for in-vivo tolerability. Biodistribution studies were conducted to showcase their effective accumulation in tumor hypoxic regions where tumor associated macrophages (TAMs) are preferentially recruited. ChiNPs modulated TAMs differentiation resulting in decrement of CD206 positive population. This immunotherapeutic action was furnished by enhanced expression of Th1 specific cytokines. ChiNPs also facilitated an anti-angiogenetic effect which further reduces the possibility of tumor progression and metastasis.

  15. Magnetic Field-Guided Cell Delivery with Nanoparticle-Loaded Human Corneal Endothelial Cells

    PubMed Central

    Moysidis, Stavros N.; Alvarez-Delfin, Karen; Peschansky, Veronica J.; Salero, Enrique; Weisman, Alejandra D.; Bartakova, Alena; Raffa, Gabriella A.; Merkhofer, Richard M.; Kador, Karl E.; Kunzevitzky, Noelia J.; Goldberg, Jeffrey L.

    2015-01-01

    To improve the delivery and integration of cell therapy using magnetic cell guidance for replacement of corneal endothelium, here we assess magnetic nanoparticles’ (MNPs) effects on human corneal endothelial cells (HCECs) in vitro. Biocompatible, 50 nm superparamagnetic nanoparticles endocytosed by cultured HCECs induced no short- or long-term change in viability or identity. Assessment of guidance of the magnetic HCECs in the presence of different magnet shapes and field strengths showed a 2.4-fold increase in delivered cell density compared to gravity alone. After cell delivery, HCECs formed a functional monolayer, with no difference in tight junction formation between MNP-loaded and control HCECs. These data suggest that nanoparticle-mediated magnetic cell delivery may increase the efficiency of cell delivery without compromising HCEC survival, identity or function. Future studies may assess the safety and efficacy of this therapeutic modality in vivo. PMID:25596075

  16. 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.

  17. Metformin-loaded alginate nanoparticles as an effective antidiabetic agent for controlled drug release.

    PubMed

    Kumar, Sandeep; Bhanjana, Gaurav; Verma, Ritesh Kumar; Dhingra, Dinesh; Dilbaghi, Neeraj; Kim, Ki-Hyun

    2017-02-01

    Present modalities for the diagnosis and treatment of diabetes still suffer from certain limitations such as erratic absorption, need of high dose, poor sensitivity or specificity, resistance, substantial morbidity and mortality, long-term complications, and patient-to-patient variability with lifetime treatment. This study focused on the development of a water-in-oil-in-water metformin nanoemulsion as an effective method in diabetes treatment. As a Biopharmaceutics Classification System (BCS) class III drug, metformin is hydrophilic in nature with high solubility and poor absorption characteristics. To simultaneously facilitate gastrointestinal absorption and intestinal permeability, metformin was loaded into alginate nanocapsules prepared by an emulsion cross-linking technology. These prepared metformin-loaded alginate nanoparticles (MLANs) were characterized using transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and photon correlation spectroscopy (PCS)-based particle size analysis. The drug loading and encapsulation efficiency in MLANs were 3.12 mg (the amount of metformin added in 100 mg of nanoparticles) and 78%, respectively. The results of in-vitro drug release studies and in-vivo efficacy tests (using animal models) demonstrated enhanced efficiency and response of MLANs relative to pure metformin. The efficacy of MLANs (46.8 mg/kg) was overall about three times higher than that of pure metformin150 mg/kg. © 2016 Royal Pharmaceutical Society.

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

    PubMed

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

    2016-04-01

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

  19. Targeted Delivery System Based on Gemcitabine-Loaded Silk Fibroin Nanoparticles for Lung Cancer Therapy.

    PubMed

    Mottaghitalab, Fatemeh; Kiani, Melika; Farokhi, Mehdi; Kundu, Subhas C; Reis, Rui L; Gholami, Mahdi; Bardania, Hassan; Dinarvand, Rassoul; Geramifar, Parham; Beiki, Davood; Atyabi, Fatemeh

    2017-09-20

    Here, a targeted delivery system was developed based on silk fibroin nanoparticles (SFNPs) for the systemic delivery of gemcitabine (Gem) to treat induced lung tumor in a mice model. For targeting the tumorigenic lung tissue, SP5-52 peptide was conjugated to Gem-loaded SFNPs. Different methods were used to characterize the structural and physicochemical properties of the SFNPs. The prepared nanoparticles (NPs) showed suitable characteristics in terms of size, zeta potential, morphology, and structural properties. Moreover, the targeted Gem-loaded SFNPs showed higher cytotoxicity, cellular uptake, and accumulation in the lung tissue in comparison to the nontargeted SFNPs and control groups. Afterward, a mice model with induced lung tumor was developed by intratracheal injection of Lewis lung carcinoma (LL/2) cells into the lungs for assessing the therapeutic efficacy of the prepared drug delivery system. The histopathological assessments and single-photon-emission computed tomography-CT radiographs showed successful lung tumor induction. Moreover, the obtained results showed higher potential of targeted Gem-loaded SFNPs in treating induced lung tumor compared with that of the control groups. Higher survival rate, less mortality, and no sign of metastasis were also observed in those animals treated with targeted NPs based on the histological and radiological analyses. This study presented an effective anticancer drug delivery system for specific targeting of induced lung tumor that could be useful in treating malignant lung cancers in future.

