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Sample records for monodisperse polylactide-co-glycolide plga

  1. Biodegradable Polylactide-co-glycolide (PLGA) Thin Films Prepared by Electrospray and Pressurized Spray Deposition

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    PLGA thin films were prepared onto irnplantable devices by the electrospray and pressurized spray method. Thin films with structural gradients were obtained by controlling four parameters consisting of solution concentration, applied voltage, air pressure, and deposition time. The surface morphologies of the deposited films were observed using scanning electron microscopy (SEM). The image analysis revealed the control factors on the preparation of PLGA thin films. The beaded structure is easily formed with a decrease in polymer concentration while the fibrous structure is easily formed with an increase in polymer concentration. With the increase in applied voltage, the surface morphologies changed continuously from a small amount of fibrous shape to a large fibrous one: a small amount of fibrous shape at 10 kV, more fibers with non-uniform diameter at 20 kV, and most fibers with uniform diameter at 30 kV. Low air pressure (0.1 MPa ) corresponded to round particles while high air pressure (0.3 MPa) corresponded to flat particles. The change in thickness from 5.34 to 10.1 μm was a result of deposition time increasing from 5 to 10 s . From our above work, films of the bead or fiber structures can be obtained by changing electrical parameters to improve the biocompatibility of the film.

  2. POLYLACTIDE-CO-GLYCOLIDE NANOPARTICLES THERAPEUTIC BENEFITS IN CANCER

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    Pramod V. Burakle

    2013-02-01

    Full Text Available Anticancer therapy majorly hindered by drug low water solubility, poor drug permeability, and high efflux of drug from cells. Nanotechnology is severing as an important tool to overcome these problems of cancer drug therapy. Nanomaterials have been used to enhance drug delivery at targeted site with less toxicity to healthy cells. Biodegradable polyester, polylactide-co-glycolide is approved for use for humans. Review is focusing on recent developments concerning polylactide-co-glycolide nanoparticles prepared for cancer treatment. We have reviewed, methods used for the preparation and characterization of polylactide-co-glycolide nanoparticles and their applications in the delivery of a number of active agents. Polylactide-co-glycolide nanoparticles have provided the necessary momentum for promising future use of these agents in cancer treatment, with higher efficacy and fewer side effects.

  3. Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents

    Directory of Open Access Journals (Sweden)

    Rouhani H

    2011-04-01

    Full Text Available R Dinarvand1,2, N Sepehri1, S Manoochehri1, H Rouhani1, F Atyabi1,21Department of Pharmaceutics, Faculty of Pharmacy, 2Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, IranAbstract: The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability, and high efflux from cells. Nanomaterials have been used to enable drug delivery with lower toxicity to healthy cells and enhanced drug delivery to tumor cells. Different nanoparticles have been developed using different polymers with or without surface modification to target tumor cells both passively and/or actively. Polylactide-co-glycolide (PLGA, a biodegradable polyester approved for human use, has been used extensively. Here we report on recent developments concerning PLGA nanoparticles prepared for cancer treatment. We review the methods used for the preparation and characterization of PLGA nanoparticles and their applications in the delivery of a number of active agents. Increasing experience in the field of preparation, characterization, and in vivo application of PLGA nanoparticles has provided the necessary momentum for promising future use of these agents in cancer treatment, with higher efficacy and fewer side effects.Keywords: nanotechnology, polymeric nanocarriers, targeting, anticancer agents, surface modification

  4. Structural and functional characterization of proteins adsorbed on hydrophilized polylactide-co-glycolide microfibers

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    Vasita R

    2011-12-01

    Full Text Available Rajesh Vasita, Dhirendra S KattiDepartment of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, Uttar Pradesh, IndiaBackground: Hydrophobic biopolymers such as polylactide-co-glycolide (PLGA, 85:15 have been extensively explored as scaffolding materials for tissue engineering applications. More recently, electrospun microfiber-based and nanofiber-based scaffolds of PLGA have received increased attention because they act as physical mimics of the fibrillar extracellular matrix. However, the hydrophobicity of the PLGA microfiber surface can limit its use in biomedical applications. Therefore, in a previous study, we fabricated Pluronic® F-108 (PF-108-blended PLGA microfibrous scaffolds that alleviated the hydrophobicity associated with PLGA by enriching the surface of microfibers with the ethylene oxide units present in PF-108.Methods: In this study, we report the influence of the extent of surface enrichment of PLGA microfibers on their interaction with two model proteins, ie, bovine serum albumin (BSA and lysozyme. BSA and lysozyme were adsorbed onto PLGA microfiber meshes (unmodified and modified and studied for the amount, secondary structure conformation, and bioactivity of released protein.Results: Irrespective of the type of protein, PF-108-blended PLGA microfibers showed significantly greater protein adsorption and release than the unblended PLGA samples. However, in comparison with BSA, lysozyme showed a 7–9-fold increase in release. The Fourier transform infrared spectroscopy studies for secondary structure determination demonstrated that irrespective of type of microfiber surface (unblended or blended, adsorbed BSA and lysozyme did not show any significant change in secondary structure (α-helical content as compared with BSA and/or lysozyme in the free powder state. Further, the bioactivity assay of lysozyme released from blended PLGA microfiber meshes demonstrated 80%–85% bioactivity, indicating that

  5. Lamination of microfibrous PLGA fabric by electrospinning a layer of collagen-hydroxyapatite composite nanofibers for bone tissue engineering

    OpenAIRE

    Kwon, Gi-Wan; Gupta, Kailash Chandra; Jung, Kyung-Hye; Kang, Inn-Kyu

    2017-01-01

    Background To mimic the muscle inspired cells adhesion through proteins secretion, the lamination of collagen?hydroxyapatite nanorod (nHA) composite nanofibers has been carried out successfully on polydopamine (PDA)-coated microfibrous polylactide-co-glycolide (PLGA) fabrics. The lamination of collagen-hydroxyapatite composite nanofibers on polydopamine-coated microfibrous PLGA fabrics was carried through electrospinning the solution of collagen containing L-glutamic acid-grafted hydroxyapati...

  6. Lamination of microfibrous PLGA fabric by electrospinning a layer of collagen-hydroxyapatite composite nanofibers for bone tissue engineering.

    Science.gov (United States)

    Kwon, Gi-Wan; Gupta, Kailash Chandra; Jung, Kyung-Hye; Kang, Inn-Kyu

    2017-01-01

    To mimic the muscle inspired cells adhesion through proteins secretion, the lamination of collagen-hydroxyapatite nanorod (nHA) composite nanofibers has been carried out successfully on polydopamine (PDA)-coated microfibrous polylactide-co-glycolide (PLGA) fabrics. The lamination of collagen-hydroxyapatite composite nanofibers on polydopamine-coated microfibrous PLGA fabrics was carried through electrospinning the solution of collagen containing L-glutamic acid-grafted hydroxyapatite nanorods (nHA-GA) at a flow rate of 1.5 mL/h and an applied voltage of 15 kV. In comparison to pristine PLGA, dopamine-coated PLGA and collagen-hydroxyapatite composite nanofiber lamination has produced more wettable surfaces and surface wettability is found to higher with dopamine-coated PLGA fabrics then pristine PLGA. The SEM micrographs have clearly indicated that the lamination of polydopamine-coated PLGA fabric with collagen-hydroxyapatite composite nanofibers has shown increased adhesion of MC3T3E1 cells in comparison to pristine PLGA fabrics. The results of these studies have clearly demonstrated that collagen-nHA composites fibers may be used to create bioactive 3D scaffolds using PLGA as an architectural support agent.

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

    Science.gov (United States)

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

    2015-08-01

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

  8. Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs: synthesis, preparation and in vitro/ex vivo characterization.

    Science.gov (United States)

    Colzani, Barbara; Speranza, Giovanna; Dorati, Rossella; Conti, Bice; Modena, Tiziana; Bruni, Giovanna; Zagato, Elisa; Vermeulen, Lotte; Dakwar, George R; Braeckmans, Kevin; Genta, Ida

    2016-09-25

    Active drug targeting and controlled release of hydrophilic macromolecular drugs represent crucial points in designing efficient polymeric drug delivery nanoplatforms. In the present work EGFR-targeted polylactide-co-glycolide (PLGA) nanoparticles were made by a blend of two different PLGA-based polymers. The first, GE11-PLGA, in which PLGA was functionalized with GE11, a small peptide and EGFR allosteric ligand, able to give nanoparticles selective targeting features. The second polymer was a PEGylated PLGA (PEG-PLGA) aimed at improving nanoparticles hydrophilicity and stealth features. GE11 and GE11-PLGA were custom synthetized through a simple and inexpensive method. The nanoprecipitation technique was exploited for the preparation of polymeric nanoparticles composed by a 1:1weight ratio between GE11-PLGA and PEG-PLGA, obtaining smart nanoplatforms with proper size for parenteral administration (143.9±5.0nm). In vitro cellular uptake in EGFR-overexpressing cell line (A549) demonstrated an active internalization of GE11-functionalized nanoparticles. GE11-PLGA/PEG-PLGA blend nanoparticles were loaded with Myoglobin, a model hydrophilic macromolecule, reaching a good loading (2.42% respect to the theoretical 4.00% w/w) and a prolonged release over 60days. GE11-PLGA/PEG-PLGA blend nanoparticles showed good in vitro stability for 30days in physiological saline solution at 4°C and for 24h in pH 7.4 or pH 5.0 buffer at 37°C respectively, giving indications about potential storage and administration conditions. Furthermore ex vivo stability study in human plasma using fluorescence Single Particle Tracking (fSPT) assessed good GE11-PLGA/PEG-PLGA nanoparticles dimensional stability after 1 and 4h. Thanks to the versatility in polymeric composition and relative tunable nanoparticles features in terms of drug incorporation and release, GE11-PLGA/PEG-PLGA blend NPs can be considered highly promising as smart nanoparticulate platforms for the treatment of diseases

  9. PLGA/TCP composite scaffold incorporating bioactive phytomolecule icaritin for enhancement of bone defect repair in rabbits.

    Science.gov (United States)

    Chen, S-H; Lei, M; Xie, X-H; Zheng, L-Z; Yao, D; Wang, X-L; Li, W; Zhao, Z; Kong, A; Xiao, D-M; Wang, D-P; Pan, X-H; Wang, Y-X; Qin, L

    2013-05-01

    Bone defect repair is challenging in orthopaedic clinics. For treatment of large bone defects, bone grafting remains the method of choice for the majority of surgeons, as it fills spaces and provides support to enhance biological bone repair. As therapeutic agents are desirable for enhancing bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier, incorporating a phytomolecule icaritin (ICT), i.e., a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high-dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of these bioactive scaffolds with slow release of osteogenic ICT, the authors established a 12 mm ulnar bone defect model in rabbits. X-ray and high-resolution peripheral quantitative computed tomography results at weeks 2, 4 and 8 post-surgery showed more newly formed bone within bone defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized bone in PLGA/TCP/ICT groups, especially in the PLGA/TCP/MICT group, with correspondingly more new vessel ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with the proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications.

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

    OpenAIRE

    Cooper, Dustin L.; Sam Harirforoosh

    2014-01-01

    Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabil...

  11. Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

    Science.gov (United States)

    Cooper, Dustin L; Harirforoosh, Sam

    2014-01-01

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

  12. Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles.

    Directory of Open Access Journals (Sweden)

    Dustin L Cooper

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

  13. Computer Modeling Assisted Design of Monodisperse PLGA Microspheres with Controlled Porosity Affords Zero Order Release of an Encapsulated Macromolecule for 3 Months

    NARCIS (Netherlands)

    Kazazi-Hyseni, Filis; Landin, Mariana; Lathuile, Audrey; Veldhuis, Gert J.; Rahimian, Sima; Hennink, Wim E.; Kok, Robbert Jan; van Nostrum, Cornelus F.

    2014-01-01

    Purpose The aim of this study was the development of poly(D,L-lactide-co-glycolide) (PLGA) microspheres with controlled porosity, to obtain microspheres that afford continuous release of a macromolecular model compound (blue dextran). Methods PLGA microspheres with a size of around 40 μm and narrow

  14. EVALUATION OF THE FUNCTIONAL PROPERTIES OF HUMAN ENDOTHELIAL AND SMOOTH MUSCLE CELLS AFTER SEEDING ON THE SURFACE OF NATURAL AND SYNTHETIC MATERIALS

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    Sh. B. Saaya

    2016-01-01

    Full Text Available At present, vascular surgery using small diameter synthetic grafts is associated with a higher incidence of complications (thrombosis, restenosis, intimal hyperplasia than in operations using autologous vessels. However, the occurrence of concomitant pathology, reoperations and multifocal vascular disease limit the use of autologous vein and arteries. The important factor providing a long-term patency is the presence of vascular cells, which produce biologically active substance and provide mechanical properties. Aim. Selection of the optimal scaffold for creating cell-seeded tissue-engineering vessels. Materials and methods. Endothelial (EC and smooth muscle cells (SMC derived from human myocardium were seeded on different surfaces: decellularized homoarteriа, хenopericardium, polytetrafl uoroethylene (PTFE, polyethylene terephthalate (PET, polycaprolactone (PCL and polylactide-co-glycolide (PLGA. Results. Synthetic biodegradable materials polycaprolactone and polylactide-co-glycolide provide cell adhesion. The cells cultured on the polycaprolactone and polylactide-coglycolide scaffolds retain their functional properties: viability and proliferative properties, maintain specifi c endothelial antigens and synthesis of extracellular matrix. Conclusion. Synthetic biodegradable polycaprolactone and polylactide-co-glycolide electrospun scaffolds can be used for creation of cell-fi lled vascular prostheses. 

  15. On-demand one-step synthesis of monodisperse functional polymeric microspheres with droplet microfluidics.

    Science.gov (United States)

    Yu, Xu; Cheng, Gong; Zhou, Ming-Da; Zheng, Si-Yang

    2015-04-07

    A simple and robust method for one-step synthesis of monodisperse functional polymeric microspheres was established by generation of reversed microemulsion droplets in aqueous phase inside microfluidic chips and controlled evaporation of the organic solvent. Using this method, water-soluble nanomaterials can be easily encapsulated into biodegradable Poly(D,L-lactic-co-glycolic acid) (PLGA) to form functional microspheres. By controlling the flow rate of microemulsion phase, PLGA polymeric microspheres with narrow size distribution and diameters in the range of ∼50-100 μm were obtained. As a demonstration of the versatility of the approach, high-quality fluorescent CdTe:Zn(2+) quantum dots (QDs) of various emission spectra, superparamagnetic Fe3O4 nanoparticles, and water-soluble carbon nanotubes (CNTs) were used to synthesize fluorescent PLGA@QDs, magnetic PLGA@Fe3O4, and PLGA@CNTs polymeric microspheres, respectively. In order to show specific applications, the PLGA@Fe3O4 were modified with polydopamine (PDA), and then the silver nanoparticles grew on the surfaces of the PLGA@Fe3O4@PDA polymeric microspheres by reducting the Ag(+) to Ag(0). The as-prepared PLGA@Fe3O4@PDA-Ag microspheres showed a highly efficient catalytic reduction of the 4-nitrophenol, a highly toxic substance. The monodisperse uniform functional PLGA polymeric microspheres can potentially be critically important for multiple biomedical applications.

  16. Magnetic poly(lactide-co-glycolide) (PLGA) and cellulose particles for MRI-based cell tracking

    Science.gov (United States)

    Nkansah, Michael K.; Thakral, Durga; Shapiro, Erik M.

    2010-01-01

    Biodegradable, superparamagnetic micro- and nanoparticles of poly(lactide-co-glycolide) (PLGA) and cellulose were designed, fabricated and characterized for magnetic cell labeling. Monodisperse nanocrystals of magnetite were incorporated into micro- and nanoparticles of PLGA and cellulose with high efficiency using an oil-in-water single emulsion technique. Superparamagnetic cores had high magnetization (72.1 emu/g). The resulting polymeric particles had smooth surface morphology and high magnetite content (43.3 wt% for PLGA and 69.6 wt% for cellulose). While PLGA and cellulose nanoparticles displayed highest r2* values per millimole of iron (399 s-1mM-1 for cellulose and 505 s-1mM-1 for PLGA), micron-sized PLGA particles had a much higher r2* per particle than either. After incubation for a month in citrate buffer (pH 5.5), magnetic PLGA particles lost close to 50% of their initial r2* molar relaxivity, while magnetic cellulose particles remained intact, preserving over 85% of their initial r2* molar relaxivity. Lastly, mesenchymal stem cells and human breast adenocarcinoma cells were magnetically labeled using these particles with no detectable cytotoxicity. These particles are ideally suited for non-invasive cell tracking in vivo via MRI and due to their vastly different degradation properties, offer unique potential for dedicated use for either short (PLGA-based particles) or long term (cellulose-based particles) experiments. PMID:21404328

  17. Engineered monodisperse mesoporous materials

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, R.S.; Small, J.H.; Lagasse, R.R.; Schroeder, J.L.; Jamison, G.M.

    1997-08-01

    Porous materials technology has developed products with a wide variety of pore sizes ranging from 1 angstrom to 100`s of microns and beyond. Beyond 15{angstrom} it becomes difficult to obtain well ordered, monodisperse pores. In this report the authors describe efforts in making novel porous material having monodisperse, controllable pore sizes spanning the mesoporous range (20--500 {angstrom}). They set forth to achieve this by using unique properties associated with block copolymers--two linear homopolymers attached at their ends. Block copolymers phase separate into monodisperse mesophases. They desired to selectively remove one of the phases and leave the other behind, giving the uniform monodisperse pores. To try to achieve this the authors used ring-opening metathesis polymerization to make the block copolymers. They synthesized a wide variety of monomers and surveyed their polymers by TGA, with the idea that one phase could be made thermally labile while the other phase would be thermally stable. In the precipitated and sol-gel processed materials, they determined by porosimetry measurements that micropores, mesopores, and macropores were created. In the film processed sample there was not much porosity present. They moved to a new system that required much lower thermal treatments to thermally remove over 90% of the labile phase. Film casting followed by thermal treatment and solvent extraction produced the desired monodisperse materials (based solely on SEM results). Modeling using Density Functional Theory was also incorporated into this project. The modeling was able to predict accurately the domain size and spacing vs. molecular weight for a model system, as well as accurate interfacial thicknesses.

  18. Thermo-sensitive hydrogel PLGA-PEG-PLGA as a vaccine delivery system for intramuscular immunization.

    Science.gov (United States)

    Wang, Xiaoyan; Zhang, Yu; Xue, Wei; Wang, Hong; Qiu, Xiaozhong; Liu, Zonghua

    2016-11-25

    In this work, we explored the potential of thermo-sensitive PLGA-PEG-PLGA with sol-gel transition temperature around 32℃ as an intramuscular vaccine delivery system by using ovalbumin as a model antigen. First, in vitro release test showed that the PLGA-PEG-PLGA-deriving hydrogels could release ovalbumin in vitro in a more sustainable way. From fluorescence living imaging, 50-200 mg/mL of PLGA-PEG-PLGA formulations could release antigen in a sustainable manner in vivo, suggesting that the PLGA-PEG-PLGA hydrogel worked as an antigen-depot. Further, the sustainable antigen release from the PLGA-PEG-PLGA hydrogels increased antigen availability in the spleens of the immunized mice. The intramuscular immunization results showed that 50-200 mg/mL of PLGA-PEG-PLGA formulations promoted significantly more potent antigen-specific IgG immune response. In addition, 200 mg/mL of PLGA-PEG-PLGA formulation significantly enhanced the secretion of both Th1 and Th2 cytokines. From in vitro splenocyte proliferation assay, 50-200 mg/mL of PLGA-PEG-PLGA formulations all initiated significantly higher splenocyte activation. These results indicate that the thermo-sensitive and injectable PLGA-PEG-PLGA hydrogels (particularly, 200 mg/mL of PLGA-PEG-PLGA-based hydrogel) own promising potential as an intramuscular vaccine delivery system.

  19. Preparation of large monodisperse vesicles.

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    Ting F Zhu

    Full Text Available Preparation of monodisperse vesicles is important both for research purposes and for practical applications. While the extrusion of vesicles through small pores (approximately 100 nm in diameter results in relatively uniform populations of vesicles, extrusion to larger sizes results in very heterogeneous populations of vesicles. Here we report a simple method for preparing large monodisperse multilamellar vesicles through a combination of extrusion and large-pore dialysis. For example, extrusion of polydisperse vesicles through 5-microm-diameter pores eliminates vesicles larger than 5 microm in diameter. Dialysis of extruded vesicles against 3-microm-pore-size polycarbonate membranes eliminates vesicles smaller than 3 microm in diameter, leaving behind a population of monodisperse vesicles with a mean diameter of approximately 4 microm. The simplicity of this method makes it an effective tool for laboratory vesicle preparation with potential applications in preparing large monodisperse liposomes for drug delivery.

  20. Development of Risperidone PLGA Microspheres

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    Susan D’Souza

    2014-01-01

    Full Text Available The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50 : 50 and 75 : 25 were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40 mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50 : 50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75 : 25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug.

  1. Enhanced efficacy of clindamycin hydrochloride encapsulated in PLA/PLGA based nanoparticle system for oral delivery.

    Science.gov (United States)

    Rauta, Pradipta Ranjan; Das, Niladri Mohan; Nayak, Debasis; Ashe, Sarbani; Nayak, Bismita

    2016-08-01

    Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram-positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L-lactide-co-glycolide) (PLGA) nano-formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH-PLA and CLH-PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH-PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies.

  2. Fluorescent labeling of degradable poly(lactide-co-glycolide) for cellular nanoparticles tracking in living cells.

    Science.gov (United States)

    Freichels, Hélène; Danhier, Fabienne; Préat, Véronique; Lecomte, Philippe; Jérôme, Christine

    2011-02-01

    Fluorescent-labeled aliphatic polyesters are essential materials for in vitro and in vivo studies of the behavior of these biodegradable polymers in interaction with cells or in a body. In particular, the direct cellular localization of drug delivery systems based on these materials allows better understanding of the internalization mechanism and determination of the pharmacokinetics. Polylactide-co-glycolide (PLGA) is a rapidly degradable copolymer widely used in pharmaceutics and nanomedecine. It was prepared by ring-opening polymerization of lactide and glycolide in order to obtain a well-defined material to investigate conditions allowing the covalent linkage of a fluorescent dye (fluorescein) while preserving the macromolecular characteristics of the polymer. The success of the functionalization was ascertained by proton nuclear magnetic resonance (1H NMR), size-exclusion chromatography (SEC) and fluorescence spectroscopy.

  3. Parenteral immunization of PLA/PLGA nanoparticle encapsulating outer membrane protein (Omp) from Aeromonas hydrophila: Evaluation of immunostimulatory action in Labeo rohita (rohu).

    Science.gov (United States)

    Rauta, Pradipta Ranjan; Nayak, Bismita

    2015-05-01

    Advanced vaccine research approaches needs to explore on biodegradable nanoparticles (NPs) based vaccine carrier that can serve as antigen delivery systems as well as immuno-stimulatory action to induce both innate and adaptive immune response in fish. Immunogenicity of PLA and PLGA NPs encapsulating outer membrane protein (Omp) antigen of Aeromonas hydrophila were evaluated through intra-peritoneal injection in fish, Labeo rohita. Antigen loaded PLA-Omp (223.5 ± 13.19 nm) and PLGA-Omp (166.4 ± 21.23 nm) NPs were prepared using double emulsion method by efficiently encapsulating the antigen reaching the encapsulation efficiency 44 ± 4.58% and 59.33 ± 5.13% respectively. Our formulated PLA Omp and PLGA-Omp NPs were in nanometer range (PLA-Omp, it showed considerably slower antigen release in vitro than PLGA-Omp NPs. Other physical properties like zetapotential values and poly dispersity index (PDI) confirmed the stability as well as monodisperse nature of the formulated nanoparticles. The spherical and isolated nature of PLA-Omp and PLGA-Omp NPs were revealed by SEM analysis. Upon immunization of all antigenic formulations (PLA-Omp NP, PLGA-Omp NP, FIA-Omp, PLA NP, PLGA NP, PBS as control), significant higher bacterial agglutination titre and haemolytic activity were observed in case of PLA-Omp and PLGA-Omp immunized groups than rest groups at both 21 days and 42 days. The specific antibody response was significantly increased and persisted up to 42 days of post immunization by PLA-Omp, PLGA-Omp, FIA-Omp. PLA-Omp NPs showed better immune response (higher bacterial agglutination titre, haemolytic activity, specific antibody titre, higher percent survival upon A. hydrophila challenge) than PLGA-Omp in L. rohita confirming its better efficacy. Comparable antibody response of PLA-Omp and PLGA-Omp with FIA-Omp treated groups suggested that PLA and PLGA could be replacement for Freund's adjuvant (for stimulating antibody response) to overcome many side effects

  4. Aerosol fabrication methods for monodisperse nanoparticles

    Science.gov (United States)

    Jiang, Xingmao; Brinker, C Jeffrey

    2014-10-21

    Exemplary embodiments provide materials and methods for forming monodisperse particles. In one embodiment, the monodisperse particles can be formed by first spraying a nanoparticle-containing dispersion into aerosol droplets and then heating the aerosol droplets in the presence of a shell precursor to form core-shell particles. By removing either the shell layer or the nanoparticle core of the core-shell particles, monodisperse nanoparticles can be formed.

  5. Silicon microfluidic flow focusing devices for the production of size-controlled PLGA based drug loaded microparticles.

    Science.gov (United States)

    Keohane, Kieran; Brennan, Des; Galvin, Paul; Griffin, Brendan T

    2014-06-05

    The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications.

  6. Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis.

    Science.gov (United States)

    Zhou, Lin; Duan, Xingmei; Zeng, Shi; Men, Ke; Zhang, Xueyan; Yang, Li; Li, Xiang

    2015-01-01

    Natural product curcumin (Cur) and H2S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer.

  7. Delivery of multiple siRNAs using lipid-coated PLGA nanoparticles for treatment of prostate cancer.

    Science.gov (United States)

    Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha; Dunn, Stuart S; Enlow, Elizabeth M; Luft, J Christopher; Tian, Shaomin; Napier, Mary E; Pohlhaus, Patrick D; Rolland, Jason P; DeSimone, Joseph M

    2012-01-11

    Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called Particle Replication In Nonwetting Templates (PRINT). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32-46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer.

  8. PLGA/alginate composite microspheres for hydrophilic protein delivery

    Energy Technology Data Exchange (ETDEWEB)

    Zhai, Peng [Department of Anatomy and Cell Biology, University of Saskatchewan, S7N5E5 (Canada); Division of Biomedical Engineering, University of Saskatchewan, S7N5A9 (Canada); Chen, X.B. [Department of Mechanical Engineering, University of Saskatchewan, S7N5A9 (Canada); Division of Biomedical Engineering, University of Saskatchewan, S7N5A9 (Canada); Schreyer, David J., E-mail: david.schreyer@usask.ca [Department of Anatomy and Cell Biology, University of Saskatchewan, S7N5E5 (Canada); Division of Biomedical Engineering, University of Saskatchewan, S7N5A9 (Canada)

    2015-11-01

    Poly(lactic-co-glycolic acid) (PLGA) microspheres and PLGA/alginate composite microspheres were prepared by a novel double emulsion and solvent evaporation technique and loaded with bovine serum albumin (BSA) or rabbit anti-laminin antibody protein. The addition of alginate and the use of a surfactant during microsphere preparation increased the encapsulation efficiency and reduced the initial burst release of hydrophilic BSA. Confocal laser scanning microcopy (CLSM) of BSA-loaded PLGA/alginate composite microspheres showed that PLGA, alginate, and BSA were distributed throughout the depths of microspheres; no core/shell structure was observed. Scanning electron microscopy revealed that PLGA microspheres erode and degrade more quickly than PLGA/alginate composite microspheres. When loaded with anti-laminin antibody, the function of released antibody was well preserved in both PLGA and PLGA/alginate composite microspheres. The biocompatibility of PLGA and PLGA/alginate microspheres were examined using four types of cultured cell lines, representing different tissue types. Cell survival was variably affected by the inclusion of alginate in composite microspheres, possibly due to the sensitivity of different cell types to excess calcium that may be released from the calcium cross-linked alginate. - Highlights: • A double emulsion technique is used to prepare protein-loaded PLGA or PLGA/alginate microspheres. • PLGA, alginate and protein are distributed evenly within microsphere structure. • Addition of alginate improves loading efficiency and slows degradation and protein release. • PLGA/alginate microspheres have favorable biocompatibility.

  9. Fabrication of Nanostructured PLGA Scaffolds Using Anodic Aluminum Oxide Templates

    CERN Document Server

    Hsueh, Cheng-Chih; Hsu, Shan-Hui; Hung, Huey-Shan

    2008-01-01

    PLGA (poly(lactic-co-glycolic acid)) is one of the most used biodegradable and biocompatible materials. Nanostructured PLGA even has great application potentials in tissue engineering. In this research, a fabrication technique for nanostructured PLGA membrane was investigated and developed. In this novel fabrication approach, an anodic aluminum oxide (AAO) film was use as the template ; the PLGA solution was then cast on it ; the vacuum air-extraction process was applied to transfer the nano porous pattern from the AAO membrane to the PLGA membrane and form nanostures on it. The cell culture experiments of the bovine endothelial cells demonstrated that the nanostructured PLGA membrane can double the cell growing rate. Compared to the conventional chemical-etching process, the physical fabrication method proposed in this research not only is simpler but also does not alter the characteristics of the PLGA. The nanostructure of the PLGA membrane can be well controlled by the AAO temperate.

  10. The in vivo performance of CaP/PLGA composites with varied PLGA microsphere sizes and inorganic compositions

    NARCIS (Netherlands)

    Hoekstra, J.W.M.; Ma, J.; Plachokova, A.S.; Bronkhorst, E.M.; Bohner, M.; Pan, J.; Meijer, G.J.; Jansen, Jan; Beucken, J.J.J.P van den

    2013-01-01

    Enrichment of calcium phosphate (CaP) bone substitutes with poly(lactic-co-glycolic acid) (PLGA) microspheres to create porosity overcomes the problem of poor CaP degradation. The degradation of CaP-PLGA composites can be customized by changing the physical and chemical properties of PLGA and/or

  11. The in vivo performance of CaP/PLGA composites with varied PLGA microsphere sizes and inorganic compositions

    NARCIS (Netherlands)

    Hoekstra, J.W.M.; Ma, J.; Plachokova, A.S.; Bronkhorst, E.M.; Bohner, M.; Pan, J.; Meijer, G.J.; Jansen, Jan; Beucken, J.J.J.P van den

    2013-01-01

    Enrichment of calcium phosphate (CaP) bone substitutes with poly(lactic-co-glycolic acid) (PLGA) microspheres to create porosity overcomes the problem of poor CaP degradation. The degradation of CaP-PLGA composites can be customized by changing the physical and chemical properties of PLGA and/or CaP

  12. PLGA microspheres encapsulating siRNA.

    Science.gov (United States)

    De Rosa, Giuseppe; Salzano, Giuseppina

    2015-01-01

    The therapeutic use of small interfering RNA (siRNA) represents a new and powerful approach to suppress the expression of pathologically genes. However, biopharmaceutical drawbacks, such as short half-life, poor cellular uptake, and unspecific distribution into the body, hamper the development of siRNA-based therapeutics. Poly(lactide-co-glycolide), (PLGA) microspheres can be a useful tool to overcome these issues. siRNA can be encapsulated into the PLGA microspheres, which protects the loaded nucleic acid against the enzymatic degradation. Moreover, PLGA microspheres can be injected directly into the action site, where the siRNA can be released in controlled manner, thus avoiding the need of frequent invasive administrations. The complete biodegradability of PLGA to monomers easily metabolized by the body, and its approval by FDA and EMA for parenteral administration, assure the safety of this copolymer and do not require the removal of the device after the complete drug release. In chapter, a basic protocol for the preparation of PLGA microspheres encapsulating siRNA is described. This protocol is based on a double emulsion/solvent evaporation technique, a well known and easy to reproduce method. This specific protocol has been developed to encapsulate a siRNA anti-TNFα in PLGA microspheres, and it has been designed and optimized to achieve high siRNA encapsulation efficiency and slow siRNA release in vitro. However, it can be extended also to other siRNA as well as other RNA or DNA-based oligonucleotides (miRNA, antisense, decoy, etc.). Depending on the applications, chemical modifications of the backbone and site-specific modification within the siRNA sequences could be required.

  13. Spontaneous Breakup of Extended Monodisperse Polymer Melts

    DEFF Research Database (Denmark)

    Rasmussen, Henrik K.; Yu, Kaijia

    2011-01-01

    We apply continuum mechanical based, numerical modeling to study the dynamics of extended monodisperse polymer melts during the relaxation. The computations are within the ideas of the microstructural ‘‘interchain pressure’’ theory. The computations show a delayed necking resulting in a rupture...

  14. Influence of PLGA and PLGA-PEG on the dissolution profile of oxaliplatin

    Directory of Open Access Journals (Sweden)

    Emiliane Daher Pereira

    Full Text Available Abstract Oxaliplatin was inserted into polymeric matrices aiming to study the interaction of this drug with these polymers and its capability to diffuse to the environment. Tested polymers were: (1 polyethylene glycol (PEG, (2 poly(lactic-co-glycolic acid (PLGA, and (3 a copolymer of them (PLGA-PEG. The latter two were synthesized by us using polycondensation in bulk. Oxaliplatin was included in the matrices by the melt mixing process followed by casting. Fourier tran sform infrared spectroscopy (FTIR, proton nuclear magnetic resonance (1H-NMR and X-ray diffraction (DRX studies of the polymers were performed proving the obtaining of the desired materials. In addition, the interaction between drug and matrices and the release profile of the oxaliplatin from these matrices were analyzed. Among them, PEG did not control the oxaliplatin release. In turn, PLGA and PLGA-PEG present drug release profiles quite similar. Oxaliplatin was completely released from PLGA and PLGA-PEG in 5 hours, by a relaxation mechanism. There was no evidence of oxaliplatin interaction with the different polymers. In addition, as the PEG improves the biocompatibility and biomasking, obtained results prove the obtaining of a drug release system, which allowed the total use of the drug improving the cancer treatment and even the welfare of the patients.

  15. Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

    Directory of Open Access Journals (Sweden)

    Zhou L

    2015-08-01

    Full Text Available Lin Zhou,1,2,* Xingmei Duan,1,2,* Shi Zeng,1 Ke Men,1 Xueyan Zhang,1 Li Yang,1 Xiang Li1 1State Key Laboratory of Biotherapy, Cancer Center and Department of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sichuan Food and Drug Safety Monitoring and Review of Certification, Adverse Reaction Monitoring Center, Drug Abuse Monitoring Center, Chengdu, People’s Republic of China *These authors contributed equally to this work Abstract: Natural product curcumin (Cur and H2S-releasing prodrug SH-aspirin (SH-ASA are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol-poly (lactide-coglycolide (mPEG-PLGA nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016 in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer. Keywords: drug delivery, cancer therapy, ovarian cancer, synergistic effect

  16. PLGA/alginate composite microspheres for hydrophilic protein delivery.

    Science.gov (United States)

    Zhai, Peng; Chen, X B; Schreyer, David J

    2015-11-01

    Poly(lactic-co-glycolic acid) (PLGA) microspheres and PLGA/alginate composite microspheres were prepared by a novel double emulsion and solvent evaporation technique and loaded with bovine serum albumin (BSA) or rabbit anti-laminin antibody protein. The addition of alginate and the use of a surfactant during microsphere preparation increased the encapsulation efficiency and reduced the initial burst release of hydrophilic BSA. Confocal laser scanning microcopy (CLSM) of BSA-loaded PLGA/alginate composite microspheres showed that PLGA, alginate, and BSA were distributed throughout the depths of microspheres; no core/shell structure was observed. Scanning electron microscopy revealed that PLGA microspheres erode and degrade more quickly than PLGA/alginate composite microspheres. When loaded with anti-laminin antibody, the function of released antibody was well preserved in both PLGA and PLGA/alginate composite microspheres. The biocompatibility of PLGA and PLGA/alginate microspheres were examined using four types of cultured cell lines, representing different tissue types. Cell survival was variably affected by the inclusion of alginate in composite microspheres, possibly due to the sensitivity of different cell types to excess calcium that may be released from the calcium cross-linked alginate.

  17. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile

    Science.gov (United States)

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug’s pharmacokinetics related to the conventional formulation. Poly(lactide-co-glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs’ long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA–PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel’s pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs. PMID:28184163

  18. Template synthesis of monodisperse carbon nanodots

    Science.gov (United States)

    Kurdyukov, D. A.; Eurov, D. A.; Stovpiaga, E. Yu.; Kirilenko, D. A.; Konyakhin, S. V.; Shvidchenko, A. V.; Golubev, V. G.

    2016-12-01

    Monodisperse carbon nanodots in pores of mesoporous silica particles are obtained by template synthesis. This method is based on introducing a precursor (organosilane) into pores, its thermal decomposition with formation of carbon nanodots, and the template removal. Structural analysis of the nanomaterial has been performed, which showed that carbon nanodots have an approximately spherical form and a graphite-like structure. According to dynamic light scattering data, the size of carbon nanodots is 3.3 ± 0.9 nm.

  19. Synthesis and application of PLGA labeled with 125I

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The weight loss in vivo degradation of poly (lactide-co-glycolide) (PLGA) radiolabeled with 125I was investigated. PLGA with molecular weight (Mw) of 84000(LA/GA=85/15) were labeled with 125I in the chloroform media by circularly heating and round films of about 15 mm in diameter were formed. The composition and Mw of the 125I-PLGA were characterized by 1H-NMR and viscosimeter. The weight loss of this copolymer in vitro and in vivo degradation was quantified by determining radioactivity of materials. The results indicated that PLGA exhibited significantly faster degradation in vivo than that of in vitro conditions.

  20. Bone Regeneration from PLGA Micro-Nanoparticles

    Directory of Open Access Journals (Sweden)

    Inmaculada Ortega-Oller

    2015-01-01

    Full Text Available Poly-lactic-co-glycolic acid (PLGA is one of the most widely used synthetic polymers for development of delivery systems for drugs and therapeutic biomolecules and as component of tissue engineering applications. Its properties and versatility allow it to be a reference polymer in manufacturing of nano- and microparticles to encapsulate and deliver a wide variety of hydrophobic and hydrophilic molecules. It additionally facilitates and extends its use to encapsulate biomolecules such as proteins or nucleic acids that can be released in a controlled way. This review focuses on the use of nano/microparticles of PLGA as a delivery system of one of the most commonly used growth factors in bone tissue engineering, the bone morphogenetic protein 2 (BMP2. Thus, all the needed requirements to reach a controlled delivery of BMP2 using PLGA particles as a main component have been examined. The problems and solutions for the adequate development of this system with a great potential in cell differentiation and proliferation processes under a bone regenerative point of view are discussed.

  1. Bioavailability of Orally Delivered Alpha- tocopherol by Poly(Lactic-Co-Glycolic) Acid (PLGA) Nanoparticles and Chitosan Covered PLGA Nanoparticles in F344 Rats

    OpenAIRE

    Lacey C. Simon; Stout, Rhett W.; Cristina Sabliov

    2016-01-01

    t is hypothesized that the bioavailability of αT (alpha- tocopherol), an antioxidant, can be improved when delivered by poly(lactic-co-glycolic) acid (PLGA) nanopar‐ ticles (NPs) and chitosan covered PLGA nanoparticles (PLGA-Chi NPs), and that the mucoadhesive properties of chitosan may enhance absorption of αT. PLGA and PLGA- Chi NPs were characterized by measuring entrapment efficiency, size, polydispersity, and zeta potential. Nano‐ particle physical stability, chemical stability of entrap...

  2. An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery

    Energy Technology Data Exchange (ETDEWEB)

    Dorati, Rossella; DeTrizio, Antonella; Genta, Ida; Grisoli, Pietro; Merelli, Alessia [Department of Drug Sciences, Viale Taramelli 12, University of Pavia, 27100, Pavia (Italy); Tomasi, Corrado [IENI CNR Lecco Unit, Via Promessi Sposi 29, 23900, Lecco (Italy); Conti, Bice, E-mail: bice.conti@unipv.it [Department of Drug Sciences, Viale Taramelli 12, University of Pavia, 27100, Pavia (Italy)

    2016-01-01

    The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-co-polyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1–97.5%), and span values of particle size distribution (1.03–1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone. - Highlights: • To get a more effective therapy for the prevention and treatment of osteomyelitis. • To exploit the local

  3. Development and validation of HPLC method for quantitative analysis of triamcinolone in biodegradable microparticles

    Directory of Open Access Journals (Sweden)

    A. A. Silva-Júnior

    2009-01-01

    Full Text Available

    A simple, rapid, selective and specific high performance liquid chromatographic (HPLC method for quantitative analysis of the triamcinolone in polylactide-co-glycolide acid (PLGA microparticles was developed. The chromatographic parameters were reversed-phase C18 column, 250mm x 4.6mm, with particle size 5 m. The column oven was thermostated at 35 ºC ± 2 ºC. The mobile phase was methanol/water 45:55 (v/v and elution was isocratic at a flow-rate of 1mL.mL-1. The determinations were performed using a UV-Vis detector at 239 nm. The injected sample volume was 10 µL. The standard curve was linear (r2 > 0.999 in the concentration range 100-2500 ng.mL-1. The method showed adequate precision, with a relative standard deviation (RSD was smaller than 3%. The accuracy was analyzed by adding a standard drug and good recovery values were obtained for all drug concentrations used. The method showed specificity and selectivity with linearity in the working range and good precision and accuracy, making it very suitable for quantitation of triamcinolone in PLGA microparticles. Keywords: triamcinolone; HPLC analytical method; PLGA microparticles; analytical method validation.

  4. The in vivo performance of CaP/PLGA composites with varied PLGA microsphere sizes and inorganic compositions.

    Science.gov (United States)

    Hoekstra, Jan Willem M; Ma, Jinling; Plachokova, Adelina S; Bronkhorst, Ewald M; Bohner, Marc; Pan, Juli; Meijer, Gert J; Jansen, John A; van den Beucken, Jeroen J J P

    2013-07-01

    Enrichment of calcium phosphate (CaP) bone substitutes with poly(lactic-co-glycolic acid) (PLGA) microspheres to create porosity overcomes the problem of poor CaP degradation. The degradation of CaP-PLGA composites can be customized by changing the physical and chemical properties of PLGA and/or CaP. However, the effect of the size of dense (solid rather than hollow) PLGA microspheres in CaP has not previously been described. The present study aimed at determining the effect of different dense (i.e. solid) PLGA microsphere sizes (small (S) ~20μm vs. large (L) ~130μm) and of CaP composition (CaP with either anhydrous dicalcium phosphate (DCP) or calcium sulphate dihydrate (CSD)) on CaP scaffold biodegradability and subsequent bone in-growth. To this end mandibular defects in minipigs were filled with pre-set CaP-PLGA implants, with autologous bone being used as a control. After 4weeks the autologous bone group outperformed all CaP-PLGA groups in terms of the amount of bone present at the defect site. On the other hand, at 12weeks substantial bone formation was observed for all CaP-PLGA groups (ranging from 47±25% to 62±15%), showing equal amounts of bone compared with the autologous bone group (82±9%), except for CaP with DCP and large PLGA microspheres (47±25%). It was concluded that in the current study design the difference in PLGA microsphere size and CaP composition led to similar results with respect to scaffold degradation and subsequent bone in-growth. Further, after 12weeks all CaP-PLGA composites proved to be effective for bone substitution.

  5. Electrospinnability of Poly Lactic-co-glycolic Acid (PLGA)

    DEFF Research Database (Denmark)

    Liu, Xiaoli; Baldursdottir, Stefania G; Aho, Johanna

    2017-01-01

    PURPOSE: In this study, the electrospinnability of poly(lactic-co-glycolic acid) (PLGA) solutions was investigated, with a focus on understanding the influence of molecular weight of PLGA, solvent type and solvent composition on the physical properties of electrospun nanofibers. METHOD: Various...

  6. Microfluidic Production of Monodisperse Perfluorocarbon Microdroplets

    Science.gov (United States)

    Li, David; Schalte, Kevin; Fowlkes, J. Brian; Bull, Joseph

    2010-11-01

    Acoustic droplet vaporization (ADV) is process in which liquid perfluorocarbon (PFC) microdroplets are vaporized using focused ultrasound to form gas bubbles that are approximately 125 times larger in volume. Gas embolotherapy is a novel cancer treatment that uses ADV in vivo to strategically form gas emoboli, which can lodge in the microcirculation and starve tumors. Current methods to produce PFC microdroplets, such has high speed shaking or sonication, result in polydisperse droplet distributions where a fraction of droplets fall within the 2-10 microns range. In the clinical application with such a droplet distribution, large droplets are filtered by the lungs and small droplets result in bubbles that are too small to lodge in the tumor vasculature. Consequently, there is a need for a monodisperse droplet distribution. A microfluidic based device has been developed in order to produce such monodisperse PFC microdroplets. The device used hydrodynamic flow focusing to create droplets with a mean diameter less than 10 microns in diameter. This work is supported by NIH grant R01EB006476.

  7. PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels for drug delivery.

    Science.gov (United States)

    Cho, Hyunah; Gao, Jieming; Kwon, Glen S

    2016-10-28

    Poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles and poly(D,L-lactic-co-glycolic acid)-block-polyethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) sol-gels have been extensively researched for systemic and localized drug delivery applications, respectively, and they have both progressed into humans for paclitaxel, an important yet poorly water-soluble chemotherapeutic agent. In this review article, preclinical and clinical research on PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels that has focused on paclitaxel will be updated, and recent research on other poorly water-soluble anticancer agents and delivery of drug combinations (i.e. multi-drug delivery) that seeks synergistic anticancer efficacy will be summarized. PEG-b-PLA micelles are a first-generation platform for the systemic multi-delivery of poorly water soluble anticancer agents. PLGA-b-PEG-b-PLGA sol-gels are a first-generation platform for the localized multi-drug delivery of water-soluble and/or poorly water-soluble anticancer agents. In summary, PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol-gels may safely enable pre-clinical evaluation and clinical translation of poorly water-soluble anticancer agents, especially for promising, rapidly emerging anticancer combinations.

  8. Elongational viscosity of monodisperse and bidisperse polystyrene melts

    DEFF Research Database (Denmark)

    Nielsen, Jens Kromann; Rasmussen, Henrik K.; Hassager, Ole

    2006-01-01

    The start-up and steady uniaxial elongational viscosity have been measured for two monodisperse polystyrene melts with molecular weights of 52 and 103 kg/mole, and for three bidisperse polystyrene melts. The monodisperse melts show a maximum in the steady elongational viscosity vs. the elongation...

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

    Directory of Open Access Journals (Sweden)

    Maji R

    2014-06-01

    Full Text Available Ruma Maji, Niladri Shekhar Dey, Bhabani Sankar Satapathy, Biswajit Mukherjee, Subhasish MondalDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata (Calcutta, IndiaBackground: 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

  10. Surface characteristics of PLA and PLGA films

    Energy Technology Data Exchange (ETDEWEB)

    Paragkumar N, Thanki [Laboratoire de Chimie-Physique Macromoleculaire (LCPM), UMR CNRS-INPL 7568, Groupe ENSIC, 1 rue Grandville, B.P. 20451, 54001 Nancy Cedex (France); Edith, Dellacherie [Laboratoire de Chimie-Physique Macromoleculaire (LCPM), UMR CNRS-INPL 7568, Groupe ENSIC, 1 rue Grandville, B.P. 20451, 54001 Nancy Cedex (France); Six, Jean-Luc [Laboratoire de Chimie-Physique Macromoleculaire (LCPM), UMR CNRS-INPL 7568, Groupe ENSIC, 1 rue Grandville, B.P. 20451, 54001 Nancy Cedex (France)]. E-mail: Jean-Luc.Six@ensic.inpl-nancy.fr

    2006-12-30

    Surface segregation and restructuring in polylactides (poly(D,L-lactide) and poly(L-lactide)) and poly(D,L-lactide-co-glycolide) (PLGA) films of various thicknesses were investigated using both attenuated total reflection FTIR (ATR-FTIR) and contact angle relaxation measurements. In case of poly(D,L-lactide) (DLPLA), it was observed that the surface segregation and the surface restructuring of methyl side groups are influenced by the polymer film thickness. This result has been confirmed by X-ray photoelectron spectroscopy (XPS). In the same way, PLGA thick films were also characterized by an extensive surface segregation of methyl side groups. Finally, surface restructuring was investigated by dynamic contact angle measurements and it was observed when film surface comes into contact with water. In parallel, we also found that poly(L-lactide) (PLLA) thin and clear films with thickness {approx}15 {mu}m undergo conformational changes on the surface upon solvent treatment with certain solvents. The solvent treated surface of PLLA becomes hazy and milky white and its hydrophobicity increases compared to untreated surface. FTIR spectroscopic analysis indicated that polymer chains at the surface undergo certain conformational changes upon solvent treatment. These changes are identified as the restricted motions of C-O-C segments and more intense and specific vibrations of methyl side groups. During solvent treatment, the change in water contact angle and FTIR spectrum of PLLA is well correlated.

  11. Polypyrrole-Coated Electrospun PLGA Nanofibers for Neural Tissue Applications

    Science.gov (United States)

    Lee, Jae Young; Bashur, Chris A.; Goldstein, Aaron S.; Schmidt, Christine E.

    2009-01-01

    Electrospinning is a promising approach to create nanofiber structures that are capable of supporting adhesion and guiding extension of neurons for nerve regeneration. Concurrently, electrical stimulation of neurons in the absence of topographical features also has been shown to guide axonal extension. Therefore, the goal of this study was to form electrically conductive nanofiber structures and to examine the combined effect of nanofiber structures and electrical stimulation. Conductive meshes were produced by growing polypyrrole (PPy) on random and aligned electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, as confirmed by scanning electron micrographs and X-ray photon spectroscopy. PPy-PLGA electrospun meshes supported the growth and differentiation of rat pheochromocytoma 12 (PC12) cells and hippocampal neurons comparable to non-coated PLGA control meshes, suggesting that PPy-PLGA may be suitable as conductive nanofibers for neuronal tissue scaffolds. Electrical stimulation studies showed that PC12 cells, stimulated with a potential of 10 mV/cm on PPy-PLGA scaffolds, exhibited 40–50% longer neurites and 40–90% more neurite formation compared to unstimulated cells on the same scaffolds. In addition, stimulation of the cells on aligned PPy-PLGA fibers resulted in longer neurites and more neurite-bearing cells than stimulation on random PPy-PLGA fibers, suggesting a combined effect of electrical stimulation and topographical guidance and the potential use of these scaffolds for neural tissue applications. PMID:19501901

  12. Combined effect of PLGA and curcumin on wound healing activity.

    Science.gov (United States)

    Chereddy, Kiran Kumar; Coco, Régis; Memvanga, Patrick B; Ucakar, Bernard; des Rieux, Anne; Vandermeulen, Gaëlle; Préat, Véronique

    2013-10-28

    Wound healing is a complex process involving many interdependent and overlapping sequences of physiological actions. The application of exogenous lactate released from poly (lactic-co-glycolic acid) (PLGA) polymer accelerated angiogenesis and wound healing processes. Curcumin is a well-known topical wound healing agent for both normal and diabetic-impaired wounds. Hence, we hypothesized that the PLGA nanoparticles encapsulating curcumin could much potentially accelerate the wound healing. In a full thickness excisional wound healing mouse model, PLGA-curcumin nanoparticles showed a twofold higher wound healing activity compared to that of PLGA or curcumin. Histology and RT-PCR studies confirmed that PLGA-curcumin nanoparticles exhibited higher re-epithelialization, granulation tissue formation and anti-inflammatory potential. PLGA nanoparticles offered various benefits for the encapsulated curcumin like protection from light degradation, enhanced water solubility and showed a sustained release of curcumin over a period of 8 days. In conclusion, we demonstrated the additive effect of lactic acid from PLGA and encapsulated curcumin for the active healing of wounds.

  13. Synthesis of monodisperse crosslinked polystyrene microspheres

    Institute of Scientific and Technical Information of China (English)

    Jiang Kai; Chen Sheng-Li; Dong Peng; Liu Renxiao

    2008-01-01

    Monodisperse crosslinked polystyrene (CPS) particles were prepared through the normal emulsion polymerization method by adding crosslinker-divinylbenzene (DVB) into the reaction system after polystyrene (PS) particles grew to ~80% of the final size. When the amount of crosslinker DVB added was less than 6.17 wt% based on styrene, the prepared CPS particles were spherical and uniform and the size of the CPS particles could be predicted through the normal emulsion method. The glass transition temperature (Tg) of the prepared CPS particles was higher than that of un-crosslinked PS particles and, the more crosslinker that was added, the higher the Tg of CPS Particles. The prepared CPS particles had strong resistance to organic solvents.

  14. Monodisperse microdroplet generation and stopping without coalescence

    Energy Technology Data Exchange (ETDEWEB)

    Beer, Neil Reginald

    2016-02-23

    A system for monodispersed microdroplet generation and trapping including providing a flow channel in a microchip; producing microdroplets in the flow channel, the microdroplets movable in the flow channel; providing carrier fluid in the flow channel using a pump or pressure source; controlling movement of the microdroplets in the flow channel and trapping the microdroplets in a desired location in the flow channel. The system includes a microchip; a flow channel in the microchip; a droplet maker that generates microdroplets, the droplet maker connected to the flow channel; a carrier fluid in the flow channel, the carrier fluid introduced to the flow channel by a source of carrier fluid, the source of carrier fluid including a pump or pressure source; a valve connected to the carrier fluid that controls flow of the carrier fluid and enables trapping of the microdroplets.

  15. Antimycobacterial activity of peptide conjugate of pyridopyrimidine derivative against Mycobacterium tuberculosis in a series of in vitro and in vivo models.

    Science.gov (United States)

    Horváti, Kata; Bacsa, Bernadett; Szabó, Nóra; Fodor, Kinga; Balka, Gyula; Rusvai, Miklós; Kiss, Éva; Mező, Gábor; Grolmusz, Vince; Vértessy, Beáta; Hudecz, Ferenc; Bősze, Szilvia

    2015-06-01

    New pyridopyrimidine derivatives were defined using a novel HTS in silico docking method (FRIGATE). The target protein was a dUTPase enzyme (EC 3.6.1.23; Rv2697) which plays a key role in nucleotide biosynthesis of Mycobacterium tuberculosis (Mtb). Top hit molecules were assayed in vitro for their antimycobacterial effect on Mtb H37Rv culture. In order to enhance the cellular uptake rate, the TB820 compound was conjugated to a peptid-based carrier and a nanoparticle type delivery system (polylactide-co-glycolide, PLGA) was applied. The conjugate had relevance to in vitro antitubercular activity with low in vitro and in vivo toxicity. In a Mtb H37Rv infected guinea pig model the in vivo efficacy of orally administrated PLGA encapsulated compound was proven: animals maintained a constant weight gain and no external clinical signs of tuberculosis were observed. All tissue homogenates from lung, liver and kidney were found negative for Mtb, and diagnostic autopsy showed that no significant malformations on the tissues occurred.

  16. Histological and morphometric aspects of ridge preservation with a moldable, in situ hardening bone graft substitute

    Directory of Open Access Journals (Sweden)

    Jurišić M.

    2013-01-01

    Full Text Available Biphasic calcium phosphates (BCP are widely used in alveolar ridge regeneration as a porous scaffold for new bone formation. The aim of this case series was to evaluate the regenerative effect of the combination of BCP and polylactide-co-glycolide (PLGA which can serve as a barrier membrane during bone regeneration. The study included five patients. Four months into the healing period, bone samples were collected for histological and morphometric analyses. The results of morphometric analysis showed that newly formed bone represented 32.2 ± 6.8% of the tissue, 31.9 ± 8.9% was occupied by residual graft and 35.9 ± 13.5% by soft tissue. Active osteogenesis was seen around the particles of the graft. The particles were occupied mostly by immature woven bone and connective tissue. The quality and quantity of newly formed bone, after the use of BCP/PLGA for ridge preservation, can be adequate for successful implant therapy after tooth extraction. [Projekat Ministarstva nauke Republike Srbije, br. OI 175021 i br. OI 173009

  17. Optical monitoring the degradation of PLGA inverse opal film

    Institute of Scientific and Technical Information of China (English)

    Li-Guo Sun; Zhuo-Ying Xie; Yuan-Jin Zhao; Hong-Mei Wei; Zhong-Ze Gu

    2013-01-01

    Implantable materials have broad applications in tissue engineering and in vivo sensors.It is essential to know the detailed information of the implantable materials during their degradation.In this paper,we developed a method to monitor the degradation process of a well-used biomaterial,poly(lactide-coglycolide) (PLGA) by taking advantage of inverse opal structure.We found that mass loss,molecular weight and glass transition temperature of PLGA during the degradation process in Hank's artificial body fluid can be in situ monitored by measuring the optical properties of PLGA inverse opal.

  18. Fabrication of functional PLGA-based electrospun scaffolds and their applications in biomedical engineering

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Wen, E-mail: wenzhao@nwpu.edu.cn [Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi' an, Shaanxi (China); Li, Jiaojiao; Jin, Kaixiang; Liu, Wenlong [Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi' an, Shaanxi (China); Qiu, Xuefeng [Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei (China); Li, Chenrui [Key Laboratory for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi' an, Shaanxi (China)

    2016-02-01

    Electrospun PLGA-based scaffolds have been applied extensively in biomedical engineering, such as tissue engineering and drug delivery system. Due to lack of the recognition sites on cells, hydropholicity and single-function, the applications of PLGA fibrous scaffolds are limited. In order to tackle these issues, many works have been done to obtain functional PLGA-based scaffolds, including surface modifications, the fabrication of PLGA-based composite scaffolds and drug-loaded scaffolds. The functional PLGA-based scaffolds have significantly improved cell adhesion, attachment and proliferation. Moreover, the current study has summarized the applications of functional PLGA-based scaffolds in wound dressing, vascular and bone tissue engineering area as well as drug delivery system. - Highlights: • We summarize the strategies to functionalize PLGA-based electrospun scaffolds. • The applications of PLGA-based scaffolds in biomedical engineering are concluded. • The future challenges and opportunities of PLGA-based scaffolds are proposed.

  19. PLGA and PHBV Microsphere Formulations and Solid-State Characterization

    DEFF Research Database (Denmark)

    Yang, Chiming; Plackett, David; Needham, David

    2009-01-01

    To develop and characterize the solid-state properties of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) microspheres for the localized and controlled release of fusidic acid (FA). The effects of FA loading and polymer composition on the mean...... diameter, encapsulation efficiency and FA released from the microspheres were determined. The solid-state and phase separation properties of the microspheres were characterized using DSC, XRPD, Raman spectroscopy, SEM, laser confocal and real time recording of single microspheres formation. Above a loading...... of 1% (w/w) FA phase separated from PLGA polymer and formed distinct spherical FA-rich amorphous microdomains throughout the PLGA microsphere. For FA-loaded PLGA microspheres, encapsulation efficiency and cumulative release increased with initial drug loading. Similarly, cumulative release from FA...

  20. Fabrication of PLGA nanoparticles with a fluidic nanoprecipitation system

    Directory of Open Access Journals (Sweden)

    Xie Hui

    2010-08-01

    Full Text Available Abstract Particle size is a key feature in determining performance of nanoparticles as drug carriers because it influences circulating half-life, cellular uptake and biodistribution. Because the size of particles has such a major impact on their performance, the uniformity of the particle population is also a significant factor. Particles comprised of the polymer poly(lactic-co-glycolic acid (PLGA are widely studied as therapeutic delivery vehicles because they are biodegradable and biocompatible. In fact, microparticles comprised of PLGA are already approved for drug delivery. Unfortunately, PLGA nanoparticles prepared by conventional methods usually lack uniformity. We developed a novel Fluidic NanoPrecipitation System (FNPS to fabricate highly uniform PLGA particles. Several parameters can be fine-tuned to generate particles of various sizes.

  1. PLGA Microspheres Incorporated Gelatin Scaffold: Microspheres Modulate Scaffold Properties

    OpenAIRE

    Indranil Banerjee; Debasish Mishra; Maiti, Tapas K.

    2009-01-01

    Freeze drying is one of the popular methods of fabrication for poly(lactide-co-glycolide) (PLGA) microspheres incorporated polymer scaffolds. However, the consequence of microspheres incorporation on physical and biological properties of scaffold has not been studied yet. In this study, attempt has been made to characterize the effect of PLGA microsphere incorporation on the physical properties of freeze-dried gelatin scaffold and its influence on cytocompatibility. Scaffolds loaded with va...

  2. Synthesis and characterization of magnetite/PLGA/chitosan nanoparticles

    Science.gov (United States)

    Ibarra, Jaime; Melendres, Julio; Almada, Mario; Burboa, María G.; Taboada, Pablo; Juárez, Josué; Valdez, Miguel A.

    2015-09-01

    In this work, we report the synthesis and characterization of a new hybrid nanoparticles system performed by magnetite nanoparticles, loaded in a PLGA matrix, and stabilized by different concentrations of chitosan. Magnetite nanoparticles were hydrophobized with oleic acid and entrapped in a PLGA matrix by the emulsion solvent evaporation method, after that, magnetite/PLGA/chitosan nanoparticles were obtained by adding dropwise magnetite/PLGA nanoparticles in chitosan solutions. Magnetite/PLGA nanoparticles produced with different molar ratios did not show significant differences in size and the 3:1 molar ratio showed best spherical shapes as well as uniform particle size. Isothermal titration calorimetry studies demonstrated that the first stage of PLGA-chitosan interaction is mostly regulated by electrostatic forces. Based on a single set of identical sites model, we obtained for the average number of binding sites a value of 3.4, which can be considered as the number of chitosan chains per nanoparticle. This value was confirmed by using a model based on the DLVO theory and fitting zeta potential measurements of magnetite/PLGA/chitosan nanoparticles. From the adjusted parameters, we found that an average number of chitosan molecules of 3.6 per nanoparticle are attached onto the surface of the PLGA matrix. Finally, we evaluated the effect of surface charge of nanoparticles on a membrane model of endothelial cells performed by a mixture of three phospholipids at the air-water interface. Different isotherms and adsorption curves show that cationic surface of charged nanoparticles strongly interact with the phospholipids mixture and these results can be the basis of future experiments to understand the nanoparticles- cell membrane interaction.

  3. Facile Method for Preparation of Silica Coated Monodisperse Superparamagnetic Microspheres

    Directory of Open Access Journals (Sweden)

    Xuan-Hung Pham

    2016-01-01

    Full Text Available This paper presents a facile method for preparation of silica coated monodisperse superparamagnetic microsphere. Herein, monodisperse porous polystyrene-divinylbenzene microbeads were prepared by seeded emulsion polymerization and subsequently sulfonated with acetic acid/H2SO4. The as-prepared sulfonated macroporous beads were magnetized in presence of Fe2+/Fe3+ under alkaline condition and were subjected to silica coating by sol-gel process, providing water compatibility, easily modifiable surface form, and chemical stability. FE-SEM, TEM, FT-IR, and TGA were employed to characterize the silica coated monodisperse magnetic beads (~7.5 μm. The proposed monodisperse magnetic beads can be used as mobile solid phase particles candidate for protein and DNA separation.

  4. Antimicrobial Properties and Cytocompatibility of PLGA/Ag Nanocomposites

    Directory of Open Access Journals (Sweden)

    Mariangela Scavone

    2016-01-01

    Full Text Available The purpose of this study was to investigate the antimicrobial properties of multifunctional nanocomposites based on poly(dl-Lactide-co-Glycolide (PLGA and increasing concentration of silver (Ag nanoparticles and their effects on cell viability for biomedical applications. PLGA nanocomposite films, produced by solvent casting with 1 wt%, 3 wt% and 7 wt% of Ag nanoparticles were investigated and surface properties were characterized by atomic force microscopy and contact angle measurements. Antibacterial tests were performed using an Escherichia coli RB and Staphylococcus aureus 8325-4 strains. The cell viability and morphology were performed with a murine fibroblast cell line (L929 and a human osteosarcoma cell line (SAOS-2 by cell viability assay and electron microscopy observations. Matrix protein secretion and deposition were also quantified by enzyme-linked immunosorbent assay (ELISA. The results suggest that the PLGA film morphology can be modified introducing a small percentage of silver nanoparticles, which induce the onset of porous round-like microstructures and also affect the wettability. The PLGA/Ag films having silver nanoparticles of more than 3 wt% showed antibacterial effects against E. coli and S. aureus. Furthermore, silver-containing PLGA films displayed also a good cytocompatibility when assayed with L929 and SAOS-2 cells; indicating the PLGA/3Ag nanocomposite film as a promising candidate for tissue engineering applications.

  5. PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy

    Directory of Open Access Journals (Sweden)

    Byeon HJ

    2015-01-01

    Full Text Available Hyeong Jun Byeon,1 Insoo Kim,1 Ji Su Choi,1 Eun Seong Lee,2 Beom Soo Shin,3 Yu Seok Youn11Department of Pharmaceutical Sciences, School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 2Division of Biotechnology, The Catholic University of Korea, Bucheon-si, Republic of Korea; 3Department of Pharmacy, College of Pharmacy, Catholic University of Daegu, Gyeongsan-si, Republic of KoreaAbstract: The aim of the current study was to investigate the antitumor potential of poly(D,L-lactic-co-glycolic acid microspheres (PLGA MSs containing polyethylene glycol (PEG-conjugated (PEGylated tumor necrosis factor–related apoptosis-inducing ligand (PEG-TRAIL. PEG-TRAIL PLGA MSs were prepared by using a water-in-oil-in-water double-emulsion method, and the apoptotic activities of supernatants released from the PLGA MSs at days 1, 3, and 7 were examined. The antitumor effect caused by PEG-TRAIL PLGA MSs was evaluated in pancreatic Mia Paca-2 cell-xenografted mice. PEG-TRAIL PLGA MS was found to be spherical and 14.4±1.06 µm in size, and its encapsulation efficiency was significantly greater than that of TRAIL MS (85.7%±4.1% vs 43.3%±10.9%, respectively. The PLGA MS gradually released PEG-TRAIL for 14 days, and the released PEG-TRAIL was shown to have clear apoptotic activity in Mia Paca-2 cells, whereas TRAIL released after 1 day had a negligible activity. Finally, PEG-TRAIL PLGA MS displayed remarkably greater antitumor efficacy than blank or TRAIL PLGA MS in Mia Paca-2 cell-xenografted mice in terms of tumor volume and weight, apparently due to increased stability and well-retained apoptotic activity of PEG-TRAIL in PLGA MS. We believe that this PLGA MS system, combined with PEG-TRAIL, should be considered a promising candidate for treating pancreatic cancer.Keywords: Poly(D,L-lactic-co-glycolic acid, controlled release, PEGylation, TRAIL, pancreatic cancer

  6. Janus nanogels of PEGylated Taxol and PLGA-PEG-PLGA copolymer for cancer therapy

    Science.gov (United States)

    Wei, Jun; Wang, Huaimin; Zhu, Meifeng; Ding, Dan; Li, Dongxia; Yin, Zhinan; Wang, Lianyong; Yang, Zhimou

    2013-09-01

    Nanogels are promising carriers for the delivery of anti-cancer drugs for cancer therapy. We report in this study on a Janus nanogel system formed by mixing a prodrug of Taxol (PEGylated Taxol) and a copolymer of PLGA-PEG-PLGA. The Janus nanogels have good stability over months in aqueous solutions and the freeze-dried powder of nanogels can be re-dispersed instantly in aqueous solutions. The Janus nanogels show an enhanced inhibition effect on tumor growth in a mice breast cancer model probably due to the enhanced uptake of the nano-sized materials by the EPR effect. What is more, the nanogels can also serve as physical carriers to co-deliver other anti-cancer drugs such as doxorubicin to further improve the anti-cancer efficacy. The results obtained from H&E staining and TUNEL assay also support the observation of tumor growth inhibition. These results suggest the potential of this novel delivery system for cancer therapy.Nanogels are promising carriers for the delivery of anti-cancer drugs for cancer therapy. We report in this study on a Janus nanogel system formed by mixing a prodrug of Taxol (PEGylated Taxol) and a copolymer of PLGA-PEG-PLGA. The Janus nanogels have good stability over months in aqueous solutions and the freeze-dried powder of nanogels can be re-dispersed instantly in aqueous solutions. The Janus nanogels show an enhanced inhibition effect on tumor growth in a mice breast cancer model probably due to the enhanced uptake of the nano-sized materials by the EPR effect. What is more, the nanogels can also serve as physical carriers to co-deliver other anti-cancer drugs such as doxorubicin to further improve the anti-cancer efficacy. The results obtained from H&E staining and TUNEL assay also support the observation of tumor growth inhibition. These results suggest the potential of this novel delivery system for cancer therapy. Electronic supplementary information (ESI) available: Synthesis and characterization of compounds, dynamic time sweep, H

  7. Rapid enumeration of phage in monodisperse emulsions.

    Science.gov (United States)

    Tjhung, Katrina F; Burnham, Sean; Anany, Hany; Griffiths, Mansel W; Derda, Ratmir

    2014-06-17

    Phage-based detection assays have been developed for the detection of viable bacteria for applications in clinical diagnosis, monitoring of water quality, and food safety. The majority of these assays deliver a positive readout in the form of newly generated progeny phages by the bacterial host of interest. Progeny phages are often visualized as plaques, or holes, in a lawn of bacteria on an agar-filled Petri dish; however, this rate-limiting step requires up to 12 h of incubation time. We have previously described an amplification of bacteriophages M13 inside droplets of media suspended in perfluorinated oil; a single phage M13 in a droplet yields 10(7) copies in 3-4 h. Here, we describe that encapsulation of reporter phages, both lytic T4-LacZ and nonlytic M13, in monodisperse droplets can also be used for rapid enumeration of phage. Compartmentalization in droplets accelerated the development of the signal from the reporter enzyme; counting of "positive" droplets yields accurate enumeration of phage particles ranging from 10(2) to 10(6) pfu/mL. For enumeration of T4-LacZ phage, the fluorescent signal appeared in as little as 90 min. Unlike bulk assays, quantification in emulsion is robust and insensitive to fluctuations in environmental conditions (e.g., temperature). Power-free emulsification using gravity-driven flow in the absence of syringe pumps and portable fluorescence imaging solutions makes this technology promising for use at the point of care in low-resource environments. This droplet-based phage enumeration method could accelerate and simplify point-of-care detection of the pathogens for which reporter bacteriophages have been developed.

  8. Stabilization of Tetanus Toxoid Encapsulated in PLGA Microspheres

    Science.gov (United States)

    Jiang, Wenlei; Schwendeman, Steven P.

    2014-01-01

    Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT) in PLGA microspheres. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: 1) protein aggregation mediated by formaldehyde and 2) acid-induced protein unfolding and epitope damage. Further, we systemically identified excipients which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA. PMID:18710256

  9. PLGA microsphere/calcium phosphate cement composites for tissue engineering: in vitro release and degradation characteristics.

    NARCIS (Netherlands)

    Habraken, W.J.E.M.; Wolke, J.G.C.; Mikos, A.G.; Jansen, J.A.

    2008-01-01

    Bone cements with biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres have already been proven to provide a macroporous calcium phosphate cement (CPC) during in situ microsphere degradation. Furthermore, in vitro/in vivo release studies with these PLGA microsphere/CPC composites (PLGA/CP

  10. Modification of PLGA Nanofibrous Mats by Electron Beam Irradiation for Soft Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Jae Baek Lee

    2015-01-01

    Full Text Available Biodegradable poly(lactide-co-glycolide (PLGA has found widespread use in modern medical practice. However, the degradation rate of PLGA should be adjusted for specific biomedical applications such as tissue engineering, drug delivery, and surgical implantation. This study focused on the effect of electron beam radiation on nanofibrous PLGA mats in terms of physical properties and degradation behavior with cell proliferation. PLGA nanofiber mats were prepared by electrospinning, and electron beam was irradiated at doses of 50, 100, 150, 200, 250, and 300 kGy. PLGA mats showed dimensional integrity after electron beam irradiation without change of fiber diameter. The degradation behavior of a control PLGA nanofiber (0 kGy and electron beam-irradiated PLGA nanofibers was analyzed by measuring the molecular weight, weight loss, change of chemical structure, and fibrous morphology. The molecular weight of the PLGA nanofibers decreased with increasing electron beam radiation dose. The mechanical properties of the PLGA nanofibrous mats were decreased with increasing electron beam irradiation dose. Cell proliferation behavior on all electron beam irradiated PLGA mats was similar to the control PLGA mats. Electron beam irradiation of PLGA nanofibrous mats is a potentially useful approach for modulating the biodegradation rate of tissue-specific nonwoven nanofibrous scaffolds, specifically for soft tissue engineering applications.

  11. Controlled release of simvastatin-loaded thermo-sensitive PLGA-PEG-PLGA hydrogel for bone tissue regeneration: in vitro and in vivo characteristics.

    Science.gov (United States)

    Yan, Qi; Xiao, Li-Qun; Tan, Lei; Sun, Wei; Wu, Tao; Chen, Liang-Wen; Mei, Yan; Shi, Bin

    2015-11-01

    Reports on the local delivery of drug loaded injectable hydrogels for bone regeneration are currently limited. This study assessed the effect of controlled simvastatin (SIM) release from a thermo-sensitive hydrogel in vitro and in vivo. We successfully manufactured and evaluated thermo-sensitive poly(d,l-lactide-co-glycolide)-poly(ethylene glycol)-poly(d,l-lactide-co-glycolide) triblock copolymers (PLGA-PEG-PLGA) loaded with SIM. The osteogenic effect of this hydrogel was tested in vitro and in vivo. MC-3T3 E1 cells proliferation and osteoblastic differentiation was analyzed after cultivation with the hydrogel extracts. Cells co-cultured with SIM/PLGA-PEG-PLGA extracts showed an increase in mineralization and osteogenic gene expression compared to the other two groups. Additionally, the characteristics of this composite in vivo were demonstrated using a rat bone defect model. The bone defects injected with SIM/PLGA-PEG-PLGA hydrogel showed increased new bone formation compared to samples treated with PLGA-PEG-PLGA and control samples. The results of this study suggest that SIM/PLGA-PEG-PLGA might provide potential therapeutic value for bone healing.

  12. Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties

    Energy Technology Data Exchange (ETDEWEB)

    Mehrasa, Mohammad [Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran (Iran, Islamic Republic of); Asadollahi, Mohammad Ali, E-mail: ma.asadollahi@ast.ui.ac.ir [Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Nasri-Nasrabadi, Bijan [Department of Chemical Engineering, Isfahan University of Technology, Isfahan (Iran, Islamic Republic of); Ghaedi, Kamran [Department of Biology, Faculty of Science, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Salehi, Hossein [Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Dolatshahi-Pirouz, Alireza [DTU Nanotech, Center for Nanomedicine and Theranostics, Technical University of Denmark (DTU), DK-2800 Kgs. Lyngby (Denmark); Arpanaei, Ayyoob, E-mail: arpanaei@yahoo.com [Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran (Iran, Islamic Republic of)

    2016-09-01

    Poly(lactic-co-glycolic acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical properties as well as in vitro degradation behavior of scaffolds were investigated. The mean diameters of nanofibers were 974 ± 68 nm for the pure PLGA scaffolds vs 832 ± 70, 764 ± 80, and 486 ± 64 for the PLGA/gelatin, PLGA/10 wt% MSNPs, and the PLGA/gelatin/10 wt% MSNPs scaffolds, respectively. The results suggested that the incorporation of gelatin and MSNPs into PLGA-based scaffolds enhances the hydrophilicity of scaffolds due to an increase of hydrophilic functional groups on the surface of nanofibers. With porosity examination, it was concluded that the incorporation of MSNPs and gelatin decrease the porosity of scaffolds. Nanoparticles also improved the tensile mechanical properties of scaffolds. Using in vitro degradation analysis, it was shown that the addition of nanoparticles to the nanofibers matrix increases the weight loss percentage of PLGA-based samples, whereas it decreases the weight loss percentage in the PLGA/gelatin composites. Cultivation of rat pheochromocytoma cell line (PC12), as precursor cells of dopaminergic neural cells, on the scaffolds demonstrated that the introduction of MSNPs into PLGA and PLGA/gelatin matrix leads to improved cell attachment and proliferation and enhances cellular processes. - Highlights: • PLGA-based random nanofibers embedded with mesoporous silica nanoparticles were fabricated using electrospinning method • Incorporation of gelatin and MSNPs into PLGA-based scaffolds increased the hydrophilicity of scaffold • Addition of nanoparticles also improved the tensile mechanical properties of scaffolds • Introduction of MSNPs led to improved cell attachment and proliferation.

  13. Polydioxanone-based bio-materials for tissue engineering and drug/gene delivery applications.

    Science.gov (United States)

    Goonoo, Nowsheen; Jeetah, Roubeena; Bhaw-Luximon, Archana; Jhurry, Dhanjay

    2015-11-01

    Since the commercialization of polydioxanone (PDX) as a biodegradable monofilament suture by Ethicon in 1981, the polymer has received only limited interest until recently. The limitations of polylactide-co-glycolide (PLGA) coupled with the growing need for materials with enhanced features and the advent of new fabrication techniques such as electrospinning have revived interest for PDX in medical devices, tissue engineering and drug delivery applications. Electrospun PDX mats show comparable mechanical properties as the major structural components of native vascular extracellular matrix (ECM) i.e. collagen and elastin. In addition, PDX's unique shape memory property provides rebound and kink resistance when fabricated into vascular conduits. The synthesis of methyl dioxanone (MeDX) monomer and copolymers of dioxanone (DX) and MeDX have opened up new perspectives for poly(ester-ether)s, enabling the design of the next generation of tissue engineering scaffolds for application in regenerating such tissues as arteries, peripheral nerve and bone. Tailoring of polymer properties and their formulation as nanoparticles, nanomicelles or nanofibers have brought along important developments in the area of controlled drug or gene delivery. This paper reviews the synthesis of PDX and its copolymers and provides for the first time an exhaustive account of its applications in the (bio)medical field with focus on tissue engineering and drug/gene delivery.

  14. Structure-Processing-Property Relationship of Poly(Glycolic Acid for Drug Delivery Systems 1: Synthesis and Catalysis

    Directory of Open Access Journals (Sweden)

    Vineet Singh

    2010-01-01

    Full Text Available Till date, market is augmented with a huge number of improved drug delivery systems. The success in this area is basically due to biodegradable polymers. Although conventional systems of drug delivery utilizing the natural and semisynthetic polymers so long but synthetic polymer gains success in the controlled drug delivery area due to better degradation profile and controlled network and functionality. The polyesters are the most studied class group due the susceptible ester linkage in their backbone. The Poly(glycolic Acid (PGA, Poly(lactic acid (PLA, and Polylactide-co-glycolide (PLGA are the best profiled polyesters and are most widely used in marketed products. These polymers, however, still are having drawbacks which failed them to be used in platform technologies like matrix systems, microspheres, and nanospheres in some cases. The common problems arose with these polymers are entrapment inefficiency, inability to degrade and release drugs with required profile, and drug instability in the microenvironment of the polymers. These problems are forcing us to develop new polymers with improved physicochemical properties. The present review gave us an insight in the various structural elements of Poly(glycolic acid, polyester, with in depth study. The first part of the review focuses on the result of studies related to synthetic methodologies and catalysts being utilized to synthesize the polyesters. However the author will also focus on the effect of processing methodologies but due some constraints those are not included in the preview of this part of review.

  15. Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Ganea, Gabriela M; Warner, Isiah M [Department of Chemistry, Louisiana State University, 434 Choppin Hall, Baton Rouge, LA 70803 (United States); Fakayode, Sayo O [Department of Chemistry, Anderson Center Modular Unit 244-B, Winston-Salem State University, Winston Salem, NC 27110 (United States); Losso, Jack N [Food Science Department, Louisiana State University Agricultural Center, 111 Food Science Building, Baton Rouge, LA 70803 (United States); Van Nostrum, Cornelus F [Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Sorbonnelaan 16, 3508 TB Utrecht (Netherlands); Sabliov, Cristina M, E-mail: iwarner@lsu.edu [Biological and Agricultural Engineering Department, Louisiana State University Agricultural Center, 141 E B Doran Building, Baton Rouge, LA 70803 (United States)

    2010-07-16

    Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl-glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl-leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml{sup -1} TQ for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 {+-} 0.002 mg ml{sup -1}) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 {+-} 5.6% after 96 h.

  16. Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles

    Science.gov (United States)

    Ganea, Gabriela M.; Fakayode, Sayo O.; Losso, Jack N.; van Nostrum, Cornelus F.; Sabliov, Cristina M.; Warner, Isiah M.

    2010-07-01

    Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl-glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl-leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml - 1 TQ for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 ± 0.002 mg ml - 1) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 ± 5.6% after 96 h.

  17. Growth Kinetics of Monodisperse Polystyrene Microspheres Prepared by Dispersion Polymerization

    Directory of Open Access Journals (Sweden)

    Fan Li

    2013-01-01

    Full Text Available Dispersion polymerization has been widely applied to the synthesis of monodisperse micron-sized polymer colloidal spheres. Many efforts have been devoted to studying the influence of initial conditions on the size and uniformity of the resultant microspheres, aiming to synthesize micron-size monodisperse colloidal spheres. However, the inner contradiction between the size and the size distribution of colloidal spheres hinders the realization of this goal. In this work, we drew our attention from the initial conditions to the growth stage of dispersion polymerization. We tracked the size evolution of colloidal sphere during the dispersion polymerization, through which we established a kinetic model that described the relationship between the monomer concentration and the reaction time. The model may provide a guideline to prepare large polymer colloidal spheres with good monodispersity by continuous monomer feeding during the growth stage to maintain the concentration of monomer at a constant value in a dispersion polymerization process.

  18. Spontaneous droplet formation techniques for monodisperse emulsions preparation – Perspectives for food applications

    NARCIS (Netherlands)

    Maan, A.A.; Schroën, C.G.P.H.; Boom, R.M.

    2011-01-01

    Spontaneous droplet formation through Laplace pressure differences is a simple method for making monodisperse emulsions and is claimed to be suited for shear and temperature sensitive products, and those requiring high monodispersity. Techniques belonging to this category include (grooved) microchan

  19. Emulsion Electrospinning as an Approach to Fabricate PLGA/Chitosan Nanofibers for Biomedical Applications

    Directory of Open Access Journals (Sweden)

    Fatemeh Ajalloueian

    2014-01-01

    Full Text Available Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction.

  20. Emulsion electrospinning as an approach to fabricate PLGA/chitosan nanofibers for biomedical applications.

    Science.gov (United States)

    Ajalloueian, Fatemeh; Tavanai, Hossein; Hilborn, Jöns; Donzel-Gargand, Olivier; Leifer, Klaus; Wickham, Abeni; Arpanaei, Ayyoob

    2014-01-01

    Novel nanofibers from blends of polylactic-co-glycolic acid (PLGA) and chitosan have been produced through an emulsion electrospinning process. The spinning solution employed polyvinyl alcohol (PVA) as the emulsifier. PVA was extracted from the electrospun nanofibers, resulting in a final scaffold consisting of a blend of PLGA and chitosan. The fraction of chitosan in the final electrospun mat was adjusted from 0 to 33%. Analyses by scanning and transmission electron microscopy show uniform nanofibers with homogenous distribution of PLGA and chitosan in their cross section. Infrared spectroscopy verifies that electrospun mats contain both PLGA and chitosan. Moreover, contact angle measurements show that the electrospun PLGA/chitosan mats are more hydrophilic than electrospun mats of pure PLGA. Tensile strengths of 4.94 MPa and 4.21 MPa for PLGA/chitosan in dry and wet conditions, respectively, illustrate that the polyblend mats of PLGA/chitosan are strong enough for many biomedical applications. Cell culture studies suggest that PLGA/chitosan nanofibers promote fibroblast attachment and proliferation compared to PLGA membranes. It can be assumed that the nanofibrous composite scaffold of PLGA/chitosan could be potentially used for skin tissue reconstruction.

  1. Preparation and Characterization of Estradiol-Loaded PLGA Nanoparticles Using Homogenization-Solvent Diffusion Method

    Directory of Open Access Journals (Sweden)

    R Dinarvand

    2008-09-01

    Full Text Available Background: The inherent shortcomings of conventional drug delivery systems containing estrogens and the potential of nanoparticles (NPs have offered tremendous scope for investigation. Although polymeric NPs have been used as drug carriers for many active agents, the use of appropriate polymer and method of NP preparation to overcome different challenges is very important. Materials and methods: Poly lactide-co-glycolide (PLGA NPs containing estradiol valerate were prepared by the modified spontaneous emulsification solvent diffusion method. Several parameters including the drug/polymer ratios in range of 2.5-10%, poly vinyl alcohol (PVA in concentration of 0-4% as stabilizer and internal phase volume and composition were examined to optimize formulation. The size distribution and morphology of the NPs, encapsulation efficacy and in vitro release profile in phosphate buffer medium (pH 7.4 during 12 hrs were then investigated. Results: The NPs prepared in this study were spherical with a relatively mono-dispersed size distribution. By adjustment of the process parameters, the size and the drug encapsulation efficacy as well as the drug release kinetics can be optimally controlled. The mean particle size of the best formula with encapsulation efficiency of 100% was 175 ± 19, in which release profile was best fitted to Higuchi's model of release which showed that release mechanism was mainly controlled by diffusion of the drug to the release medium. Conclusion: According to the size and surface properties of the prepared particles, it may be concluded that they are a good formulation for non-parenteral routes of administration.

  2. Cytotoxicity and intracellular fate of PLGA and chitosan-coated PLGA nanoparticles in Madin-Darby bovine kidney (MDBK) and human colorectal adenocarcinoma (Colo 205) cells.

    Science.gov (United States)

    Trif, Mihaela; Florian, Paula E; Roseanu, Anca; Moisei, Magdalena; Craciunescu, Oana; Astete, Carlos E; Sabliov, Cristina M

    2015-11-01

    Polymeric nanoparticles (NPs) are known to facilitate intracellular uptake of drugs to improve their efficacy, with minimum bioreactivity. The goal of this study was to assess cellular uptake and trafficking of PLGA NPs and chitosan (Chi)-covered PLGA NPs in Madin-Darby bovine kidney (MDBK) and human colorectal adenocarcinoma (Colo 205) cells. Both PLGA and Chi-PLGA NPs were not cytotoxic to the studied cells at concentrations up to 2500 μg/mL. The positive charge conferred by the chitosan deposition on the PLGA NPs improved NPs uptake by MDBK cells. In this cell line, Chi-PLGA NPs colocalized partially with early endosomes compartment and showed a more consistent perinuclear localization than PLGA NPs. Kinetic uptake of PLGA NPs by Colo 205 was slower than that by MDBK cells, detected only at 24 h, exceeding that of Chi-PLGA NPs. This study offers new insights on NP interaction with target cells supporting the use of NPs as novel nutraceuticals/drug delivery systems in metabolic disorders or cancer therapy. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 3599-3611, 2015.

  3. PLGA纳米粒抗肿瘤药物载体的研究进展%Progress in the study of poly (lactide-co-glycolide) nanoparticles for anticancer a-gents delivery

    Institute of Scientific and Technical Information of China (English)

    李方园; 姜永莉; 成颖

    2013-01-01

    Objective To summarize the progress in the study of poly (lactide-co-glycolide) (PLGA ) nanoparticles for delivery of anticancer agents .Method The latest domestic and foreign literatures of the application of PLGA nanoparticles as an anticancer drug carrier in the field of active and passive targeting were reviewed .Result Because nanomaterials can enhance drug delivery to tumor cells and polylactide-co-glycolide is a biodegradable and biocompatible polyester approved for human use by FDA ,in recent years PLGA becomes a research hotspot .Conclusion Poly(lactide-co-glycolide) nanoparticles used for anticancer agents delivery has a promising prospect .%目的:阐述近年来PLGA 纳米粒作为抗肿瘤药物载体的研究进展。方法归纳国内外最新的文献报道,对PLGA纳米粒作为抗肿瘤药物载体在主动与被动靶向方面的应用研究进展进行综述。结果由于纳米材料可以增强抗肿瘤药物的靶向作用,而PLGA是经FDA认证的具有生物降解性及生物相容性的功能高分子有机聚合物,已经被广泛地应用于抗肿瘤药物的载体研究。结论 PLGA纳米粒作为抗肿瘤药物载体具有广阔的应用前景。

  4. Thermoplastic polyurethanes with TDI-based monodisperse hard segments

    NARCIS (Netherlands)

    De, D.; Araichimani, A.; ten Hoopen, Hermina W.M.; Gaymans, R.J.

    2009-01-01

    Polyurethanes with PTMO soft segments and toluene diisocyanate diamide as urethane segment were studied. The toluene diisocyanate diamide urethane segment was monodisperse in length. The soft segment length was changed by extending PTMO with TDI units to a soft segment length varying from 2 250 to

  5. Highly monodisperse bismuth nanoparticles and their three-dimensional superlattices.

    Science.gov (United States)

    Yarema, Maksym; Kovalenko, Maksym V; Hesser, Günter; Talapin, Dmitri V; Heiss, Wolfgang

    2010-11-01

    A simple and reproducible synthesis of highly monodisperse and ligand-protected bismuth nanoparticles (Bi NPs) is reported. The size of the single-crystalline and spherically shaped NPs is controlled between 11 and 22 nm mainly by the reaction temperature. The high uniformity of the NPs allows their self-assembly into long-range-ordered two- and three-dimensional superstructures.

  6. A general approach for monodisperse colloidal perovskites, Chemistry of Materials

    NARCIS (Netherlands)

    Demirors, A.F.; Imhof, A.