  20. 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.

  1. 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

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

    PubMed

    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 Mn(2+) 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.

  3. 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.

  4. Enhanced antibacterial activity of roxithromycin loaded pegylated poly lactide-co-glycolide nanoparticles

    PubMed Central

    2012-01-01

    Background and the purpose of the study The purpose of this study was to prepare pegylated poly lactide-co-glycolide (PEG-PLGA) nanoparticles (NPs) loaded with roxithromycin (RXN) with appropriate physicochemical properties and antibacterial activity. Roxithromycin, a semi-synthetic derivative of erythromycin, is more stable than erythromycin under acidic conditions and exhibits improved clinical effects. Methods RXN was loaded in pegylated PLGA NPs in different drug;polymer ratios by solvent evaporation technique and characterized for their size and size distribution, surface charge, surface morphology, drug loading, in vitro drug release profile, and in vitro antibacterial effects on S. aureus, B. subtilis, and S. epidermidis. Results and conclusion NPs were spherical with a relatively mono-dispersed size distribution. The particle size of nanoparticles ranged from 150 to 200 nm. NPs with entrapment efficiency of up to 80.0±6.5% and drug loading of up to 13.0±1.0% were prepared. In vitro release study showed an early burst release of about 50.03±0.99% at 6.5 h and then a slow and steady release of RXN was observed after the burst release. In vitro antibacterial effects determined that the minimal inhibitory concentration (MIC) of RXN loaded PEG-PLGA NPs were 9 times lower on S. aureus, 4.5 times lower on B. subtilis, and 4.5 times lower on S. epidermidis compared to RXN solution. In conclusion it was shown that polymeric NPs enhanced the antibacterial efficacy of RXN substantially. PMID:23351784

  5. Enhanced oral bioavailability of insulin-loaded solid lipid nanoparticles: pharmacokinetic bioavailability of insulin-loaded solid lipid nanoparticles in diabetic rats.

    PubMed

    Ansari, Mohammad Javed; Anwer, Md Khalid; Jamil, Shahid; Al-Shdefat, Ramadan; Ali, Bahaa E; Ahmad, Mohammad Muqtader; Ansari, Mohammad Nazam

    2016-07-01

    Insulin is a hormone used in the treatment of diabetes mellitus. Multiple injections of insulin every day may causes pain, allergic reactions at injection site, which lead to low patient compliance. The aim of this work was to develop and evaluate an efficient solid lipid nanoparticle (SLN) carrier for oral delivery of insulin. SLNs were prepared by double emulsion solvent evaporation (w/o/w) technique, employing glyceryltrimyristate (Dynasan 114) as lipid phase and soy lecithin and polyvinyl alcohol as primary and secondary emulsifier, respectively, and evaluated in vitro for particle size, polydispersity index (PDI) and drug entrapment. Among the eight different developed formulae (F1-F8), F7 showed an average particle size (99 nm), PDI (0.021), high entrapment of drug (56.5%). The optimized formulation (F7) was further evaluated by FT-IR, DSC, XRD, in vitro release, permeation, stability, bioavailability and pharmacological studies. Insulin-loaded SLNs showed better protection from gastrointestinal environment as evident from the relative bioavailability, which was enhanced five times as compared to the insulin solution. A significant enhancement of relative bioavailability of insulin was observed, i.e. approximately five times of pure insulin solution when loaded in SLN (8.26% versus 1.7% only).

  6. Target-specific porphyrin-loaded hybrid nanoparticles to improve photodynamic therapy for cancer treatment

    NASA Astrophysics Data System (ADS)

    Vivero-Escoto, Juan L.; Vega, Daniel L.

    2017-02-01

    Photodynamic therapy (PDT) has emerged as an alternative approach to chemotherapy and radiotherapy for cancer treatment. The photosensitizer (PS) is perhaps the most critical component of PDT, and continues to be an area of intense scientific research. Traditionally, PS molecules like porphyrins have dominated the field. Nevertheless, these PS agents have several disadvantages, with low water solubility, poor light absorption, and reduced selectivity for targeted tissues being some of the main drawbacks. Polysilsesquioxane (PSilQ) nanoparticles provide an interesting platform for developing PS-loaded hybrid nanocarriers. Several advantages can be foreseen by using this platform such as carrying a large payload of PS molecules; their surface and composition can be tailored to develop multifunctional systems (e.g. target-specific); and due to their small size, nanoparticles can penetrate deep into tissues and be readily internalized by cells. In this work, porphyrin-loaded PSilQ nanoparticles with a high payload of photosensitizers were synthesized, characterized, and applied in vitro. The network of this nanomaterial is formed by porphyrin-based photosensitizers chemically connected via a redox-responsive linker. Under reducing environment such as the one found in cancer cells the nanoparticles can be degraded to efficiently release single photosensitizers in the cytoplasm. The platform was further functionalized with polyethylene glycol (PEG) and folic acid as targeting ligand to improve its biocompatibility and target specificity toward cancer cells overexpressing folate receptors. The effectiveness of this porphyrin-based hybrid nanomaterial was successfully demonstrated in vitro using MDA-MB-231 breast cancer cell line.

  7. Characterization and anti-proliferative activity of curcumin loaded chitosan nanoparticles in cervical cancer.

    PubMed

    Khan, Md Asad; Zafaryab, Md; Mehdi, Syed Hassan; Ahmad, Irfan; Rizvi, M Moshahid A

    2016-12-01

    In the present study the chitosan nanoparticles (CsNPs) and curcumin loaded chitosan nanoparticles (CLCsNPs) were synthesized by tripolyphosphate (TPP) cross-linking method. The nanoparticles were prepared within a zone of appropriate chitosan and TPP concentrations. The average size of CsNPs and CLCsNPs were approximately 189±11.8nm and 197±16.8nm, exhibited a zeta potential of +76±5.6mV and +71±6.4mV respectively and drug entrapment efficiency was ≈85%. The CLCsNPs and CsNPs were further characterized by different physicochemical methods like transmission electron microscopy (TEM), dynamic light scattering (DLS), HPLC, MALDI-TOF, FT-IR, XRD and UV-vis Spectroscopy. In vitro studies revealed a fast release of ≈35% at pH 5 and ≈25% at pH 7.4 of the drug during the first 3h, followed by controlled release of curcumin over a period of 120h and sustained anti-proliferative activity of the drug in a dose and time dependent manner of CLCsNPs and combination with methyl jasmonate. The higher cytotoxicity effect of CLCsNPs may be due to their higher cellular uptake as compared to curcumin. Chitosan nanoparticles were not only stable but also a nontoxic. Our data suggested that curcumin loaded nanoformulations, therefore, might be promising candidates in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  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. Design of amine-modified graft polyesters for effective gene delivery using DNA-loaded nanoparticles.

    PubMed

    Oster, Christine G; Wittmar, Matthias; Unger, Florian; Barbu-Tudoran, Lucian; Schaper, Andreas K; Kissel, Thomas

    2004-06-01

    The purpose of this study was the design of a polymeric platform for effective gene delivery using DNA-loaded nanoparticles. The polymers were synthesized by carbonyldiimidazole (CDI)-mediated coupling of diamines diethylaminopropylamine (DEAPA), dimethylaminopropylamine (DMAPA) or diethylaminoethylamine (DEAEA) to poly(vinyl alcohol) (PVA) with subsequent grafting of D,L-lactide and glycolide (1:1) in the stoichiometric ratios of 1:10 and 1:20 (free hydroxyl groups/monomer units). The polymers were characterized by 1H-NMR, gel permeation chromatography-multiple-angle laser-light-scattering, and differential scanning calorimetry. DNA-loaded nanoparticles prepared by a modified solvent displacement method were characterized with regard to their zeta (zeta)-potential and size. The transfection efficiency was assessed with the plasmid DNA pCMV-luc in L929 mouse fibroblasts. The polymers were composed of highly branched, biodegradable cationic polyesters exhibiting amphiphilic properties. The amine modification enhanced the rapid polymer degradation and resulted in the interaction with DNA during particle preparation. The nanoparticles exhibited positive zeta-potentials up to +42 mV and high transfection efficiencies, comparable to polyethylenimine (PEI) 25 kDa/DNA complexes at a nitrogen to phosphate ratio of 5. The polymers combined amine-functions and short poly(D,L-lactic-co-glycolic acid) (PLGA) chains resulting in water-insoluble polymers capable of forming biodegradable DNA nanoparticles through coulombic interactions and polyester precipitation in aqueous medium. The high transfection efficiency was based on fast polymer degradation and the conservation of DNA bioactivity.