    2009-01-01

    We describe a novel general method for synthesizing monodisperse colloidal perovskite particles at room temperature by postsynthesis addition of metal hydroxides to amorphous titania colloids. In previous work, we used titania particles to synthesize homogenously mixed silica-titania composite parti

  7. Surface functionalisation of PLGA nanoparticles for gene silencing

    DEFF Research Database (Denmark)

    Andersen, Morten Østergaard; Lichawska, Agata; Arpanaei, Ayyoob

    2010-01-01

    This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using be...

  8. Quantification of biodegradable PLGA nanoparticles for drug targeting

    Directory of Open Access Journals (Sweden)

    Nadira Ibrišimović

    2010-11-01

    Full Text Available Objective. The aim of this work was the development of appropriate analytical methods and assays for determining and monitoring composition and degradation of nanoparticles built from PLGA (poly D, L-lactid-co-glycolid, which can be reloaded with different drugs. A sensitive and precise method for monitoring of nanoparticle degradation in vitro was developed and optimized. Nanoparticles allow a selective enrichment of different drugs and knowledge of the nature and type of their degradation is essential for characterization and control of drug release and dosage. Materials and methods. The first method developed during this work to quantify the PLGA polymer matrix use advantage of the chemical reaction of aliphatic carboxylic acids with ferric chloride (FeCl3 thus quantifying both degradation products of PLGA, lactic and glycol acids, at the same time. A second assay method of choice was to react to the polymer hydrolysate with lactate dehydrogenase, thus assaying selectively the lactic acid part. Results. During development of both of described methods was possible to determine dynamic range for PLGA matrix and nanoparticles, as well as to characterize impact of Pluronic F-68 and glycolic acid on lactate dehydrogenase activity. Conclusion. During our work we were able to develop two sensitive methods for monitoring of biodegradation of polymers which are consecutively used as a nanoparticle matrix in drug targeting.

  9. PLGA and PHBV Microsphere Formulations and Solid-State Characterization

    DEFF Research Database (Denmark)

    Yang, Chiming; Plackett, David; Needham, David

    2009-01-01

    To develop and characterize the solid-state properties of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) (PHBV) microspheres for the localized and controlled release of fusidic acid (FA). The effects of FA loading and polymer composition on the mean...

  10. Heuristic modeling of macromolecule release from PLGA microspheres

    Directory of Open Access Journals (Sweden)

    Szlęk J

    2013-12-01

    Full Text Available Jakub Szlęk,1 Adam Pacławski,1 Raymond Lau,2 Renata Jachowicz,1 Aleksander Mendyk11Department of Pharmaceutical Technology and Biopharmaceutics, Jagiellonian University Medical College, Krakow, Poland; 2School of Chemical and Biomedical Engineering, Nanyang Technological University (NTU, SingaporeAbstract: Dissolution of protein macromolecules from poly(lactic-co-glycolic acid (PLGA particles is a complex process and still not fully understood. As such, there are difficulties in obtaining a predictive model that could be of fundamental significance in design, development, and optimization for medical applications and toxicity evaluation of PLGA-based multiparticulate dosage form. In the present study, two models with comparable goodness of fit were proposed for the prediction of the macromolecule dissolution profile from PLGA micro- and nanoparticles. In both cases, heuristic techniques, such as artificial neural networks (ANNs, feature selection, and genetic programming were employed. Feature selection provided by fscaret package and sensitivity analysis performed by ANNs reduced the original input vector from a total of 300 input variables to 21, 17, 16, and eleven; to achieve a better insight into generalization error, two cut-off points for every method was proposed. The best ANNs model results were obtained by monotone multi-layer perceptron neural network (MON-MLP networks with a root-mean-square error (RMSE of 15.4, and the input vector consisted of eleven inputs. The complicated classical equation derived from a database consisting of 17 inputs was able to yield a better generalization error (RMSE of 14.3. The equation was characterized by four parameters, thus feasible (applicable to standard nonlinear regression techniques. Heuristic modeling led to the ANN model describing macromolecules release profiles from PLGA microspheres with good predictive efficiency. Moreover genetic programming technique resulted in classical equation with

  11. Preparation and Evaluation of PLGA-Coated Capsaicin Magnetic Nanoparticles.

    Science.gov (United States)

    Baskaran, Mrudhula; Baskaran, Padmamalini; Arulsamy, Navamoney; Thyagarajan, Baskaran

    2017-06-01

    Drugs used in the treatment of diseases can cause several unwanted systemic side effects. A site-specific drug delivery system can eliminate such consequences by delivering drugs to certain target areas of the body where therapeutic effects are required. Here we present the preparation and evaluation of magnetic nanoparticles of capsaicin, the active ingredient in chili peppers, coated with poly-L-lactide co-glycolide (PLGA), a FDA-approved biodegradable bioavailable polymer. PCMN were prepared by solvent-evaporation/coprecipitation technique and their physicochemical and pharmacological characteristics evaluated in vitro. Further, effective pain/inflammation therapeutics of PCMN in a mouse model of inflammation was also studied. We also prepared and evaluated the subcellular localization of PLGA coated fluorescence magnetic nanoparticle (PFMN) in vitro in HEK293 cells. Transmission electron microscopic images of PCMN showed that the size of the nanoparticles were of the order of 10-20 nm. PCMN showed approximately 9.29% drug loading and 89.15% encapsulation efficiencies. In vitro dissolution studies showed an increased solubility of capsaicin due to the nano-size of the PCMN, while PLGA coating allowed sustained release of capsaicin in vitro. The PCMN also reduced paw edema after injection in mice, and confocal microscopy revealed the successful intracellular localization of PLGA-coated fluorescein magnetic nanoparticles in HEK293 cells. The PCMN provided a sustained release of capsaicin in vitro and inhibited carrageenan-induced inflammatory pain in mouse model in vivo. These data suggest that PLGA coating of capsaicin magnetic nanoparticles have the potential to be amenable for a sustained release of capsaicin to relieve pain.

  12. Caffeic Acid-PLGA Conjugate to Design Protein Drug Delivery Systems Stable to Irradiation

    Directory of Open Access Journals (Sweden)

    Francesca Selmin

    2015-01-01

    Full Text Available This work reports the feasibility of caffeic acid grafted PLGA (g-CA-PLGA to design biodegradable sterile microspheres for the delivery of proteins. Ovalbumin (OVA was selected as model compound because of its sensitiveness of γ-radiation. The adopted grafting procedure allowed us to obtain a material with good free radical scavenging properties, without a significant modification of Mw and Tg of the starting PLGA (Mw PLGA = 26.3 ± 1.3 kDa vs. Mw g-CA-PLGA = 22.8 ± 0.7 kDa; Tg PLGA = 47.7 ± 0.8 °C vs. Tg g-CA-PLGA = 47.4 ± 0.2 °C. By using a W1/O/W2 technique, g-CA-PLGA improved the encapsulation efficiency (EE, suggesting that the presence of caffeic residues improved the compatibility between components (EEPLGA = 35.0% ± 0.7% vs. EEg-CA-PLGA = 95.6% ± 2.7%. Microspheres particle size distribution ranged from 15 to 50 µm. The zeta-potential values of placebo and loaded microspheres were −25 mV and −15 mV, respectively. The irradiation of g-CA-PLGA at the dose of 25 kGy caused a less than 1% variation of Mw and the degradation patterns of the non-irradiated and irradiated microspheres were superimposable. The OVA content in g-CA-PLGA microspheres decreased to a lower extent with respect to PLGA microspheres. These results suggest that g-CA-PLGA is a promising biodegradable material to microencapsulate biological drugs.

  13. Incorporation of mesoporous silica nanoparticles into random electrospun PLGA and PLGA/gelatin nanofibrous scaffolds enhances mechanical and cell proliferation properties

    DEFF Research Database (Denmark)

    Mehrasa, Mohammad; Asadollahi, Mohammad Ali; Nasri-Nasrabadi, Bijan

    2016-01-01

    Poly(lactic-co-glycolic.acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical...

  14. Fabrication of functional PLGA-based electrospun scaffolds and their applications in biomedical engineering.

    Science.gov (United States)

    Zhao, Wen; Li, Jiaojiao; Jin, Kaixiang; Liu, Wenlong; Qiu, Xuefeng; Li, Chenrui

    2016-02-01

    Electrospun PLGA-based scaffolds have been applied extensively in biomedical engineering, such as tissue engineering and drug delivery system. Due to lack of the recognition sites on cells, hydropholicity and single-function, the applications of PLGA fibrous scaffolds are limited. In order to tackle these issues, many works have been done to obtain functional PLGA-based scaffolds, including surface modifications, the fabrication of PLGA-based composite scaffolds and drug-loaded scaffolds. The functional PLGA-based scaffolds have significantly improved cell adhesion, attachment and proliferation. Moreover, the current study has summarized the applications of functional PLGA-based scaffolds in wound dressing, vascular and bone tissue engineering area as well as drug delivery system.

  15. A co-flow-focusing monodisperse microbubble generator

    KAUST Repository

    Zhang, Jiaming

    2014-02-14

    We use a simple and inexpensive microfluidic device, which is based on microscope glass slides and two tapered glass capillaries, to produce monodisperse microbubbles. The innermost capillary used for transporting the gas is inserted into the second capillary, with its 2 μm sharp tip aligned with the center of the converging-diverging throat of the second capillary. This configuration provides a small and smooth gas flow rate, and a high velocity gradient at the tube outlet. Highly monodisperse microbubbles with diameters ranging from 3.5 to 60 microns have been successfully produced at a rate of up to 40 kHz. A simple scaling law, which is based on the capillary number and liquid-to-gas flow rate ratio, successfully predicts the bubble size. © 2014 IOP Publishing Ltd.

  16. Synthesis and antimicrobial activity of monodisperse copper nanoparticles.

    Science.gov (United States)

    Kruk, Tomasz; Szczepanowicz, Krzysztof; Stefańska, Joanna; Socha, Robert P; Warszyński, Piotr

    2015-04-01

    Metallic monodisperse copper nanoparticles at a relatively high concentration (300 ppm CuNPs) have been synthesized by the reduction of copper salt with hydrazine in the aqueous SDS solution. The average particles size and the distribution size were characterized by Dynamic Light Scattering (DLS), Nanosight-Nanoparticle Tracking Analysis (NTA). The morphology and structure of nanoparticles were investigated using Scanning Electron Microscopy (SEM). The chemical composition of the copper nanoparticles was determined by X-ray Photoelectron Spectroscopy (XPS). Monodisperse copper nanoparticles with average diameter 50 nm were received. UV/vis absorption spectra confirmed the formation of the nanoparticles with the characteristic peak 550 nm. The antimicrobial studies showed that the copper nanoparticles had high activity against Gram-positive bacteria, standard and clinical strains, including methicillin-resistant Staphylococcus aureus, comparable to silver nanoparticles and some antibiotics. They also exhibited antifungal activity against Candida species. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Synthesis of Monodisperse Iron Oxide Nanoparticles without Surfactants

    Directory of Open Access Journals (Sweden)

    Xiao-Chen Yang

    2014-01-01

    Full Text Available Monodisperse iron oxide nanoparticles could be successfully synthesized with two kinds of precipitants through a precipitation method. As-prepared nanoparticles in the size around 10 nm with regular spherical-like shape were achieved by adjusting pH values. NaOH and NH3·H2O were used as two precipitants for comparison. The average size of nanoparticles with NH3·H2O precipitant got smaller and represented better dispersibility, while nanoparticles with NaOH precipitant represented better magnetic property. This work provided a simple method without using any organic solvents, organic metal salts, or surfactants which could easily obtain monodisperse nanoparticles with tunable morphology.

  18. Preparation and Characterization of Monodisperse Nickel Nanoparticles by Polyol Process

    Institute of Scientific and Technical Information of China (English)

    LI Peng; GUAN Jianguo; ZHANG Qingjie; ZHAO Wenyu

    2005-01-01

    Polymer-protected monodisperse nickel nanoparticles were synthesized by a modified polyol reduction method in the presence of poly ( N-vinyl- 2-pyrrolidone ). These nanoparticles were characterized by transmission electron microscopy (TEM), X- ray diffraction ( XRD ), selected area electron diffraction ( SAED ), as well as vibrating sample magnetometer (VSM). The experimental results show that the addition of PVP and the concentration of NaOH have strong influences on the size, agglomeration and uniformity of nanoparticles. In the presence of PVP and NaOH with low concentrations, monodisperse nickel nanoparticles with average diameters about 42 nm were obtained and characterized to be pure nickel crystalline with fcc structure. Secondary structures such as clusters, loops, and strings resulted from magnetic interactions between particles were observed. The chemical interaction between the PVP and nickel nanoparticles was found by FTIR. The saturation magnetization ( Ms ), remanent magnetization (Mr) and coercivity ( Hc ) of these nickel nanoparticles are lower than those of bulk nickel.

  19. Monodispersive CoPt Nanoparticles Synthesized Using Chemical Reduction Method

    Institute of Scientific and Technical Information of China (English)

    SHEN Cheng-Min; HUI Chao; YANG Tian-Zhong; XIAO Cong-Wen; CHEN Shu-Tang; DING Hao; GAO Hong-Jun

    2008-01-01

    @@ Monodispersive CoPt nanoparticles in sizes of about 2.2 nm are synthesized by superhydride reduction of CoCl2 and PtCl2 in diphenyl ether. The as-prepared nanoparticles show a chemically disordered A1 structure and are superparamagnetic. Thermal annealing transforms the A1 structure into chemically ordered L1o structure and the particles are ferromagnetic at room temperature.

  20. Monodisperse magnesium hydride nanoparticles uniformly self-assembled on graphene.

    Science.gov (United States)

    Xia, Guanglin; Tan, Yingbin; Chen, Xiaowei; Sun, Dalin; Guo, Zaiping; Liu, Huakun; Ouyang, Liuzhang; Zhu, Min; Yu, Xuebin

    2015-10-21

    Monodisperse MgH2 nanoparticles with homogeneous distribution and a high loading percent are developed through hydrogenation-induced self-assembly under the structure-directing role of graphene. Graphene acts not only as a structural support, but also as a space barrier to prevent the growth of MgH2 nanoparticles and as a thermally conductive pathway, leading to outstanding performance.

  1. Facile Synthesis of Monodisperse CdS Nanocrystals via Microreaction

    Directory of Open Access Journals (Sweden)

    Zhou Xinggui

    2009-01-01

    Full Text Available Abstract CdS-based nanocrystals (NCs have attracted extensive interest due to their potential application as key luminescent materials for blue and white LEDs. In this research, the continuous synthesis of monodisperse CdS NCs was demonstrated utilizing a capillary microreactor. The enhanced heat and mass transfer in the microreactor was useful to reduce the reaction temperature and residence time to synthesize monodisperse CdS NCs. The superior stability of the microreactor and its continuous operation allowed the investigation of synthesis parameters with high efficiency. Reaction temperature was found to be a key parameter for balancing the reactivity of CdS precursors, while residence time was shown to be an important factor that governs the size and size distribution of the CdS NCs. Furthermore, variation of OA concentration was demonstrated to be a facile tuning mechanism for controlling the size of the CdS NCs. The variation of the volume percentage of OA from 10.5 to 51.2% and the variation of the residence time from 17 to 136 s facilitated the synthesis of monodisperse CdS NCs in the size range of 3.0–5.4 nm, and the NCs produced photoluminescent emissions in the range of 391–463 nm.

  2. Fabrication of pillared PLGA microvessel scaffold using femtosecond laser ablation

    Directory of Open Access Journals (Sweden)

    Wang GJ

    2012-04-01

    Full Text Available Hsiao-Wei Wang1, Chung-Wei Cheng2, Ching-Wen Li3, Han-Wei Chang4, Ping-Han Wu2, Gou-Jen Wang 1Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, Taiwan, 2Laser Application Technology Center, Industrial Technology Research Institute, Tainan County, Taiwan, 3Department of Mechanical Engineering, 4Department of Chemical Engineering, National Chung Hsing University, Taichung, Taiwan, People’s Republic of ChinaAbstract: One of the persistent challenges confronting tissue engineering is the lack of intrinsic microvessels for the transportation of nutrients and metabolites. An artificial microvascular system could be a feasible solution to this problem. In this study, the femtosecond laser ablation technique was implemented for the fabrication of pillared microvessel scaffolds of polylactic-co-glycolic acid (PLGA. This novel scaffold facilitates implementation of the conventional cell seeding process. The progress of cell growth can be observed in vitro by optical microscopy. The problems of becoming milky or completely opaque with the conventional PLGA scaffold after cell seeding can be resolved. In this study, PLGA microvessel scaffolds consisting of 47 µm × 80 µm pillared branches were produced. Results of cell culturing of bovine endothelial cells demonstrate that the cells adhere well and grow to surround each branch of the proposed pillared microvessel networks.Keywords: femtosecond laser ablation, pillared microvessel scaffold, polylactic-co-glycolic acid, bovine endothelial cells

  3. Fabrication of Plga/Hap and Plga/Phb/Hap Fibrous Nanocomposite Materials for Osseous Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Krucińska Izabella

    2014-06-01

    Full Text Available The study presents the manufacturing of nanofibrous structures as osteoconductive, osteoinductive materials for osseous tissue regeneration. The fibrous structures were obtained by electrospinning of poly(l-lactide-coglicolide (PLGA with addition of hydroxyapatite (HAp and of a blend of PLGA with polyhydroxybutyrate with HAp added. The polymers used in the experiment were synthesised by an innovative method with a zirconium catalyst. First, the optimal electrospinning process parameters were selected. For the characterisation of the obtained osseous tissue reconstruction materials, the physical, macroscopic, functional, mechanical and thermal properties as well as crystallinity index were studied. The study of the radiation sterilisation influence on average molar mass, thermal and mechanical properties was made in order to analyse the degradation effect.

  4. Understanding greater cardiomyocyte functions on aligned compared to random carbon nanofibers in PLGA

    Directory of Open Access Journals (Sweden)

    Asiri AM

    2014-12-01

    Full Text Available Abdullah M Asiri,1 Hadi M Marwani,1 Sher Bahadar Khan,1 Thomas J Webster1,2 1Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA Abstract: Previous studies have demonstrated greater cardiomyocyte density on carbon nanofibers (CNFs aligned (compared to randomly oriented in poly(lactic-co-glycolic acid (PLGA composites. Although such studies demonstrated a closer mimicking of anisotropic electrical and mechanical properties for such aligned (compared to randomly oriented CNFs in PLGA composites, the objective of the present in vitro study was to elucidate a deeper mechanistic understanding of how cardiomyocyte densities recognize such materials to respond more favorably. Results showed lower wettability (greater hydrophobicity of CNFs embedded in PLGA compared to pure PLGA, thus providing evidence of selectively lower wettability in aligned CNF regions. Furthermore, the results correlated these changes in hydrophobicity with increased adsorption of fibronectin, laminin, and vitronectin (all proteins known to increase cardiomyocyte adhesion and functions on CNFs in PLGA compared to pure PLGA, thus providing evidence of selective initial protein adsorption cues on such CNF regions to promote cardiomyocyte adhesion and growth. Lastly, results of the present in vitro study further confirmed increased cardiomyocyte functions by demonstrating greater expression of important cardiomyocyte biomarkers (such as Troponin-T, Connexin-43, and α-sarcomeric actin when CNFs were aligned compared to randomly oriented in PLGA. In summary, this study provided evidence that cardiomyocyte functions are improved on CNFs aligned in PLGA compared to randomly oriented in PLGA since CNFs are more hydrophobic than PLGA and attract the adsorption of key proteins (fibronectin, laminin, and vironectin that are known to promote cardiomyocyte adhesion

  5. Cell Compatibility of Composite Biomaterials Composed of PLGA and Calcium Phosphate Compound%PLGA-磷酸钙盐复合材料的细胞相容性研究

    Institute of Scientific and Technical Information of China (English)

    郑莉琴; 王也; 林运鸿

    2011-01-01

    The mouse E13. 5 molar tooth germ cells were accessed as the seeding cells. The attachment efficiency,distribution of cells after attaching,the effect of different biomate-rials on the proliferation and differentiation of tooth germ cells were evaluated. The in vitro assay demonstrated that PLGA/HA was more useful for cell attachment, the in vivo assay demonstrated that PLGA/HA was more useful for cell proliferation, and PLGA/TCP and PLGA/CDHA were useful for cell differentiation. In conclusion, PLGA/TCP and PLGA/ CDHA have good cell compatibility, and it's hopeful to be used in the tooth regeneration.%用小鼠E13.5磨牙牙胚细胞作为种子细胞,观察4种生物材料对牙胚细胞的细胞黏附情况及其对牙胚细胞增殖分化的影响.体外实验表明PLGA/HA有利于细胞黏附,体内实验表明PLGA/HA有利于细胞增殖,PLGA/TCP和PLGA/CDHA有利于细胞分化.最终认为PLGA/TCP和PLGA/CDHA的细胞相容性最好,可望成为牙齿再生的生物材料.

  6. Morphologically and size uniform monodisperse particles and their shape-directed self-assembly

    Science.gov (United States)

    Collins, Joshua E.; Bell, Howard Y.; Ye, Xingchen; Murray, Christopher Bruce

    2015-11-17

    Monodisperse particles having: a single pure crystalline phase of a rare earth-containing lattice, a uniform three-dimensional size, and a uniform polyhedral morphology are disclosed. Due to their uniform size and shape, the monodisperse particles self assemble into superlattices. The particles may be luminescent particles such as down-converting phosphor particles and up-converting phosphors. The monodisperse particles of the invention have a rare earth-containing lattice which in one embodiment may be an yttrium-containing lattice or in another may be a lanthanide-containing lattice. The monodisperse particles may have different optical properties based on their composition, their size, and/or their morphology (or shape). Also disclosed is a combination of at least two types of monodisperse particles, where each type is a plurality of monodisperse particles having a single pure crystalline phase of a rare earth-containing lattice, a uniform three-dimensional size, and a uniform polyhedral morphology; and where the types of monodisperse particles differ from one another by composition, by size, or by morphology. In a preferred embodiment, the types of monodisperse particles have the same composition but different morphologies. Methods of making and methods of using the monodisperse particles are disclosed.

  7. Morphologically and size uniform monodisperse particles and their shape-directed self-assembly

    Energy Technology Data Exchange (ETDEWEB)

    Collins, Joshua E.; Bell, Howard Y.; Ye, Xingchen; Murray, Christopher Bruce

    2017-09-12

    Monodisperse particles having: a single pure crystalline phase of a rare earth-containing lattice, a uniform three-dimensional size, and a uniform polyhedral morphology are disclosed. Due to their uniform size and shape, the monodisperse particles self assemble into superlattices. The particles may be luminescent particles such as down-converting phosphor particles and up-converting phosphors. The monodisperse particles of the invention have a rare earth-containing lattice which in one embodiment may be an yttrium-containing lattice or in another may be a lanthanide-containing lattice. The monodisperse particles may have different optical properties based on their composition, their size, and/or their morphology (or shape). Also disclosed is a combination of at least two types of monodisperse particles, where each type is a plurality of monodisperse particles having a single pure crystalline phase of a rare earth-containing lattice, a uniform three-dimensional size, and a uniform polyhedral morphology; and where the types of monodisperse particles differ from one another by composition, by size, or by morphology. In a preferred embodiment, the types of monodisperse particles have the same composition but different morphologies. Methods of making and methods of using the monodisperse particles are disclosed.

  8. Hyaluronic Acid/PLGA Core/Shell Fiber Matrices Loaded with EGCG Beneficial to Diabetic Wound Healing.

    Science.gov (United States)

    Shin, Yong Cheol; Shin, Dong-Myeong; Lee, Eun Ji; Lee, Jong Ho; Kim, Ji Eun; Song, Sung Hwa; Hwang, Dae-Youn; Lee, Jun Jae; Kim, Bongju; Lim, Dohyung; Hyon, Suong-Hyu; Lim, Young-Jun; Han, Dong-Wook

    2016-12-01

    During the last few decades, considerable research on diabetic wound healing strategies has been performed, but complete diabetic wound healing remains an unsolved problem, which constitutes an enormous biomedical burden. Herein, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber matrices loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) are fabricated by coaxial electrospinning. HA/PLGA-E core/shell fiber matrices are composed of randomly-oriented sub-micrometer fibers and have a 3D porous network structure. EGCG is uniformly dispersed in the shell and sustainedly released from the matrices in a stepwise manner by controlled diffusion and PLGA degradation over four weeks. EGCG does not adversely affect the thermomechanical properties of HA/PLGA-E matrices. The number of human dermal fibroblasts attached on HA/PLGA-E matrices is appreciably higher than that on HA/PLGA counterparts, while their proliferation is steadily retained on HA/PLGA-E matrices. The wound healing activity of HA/PLGA-E matrices is evaluated in streptozotocin-induced diabetic rats. After two weeks of surgical treatment, the wound areas are significantly reduced by the coverage with HA/PLGA-E matrices resulting from enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or HA/PLGA. In conclusion, the HA/PLGA-E matrices can be potentially exploited to craft strategies for the acceleration of diabetic wound healing and skin regeneration.

  9. Monitoring model drug microencapsulation in PLGA scaffolds using X-ray powder diffraction

    OpenAIRE

    Adeyinka Aina; Manish Gupta; Yamina Boukari; Andrew Morris; Nashiru Billa; Stephen Doughty

    2015-01-01

    The microencapsulation of three model drugs; metronidazole, paracetamol and sulphapyridine into Poly (dl-Lactide-Co-Glycolide) (PLGA) scaffolds were probed using X-ray Powder Diffraction (XRPD). Changes in the diffraction patterns of the PLGA scaffolds after encapsulation was suggestive of a chemical interaction between the pure drugs and the scaffolds and not a physical intermixture.

  10. Monitoring model drug microencapsulation in PLGA scaffolds using X-ray powder d

    Directory of Open Access Journals (Sweden)

    Adeyinka Aina

    2016-03-01

    Full Text Available The microencapsulation of three model drugs; metronidazole, paracetamol and sulphapyridine into Poly (dl-Lactide-Co-Glycolide (PLGA scaffolds were probed using X-ray Powder Diffraction (XRPD. Changes in the diffraction patterns of the PLGA scaffolds after encapsulation was suggestive of a chemical interaction between the pure drugs and the scaffolds and not a physical intermixture.

  11. Monitoring model drug microencapsulation in PLGA scaffolds using X-ray powder diffraction.

    Science.gov (United States)

    Aina, Adeyinka; Gupta, Manish; Boukari, Yamina; Morris, Andrew; Billa, Nashiru; Doughty, Stephen

    2016-03-01

    The microencapsulation of three model drugs; metronidazole, paracetamol and sulphapyridine into Poly (dl-Lactide-Co-Glycolide) (PLGA) scaffolds were probed using X-ray Powder Diffraction (XRPD). Changes in the diffraction patterns of the PLGA scaffolds after encapsulation was suggestive of a chemical interaction between the pure drugs and the scaffolds and not a physical intermixture.

  12. PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing.

    Science.gov (United States)

    Chereddy, Kiran Kumar; Her, Charles-Henry; Comune, Michela; Moia, Claudia; Lopes, Alessandra; Porporato, Paolo E; Vanacker, Julie; Lam, Martin C; Steinstraesser, Lars; Sonveaux, Pierre; Zhu, Huijun; Ferreira, Lino S; Vandermeulen, Gaëlle; Préat, Véronique

    2014-11-28

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Poly (lactic-co-glycolic acid) (PLGA) supplies lactate that accelerates neovascularization and promotes wound healing. LL37 is an endogenous human host defense peptide that modulates wound healing and angiogenesis and fights infection. Hence, we hypothesized that the administration of LL37 encapsulated in PLGA nanoparticles (PLGA-LL37 NP) promotes wound closure due to the sustained release of both LL37 and lactate. In full thickness excisional wounds, the treatment with PLGA-LL37 NP significantly accelerated wound healing compared to PLGA or LL37 administration alone. PLGA-LL37 NP-treated wounds displayed advanced granulation tissue formation by significant higher collagen deposition, re-epithelialized and neovascularized composition. PLGA-LL37 NP improved angiogenesis, significantly up-regulated IL-6 and VEGFa expression, and modulated the inflammatory wound response. In vitro, PLGA-LL37 NP induced enhanced cell migration but had no effect on the metabolism and proliferation of keratinocytes. It displayed antimicrobial activity on Escherichia coli. In conclusion, we developed a biodegradable drug delivery system that accelerated healing processes due to the combined effects of lactate and LL37 released from the nanoparticles. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Biocompatibility and degradation characteristics of PLGA-based electrospun nanofibrous scaffolds with nanoapatite incorporation.

    NARCIS (Netherlands)

    Ji, W.; Yang, F.; Seyednejad, H.; Chen, Z.; Hennink, W.E.; Anderson, J.M.; Beucken, J.J.J.P van den; Jansen, J.A.

    2012-01-01

    The aim of current study was to evaluate the effect of nano-apatitic particles (nAp) incorporation on the degradation characteristics and biocompatibility of poly(lactide-co-glycolide) (PLGA)-based nanofibrous scaffolds. Composite PLGA/poly(varepsilon-caprolactone) (PCL) blended (w/w = 3/1) polymeri

  14. In vivo evaluation of the biodistribution and safety of PLGA nanoparticles as drug delivery systems

    CSIR Research Space (South Africa)

    Semete, B

    2010-10-01

    Full Text Available was conducted to assess the cell viability following exposure to PLGA nanoparticles. Viability was determined by means of a WST assay, wherein cell viability of greater than 75% was observed for both PLGA and amorphous fumed silica particles and ferrous oxide...

  15. Preclinical Development and In Vivo Efficacy of Ceftiofur-PLGA Microparticles.

    Directory of Open Access Journals (Sweden)

    Cristian Vilos

    Full Text Available Drug delivery systems based on polymeric microparticles represent an interesting field of development for the treatment of several infectious diseases for humans and animals. In this work, we developed PLGA microparticles loaded with ceftiofur (PLGA-cef, a third- generation cephalosporin that is used exclusively used in animals. PLGA-cef was prepared by the double emulsion w/o/w method, and exhibited a diameter in the range of 1.5-2.2 μm, and a negative ζ potential in the range of -35 to -55 mV. The loading yield of PLGA-cef was ~7% and encapsulation efficiency was approximately 40%. The pharmacokinetic study demonstrated a sustained release profile of ceftiofur for 20 days. PLGA-cef administrated in a single dose was more effective than ceftiofur non-encapsulated in rats challenged with S. Typhimurium. The in vivo toxicological evaluation showed that PLGA-cef did not affect the blood biochemical, hematological and hemostasis parameters. Overall, the PLGA-cef showed slow in vivo release profile, high antibacterial efficacy, and low toxicity. The results obtained supports the safe application of PLGA-cef as sustained release platform in the veterinary industry.

  16. Size effect of PLGA spheres on drug loading efficiency and release profiles

    NARCIS (Netherlands)

    Dawes, G.J.S.; Fratila-Apachitei, L.E.; Mulia, K.; Apachitei, I.; Witkamp, G.-J.; Duszczyk, J.

    2009-01-01

    Drug delivery systems (DDS) based on poly (lactide-co-glycolide) (PLGA) microspheres and nanospheres have been separately studied in previous works as a means of delivering bioactive compounds over an extended period of time. In the present study, two DDS having different sizes of the PLGA spheres w

  17. POE/PLGA composite microspheres: formation and in vitro behavior of double walled microspheres.

    Science.gov (United States)

    Yang, Yi-Yan; Shi, Meng; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

    2003-03-07

    The poly(ortho ester) (POE) and poly(D,L-lactide-co-glycolide) 50:50 (PLGA) composite microspheres were fabricated by a water-in-oil-in-water (w/o/w) double emulsion process. The morphology of the composite microspheres varied depending on POE content. When the POE content was 50, 60 or 70% in weight, the double walled microspheres with a dense core of POE and a porous shell of PLGA were formed. The formation of the double walled POE/PLGA microspheres was analysed. Their in vitro degradation behavior was characterized by scanning electron microscopy, gel permeation chromatography, Fourier-transform infrared microscopy and nuclear magnetic resonance spectroscopy (NMR). It was found that compared to the neat POE or PLGA microspheres, distinct degradation mechanism was achieved in the double walled POE/PLGA microspheres system. The degradation of the POE core was accelerated due to the acidic microenvironment produced by the hydrolysis of the outer PLGA layer. The formation of hollow microspheres became pronounced after the first week in vitro. 1H NMR spectra showed that the POE core was completely degraded after 4 weeks. On the other hand, the outer PLGA layer experienced slightly retarded degradation after the POE core disappeared. PLGA in the double walled microspheres kept more than 32% of its initial molecular weight over a period of 7 weeks.

  18. A Facile Solvothermal Synthesis of Monodisperse Ni Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    YU Peng-fei; CUI Bin; ZHANG Yan; SHI Qi-zhen

    2008-01-01

    A simple solvothermal approach was developed to synthesize uniform spherical monodisperse Ni nanoparticles, which can easily disperse in nonpolar solvents to form homogenous colloidal solution. The as-prepared sample was characterized by XRD, TEM, and FTIR. The results indicate that Ni nanoparticles have the structure of face-centered cube and a narrow distribution with a diameter of (3.5±0.5) nm. The FTIR spectrum reveals that the as a surfactant. The probable formation mechanism of the spherical nanoparticles was also discussed.

  19. Structural disorder versus spin canting in monodisperse maghemite nanocrystals

    Energy Technology Data Exchange (ETDEWEB)

    Kubickova, S.; Vejpravova, J., E-mail: vejpravo@fzu.cz [Department of Magnetic Nanosystems, Institute of Physics of the ASCR, v.v.i., Na Slovance 2, 182 21 Prague (Czech Republic); Niznansky, D. [Faculty of Science, Department of Inorganic Chemistry, Charles University in Prague, Albertov 2030, 128 40 Prague (Czech Republic); Morales Herrero, M. P. [Instituto de Ciencia de Materiales de Madrid, CSIC, C/Sor Juana Ins de la Cruz 3, Campus de Cantoblanco, 28049 Madrid (Spain); Salas, G. [Instituto de Ciencia de Materiales de Madrid, CSIC, C/Sor Juana Ins de la Cruz 3, Campus de Cantoblanco, 28049 Madrid (Spain); Instituto Madrileno de Estudios Avanzados en Nanociencia, Campus Universitario de Cantoblanco, 28049 Madrid (Spain)

    2014-06-02

    Monodisperse maghemite nanoparticles with diameter ranging from 7 to 20 nm were examined by the In-field Mössbauer Spectroscopy (IFMS) in varying external magnetic field up to 6 T. Surprisingly, the small-sized particles (7 nm) exhibit nearly no spin canting in contrast to the larger particles with lower surface-to-volume ratio. We demonstrate that the observed phenomenon is originated by lower relative crystallinity of the larger particles with different internal structure. Hence, the persistence of the 2nd and 5th absorption lines in the IFMS cannot be unambiguously assigned to the surface spins.

  20. Monodisperse Silver Nanoparticles Synthesized by a Microwave-Assisted Method

    Institute of Scientific and Technical Information of China (English)

    ZHU Shao-Peng; TANG Shao-Chun; MENG Xiang-Kang

    2009-01-01

    Silver nanoparticles with an average size of about 2Onto are synthesized in a colloidal solution with the aid of microwave irradiation. Neither additional reductant nor stabilizer is required in this microwave-assisted method.The color of the colloidal solution is found to be dark green, different from the characteristic yellow of silver colloidal solutions. The silver nanoparticles in the colloidal solution have a narrow size distribution and large yield quantity. UV-visible absorption spectroscopy analysis reveals that the as-synthesized monodisperse silver nanoparticles have exceptional optical properties. Raman spectroscopy measurements demonstrate that these silver nanoparticles exhibit a notable surface-enhanced Raman scattering ability.

  1. MONODISPERSE MICRON-SIZED POLYACRYLAMIDE PARTICLES SYNTHESIZED BY DISPERSION POLYMERIZATION

    Institute of Scientific and Technical Information of China (English)

    Xin Hou; Bo Gao; Zhe-guo Zhang; Kang-de Yao

    2007-01-01

    Monodisperse micron-sized polyacrylamide (PAM) particles with a regular shape have been successfully prepared through dispersion polymerization of the monomer using a rotary reactor. FTIR and NMR spectroscopic results demonstrated the formation of PAM. POM and TEM observations revealed that PAM particles had a regular shape and good dispersity. A thick layer of surfactant (PVP) still existed on PAM particles after multiple centrifugation and ultrasonic re-dispersion in ethanol, which indicates a strong interaction between PVP and PAM. The effects of various polymerization factors on the average size of PAM particles have also been studied.

  2. In vitro biocompatibility of polypyrrole/PLGA conductive nanofiber scaffold with cultured rat hepatocytes

    Science.gov (United States)

    Chu, Xue-Hui; Xu, Qian; Feng, Zhang-Qi; Xiao, Jiang-Qiang; Li, Qiang; Sun, Xi-Tai; Cao, Yang; Ding, Yi-Tao

    2014-09-01

    To intruduce conductive biomaterial into liver tissue engineering, a conductive nanofiber scaffold, polypyrrole/poly(lactic-co-glycolic)acid(PLGA), was designed and prepared via electro-spinning and oxidative polymerization. Effects of the scaffold on hepatocyte adhesion, viability and function were then investigated. SEM revealed pseudopodium formation and abundant extracellular matrix on the surface of PLGA membrane and polypyrrole/PLGA membrane. The adhesion rate, cellular activity, urea synthesis and albumin secretion of the hepatocytes cultured on polypyrrole/PLGA group were similar to those on the PLGA group, but were significantly higher than those on the control group. There were no significant differences in concentrations of LDH and TNF-α among three groups. These results suggested the potential application of this conductive nanofiber scaffold as a suitable substratum for hepatocyte culturing in liver tissue engineering.

  3. Fabrication and in vitro biocompatibility of biomorphic PLGA/nHA composite scaffolds for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Junmin, E-mail: jmqian@mail.xjtu.edu.cn; Xu, Weijun; Yong, Xueqing; Jin, Xinxia; Zhang, Wei

    2014-03-01

    In this study, biomorphic poly(DL-lactic-co-glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164 ± 52 μm and 13 ± 8 μm, respectively, with a porosity of 89.3 ± 1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400 μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering. - Highlights: • Novel biomimetic PLGA/nHA composite scaffolds were successfully prepared. • nHA addition improved elastic modulus of PLGA scaffold and decreased its crystallinity. • PLGA/nHA composite scaffolds had better biocompatibility than PLGA scaffolds. • Biomorphic PLGA/nHA composite scaffold had great potential in bone tissue engineering.

  4. Physiologically based pharmacokinetic modeling of PLGA nanoparticles with varied mPEG content

    Directory of Open Access Journals (Sweden)

    Avgoustakis K

    2012-03-01

    Full Text Available Mingguang Li1, Zoi Panagi2, Konstantinos Avgoustakis2, Joshua Reineke11Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA; 2Pharmaceutical Technology Laboratory, Department of Pharmacy, University of Patras, Rion, Patras, GreeceAbstract: Biodistribution of nanoparticles is dependent on their physicochemical properties (such as size, surface charge, and surface hydrophilicity. Clear and systematic understanding of nanoparticle properties' effects on their in vivo performance is of fundamental significance in nanoparticle design, development and optimization for medical applications, and toxicity evaluation. In the present study, a physiologically based pharmacokinetic model was utilized to interpret the effects of nanoparticle properties on previously published biodistribution data. Biodistribution data for five poly(lactic-co-glycolic acid (PLGA nanoparticle formulations prepared with varied content of monomethoxypoly (ethyleneglycol (mPEG (PLGA, PLGA-mPEG256, PLGA-mPEG153, PLGA-mPEG51, PLGA-mPEG34 were collected in mice after intravenous injection. A physiologically based pharmacokinetic model was developed and evaluated to simulate the mass-time profiles of nanoparticle distribution in tissues. In anticipation that the biodistribution of new nanoparticle formulations could be predicted from the physiologically based pharmacokinetic model, multivariate regression analysis was performed to build the relationship between nanoparticle properties (size, zeta potential, and number of PEG molecules per unit surface area and biodistribution parameters. Based on these relationships, characterized physicochemical properties of PLGA-mPEG495 nanoparticles (a sixth formulation were used to calculate (predict biodistribution profiles. For all five initial formulations, the developed model adequately simulates the experimental data indicating that the model is suitable for

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

    Directory of Open Access Journals (Sweden)

    Ma YR

    2012-02-01

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

  6. Persistence, distribution, and impact of distinctly segmented microparticles on cochlear health following in vivo infusion.

    Science.gov (United States)

    Ross, Astin M; Rahmani, Sahar; Prieskorn, Diane M; Dishman, Acacia F; Miller, Josef M; Lahann, Joerg; Altschuler, Richard A

    2016-06-01

    Delivery of pharmaceuticals to the cochleae of patients with auditory dysfunction could potentially have many benefits from enhancing auditory nerve survival to protecting remaining sensory cells and their neuronal connections. Treatment would require platforms to enable drug delivery directly to the cochlea and increase the potential efficacy of intervention. Cochlear implant recipients are a specific patient subset that could benefit from local drug delivery as more candidates have residual hearing; and since residual hearing directly contributes to post-implantation hearing outcomes, it requires protection from implant insertion-induced trauma. This study assessed the feasibility of utilizing microparticles for drug delivery into cochlear fluids, testing persistence, distribution, biocompatibility, and drug release characteristics. To allow for delivery of multiple therapeutics, particles were composed of two distinct compartments; one containing polylactide-co-glycolide (PLGA), and one composed of acetal-modified dextran and PLGA. Following in vivo infusion, image analysis revealed microparticle persistence in the cochlea for at least 7 days post-infusion, primarily in the first and second turns. The majority of subjects maintained or had only slight elevation in auditory brainstem response thresholds at 7 days post-infusion compared to pre-infusion baselines. There was only minor to limited loss of cochlear hair cells and negligible immune response based on CD45+ immunolabling. When Piribedil-loaded microparticles were infused, Piribedil was detectable within the cochlear fluids at 7 days post-infusion. These results indicate that segmented microparticles are relatively inert, can persist, release their contents, and be functionally and biologically compatible with cochlear function and therefore are promising vehicles for cochlear drug delivery. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1510-1522, 2016.

  7. Multimodal delivery of irinotecan from microparticles with two distinct compartments.

    Science.gov (United States)

    Rahmani, Sahar; Park, Tae-Hong; Dishman, Acacia Frances; Lahann, Joerg

    2013-11-28

    In the last several decades, research in the field of drug delivery has been challenged with the fabrication of carrier systems engineered to deliver therapeutics to the target site with sustained and controlled release kinetics. Herein, we report the fabrication of microparticles composed of two distinct compartments: i) one compartment containing a pH responsive polymer, acetal-modified dextran, and PLGA (polylactide-co-glycolide), and ii) one compartment composed entirely of PLGA. We demonstrate the complete release of dextran from the microparticles during a 10-hour period in an acidic pH environment and the complete degradation of one compartment in less than 24h. This is in congruence with the stability of the same microparticles in neutral pH over the 24-hour period. Such microparticles can be used as pH responsive carrier systems for drug delivery applications where their cargo will only be released when the optimum pH window is reached. The feasibility of the microparticle system for such an application was confirmed by encapsulating a cancer therapeutic, irinotecan, in the compartment containing the acetal-modified dextran polymer and the pH dependent release over a 5-day period was studied. It was found that upon pH change to an acidic environment, over 50% of the drug was first released at a rapid rate for 10h, similar to that observed for the dextran release, before continuing at a more controlled rate for 4 days. As such, these microparticles can play an important role in the fabrication of novel drug delivery systems due to the selective, controlled, and pH responsive release of their encapsulated therapeutics.

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

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Nansha [Chinese Academy of Science, Research Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology (China); Chen, Zhihong [Guangdong Medical College, Analysis Centre (China); Xiao, Xiaojun [Shenzhen University, Institute of Allergy and Immunology, School of Medicine (China); Ruan, Changshun [Chinese Academy of Science, Research Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology (China); Mei, Lin [Tsinghua University, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen (China); Liu, Zhigang, E-mail: lzg@szu.edu.cn [Shenzhen University, Institute of Allergy and Immunology, School of Medicine (China); Zeng, Xiaowei, E-mail: zeng.xiaowei@sz.tsinghua.edu.cn [Tsinghua University, The Shenzhen Key Lab of Gene and Antibody Therapy, and Division of Life and Health Sciences, Graduate School at Shenzhen (China)

    2015-08-15

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

  9. A novel method for preparing monodispersed polystyrene nanoparticles

    Institute of Scientific and Technical Information of China (English)

    LIU Kaiyi; WANG Zhaoqun

    2007-01-01

    A preparation manner for monodispersed polystyrene(PS)nanoparticles polymerized by using a novel addition procedure of a monomer is suggested.In systems containing a smaller amount of surfactant compared with conventional microemulsion polymerization,the polymerization processes consists of three stages:adding dropwise the first part of the monomer for a few minutes at 80℃ and polymerizing for 1 h;adding collectively the residual part of the monomer and polymerizing at the same temperature for another 1 h;and then polymerizing at 85℃ for another 1 h.Based on discussions on the nucleation mechanism of particles in the polymerization system,the influences of monomer weight added dropwise,and amounts of initiator and emulsifier on the size and distribution of PS particles were investigated.PS nanoparticles with smaller diameter such as a number-average diameter of 18.7 nm and better monodispersity were obtained since the dropped styrene amount was suitable under 20wt-% emulsifier amount and 3wt-% initiator amount based on the monomer.

  10. Interchain tube pressure effect in extensional flows of oligomer diluted nearly monodisperse polystyrene melts

    DEFF Research Database (Denmark)

    Rasmussen, Henrik K.; Huang, Qian

    2014-01-01

    We have derived a constitutive equation to explain the extensional dynamics of oligomer-diluted monodisperse polymers, if the length of the diluent has at least two Kuhn steps. These polymer systems have a flow dynamics which distinguish from pure monodisperse melts and solutions thereof, if the ...

  11. Monodisperse Femto- to Atto-liter Droplet Formation Using a Nano-Microchannel Interface

    NARCIS (Netherlands)

    Shui, Lingling; Berg, van den Albert; Eijkel, Jan C.T.; Kim, Tae Song; Lee, Yoon-Sik; Chung, Taek-Dong; Jeon, Noo Li; Suh, Kahp-Yang; Choo, Jaebum; Kim, Yong-Kweon

    2009-01-01

    We demonstrate the production of sub-micrometer diameter monodisperse droplets by using a nano-micro channel interface. A perfectly steady nanoscopic liquid filament can be formed by a geometric confinement which eventually gives rise to a stable production of nearly perfectly monodisperse droplets.

  12. Surface properties of poly(ethylene oxide)-based segmented block copolymers with monodisperse hard segments

    NARCIS (Netherlands)

    Husken, D.; Feijen, Jan; Gaymans, R.J.

    2009-01-01

    The surface properties of segmented block copolymers based on poly(ethylene oxide) (PEO) segments and monodisperse crystallizable tetra-amide segments were studied. The monodisperse crystallizable segments (T6T6T) were based on terephthalate (T) and hexamethylenediamine (6). Due to the crystallinity

  13. Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir.

    Science.gov (United States)

    Gupta, Swati; Agarwal, Abhinav; Gupta, Nishant Kumar; Saraogi, Gauravkant; Agrawal, Himanshu; Agrawal, G P

    2013-12-01

    The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders.

  14. Porosity and mechanically optimized PLGA based in situ hardening systems.

    Science.gov (United States)

    Schloegl, W; Marschall, V; Witting, M Y; Volkmer, E; Drosse, I; Leicht, U; Schieker, M; Wiggenhorn, M; Schaubhut, F; Zahler, S; Friess, W

    2012-11-01

    Goal of the present study was to develop and to characterize in situ-hardening, porous PLGA-based systems for their future application as bone grafting materials. Therefore, we investigated the precipitation behavior of formulations containing PLGA and a water-miscible solvent, DMSO, PEG 400, and NMP. To increase porosity, a pore forming agent (NaCMC) was added and to enhance mechanical properties of the system, an inorganic filler (α-TCP) was incorporated. The behavior upon contact with water and the influence of the prior addition of aqueous media on the morphology of the corresponding hardened implants were investigated. We proved cell-compatibility by live/dead assays for the hardened porous polymer/ceramic-composite scaffolds. The IsHS formulations can therefore be used to manufacture hardened scaffolds ex vivo by using molds with the desired shape and size. Cells were further successfully incorporated into the IsHS by precultivating the cells on the α-TCP-powder prior to their admixing to the formulation. However, cell viability could not be maintained due to toxicity of the tested solvents. But, the results demonstrate that in vivo cells should well penetrate, adhere, and proliferate in the hardened scaffolds. Consequently, we consider the in situ hardening system being an excellent candidate as a filling material for non-weight-bearing orthopedic indications, as the resulting properties of the hardened implant fulfill indication-specific needs like mechanical stability, elasticity, and porosity.

  15. Microencapsulation of a synbiotic into PLGA/alginate multiparticulate gels.

    Science.gov (United States)

    Cook, Michael T; Tzortzis, George; Charalampopoulos, Dimitris; Khutoryanskiy, Vitaliy V

    2014-05-15

    Probiotic bacteria have gained popularity as a defence against disorders of the bowel. However, the acid sensitivity of these cells results in a loss of viability during gastric passage and, consequently, a loss of efficacy. Probiotic treatment can be supplemented using 'prebiotics', which are carbohydrates fermented specifically by probiotic cells in the body. This combination of probiotic and prebiotic is termed a 'synbiotic'. Within this article a multiparticulate dosage form has been developed, consisting of poly(d,l-lactic-co-glycolic acid) (PLGA) microcapsules containing prebiotic Bimuno™ incorporated into an alginate-chitosan matrix containing probiotic Bifidobacterium breve. The aim of this multiparticulate was that, in vivo, the probiotic would be protected against gastric acid and the release of the prebiotic would occur in the distal colon. After microscopic investigation, this synbiotic multiparticulate was shown to control the release of the prebiotic during in vitro gastrointestinal transit, with the release of galacto-oligosaccharides (GOS) initially occurred over 6h, but with a triphasic release pattern giving further release over 288 h. Encapsulation of B. breve in multiparticulates resulted in a survival of 8.0 ± 0.3 logCFU/mL cells in acid, an improvement over alginate-chitosan microencapsulation of 1.4 logCFU/mL. This was attributed to increased hydrophobicity by the incorporation of PLGA particles. Copyright © 2014. Published by Elsevier B.V.

  16. Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles.

    Science.gov (United States)

    Wischke, Christian; Schwendeman, Steven P

    2008-12-08

    Injectable biodegradable and biocompatible copolymers of lactic and glycolic acid (PLGA) are an important advanced delivery system for week-to-month controlled release of hydrophobic drugs (e.g., from biopharmaceutical classification system class IV), which often display poor oral bioavailability. The basic principles and considerations to develop such microparticle formulations is reviewed here based on a comprehensive study of papers and patents from the beginnings of hydrophobic drug encapsulation in polylactic acid and PLGA up through the very recent literature. Challenges with the diversity of drug properties, microencapsulation methods, and organic solvents are evaluated in light of the precedence of commercialized formulations and with a focus on decreasing the time to lab-scale encapsulation of water-insoluble drug candidates in the early stage of drug development. The influence of key formulation variables on final microparticle characteristics, and how best to avoid undesired microparticle properties, is analyzed mechanistically. Finally, concepts are developed to manage the common issues of maintaining sink conditions for in vitro drug release assays of hydrophobic compounds. Overall, against the backdrop of an increasing number of new, poorly orally available drug entities entering development, microparticle delivery systems may be a viable strategy to rescue an otherwise undeliverable substance.

  17. Development and evaluation of PLGA polymer based nanoparticles of quercetin.

    Science.gov (United States)

    Anwer, Md Khalid; Al-Mansoor, Mohammed A; Jamil, Shahid; Al-Shdefat, Ramadan; Ansari, Mohammad Nazam; Shakeel, Faiyaz

    2016-11-01

    Quercetin is the most abundant antioxidant found in the human diet. Low aqueous solubility of quercetin limits its bioavailability and hence therapeutic effects. Therefore, the aim of the present study was to develop a poly lactide-co-glycolic acid (PLGA) polymer based nanoparticles of quercetin with a view to improve its aqueous solubility and examine the effect on its antioxidant and diuretic properties. Nanoparticles of quercetin were developed by single emulsion-solvent evaporation technique and evaluated in vitro for differential scanning calorimetry (DSC), Fourier transforms infra-red (FTIR) spectroscopy, particle size, polydispersity index and drug entrapment efficiency. Among the five different formulations (F1, F2, F3, F4 and F5), F2 and F3 were optimized with an average particle size of 189nm and 186nm and high entrapment values of 86.48%, 83.71%, respectively. SEM images of confirmed that prepared nanoparticles were spherical in shape with a smooth surface. In vitro release and anti-oxidant activity confirmed significant results. Furthermore, its in vivo diuretic activity was much better as compared to pure quercetin. The overall results suggest that PLGA polymer based nanoparticle could be a potential option for quercetin delivery.

  18. Antioxidant Effects of Quercetin and Catechin Encapsulated into PLGA Nanoparticles

    Directory of Open Access Journals (Sweden)

    Hector Pool

    2012-01-01

    Full Text Available Polymeric nanoparticles (PLGA have been developed for the encapsulation and controlled release of quercetin and catechin. Nanoparticles were fabricated using a solvent displacement method. Physicochemical properties were measured by light scattering, scanning electron microscopy and ζ-potential, X-ray diffraction, infrared spectroscopy and differential scanning calorimetry. Encapsulation efficiency and in vitro release profiles were obtained from differential pulse voltammetry experiments. Antioxidant properties of free and encapsulated flavonoids were determined by TBARS, fluorescence spectroscopy and standard chelating activity methods. Relatively small (d≈ 400 nm polymeric nanoparticles were obtained containing quercetin or catechin in a non-crystalline form (EE ≈ 79% and the main interactions between the polymer and each flavonoid were found to consist of hydrogen bonds. In vitro release profiles were pH-dependant, the more acidic pH, the faster release of each flavonoid from the polymeric nanoparticles. The inhibition of the action of free radicals and chelating properties, were also enhanced when quercetin and catechin were encapsulated within PLGA nanoparticles. The information obtained from this study will facilitate the design and fabrication of polymeric nanoparticles as possible oral delivery systems for encapsulation, protection and controlled release of flavonoids aimed to prevent oxidative stress in human body or food products.

  19. Immunization against leishmaniasis by PLGA nanospheres loaded with an experimental autoclaved Leishmania major (ALM) and Quillaja saponins.

    Science.gov (United States)

    Tafaghodi, M; Eskandari, M; Kharazizadeh, M; Khamesipour, A; Jaafari, M R

    2010-12-01

    Immune responses against the Leishmania antigens are not sufficient to protect against a leishmania challenge. Therefore these antigens need to be potentiated by various adjuvants and delivery systems. In this study, Poly (d,l-lactide-co-glycolide (PLGA) nanospheres as antigen delivery system and Quillaja saponins (QS) as immunoadjuvant have been used to enhance the immune response against autoclaved Leishmania major (ALM). PLGA nanospheres were prepared by a double-emulsion (W/O/W) technique. Particulate characteristics were studied by scanning electron microscopy and particle size analysis. Mean diameter for nanospheres loaded with ALM+QS was 294 ± 106 nm. BALB/c mice were immunized three times in 3-weeks intervals using ALM plus QS loaded nanospheres [(ALM+QS)PLGA], ALM encapsulated with PLGA nanospheres [(ALM)PLGA], (ALM)PLGA + QS, ALM + QS, ALM alone or PBS. The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection, showed by significantly (P < 0.05) smaller footpad, were observed in mice immunized with (ALM)PLGA. The (ALM+QS)PLGA group showed the least protection and highest swelling, while the (ALM)PLGA+QS, ALM+QS and ALM showed an intermediate protection with no significant difference. The mice immunized with ALM and ALM+QS showed the highest IgG2a/IgG1 ratio (P < 0.01), followed by (ALM)PLGA+QS. The highest IFN-γ and lowest IL-4 production was seen in (ALM)PLGA+QS, ALM+QS groups. The highest parasite burden was observed in (ALM)PLGA+QS and (ALM+QS)PLGA groups. It is concluded that PLGA nanospheres as a vaccine delivery system could increase the protective immune responses, but QS adjuvant has a reverse effect on protective immune responses and the least protective responses were seen in the presence of this adjuvant.

  20. PLGA Nanoparticles for Ultrasound-Mediated Gene Delivery to Solid Tumors

    Directory of Open Access Journals (Sweden)

    Marxa Figueiredo

    2012-01-01

    Full Text Available This paper focuses on novel approaches in the field of nanotechnology-based carriers utilizing ultrasound stimuli as a means to spatially target gene delivery in vivo, using nanoparticles made with either poly(lactic-co-glycolic acid (PLGA or other polymers. We specifically discuss the potential for gene delivery by particles that are echogenic (amenable to destruction by ultrasound composed either of polymers (PLGA, polystyrene or other contrast agent materials (Optison, SonoVue microbubbles. The use of ultrasound is an efficient tool to further enhance gene delivery by PLGA or other echogenic particles in vivo. Echogenic PLGA nanoparticles are an attractive strategy for ultrasound-mediated gene delivery since this polymer is currently approved by the US Food and Drug Administration for drug delivery and diagnostics in cancer, cardiovascular disease, and also other applications such as vaccines and tissue engineering. This paper will review recent successes and the potential of applying PLGA nanoparticles for gene delivery, which include (a echogenic PLGA used with ultrasound to enhance local gene delivery in tumors or muscle and (b PLGA nanoparticles currently under development, which could benefit in the future from ultrasound-enhanced tumor targeted gene delivery.

  1. Modiifcation ofb-TCP/PLGA Scaffold and Its Effect on Bone Regeneration in vivo

    Institute of Scientific and Technical Information of China (English)

    LIN Liulan; GAO Haitao

    2016-01-01

    In order to look for the best proportion ofβ-tricalcium phosphate(β-TCP) and poly(lactide-co-glycolide) (PLGA) we fabricated porous compositesβ-TCP/PLGA scaffold using freeze-drying method. Morphological characterization using scanning electron microscopy showed that the interconnected pore distribution was even and there was no signiifcant difference with the increase of PLGA content. Moreover, the porosity, compressive strength and degradation in vitro were characterized. The fabricated scaffolds with increased PLGA in the compositesβ-TCP/PLGA scaffolds will get stronger mechanical property and better appearance, furthermore, get suitable environment for cells. According to the evaluation indexes for the tissue engineering scaffold, the group of scaffold (β-TCP/PLGA=6:4) was selected to evaluate the induced cell adhesion and proliferative ability of the scaffolds. Then as transplant embed into the bone critical defect sites on rats femur. The repairing processes of bone defect sites were characterized by X-ray analysis within 12 weeks. X-ray analysis showed that the bone defect sites all displayed the formation of callus obviously, In summary, our data suggest that the scaffold (β-TCP/PLGA=6:4) has a promising clinical future in regeneration of bone critical defects .

  2. Osteointegration of PLGA implants with nanostructured or microsized β-TCP particles in a minipig model.

    Science.gov (United States)

    Kulkova, Julia; Moritz, Niko; Suokas, Esa O; Strandberg, Niko; Leino, Kari A; Laitio, Timo T; Aro, Hannu T

    2014-12-01

    Bioresorbable suture anchors and interference screws have certain benefits over equivalent titanium-alloy implants. However, there is a need for compositional improvement of currently used bioresorbable implants. We hypothesized that implants made of poly(l-lactide-co-glycolide) (PLGA) compounded with nanostructured particles of beta-tricalcium phosphate (β-TCP) would induce stronger osteointegration than implants made of PLGA compounded with microsized β-TCP particles. The experimental nanostructured self-reinforced PLGA (85L:15G)/β-TCP composite was made by high-energy ball-milling. Self-reinforced microsized PLGA (95L:5G)/β-TCP composite was prepared by melt-compounding. The composites were characterized by gas chromatography, Ubbelohde viscometry, scanning electron microscopy, laser diffractometry, and standard mechanical tests. Four groups of implants were prepared for the controlled laboratory study employing a minipig animal model. Implants in the first two groups were prepared from nanostructured and microsized PLGA/β-TCP composites respectively. Microroughened titanium-alloy (Ti6Al4V) implants served as positive intra-animal control, and pure PLGA implants as negative control. Cone-shaped implants were inserted in a random order unilaterally in the anterior cortex of the femoral shaft. Eight weeks after surgery, the mechanical strength of osteointegration of the implants was measured by a push-out test. The quality of new bone surrounding the implant was assessed by microcomputed tomography and histology. Implants made of nanostructured PLGA/β-TCP composite did not show improved mechanical osteointegration compared with the implants made of microsized PLGA/β-TCP composite. In the intra-animal comparison, the push-out force of two PLGA/β-TCP composites was 35-60% of that obtained with Ti6Al4V implants. The implant materials did not result in distinct differences in quality of new bone surrounding the implant.

  3. Preparation and efficacy of Newcastle disease virus DNA vaccine encapsulated in PLGA nanoparticles.

    Directory of Open Access Journals (Sweden)

    Kai Zhao

    Full Text Available BACKGROUND: Although the Newcastle disease virus (NDV inactivated vaccines and attenuated live vaccines have been used to prevent and control Newcastle disease (ND for years, there are some disadvantages. Recently, newly developed DNA vaccines have the potential to overcome these disadvantages. The low delivery efficiency, however, hindered the application of DNA vaccines for ND in practice. METHODOLOGY/PRINCIPAL FINDINGS: The eukaryotic expression plasmid pVAX1-F (o DNA that expressed the F gene of NDV encapsulated in PLGA nanoparticles (pFNDV-PLGA-NPs were prepared by a double emulsion-solvent evaporation method and optimal preparation conditions of the pFNDV-PLGA-NPs were determined. Under the optimal conditions, the pFNDV-PLGA-NPs were produced in good morphology and had high stability with a mean diameter of 433.5 ± 7.5 nm, with encapsulation efficiency of 91.8 ± 0.3% and a Zeta potential of +2.7 mV. Release assay in vitro showed that the fusion gene plasmid DNA could be sustainably released from the pFNDV-PLGA-NPs up to 93.14% of the total amount. Cell transfection test indicated that the vaccine expressed and maintained its bioactivity. Immunization results showed that better immune responses of SPF chickens immunized with the pFNDV-PLGA-NPs were induced compared to the chickens immunized with the DNA vaccine alone. In addition, the safety of mucosal immunity delivery system of the pFNDV-PLGA-NPs was also tested in an in vitro cytotoxicity assay. CONCLUSIONS/SIGNIFICANCE: The pFNDV-PLGA-NPs could induce stronger cellular, humoral, and mucosal immune responses and reached the sustained release effect. These results laid a foundation for further development of vaccines and drugs in PLGA nanoparticles.

  4. Porous magnesium/PLGA composite scaffolds for enhanced bone regeneration following tooth extraction.

    Science.gov (United States)

    Brown, Andrew; Zaky, Samer; Ray, Herbert; Sfeir, Charles

    2015-01-01

    Sixty percent of implant-supported dental prostheses require bone grafting to enhance bone quantity and quality prior to implant placement. We have developed a metallic magnesium particle/PLGA composite scaffold to overcome the limitations of currently used dental bone grafting materials. This is the first report of porous metallic magnesium/PLGA scaffolds synthesized using a solvent casting, salt leaching method. We found that incorporation of varying amounts of magnesium into the PLGA scaffolds increased the compressive strength and modulus, as well as provided a porous structure suitable for cell infiltration, as measured by mercury intrusion porosimetry. Additionally, combining basic-degrading magnesium with acidic-degrading PLGA led to an overall pH buffering effect and long-term release of magnesium over the course of a 10-week degradation assay, as measured with inductively coupled plasma-atomic emission spectroscopy. Using an indirect proliferation assay adapted from ISO 10993:5, it was found that extracts of medium from degrading magnesium/PLGA scaffolds increased bone marrow stromal cell proliferation in vitro, a phenomenon observed by other groups investigating magnesium's impact on cells. Finally, magnesium/PLGA scaffold biocompatibility was assessed in a canine socket preservation model. Micro-computed tomography and histological analysis showed the magnesium/PLGA scaffolds to be safer and more effective at preserving bone height than empty controls. Three-dimensional magnesium/PLGA composite scaffolds show promise for dental socket preservation and also, potentially, orthopedic bone regeneration. These scaffolds could decrease inflammation observed with clinically used PLGA devices, as well as enhance osteogenesis, as observed with previously studied magnesium devices.

  5. BMP-2 immobilized PLGA/hydroxyapatite fibrous scaffold via polydopamine stimulates osteoblast growth.

    Science.gov (United States)

    Zhao, Xingyu; Han, Yu; Li, Jiawei; Cai, Bo; Gao, Hang; Feng, Wei; Li, Shuqiang; Liu, Jianguo; Li, Dongsong

    2017-09-01

    Combining biomaterials scaffolds with bone morphogenetic protein-2 (BMP-2) is currently used to promote the regeneration of bone tissue. However, the traditional strategies used to add BMP-2 into the polymer scaffolds directly suffer from limitations that can result in lower growth factor loading and damage the bioactivity of growth factors. In this study, we report the fabrication of poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HA) composite fibrous scaffolds via melt-spinning method to mimic native extracellular matrix (ECM). In order to effectively immobilize BMP-2 on PLGA/HA composite fibrous scaffolds, the surface of the scaffold was modified with polydopamine (PDA) (PDA-PLGA/HA). PDA was chosen as an adhesive polymeric bridge-layer between PLGA/HA fibrous scaffolds and BMP-2. Analysis of the scaffold using scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscope revealed that the PDA coating was attached to the scaffold surface. Moreover, analysis of the scaffold using water contact angle demonstrated an increased hydrophilicity via PDA modification. Furthermore, the PDA coating effectively immobilized BMP-2 on the PDA-PLGA/HA fibrous scaffold and a sustained release profile of BMP-2 was achieved in the BMP-2-immobilized PLGA/HA fibrous scaffold. In vitro experiments showed that BMP-2-immobilized PLGA/HA fibrous scaffold significantly promoted the attachment and proliferation of MC3T3-E1 cells. More importantly, the ALP activity, mRNA expression of osteosis-related genes and calcium deposition in MC3T3-E1 cells cultured on BMP-2-immobilized PLGA/HA fibrous scaffold were significantly increased. These results collectively demonstrate that the BMP-2-immobilized PLGA/HA fibrous scaffold is a promising candidate for bone regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Poly Lactic-co-Glycolic Acid (PLGA as Biodegradable Controlled Drug Delivery Carrier

    Directory of Open Access Journals (Sweden)

    Steven J. Siegel

    2011-08-01

    Full Text Available In past two decades poly lactic-co-glycolic acid (PLGA has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release.

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

    Directory of Open Access Journals (Sweden)

    Lekha Nair K

    2011-08-01

    Full Text Available K Lekha Nair1, Sankar Jagadeeshan2, S Asha Nair2, GS Vinod Kumar11Chemical Biology, Molecular Medicine Division, 2Cancer Research, Rajiv Gandhi Centre for Biotechnology, Poojappura, Thiruvananthapuram, Kerala, IndiaAbstract: Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU-entrapped poly (D, L-lactic-co-glycolic acid (PLGA nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG and breast adenocarcinoma (MCF7 cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate

  8. Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier

    Science.gov (United States)

    Makadia, Hirenkumar K.; Siegel, Steven J.

    2011-01-01

    In past two decades poly lactic-co-glycolic acid (PLGA) has been among the most attractive polymeric candidates used to fabricate devices for drug delivery and tissue engineering applications. PLGA is biocompatible and biodegradable, exhibits a wide range of erosion times, has tunable mechanical properties and most importantly, is a FDA approved polymer. In particular, PLGA has been extensively studied for the development of devices for controlled delivery of small molecule drugs, proteins and other macromolecules in commercial use and in research. This manuscript describes the various fabrication techniques for these devices and the factors affecting their degradation and drug release. PMID:22577513

  9. PLK1shRNA and doxorubicin co-loaded thermosensitive PLGA-PEG-PLGA hydrogels for osteosarcoma treatment.

    Science.gov (United States)

    Ma, Hecheng; He, Chaoliang; Cheng, Yilong; Li, Dongsong; Gong, Yubao; Liu, Jianguo; Tian, Huayu; Chen, Xuesi

    2014-10-01

    Combination cancer therapy has emerged as crucial approach for achieving superior anti-cancer efficacy. In this study, we developed a strategy by localized co-delivery of PLK1shRNA/polylysine-modified polyethylenimine (PEI-Lys) complexes and doxorubicin (DOX) using biodegradable, thermosensitive PLGA-PEG-PLGA hydrogels for treatment of osteosarcoma. When incubated with osteosarcoma Saos-2 and MG-63 cells, the hydrogel containing PLK1shRNA/PEI-Lys and DOX displayed significant synergistic effects in promoting the apoptosis of osteosarcoma cells in vitro. After subcutaneous injection of the hydrogel containing PLK1shRNA/PEI-Lys and DOX beside the tumors of nude mice bearing osteosarcoma Saos-2 xenografts, the hydrogels exhibited superior antitumor efficacy in vivo compared to the hydrogels loaded with PLK1shRNA/PEI-Lys or DOX alone. It is noteworthy that the combination treatment in vivo led to almost complete suppression of tumor growth up to 16 days, significantly enhanced PLK1 silencing, higher apoptosis of tumor masses, as well as increased cell cycle regulation. Additionally, ex vivo histological analysis of major organs of the mice indicated that the localized treatments showed no obvious damage to the organs, suggesting lower systemic toxicity of the treatments. Therefore, the strategy of localized, sustained co-delivery of PLK1shRNA and DOX by using the biodegradable, injectable hydrogel may have potential for efficient clinical treatment of osteosarcoma. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. MONODISPERSED AND NANOSIZED DENDRIMER/POLYSTYRENE LATEX PARTICLES

    Institute of Scientific and Technical Information of China (English)

    Changfeng Yi; Zushun Xu; Warren T. Ford

    2004-01-01

    Emulsion polymerization of styrene was carried out using dendrimer DAB-dendr-(NH2)64 as seed. The size and size distribution of the emulsion particles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and the effects of emulsion polymerization conditions on the preparation of emulsion particle were investigated. It has been found that the nanosized dendrimer/polystyrene polymer emulsion particles obtained were in the range of 26~64 nm in diameter, and were monodisperse; the size and size distribution of emulsion particles were influenced by the contents of dendrimer DAB-dendr-(NH2)64, emulsifier and initiator, as well as the pH value.

  11. Selection of quasi-monodisperse super-micron aerosol particles

    Science.gov (United States)

    Rösch, Michael; Pfeifer, Sascha; Wiedensohler, Alfred; Stratmann, Frank

    2014-05-01

    Size-segregated quasi monodisperse particles are essential for e.g. fundamental research concerning cloud microphysical processes. Commonly a DMA (Differential Mobility Analyzer) is used to produce quasi-monodisperse submicron particles. Thereto first, polydisperse aerosol particles are bipolarly charged by a neutralizer, and then selected according to their electrical mobility with the DMA [Knutson et al. 1975]. Selecting a certain electrical mobility with a DMA results in a particle size distribution, which contains singly charged particles as well as undesired multiply charged larger particles. Often these larger particles need to either be removed from the generated aerosol or their signals have to be corrected for in the data inversion and interpretation process. This problem becomes even more serious when considering super-micron particles. Here we will present two different techniques for generating quasi-monodisperse super-micron aerosol particles with no or only an insignificant number of larger sized particles being present. First, we use a combination of a cyclone with adjustable aerodynamic cut-off diameter and our custom-built Maxi-DMA [Raddatz et al. 2013]. The cyclone removes particles larger than the desired ones prior to mobility selection with the DMA. This results in a reduction of the number of multiply charged particles of up to 99.8%. Second, we utilize a new combination of cyclone and PCVI (Pumped Counterflow Virtual Impactor), which is based on purely inertial separation and avoids particle charging. The PCVI instrument was previously described by Boulter et al. (2006) and Kulkarni et al. (2011). With our two setups we are able to produce quasi-monodisperse aerosol particles in the diameter range from 0.5 to 4.4 µm without a significant number of larger undesired particles being present. Acknowledgements: This work was done within the framework of the DFG funded Ice Nucleation research UnIT (INUIT, FOR 1525) under WE 4722/1-1. References

  12. Monodisperse Clusters in Charged Attractive Colloids: Linear Renormalization of Repulsion.

    Science.gov (United States)

    Růžička, Štěpán; Allen, Michael P

    2015-08-11

    Experiments done on polydisperse particles of cadmium selenide have recently shown that the particles form spherical isolated clusters with low polydispersity of cluster size. The computer simulation model of Xia et al. ( Nat. Nanotechnol. 2011 , 6 , 580 ) explaining this behavior used a short-range van der Waals attraction combined with a variable long-range screened electrostatic repulsion, depending linearly on the volume of the clusters. In this work, we term this dependence "linear renormalization" of the repulsive term, and we use advanced Monte Carlo simulations to investigate the kinetically slowed down phase separation in a similar but simpler model. We show that amorphous drops do not dissolve and crystallinity evolves very slowly under linear renormalization, and we confirm that low polydispersity of cluster size can also be achieved using this model. The results indicate that the linear renormalization generally leads to monodisperse clusters.

  13. Solvent: A Key in Digestive Ripening for Monodisperse Au Nanoparticles

    Science.gov (United States)

    Wang, Peng; Qi, Xuan; Zhang, Xuemin; Wang, Tieqiang; Li, Yunong; Zhang, Kai; Zhao, Shuang; Zhou, Jun; Fu, Yu

    2017-01-01

    This work has mainly investigated the influence of the solvent on the nanoparticles distribution in digestive ripening. The experiments suggested that the solvents played a key role in digestive ripening of Au nanoparticles (Au NPs). For the benzol solvents, the resulting size distribution of Au NPs was inversely related to the solvent polarity. It may be interpreted by the low Gibbs free energy of nanoparticles in the high polarity medium, which was supposedly in favor of reducing the nanoparticles distribution. Through digestive ripening in the highly polar benzol solvent of p-chlorotoluene, monodisperse Au NPs with relative standard deviation (RSD) of 4.8% were achieved. This indicated that digestive ripening was an effective and practical way to prepare high-quality nanoparticles, which holds great promise for the nanoscience and nanotechnology.

  14. Structure and Hydration of Highly Branched, Monodisperse Phytoglycogen Nanoparticles

    Science.gov (United States)

    Atkinson, John; Nickels, Jonathan; Stanley, Christopher; Diallo, Souleymane; Katsaras, John; Dutcher, John

    Monodisperse phytoglycogen nanoparticles are a promising, new soft colloidal nanomaterial with many applications in the personal care, food, nutraceutical and pharmaceutical industries. These applications rely on exceptional properties that emerge from the highly branched structure of phytoglycogen and its interaction with water, such as extraordinarily high water retention, and low viscosity and exceptional stability in water. The structure and hydration of the nanoparticles was characterized using small angle neutron scattering (SANS) and quasielastic neutron scattering (QENS). SANS allowed us to determine the size of the nanoparticles, evaluate their radial density profile, quantify the particle-to-particle spacing, and determine their water content. The results show clearly that the nanoparticles are highly hydrated, with each nanoparticle containing 250% of its mass in water, and that aqueous dispersions approach a jamming transition at ~ 25% (w/w). QENS experiments provided an independent and consistent measure of the high level of hydration of the particles.

  15. In vitro drug release behavior, mechanism and antimicrobial activity of rifampicin loaded low molecular weight PLGA-PEG-PLGA triblock copolymeric nanospheres.

    Science.gov (United States)

    Gajendiran, M; Divakar, S; Raaman, N; Balasubramanian, S

    2013-12-01

    Poly (lactic-co-glycolic acid) (PLGA (92:8)) and a series of PLGA-PEG-PLGA tri block copolymers were synthesized by direct melt polycondensation. The copolymers were characterized by FTIR, and 1HNMR spectroscopic techniques, viscosity, gel permeation chromatography (GPC) and powder x-ray diffraction (XRD). The rifampicin (RIF) loaded polymeric nanospheres (NPs) were prepared by ultrasonication-W/O emulsification technique. The NPs have been characterized by field emission scanning electron microscopy (FESEM), TEM, powder X-ray diffraction (XRD), UVvisible spectroscopy and DLS measurements. The drug loaded triblock copolymeric NPs have five folds higher drug content and drug loading efficiency than that of PLGA microspheres (MPs). The in vitro drug release study shows that the drug loaded NPs showed an initial burst release after that sustained release up to 72 h. All the triblock copolymeric NPs follow anomalous drug diffusion mechanism while the PLGA MPs follow non-Fickian super case-II mechanism up to 12 h. The overall in-vitro release follows second order polynomial kinetics up to 72 h. The antimicrobial activity of the RIF loaded polymer NPs was compared with that of pure RIF and tetracycline (TA). The RIF loaded triblock copolymeric NPs inhibited the bacterial growth more effectively than the pure RIF and TA.

  16. Curcumin loaded PLGA-poloxamer blend nanoparticles induce cell cycle arrest in mesothelioma cells.

    Science.gov (United States)

    Mayol, Laura; Serri, Carla; Menale, Ciro; Crispi, Stefania; Piccolo, Maria Teresa; Mita, Luigi; Giarra, Simona; Forte, Maurizio; Saija, Antonina; Biondi, Marco; Mita, Damiano Gustavo

    2015-06-01

    The pharmacological potential of curcumin (CURC) is severely restricted because of its low water solubility/absorption, short half-life and poor bioavailability. To overcome these issues, CURC-loaded nanoparticles (NPs) were produced by a double emulsion technique. In particular, NPs were made up of an amphiphilic blend of poloxamers and PLGA to confer stealth properties to the NPs to take advantage of the enhanced permeability and retention (EPR) effect. Different surface properties of NPs made up of bare PLGA and PLGA/poloxamer blend were confirmed by the different interactions of these NPs with serum proteins and also by their ability to be internalized by mesothelioma cell line. The uptake of PLGA/poloxamer NPs induces a persistent block in G0/G1 phase of the cell cycle up to 72 h, thus overcoming the drug tolerance phenomenon, normally evidenced with free CURC.

  17. Curdlan-conjugated PLGA nanoparticles possess macrophage stimulant activity and drug delivery capabilities

    CSIR Research Space (South Africa)

    Tukulula, M

    2015-02-01

    Full Text Available There is significant interest in the application of nanoparticles to deliver immunostimulatory signals to cells. We hypothesized that curdlan (immune stimulating polymer) could be conjugated to PLGA and nanoparticles from this copolymer would...

  18. In-vitro anticancer and antimicrobial activities of PLGA/silver nanofiber composites prepared by electrospinning.

    Science.gov (United States)

    Almajhdi, Fahad N; Fouad, H; Khalil, Khalil Abdelrazek; Awad, Hanem M; Mohamed, Sahar H S; Elsarnagawy, T; Albarrag, Ahmed M; Al-Jassir, Fawzi F; Abdo, Hany S

    2014-04-01

    In the present work, a series of 0, 1 and 7 wt% silver nano-particles (Ag NPs) incorporated poly lactic-co-glycolic acid (PLGA) nano-fibers were synthesized by the electrospinning process. The PLGA/Ag nano-fibers sheets were characterized using SEM, TEM and DSC analyses. The three synthesized PLGA/silver nano-fiber composites were screened for anticancer activity against liver cancer cell line using MTT and LDH assays. The anticancer activity of PLGA nano-fibers showed a remarkable improvement due to increasing the concentration of the Ag NPs. In addition to the given result, PLGA nano-fibers did not show any cytotoxic effect. However, PLGA nano-fibers that contain 1 % nano silver showed anticancer activity of 8.8 %, through increasing the concentration of the nano silver to 7 % onto PLGA nano-fibers, the anticancer activity was enhanced to a 67.6 %. Furthermore, the antibacterial activities of these three nano-fibers, against the five bacteria strains namely; E.coli o157:H7 ATCC 51659, Staphylococcus aureus ATCC 13565, Bacillus cereus EMCC 1080, Listeria monocytogenes EMCC 1875 and Salmonella typhimurium ATCC25566 using the disc diffusion method, were evaluated. Sample with an enhanced inhibitory effect was PLGA/Ag NPs (7 %) which inhibited all strains (inhibition zone diameter 10 mm); PLGA/Ag NPs (1 %) sample inhibited only one strain (B. cereus) with zone diameter 8 mm. The PLGA nano-fiber sample has not shown any antimicrobial activity. Based on the anticancer as well as the antimicrobial results in this study, it can be postulated that: PLGA nanofibers containing 7 % nano silver are suitable as anticancer- and antibiotic-drug delivery systems, as they will increase the anticancer as well as the antibiotic drug potency without cytotoxicity effect on the normal cells. These findings also suggest that Ag NPs, of the size (5-10 nm) evaluated in the present study, are appropriate for therapeutic application from a safety standpoint.

  19. Mannan-Modified PLGA Nanoparticles for Targeted Gene Delivery

    Directory of Open Access Journals (Sweden)

    Fansheng Kong

    2012-01-01

    Full Text Available The studies of targeted gene delivery nanocarriers have gained increasing attention during the past decades. In this study, mannan modified DNA loaded bioadhesive PLGA nanoparticles (MAN-DNA-NPs were investigated for targeted gene delivery to the Kupffer cells (KCs. Bioadhesive PLGA nanoparticles were prepared and subsequently bound with pEGFP. Following the coupling of the mannan-based PE-grafted ligands (MAN-PE with the DNA-NPs, the MAN-DNA-NPs were delivered intravenously to rats. The transfection efficiency was determined from the isolated KCs and flow cytometry was applied for the quantitation of gene expression after 48 h post transfection. The size of the MAN-DNA-NPs was found to be around 190 nm and the Zeta potential was determined to be −15.46mV. The pEGFP binding capacity of MAN-DNA-NPs was (88.9±5.8% and the in vitro release profiles of the MAN-DNA-NPs follow the Higuchi model. When compared with non-modified DNA-NPs and Lipofectamine 2000-DNA, MAN-DNA-NPs produced the highest gene expressions, especially in vivo. The in vivo data from flow cytometry analysis showed that MAN-DNA-NPs displayed a remarkably higher transfection efficiency (39% than non-modified DNA-NPs (25% and Lipofectamine 2000-DNA (23% in KCs. The results illustrate that MAN-DNA-NPs have the ability to target liver KCs and could function as promising active targeting drug delivery vectors.

  20. Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis.

    Science.gov (United States)

    Arias, José L; Unciti-Broceta, Juan D; Maceira, José; Del Castillo, Teresa; Hernández-Quero, José; Magez, Stefan; Soriano, Miguel; García-Salcedo, José A

    2015-01-10

    Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D,L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogen Trypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug for T. b. gambiense acute infection. An in vitro effectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore, in vivo therapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases.

  1. Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers.

    Directory of Open Access Journals (Sweden)

    Stefanie Wohlfart

    Full Text Available BACKGROUND: Chemotherapy of glioblastoma is largely ineffective as the blood-brain barrier (BBB prevents entry of most anticancer agents into the brain. For an efficient treatment of glioblastomas it is necessary to deliver anti-cancer drugs across the intact BBB. Poly(lactic-co-glycolic acid (PLGA nanoparticles coated with poloxamer 188 hold great promise as drug carriers for brain delivery after their intravenous injection. In the present study the anti-tumour efficacy of the surfactant-coated doxorubicin-loaded PLGA nanoparticles against rat glioblastoma 101/8 was investigated using histological and immunohistochemical methods. METHODOLOGY: The particles were prepared by a high-pressure solvent evaporation technique using 1% polyvinylalcohol (PLGA/PVA or human serum albumin (PLGA/HSA as stabilizers. Additionally, lecithin-containing PLGA/HSA particles (Dox-Lecithin-PLGA/HSA were prepared. For evaluation of the antitumour efficacy the glioblastoma-bearing rats were treated intravenously with the doxorubicin-loaded nanoparticles coated with poloxamer 188 using the following treatment regimen: 3 × 2.5 mg/kg on day 2, 5 and 8 after tumour implantation; doxorubicin and poloxamer 188 solutions were used as controls. On day 18, the rats were sacrificed and the antitumour effect was determined by measurement of tumour size, necrotic areas, proliferation index, and expression of GFAP and VEGF as well as Isolectin B4, a marker for the vessel density. CONCLUSION: The results reveal a considerable anti-tumour effect of the doxorubicin-loaded nanoparticles. The overall best results were observed for Dox-Lecithin-PLGA/HSA. These data demonstrate that the poloxamer 188-coated PLGA nanoparticles enable delivery of doxorubicin across the blood-brain barrier in the therapeutically effective concentrations.

  2. Biofabrication of a PLGA-TCP-based porous bioactive bone substitute with sustained release of icaritin.

    Science.gov (United States)

    Xie, Xin-Hui; Wang, Xin-Luan; Zhang, Ge; He, Yi-Xin; Leng, Yang; Tang, Ting-Ting; Pan, Xiaohua; Qin, Ling

    2015-08-01

    A phytomolecule, icaritin, has been identified and shown to be osteopromotive for the prevention of osteoporosis and osteonecrosis. This study aimed to produce a bioactive poly (l-lactide-co-glycolide)-tricalcium phosphate (PLGA-TCP)-based porous scaffold incorporating the osteopromotive phytomolecule icaritin, using a fine spinning technology. Both the structure and the composition of icaritin-releasing PLGA-TCP-based scaffolds were evaluated by scanning electron microscopy (SEM). The porosity was quantified by both water absorption and micro-computed tomography (micro-CT). The mechanical properties were evaluated using a compression test. In vitro release of icaritin from the PLGA-TCP scaffold was quantified by high-performance liquid chromatography (HPLC). The attachment, proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the composite scaffold were evaluated. Both an in vitro cytotoxicity test and an in vivo test via muscular implantation were conducted to confirm the scaffold's biocompatibility. The results showed that the PLGA-TCP-icaritin composite scaffold was porous, with interconnected macro- (about 480 µm) and micropores (2-15 µm). The mechanical properties of the PLGA-TCP-icaritin scaffold were comparable with those of the pure PLGA-TCP scaffold, yet was spinning direction-dependent. Icaritin content was detected in the medium and increased with time. The PLGA-TCP-icaritin scaffold facilitated the attachment, proliferation and osteogenic differentiation of BMSCs. In vitro cytotoxicity test and in vivo intramuscular implantation showed that the composite scaffold had no toxicity with good biocompatibility. In conclusion, an osteopromotive phytomolecule, icaritin, was successfully incorporated into PLGA-TCP to form an innovative porous composite scaffold with sustained release of osteopromotive icaritin, and this scaffold had good biocompatibility and osteopromotion, suggesting its potential for orthopaedic

  3. Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior

    Science.gov (United States)

    Yao, Shenglian; Liu, Huiying; Yu, Shukui; Li, Yuanyuan; Wang, Xiumei; Wang, Luning

    2016-01-01

    The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system. In this study, two kind of aqueous model drugs with different molecule weight, Congo red and albumin from bovine serum (BSA) were nano-encapsulated in poly (dl-lactic-co-glycolic acid) (PLGA) microspheres by emulsion electrospray. In the preparation process, the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution. The emulsion was then electrosprayed to fabricate drug-nanoencapsulated PLGA microspheres. The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase (Vw/Vo) and the molecule weight of model drugs. Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to Vw/Vo. With the increase of the volume ratio of aqueous drug phase, the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate. Moreover, BSA showed a slower release rate from PLGA microspheres comparing to Congo red, which indicated the drug release rate could be affected by not only Vw/Vo but also the molecule weight of model drug. In brief, the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple system to achieve controlled drug release at a desired rate satisfying the need of the practices. PMID:27699061

  4. Optimization of PLGA nanoparticles formulation containing L-DOPA by applying the central composite design.

    Science.gov (United States)

    Zhou, Yong Zhi; Alany, Raid G; Chuang, Victor; Wen, Jingyuan

    2013-02-01

    The aim of this work was to prepare L-DOPA loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles by a modified water-in-oil-in-water (W(1)/O/W(2)) emulsification solvent evaporation method. A central composite design was applied for optimization of the formulation parameters and for studying the effects of three independent variables: PLGA concentration, polyvinyl alcohol (PVA) concentration and organic solvent removal rate on the particle size and the entrapment efficiency (response variables). Second-order models were obtained to adequately describe the influence of the independent variables on the selected responses. The analysis of variance showed that the three independent variables had significant effects (p overlay contour plots, the optimal preparation area can be highlighted. It was found that the optimum values of the responses could be obtained at higher concentration of PLGA (5%, w/v) and PVA (6%, w/v); and faster organic solvent removal rate (700 rpm). The corresponding particle size was 256.2 nm and the entrapment efficiency was 62.19%. FTIR investigation confirmed that the L-DOPA and PLGA polymer maintained its backbone structure in the fabrication of nanoparticles. The scanning electron microscopic images of nanoparticles showed that all particles had spherical shape with porous outer skin. The results suggested that PLGA nanoparticles might represent a promising formulation for brain delivery of L-DOPA. The preparation of L-DOPA loaded PLGA nanoparticles can be optimized by the central composite design.

  5. pH-Responsive PLGA Nanoparticle for Controlled Payload Delivery of Diclofenac Sodium.

    Science.gov (United States)

    Khanal, Shalil; Adhikari, Udhab; Rijal, Nava P; Bhattarai, Shanta R; Sankar, Jagannathan; Bhattarai, Narayan

    2016-08-02

    Poly(lactic-co-glycolic acid) (PLGA) based nanoparticles have gained increasing attention in delivery applications due to their capability for controlled drug release characteristics, biocompatibility, and tunable mechanical, as well as degradation, properties. However, thorough study is always required while evaluating potential toxicity of the particles from dose dumping, inconsistent release and drug-polymer interactions. In this research, we developed PLGA nanoparticles modified by chitosan (CS), a cationic and pH responsive polysaccharide that bears repetitive amine groups in its backbone. We used a model drug, diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug (NSAID), to study the drug loading and release characteristics. PLGA nanoparticles were synthesized by double-emulsion solvent evaporation technique. The nanoparticles were evaluated based on their particle size, surface charge, entrapment efficacy, and effect of pH in drug release profile. About 390-420 nm of average diameters and uniform morphology of the particles were confirmed by scanning electron microscope (SEM) imaging and dynamic light scattering (DLS) measurement. Chitosan coating over PLGA surface was confirmed by FTIR and DLS. Drug entrapment efficacy was up to 52%. Chitosan coated PLGA showed a pH responsive drug release in in vitro. The release was about 45% more at pH 5.5 than at pH 7.4. The results of our study indicated the development of chitosan coating over PLGA nanoparticle for pH dependent controlled release DS drug for therapeutic applications.