  10. Development of DH-I-180-3 loaded lipid nanoparticle for photodynamic therapy.

    PubMed

    Park, Jun-Hyung; Ban, Sang-Jun; Ahmed, Taksim; Choi, Hong Seok; Yoon, Hyo-Eun; Yoon, Jung-Hoon; Choi, Hoo-Kyun

    2015-08-01

    Photodynamic therapy (PDT) is a promising noninvasive treatment modality for cancer. Photosensitizer and specific wave length of light are the key component of PDT. DH-I-180-3, a second generation photosensitizer, was incorporated into lipid nanoparticle for simultaneous fluorescent imaging and targeting therapy. Solid lipid nanoparticle (SLN) and nanostructured lipid carriers (NLC) based on poloxamer 188 as surfactant and lecithin as co-surfactant were prepared using solvent evaporation and hot homogenization technique. Stearic acid and Capmul(®) MCM C8 were utilized as solid lipid and liquid lipid, respectively. The particle size of SLN and NLCs was around 200 nm and decreased when a part of stearic acid was replaced with Capmul(®) MCM C8. Drug loading efficacy was significantly enhanced when the percentage amount of liquid lipid increased. All the polydispersity indices of the SLN/NLCs were below 0.3, and displayed a narrow particle size distribution. Zeta potentials of all the lipid nanoparticles were below -30 mV, maintaining sufficient repulsive force and achieving enhanced physical stability. No significant change in the particle size and polydispersity index was observed from lyophilized SLN/NLCs. When the photocytotoxic effects of the formulations were evaluated in MCF-7 cells, GI 50 of SLN was less than half of DH-I-180-3 solution, and NLCs containing either 5 or 15%w/w of Capmul(®) MCM C8 exerted higher cytotoxicity than SLN. The fluorescence microscope images displayed enhanced cellular accumulation of DH-I-180-3 loaded in SLN and NLCs, which was closely correlated with the photocytotoxicity results. It was concluded that the incorporation of DH-I-180-3 into the nanoparticles enhanced their targeting efficacy and improved photocytotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Lipid/alginate nanoparticle-loaded in situ gelling system tailored for dexamethasone nasal delivery.

    PubMed

    Dukovski, Bisera Jurišić; Plantić, Ivana; Čunčić, Ivan; Krtalić, Iva; Juretić, Marina; Pepić, Ivan; Lovrić, Jasmina; Hafner, Anita

    2017-05-31

    In this study, we suggest the development of nanoparticle loaded in situ gelling system suitable for corticosteroid nasal delivery. We propose lipid/alginate nanoparticles (size 252.3±2.4nm, polydispersity index 0.241, zeta-potential -31.7±1.0mV, dexamethasone (Dex) content 255±7μgml(-1)) dispersed in pectin solution (5mgml(-1)) that undergoes a sol-gel phase transition triggered by Ca(2+) present in nasal mucosa. The viscoelasticity of gel obtained by mixing nanoparticle suspension in pectin continuous phase with simulated nasal fluid (1:1V/V) is characterised by a log-linear shear thinning viscosity behaviour. Observed viscosity corresponds to the range of viscosities of nasal mucus at physiological as well as under disease conditions. Nanoparticle-loaded gel was biocompatible with the selected epithelial cell model and, in comparison to dexamethasone solution, provided reduction in Dex release (t50% 2.1h and 0.6h, respectively) and moderated transepithelial permeation in vitro (Papp 7.88±0.15 and 9.73±0.57×10(-6)cms(-1), respectively). In conclusion, this study showed the potential of the proposed system to provide local therapeutic effect upon administration of a lower corticosteroid dose and minimize the possibility for adverse effects as it can be easily sprayed as solution and delivered beyond nasal valve, ensure prolonged contact time with nasal mucosa upon gelation, and moderate corticosteroid release and permeation. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.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

  13. Influence of polymers ratio on insulin-loaded nanoparticles based on poly-epsilon-caprolactone and Eudragit RS for oral administration.

    PubMed

    Socha, M; Sapin, A; Damgé, C; Maincent, P

    2009-11-01

    Nanoparticles loaded with two different commercial insulins (Actrapid, Novorapid and based on different blends of a biodegradable polyester (poly-epsilon-caprolactone) and a polycationic non-biodegradable acrylic polymer (Eudragit RS) were characterized in vitro. The zeta potential was positive whenever Eudragit RS was part of the nanoparticles matrix. The encapsulation efficiency was ~ 96% except for Novorapid-loaded particles of poly-epsilon-caprolactone (only 35%). In vitro release studies revealed a burst release from nanoparticles, which may be of interest for oral delivery. Novorapid-loaded nanoparticles were orally administered to diabetic rats and allowed the glycemia to be decreased when compared with free nanoparticles.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Ultrasound-guided Delivery of microRNA Loaded Nanoparticles into Cancer

    PubMed Central

    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.