  6. pH-Responsive PLGA Nanoparticle for Controlled Payload Delivery of Diclofenac Sodium

    Directory of Open Access Journals (Sweden)

    Shalil Khanal

    2016-08-01

    Full Text Available Poly(lactic-co-glycolic acid (PLGA based nanoparticles have gained increasing attention in delivery applications due to their capability for controlled drug release characteristics, biocompatibility, and tunable mechanical, as well as degradation, properties. However, thorough study is always required while evaluating potential toxicity of the particles from dose dumping, inconsistent release and drug-polymer interactions. In this research, we developed PLGA nanoparticles modified by chitosan (CS, a cationic and pH responsive polysaccharide that bears repetitive amine groups in its backbone. We used a model drug, diclofenac sodium (DS, a nonsteroidal anti-inflammatory drug (NSAID, to study the drug loading and release characteristics. PLGA nanoparticles were synthesized by double-emulsion solvent evaporation technique. The nanoparticles were evaluated based on their particle size, surface charge, entrapment efficacy, and effect of pH in drug release profile. About 390–420 nm of average diameters and uniform morphology of the particles were confirmed by scanning electron microscope (SEM imaging and dynamic light scattering (DLS measurement. Chitosan coating over PLGA surface was confirmed by FTIR and DLS. Drug entrapment efficacy was up to 52%. Chitosan coated PLGA showed a pH responsive drug release in in vitro. The release was about 45% more at pH 5.5 than at pH 7.4. The results of our study indicated the development of chitosan coating over PLGA nanoparticle for pH dependent controlled release DS drug for therapeutic applications.

  7. Development of VEGF-loaded PLGA matrices in association with mesenchymal stem cells for tissue engineering.

    Science.gov (United States)

    Rosa, A R; Steffens, D; Santi, B; Quintiliano, K; Steffen, N; Pilger, D A; Pranke, P

    2017-08-07

    The association of bioactive molecules, such as vascular endothelial growth factor (VEGF), with nanofibers facilitates their controlled release, which could contribute to cellular migration and differentiation in tissue regeneration. In this research, the influence of their incorporation on a polylactic-co-glycolic acid (PLGA) scaffold produced by electrospinning on cell adhesion and viability and cytotoxicity was carried out in three groups: 1) PLGA/BSA/VEGF; 2) PLGA/BSA, and 3) PLGA. Morphology, fiber diameter, contact angle, loading efficiency and controlled release of VEGF of the biomaterials, among others, were measured. The nanofibers showed smooth surfaces without beads and with interconnected pores. PLGA/BSA/VEGF showed the smallest water contact angle and VEGF released for up to 160 h. An improvement in cell adhesion was observed for the PLGA/BSA/VEGF scaffolds compared to the other groups and the scaffolds were non-toxic for the cells. Therefore, the scaffolds were shown to be a good strategy for sustained delivery of VEGF and may be a useful tool for tissue engineering.

  8. Development of VEGF-loaded PLGA matrices in association with mesenchymal stem cells for tissue engineering

    Directory of Open Access Journals (Sweden)

    A.R. Rosa

    Full Text Available The association of bioactive molecules, such as vascular endothelial growth factor (VEGF, with nanofibers facilitates their controlled release, which could contribute to cellular migration and differentiation in tissue regeneration. In this research, the influence of their incorporation on a polylactic-co-glycolic acid (PLGA scaffold produced by electrospinning on cell adhesion and viability and cytotoxicity was carried out in three groups: 1 PLGA/BSA/VEGF; 2 PLGA/BSA, and 3 PLGA. Morphology, fiber diameter, contact angle, loading efficiency and controlled release of VEGF of the biomaterials, among others, were measured. The nanofibers showed smooth surfaces without beads and with interconnected pores. PLGA/BSA/VEGF showed the smallest water contact angle and VEGF released for up to 160 h. An improvement in cell adhesion was observed for the PLGA/BSA/VEGF scaffolds compared to the other groups and the scaffolds were non-toxic for the cells. Therefore, the scaffolds were shown to be a good strategy for sustained delivery of VEGF and may be a useful tool for tissue engineering.

  9. The fabrication of PLGA microvessel scaffolds with nano-patterned inner walls.

    Science.gov (United States)

    Wang, Gou-Jen; Lin, Yan-Cheng; Hsu, Shan-Hui

    2010-10-01

    Poly (lactic-co-glycolic acid) (PLGA) is one of the most commonly used biodegradable, biocompatible materials. Nanostructured PLGA has immense potential for application in tissue engineering. In this article we discuss a novel approach for the fabrication of PLGA microvessel scaffolds with nanostructured inner walls. In this novel nano-patterning approach, the thermal reflow technique is first adapted to fabricate a semi-cylindrical photoresist master mold. A thin film of titanium and a thin film of aluminum are sputtered in sequence on the semi-cylindrical microvessel network. Aluminum foil anodization is then executed to transform the aluminum thin film into a porous anodic aluminum oxide (AAO) film. During the casting process a PLGA solution is cast on the AAO film to build up semi-cylindrical PLGA microstructures with nanostructured inner walls after which inductive coupled plasma (ICP) is implemented to assist bonding of the two PLGA structures. The result is the building of a network of microchannels with nano-patterned inner walls. Bovine endothelial cells (BECs) are carefully cultured in the scaffold via semi-dynamic seeding for 7 days. Observations show that the BECs grew more separately in a nano-patterned microvessel scaffold than they did in a smooth surface scaffold.

  10. Current strategies in modification of PLGA-based gene delivery system.

    Science.gov (United States)

    Ramezani, Mohammad; Ebrahimian, Mahboubeh; Hashemi, Maryam

    2016-12-05

    The successful gene therapy has been limited by safe and efficient delivery of nucleic acid to the target cells. Poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) are able to deliver drugs and gene efficiently. This formulation has several advantages in comparison with other formulations including improvement of solubility, stability, controlling of degradation and release of the entrapped agents. For application of PLGA as gene carrier, there exist many challenges. PLGA nanoparticles could protect the encapsulated DNA from in vivo degradation but the DNA release is slowl and their negative charge acts as a barrier to DNA incorporation and delivery. Also, during the preparation process, DNA could be exposed to high shear stress and organic solvents which could result in its inactivation. Moreover, PLGA NPs could be modified with different agents to reduce its cytotoxicity, to enhance the delivery efficiency and to target it to specific tissues/cells. This review summarizes different methods used for the preparation of PLGA NPs as gene carriers and recent strategies for modification of PLGA particles applied in gene therapy.

  11. Mapping force of interaction between PLGA nanoparticle with cell membrane using optical tweezers

    Science.gov (United States)

    Chhajed, Suyash; Gu, Ling; Homayoni, Homa; Nguyen, Kytai; Mohanty, Samarendra

    2011-03-01

    Drug delivery using magnetic (Fe 3 O4) Poly Lactic-co-Glycolic Acid (PLGA) nanoparticles is finding increasing usage in therapeutic applications due to its biodegradability, biocompatibility and targeted localization. Since optical tweezers allow non-contact, highly sensitive force measurement, we utilized optical tweezers for studying interaction forces between the Fe 3 O4 -PLGA nanoparticles with prostate cancer PC3 cells. Presence of Fe 3 O4 within the PLGA shell allowed efficient trapping of these nanoparticles in near-IR optical tweezers. The conglomerated PLGA nanoparticles could be dispersed by use of the optical tweezers. Calibration of trapping stiffness as a function of laser beam power was carried out using equipartition theorem method, where the mean square displacement was measured with high precision using time-lapse fluorescence imaging of the nanoparticles. After the trapped PLGA nanoparticle was brought in close vicinity of the PC3 cell membrane, displacement of the nanoparticle from trap center was measured as a function of time. In short time scale (30 sec) , whiletheforceofinteractionwaswithin 0.2 pN , theforceincreasedbeyond 1 pNatlongertimescales (~ 10 min). We will present the results of the time-varying force of interactions between PLGA nanoparticles with PC3 cells using optical tweezers.

  12. Morphological Effects of HA on the Cell Compatibility of Electrospun HA/PLGA Composite Nanofiber Scaffolds

    Directory of Open Access Journals (Sweden)

    Adnan Haider

    2014-01-01

    Full Text Available Tissue engineering is faced with an uphill challenge to design a platform with appropriate topography and suitable surface chemistry, which could encourage desired cellular activities and guide bone tissue regeneration. To develop such scaffolds, composite nanofiber scaffolds of nHA and sHA with PLGA were fabricated using electrospinning technique. nHA was synthesized using precipitation method, whereas sHA was purchased. The nHA and sHA were suspended in PLGA solution separately and electrospun at optimized electrospinning parameters. The composite nanofiber scaffolds were characterized by FE-SEM, EDX analysis, TEM, XRD analysis, FTIR, and X-ray photoelectron. The potential of the HA/PLGA composite nanofiber as bone scaffolds in terms of their bioactivity and biocompatibility was assessed by culturing the osteoblastic cells onto the composite nanofiber scaffolds. The results from in vitro studies revealed that the nHA/PLGA composite nanofiber scaffolds showed higher cellular adhesion, proliferation, and enhanced osteogenesis performance, along with increased Ca+2 ions release compared to the sHA/PLGA composite nanofiber scaffolds and pristine PLGA nanofiber scaffold. The results show that the structural dependent property of HA might affect its potential as bone scaffold and implantable materials in regenerative medicine and clinical tissue engineering.

  13. Monodispersed Zinc Oxide Nanoparticle-Dye Dyads and Triads

    Energy Technology Data Exchange (ETDEWEB)

    Gladfelter, Wayne L. [Univ. of Minnesota, Minneapolis, MN (United States); Blank, David A. [Univ. of Minnesota, Minneapolis, MN (United States); Mann, Kent R. [Univ. of Minnesota, Minneapolis, MN (United States)

    2017-06-22

    events at a fundamental level. This was combined with the synthesis of a broad range of sensitizers that provide systematic variation of the energetics, excited state dynamics, structure and interfacial bonding. The key is that the monodisperse nature and high dispersibility of the ZnO NCs made these experiments reproducible; in essence, the measurements were on discrete molecular species rather than on the complicated mixtures that resulted from the typical fabrication of functional photovoltaic cells. The monodispersed nature of the NCs also allowed the use of quantum confinement to investigate the role of donor/acceptor energetic alignment in chemically identical systems. The results added significantly to our basic understanding of energy and charge transfer events at molecule-semiconductor interfaces and will help the R&D community realize zinc oxide's full potential in solar cell applications.

  14. Immunization against leishmaniasis by PLGA nanospheres encapsulated with autoclaved Leishmania major (ALM) and CpG-ODN.

    Science.gov (United States)

    Tafaghodi, Mohsen; Khamesipour, Ali; Jaafari, Mahmoud R

    2011-05-01

    Various adjuvants and delivery systems have been evaluated for increasing the protective immune responses against leishmaniasis and mostly have been shown not to be effective enough. In this study, poly(D,L-lactide-co-glycolide) (PLGA) nanospheres as an antigen delivery system and CpG-ODN as an immunoadjuvant have been used for the first time to enhance the immune response against autoclaved Leishmania major (ALM). PLGA nanospheres were prepared by a double-emulsion (W/O/W) technique. Particulate characteristics were studied by scanning electron microscopy and particle size analysis. Mean diameter of ALM + CpG-ODN-loaded nanospheres was 300 ± 128 nm. BALB/c mice were immunized three times in 3-week intervals using ALM plus CpG-ODN-loaded nanospheres [(ALM + CpG-ODN)(PLGA)], ALM encapsulated PLGA nanospheres [(ALM)(PLGA)], (ALM)(PLGA) + CpG, ALM + CpG, ALM alone, or phosphate buffer solution (PBS). The intensity of infection induced by L. major challenge was assessed by measuring size of footpad swelling. The strongest protection, showed by significantly (P<0.05) smaller footpad, was observed in mice immunized with (ALM + CpG-ODN)(PLGA). The (ALM)(PLGA), (ALM)(PLGA) + CpG, and ALM + CpG were also showed a significantly (P<0.05) smaller footpad swelling compared to the groups received either PBS or ALM alone. The mice immunized with (ALM + CpG-ODN)(PLGA), (ALM)(PLGA) + CpG, and ALM + CpG showed the highest IgG2a/IgG1 ratio, interferon-γ production, and lowest interleukin-4 production compared to the other groups. It is concluded that when both PLGA nanospheres and CpG-ODN adjuvants were used simultaneously, it induce stronger immune response and enhance protection rate against Leishmania infection.

  15. Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties.

    Science.gov (United States)

    Shi, Meng; Yang, Yi-Yan; Chaw, Cheng-Shu; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

    2003-04-29

    The poly(orthoester) (POE)-poly(D,L-lactide-co-glycolide) (50:50) (PLGA) double-walled microspheres with 50% POE in weight were loaded with hydrophilic bovine serum albumin (BSA) and hydrophobic cyclosporin A (CyA). Most of the BSA and CyA was entrapped within the shell and core, respectively, because of the difference in their hydrophilicity. The morphologies and release mechanisms of proteins-loaded double-walled POE/PLGA microspheres were investigated. Scanning electron microscope studies revealed that the CyA-BSA-loaded double-walled POE/PLGA microspheres yielded a more porous surface and PLGA shell than those without BSA. The neat POE and PLGA yielded slow and incomplete CyA and BSA release. In contrast, nearly complete BSA and more than 95% CyA were released in a sustained manner from the double-walled POE/PLGA microspheres. Both the BSA- and CyA-BSA-loaded POE/PLGA microspheres yielded a sustained BSA release over 5 days. The CyA release pattern of the CyA-loaded double-walled POE/PLGA microspheres was biphasic, characterized by a slow release over 15 days followed by a sustained release over 27 days. However, the CyA-BSA-loaded double-walled POE/PLGA microspheres provided a more constant and faster CyA release due to their more porous shell. In the CyA-BSA-loaded double-walled POE/PLGA microspheres system, the PLGA layer acted as a carrier for BSA and mild reservoir for CyA. During the first 5 days, most BSA was released from the shell but only 14% CyA was left from the microspheres. Subsequently, more than 80% CyA were released in the next 25 days. The distinct structure of double-walled POE/PLGA microspheres would make an interesting device for controlled delivery of therapeutic agents.

  16. Efficient thermolysis route to monodisperse Cu₂ZnSnS₄ nanocrystals with controlled shape and structure

    National Research Council Canada - National Science Library

    Zhang, Xiaoyan; Guo, Guobiao; Ji, Cheng; Huang, Kai; Zha, Chenyang; Wang, Yifeng; Shen, Liming; Gupta, Arunava; Bao, Ningzhong

    2014-01-01

    Monodisperse Cu2ZnSnS4 (CZTS) nanocrystals with tunable shape, crystalline phase, and composition are synthesized by efficient thermolysis of a single source precursor of mixed metal-oleate complexes in hot organic solvents...

  17. Cr/alpha-Cr2O3 monodispersed spherical core-shell particles based solar absorbers

    CSIR Research Space (South Africa)

    Khamlich, S

    2011-07-01

    Full Text Available Monodispersed spherical core-shell particles of Cr/alpha-Cr2O3 cermet ACG coatings investigated within this contribution could be successfully employed in thermal converters. Their selectivity depends on their chemical, physical and structural...

  18. 新型聚乳酸复合支架材料在组织工程骨构建中的实验研究%The Experimental Study of Modified Polylactic Acid Scaffoldings in Preparation of Tissue-Engineered Bone

    Institute of Scientific and Technical Information of China (English)

    王淑红; 潘可风

    2005-01-01

    目的:探索新型聚乳酸复合支架材料对兔骨髓基质细胞(bone marrow stromal cells,BMSC)生物学行为的影响及组织工程骨的构建方法.方法:实验组选择兔骨MSC诱导生成成骨细胞,接种于改良型聚乳酸复合新材料,包括新型聚乳酸(polylactic acid,PLA)、聚乳酸-乙醇酸共聚物(polylactide-co-glycolide,PLGA)、聚乳酸-乙二醇共聚物(polylactic acid-polyethylene glycol block copolymers,PLA-PEG)复合制作的三维支架中培养,用无机材料磷酸三钙(tricalcium phosphate,TCP)作为对照组,观察种子细胞在支架材料上的吸附迁移、生长增殖情况.结果:成骨细胞在新型三维支架材料表面分布较为均匀,生物学行为活跃.结论:可以通过MSC诱导获得成骨细胞.PLA、PLGA、PLA-PEG、TCP具有良好的生物相容性,可作为支架材料与成骨细胞共同培养,获得具有成骨能力的三维立体结构组织工程骨.

  19. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-01

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity.

  20. Aspects of Microparticle Utilization for Potentiation of Novel Vaccines: Promises and Risks

    Science.gov (United States)

    Ilyinskii, P.

    Many recombinant vaccines against novel (HIV, HCV) or ever-changing (influenza) infectious agents require the presence of adjuvants/delivery vehicles to induce strong immune responses. The necessity of their improvement led to the major effort towards development of vaccine delivery systems that are generally particulate (e.g., nano- and microparticles) and have comparable dimensions to the pathogens (viruses or bacteria). The mode of action of these adjuvants is not fully understood but implies the stimulation of the innate or antigen-specific immune responses, and/or the increase of antigen uptake or processing by antigen-presenting cells (APC). Moreover, enhancement of adjuvant activity through the use of micro- and nanoparticulate delivery systems often resulted from the synergistic effects producing immune responses stronger than those elicited by the adjuvant or delivery system alone. Among particulate adjuvants, biodegradable micro- and nanoparticles of poly(D,L-lactide-co-glycoside) (PLGA) or poly(D,L-lactide) (PLA) have been reported to enhance both humoral and cellular immune responses against an encapsulated protein antigen. Cationic and anionic polylactide co-glycolide (PLG) microparticles have been successfully used to adsorb a variety of agents, which include plasmid DNA, recombinant proteins and adjuvant active oligonucleotides and are also currently tested in several vaccine applications. Another approach envisions specific targeting of APC, especially peripheral DC and exploitation of particulate systems that are small enough for lymphatic uptake (polystyrene nanobeads). Micro- and nanoparticles offer the possibility of enhancement of their uptake by appropriate cells through manipulation of their surface properties. Still, questions regarding toxicity and molecular interaction between micro- and nano-particles and immune cells, tissues and whole organisms remain to be addressed. These risks and other possible side effects should be assessed in

  1. Facile and Scalable Synthesis of Monodispersed Spherical Capsules with a Mesoporous Shell

    KAUST Repository

    Qi, Genggeng

    2010-05-11

    Monodispersed HMSs with tunable particle size and shell thickness were successfully synthesized using relatively concentrated polystyrene latex templates and a silica precursor in a weakly basic ethanol/water mixture. The particle size of the capsules can vary from 100 nm to micrometers. These highly engineered monodispersed capsules synthesized by a facile and scalable process may find applications in drug delivery, catalysis, separationm or as biological and chemical microreactors. © 2010 American Chemical Society.

  2. Preparation of Monodisperse Nanoparticle of Layered Double Hydroxides and Polyoxyethylene Sulfate

    Institute of Scientific and Technical Information of China (English)

    XU Huizhong; QIN Lianjie; ZHANG Hong; YANG Qinzheng; YANG Jing

    2005-01-01

    In order to obtain the bio-molecule/ LDHs nanocomposites having regular crystal structure,three nanocomposites of layered double hydroxides and polyoxyethylene sulfates were prepared by ion-exchange method. TEM analysis reveals that the monodisperse rigid .sphere of approximately 200 nm in diameter could be gotten when the intergallery anion was PEGS-400. Such monodisperse nanoparticle could be used as a promising precursor for preparing bio-molecule/LDHs nanocomposites.

  3. In vitro evaluation of 5-aminolevulinic acid (ALA loaded PLGA nanoparticles

    Directory of Open Access Journals (Sweden)

    Shi L

    2013-07-01

    Full Text Available Lei Shi,1 Xiuli Wang,1 Feng Zhao,2 Hansen Luan,2 Qingfeng Tu,1 Zheng Huang,3 Hao Wang,2 Hongwei Wang1,41Shanghai Skin Disease Hospital, Shanghai, People's Republic of China; 2National Pharmaceutical Engineering Research Center, China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China; 3Ministry of Education (MOE Key Laboratory of OptoElectronic Science and Technology for Medicine, Fujian Normal University, Fuzhou, People's Republic of China; 4Huadong Hospital, Fudan University, Shanghai, People's Republic of ChinaBackground: 5-Aminolevulinic acid (ALA is a prodrug for topical photodynamic therapy. The effectiveness of topical ALA can be limited by its bioavailability. The aim of this study was to develop a novel ALA delivery approach using poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs.Methods: A modified double emulsion solvent evaporation method was used to prepare ALA loaded PLGA NPs (ALA PLGA NPs. The characteristics, uptake, protoporphyrin IX fluorescence kinetics, and cytotoxicity of ALA PLGA NPs toward a human skin squamous cell carcinoma cell line were examined.Results: The mean particle size of spherical ALA PLGA NPs was 65.6 nm ± 26 nm with a polydispersity index of 0.62. The encapsulation efficiency was 65.8% ± 7.2% and ALA loading capacity was 0.62% ± 0.27%. When ALA was dispersed in PLGA NPs, it turned into an amorphous phase. ALA PLGA NPs could be taken up by squamous cell carcinoma cells and localized in the cytoplasm. The protoporphyrin IX fluorescence kinetics and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay showed that ALA PLGA NPs were more effective than free ALA of the same concentration.Conclusion: PLGA NPs provide a promising ALA delivery strategy for topical ALA-photodynamic therapy of skin squamous cell carcinoma.Keywords: 5-Aminolevulinic acid (ALA, nanoparticles, poly(lactic-co-glycolic acid (PLGA, skin squamous cell carcinoma, photodynamic therapy (PDT

  4. Injectable PLGA microsphere/calcium phosphate cements: physical properties and degradation characteristics.

    Science.gov (United States)

    Habraken, W J E M; Wolke, J G C; Mikos, A G; Jansen, J A

    2006-01-01

    Calcium phosphate (CaP) cements show an excellent biocompatibility and often have a high mechanical strength, but in general degrade relatively slow. To increase degradation rates, macropores can be introduced into the cement, e.g., by the inclusion of biodegradable microspheres into the cement. The aim of this research is to develop an injectable PLGA microsphere/CaP cement with sufficient setting/cohesive properties and good mechanical and physical properties. PLGA microspheres were prepared using a water-in-oil-in-water double-emulsion technique. The CaP-cement used was Calcibon, a commercially available hydroxyapatite-based cement. 10:90 and 20:80 dry wt% PLGA microsphere/CaP cylindrical scaffolds were prepared as well as microporous cement (reference material). Injectability, setting time, cohesive properties and porosity were determined. Also, a 12-week degradation study in PBS (37 degree C) was performed. Results showed that injectability decreased with an increase in PLGA microsphere content. Initial and final setting time of the PLGA/CaP samples was higher than the microporous sample. Porosity of the different formulations was 40.8% (microporous), 60.2% (10:90) and 69.3% (20:80). The degradation study showed distinct mass loss and a pH decrease of the surrounding medium starting from week 6 with the 10:90 and 20:80 formulations, indicating PLGA erosion. Compression strength of the PLGA microsphere/CaP samples decreased siginificantly in time, the microporous sample remained constant. After 12 weeks both PLGA/CaP samples showed a structure of spherical micropores and had a compressive strength of 12.2 MPa (10:90) and 4.3 MPa (20:80). Signs of cement degradation were also found with the 20:80 formulation. In conclusion, all physical parameters were well within workable ranges with both 10:90 and 20:80 PLGA microsphere/CaP cements. After 12 weeks the PLGA was totally degraded and a highly porous, but strong scaffold remained.

  5. Microencapsulation of chemotherapeutics into monodisperse and tunable biodegradable polymers via electrified liquid jets: control of size, shape, and drug release.

    Science.gov (United States)

    Fattahi, Pouria; Borhan, Ali; Abidian, Mohammad Reza

    2013-09-06

    This paper describes microencapsulation of antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU, Carmustine) into biodegradable polymer poly(lactic-co-glycolic) acid (PLGA) using an electrojetting technique. The resulting BCNU-loaded PLGA microcapsules have significantly higher drug encapsulation efficiency, more tunable drug loading capacity, and (3) narrower size distribution than those generated using other encapsulation methods.

  6. Periodic jetting and monodisperse jet drops from oblique gas injection

    Science.gov (United States)

    McRae, Oliver; Gaillard, Antoine; Bird, James C.

    2017-07-01

    When air is blown in a straw or tube near an air-liquid interface, typically one of two behaviors is observed: a dimple in the liquid's surface, or a frenzy of sputtering bubbles, waves, and spray. Here we report and characterize an intermediate regime that can develop when a confined air jet enters the interface at an angle. This regime is oscillatory with a distinct characteristic frequency and can develop periodic angled jets that can break up into monodisperse aerosols. The underlying mechanisms responsible for this highly periodic regime are not well understood. Here we flow a continuous stream of gas through a tube near a liquid surface, observing both optically and acoustically the deformation of the liquid-air interface as various parameters are systematically adjusted. We show that the Kelvin-Helmholtz instability is responsible for the inception of waves within a cavity formed by the gas. Inertia, gravity, and capillary forces both shape the cavity and govern the frequency and amplitude of these gas-induced cavity waves. The flapping cavity focuses the waves into a series of periodic jets that can break up into droplets following the Rayleigh-Plateau instability. We present scaling arguments to rationalize the fundamental frequencies driving this system, as well as the conditions that bound the periodic regime. These frequencies and conditions compare well with our experimental results.

  7. Jamming of Monodisperse Cylindrical Grains in Featureless Vertical Channels

    Science.gov (United States)

    Friedl, Nicholas; Baxter, G. William

    2014-03-01

    We study jamming of low aspect-ratio cylindrical Delrin grains falling through a featureless vertical channel under the influence of gravity. These grains have an aspect-ratio less than two (H/D aspirin tablets, 35mm film canisters, poker chips, or coins. Monodisperse grains are allowed to fall under the influence of gravity through a uniform channel of square cross-section where the channel width is greater than the grain size and constant along the length of the channel. No combination of grain heights and diameters is equal to the channel width. Collections of grains sometimes form jams, stable structures in which the grains are supported by the channel walls and not by grains or walls beneath them. The probability of a jam occurring and the jam's strength are influenced by the grain dimensions and channel width. We will present experimental measurements of the jamming probability and jam strength and discuss the relationship of these results to other experiments and theories. Supported by an Undergraduate Research Grant from Penn State Erie, The Behrend College.

  8. Biotemplate synthesis of monodispersed iron phosphate hollow microspheres.

    Science.gov (United States)

    Cao, Feng; Li, Dongxu

    2010-03-01

    Monodispersed iron phosphate hollow microspheres with a high degree of crystallization were prepared through a facile in situ deposition method using rape pollen grains as a biotemplate. The functional group on the surface of the pollen grains could adsorb Fe(3+), which provided the nucleation sites for growth of iron phosphate nanoparticles. After being sintered at 600 degrees C for 10 h, the pollen grains were removed and iron phosphate hollow microspheres were obtained. A scanning electron microscope and x-ray diffraction were applied to characterize the morphology and crystalline structure of the pollen grains, iron phosphate-coated pollen grains and iron phosphate hollow microspheres. Differential scanning calorimetry and thermogravity analyses were performed to investigate the thermal behavior of the iron phosphate-coated pollen grains during the calcinations. Energy dispersive spectroscopy and Fourier transform infrared spectroscopy were utilized to investigate the interaction between the pollen grains and iron phosphate. The effect of the pollen wall on the surface morphology of these iron phosphate hollow microspheres was also proven in this work.

  9. Monodisperse Platinum and Rhodium Nanoparticles as Model Heterogeneous Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Grass, Michael Edward [Univ. of California, Berkeley, CA (United States)

    2008-09-01

    Model heterogeneous catalysts have been synthesized and studied to better understand how the surface structure of noble metal nanoparticles affects catalytic performance. In this project, monodisperse rhodium and platinum nanoparticles of controlled size and shape have been synthesized by solution phase polyol reduction, stabilized by polyvinylpyrrolidone (PVP). Model catalysts have been developed using these nanoparticles by two methods: synthesis of mesoporous silica (SBA-15) in the presence of nanoparticles (nanoparticle encapsulation, NE) to form a composite of metal nanoparticles supported on SBA-15 and by deposition of the particles onto a silicon wafer using Langmuir-Blodgett (LB) monolayer deposition. The particle shapes were analyzed by transmission electron microscopy (TEM) and high resolution TEM (HRTEM) and the sizes were determined by TEM, X-ray diffraction (XRD), and in the case of NE samples, room temperature H2 and CO adsorption isotherms. Catalytic studies were carried out in homebuilt gas-phase reactors. For the nanoparticles supported on SBA-15, the catalysts are in powder form and were studied using the homebuilt systems as plug-flow reactors. In the case of nanoparticles deposited on silicon wafers, the same systems were operated as batch reactors. This dissertation has focused on the synthesis, characterization, and reaction studies of model noble metal heterogeneous catalysts. Careful control of particle size and shape has been accomplished though solution phase synthesis of Pt and Rh nanoparticles in order to elucidate further structure-reactivity relationships in noble metal catalysis.

  10. Facile Synthesis of Monodisperse Gold Nanocrystals Using Virola oleifera

    Science.gov (United States)

    Milaneze, Bárbara A.; Oliveira, Jairo P.; Augusto, Ingrid; Keijok, Wanderson J.; Côrrea, Andressa S.; Ferreira, Débora M.; Nunes, Otalíbio C.; Gonçalves, Rita de Cássia R.; Kitagawa, Rodrigo R.; Celante, Vinícius G.; da Silva, André Romero; Pereira, Ana Claudia H.; Endringer, Denise C.; Schuenck, Ricardo P.; Guimarães, Marco C. C.

    2016-10-01

    The development of new routes and strategies for nanotechnology applications that only employ green synthesis has inspired investigators to devise natural systems. Among these systems, the synthesis of gold nanoparticles using plant extracts has been actively developed as an alternative, efficient, cost-effective, and environmentally safe method for producing nanoparticles, and this approach is also suitable for large-scale synthesis. This study reports reproducible and completely natural gold nanocrystals that were synthesized using Virola oleifera extract. V. oleifera resin is rich in epicatechin, ferulic acid, gallic acid, and flavonoids (i.e., quercetin and eriodictyol). These gold nanoparticles play three roles. First, these nanoparticles exhibit remarkable stability based on their zeta potential. Second, these nanoparticles are functionalized with flavonoids, and third, an efficient, economical, and environmentally friendly mechanism can be employed to produce green nanoparticles with organic compounds on the surface. Our model is capable of reducing the resin of V. oleifera, which creates stability and opens a new avenue for biological applications. This method does not require painstaking conditions or hazardous agents and is a rapid, efficient, and green approach for the fabrication of monodisperse gold nanoparticles.

  11. Ultrasonically Aided Electrospray source for monodisperse, charged nanoparticles

    Science.gov (United States)

    Song, Weidong

    This dissertation presents a new method of producing nearly monodisperse electrospray using charged capillary standing waves. This method, based on the Ultrasonically Aided Electrospraying (UAE) technology concept invented by the author, includes the steps of dispensing a liquid on the top surface of a diaphragm so as to form a liquid film on the surface of the diaphragm, setting the diaphragm into vibration using piezoelectric transducers so as to induce capillary standing waves in the liquid film, applying electric charge to the capillary standing waves so that electrospray is extracted from the crests of the capillary standing waves. Theoretical analysis on the formation of charged particles from charged capillary standing waves at critically stable condition is performed. An experimental UAE system is designed, built, and tested and the performance of this new technology concept is assessed. Experimental results validate the capabilities of the UAE concept. The method has several applications including electric space propulsion, nano particulate technologies, nanoparticle spray coating and painting techniques, semiconductor fabrication and biomedical processes. Two example applications in electric space propulsion and nanoparticle spray coating are introduced.

  12. Spark Ignition of Monodisperse Fuel Sprays. Ph.D. Thesis

    Science.gov (United States)

    Danis, Allen M.; Cernansky, Nicholas P.; Namer, Izak

    1987-01-01

    A study of spark ignition energy requirements was conducted with a monodisperse spray system allowing independent control of droplet size, equivalent ratio, and fuel type. Minimum ignition energies were measured for n-heptane and methanol sprays characterized at the spark gap in terms of droplet diameter, equivalence ratio (number density) and extent of prevaporization. In addition to sprays, minimum ignition energies were measured for completely prevaporized mixtures of the same fuels over a range of equivalence ratios to provide data at the lower limit of droplet size. Results showed that spray ignition was enhanced with decreasing droplet size and increasing equivalence ratio over the ranges of the parameters studied. By comparing spray and prevaporized ignition results, the existence of an optimum droplet size for ignition was indicated for both fuels. Fuel volatility was seen to be a critical factor in spray ignition. The spray ignition results were analyzed using two different empirical ignition models for quiescent mixtures. Both models accurately predicted the experimental ignition energies for the majority of the spray conditions. Spray ignition was observed to be probabilistic in nature, and ignition was quantified in terms of an ignition frequency for a given spark energy. A model was developed to predict ignition frequencies based on the variation in spark energy and equivalence ratio in the spark gap. The resulting ignition frequency simulations were nearly identical to the experimentally observed values.

  13. Biotemplate synthesis of monodispersed iron phosphate hollow microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Cao Feng; Li Dongxu, E-mail: dongxuli@njut.edu.c [College of Materials Science and Engineering, Nanjing University of Technology, Jiangsu Nanjing 210009 (China)

    2010-03-15

    Monodispersed iron phosphate hollow microspheres with a high degree of crystallization were prepared through a facile in situ deposition method using rape pollen grains as a biotemplate. The functional group on the surface of the pollen grains could adsorb Fe{sup 3+}, which provided the nucleation sites for growth of iron phosphate nanoparticles. After being sintered at 600 deg. C for 10 h, the pollen grains were removed and iron phosphate hollow microspheres were obtained. A scanning electron microscope and x-ray diffraction were applied to characterize the morphology and crystalline structure of the pollen grains, iron phosphate-coated pollen grains and iron phosphate hollow microspheres. Differential scanning calorimetry and thermogravity analyses were performed to investigate the thermal behavior of the iron phosphate-coated pollen grains during the calcinations. Energy dispersive spectroscopy and Fourier transform infrared spectroscopy were utilized to investigate the interaction between the pollen grains and iron phosphate. The effect of the pollen wall on the surface morphology of these iron phosphate hollow microspheres was also proven in this work.

  14. Formation of monodisperse mesoporous silica microparticles via spray-drying.

    Science.gov (United States)

    Waldron, Kathryn; Wu, Winston Duo; Wu, Zhangxiong; Liu, Wenjie; Selomulya, Cordelia; Zhao, Dongyuan; Chen, Xiao Dong

    2014-03-15

    In this work, a protocol to synthesize monodisperse mesoporous silica microparticles via a unique microfluidic jet spray-drying route is reported for the first time. The microparticles demonstrated highly ordered hexagonal mesostructures with surface areas ranging from ~900 up to 1500 m(2)/g and pore volumes from ~0.6 to 0.8 cm(3)/g. The particle size could be easily controlled from ~50 to 100 μm from the same diameter nozzle via changing the initial solute content, or changing the drying temperature. The ratio of the surfactant (CTAB) and silica (TEOS), and the amount of water in the precursor were found to affect the degree of ordering of mesopores by promoting either the self-assembly of the surfactant-silica micelles or the condensation of the silica as two competing processes in evaporation induced self-assembly. The drying rate and the curvature of particles also affected the self-assembly of the mesostructure. The particle mesostructure is not influenced by the inlet drying temperature in the range of 92-160 °C, with even a relatively low temperature of 92 °C producing highly ordered mesoporous microparticles. The spray-drying derived mesoporous silica microparticles, while of larger sizes and more rapidly synthesized, showed a comparable performance with the conventional mesoporous silica MCM-41 in controlled release of a dye, Rhodamine B, indicating that these spray dried microparticles could be used for the immobilisation and controlled release of small molecules.

  15. Monodisperse droplet generation for microscale mass transfer studies

    Science.gov (United States)

    Roberts, Christine; Rao, Rekha; Grillet, Anne; Jove-Colon, Carlos; Brooks, Carlton; Nemer, Martin

    2011-11-01

    Understanding interfacial mass transport on a droplet scale is essential for modeling liquid-liquid extraction processes. A thin flow-focusing microfluidic channel is evaluated for generating monodisperse liquid droplets for microscale mass transport studies. Surface treatment of the microfluidic device allows creation of both oil in water and water in oil emulsions, facilitating a large parameter study of viscosity and flow rate ratios. The unusually thin channel height promotes a flow regime where no droplets form. Through confocal microscopy, this regime is shown to be highly influenced by the contact angle of the liquids with the channel. Drop sizes are found to scale with a modified capillary number. Liquid streamlines within the droplets are inferred by high speed imagery of microparticles dispersed in the droplet phase. Finally, species mass transfer to the droplet fluid is quantitatively measured using high speed imaging. Sandia National Laboratories is a multi-program laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85.

  16. Effects of chemically modified nanostructured PLGA on functioning of lung and breast cancer cells

    Directory of Open Access Journals (Sweden)

    Zhang L

    2013-05-01

    Full Text Available Lijuan Zhang,1 Thomas J Webster21Department of Chemistry, 2School of Engineering, Brown University, Providence, RI, USABackground: The aim of this study was to investigate the effects of poly-lactic-co-glycolic acid (PLGA nanotopographies with alginate or chitosan protein preadsorption on the functioning of healthy and cancerous lung and breast cells, including adhesion, proliferation, apoptosis, and release of vascular endothelial growth factor (VEGF, which promotes tumor angiogenesis and secretion.Methods: We used a well established cast-mold technique to create nanoscale surface features on PLGA. Some of the nanomodified PLGA films were then exposed to alginate and chitosan. Surface roughness and the presence of protein was confirmed by atomic force microscopy. Surface energy was quantified by contact angle measurement.Results: Nanostructured PLGA surfaces with 23 nm features decreased synthesis of VEGF in both lung and breast cancer cells compared with conventional PLGA. Preadsorbing alginate further decreased cancer cell function, with nanostructured PLGA preadsorbed with alginate achieving the greatest decrease in synthesis of VEGF in both lung and breast cancer cells. In contrast, compared with nonmodified smooth PLGA, healthy cell functions were either not altered (ie, breast or were enhanced (ie, lung by use of nanostructured features and alginate or chitosan protein preadsorption.Conclusion: Using this technique, we developed surface nanometric roughness and modification of surface chemistry that could selectively decrease breast and lung cancer cell functioning without the need for chemotherapeutics. This technique requires further study in a wide range of anticancer and regenerative medicine applications.Keywords: breast, lung, cancer, nanotechnology, alginate, chitosan

  17. Micro/Nano Multilayered Scaffolds of PLGA and Collagen by Alternately Electrospinning for Bone Tissue Engineering.

    Science.gov (United States)

    Kwak, Sanghwa; Haider, Adnan; Gupta, Kailash Chandra; Kim, Sukyoung; Kang, Inn-Kyu

    2016-12-01

    The dual extrusion electrospinning technique was used to fabricate multilayered 3D scaffolds by stacking microfibrous meshes of poly(lactic acid-co-glycolic acid) (PLGA) in alternate fashion to micro/nano mixed fibrous meshes of PLGA and collagen. To fabricate the multilayered scaffold, 35 wt% solution of PLGA in THF-DMF binary solvent (3:1) and 5 wt% solution of collagen in hexafluoroisopropanol (HFIP) with and without hydroxyapatite nanorods (nHA) were used. The dual and individual electrospinning of PLGA and collagen were carried out at flow rates of 1.0 and 0.5 mL/h, respectively, at an applied voltage of 20 kV. The density of collagen fibers in multilayered scaffolds has controlled the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. The homogeneous dispersion of glutamic acid-modified hydroxyapatite nanorods (nHA-GA) in collagen solution has improved the osteogenic properties of fabricated multilayered scaffolds. The fabricated multilayered scaffolds were characterized using FT-IR, X-ray photoelectron spectroscopy, and transmission electron microscopy (TEM). The scanning electron microscopy (FE-SEM) was used to evaluate the adhesion and spreads of MC3T3-E1 cells on multilayered scaffolds. The activity of MC3T3-E1 cells on the multilayered scaffolds was evaluated by applying MTT, alkaline phosphatase, Alizarin Red, von Kossa, and cytoskeleton F-actin assaying protocols. The micro/nano fibrous PLGA-Col-HA scaffolds were found to be highly bioactive in comparison to pristine microfibrous PLGA and micro/nano mixed fibrous PLGA and Col scaffolds.

  18. A mPEG-PLGA-b-PLL copolymer carrier for adriamycin and siRNA delivery.

    Science.gov (United States)

    Liu, Peifeng; Yu, Hui; Sun, Ying; Zhu, Mingjie; Duan, Yourong

    2012-06-01

    A amphiphilic block copolymer composed of conventional monomethoxy (polyethylene glycol)-poly (d,l-lactide-co-glycolide)-poly (l-lysine) (mPEG-PLGA-b-PLL) was synthesized. The chemical structure of this copolymer and its precursors was confirmed by Fourier Transform Infrared Spectroscopy (FTIR), (1)H Nuclear Magnetic Resonance ((1)H NMR) and Gel Permeation Chromatography (GPC). The copolymer was used to prepare nanoparticles (NPs) that were then loaded with either the anti-cancer drug adriamycin or small interfering RNA-negative (siRNA) using a double emulsion method. MTT assays used to study the in vitro cytotoxicity of mPEG-PLGA-b-PLL NPs showed that these particles were not toxic in huh-7 hepatic carcinoma cells. Confocal laser scanning microscopy (CLSM) and flow cytometer analysis results demonstrated efficient mPEG-PLGA-b-PLL NPs-mediated delivery of both adriamycin and siRNA into the cells. In vivo the targeting delivery of adriamycin or siRNA mediated by mPEG-PLGA-b-PLL NPs in the huh-7 hepatic carcinoma-bearing mice was evaluated using a fluorescence imaging system. The targeting delivery results and froze section analysis confirmed that drug or siRNA is deliver to tumor more efficiently by mPEG-PLGA-b-PLL NPs than free drug or Lipofectamine™2000. The high efficiency delivery of mPEG-PLGA-b-PLL NPs mainly due to the enhancement of cellular uptake. These results imply that mPEG-PLGA-b-PLL NPs have a great potential to be used as an effective carriers for adriamycin or siRNA. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  19. Facile fabrication of biocompatible PLGA drug-carrying microspheres by O/W pickering emulsions.

    Science.gov (United States)

    Wei, Zengjiang; Wang, Chaoyang; Liu, Hao; Zou, Shengwen; Tong, Zhen

    2012-03-01

    This study is focused on the preparation of Ibuprofen (IBU) loaded micrometer-sized poly(lactic-co-glycolic acid) (PLGA) microspheres and process variables on the size, drug loading and release during preparation of formulation. Silicon dioxide (SiO(2)) nanoparticle-coated PLGA microspheres were fabricated via a combined system of "Pickering-type" emulsion route and solvent volatilization method in the absence of any molecular surfactants. Stable oil-in-water emulsions were prepared using SiO(2) nanoparticles as a particulate emulsifier and a dichloromethane (CH(2)Cl(2)) solution of PLGA as an oil phase. The SiO(2) nanoparticle-coated PLGA microspheres were fabricated by the evaporation of CH(2)Cl(2) in situ, and then bare-PLGA microspheres were prepared by removal of the SiO(2) nanoparticles using HF aqueous solution. The two types of microspheres were characterized in terms of size, component and morphology using scanning electronic microscope (SEM), Fourier-transform infrared, optical microscope, and so on. Moreover, IBU was encapsulated into the hybrid beads by dispersing them in the CH(2)Cl(2) solution of PLGA in the fabrication process. The sustained release could be obtained due to the barrier of the polymeric matrix (PLGA). More over, the release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion. The combined system of Pickering emulsion and solvent volatilization opens up a new route to fabricate a variety of microspheres. The resulting microspheres may find applications as delivery vehicles for biomolecules, drugs, cosmetics and living cells. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Stimulated myoblast differentiation on graphene oxide-impregnated PLGA-collagen hybrid fibre matrices.

    Science.gov (United States)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Kim, Yong-Joo; Hyun, Jung Keun; Jung, Tae-Gon; Hong, Suck Won; Han, Dong-Wook

    2015-03-12

    Electrospinning is a simple and effective method for fabricating micro- and nanofiber matrices. Electrospun fibre matrices have numerous advantages for use as tissue engineering scaffolds, such as high surface area-to-volume ratio, mass production capability and structural similarity to the natural extracellular matrix (ECM). Therefore, electrospun matrices, which are composed of biocompatible polymers and various biomaterials, have been developed as biomimetic scaffolds for the tissue engineering applications. In particular, graphene oxide (GO) has recently been considered as a novel biomaterial for skeletal muscle regeneration because it can promote the growth and differentiation of myoblasts. Therefore, the aim of the present study was to fabricate the hybrid fibre matrices that stimulate myoblasts differentiation for skeletal muscle regeneration. Hybrid fibre matrices composed of poly(lactic-co-glycolic acid, PLGA) and collagen (Col) impregnated with GO (GO-PLGA-Col) were successfully fabricated using an electrospinning process. Our results indicated that the GO-PLGA-Col hybrid matrices were comprised of randomly-oriented continuous fibres with a three-dimensional non-woven porous structure. Compositional analysis showed that GO was dispersed uniformly throughout the GO-PLGA-Col matrices. In addition, the hydrophilicity of the fabricated matrices was significantly increased by blending with a small amount of Col and GO. The attachment and proliferation of the C2C12 skeletal myoblasts were significantly enhanced on the GO-PLGA-Col hybrid matrices. Furthermore, the GO-PLGA-Col matrices stimulated the myogenic differentiation of C2C12 skeletal myoblasts, which was enhanced further under the culture conditions of the differentiation media. Taking our findings into consideration, it is suggested that the GO-PLGA-Col hybrid fibre matrices can be exploited as potential biomimetic scaffolds for skeletal tissue engineering and regeneration because these GO

  1. Micro/Nano Multilayered Scaffolds of PLGA and Collagen by Alternately Electrospinning for Bone Tissue Engineering

    Science.gov (United States)

    Kwak, Sanghwa; Haider, Adnan; Gupta, Kailash Chandra; Kim, Sukyoung; Kang, Inn-Kyu

    2016-07-01

    The dual extrusion electrospinning technique was used to fabricate multilayered 3D scaffolds by stacking microfibrous meshes of poly(lactic acid-co-glycolic acid) (PLGA) in alternate fashion to micro/nano mixed fibrous meshes of PLGA and collagen. To fabricate the multilayered scaffold, 35 wt% solution of PLGA in THF-DMF binary solvent (3:1) and 5 wt% solution of collagen in hexafluoroisopropanol (HFIP) with and without hydroxyapatite nanorods (nHA) were used. The dual and individual electrospinning of PLGA and collagen were carried out at flow rates of 1.0 and 0.5 mL/h, respectively, at an applied voltage of 20 kV. The density of collagen fibers in multilayered scaffolds has controlled the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. The homogeneous dispersion of glutamic acid-modified hydroxyapatite nanorods (nHA-GA) in collagen solution has improved the osteogenic properties of fabricated multilayered scaffolds. The fabricated multilayered scaffolds were characterized using FT-IR, X-ray photoelectron spectroscopy, and transmission electron microscopy (TEM). The scanning electron microscopy (FE-SEM) was used to evaluate the adhesion and spreads of MC3T3-E1 cells on multilayered scaffolds. The activity of MC3T3-E1 cells on the multilayered scaffolds was evaluated by applying MTT, alkaline phosphatase, Alizarin Red, von Kossa, and cytoskeleton F-actin assaying protocols. The micro/nano fibrous PLGA-Col-HA scaffolds were found to be highly bioactive in comparison to pristine microfibrous PLGA and micro/nano mixed fibrous PLGA and Col scaffolds.

  2. Combination antiretroviral drugs in PLGA nanoparticle for HIV-1

    Directory of Open Access Journals (Sweden)

    Sharma Akhilesh

    2009-12-01

    Full Text Available Abstract Background Combination antiretroviral (AR therapy continues to be the mainstay for HIV treatment. However, antiretroviral drug nonadherence can lead to the development of resistance and treatment failure. We have designed nanoparticles (NP that contain three AR drugs and characterized the size, shape, and surface charge. Additionally, we investigated the in vitro release of the AR drugs from the NP using peripheral blood mononuclear cells (PBMCs. Methods Poly-(lactic-co-glycolic acid (PLGA nanoparticles (NPs containing ritonavir (RTV, lopinavir (LPV, and efavirenz (EFV were fabricated using multiple emulsion-solvent evaporation procedure. The nanoparticles were characterized by electron microscopy and zeta potential for size, shape, and charge. The intracellular concentration of AR drugs was determined over 28 days from NPs incubated with PBMCs. Macrophages were imaged by fluorescent microscopy and flow cytometry after incubation with fluorescent NPs. Finally, macrophage cytotoxicity was determined by MTT assay. Results Nanoparticle size averaged 262 ± 83.9 nm and zeta potential -11.4 ± 2.4. AR loading averaged 4% (w/v. Antiretroviral drug levels were determined in PBMCs after 100 μg of NP in 75 μL PBS was added to media. Intracellular peak AR levels from NPs (day 4 were RTV 2.5 ± 1.1; LPV 4.1 ± 2.0; and EFV 10.6 ± 2.7 μg and continued until day 28 (all AR ≥ 0.9 μg. Free drugs (25 μg of each drug in 25 μL ethanol added to PBMCs served as control were eliminated by 2 days. Fluorescence microscopy and flow cytometry demonstrated phagocytosis of NP into monocytes-derived macrophages (MDMs. Cellular MTT assay performed on MDMs demonstrated that NPs are not significantly cytotoxic. Conclusion These results demonstrated AR NPs could be fabricated containing three antiretroviral drugs (RTV, LPV, EFV. Sustained release of AR from PLGA NP show high drug levels in PBMCs until day 28 without cytotoxicity.

  3. Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles

    Directory of Open Access Journals (Sweden)

    Zulaikha A. Busari

    2017-09-01

    Full Text Available Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric, a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic acid (PLGA nanoparticles. Curcumin was loaded with poly (D,L-lactic-co-glycolic acid (PLGA using solvent evaporation from oil-in-water single emulsion method. The nanoparticles were characterized and evaluated in vivo for antimalarial activities using Peter’s 4-day suppressive protocol in mice model. Hematological and hepatic toxicity assays were performed on whole blood and plasma, respectively. In vivo anti-parasitic test and toxicity assays for free and encapsulated drug were performed at 5 and 10 mg/kg. In vitro cytotoxicity of free and PLGA encapsulated curcumin (Cur-PLGA to RAW 264.7 cell line was also determined at varying concentrations (1000–7.8 μg/mL. The size and entrapment efficiency of the nanoparticulate drug formulated was 291.2 ± 82.1 nm and 21.8 ± 0.4 respectively. The percentage parasite suppression (56.8% at 5 mg/kg was significantly higher than in free drug (40.5% of similar concentration (p < 0.05 but not at 10 mg/kg (49.5% at 4-day post-treatment. There were no significant differences in most of the recorded blood parameters in free curcumin and PLGA encapsulated nanoparticulate form (p > 0.05 except in lymphocytes which were significantly higher in Cur-PLGA compared to the free drug (p < 0.05. There were no significant differences in hepatotoxic biomarkers; aspartate aminotransferase and alanine aminotransferase concentrations in various treatment groups (p > 0.05. At higher concentrations (1000 and 500 μg/mL, Cur-PLGA

  4. Controlled synthesis and magnetic properties of monodispersed ceria nanoparticles

    Directory of Open Access Journals (Sweden)

    Sumeet Kumar

    2015-02-01

    Full Text Available In the present study, monodispersed CeO2 nanoparticles (NPs of size 8.5 ± 1.0, 11.4 ± 1.0 and 15.4 ± 1.0 nm were synthesized using the sol-gel method. Size-dependent structural, optical and magnetic properties of as-prepared samples were investigated by X-ray diffraction (XRD, field emission scanning electron microscope (FE-SEM, high resolution transmission electron microscopy (HR-TEM, ultra-violet visible (UV-VIS spectroscopy, Raman spectroscopy and vibrating sample magnetometer (VSM measurements. The value of optical band gap is calculated for each particle size. The decrease in the value of optical band gap with increase of particle size may be attributed to the quantum confinement, which causes to produce localized states created by the oxygen vacancies due to the conversion of Ce4+ into Ce3+ at higher calcination temperature. The Raman spectra showed a peak at ∼461 cm-1 for the particle size 8.5 nm, which is attributed to the 1LO phonon mode. The shift in the Raman peak could be due to lattice strain developed due to variation in particle size. Weak ferromagnetism at room temperature is observed for each particle size. The values of saturation magnetization (Ms, coercivity (Hc and retentivity (Mr are increased with increase of particle size. The increase of Ms and Mr for larger particle size may be explained by increase of density of oxygen vacancies at higher calcination temperature. The latter causes high concentrations of Ce3+ ions activate more coupling between the individual magnetic moments of the Ce ions, leading to an increase of Ms value with the particle size. Moreover, the oxygen vacancies may also produce magnetic moment by polarizing spins of f electrons of cerium (Ce ions located around oxygen vacancies, which causes ferromagnetism in pure CeO2 samples.

  5. Controlled synthesis and magnetic properties of monodispersed ceria nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Sumeet; Ojha, Animesh K. [Department of Physics, Motilal Nehru National Institute of Technology, Allahabad-211004 (India); Srivastava, Manish, E-mail: 84.srivastava@gmail.com, E-mail: manish-mani84@rediffmail.com [Department of Physics and Astrophysics, University of Delhi, Delhi-110007 (India); Singh, Jay [Department of Applied Chemistry and Polymer Technology, Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, Delhi 110042 (India); Layek, Samar [Department of Physics, Indian Institute of Technology, Kanpur 208016 (India); Yashpal, Madhu [Electron Microscope Facility, Department of Anatomy Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005 (India); Materny, Arnulf [Center for Functional Materials and Nanomolecular Science, Jacobs University Bremen, Campus Ring, 28759 Bremen (Germany)

    2015-02-15

    In the present study, monodispersed CeO{sub 2} nanoparticles (NPs) of size 8.5 ± 1.0, 11.4 ± 1.0 and 15.4 ± 1.0 nm were synthesized using the sol-gel method. Size-dependent structural, optical and magnetic properties of as-prepared samples were investigated by X-ray diffraction (XRD), field emission scanning electron microscope (FE-SEM), high resolution transmission electron microscopy (HR-TEM), ultra-violet visible (UV-VIS) spectroscopy, Raman spectroscopy and vibrating sample magnetometer (VSM) measurements. The value of optical band gap is calculated for each particle size. The decrease in the value of optical band gap with increase of particle size may be attributed to the quantum confinement, which causes to produce localized states created by the oxygen vacancies due to the conversion of Ce{sup 4+} into Ce{sup 3+} at higher calcination temperature. The Raman spectra showed a peak at ∼461 cm{sup -1} for the particle size 8.5 nm, which is attributed to the 1LO phonon mode. The shift in the Raman peak could be due to lattice strain developed due to variation in particle size. Weak ferromagnetism at room temperature is observed for each particle size. The values of saturation magnetization (Ms), coercivity (Hc) and retentivity (Mr) are increased with increase of particle size. The increase of Ms and Mr for larger particle size may be explained by increase of density of oxygen vacancies at higher calcination temperature. The latter causes high concentrations of Ce{sup 3+} ions activate more coupling between the individual magnetic moments of the Ce ions, leading to an increase of Ms value with the particle size. Moreover, the oxygen vacancies may also produce magnetic moment by polarizing spins of f electrons of cerium (Ce) ions located around oxygen vacancies, which causes ferromagnetism in pure CeO{sub 2} samples.

  6. Tropoelastin coated PLLA-PLGA scaffolds promote vascular network formation.

    Science.gov (United States)

    Landau, Shira; Szklanny, Ariel A; Yeo, Giselle C; Shandalov, Yulia; Kosobrodova, Elena; Weiss, Anthony S; Levenberg, Shulamit

    2017-04-01

    The robust repair of large wounds and tissue defects relies on blood flow. This vascularization is the major challenge faced by tissue engineering on the path to forming thick, implantable tissue constructs. Without this vasculature, oxygen and nutrients cannot reach the cells located far from host blood vessels. To make viable constructs, tissue engineering takes advantage of the mechanical properties of synthetic materials, while combining them with ECM proteins to create a natural environment for the tissue-specific cells. Tropoelastin, the precursor of the elastin, is the ECM protein responsible for elasticity in diverse tissues, including robust blood vessels. Here, we seeded endothelial cells with supporting cells on PLLA/PLGA scaffolds treated with tropoelastin, and examined the morphology, expansion and maturity of the newly formed vessels. Our results demonstrate that the treated scaffolds elicit a more expanded, complex and developed vascularization in comparison to the untreated group. Implantation of tropoelastin-treated scaffolds into mouse abdominal muscle resulted in enhanced perfusion of the penetrating vasculature and improved integration. This study points to the great potential of these combined materials in promoting the vascularization of implanted engineered constructs, which can be further exploited in the fabrication of clinically relevant engineered tissues.

  7. Enhanced photodynamic efficacy of PLGA-encapsulated 5-ALA nanoparticles in mice bearing Ehrlich ascites carcinoma

    Science.gov (United States)

    Shaker, Maryam N.; Ramadan, Heba S.; Mohamed, Moustafa M.; El khatib, Ahmed M.; Roston, Gamal D.

    2014-10-01

    Nanoparticles (NPs) fabricated from the biodegradable copolymer poly(lactic- co-glycolic acid) (PLGA) were investigated as a drug delivery system to enhance the photodynamic efficacy of 5-aminolevulinic acid (5-ALA) in mice bearing Ehrlich ascites carcinoma. The PLGA-encapsulated 5-ALA NPs were prepared using binary organic solvent diffusion method and characterized in terms of shape and particle size. The in vivo photodynamic efficiency in Ehrlich ascites-bearing mice was studied. The obtained particles were uniform in size with spherical shape of mean size of 249.5 nm as obtained by particle size analyzer and the in vitro release studies demonstrated a controlled release profile of 5-ALA. Tumor-bearing mice injected with PLGA-encapsulated 5-ALA NPs exhibited significantly smaller mean tumor volume, increased tumor growth delay compared with the control group and the group injected with free 5-ALA during the time course of the experiment. Histopathological examination of tumor from mice treated with PLGA-encapsulated 5-ALA NPs showed regression of tumor cells, in contrast to those obtained from mice treated with free 5-ALA. The results indicate that PLGA-encapsulated 5-ALA NPs are a successful delivery system for improving photodynamic activity in the target tissue.

  8. Triple-layered PLGA/nanoapatite/lauric acid graded composite membrane for periodontal guided bone regeneration.

    Science.gov (United States)

    Jamuna-Thevi, Kalitheertha; Saarani, Nur Najiha; Abdul Kadir, Mohamed Rafiq; Hermawan, Hendra

    2014-10-01

    This paper discusses the successful fabrication of a novel triple-layered poly(lactic-co-glycolic acid) (PLGA)-based composite membrane using only a single step that combines the techniques of solvent casting and thermally induced phase separation/solvent leaching. The resulting graded membrane consists of a small pore size layer-1 containing 10 wt% non-stoichiometric nanoapatite (NAp)+1-3 wt% lauric acid (LA) for fibroblastic cell and bacterial inhibition, an intermediate layer-2 with 20-50 wt% NAp+1 wt% LA, and a large pore size layer-3 containing 30-100 wt% NAp without LA to allow bone cell growth. The synergic effects of 10-30 wt% NAp and 1 wt% LA in the membrane demonstrated higher tensile strength (0.61 MPa) and a more elastic behavior (16.1% elongation at break) in 3 wt% LA added membrane compared with the pure PLGA (0.49 MPa, 9.1%). The addition of LA resulted in a remarkable plasticizing effect on PLGA at 3 wt% due to weak intermolecular interactions in PLGA. The pure and composite PLGA membranes had good cell viability toward human skin fibroblast, regardless of LA and NAp contents.

  9. Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

    Science.gov (United States)

    Ding, Hong; Yong, Ken-Tye; Roy, Indrajit; Hu, Rui; Wu, Fang; Zhao, Lingling; Law, Wing-Cheung; Zhao, Weiwei; Ji, Wei; Liu, Liwei; Bergey, Earl J.; Prasad, Paras N.

    2011-04-01

    In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l - 1. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the αvβ3 integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

  10. Experimental Research on Ectopic Osteogenesis of BMP2-derived Peptide P24 Combined with PLGA Copolymers

    Institute of Scientific and Technical Information of China (English)

    DUAN Zhixia; ZHENG Qixin; GUO Xiaodong; YUAN Quan; CHEN Shunguang

    2007-01-01

    To experimentally evaluate the ectopic osteogenetic capacity of synthesized BMP2-derived peptide P24 combined with poly lactic-co-glycolic acid (PLGA), Wistar rats were divided into two groups: group A, in which BMP2-derived peptide P24/PLGA complex was implanted,and group B which received simple PLGA implant. The complex was respectively implanted into the back muscles of rats. Samples were taken the 1 st, 4 th, 8 th, and the 12 th week after the implantation.Their bone formation was detected by X-ray examination, and tissue response was histologically observed. Western blotting was used for the detection of the expression of collagen Ⅰ (Col- Ⅰ ) and osteopontin (OPN). There was acute inflammation in the tissue around both types of implants at early stage. The cartilage was found around implant areas 4 weeks after the implantation of BMP2-derived peptide p24/PLGA complex, 8 weeks after the implantation, osteoblasts were found, and 12 weeks after the implantation, typical trabecular bone structure was observed. In group B, after 12 weeks, no osteoblasts were found. It is concluded that PLGA is an ideal scaffold material for bone tissue engineering. BMP2-derived peptide can start endochondral ossification and is more effective in inducing ectopic osteogenesis.

  11. Toxicity of surface-modified PLGA nanoparticles toward lung alveolar epithelial cells.

    Science.gov (United States)

    Grabowski, Nadège; Hillaireau, Hervé; Vergnaud, Juliette; Santiago, Letícia Aragão; Kerdine-Romer, Saadia; Pallardy, Marc; Tsapis, Nicolas; Fattal, Elias

    2013-10-01

    In vitro cytotoxicity and inflammatory response following exposure to nanoparticles (NPs) made of poly(lactide-co-glycolide) (PLGA) have been investigated on A549 human lung epithelial cells. Three different PLGA NPs (230 nm) were obtained using different stabilizers (polyvinyl alcohol, chitosan, or Pluronic(®) F68) to form respectively neutral, positively or negatively charged NPs. Polystyrene NPs were used as polymeric but non-biodegradable NPs, and titanium dioxide (anatase and rutile) as inorganic NPs, for comparison. Cytotoxicity was evaluated through mitochondrial activity as well as membrane integrity (lactate dehydrogenase release, trypan blue exclusion, propidium iodide staining). The cytotoxicity of PLGA-based and polystyrene NPs was lower or equivalent to the one observed after exposure to titanium dioxide NPs. The inflammatory response, evaluated through the release of the IL-6, IL-8, MCP-1, TNF-α cytokines, was low for all NPs. However, some differences were observed, especially for negative PLGA NPs that led to a higher inflammatory response, which can be correlated to a higher uptake of these NPs. Taken together, these results show that both coating of PLGA NPs and the nature of the core play a key role in cell response.

  12. PLGA based drug delivery systems: Promising carriers for wound healing activity.

    Science.gov (United States)

    Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

    2016-03-01

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.

  13. The Construction and Investigation of PLGA Artificial Bone by Biomimetic Mineralization

    Institute of Scientific and Technical Information of China (English)

    ZHAO Ming; ZHENG Qixin; WANG Jinguang; WANG yuntao; HAO Jie

    2005-01-01

    To modify the surface property of poly lactide co-glycolide (PLGA) by biomimetic mineralization to construct a new kind of artificial bone. PLGA films and 3 diamensional (3-D) porous scaffolds hydrolyzed in alkaline solution were minerilized in SBF for 14 days. The morphology and composition of the mineral grown on PLGA were analyzed with SEM, FTIR and XRD. The porosity of the scaffolds was detected by using the liquid displacement method. The compressive strength of the scaffolds was detected by using a Shimadzu universal mechanic tester. An obvious mineral coating was detected on the surface of films and scaffolds. The main component of the mineral was carbonated hydroxyapatite (HA) similar to the major mineral component of bone tissues. The porosity of the un-mineralized and mineralized porous scaffolds was (84.86±8.52) % and (79.70±7.70) % respectively. The compressive strength was 0. 784±0. 156 N/mm2 in un-mineralized 3-D porous PLGA and 0. 858±0. 145 N/mm2 in mineralized 3-D porous PLGA. There were no significant differences between the mineralized and un-mineralized scaffolds (P>0. 05) in porosity and biomechanics. Biomimetic mineralization is a suitable method to construct artificial bone.

  14. Immunosuppressive Activity of Size-Controlled PEG-PLGA Nanoparticles Containing Encapsulated Cyclosporine A

    Directory of Open Access Journals (Sweden)

    Li Tang

    2012-01-01

    Full Text Available We encapsulated cyclosporine A (CsA in poly(ethylene glycol-b-poly(d,l-lactide-co-glycolide (PEG-PLGA nanoparticles (NPs by nanoprecipitation of CsA and PEG-PLGA. The resulting CsA/PEG-PLGA-NPs were <100 nm in diameter with a narrow particle size distribution. The NP size could be controlled by tuning the polymer concentration, solvent, or water/solvent ratio during formulation. The PEGylated NPs maintained non-aggregated in salt solution. Solid NPs lyoprotected with bovine serum albumin were prepared for the convenience of storage and transportation. The release kinetics of CsA (55.6% released on Day 1 showed potential for maintaining therapeutic CsA concentrations in vivo. In T-cell assays, both free CsA and CsA/PEG-PLGA-NPs suppressed T-cell proliferation and production of inflammatory cytokines dose dependently. In a mixed lymphocyte reaction assay, the IC50 values for free CsA and CsA/PEG-PLGA-NPs were found to be 30 and 35 ng/mL, respectively. This nanoparticulate CsA delivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency and potentially reduced toxicity.

  15. Biodegradable effect of PLGA membrane in alveolar bone regeneration on beagle dog.

    Science.gov (United States)

    Hua, Nan; Ti, Vivian Lao; Xu, Yuanzhi

    2014-11-01

    Guided bone regeneration (GBR) is a principle adopted from guided tissue regeneration (GTR). Wherein, GBR is used for the healing of peri-implant bony dehiscences, for the immediate placement of implants into extraction sockets and for the augmentation of atrophic alveolar ridges. This procedure is done by the placement of a resorbable or non-resorbable membrane that will exclude undesirable types of tissue growth between the extraction socket and the soft tissue to allow only bone cells to regenerate in the surgically treated lesion. Here, we investigated the biodegradable effect of polylactic-co-glycolic acid (PLGA) membrane in the alveolar bone on Beagle dogs. Results show that both collagen and PLGA membrane had been fully resorbed, biodegraded, at four weeks post-operative reentry into the alveolar bone. Histological results under light microscopy revealed formation of new bone trabeculae in the extraction sites on both collagen and PLGA membrane. In conclusion, PLGA membrane could be a potential biomaterials for use on GBR and GTR. Nevertheless, further studies will be necessary to elucidate the efficiency and cost effectiveness of PLGA as GBR membrane in clinical.

  16. In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

    Science.gov (United States)

    Zhang, Jiang; Liu, Yang; Luo, Rifang; Chen, Si; Li, Xin; Yuan, Shuheng; Wang, Jin; Huang, Nan

    2015-02-01

    Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and proliferation of smooth muscle cells.

  17. Apatite coating of electrospun PLGA fibers using a PVA vehicle system carrying calcium ions.

    Science.gov (United States)

    Kim, In Ae; Rhee, Sang-Hoon

    2010-01-01

    A novel method to coat electrospun poly(D,L-lactic-co-glycolic acid) (PLGA) fiber surfaces evenly and efficiently with low-crystalline carbonate apatite crystals using a poly(vinyl alcohol) (PVA) vehicle system carrying calcium ions was presented. A non-woven PLGA fabric was prepared by electrospinning: a 10 wt% PLGA solution was prepared using 1,1,3,3-hexafluoro-2-propanol as a solvent and electrospun under a electrical field of 1 kV/cm using a syringe pump with a flowing rate of 3 ml/h. The non-woven PLGA fabric, 12 mm in diameter and 1 mm in thickness, was cut and then coated with a PVA solution containing calcium chloride dihydrate (specimen PPC). As controls, pure non-woven PLGA fabric (specimen P) and fabric coated with a calcium chloride dihydrate solution without PVA (specimen PC) were also prepared. Three specimens were exposed to simulated body fluid for 1 week and this exposure led to form uniform and complete apatite coating layer on the fiber surfaces of specimen PPC. However, no apatite had formed to the fiber surfaces of specimen P and only inhomogeneous coating occurred on the fiber surfaces of specimen PC. These results were explained in terms of the calcium chelating and adhesive properties of PVA vehicle system. The practical implication of the results is that this method provides a simple but efficient technique for coating the fiber surface of an initially non-bioactive material with low-crystalline carbonate apatite.

  18. Evaluation of the effect of crocetin on antitumor activity of doxorubicin encapsulated in PLGA nanoparticles

    Directory of Open Access Journals (Sweden)

    F. A Langroodi

    2016-01-01

    Full Text Available Objective(s: The current study reports investigation of codelivery by PLGA nanoparticles (NPs loaded with crocetin (Cro, a natural carotenoid dicarboxylicHYPERLINK “http://en.wikipedia.org/wiki/Carboxylic_acid” acid that is found in the crocus flower, and Doxorubicin (DOX. Materials and Methods: Double emulsion/solvent evaporation method was used for preparation of PLGA nanoparticles containing Dox and Cro. Characterizations of prepared NPs were investigated by atomic force microscopy (AFM and dynamic light scattering analysis. In vitro Cytotoxicity of DOX and Cro loaded PLGA NPs (PLGA-DOX-Cro on MCF-7 cell line was evaluated using MTT test. Flow cytometry experiments were implemented to distinguish cells undergoing apoptosis from those undergoing necrosis. Furthermore the expression of caspase 3 was examined by western blot analysis. Results: The prepared formulations had size of 150- 300 nm. Furthermore, PLGA-DOX-Cro nanoparticles inhibited MCF-7 tumor cells growth more efficiently than either DOX or Cro alone at the same concentrations, as quantified by MTT assay and flow cytometry. Studies on cellular uptake of DOX-Cro-NPs demonstrated that NPs were effectively taken up by MCF-7 tumor cells. Conclusion: This study suggested that DOX-Cro-NPs may have promising applications in breast cancer therapy.

  19. Mn(2+)-coordinated PDA@DOX/PLGA nanoparticles as a smart theranostic agent for synergistic chemo-photothermal tumor therapy.

    Science.gov (United States)

    Xi, Juqun; Da, Lanyue; Yang, Changshui; Chen, Rui; Gao, Lizeng; Fan, Lei; Han, Jie

    2017-01-01

    Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn(2+)-coordinated doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn(2+) ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn(2+)-PDA@DOX/PLGA nanoparticles. In our system, Mn(2+)-PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn(2+) could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn(2+)-PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties.

  20. Mn2+-coordinated PDA@DOX/PLGA nanoparticles as a smart theranostic agent for synergistic chemo-photothermal tumor therapy

    Science.gov (United States)

    Xi, Juqun; Da, Lanyue; Yang, Changshui; Chen, Rui; Gao, Lizeng; Fan, Lei; Han, Jie

    2017-01-01

    Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn2+-coordinated doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn2+ ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn2+-PDA@DOX/PLGA nanoparticles. In our system, Mn2+-PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn2+ could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn2+-PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties. PMID:28479854

  1. Development of Poly Lactic/Glycolic Acid (PLGA Microspheres for Controlled Release of Rho-Associated Kinase Inhibitor

    Directory of Open Access Journals (Sweden)

    Sho Koda

    2017-01-01

    Full Text Available Purpose. The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA as a drug delivery carrier of Rho kinase (ROCK inhibitor for the treatment of corneal endothelial disease. Method. ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1, and a double emulsion [(W1/O/W2] was formed with dichloromethane (O and polyvinyl alcohol (W2. Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography. PLGA was injected into the anterior chamber or subconjunctiva in rabbit eyes, and ocular complication was evaluated by slitlamp microscope and histological analysis. Results. Y-27632 incorporated PLGA microspheres with different molecular weights, and different composition ratios of lactic acid and glycolic acid were fabricated. A high molecular weight and low content of glycolic acid produced a slower and longer release. The Y-27632 released from PLGA microspheres significantly promoted the cell proliferation of cultured corneal endothelial cells. The injection of PLGA did not induce any evident eye complication. Conclusions. ROCK inhibitor-incorporated PLGA microspheres were fabricated, and the microspheres achieved the sustained release of ROCK inhibitor over 7–10 days in vitro. Our data should encourage researchers to use PLGA microspheres for treating corneal endothelial diseases.

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

    DEFF Research Database (Denmark)

    Garcia Diaz, Maria; Foged, Camilla; Nielsen, Hanne Mørck

    2015-01-01

    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...

  3. Development of Poly Lactic/Glycolic Acid (PLGA) Microspheres for Controlled Release of Rho-Associated Kinase Inhibitor.

    Science.gov (United States)

    Koda, Sho; Okumura, Naoki; Kitano, Junji; Koizumi, Noriko; Tabata, Yasuhiko

    2017-01-01

    The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA) as a drug delivery carrier of Rho kinase (ROCK) inhibitor for the treatment of corneal endothelial disease. ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1), and a double emulsion [(W1/O)/W2] was formed with dichloromethane (O) and polyvinyl alcohol (W2). Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography. PLGA was injected into the anterior chamber or subconjunctiva in rabbit eyes, and ocular complication was evaluated by slitlamp microscope and histological analysis. Y-27632 incorporated PLGA microspheres with different molecular weights, and different composition ratios of lactic acid and glycolic acid were fabricated. A high molecular weight and low content of glycolic acid produced a slower and longer release. The Y-27632 released from PLGA microspheres significantly promoted the cell proliferation of cultured corneal endothelial cells. The injection of PLGA did not induce any evident eye complication. ROCK inhibitor-incorporated PLGA microspheres were fabricated, and the microspheres achieved the sustained release of ROCK inhibitor over 7-10 days in vitro. Our data should encourage researchers to use PLGA microspheres for treating corneal endothelial diseases.

  4. Bone induction by biomimetic PLGA copolymer loaded with a novel synthetic RADA16-P24 peptide in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Haitao; Hao, Shaofei [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Zheng, Qixin, E-mail: zheng-qx@163.com [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Li, Jingfeng [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zheng, Jin; Hu, Zhilei; Yang, Shuhua; Guo, Xiaodong [Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022 (China); Yang, Qin [Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2013-08-01

    Bone morphogenetic protein-2 (BMP-2) is a key bone morphogenetic protein, and poly(lactic-co-glycolic acid) (PLGA) has been widely used as scaffold for clinical use to carry treatment protein. In the previous studies, we have synthesized BMP-2-related peptide (P24) and found its capacity of inducing bone regeneration. In this research, we have synthesized a new amphiphilic peptide Ac-RADA RADA RADA RADA S[PO4]KIPKASSVPTELSAISTLYLDDD-CONH2 (RADA16-P24) with an assembly peptide RADA16-Ion the P24 item of BMP2 to form divalent ion-induced gelatin. Two methods of physisorption and chemical cross-linking were used to bind RADA16-P24 onto the surface of the copolymer PLGA to synthesize RADA16-P24–PLGA, and its capacity of attaching bone marrow stromal cells (BMSCs) was evaluated in vitro and inducing ectopic bone formation was examined in vivo. In vitro our results demonstrated that RADA16-P24–PLGA copolymer prepared by physisorbing or prepared by chemical cross-linking had a peptide binding rate of (2.0180 ± 0.5296)% or (10.0820 ± 0.8405)% respectively (P < 0.05). In addition the BMSCs proliferated vigorously in the RADA16-P24–PLGA biomaterials. Significantly the percentage of BMSCs attached to RADA16-P24–PLGA composite prepared by chemical cross-linking and physisorbing were (71.4 ± 7.5) % or (46.7 ± 5.8) % (P < 0.05). The in vivo study showed that RADA16-P24–PLGA chemical cross-linking could better induce ectopic bone formation compared with RADA16-P24–PLGA physisorbing and PLGA. It is concluded that the PLGA copolymer is a good RADA16-P24 carrier. This novel RADA16-P24–PLGA composite has strong osteogenic capability. - Highlights: • We have synthesized a new RADA16-P24 amphiphilic peptide. • It is an assembly peptide RADA16-Ion the P24 to form divalent ion-induced gelatin. • RADA16-P24/PLGA could better induce etopia osteogenesis compared with PLGA. • RADA16-P24–PLGA has strong osteogenic capability.

  5. Interaction between dimethyldioctadecylammonium bromide-modified PLGA microspheres and hyaluronic acid

    Science.gov (United States)

    Mulia, Kamarza; Devi, Krisanti, Elsa

    2017-02-01

    In application of intravitreal injection, an extended drug delivery system is desired so that the frequency of injection to treat diabetic retinopathy may be reduced. Poly(lactic-co-glycolic acid) polymer (PLGA) was used to encapsulate a model drug in the form of microspheres. The zeta potential of dimethyldioctadecylammonium bromide (DDAB)-modified PLGA microspheres in water was proportional to the DDAB concentration used in the preparation step, up to +57.8 mV. The scanning electron microscope pictures and the zeta potential data (SEM) confirmed that the surface of the PLGA has been modified by the cationic surfactant and that electrostatic interaction between the positively charged microspheres and the negatively charged vitreous were present.

  6. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    DEFF Research Database (Denmark)

    Guo, Wenjia; Quan, Peng; Fang, Liang

    2015-01-01

    The purpose of this study was to develop a PLGA microspheres-based donepezil (DP) formulation which was expected to sustain release of DP for one week with high encapsulation efficiency (EE). DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion......-solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared...... was in amorphous state or molecularly dispersed in microspheres. The Tg of PLGA was increased with the addition of DP. The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model, which suggested the diffusion governing...

  7. PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.

    Directory of Open Access Journals (Sweden)

    Xiaoyu Hu

    Full Text Available Opioid-induced hyperalgesia (OIH is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin's mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling.

  8. PLGA-Curcumin Attenuates Opioid-Induced Hyperalgesia and Inhibits Spinal CaMKIIα.

    Science.gov (United States)

    Hu, Xiaoyu; Huang, Fang; Szymusiak, Magdalena; Tian, Xuebi; Liu, Ying; Wang, Zaijie Jim

    2016-01-01

    Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin's mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling.

  9. PLGA nanoparticles as a platform for vitamin D-based cancer therapy.

    Science.gov (United States)

    Ramalho, Maria J; Loureiro, Joana A; Gomes, Bárbara; Frasco, Manuela F; Coelho, Manuel A N; Pereira, M Carmo

    2015-01-01

    Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were studied as drug delivery vehicles for calcitriol, the active form of vitamin D3. In vitro effects of calcitriol encapsulated in PLGA nanoparticles were evaluated with respect to free calcitriol on human pancreatic cell lines, S2-013 and hTERT-HPNE, and the lung cancer cell line A549. Encapsulated calcitriol retained its biological activity, reducing the cell growth. Cytotoxicity assays demonstrated that encapsulation of calcitriol enhanced its inhibitory effect on cell growth at a concentration of 2.4 μM for the S2-013 cells (91%) and for A549 cells (70%) comparared to the free calcitriol results. At this concentration the inhibitory effect on nontumor cells (hTERT-HPNE) decreased to 65%. This study highlights the ability of PLGA nanoparticles to deliver vitamin D3 into cancer cells, with major effects regarding cancer cell cycle arrest and major changes in the cell morphological features.

  10. Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Aravind, Athulya; Nair, Remya; Raveendran, Sreejith; Veeranarayanan, Srivani; Nagaoka, Yutaka; Fukuda, Takahiro; Hasumura, Takahashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D., E-mail: sakthi@toyo.jp

    2013-10-15

    Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions. - Highlights: • Aptamer escorted, theranostic biodegradable PLGA carriers were developed. • Can target cancer cells, control drug release, image and magnetically guide. • Highly specific to the targeted cancer cells thus delivering

  11. Electrospraying technique for the fabrication of metronidazole contained PLGA particles and their release profile

    Energy Technology Data Exchange (ETDEWEB)

    Prabhakaran, Molamma P., E-mail: nnimpp@nus.edu.sg [Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Zamani, Maedeh [Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Felice, Betiana [Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore); Laboratorio de Medios e Interfases, Departamento de Bioingeniería, Universidad Nacional de Tucumán, Av. Independencia 1800, Tucumán (Argentina); Ramakrishna, Seeram [Center for Nanofibers and Nanotechnology, Department of Mechanical Engineering, Faculty of Engineering, National University of Singapore, 2 Engineering Drive 3, Singapore 117576 (Singapore)

    2015-11-01

    Advanced engineering of materials for the development of drug delivery devices provides scope for novel and versatile strategies for treatment of various diseases. ‘Electrospraying’ was used to prepare PLGA microparticles and further encapsulate the drug, metronidazole (Met) within the particles to function as a drug delivery system. Two different solvents were utilized for the preparation of drug loaded PLGA particles, whereby the polymeric solution in dichloromethane (DCM) produced particles of bigger sizes than using trifluoroethanol (TFE). Scanning electron microscopy showed the spherical morphology of the particles, with sizes of 3946 ± 407 nm and 1774 ± 167 nm, respectively for PLGA-Met(DCM) and PLGA-Met(TFE). The FTIR spectroscopy proved the incorporation of metronidazole in the polymer, but without any specific drug–polymer interaction. The release of the drug from the particles was studied in phosphate buffered saline, where a sustained drug release was obtained for at least 41 days. Cytotoxicity evaluation of the drug extract using mesenchymal stem cells (MSCs) showed not hindering the proliferation of MSCs, and the cell phenotype was retained after incubation in the drug containing media. Electrospraying is suggested as a cost-effective and single step process for the preparation of polymeric microparticles for prolonged and controlled release of drug. - Highlights: • Electrospraying as a novel method for the fabrication of drug delivery device • Metronidazole encapsulated PLGA particles were fabricated by electrospraying. • Solvent DCM produced particles of double the size than using TFE. • Sustained release of metronidazole studied for a period of 41 days • Drug release pattern from particles followed Fickian diffusion. • PLGA-metronidazole particles can function as a substrate for periodontal regeneration.

  12. Synthesis and characterization of PLGA nanoparticles containing mixture of curcuminoids for optimization of photodynamic inactivation

    Science.gov (United States)

    Suzuki, Isabella L.; Inada, Natália M.; Marangoni, Valéria S.; Corrêa, Thaila Q.; Zucolotto, Valtencir; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-03-01

    Because of excessive use of antibiotics there is a growth in the number of resistant strains. Due to this growth of multiresistant bacteria, the number of searches looking for alternatives antibacterial therapeutic has increased, and among them is the antimicrobial photodynamic therapy (aPDT) or photodynamic inactivation (PDI). The photodynamic inactivation involves the action of a photosensitizer (PS), activated by a specific wavelength, in the present of oxygen, resulting in cytotoxic effect. Natural curcumin, consists of a mixture of three curcuminoids: curcumin, demethoxycurcumin and bis-demethoxycurcumin. Curcumin has various pharmacological properties, however, has extremely low solubility in aqueous solutions, which difficult the use as therapeutic agent. The present study aims to develop polymeric PLGA nanoparticles containing curcuminoids to improve water solubility, increase bioavailability providing protection from degradation (chemistry and physics), and to verify the efficacy in photodynamic inactivation of microorganisms. The PLGA-CURC were synthesized by nanoprecipitation, resulting in two different systems, with an average size of 172 nm and 70% encapsulation efficiency for PLGA-CURC1, and 215 nm and 80% for PLGA-CURC2. Stability tests showed the polymer protected the curcuminoids against premature degradation. Microbiological tests in vitro with curcuminoids water solution and both suspension of PLGA-CURC were efficient in Gram-positive bacterium and fungus. However, the solution presented dark toxicity at high concentrations, unlike the nanoparticles. Thus, it was concluded that it was possible to let curcuminoids water soluble by encapsulation in PLGA nanoparticles, to ensure improved stability in aqueous medium (storage), and to inactivate bacteria and fungus.

  13. Biodegradable PLGA-b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Locatelli, Erica; Comes Franchini, Mauro, E-mail: mauro.comesfranchini@unibo.it [University of Bologna, Dipartimento di Chimica Industriale Toso Montanari (Italy)

    2012-12-15

    During the past decades many synthetic polymers have been studied for nanomedicine applications and in particular as drug delivery systems. For this purpose, polymers must be non-toxic, biodegradable, and biocompatible. Polylactic-co-glycolic acid (PLGA) is one of the most studied polymers due to its complete biodegradability and ability to self-assemble into nanometric micelles that are able to entrap small molecules like drugs and to release them into body in a time-dependent manner. Despite fine qualities, using PLGA polymeric nanoparticles for in vivo applications still remains an open challenge due to many factors such as poor stability in water, big diameter (150-200 nm), and the removal of these nanocarriers from the blood stream by the liver and spleen thus reducing the concentration of drugs drastically in tumor tissue. Polyethylene glycol (PEG) is the most used polymers for drug delivery applications and the first PEGylated product is already on the market for over 20 years. This is due to its stealth behavior that inhibits the fast recognition by the immune system (opsonization) and generally leads to a reduced blood clearance of nanocarriers increasing blood circulation time. Furthermore, PEG is hydrophilic and able to stabilize nanoparticles by steric and not ionic effects especially in water. PLGA-PEG block copolymer is an emergent system because it can be easily synthesized and it possesses all good qualities of PLGA and also PEG capability so in the last decade it arose as one of the most promising systems for nanoparticles formation, drug loading, and in vivo drug delivery applications. This review will discuss briefly on PLGA-b-PEG synthesis and physicochemical properties, together with its improved qualities with respect to the single PLGA and PEG polymers. Moreover, we will focus on but in particular will treat nanoparticles formation and uses as new drug delivery system for nanomedical applications.

  14. Cationic nanoparticles with quaternary ammonium-functionalized PLGA-PEG-based copolymers for potent gene transfection

    Science.gov (United States)

    Wang, Yan-Hsung; Fu, Yin-Chih; Chiu, Hui-Chi; Wang, Chau-Zen; Lo, Shao-Ping; Ho, Mei-Ling; Liu, Po-Len; Wang, Chih-Kuang

    2013-11-01

    The objective of the present work was to develop new cationic nanoparticles (cNPs) with amphiphilic cationic copolymers for the delivery of plasmid DNA (pDNA). Cationic copolymers were built on the synthesis of quaternary ammonium salt compounds from diethylenetriamine (DETA) to include the positively charged head group and amphiphilic multi-grafts. PLGA- phe-PEG- qDETA (PPD), phe-PEG- qDETA-PLGA (PDP), and PLGA- phe-PEG- qDETA-PLGA (PPDP) cationic copolymers were created by this moiety of DETA quaternary ammonium, heterobifunctional polyethylene glycol (COOH-PEG-NH2), phenylalanine ( phe), and poly(lactic- co-glycolic acid) (PLGA). These new cNPs were prepared by the water miscible solvent displacement method. They exhibit good pDNA binding ability, as shown in a retardation assay that occurred at a particle size of 217 nm. The zeta potential was approximately +21 mV when the cNP concentration was 25 mg/ml. The new cNPs also have a better buffering capacity than PLGA NPs. However, the pDNA binding ability was demonstrated starting at a weight ratio of approximately 6.25 cNPs/pDNA. Gene transfection results showed that these cNPs had transfection effects similar to those of Lipofectamine 2000 in 293T cells. Furthermore, cNPs can also transfect human adipose-derived stem cells. The results indicate that the newly developed cNP is a promising candidate for a novel gene delivery vehicle.

  15. In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jiang; Liu, Yang; Luo, Rifang; Chen, Si; Li, Xin; Yuan, Shuheng; Wang, Jin, E-mail: jinxxwang@263.net; Huang, Nan

    2015-02-15

    Highlights: • Biodegradable dexamethasone-eluting PLGA stent coatings were developed. • Stent coatings can withstand the compressive and tensile strains without cracking. • Stent coatings presented favorable release kinetic for the lesion site. • Stent coatings can effectively inhibit the adhesion and activation of platelets. • Stent coatings can effectively inhibit the proliferation of SMC. - Abstract: Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and

  16. Solvothermal synthesis and characterization of monodisperse superparamagnetic iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Li, Shichuan; Zhang, Tonglai; Tang, Runze; Qiu, Hao [State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081 (China); Wang, Caiqin [Shandong Special Industry Group Co., Ltd, Shandong 255201 (China); Zhou, Zunning [State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology, Beijing 100081 (China)

    2015-04-01

    A series of magnetic iron oxide nanoparticle clusters with different structure guide agents were synthesized by a modified solvothermal method and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), thermogravimetric analyses (TG), a vibrating sample magnetometer (VSM) and Fourier transform infrared spectroscopy (FTIR). It is found that the superparamagnetic nanoparticles guided by NaCit (sodium citrate) have high saturation magnetization (M{sub s}) of 69.641 emu/g and low retentivity (M{sub r}) of 0.8 emu/g. Guiding to form superparamagnetic clusters with size range of 80–110 nm, the adherent small-molecule citrate groups on the surface prevent the prefabricated ferrite crystals growing further. In contrast, the primary small crystal guided and stabilized by the PVP long-chain molecules assemble freely to larger ones and stop growing in size range of 100–150 nm, which has saturation magnetization (M{sub s}) of 97.979 emu/g and retentivity (M{sub r}) of 46.323 emu/g. The relevant formation mechanisms of the two types of samples are proposed at the end. The superparamagnetic ferrite clusters guided by sodium citrate are expected to be used for movement controlling of passive interference particles to avoid aggregation and the sample guided by PVP will be a candidate of nanometer wave absorbing material. - Highlights: • A facile synthesis of two kinds of monodisperse iron oxide nano-particle clusters was performed via a modified one-step solvothermal method in this work. • The NaCit and PVP as different guiding agents are used to control the formation and aggregation of nano-crystals during reacting and the ripening processes. • The superparamagnetic NaCit–Fe{sub 3}O{sub 4} samples have high saturation magnetization (M{sub s}) of 69.641 emu/g and low retentivity (M{sub r}) of 0.8 emu/g. • The relevant formation mechanisms of the two types of samples are proposed.