    2015-01-01

    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 (<1 nm) molecules has been shown at acoustic pressures below 1MPa both in vitro and in vivo, the delivery efficiency of larger (>100 nm) 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 6.9 MPa. 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 6.9 MPa resulted in a nearly 50-fold increase in cavitation in phantom experiments. In vivo, as the pressures increased from 1.7 to 6.9 MPa, the amount of nanoparticles deposited in cancer xenografts was increased from 4- to 14-fold, and the median penetration

  20. 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

  1. Preparation, characterization, and optimization of primaquine-loaded solid lipid nanoparticles

    PubMed Central

    Omwoyo, Wesley Nyaigoti; Ogutu, Bernhards; Oloo, Florence; Swai, Hulda; Kalombo, Lonji; Melariri, Paula; Mahanga, Geoffrey Maroa; Gathirwa, Jeremiah Waweru

    2014-01-01

    Primaquine (PQ) is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. PQ use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. Nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing toxicity. The aim of this work was to design, synthesize, and characterize PQ-loaded solid lipid nanoparticles (SLNs) (PQ-SLNs) as a potential drug-delivery system. SLNs were prepared by a modified solvent emulsification evaporation method based on a water-in-oil-in-water (w/o/w) double emulsion. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the PQ-SLNs were 236 nm, +23 mV, 14%, and 75%, respectively. The zeta potential of the SLNs changed dramatically, from −6.54 mV to +23.0 mV, by binding positively charged chitosan as surface modifier. A spherical morphology of PQ-SLNs was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. Differential scanning calorimeter thermograms demonstrated presence of drug in drug-loaded nanoparticles along with disappearance of decomposition exotherms, suggesting increased physical stability of drug in prepared formulations. Negligible changes in characteristic peaks of drug in Fourier transform infrared spectra indicated absence of any interaction among the various components entrapped in the nanoparticle formulation. The nanoformulated PQ was 20% more effective as compared with conventional oral dose when tested in Plasmodium berghei-infected Swiss albino mice. This study demonstrated an efficient method of forming a nanomedicine delivery system for antimalarial drugs. PMID:25143734

  2. Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats.

    PubMed

    Khalil, Najeh Maissar; do Nascimento, Thuane Castro Frabel; Casa, Diani Meza; Dalmolin, Luciana Facco; de Mattos, Ana Cristina; Hoss, Ivonete; Romano, Marco Aurélio; Mainardes, Rubiana Mara

    2013-01-01

    The aim of this study was to assess the potential of nanoparticles to improve the pharmacokinetics of curcumin, with a primary goal of enhancing its bioavailability. Polylactic-co-glycolic acid (PLGA) and PLGA-polyethylene glycol (PEG) (PLGA-PEG) blend nanoparticles containing curcumin were obtained by a single-emulsion solvent-evaporation technique, resulting in particles size smaller than 200 nm. The encapsulation efficiency was over 70% for both formulations. The in vitro release study showed that curcumin was released more slowly from the PLGA nanoparticles than from the PLGA-PEG nanoparticles. A LC-MS/MS method was developed and validated to quantify curcumin in rat plasma. The nanoparticles were orally administered at a single dose in rats, and the pharmacokinetic parameters were evaluated and compared with the curcumin aqueous suspension. It was observed that both nanoparticles formulations were able to sustain the curcumin delivery over time, but greater efficiency was obtained with the PLGA-PEG nanoparticles, which showed better results in all of the pharmacokinetic parameters analyzed. The PLGA and PLGA-PEG nanoparticles increased the curcumin mean half-life in approximately 4 and 6h, respectively, and the C(max) of curcumin increased 2.9- and 7.4-fold, respectively. The distribution and metabolism of curcumin decreased when it was carried by nanoparticles, particularly PLGA-PEG nanoparticles. The bioavailability of curcumin-loaded PLGA-PEG nanoparticles was 3.5-fold greater than the curcumin from PLGA nanoparticles. Compared to the curcumin aqueous suspension, the PLGA and PLGA-PEG nanoparticles increased the curcumin bioavailability by 15.6- and 55.4-fold, respectively. These results suggest that PLGA and, in particular, PLGA-PEG blend nanoparticles are potential carriers for the oral delivery of curcumin. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. 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

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

    PubMed

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

    2012-01-01

    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. 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. 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. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. Intraocular injection of tamoxifen-loaded nanoparticles: a new treatment of experimental autoimmune uveoretinitis.

    PubMed

    de Kozak, Yvonne; Andrieux, Karine; Villarroya, Henri; Klein, Christophe; Thillaye-Goldenberg, Brigitte; Naud, Marie-Christine; Garcia, Elisabeth; Couvreur, Patrick

    2004-12-01

    In this study, we tested the efficiency of an intravitreal injection of tamoxifen, a non-steroidal estrogen receptor modulator, in retinal soluble antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). To increase the bioavailability of tamoxifen, we incorporated tamoxifen into polyethylene glycol (PEG)-coated nanoparticles (NP-PEG-TAM). The localization of the nanoparticles within the eye was investigated using fluorescent-labeled PEG-coated nanoparticles after injection into the vitreous cavity of rats with EAU. Some nanoparticles were distributed extracellularly throughout the ocular tissues, others were concentrated in resident ocular cells and in infiltrating macrophages. Whereas the injection of free tamoxifen did not alter the course of EAU, injection of NP-PEG-TAM performed 1-2 days before the expected onset of the disease in controls resulted in significant inhibition of EAU. NP-PEG-TAM injection significantly reduced EAU compared to injection of NP-PEG-TAM with 17beta-estradiol (E2), suggesting that tamoxifen is acting as a partial antagonist to E2. Diminished infiltration by MHC class II(+) inflammatory cells and low expression of TNF-alpha, IL-1beta, and RANTES mRNA were noted in eyes of NP-PEG-TAM-treated rats. Intravitreal injection of NP-PEG-TAM decreased S-Ag lymphocyte proliferation, IFN-gamma production by inguinal lymph node cells, and specific delayed-type hypersensitivity indicative of a reduced Th1-type response. It increased the anti-S-Ag IgG1 isotype indicating an antibody class switch to Th2 response. These data suggest that NP-PEG-TAM inhibition of EAU could result from a form of immune deviation. Tamoxifen-loaded nanoparticles may represent a new option for the treatment of experimental uveitis.

  10. Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery.

    PubMed

    Alex, Angel Treasa; Joseph, Alex; Shavi, Gopal; Rao, Josyula Venkata; Udupa, Nayanabhirama

    2016-09-01

    The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood-brain barrier. Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route. Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells. The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential -16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone. CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. 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.

  17. Formulation of Carbapenems Loaded Gold Nanoparticles to Combat Multi-antibiotic Bacterial Resistance: In vitro Antibacterial Study.

    PubMed

    Shaker, Mohamed A; Shaaban, Mona I

    2017-04-11

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

  18. 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.

  19. 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

  20. Improved Oral Bioavailability, Therapeutic Efficacy, and Reduced Toxicity of Tamoxifen-Loaded Liquid Crystalline Nanoparticles.

    PubMed

    Jain, Sanyog; Heeralal, B; Swami, Rajan; Swarnakar, Nitin K; Kushwah, Varun

    2017-08-07

    Present investigation deals with formulation and evaluation of tamoxifen (TMX)-loaded liquid crystalline nanoparticles (TMX-LCNPs) for improving oral bioavailability and safety of the existing treatment. Hexagonal Glyceryl monooleate-based TMX-LCNPs (GLCNPs) and Phytantriol-based TMX-LCNPs (PLCNPs) were prepared by dilution-through-hydrotrope method for oral administration. Oleic acid was incorporated in the lipid matrix to enhance the drug loading in the LCNPs. Optimized LCNPs displayed small particle size with a narrow distribution, sustained drug release and high gastrointestinal stability. TMX-LCNPs were found to be considerably higher cytotoxic to MCF-7 cells as compared to free TMX. Substantial fold enhancement in oral bioavailability (~7- and ~5-folds with TMX-GLCNPs and TMX-PLCNPs, respectively) was evident followed by significant reduction in tumor burden with lesser hepatotoxicity. Out of the two LCNP formulations, PLCNPs were found to be better in convalescing the disease.

  1. 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.

  2. 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.

  3. 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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy.

    PubMed

    Wei, Yi; Gao, Li; Wang, Lu; Shi, Lin; Wei, Erdong; Zhou, Baotong; Zhou, Li; Ge, Bo

    2017-11-01

    We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand-receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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

  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. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Enhanced Pro-Apoptotic Effect of Tetrandrine Loaded Nanoparticles Against Osteosarcoma Cells.