  17. Fabrication of biodegradable polymer (PLGA) microstructures and applications in controlled drug delivery

    Science.gov (United States)

    Yang, Ren; Chen, Tianning; Chen, Hualing; Wang, Wanjun

    2004-01-01

    Using biodegradable polymers for implantable drug delivery purposes has been a very important research area and industry for many years. Polymers, such as PLGA, have been the most attractive one because it does not require removal after the drug has been released. We report a research effort to microfabricate high aspect ratio microstructures of PLGA and its potential applications in implantable drug delivery. The prototypes of packaged cells with dyes have also been made and currently under test for linear release of sample dyes.

  18. Silver ion beam irradiation effects on poly(lactide-co-glycolide) (PLGA)/clay nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Manpreet; Singh, Surinder [Guru Nanak Dev University, Department of Physics, Amritsar (India); Mehta, Rajeev [Thapar University, Department of Chemical Engineering, Patiala (India)

    2014-12-15

    Swift heavy ions induced modification of thin films of blends of poly(lactide-co-glycolide) (PLGA) (50:50) with organically modified nanoclay (Cloisite {sup registered} 30B) has been studied, using optical, structural and surface morphological analysis. Presence of nanoclay is found to enhance the properties of this degradable copolymer by reducing the rate of degradation even at high irradiation fluence. Optical and structural analysis of the polymer nanocomposites suggests that both the cross-linking and chain scission phenomenon are caused by swift heavy ion irradiation. XRD measurements show intercalation of PLGA in the clay galleries. Surface morphology of a nanocomposite indicates significant changes after irradiation at various fluences. (orig.)

  19. Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

    Directory of Open Access Journals (Sweden)

    Zhuo Ye

    2015-08-01

    Full Text Available AIM:To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid (PLGA microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.METHODS:Bevacizumab was encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil (S/O/hO method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.RESULTS:The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes (P<0.05. The AUC0-t of the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly. The immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA in rabbit eye tissues was still observed up to 42d. It was longer than that of the soluble form.CONCLUSION: The result of

  20. Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits

    Institute of Scientific and Technical Information of China (English)

    Zhuo; Ye; Yan-Li; Ji; Xiang; Ma; Jian-Guo; Wen; Wei; Wei; Shu-Man; Huang

    2015-01-01

    · AIM: To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly(L-lactic-co-glycolic acid)(PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.·METHODS: Bevacizumab was encapsulated into PLGA microsphere via the solid- in- oil- in- hydrophilic oil(S/O/h O) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at day 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.·RESULTS: The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than thatof bevacizumab solution. The T1/2of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2of intravitreal injection of soluble bevacizumab is 3.91 d in vitreous and4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes(P <0.05). The AUC0-tof the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly.The immunofluorescence staining of PLGA-encapsulated bevacizumab(b-PLGA) in rabbit eye tissues was still observed up to 42 d. It was longer than that of the soluble form.· CONCLUSION: The result of this

  1. Monodisperse, submicrometer droplets via condensation of microfluidic-generated gas bubbles.

    Science.gov (United States)

    Seo, Minseok; Matsuura, Naomi

    2012-09-10

    Microfluidics (MFs) can produce monodisperse droplets with precise size control. However, the synthesis of monodisperse droplets much smaller than the minimum feature size of the microfluidic device (MFD) remains challenging, thus limiting the production of submicrometer droplets. To overcome the minimum micrometer-scale droplet sizes that can be generated using typical MFDs, the droplet material is heated above its boiling point (bp), and then MFs is used to produce monodisperse micrometer-scale bubbles (MBs) that are easily formed in the size regime where standard MFDs have excellent size control. After MBs are formed, they are cooled, condensing into dramatically smaller droplets that are beyond the size limit achievable using the original MFD, with a size decrease corresponding to the density difference between the gas and liquid phases of the droplet material. Herein, it is shown experimentally that monodisperse, submicrometer droplets of predictable sizes can be condensed from a monodisperse population of MBs as generated by MFs. Using perfluoropentane (PFP) as a representative solvent due to its low bp (29.2 °C), it is demonstrated that monodisperse PFP MBs can be produced at MFD temperatures >3.6 °C above the bp of PFP over a wide range of sizes (i.e., diameters from 2 to 200 μm). Independent of initial size, the generated MBs shrink rapidly in size from about 3 to 0 °C above the bp of PFP, corresponding to a phase change from gas to liquid, after which they shrink more slowly to form fully condensed droplets with diameters 5.0 ± 0.1 times smaller than the initial size of the MBs, even in the submicrometer size regime. This new method is versatile and flexible, and may be applied to any type of low-bp solvent for the manufacture of different submicrometer droplets for which precisely controlled dimensions are required.

  2. PREPARATION OF MONODISPERSE CROSSLINKED POLYMER MICROSPHERES HAVING CHLOROMETHYL GROUP BY DISTILLATION-PRECIPITATION POLYMERIZATION

    Institute of Scientific and Technical Information of China (English)

    Shu-Feng Li; Xin-Lin Yang; Wen-Qiang Huang

    2005-01-01

    Monodisperse crosslinked poly(chloromethylstyrene-co-divinylbenzene) (poly(CMSt-co-DVB)) microspheres were prepared by distillation-precipitation copolymerization of chloromethylstyrene (CMSt) and divinylbenzene (DVB) in neat acetonitrile. The polymer particles had clean surfaces due to the absence of any added stabilizer. The size of the particles ranges from 2.59 μm to 3.19 μm and with mono-dispersity around 1.002-1.014. The effects of monomer feed in copolymerization on the microsphere formation were described. The polymer microspheres were characterized by SEM and chlorinity elemental analysis.

  3. A facile method to produce highly monodispersed nanospheres of cystine aggregates

    Science.gov (United States)

    Han, Hongliang; Wang, Chungang; Ma, Zhanfang; Su, Zhongmin

    2006-10-01

    Multiple shapes of nano- and micro-structured cystine aggregates, including spheres, rods, spindles, dendrites, and multipods, were easily synthesized just by adjusting the concentrations and pH values of L-Cysteine solutions under ultrasonic irritation. Importantly, highly monodispersed nanospheres of cystine aggregates 225 nm in diameter without any other shapes were easily obtained for the system of 0.1 M L-Cysteine with pH 8. This will provide a very simple and effective approach to produce monodispersed cystine microspheres, which could promote new possibilities for future applications in biosensor, drug delivery, medicine, and the production of nanomaterials.

  4. A facile method to produce highly monodispersed nanospheres of cystine aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Han Hongliang; Wang Chungang; Ma Zhanfang; Su Zhongmin [Chemistry Department, Northeast Normal University, Changchun 130024 (China)

    2006-10-28

    Multiple shapes of nano- and micro-structured cystine aggregates, including spheres, rods, spindles, dendrites, and multipods, were easily synthesized just by adjusting the concentrations and pH values of L-Cysteine solutions under ultrasonic irritation. Importantly, highly monodispersed nanospheres of cystine aggregates 225 nm in diameter without any other shapes were easily obtained for the system of 0.1 M L-Cysteine with pH 8. This will provide a very simple and effective approach to produce monodispersed cystine microspheres, which could promote new possibilities for future applications in biosensor, drug delivery, medicine, and the production of nanomaterials.

  5. Effects of lactic acid and glycolic acid on human osteoblasts: a way to understand PLGA involvement in PLGA/calcium phosphate composite failure.

    Science.gov (United States)

    Meyer, Florent; Wardale, John; Best, Serena; Cameron, Ruth; Rushton, Neil; Brooks, Roger

    2012-06-01

    The use of degradable composite materials in orthopedics remains a field of intense research due to their ability to support new bone formation and degrade in a controlled manner, broadening their use for orthopedic applications. Poly (lactide-co-glycolide) acid (PLGA), a degradable biopolymer, is now a popular material for different orthopedic applications and is proposed for use in tissue engineering scaffolds either alone or combined with bioactive ceramics. Interference screws composed of calcium phosphates and PLGA are readily available in the market. However, some reports highlight problems of screw migration or aseptic cyst formation following screw degradation. In order to understand these phenomena and to help to improve implant formulation, we have evaluated the effects of PLGA degradation products: lactic acid and glycolic acid on human osteoblasts in vitro. Cell proliferation, differentiation, and matrix mineralization, important for bone healing were studied. It was found that the toxicity of polymer degradation products under buffering conditions was limited to high concentrations. However, non-toxic concentrations led to a decrease in cell proliferation, rapid cell differentiation, and mineralization failure. Calcium, whilst stimulating cell proliferation was not able to overcome the negative effects of high concentrations of lactic and glycolic acids on osteoblasts. These effects help to explain recently reported clinical failures of calcium phosphate/PLGA composites, but further in vitro analyses are needed to mimic the dynamic situation which occurs in the body by, for example, culture of osteoblasts with materials that have been pre-degraded to different extents and thus be able to relate these findings to the degradation studies that have been performed previously.

  6. Bone induction by biomimetic PLGA-(PEG-ASP)n copolymer loaded with a novel synthetic BMP-2-related peptide in vitro and in vivo.

    Science.gov (United States)

    Lin, Zhen-Yu; Duan, Zhi-Xia; Guo, Xiao-Dong; Li, Jing-Feng; Lu, Hong-Wei; Zheng, Qi-Xin; Quan, Da-Ping; Yang, Shu-Hua

    2010-06-01

    BMP-2 is one of the most important growth factors of bone regeneration. Polylactide-co-glycolic acid (PLGA), which is used as a biodegradable scaffold for delivering therapeutic agents, has been intensively investigated. In previous studies, we synthesized a novel BMP-2-related peptide (designated P24) and found that it could enhance the osteoblastic differentiation of bone marrow stromal cells (BMSCs). The objective of this study was to construct a biomimetic composite by incorporating P24 into a modified PLGA-(PEG-ASP)n copolymer to promote bone formation. In vitro, our results demonstrated that PLGA-(PEG-ASP)n scaffolds were shown to be an efficient system for sustained release of P24. Significantly more BMSCs attached to the P24/PLGA-(PEG-ASP)n and PLGA-(PEG-ASP)n membranes than to PLGA, and the cells in the two groups subsequently proliferated more vigorously than those in the PLGA group. The expression of osteogenic markers in P24/PLGA-(PEG-ASP)n group was stronger than that in the PLGA-(PEG-ASP)n and PLGA groups. Radiographic and histological examination, Western blotting and RT-PCR showed that P24/PLGA-(PEG-ASP)n scaffold could induce more effective ectopic bone formation in vivo, as compared with PLGA-(PEG-ASP)n or gelatin sponge alone. It is concluded that the PLGA-(PEG-ASP)n copolymer is a good P24 carrier and can serve as a good scaffold for controlled release of P24. This novel P24/PLGA-(PEG-ASP)n composite promises to be an excellent biomaterial for inducing bone regeneration. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  7. Preparation and Characterization of Soluble Eggshell Membrane Protein/PLGA Electrospun Nanofibers for Guided Tissue Regeneration Membrane

    Directory of Open Access Journals (Sweden)

    Jun Jia

    2012-01-01

    Full Text Available Guided tissue regeneration (GTR is a widely used method in periodontal therapy, which involves the placement of a barrier membrane to exclude migration of epithelium and ensure repopulation of periodontal ligament cells. The objective of this study is to prepare and evaluate a new type of soluble eggshell membrane protein (SEP/poly (lactic-co-glycolic acid (PLGA nanofibers using electrospinning method for GTR membrane application. SEP/PLGA nanofibers were successfully prepared with various blending ratios. The morphology, chemical composition, surface wettability, and mechanical properties of the nanofibers were characterized using scanning electron microscopy (SEM, contact angle measurement, Fourier transform-infrared spectroscopy (FTIR, and a universal testing machine. L-929 fibroblast cells were used to evaluate the biocompatibility of SEP/PLGA nanofibers and investigate the interaction between cells and nanofibers. Results showed that the SEP/PLGA electrospun membrane was composed of uniform, bead-free nanofibers, which formed an interconnected porous network structure. Mechanical property of SEP has been greatly improved by the addition of PLGA. The biological study results showed that SEP/PLGA nanofibers could enhance cell attachment, spreading, and proliferation. The study indicated the potential of SEP/PLGA nanofibers for GTR application and provided a basis for future optimization.

  8. In vitro and In vivo Evaluation of the Developed PLGA/HAp/Zein Scaffolds for Bone-Cartilage Interface Regeneration

    Institute of Scientific and Technical Information of China (English)

    LIN Yong Xin; DING Zhi Yong; ZHOU Xiao Bin; LI Si Tao; XIE De Ming; LI Zhi Zhong; SUN Guo Dong

    2015-01-01

    Objective To investigate the effect of electronspun PLGA/HAp/Zein scaffolds on the repair of cartilage defects. Methods The PLGA/HAp/Zein composite scaffolds were fabricated by electrospinning method. The physiochemical properties and biocompatibility of the scaffolds were separately characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), and fourier transform infrared spectroscopy (FTIR), human umbilical cord mesenchymal stem cells (hUC-MSCs) culture and animal experiments. Results The prepared PLGA/HAp/Zein scaffolds showed fibrous structure with homogenous distribution. hUC-MSCs could attach to and grow well on PLGA/HAp/Zein scaffolds, and there was no significant difference between cell proliferation on scaffolds and that without scaffolds (P>0.05). The PLGA/HAp/Zein scaffolds possessed excellent ability to promote in vivo cartilage formation. Moreover, there was a large amount of immature chondrocytes and matrix with cartilage lacuna on PLGA/HAp/Zein scaffolds. Conclusion The data suggest that the PLGA/HAp/Zein scaffolds possess good biocompatibility, which are anticipated to be potentially applied in cartilage tissue engineering and reconstruction.

  9. Electrospun PDLLA/PLGA composite membranes for potential application in guided tissue regeneration.

    Science.gov (United States)

    Zhang, Ershuai; Zhu, Chuanshun; Yang, Jun; Sun, Hong; Zhang, Xiaomin; Li, Suhua; Wang, Yonglan; Sun, Lu; Yao, Fanglian

    2016-01-01

    With the aim to explore a membrane system with appropriate degradation rate and excellent cell-occlusiveness for guided tissue regeneration (GTR), a series of poly(D, L-lactic acid) (PDLLA)/poly(D, L-lactic-co-glycolic acid) (PLGA) (100/0, 70/30, 50/50, 30/70, 0/100, w/w) composite membranes were fabricated via electrospinning. The fabricated membranes were evaluated by morphological characterization, water contact angle measurement and tensile test. In vitro degradation was characterized in terms of the weight loss and the morphological change. Moreover, in vitro cytologic research revealed that PDLLA/PLGA composite membranes could efficiently inhibit the infiltration of 293 T cells. Finally, subcutaneous implant test on SD rat in vivo showed that PDLLA/PLGA (70/30, 50/50) composite membranes could function well as a physical barrier to prevent cellular infiltration within 13 weeks. These results suggested that electrospun PDLLA/PLGA (50/50) composite membranes could serve as a promising barrier membrane for guided tissue regeneration due to suitable biodegradability, preferable mechanical properties and excellent cellular shielding effects.

  10. Controlled release of dexamethasone from porous PLGA scaffolds under cyclic loading

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Poly(L-lactide)-b-poly(ethylene glycol)(PLLA-PEG) microspheres containing dexamethasone(Dex) have been fabricated using a spray-drying technique.Porous poly(lactic-co-glycolic acid)(PLGA) scaffolds were prepared using a method combining thermally induced phase separation and porogen leaching.A post-seeding technique was used to immobilize Dex-containing PLLA-PEG microspheres on porous PLGA scaffolds,and drug-containing microspheres-scaffolds(MS-S) were obtained.Simple Dex-containing scaffolds(D-S) were also made as the control by directly dissolving Dex in the PLGA solution during scaffold fabrication.The morphologies of microspheres and scaffolds were studied by scanning electron microscopy.Drug release profiles of both MS-S and D-S were determined under cyclic loading and shaking water bath,respectively.The cumulative release of Dex was measured using an ultraviolet visible spectrophotometer.The results show that the incorporation of Dex and microspheres had little effect on the overall morphology of the porous PLGA scaffolds.Cyclic loading significantly accelerated the release of Dex from the drug-containing scaffolds.Compared with D-S,MS-S reduced the drug release rate.The controlled drug delivery of tissue engineering scaffolds under cyclic loading is a key factor to mimic the in vivo mechanical environments and achieve optical clinical efficacy.

  11. Glycolic Acid-Catalyzed Deamidation of Asparagine Residues in Degrading PLGA Matrices: A Computational Study

    Directory of Open Access Journals (Sweden)

    Noriyoshi Manabe

    2015-03-01

    Full Text Available Poly(lactic-co-glycolic acid (PLGA is a strong candidate for being a drug carrier in drug delivery systems because of its biocompatibility and biodegradability. However, in degrading PLGA matrices, the encapsulated peptide and protein drugs can undergo various degradation reactions, including deamidation at asparagine (Asn residues to give a succinimide species, which may affect their potency and/or safety. Here, we show computationally that glycolic acid (GA in its undissociated form, which can exist in high concentration in degrading PLGA matrices, can catalyze the succinimide formation from Asn residues by acting as a proton-transfer mediator. A two-step mechanism was studied by quantum-chemical calculations using Ace-Asn-Nme (Ace = acetyl, Nme = NHCH3 as a model compound. The first step is cyclization (intramolecular addition to form a tetrahedral intermediate, and the second step is elimination of ammonia from the intermediate. Both steps involve an extensive bond reorganization mediated by a GA molecule, and the first step was predicted to be rate-determining. The present findings are expected to be useful in the design of more effective and safe PLGA devices.

  12. Effects of protein binding on the biodistribution of PEGylated PLGA nanoparticles post oral administration

    CSIR Research Space (South Africa)

    Semete, B

    2012-03-01

    Full Text Available detected in plasma was higher than that of uncoated PLGA particles, indicating that systemic circulation time can also be increased with oral formulations. The difference in the in vitro protein binding as a result of the different poloxamers used versus...

  13. Effect of blending HA-g-PLLA on xanthohumol-loaded PLGA fiber membrane.

    Science.gov (United States)

    Qiao, Tiankui; Jiang, Suchen; Song, Ping; Song, Xiaofeng; Liu, Qimin; Wang, Lijuan; Chen, Xuesi

    2016-10-01

    Electropsun poly (lactide-co-glycolide) (PLGA) fiber membrane loaded xanthohumol (XN) has been developed using a co-solvent system of chloroform and dimethylformamide. To enhance its biological functionality as bone tissue engineering scaffolds, 5wt% hydroxyapatite grafted poly (l-lactic acid) (HA-g-PLLA) is blended into the spinning solution. The purpose of the present work is to disclose the effect of blending HA-g-PLLA on the corresponding properties of the medicated fiber membrane including morphology, thermodynamics, wettability, drug release, mechanics as well as cytotoxicity. XN and HA-g-PLLA can be well blended with PLGA to make fibers. Blending HA-g-PLLA not only turns amorphous XN/PLGA fiber membrane into crystal structure, but also changes the membranous wettability. Various medicated membranes exhibit the sustained release profiles. Drug release rate of the ternary membrane with HA-g-PLLA is slower compared to the binary XN/PLGA, and for the ternary membrane, the drug release accelerates with increasing XN content. A model is proposed to account for the drug release process. Tensile testing shows that at 10% of XN, the comprehensive mechanics of the ternary is preferable to the binary. At the same time, these fiber membranes are no cytotoxicity.

  14. Electrospinning of PLGA/gum tragacanth nanofibers containing tetracycline hydrochloride for periodontal regeneration.

    Science.gov (United States)

    Ranjbar-Mohammadi, Marziyeh; Zamani, M; Prabhakaran, M P; Bahrami, S Hajir; Ramakrishna, S

    2016-01-01

    Controlled drug release is a process in which a predetermined amount of drug is released for longer period of time, ranging from days to months, in a controlled manner. In this study, novel drug delivery devices were fabricated via blend electrospinning and coaxial electrospinning using poly lactic glycolic acid (PLGA), gum tragacanth (GT) and tetracycline hydrochloride (TCH) as a hydrophilic model drug in different compositions and their performance as a drug carrier scaffold was evaluated. Scanning electron microscopy (SEM) results showed that fabricated PLGA, blend PLGA/GT and core shell PLGA/GT nanofibers had a smooth and bead-less morphology with the diameter ranging from 180 to 460 nm. Drug release studies showed that both the fraction of GT within blend nanofibers and the core-shell structure can effectively control TCH release rate from the nanofibrous membranes. By incorporation of TCH into core-shell nanofibers, drug release was sustained for 75 days with only 19% of burst release within the first 2h. The prolonged drug release, together with proven biocompatibility, antibacterial and mechanical properties of drug loaded core shell nanofibers make them a promising candidate to be used as drug delivery system for periodontal diseases.

  15. Curcumin loaded-PLGA nanoparticles conjugated with Tet-1 peptide for potential use in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Anila Mathew

    Full Text Available Alzheimer's disease is a growing concern in the modern world. As the currently available medications are not very promising, there is an increased need for the fabrication of newer drugs. Curcumin is a plant derived compound which has potential activities beneficial for the treatment of Alzheimer's disease. Anti-amyloid activity and anti-oxidant activity of curcumin is highly beneficial for the treatment of Alzheimer's disease. The insolubility of curcumin in water restricts its use to a great extend, which can be overcome by the synthesis of curcumin nanoparticles. In our work, we have successfully synthesized water-soluble PLGA coated- curcumin nanoparticles and characterized it using different techniques. As drug targeting to diseases of cerebral origin are difficult due to the stringency of blood-brain barrier, we have coupled the nanoparticle with Tet-1 peptide, which has the affinity to neurons and possess retrograde transportation properties. Our results suggest that curcumin encapsulated-PLGA nanoparticles are able to destroy amyloid aggregates, exhibit anti-oxidative property and are non-cytotoxic. The encapsulation of the curcumin in PLGA does not destroy its inherent properties and so, the PLGA-curcumin nanoparticles can be used as a drug with multiple functions in treating Alzheimer's disease proving it to be a potential therapeutic tool against this dreaded disease.

  16. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    CSIR Research Space (South Africa)

    Mandiwana, V

    2015-09-01

    Full Text Available the biodistribution of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([(sup153)Sm]Sm(sub2)O(sub3)) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear...

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant, E-mail: pmishra@dbeb.iitd.ac.in [Indian Institute of Technology Delhi, Department of Biochemical Engineering and Biotechnology (India)

    2013-03-15

    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 {mu}m, 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.

  19. AS1411 aptamer tagged PLGA-lecithin-PEG nanoparticles for tumor cell targeting and drug delivery.

    Science.gov (United States)

    Aravind, Athulya; Jeyamohan, Prashanti; Nair, Remya; Veeranarayanan, Srivani; Nagaoka, Yutaka; Yoshida, Yasuhiko; Maekawa, Toru; Kumar, D Sakthi

    2012-11-01

    Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery.

  20. Design of PLGA-based depot delivery systems for biopharmaceuticals prepared by spray drying

    DEFF Research Database (Denmark)

    Wan, Feng; Yang, Mingshi

    2016-01-01

    and peptide drugs with a steady pharmacokinetic/pharmacodynamic profile maintained for a long period. However, the development of PLGA-based microparticle systems is still impeded by lack of easy, fast, effective manufacturing technologies. The aim of this paper is to review recent advances in spray drying...... parameters on the critical quality attributes of the spray-dried microparticles....

  1. Chitosan/siRNA nanoparticles encapsulated in PLGA nanofibers for siRNA delivery

    DEFF Research Database (Denmark)

    Chen, Menglin; Gao, Shan; Dong, Mingdong

    2012-01-01

    Composite nanofibers of biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) encapsulating chitosan/siRNA nanoparticles (NPs) were prepared by electrospinning. Acidic/alkaline hydrolysis and a bulk/surface degradation mechanism were investigated in order to achieve an optimized release profile...

  2. Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells

    Directory of Open Access Journals (Sweden)

    Mura S

    2011-10-01

    Full Text Available Simona Mura1,2, Herve Hillaireau1,2, Julien Nicolas1,2, Benjamin Le Droumaguet1,2, Claire Gueutin1,2, Sandrine Zanna3, Nicolas Tsapis1,2, Elias Fattal1,2 1Univ Paris-Sud, UMR 8612, Châtenay Malabry, F-92296; 2CNRS, Châtenay Malabry, F-92296; 3Laboratoire de Physico-Chimie des Surfaces, CNRS-ENSCP (UMR 7045, Ecole Nationale Superiore de Chimie de Paris, France Background: Because of the described hazards related to inhalation of manufactured nanoparticles, we investigated the lung toxicity of biodegradable poly (lactide-co-glycolide (PLGA nanoparticles displaying various surface properties on human bronchial Calu-3 cells. Methods: Positively and negatively charged as well as neutral nanoparticles were tailored by coating their surface with chitosan, Poloxamer, or poly (vinyl alcohol, respectively. Nanoparticles were characterized in terms of size, zeta potential, and surface chemical composition, confirming modifications provided by hydrophilic polymers. Results: Although nanoparticle internalization by lung cells was clearly demonstrated, the cytotoxicity of the nanoparticles was very limited, with an absence of inflammatory response, regardless of the surface properties of the PLGA nanoparticles. Conclusion: These in vitro results highlight the safety of biodegradable PLGA nanoparticles in the bronchial epithelium and provide initial data on their potential effects and the risks associated with their use as nanomedicines. Keywords: nanoparticles, PLGA, surface properties, Calu-3, toxicity, inflammation

  3. Degradation of electrospun PLGA-chitosan/PVA membranes and their cytocompatibility in vitro.

    Science.gov (United States)

    Duan, Bin; Wu, Lili; Li, Xiaoran; Yuan, Xiaoyan; Li, Xiulan; Zhang, Yang; Yao, Kangde

    2007-01-01

    Nanofibrious composite poly(lactide-co-glycolide) (PLGA) and chitosan/poly(vinyl alcohol) (PVA) membranes were prepared by simultaneously electrospinning PLGA and chitosan/PVA from two different syringes. The in vitro degradation of PLGA and cross-linked composite membranes was examined for up to 10 weeks in phosphate-buffered saline (PBS, pH 7.4) at 37 degrees C. The pH of PBS, the weight average molecular weight of PLGA, fiber morphology and mechanical properties, including tensile strength, Young's modulus and elongation-at-break, were measured as a function of degradation time. The fibrous composite membranes were further investigated as a promising scaffold for human embryo skin fibroblasts (hESFs) culture. The cell adhesion and morphology of hESFs seeded on each electrospun membrane was observed using scanning electron microscope and inverted phase contrast microscopy after Wright-Giemsa staining. The introduction of chitosan/PVA component changed the hydrophilic/hydrophobic balance and, thus, influenced degradation behavior and mechanical properties of the composite membranes during degradation. The cells could not only favorably attach and grow well on the composite membranes, but were also able to migrate and infiltrate the membranes. Therefore, the results suggest that the composite membranes can positively mimic the structure of natural extracellular matrices and have the potential for application as three-dimensional tissue-engineering scaffolds.

  4. Glycolic acid-catalyzed deamidation of asparagine residues in degrading PLGA matrices: a computational study.

    Science.gov (United States)

    Manabe, Noriyoshi; Kirikoshi, Ryota; Takahashi, Ohgi

    2015-03-31

    Poly(lactic-co-glycolic acid) (PLGA) is a strong candidate for being a drug carrier in drug delivery systems because of its biocompatibility and biodegradability. However, in degrading PLGA matrices, the encapsulated peptide and protein drugs can undergo various degradation reactions, including deamidation at asparagine (Asn) residues to give a succinimide species, which may affect their potency and/or safety. Here, we show computationally that glycolic acid (GA) in its undissociated form, which can exist in high concentration in degrading PLGA matrices, can catalyze the succinimide formation from Asn residues by acting as a proton-transfer mediator. A two-step mechanism was studied by quantum-chemical calculations using Ace-Asn-Nme (Ace = acetyl, Nme = NHCH3) as a model compound. The first step is cyclization (intramolecular addition) to form a tetrahedral intermediate, and the second step is elimination of ammonia from the intermediate. Both steps involve an extensive bond reorganization mediated by a GA molecule, and the first step was predicted to be rate-determining. The present findings are expected to be useful in the design of more effective and safe PLGA devices.

  5. Preparation and Haemocompatibility of Regular Array Microporous PLGA Films on Stainless Steel Surface

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Regular array microporous films from poly ( L-lactic-co-glycolic acid) ( PLGA ) were prepared on stainless steel substrates utilizing the condensation of water droplets on polymer solutions. The size of the pores and regularity can be controlled by atmospheric humidity and concentration of polymer solution. The microporons films have strong hydrophobicity and good haemocompatibility.

  6. Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles.

    Science.gov (United States)

    Sharma, Deepak; Sharma, Rakesh Kumar; Sharma, Navneet; Gabrani, Reema; Sharma, Sanjeev K; Ali, Javed; Dang, Shweta

    2015-10-01

    The objective of the present investigation was to optimize diazepam (Dzp)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) to achieve delivery in the brain through intranasal administration. Dzp nanoparticles (DNP) were formulated by nanoprecipitation and optimized using Box-Behnken design. The influence of various independent process variables (polymer, surfactant, aqueous to organic (w/o) phase ratio, and drug) on resulting properties of DNP (z-average and drug entrapment) was investigated. Developed DNP showed z-average 148-337 d.nm, polydispersity index 0.04-0.45, drug entrapment 69-92%, and zeta potential in the range of -15 to -29.24 mV. Optimized DNP were further analyzed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), ex-vivo drug release, and in-vitro cytotoxicity. Ex-vivo drug release study via sheep nasal mucosa from DNP showed a controlled release of 64.4% for 24 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay performed on Vero cell line showed less toxicity for DNP as compared to Dzp suspension (DS). Gamma scintigraphy and biodistribution study of DNP and DS was performed on Sprague-Dawley rats using technetium-99m-labeled ((99m)Tc) Dzp formulations to investigate the nose-to-brain drug delivery pathway. Brain/blood uptake ratios, drug targeting efficiency, and direct nose-to-brain transport were found to be 1.23-1.45, 258, and 61% for (99m)Tc-DNP (i.n) compared to (99m)Tc-DS (i.n) (0.38-1.06, 125, and 1%). Scintigraphy images showed uptake of Dzp from nose-to-brain, and this observation was in agreement with the biodistribution results. These results suggest that the developed poly(D,L-lactide-co-glycolide) (PLGA) NP could serve as a potential carrier of Dzp for nose-to-brain delivery in outpatient management of status epilepticus.

  7. Surface modified PLGA nanoparticles for brain targeting of Bacoside-A.

    Science.gov (United States)

    Jose, S; Sowmya, S; Cinu, T A; Aleykutty, N A; Thomas, S; Souto, E B

    2014-10-15

    The present paper focuses on the development and in vitro/in vivo characterization of nanoparticles composed of poly-(D,L)-Lactide-co-Glycolide (PLGA) loading Bacoside-A, as a new approach for the brain delivery of the neuroprotective drug for the treatment of neurodegenerative disorders (e.g. Alzheimer Disease). Bacoside-A-loaded PLGA nanoparticles were prepared via o/w emulsion solvent evaporation technique. Surface of the nanoparticles were modified by coating with polysorbate 80 to facilitate the crossing of the blood brain barrier (BBB), and the processing parameters (i.e. sonication time, the concentration of polymer (PLGA) and surfactant (polysorbate 80), and drug-polymer ratio) were optimized with the aim to achieve a high production yield. Brain targeting potential of the nanoparticles was evaluated by in vivo studies using Wistar albino rats. The nanoparticles produced by optimal formulation were within the nanosized range (70-200 nm) with relatively low polydispersity index (0.391 ± 1.2). The encapsulation efficiency of Bacoside-A in PLGA nanoparticles was 57.11 ± 7.11%, with a drug loading capacity of 20.5 ± 1.98%. SEM images showed the spherical shape of the PLGA nanoparticles, whereas their low crystallinity was demonstrated by X-ray studies, which also confirmed no chemical interactions between the drug and polymer molecules. The in vitro release of Bacoside-A from the PLGA nanoparticles followed a sustained release pattern with a maximum release of up to 83.04 ± 2.55% in 48 h. When compared to pure drug solution (2.56 ± 1.23 μg/g tissue), in vivo study demonstrated higher brain concentration of Bacoside-A (23.94 ± 1.74 μg/g tissue) suggesting a significant role of surface coated nanoparticles on brain targeting. The results indicate the potential of surface modified PLGA nanoparticles for the delivery of Bacoside-A to the brain.

  8. Effects of Caryota mitis profilin-loaded PLGA nanoparticles in a murine model of allergic asthma

    Directory of Open Access Journals (Sweden)

    Xiao X

    2013-11-01

    Full Text Available Xiaojun Xiao,1,* Xiaowei Zeng,2,* Xinxin Zhang,3,* Li Ma,3 Xiaoyu Liu,1 Haiqiong Yu,1 Lin Mei,2 Zhigang Liu1 1Institute of Allergy and Immunology, School of Medicine, Shenzhen University, Shenzhen, 2Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, 3Faculty of Basic Medical Science, Nanchang University, Nanchang, People's Republic of China *These authors contributed equally to this work Background: Pollen allergy is the most common allergic disease. However, tropical pollens, such as those of Palmae, have seldom been investigated compared with the specific immunotherapy studies done on hyperallergenic birch, olive, and ragweed pollens. Although poly(lactic-co-glycolic acid (PLGA has been extensively applied as a biodegradable polymer in medical devices, it has rarely been utilized as a vaccine adjuvant to prevent and treat allergic disease. In this study, we investigated the immunotherapeutic effects of recombinant Caryota mitis profilin (rCmP-loaded PLGA nanoparticles and the underlying mechanisms involved. Methods: A mouse model of allergenic asthma was established for specific immunotherapy using rCmP-loaded PLGA nanoparticles as the adjuvant. The model was evaluated by determining airway hyperresponsiveness and levels of serum-specific antibodies (IgE, IgG, and IgG2a and cytokines, and observing histologic sections of lung tissue. Results: The rCmP-loaded PLGA nanoparticles effectively inhibited generation of specific IgE and secretion of the Th2 cytokine interleukin-4, facilitated generation of specific IgG2a and secretion of the Th1 cytokine interferon-gamma, converted the Th2 response to Th1, and evidently alleviated allergic symptoms. Conclusion: PLGA functions more appropriately as a specific immunotherapy adjuvant for allergen vaccines than does conventional Al(OH3 due to its superior efficacy, longer potency, and markedly fewer side effects. The rCmP-loaded PLGA nanoparticles developed

  9. PLGA nanofibers blended with designer self-assembling peptides for peripheral neural regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Nune, Manasa; Krishnan, Uma Maheswari; Sethuraman, Swaminathan, E-mail: swami@sastra.edu

    2016-05-01

    Electrospun nanofibers are attractive candidates for neural regeneration due to similarity to the extracellular matrix. Several synthetic polymers have been used but they lack in providing the essential biorecognition motifs on their surfaces. Self-assembling peptide nanofiber scaffolds (SAPNFs) like RADA16 and recently, designer SAPs with functional motifs RADA16-I-BMHP1 areexamples, which showed successful spinal cord regeneration. But these peptide nanofiber scaffolds have poor mechanical properties and faster degradation rates that limit their use for larger nerve defects. Hence, we have developed a novel hybrid nanofiber scaffold of polymer poly(L-lactide-co-glycolide) (PLGA) and RADA16-I-BMHP1. The scaffolds were characterized for the presence of peptides both qualitatively and quantitatively using several techniques like SEM, EDX, FTIR, CHN analysis, Circular Dichroism analysis, Confocal and thermal analysis. Peptide self-assembly was retained post-electrospinning and formed rod-like nanostructures on PLGA nanofibers. In vitro cell compatibility was studied using rat Schwann cells and their adhesion, proliferation and gene expression levels on the designed scaffolds were evaluated. Our results have revealed the significant effects of the peptide blended scaffolds on promoting Schwann cell adhesion, extension and phenotypic expression. Neural development markers (SEM3F, NRP2 & PLX1) gene expression levels were significantly upregulated in peptide blended scaffolds compared to the PLGA scaffolds. Thus the hybrid blended novel designer scaffolds seem to be promising candidates for successful and functional regeneration of the peripheral nerve. - Highlights: • A novel blended scaffold of polymer PLGA and designer self-assembling peptide RADA16-I-BMPH1 was designed • The peptide retained the self-assembling features and formed rod like nanostructures on top of PLGA nanofibers • PLGA-peptide scaffolds have promoted the Schwann cell bipolar extension and

  10. Porous nano-hydroxyapatite/collagen scaffold containing drug-loaded ADM-PLGA microspheres for bone cancer treatment.

    Science.gov (United States)

    Rong, Zi-Jie; Yang, Lian-Jun; Cai, Bao-Ta; Zhu, Li-Xin; Cao, Yan-Lin; Wu, Guo-Feng; Zhang, Zan-Jie

    2016-05-01

    To develop adriamycin (ADM)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite/collagen scaffold (ADM-PLGA-NHAC). To provide novel strategies for future treatment of osteosarcoma, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of ADM-PLGA-NHAC on the osteosarcoma MG63 cells, and its bone repair capacity, were investigated in vivo and in vitro. The PLGA copolymer was utilized as a drug carrier to deliver ADM-PLGA nanoparticles (ADM-PLGA-NP). Porous nano-hydroxyapatite and collagen were used to materials to produce the porous nano-hydroxyapatite/collagen scaffold (NHAC), into which the ADM-PLGA-NP was loaded. The performance of the drug-carrying scaffold was assessed using multiple techniques, including scanning electron microscopy and in vitro extended release. The antineoplastic activities of scaffold extracts on the human osteosarcoma MG63 cell line were evaluated in vitro using the cell counting kit-8 (CCK8) method and live-dead cell staining. The bone repair ability of the scaffold was assessed based on the establishment of a femoral condyle defect model in rabbits. ADM-PLGA-NHAC and NHAC were implanted into the rat muscle bag for immune response experiments. A tumor-bearing nude mice model was created, and the TUNEL and HE staining results were observed under optical microscopy to evaluate the antineoplastic activity and toxic side effects of the scaffold. The composite scaffold demonstrated extraordinary extended-release properties, and its extracts also exhibited significant inhibition of the growth of osteosarcoma MG63 cells. In the bone repair experiment, no significant difference was observed between ADM-PLGA-NHAC and NHAC by itself. In the immune response experiments, ADM-PLGA-NHAC exhibited remarkable biocompatibility. The in vivo antitumor experiment revealed that the implantation of ADM-PLGA-NHAC in the tumor resulted in a improved antineoplastic

  11. PLGA nanofiber membranes loaded with epigallocatechin-3-O-gallate are beneficial to prevention of postsurgical adhesions

    Directory of Open Access Journals (Sweden)

    Shin YC

    2014-08-01

    Full Text Available Yong Cheol Shin,1,* Won Jun Yang,1,* Jong Ho Lee,1 Jin-Woo Oh,2 Tai Wan Kim,3 Jong-Chul Park,4 Suong-Hyu Hyon,5 Dong-Wook Han1 1Department of Cogno-Mechatronics Engineering, Pusan National University, Busan, Republic of Korea; 2Department of Nanomaterials Engineering, College of Nanoscience and Nanotechnology, Pusan National University, Busan, Republic of Korea; 3Department of Design, College of Arts, Pusan National University, Busan, Republic of Korea; 4Department of Medical Engineering, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Center for Fiber and Textile Science, Kyoto Institute of Technology, Kyoto, Japan *These authors contributed equally to this work Abstract: This study concentrates on the development of biodegradable nanofiber membranes with controlled drug release to ensure reduced tissue adhesion and accelerated healing. Nanofibers of poly(lactic-co-glycolic acid (PLGA loaded with epigallocatechin-3-O-gallate (EGCG, the most bioactive polyphenolic compound in green tea, were electrospun. The physicochemical and biomechanical properties of EGCG-releasing PLGA (E-PLGA nanofiber membranes were characterized by atomic force microscopy, EGCG release and degradation profiles, and tensile testing. In vitro antioxidant activity and hemocompatibility were evaluated by measuring scavenged reactive oxygen species levels and activated partial thromboplastin time, respectively. In vivo antiadhesion efficacy was examined on the rat peritonea with a surgical incision. The average fiber diameter of E-PLGA membranes was approximately 300–500 nm, which was almost similar to that of pure PLGA equivalents. E-PLGA membranes showed sustained EGCG release mediated by controlled diffusion and PLGA degradation over 28 days. EGCG did not adversely affect the tensile strength of PLGA membranes, whereas it significantly decreased the elastic modulus and increased the strain at break. E-PLGA membranes were significantly effective in

  12. Conventional and microwave hydrothermal synthesis of monodispersed metal oxide nanoparticles at liquid-liquid interface

    Science.gov (United States)

    Monodispersed nanoparticles of metal oxide including ferrites MFe2O4 (M=, Ni, Co, Mn) and γ-Fe2O3, Ta2O5 etc. have been synthesized using a water-toluene interface under both conventional and microwave hydrothermal conditions. This general synthesis procedure uses readily availab...

  13. Monodispersed water-in-oil emulsions prepared with semi-metal microfluidic EDGE systems

    NARCIS (Netherlands)

    Maan, A.A.; Schroën, C.G.P.H.; Boom, R.M.

    2013-01-01

    Monodispersed water-in-oil emulsions were prepared with EDGE (Edge based Droplet GEneration) systems, which generate many droplets simultaneously from one junction. The devices (with plateau height of 1.0 µm) were coated with Cu and CuNi having the same hydrophobicity but different surface

  14. Lock and key colloids through polymerization-induced buckling of monodisperse silicon oil droplets

    NARCIS (Netherlands)

    Sacanna, S.|info:eu-repo/dai/nl/311471676; Irvine, W.T.M.; Rossi, L.|info:eu-repo/dai/nl/314410376; Pine, D.J.

    2011-01-01

    We have developed a new simple method to fabricate bulk amounts of colloidal spheres with well defined cavities from monodisperse emulsions. Herein, we describe the formation mechanism of ‘‘reactive’’ silicon oil droplets that deform to reproducible shapes via a polymerization-induced buckling

  15. Composite PLGA/AgNpPGA/AscH nanospheres with combined osteoinductive, antioxidative, and antimicrobial activities.

    Science.gov (United States)

    Stevanović, Magdalena; Uskoković, Vuk; Filipović, Miloš; Škapin, Srečo D; Uskoković, Dragan

    2013-09-25

    The global rise in the resistance of pathogens to conventional antibiotics has created an intensive search for alternative materials with antimicrobial properties. This study is performed with an intention to investigate the combined effects of poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) and ascorbic acid (AscH) encapsulated within freeze-dried poly(lactide-co-glycolide) (PLGA) nanospheres to obtain a nanomaterial with simultaneous osteoinductive, antioxidative, and prolonged antimicrobial properties. The influence of PLGA/AgNpPGA/AscH particles on (i) viability and superoxide production of human umbilical vein endothelial cells in vitro, (ii) morphology and expression of osteogenic markers in osteoblastic MC3T3-E1 cells in vitro, and (iii) antimicrobial activity against a Gram-positive bacterium, methicillin-resistant Staphylococcus aureus, and a Gram-negative bacterium, Escherichia coli, was investigated. PLGA/AgNpPGA/AscH nanoparticles showed a superior and extended antibacterial activity against both types of bacteria. The nanoparticles appeared to be capable of delivering ascorbate to the cells, which was evidenced by the significant decrease in the level of superoxides in human umbilical vein endothelial cells and which could have a therapeutic potential in preventing oxidative stress. PLGA/AgNpPGA/AscH nanoparticles had a positive effect on MC3T3-E1 osteoblastic cells in vitro, promoting: (i) an intimate contact with the cells and preservation of their healthy morphologies; (ii) unreduced cell viability; and (iii) multiple-fold upregulation of two osteogenic markers: osteocalcin and type I procollagen. It is concluded that PLGA/AgNpPGA/AscH nanospheres present a promising new material for the treatment of infections and use in wound dressings and other prophylactic applications.