    PubMed

    Tian, Yong; Yin, Haitao; Xu, Huae

    2016-01-01

    Tetrandrine (Tet), a kind of herbal medicine belonging to the family of bis-benzylisoquinoline alkaloid, has gained more attraction for its potential anti-tumor effects. However, its potential utilization in clinic is greatly hampered by the poor pharmacokinetcs profile due to its insolubility. Recently, biodegradable polymeric nanoparticles with amphilic copolymers as drug carriers have shown better bioavailability against tumor as promising tumor-targeted drug delivery system. In the current study, Tet-loaded nanoparticles (Tet-NPs) was prepared with amphiphilic block copolymer as drug carriers. The physiochemical characterization, in vitro and in vivo antitumor effect of nanoparticles were evaluated. In vitro study demonstrated the superior cell inhibitory effect of Tet-NPs. Most importantly, the viability of cells exposed to Tet-NPs was significant lower than that of cells treated with free Tet at lower equivalent doses. Moreover, Tet- NPs induced apoptosis and inhibited the proliferation of cells more effectively than free did at the equivalent concentration. Western blot showed that the expression of anti-apoptotic protein Bcl-2, Bcl-XL was significantly promoted while the pro-apoptotic Bax was significantly inhibited by the treatment of Tet-NPs. Data from the current study suggested that Tet-NPs is a promising delivery nano-system for the treatment of osteosarcoma.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  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. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

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

    PubMed

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

    2016-01-18

    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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  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. Experimental and Mathematical Studies on the Drug Release Properties of Aspirin Loaded Chitosan Nanoparticles

    PubMed Central

    Wan, Ajun; Shi, Yifei; Zhang, Yueyue; Chen, Yupeng

    2014-01-01

    The study of drug release dynamic is aiming at understanding the process that drugs release in human body and its dynamic characteristics. It is of great significance since these characteristics are closely related to the dose, dosage form, and effect of the drugs. The Noyes-Whitney function is used to represent how the solid material is dissolved into solution, and it is well used in study of drug dynamic. In this research, aspirin (acetylsalicylic acid (ASA)) has been encapsulated with different grades of chitosan (CS) varying in molecular weight (Mw) for the purpose of controlled release. The encapsulation was accomplished by ionic gelation technology based on assembly of positively charged chitosan and negatively charged sodium tripolyphosphate (TPP). The encapsulation efficiency, loading capacity, and drug release behavior of aspirin loaded chitosan nanoparticles (CS-NPs) were studied. It was found that the concentration of TPP and Aspirin, molecular weights of chitosan have important effect on the drug release patterns from chitosan nanoparticles. The results for simulation studies show that the Noyes-Whitney equation can be successfully used to interpret the drug release characteristics reflected by our experimental data. PMID:24987696

  18. Preparation and evaluation of novel octylmethoxycinnamate-loaded solid lipid nanoparticles.

    PubMed

    Liu, X-h; Liang, X-z; Fang, X; Zhang, W-P

    2015-08-01

    Octylmethoxycinnamate (OMC)-loaded solid lipid nanoparticles (SLNs) were prepared by ultrasonic emulsification method. Effects of process variables and formulation composition were investigated on particle size and polydispersity index (PI), and the UV absorbance. Effect of OMC concentration on entrapment efficiency (EE) was also studied. The optimal formulation was characterized and evaluated by environment emission scanning electron microscopy (ESEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). In addition, the degradations of OMC from SLNs and OMC conventional emulsion were compared. The composition of optimal formulation was determined as 5% (w/w) of solid lipid, 7% (w/w) of emulsifier and 9% of loaded OMC, resulting in a particle size of 392.8 nm, and EE of 88.73%, LD of 38.05% under the preparation condition of 6 min of sonication, 400 W of sonication power. ESEM study showed spherical particles with smooth surface. DSC studies indicated OMC encapsulation within the nanoparticle matrix. The characteristic peaks for OMC-SLNs stood at 1710, 1604, 1513, 1465 and 830.3 cm(-1) . The degradation rate of OMC was decreased when using SLNs formulations compared to conventional emulsion. Hence, the developed SLNs can be used as sunscreen carrier for improve the stability. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. Doxorubicin loaded magnetic gold nanoparticles for in vivo targeted drug delivery.

    PubMed

    Elbialy, Nihal Saad; Fathy, Mohamed Mahmoud; Khalil, Wafaa Mohamed

    2015-07-25

    Treatment of approximately 50% of human cancers includes the use of chemotherapy. The major problem associated with chemotherapy is the inability to deliver pharmaceuticals to specific site of the body without inducing normal tissue toxicity. Latterly, magnetic targeted drug delivery (MTD) has been used to improve the therapeutic performance of the chemotherapeutic agents and reduce the severe side effects associated with the conventional chemotherapy for malignant tumors. In this study, we were focused on designing biocompatible magnetic nanoparticles that can be used as a nanocarrier's candidate for MTD regimen. Magnetic gold nanoparticles (MGNPs) were prepared and functionalized with thiol-terminated polyethylene glycol (PEG), then loaded with anti-cancer drug doxorubicin (DOX). The physical properties of the prepared NPs were characterized using different techniques. Transmission electron microscopy (TEM) revealed the spherical mono-dispersed nature of the prepared MGNPs with size about 22 nm. Energy dispersive X-ray spectroscopy (EDX) assured the existence of both iron and gold elements in the prepared nanoparticles. Fourier transform infrared (FTIR) spectroscopy assessment revealed that PEG and DOX molecules were successfully loaded on the MGNPs surfaces, and the amine group of DOX is the active attachment site to MGNPs. In vivo studies proved that magnetic targeted drug delivery can provide a higher accumulation of drug throughout tumor compared with that delivered by passive targeting. This clearly appeared in tumor growth inhibition assessment, biodistribution of DOX in different body organs in addition to the histopathological examinations of treated and untreated Ehrlich carcinoma. To assess the in vivo toxic effect of the prepared formulations, several biochemical parameters such as aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), urea, uric acid and creatinine were measured. MTD

  5. 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.

  6. 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

  7. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Design, characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting.

    PubMed

    Jafarieh, Omidreza; Md, Shadab; Ali, Mushir; Baboota, Sanjula; Sahni, J K; Kumari, Bhavna; Bhatnagar, Aseem; Ali, Javed

    2015-01-01

    Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra. The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson's drug ropinirole (RH) to the brain using polymeric nanoparticles. Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration. The RH-CSNPs showed sustained release profiles for up to 18 h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210 ± 0.52), followed by kidneys (6.862 ± 0.62), intestine (4.862 ± 0.45), and lungs (4.640 ± 0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251 ± 0.09 and 0.386 ± 0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5 h are indicative of direct nose to brain transport, bypassing the blood-brain barrier (BBB). The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.

  9. 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

  10. Structural characterization of nanoparticles loaded with garlic essential oil and their insecticidal activity against Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae).

    PubMed

    Yang, Feng-Lian; Li, Xue-Gang; Zhu, Fen; Lei, Chao-Liang

    2009-11-11

    The aim of this work was to characterize polyethylene glycol (PEG) coated nanoparticles loaded with garlic essential oil and to evaluate their insecticidal activity against adult Tribolium castaneum . Preparation of nanoparticles was carried out using the melt-dispersion method, a very simple, convenient, and low-cost technique. The oil-loading efficiency could reach 80% at the optimal ratio of essential oil to PEG (10%). The morphology results and nanoparticle size showed that the nanoparticles had a round appearance and good dispersion, <240 nm in the average diameter, characterized by transmission electron microscope and dynamic light scattering, respectively. The abundance and percentage content of the major components did not show any significant difference between free and nanoencapsulated oil when analyzed by gas chromatography-mass spectrometry. The control efficacy against adult T. castaneum remained over 80% after five months, presumably due to the slow and persistent release of the active components from the nanoparticles. In contrast, the control efficacy of free garlic essential oil at the similar concentration (640 mg/kg) was only 11%. This indicates that it is feasible to use the PEG coating nanoparticles loaded with garlic essential oil to control the store-product pests.

  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. Otoprotective properties of 6α-methylprednisolone-loaded nanoparticles against cisplatin: In vitro and in vivo correlation.

    PubMed

    Martín-Saldaña, Sergio; Palao-Suay, Raquel; Trinidad, Almudena; Aguilar, María Rosa; Ramírez-Camacho, Rafael; San Román, Julio

    2016-05-01

    6α-Methylprednisolone-loaded surfactant-free nanoparticles have been developed to palliate cisplatin ototoxicity. Nanoparticles were based on two different amphiphilic pseudo-block copolymers obtained by free radical polymerization and based on N-vinyl pyrrolidone and a methacrylic derivative of α-tocopheryl succinate or α-tocopherol. Copolymers formed spherical nanoparticles by nanoprecipitation in aqueous media that were able to encapsulate 6α-methylprednisolone in their inner core. The obtained nanovehicles were tested in vitro using HEI-OC1 cells and in vivo in a murine model. Unloaded nanoparticles were not able to significantly reduce the cisplatin ototoxicity. Loaded nanoparticles reduced cisplatin-ototoxicity in vitro being more active those based on the methacrylic derivative of vitamin E, due to their higher encapsulation efficiency. This formulation was able to protect hair cells in the base of the cochlea, having a positive effect in the highest frequencies tested in a murine model. A good correlation between the in vitro and the in vivo experiments was found. Cisplatin is a commonly used chemotherapeutic agent against many cancers clinically. However, one of the significant side-effects remains ototoxicity. Here, the authors presented their data on using 6α-methylprednisolone-loaded nanoparticles in the reduction of ototoxicity in in-vitro and in-vivo experiments. Early promising results should enable further refinement of adopting this new approach in future experiments. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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