  16. Electrospinning of PLGA/gum tragacanth nanofibers containing tetracycline hydrochloride for periodontal regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Ranjbar-Mohammadi, Marziyeh [Textile Engineering Group, Department of Engineering, University of Bonab, Bonab (Iran, Islamic Republic of); Zamani, M. [Mechanical Engineering Department, National University of Singapore (Singapore); Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore (Singapore); Prabhakaran, M.P., E-mail: nnimpp@nus.edu.sg [Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore (Singapore); Bahrami, S. Hajir, E-mail: hajirb@aut.ac.ir [Textile Engineering Department, Amirkabir University of Technology, Tehran (Iran, Islamic Republic of); Ramakrishna, S. [Mechanical Engineering Department, National University of Singapore (Singapore); Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore (Singapore)

    2016-01-01

    Controlled drug release is a process in which a predetermined amount of drug is released for longer period of time, ranging from days to months, in a controlled manner. In this study, novel drug delivery devices were fabricated via blend electrospinning and coaxial electrospinning using poly lactic glycolic acid (PLGA), gum tragacanth (GT) and tetracycline hydrochloride (TCH) as a hydrophilic model drug in different compositions and their performance as a drug carrier scaffold was evaluated. Scanning electron microscopy (SEM) results showed that fabricated PLGA, blend PLGA/GT and core shell PLGA/GT nanofibers had a smooth and bead-less morphology with the diameter ranging from 180 to 460 nm. Drug release studies showed that both the fraction of GT within blend nanofibers and the core–shell structure can effectively control TCH release rate from the nanofibrous membranes. By incorporation of TCH into core–shell nanofibers, drug release was sustained for 75 days with only 19% of burst release within the first 2 h. The prolonged drug release, together with proven biocompatibility, antibacterial and mechanical properties of drug loaded core shell nanofibers make them a promising candidate to be used as drug delivery system for periodontal diseases. - Highlights: • Novel drug loaded blend (PG-TCH) and core shell nanofibers (PG(cs)-TCH) from PLGA and gum tragacanth (GT) fabricated • Prolonged release of TCH with lower burst release and high mechanical strength in wet and dry conditions for nanofibers • Proven cytocompatibility properties and low rigidity/stiffness suggest PG(cs)-TCH nanfiber for periodontal regeneration.

  17. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mandiwana, Vusani, E-mail: VMandiwana@csir.co.za; Kalombo, Lonji, E-mail: LKalombo@csir.co.za [Centre of Polymers and Composites, CSIR (South Africa); Venter, Kobus, E-mail: Kobus.Venter@mrc.ac.za [South African Medical Research Council (South Africa); Sathekge, Mike, E-mail: Mike.Sathekge@up.ac.za [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine (South Africa); Grobler, Anne, E-mail: Anne.Grobler@nwu.ac.za; Zeevaart, Jan Rijn, E-mail: zeevaart@necsa.co.za [North-West University, DST/NWU Preclinical Drug Development Platform (South Africa)

    2015-09-15

    Developing nanoparticulate delivery systems that will allow easy movement and localization of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([{sup 153}Sm]Sm{sub 2}O{sub 3}) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive {sup 153}Sm-loaded-PLGA nanoparticles. The nanoparticles were characterized for size, zeta potential, and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The {sup 153}Sm-loaded-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The zeta potential ranged between 5 and 20 mV. The [{sup 153}Sm]Sm{sub 2}O{sub 3} loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles. While the IV injected [{sup 153}Sm]Sm{sub 2}O{sub 3}-loaded PLGA nanoparticles exhibited the highest localization of nanoparticles in the spleen (8.63 %ID/g) and liver (3.07 %ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen. From the biodistribution data obtained, it is clear that polymeric nanoscale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.

  18. PLGA implants: How Poloxamer/PEO addition slows down or accelerates polymer degradation and drug release.

    Science.gov (United States)

    Hamoudi-Ben Yelles, M C; Tran Tan, V; Danede, F; Willart, J F; Siepmann, J

    2017-03-08

    The aim of this study was to evaluate the impact of the addition of small amounts of hydrophilic polymers (Poloxamer 188 and PEO 200kDa) to PLGA-based implants loaded with prilocaine. Special emphasis was placed on the importance of the type of preparation technique: direct compression of milled drug-polymer powder blends versus compression of drug loaded microparticles (prepared by spray-drying). The implants were thoroughly characterized before and upon exposure to phosphate buffer pH7.4, e.g. using optical and scanning electron microscopy, X-ray diffraction, DSC and GPC. Interestingly, the addition of Poloxamer/PEO to the PLGA implants had opposite effects on the resulting drug release kinetics, depending on the type of preparation method: in the case of implants prepared by compression of milled drug-polymer powder blends, drug release was accelerated, whereas it was slowed down when the implants were prepared by compression of drug loaded PLGA microparticles. These phenomena could be explained by the swelling/disintegration behavior of the implants upon exposure to the release medium. Systems consisting of compressed microparticles remained intact and autocatalytic effects were of major importance. The presence of a hydrophilic polymer facilitated water penetration into these devices, slowing down PLGA degradation and drug release. In contrast, implants consisting of compressed drug-polymer powder blends rapidly (at least partially) disintegrated and autocatalysis was much less important. In these cases, the addition of a hydrophilic polymer facilitated ester bond cleavage, leading to accelerated PLGA degradation and drug release.

  19. Immunotoxicity and genotoxicity testing of PLGA-PEO nanoparticles in human blood cell model.

    Science.gov (United States)

    Tulinska, Jana; Kazimirova, Alena; Kuricova, Miroslava; Barancokova, Magdalena; Liskova, Aurelia; Neubauerova, Eva; Drlickova, Martina; Ciampor, Fedor; Vavra, Ivo; Bilanicova, Dagmar; Pojana, Giulio; Staruchova, Marta; Horvathova, Mira; Jahnova, Eva; Volkovova, Katarina; Bartusova, Maria; Cagalinec, Michal; Dusinska, Maria

    2015-05-01

    A human blood cell model for immunotoxicity and genotoxicity testing was used to measure the response to polylactic-co-glycolic acid (PLGA-PEO) nanoparticle (NP) (0.12, 3, 15 and 75 μg/cm(2) exposure in fresh peripheral whole blood cultures/isolated peripheral blood mononuclear cell cultures from human volunteers (n = 9-13). PLGA-PEO NPs were not toxic up to dose 3 μg/cm(2); dose of 75 μg/cm(2) displays significant decrease in [(3)H]-thymidine incorporation into DNA of proliferating cells after 4 h (70% of control) and 48 h (84%) exposure to NPs. In non-cytotoxic concentrations, in vitro assessment of the immunotoxic effects displayed moderate but significant suppression of proliferative activity of T-lymphocytes and T-dependent B-cell response in cultures stimulated with PWM > CON A, and no changes in PHA cultures. Decrease in proliferative function was the most significant in T-cells stimulated with CD3 antigen (up to 84%). Cytotoxicity of natural killer cells was suppressed moderately (92%) but significantly in middle-dosed cultures (4 h exposure). On the other hand, in low PLGA-PEO NPs dosed cultures, significant stimulation of phagocytic activity of granulocytes (119%) > monocytes (117%) and respiratory burst of phagocytes (122%) was recorded. Genotoxicity assessment revealed no increase in the number of micronucleated binucleated cells and no induction of SBs or oxidised DNA bases in PLGA-PEO-treated cells. To conclude on immuno- and genotoxicity of PLGA-PEO NPs, more experiments with various particle size, charge and composition need to be done.

  20. Aptamer conjugated paclitaxel and magnetic fluid loaded fluorescently tagged PLGA nanoparticles for targeted cancer therapy

    Science.gov (United States)

    Aravind, Athulya; Nair, Remya; Raveendran, Sreejith; Veeranarayanan, Srivani; Nagaoka, Yutaka; Fukuda, Takahiro; Hasumura, Takahashi; Morimoto, Hisao; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

    2013-10-01

    Controlled and targeted drug delivery is an essential criterion in cancer therapy to reduce the side effects caused by non-specific drug release and toxicity. Targeted chemotherapy, sustained drug release and optical imaging have been achieved using a multifunctional nanocarrier constructed from poly (D, L-lactide-co-glycolide) nanoparticles (PLGA NPs), an anticancer drug paclitaxel (PTX), a fluorescent dye Nile red (NR), magnetic fluid (MF) and aptamers (Apt, AS1411, anti-nucleolin aptamer). The magnetic fluid and paclitaxel loaded fluorescently labeled PLGA NPs (MF-PTX-NR-PLGA NPs) were synthesized by a single-emulsion technique/solvent evaporation method using a chemical cross linker bis (sulfosuccinimidyl) suberate (BS3) to enable binding of aptamer on to the surface of the nanoparticles. Targeting aptamers were then introduced to the particles through the reaction with the cross linker to target the nucleolin receptors over expressed on the cancer cell surface. Specific binding and uptake of the aptamer conjugated magnetic fluid loaded fluorescently tagged PLGA NPs (Apt-MF-NR-PLGA NPs) to the target cancer cells induced by aptamers was observed using confocal microscopy. Cytotoxicity assay conducted in two cell lines (L929 and MCF-7) confirmed that targeted MCF-7 cancer cells were killed while control cells were unharmed. In addition, aptamer mediated delivery resulting in enhanced binding and uptake to the target cancer cells exhibited increased therapeutic effect of the drug. Moreover, these aptamer conjugated magnetic polymer vehicles apart from actively transporting drugs into specifically targeted tumor regions can also be used to induce hyperthermia or for facilitating magnetic guiding of particles to the tumor regions.

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

    Directory of Open Access Journals (Sweden)

    Gui-Feng Tong

    2017-09-01

    Full Text Available 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.

  2. Hybrid scaffolds based on PLGA and silk for bone tissue engineering.

    Science.gov (United States)

    Sheikh, Faheem A; Ju, Hyung Woo; Moon, Bo Mi; Lee, Ok Joo; Kim, Jung-Ho; Park, Hyun Jung; Kim, Dong Wook; Kim, Dong-Kyu; Jang, Ji Eun; Khang, Gilson; Park, Chan Hum

    2016-03-01

    Porous silk scaffolds, which are considered to be natural polymers, cannot be used alone because they have a long degradation rate, which makes it difficult for them to be replaced by the surrounding tissue. Scaffolds composed of synthetic polymers, such as PLGA, have a short degradation rate, lack hydrophilicity and their release of toxic by-products makes them difficult to use. The present investigations aimed to study hybrid scaffolds fabricated from PLGA, silk and hydroxyapatite nanoparticles (Hap NPs) for optimized bone tissue engineering. The results from variable-pressure field emission scanning electron microscopy (VP-FE-SEM), equipped with EDS, confirmed that the fabricated scaffolds had a porous architecture, and the location of each component present in the scaffolds was examined. Contact angle measurements confirmed that the introduction of silk and HAp NPs helped to change the hydrophobic nature of PLGA to hydrophilic, which is the main constraint for PLGA used as a biomaterial. Thermo-gravimetric analysis (TGA) and FT-IR spectroscopy confirmed thermal decomposition and different vibrations caused in functional groups of compounds used to fabricate the scaffolds, which reflected improvement in their mechanical properties. After culturing osteoblasts for 1, 7 and 14 days in the presence of scaffolds, their viability was checked by MTT assay. The fluorescent microscopy results revealed that the introduction of silk and HAp NPs had a favourable impact on the infiltration of osteoblasts. In vivo experiments were conducted by implanting scaffolds in rat calvariae for 4 weeks. Histological examinations and micro-CT scans from these experiments revealed beneficial attributes offered by silk fibroin and HAp NPs to PLGA-based scaffolds for bone induction.

  3. Bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles as novel tumor targeting carriers

    Energy Technology Data Exchange (ETDEWEB)

    Ding Hong; Yong, Ken-Tye; Roy, Indrajit; Hu Rui; Zhao Lingling; Law, Wing-Cheung; Ji Wei; Liu Liwei; Bergey, Earl J; Prasad, Paras N [Department of Chemistry, Institute for Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Wu Fang [Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 (United States); Zhao Weiwei, E-mail: bergeye@buffalo.edu, E-mail: pnprasad@buffalo.edu [Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, NY 14215 (United States)

    2011-04-22

    In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l{sup -1}. Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the {alpha}{sub v{beta}3} integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

  4. Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres-Focus on Feature Selection.

    Directory of Open Access Journals (Sweden)

    Hossam M Zawbaa

    Full Text Available Poly-lactide-co-glycolide (PLGA is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP, multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR. The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven.

  5. PLGA nanoparticles codeliver paclitaxel and Stat3 siRNA to overcome cellular resistance in lung cancer cells

    Directory of Open Access Journals (Sweden)

    Su WP

    2012-08-01

    Full Text Available Wen-Pin Su,1,2 Fong-Yu Cheng,3 Dar-Bin Shieh,3–6 Chen-Sheng Yeh,5–7 Wu-Chou Su1,2,81Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University; 2Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; 3Institute of Oral Medicine, College of Medicine, National Cheng Kung University; 4Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; 5Advanced Optoelectronic Technology Center; 6Center for Frontier Materials and Micro/Nano Science and Technology, and 7Department of Chemistry, National Cheng Kung University; 8Cancer Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.Abstract: Background: Effective cancer chemotherapy remains an important issue in cancer treatment, and signal transducer and activator of transcription-3 (Stat3 activation leads to cellular resistance of anticancer agents. Polymers are ideal vectors to carry both chemotherapeutics and small interfering ribonucleic acid (siRNA to enhance antitumor efficacy. In this paper, poly(lactic-co-glycolic acid (PLGA nanoparticles loaded with paclitaxel and Stat3 siRNA were successfully synthesized, and their applications in cancer cells were investigated.Methods: Firstly, paclitaxel was enclosed by PLGA nanoparticles through solvent evaporation. They were then coated with cationic polyethylenimine polymer (PLGA-PEI-TAX, enabling it to carry Stat3 siRNA on its surface through electrostatic interactions (PLGA-PEI-TAX-S3SI. The size, zeta potential, deliver efficacy, and release profile of the PLGA nanocomplexes were characterized in vitro. The cellular uptake, intracellular nanoparticle trajectory, and subsequent cellular events were evaluated after treatment with various PLGA nanocomplexes in human lung cancer A549 cells and A549-derived paclitaxel

  6. Critical solvent properties affecting the particle formation process and characteristics of celecoxib-loaded PLGA microparticles via spray-drying

    DEFF Research Database (Denmark)

    Wan, Feng; Bohr, Adam; Maltesen, Morten Jonas;

    2013-01-01

    ) microparticles prepared by spray-drying. METHODS: Binary mixtures of acetone and methanol at different molar ratios were applied to dissolve celecoxib and PLGA prior to spray-drying. The resulting microparticles were characterized with respect to morphology, texture, surface chemistry, solid state properties...... by the PLGA precipitation rate, which is solvent-dependent, and the migration rate of celecoxib molecules during drying. The texture and surface chemistry of the spray-dried PLGA microparticles can therefore be tailored by adjusting the solvent composition....... power of the feed solution. An obvious burst release was observed for the microparticles prepared by the feed solutions with the highest amount of poor solvent for PLGA. TGA analysis revealed distinct drying kinetics for the binary mixtures. CONCLUSIONS: The particle formation process is mainly governed...

  7. A Rapid Reversed-Phase HPLC Method for Analysis of Trans-Resveratrol in PLGA Nanoparticulate Formulation

    OpenAIRE

    Singh, Gurinder; Pai, Roopa S.

    2014-01-01

    A rapid reversed-phase high performance liquid chromatography (RP-HPLC) method was developed for the determination of trans-resveratrol (t-RVT) in PLGA nanoparticle formulation. A new formulation of t-RVT loaded PLGA nanoparticles (NPs) with potential stealth properties was prepared by nanoprecipitation method in our laboratory. The desired chromatographic separation was achieved on a Phenomenex C18 column under isocratic conditions using UV detection at 306 nm. The optimized mobile phase con...

  8. Intravital Microscopic Evidence that Polylactide-Polyglycolide (PLGA) delays Neo-Osteogenesis and Neo-Angiogenesis in Healing Bone

    Science.gov (United States)

    1993-01-01

    INTRAVrrAL MICROSCOPIC EVIDENCE THAT POLYLACTIDE -POLYGLYCOLIDE (PLGA) DELAYS NEO-OSTEOGENESIS AND NEO-ANGIOGENESIS IN HEMAUNG BON H. Winet ,, J.O...healing in a BCI loaded with an erodible returns to an acceptable level of function, no further copolymer, PLGA ( polylactide -polyglycolide). To surgery is...also must be biocompatible, to the extent that Key Words: Bio-erodible implants, polylactide -poly- they generate no significant foreign-body reaction

  9. In Vitro Assessment of Antibacterial Activity and Cytocompatibility of Quercetin-Containing PLGA Nanofibrous Scaffolds for Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Zhi-Cai Xing

    2012-01-01

    Full Text Available Flavonoids, such as quercetin, have been reported to exhibit a wide range of biological activities related to their antioxidant capacity. The aim of this study was to investigate the protective effect of quercetin on cell adhesion, and the viability and proliferation of KB epithelial cells. Quercetin- (1, 5 wt%-containing poly (l-lactide-co-glycolide (PLGA nanofibrous scaffolds (PLGA/Q 1, PLGA/Q 5 were prepared by electrospinning technique and their antibacterial properties were examined. Two types of bacteria strains, Staphylococcus aureus (SA and Klebsiella pneumoniae (KP, were used to evaluate the antibacterial properties of the scaffolds. The results showed that the quercetin-containing PLGA nanofibrous scaffolds exhibited significant antibacterial effects against the two bacterial strains. KB epithelial cells were also used to evaluate the cytocompatibility of the scaffolds. From the results, it was found that the PLGA nanofibrous scaffolds with 1 wt% of quercetin had good cell compatibility. It is considered that the PLGA nanofibrous scaffolds with 1 wt% quercetin have potential to be used in tissue engineering.

  10. Cell-adhesive RGD peptide-displaying M13 bacteriophage/PLGA nanofiber matrices for growth of fibroblasts.

    Science.gov (United States)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Linhua; Kim, Min Jeong; Oh, Jin-Woo; Kim, Tai Wan; Han, Dong-Wook

    2014-01-01

    M13 bacteriophages can be readily fabricated as nanofibers due to non-toxic bacterial virus with a nanofiber-like shape. In the present study, we prepared hybrid nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 bacteriophages which were genetically modified to display the RGD peptide on their surface (RGD-M13 phage). The surface morphology and chemical composition of hybrid nanofiber matrices were characterized by scanning electron microscopy (SEM) and Raman spectroscopy, respectively. Immunofluorescence staining was conducted to investigate the existence of M13 bacteriophages in RGD-M13 phage/PLGA hybrid nanofibers. In addition, the attachment and proliferation of three different types of fibroblasts on RGD-M13 phage/PLGA nanofiber matrices were evaluated to explore how fibroblasts interact with these matrices. SEM images showed that RGD-M13 phage/PLGA hybrid matrices had the non-woven porous structure, quite similar to that of natural extracellular matrices, having an average fiber diameter of about 190 nm. Immunofluorescence images and Raman spectra revealed that RGD-M13 phages were homogeneously distributed in entire matrices. Moreover, the attachment and proliferation of fibroblasts cultured on RGD-M13 phage/PLGA matrices were significantly enhanced due to enriched RGD moieties on hybrid matrices. These results suggest that RGD-M13 phage/PLGA matrices can be efficiently used as biomimetic scaffolds for tissue engineering applications.

  11. Fabricating a pearl/PLGA composite scaffold by the low-temperature deposition manufacturing technique for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Xu Mingen; Li Yanlei; Suo Hairui; Wang Qiujun; Ge Yakun; Xu Ying [Center Laboratory of Biomanufacture and Tissue Engineering, Hang Zhou Dianzi University, Hangzhou 310018 (China); Yan Yongnian; Liu Li, E-mail: xumingen@tsinghua.edu.c, E-mail: xumingen@hdu.edu.c [Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China)

    2010-06-15

    Here we developed a composite scaffold of pearl/poly(lactic-co-glycolic acid) (pearl/PLGA) utilizing the low-temperature deposition manufacturing (LDM). LDM makes it possible to fabricate scaffolds with designed microstructure and macrostructure, while keeping the bioactivity of biomaterials by working at a low temperature. Process optimization was carried out to fabricate a mixture of pearl powder, PLGA and 1,4-dioxane with the designed hierarchical structures, and freeze-dried at a temperature of -40 deg. C. Scaffolds with square and designated bone shape were fabricated by following the 3D model. Marrow stem cells (MSCs) were seeded on the pearl/PLGA scaffold and then cultured in a rotating cell culture system. The adhesion, proliferation and differentiation of MSCs into osteoblasts were determined using scanning electronic microscopy, WST-1 assay, alkaline phosphatase activity assay, immunofluorescence staining and real-time reverse transcription polymerase chain reaction. The results showed that the composite scaffold had high porosity (81.98 +- 3.75%), proper pore size (micropores: <10 mum; macropore: 495 +- 54 mum) and mechanical property (compressive strength: 0.81 +- 0.04 MPa; elastic modulus: 23.14 +- 0.75 MPa). The pearl/PLGA scaffolds exhibited better biocompatibility and osteoconductivity compared with the tricalcium phosphate/PLGA scaffold. All these results indicate that the pearl/PLGA scaffolds fulfill the basic requirements of bone tissue engineering scaffold.

  12. PEGylated PLGA Nanoparticles as Tumor Ecrosis Factor-α Receptor Blocking Peptide Carriers: Preparation,Characterization and Release in vitro

    Institute of Scientific and Technical Information of China (English)

    LIU Wei; YANG Anshu; LI Zhuoya; XU Huibi; YANG Xiangliang

    2007-01-01

    To assess the merits of PEGylated poly (lactic-co-glycolic acid) (PEG-PLGA) nanoparticles as drug carriers for tumor necrosis factor-α receptor blocking peptide (TNFR-BP), PEG-PLGA copolymer,which could be used to prepare the stealth nanoparticles, was synthesized with methoxypolyethyleneglycol,DL-lactide and glycolide. The structure of PEG-PLGA was confirmed with 1H-NMR and FT-IR spectroscopy,and the molecular weight (MW) was determined by gel permeation chromatography. Fluorescent FITC-TNFR-BP was chosen as model protein and encapsulated within PEG-PLGA nanoparticles using the double emulsion method. Atomic force microscopy and photon correlation spectroscopy were employed to characterize the stealth nanoparticles fabricated for morphology, size with polydispersity index and zeta potential. Encapsulation efficiency (EE) and the release of FITC-TNFR-BP in nanoparticles in vitro were measured by the fluorescence measurement. The stealth nanoparticles were found to have the mean diameter less than 270 nm and zeta potential less than-20 mV. In all nanoparticle formulations, more than 45% of EE were obtained. FITC-TNFR-BP release from the PEG-PLGA nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. The experimental results show that PEG-PLGA nanoparticles possess the potential to develop as drug carriers for controlled release applications of TNFR-BP.

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

    Science.gov (United States)

    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.

  14. In vitro Study on Biodegradable AZ31 Magnesium Alloy Fibers Reinforced PLGA Composite

    Institute of Scientific and Technical Information of China (English)

    Y.H.Wu; N.Li; Y.Cheng; Y.F.Zheng; Y.Han

    2013-01-01

    AZ31 magnesium alloy fibers reinforced poly(lactic-co-glycolic acid) (PLGA) composites were prepared and their mechanical property,immersion corrosion behavior and biocompatibility were studied.The tensile test showed that with the addition of AZ31 fibers,the composites had a significant increment in tensile strength and elongation.For the direct cell attachment test,all the cells showed a healthy morphology and spread well on the experimental sample surfaces.The immersion results indicated that pH values of the immersion medium increased with increasing AZ31 fiber contents.All the in vitro experimental results indicated that this new kind of magnesium alloy fibers reinforced PLGA composites show a potential for future biomedical applications.

  15. Hierarchical porous bioactive glasses/PLGA-magnetic SBA-15 for dual-drug release.

    Science.gov (United States)

    Ma, Jie; Lin, Huiming; Li, Xiaofeng; Bian, Chunhui; Xiang, Di; Han, Xiao; Wu, Xiaodan; Qu, Fengyu

    2014-06-01

    The hierarchical porous bioglass combined with magnetic SBA-15 was synthesized. The bioactive glass materials possess a hierarchical porous structure with the macroporous (50μm) and the mesoporous (3.86nm) structures derived from the plant template (cattail stem) and triblock polyethylene oxide-propylene oxide block copolymer (P123), respectively. Magnetic SBA-15 was synthesized by adopting the post assembly method using Fe(NO3)3 as iron source and ethylene glycol as reduction. After coating PLGA, PLGA-IBU-magnetic SBA-15 also possessed super-paramagnetism and the corresponding saturation magnetizations (Ms) could reach 2.6emug(-1). Metformin HCl (MH) and ibuprofen (IBU) were used as model drugs, and the drug release kinetics was studied. MH and IBU could release 60% and 85% from the sample respectively. The system shows excellent dual-drug controlled delivery performance and good bioactivity in vitro that leads to good potential application on bone regeneration.

  16. Enhanced singlet oxygen generation from PLGA loaded with verteporfin and gold nanoparticles

    Science.gov (United States)

    Deng, Wei; Kautzka, Zofia; Goldys, Ewa M.

    2016-12-01

    In this study, poly(lactic-co-glycolic acid) (PLGA) nanocomposites were developed by incorporating a photosensitizer, verteporfin and gold nanoparticles into this polymeric matrix and utilised for enhanced photoynamic therapy. Both enhanced fluorescence and singlet oxygen generation from verteporfin were observed in this new formulation under both 425nm LED and 405nm laser illumination. A maximum enhancement factor of 2.5 for fluorescence and 1.84 for 1O2 generation was obtained when the molar ratio of gold:VP was 5:1 and excited at 425 nm, compared with PLGA doped with verteporfin only. The experiment results could be explained by the local electric field enhancement of gold nanoparticles. Furthermore, in vitro cell-killing effect on human pancreatic cancer cells was also demonstrated by using this new formulation following light exposure, indicating the utility of these nanocomposites for enhanced photodynamic therapy.

  17. Recent advances in the preparation progress of protein/peptide drug loaded PLA/PLGA microspheres.

    Science.gov (United States)

    Xu, Feng-Hua; Zhang, Qiang

    2007-01-01

    Sustained release drug delivery from microparticles is an excellent alternative for daily protein/peptide drug administration protocol. Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) are the most commonly used polymer carriers in the development of protein/peptide microspheres. Basically there are three preparation methods for PLA/PLGA microspheres: the solvent extraction/evaporation based multiple emulsion (W/O/W emulsion) method, the phase separation method and the spray drying method. The stability of the protein/pipetide loaded, encapsulation efficiency, and the burst effect of the microspheres are key problems usually met in the preparation of microspheres. In this review the preparation techniques and progress in the development of protein/pipetide microspheres which aimed to stabilize protein/peptide structural integrity, keep the bioactivity of drugs, increase the encapsulation efficiency and improve the release profile were summarized and evaluated.

  18. Fabrication aspects of PLA-CaP/PLGA-CaP composites for orthopedic applications: a review.

    Science.gov (United States)

    Zhou, Huan; Lawrence, Joseph G; Bhaduri, Sarit B

    2012-07-01

    For several decades, composites made of polylactic acid-calcium phosphates (PLA-CaP) and polylactic acid-co-glycolic acid-calcium phosphates (PLGA-CaP) have seen widespread uses in orthopedic applications. This paper reviews the fabrication aspects of these composites, following the ubiquitous materials science approach by studying "processing-structure-property" correlations. Various fabrication processes such as microencapsulation, phase separation, electrospinning, supercritical gas foaming, etc., are reviewed, with specific examples of their applications in fabricating these composites. The effect of the incorporation of CaP materials on the mechanical and biological performance of PLA/PLGA is addressed. In addition, this paper describes the state of the art on challenges and innovations concerning CaP dispersion, incorporation of biomolecules/stem cells and long-term degradation of the composites.

  19. Enhanced transdermal delivery of indomethacin-loaded PLGA nanoparticles by iontophoresis.

    Science.gov (United States)

    Tomoda, Keishiro; Terashima, Hiroto; Suzuki, Kenichi; Inagi, Toshio; Terada, Hiroshi; Makino, Kimiko

    2011-12-01

    Nanoparticles effectively deliver therapeutic agent by penetrating into the skin. Indomethacin (IM) and coumarin-6 were loaded in PLGA nanoparticles with an average diameter of 100 nm. IM and coumarin-6 were chosen as a model drug and as a fluorescent marker, respectively. The surfaces of the nanoparticles were negatively charged. Permeability of IM-loaded PLGA nanoparticles through rat skin was studied. Higher amount of IM was delivered through skin when IM was loaded in nanoparticles than IM was free molecules. Also, iontophoresis was applied to enhance the permeability of nanoparticles. When iontophoresis with 3 V/cm was applied, permeability of IM was much higher than that obtained by simple diffusion of nanoparticles through skin. The combination of charged nanoparticle system with iontophoresis is useful for effective transdermal delivery of therapeutic agents.

  20. Enhanced transdermal delivery of indomethacin using combination of PLGA nanoparticles and iontophoresis in vivo.

    Science.gov (United States)

    Tomoda, Keishiro; Terashima, Hiroto; Suzuki, Kenichi; Inagi, Toshio; Terada, Hiroshi; Makino, Kimiko

    2012-04-01

    Nanoparticles effectively deliver therapeutic agent by penetrating into the rat skin in vivo. Indomethacin (IM) and coumarin-6 were loaded in PLGA nanoparticles with an average diameter of 100 nm. Indomethacin (IM) and coumarin-6 were chosen as a model drug and as a fluorescent marker, respectively. The surfaces of the nanoparticles were negatively charged. Permeability of IM-loaded PLGA nanoparticles through rat skin was studied in vivo. Higher amount of IM was delivered through skin when IM was loaded in nanoparticles than IM was free molecules. Also, iontophoresis was applied to enhance the permeability of nanoparticles. When iontophoresis was applied at 0.05 mA/cm(2), permeability of IM was much higher than that obtained by simple diffusion of nanoparticles through skin. The combination of charged nanoparticle system with iontophoresis is useful for effective transdermal systemic delivery of therapeutic agents.

  1. Effect of Mixed Solvent on Fabrication, Morphology and Monodispersity of Microspheres with Hydrophobic Poly(butyl methacrylate) Shells

    Institute of Scientific and Technical Information of China (English)

    XIAO Xincai; LU Cheng

    2012-01-01

    Monodisperse microspheres (mean diameter 200-300 nm) with polystyrene cores and poly(acrylamide-co-buty1 methacrylate) shells were prepared by using a free radical polymerization method.Moreover,the effect of mixed solvent on the preparation,morphology and monodispersity was investigated.The experimental results showed that solubility parameter of butyl methacrylate and solvent affected mainly the molding of monodisperse core-shell microspheres.When the microspheres were fabricated in a sequential synthesis process,addition of hydrophilic and organic solvent including butyl methacrylate led to spherical degree of the particles becoming worse,and the mean diameter of the microspheres decreased and the monodispersity became better with increasing the crosslinker methylenebisacrylamide dosage.

  2. The effect of poly(lactic-co-glycolic acid) (PLGA) coating on the mechanical, biodegradable, bioactive properties and drug release of porous calcium silicate scaffolds.

    Science.gov (United States)

    Zhao, Lang; Wu, Chengtie; Lin, Kaili; Chang, Jiang

    2012-01-01

    Ideal scaffolds for bone tissue engineering require 3D interconnected porous structures, enough mechanical strength for hand of treatment as well as proper bioactivity and biodegradability. Calcium silicate (CaSiO3, CS) scaffolds have been studied for bone tissue engineering application due to their excellent bioactivity. However, the main disadvantages of CS scaffolds are their low mechanical strength and high alkaline ionic products. In this study, sintered CS scaffolds were prepared and coated with poly(lactic-co-glycolic acid) (PLGA), and the effect of PLGA coating on the mechanical, biodegradable, bioactive properties and drug release of porous CS scaffolds were investigated. The results showed that the PLGA-coated CS scaffolds maintained large pore size and high porosity. The compressive strength of PLGA/CS scaffolds was significantly improved compared to pure CS scaffolds, and increased with the increase of intrinsic viscosity and concentration of PLGA. In addition, the PLGA coating neutralized alkaline level resulted from the ionic products of CS scaffolds and reduced the pH value of biological solution during the degradation of scaffolds. It was found that PLGA/CS scaffolds still maintained excellent apatite-mineralization ability in SBF. Furthermore, the PLGA coating effectively inhibited the burst release and maintained a sustained release of drugs from the CS scaffolds. Our results indicate that the PLGA/CS scaffolds have great potential for bone tissue engineering application by the virtue of improved mechanical strength, and excellent bioactivity, degradation as well as drug-delivery property.

  3. Drug release behavior of poly (lactic-glycolic acid) grafting from sodium alginate (ALG-g-PLGA) prepared by direct polycondensation.

    Science.gov (United States)

    Shi, Gang; Ding, Yuanyuan; Zhang, Xin; Wu, Luyan; He, Fei; Ni, Caihua

    2015-01-01

    Hydrophobically modified sodium alginate, poly (lactic-glycolic acid) grafting from sodium alginate (ALG-g-PLGA), was successfully synthesized through direct one-step polymerization of sodium alginate, glycolic acid, and lactic acid. ALG-g-PLGA self-assembled to colloidal nanoparticles and subsequently hydrogel microspheres were obtained by crosslinking ALG-g-PLGA nanoparticles in the solution of calcium chloride. The modified hydrogel microspheres could be used as the drug delivery vehicles for a hydrophobic ibuprofen. Compared with sodium alginate, ALG-g-PLGA demonstrated an improved drug loading rate, encapsulation efficiency, and prolonged release speed. The products, as novel and highly promising biomaterials, have potential applications.

  4. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique.

    Science.gov (United States)

    Fan, Wen; Yan, Wei; Xu, Zushun; Ni, Hong

    2012-02-01

    Chitosan nanoparticles have been extensively studied for drug and gene delivery. In this paper, monodisperse, low molecular weight (LMW) chitosan nanoparticles were prepared by a novel method based on ionic gelation using sodium tripolyphosphate (TPP) as cross-linking agent. The objective of this study was to solve the problem of preparation of chitosan/TPP nanoparticles with high degree of monodispersity and stability, and investigate the effect of various parameters on the formation of LMW chitosan/TPP nanoparticles. It was found that the particle size distribution of the nanoparticles could be significantly narrowed by a combination of decreasing the concentration of acetic acid and reducing the ambient temperature during cross-linking process. The optimized nanoparticles exhibited a mean hydrodynamic diameter of 138 nm with a polydispersity index (PDI) of 0.026 and a zeta potential of +35 mV, the nanoparticles had good storage stability at room temperature up to at least 20 days.

  5. Controlled Synthesis and Characterization of Monodisperse Fe3O4 Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    SHI,Rongrong; GAO,Guanhua; YI,Ran; ZHOU,Kechao; QIU,Guanzhou; LIU,Xiaohe

    2009-01-01

    Monodisperse Fe3O4 nanoparticles were successfully synthesized through the thermal decomposition of iron acetylacetonate in octadecene solvent in the presence of oleic acid and oleylamine.The influences of experimental parameters,such as reacting temperature,amounts and kinds of surfactants,solvents,oleic acid and oleylamine,on the size and shape of monodisperse Fe3O4 nanoparticles were discussed.The phase structures,morphology,and size of the as-prepared products were investigated in detail by X-ray diffraction (XRD),transmission electron microscopy (TEM),selected area electron diffraction (SAED) and high-resolution transmission electron microscopy (HRTEM).Magnetic property was measured using a vibrating sample magnetometer (VSM) at room temperature,which revealed that Fe3O4 nanoparticles were of ferromagnetism with a saturation magnetization (Ms) of 74.0 emu/g and coercivity (Hc) of 72.6 Oe.

  6. Simple and inexpensive microfluidic devices for the generation of monodisperse multiple emulsions

    KAUST Repository

    Li, Erqiang

    2013-12-16

    Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology. Polydimethylsiloxane soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. Here, we report the design and fabrication of simple and inexpensive microfluidic devices based on microscope glass slides and pulled glass capillaries, for generating monodisperse multiple emulsions. The advantages of our method lie in a simple manufacturing procedure, inexpensive processing equipment and flexibility in the surface modification of the designed microfluidic devices. Different types of devices have been designed and tested and the experimental results demonstrated their robustness for preparing monodisperse single, double, triple and multi-component emulsions. © 2014 IOP Publishing Ltd.

  7. Micro-spherical cochleate composites: method development for monodispersed cochleate system.

    Science.gov (United States)

    Nagarsekar, Kalpa; Ashtikar, Mukul; Steiniger, Frank; Thamm, Jana; Schacher, Felix H; Fahr, Alfred

    2017-03-01

    Cochleates have been of increasing interest in pharmaceutical research due to their extraordinary stability. However the existing techniques used in the production of cochleates still need significant improvements to achieve sufficiently monodispersed formulations. In this study, we report a simple method for the production of spherical composite microparticles (3-5 μm in diameter) made up of nanocochleates from phosphatidylserine and calcium (as binding agent). Formulations obtained from the proposed method were evaluated using electron microscopy and small angle X-ray scattering and were compared with conventional cochleate preparation techniques. In this new method, an ethanolic lipid solution and aqueous solution of a binding agent is subjected to rapid and uniform mixing with a microfluidic device. The presence of high concentration of organic solvent promotes the formation of composite microparticles made of nanocochleates. This simple methodology eliminates elaborate preparation methods, while providing a monodisperse cochleate system with analogous quality.

  8. Enhanced thermal stability of monodispersed silver cluster arrays assembled on block copolymer scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Xu, C H; Chen, X; Liu, Y J; Xie, B; Han, M [National Laboratory of Solid State Microstructures and Department of Materials Science and Engineering, Nanjing University, Nanjing 210093 (China); Song, F Q; Wang, G H, E-mail: sjhanmin@nju.edu.cn [National Laboratory of Solid State Microstructures and Department of Physics, Nanjing University, Nanjing 210093 (China)

    2010-05-14

    Triblock copolymer poly(styrene-b-butadiene-b-styrene) (SBS) films with long-range ordered self-assembled nanopatterns are used as templates to selectively adsorb soft-landing silver clusters. Closely spaced cluster arrays with high monodispersity are formed through the confinement of the block copolymer scaffolds, and show a much enhanced thermal stability as compared with the cluster assemblies on the surfaces of covalent amorphous solids, or even on the disordered SBS films. Their morphologies are barely influenced by long time thermal annealing at a temperature as high as 180 deg. C, while in the latter case intense aggregations and coalescences of silver clusters are commonly observed upon annealing. The different thermal stabilities of the cluster assemblies also induce different evolutions of their optical extinction spectra under annealing. This promises a simple way to control the monodispersity and thermal stability of metal cluster assembly via self-assembled block copolymer template.

  9. A granocentric model captures the statistical properties of monodisperse random packings

    CERN Document Server

    Newhall, Katherine A; Vanden-Eijnden, Eric; Brujic, Jasna

    2012-01-01

    We present a generalization of the granocentric model proposed in [Clusel et al., Nature, 2009, 460, 611615] that is capable of describing the local fluctuations inside not only polydisperse but also monodisperse packings of spheres. This minimal model does not take into account the relative particle positions, yet it captures positional disorder through local stochastic processes sampled by efficient Monte Carlo methods. The disorder is characterized by the distributions of local parameters, such as the number of neighbors and contacts, filled solid angle around a central particle and the cell volumes. The model predictions are in good agreement with our experimental data on monodisperse random close packings of PMMA particles. Moreover, the model can be used to predict the distributions of local fluctuations in any packing, as long as the average number of neighbors, contacts and the packing fraction are known. These distributions give a microscopic foundation to the statistical mechanics framework for jamm...

  10. Understanding and Controlling the Growth of Monodisperse CdS Nanowires in Solution

    DEFF Research Database (Denmark)

    Xi, Lifei; Tan, Winnie Xiu Wen; Boothroyd, Chris;

    2008-01-01

    diffusion rate of the precursor and hence low reactivity. Therefore, ODPA is good for generating nearly monodisperse and high aspect ratio US nanowires. Our nanowires have a high degree of dispersibility and thus can be easily processed for potential applications as solar cells and transistors. Finally......Cadmium sulfide (CdS) nanowires with a monodisperse diameter of 3.5 nm and length of about 600 nm were successfully synthesized using a simple and reproducible hot coordination solvents method. Structural characterization showed that the one-dimensional nanowires grow along the [001] direction......, we propose that the ODPA-to-Cd mole ratio is the key factor affecting the morphology of the nanowires because it affects both the cleavage rate of the P=S double bond and the nucleation/growth rate of the anisotropic nanocrystals. In addition, it was found that Cd-ODPA complexes give rise to a low...

  11. Fabrication of monodisperse magnetic nanoparticles released in solution using a block copolymer template

    Science.gov (United States)

    Morcrette, Mélissa; Ortiz, Guillermo; Tallegas, Salomé; Joisten, Hélène; Tiron, Raluca; Baron, Thierry; Hou, Yanxia; Lequien, Stéphane; Bsiesy, Ahmad; Dieny, Bernard

    2017-07-01

    This paper describes a fabrication process of monodisperse magnetic nanoparticles released in solution, based on combined ‘top-down’ and ‘bottom-up’ approaches. The process involves the use of a self-assembled PS-PMMA block copolymer formed on a sacrificial layer. Such an approach was so far mostly explored for the preparation of patterned magnetic media for ultrahigh density magnetic storage. It is here extended to the preparation of released monodisperse nanoparticles for biomedical applications. A special sacrificial layer had to be developed compatible with the copolymer self-organization. The resulting nanoparticles exhibit very narrow size dispersion (≈7%) and can be good candidates as contrast agents for medical imaging i.e. magnetic resonance imaging or magnetic particle imaging. The approach provides a great freedom in the choice of the particles shapes and compositions. In particular, they can be made of biocompatible magnetic material.

  12. Co-encapsulation of lyoprotectants improves the stability of protein-loaded PLGA nanoparticles upon lyophilization

    DEFF Research Database (Denmark)

    Fonte, Pedro; Araújo, Francisca; Seabra, Vítor;

    2015-01-01

    The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with insulin into PLGA nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely trehalose, glucose, sucrose, fructose and sorbitol...... confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The insulin in vitro release studies demonstrated that formulations with co-encapsulated trehalose, glucose, sucrose, fructose and sorbitol...

  13. Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jianhua; Yang, Qiu; Cheng, Niangmei [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Tao, Xiaojun [Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, 410013, Hunan (China); Zhang, Zhihua; Sun, Xiaomin [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Zhang, Qiqing, E-mail: zhangqiq@126.com [Institute of Biomedical and Pharmaceutical Technology, Fuzhou University, Fuzhou 350002 (China); Key Laboratory of Biomedical Materials of Tianjin, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192 (China)

    2016-04-01

    For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration. - Highlights: • Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere proposed for cartilage repair was created. • In vivo, scaffold could enhance cartilage regeneration and integration between the repaired and surrounding cartilage. • In vitro, scaffold exhibits excellent characteristics, such as, improved porosity water absorption and good cell affinity.

  14. Surface hydrophilicity of PLGA fibers governs in vitro mineralization and osteogenic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, Minnah; Arora, Aditya; Katti, Dhirendra S., E-mail: dsk@iitk.ac.in

    2014-12-01

    Interfacial properties of biomaterials play an important role in governing their interaction with biological microenvironments. This work investigates the role of surface hydrophilicity of electrospun poly(lactide-co-glycolide) (PLGA) fibers in determining their biological response. For this, PLGA is blended with varying amounts of Pluronic®F-108 and electrospun to fabricate microfibers with varying surface hydrophilicity. The results of mineralization study in simulated body fluid (SBF) demonstrate a significant enhancement in mineralization with an increase in surface hydrophilicity. While presence of serum proteins in SBF reduces absolute mineral content, mineralization continues to be higher on samples with higher surface hydrophilicity. The results from in vitro cell culture studies demonstrate a marked improvement in mesenchymal stem cell —adhesion, elongation, proliferation, infiltration, osteogenic differentiation and matrix mineralization on hydrophilized fibers. Therefore, hydrophilized PLGA fibers are advantageous both in terms of mineralization and elicitation of favorable cell response. Since most of the polymeric materials being used in orthopedics are hydrophobic in nature, the results from this study have strong implications in the future design of interfaces of such hydrophobic materials. In addition, the work proposes a facile method for the modification of electrospun fibers of hydrophobic polymers by blending with a poloxamer for improved bone tissue regeneration. - Highlights: • Surface hydrophilicity of PLGA modulated by blending with Pluronic F-108. • Hydrophilized fibers support better in vitro mineralization. • Mineralization trends retained in the presence of adsorbed serum proteins. • Hydrophilized fibers promote better cell adhesion and proliferation. • Hydrophilized fibers also enable better osteogenic differentiation.

  15. Towards Cluster-Assembled Materials of True Monodispersity in Size and Chemical Environment: Synthesis, Dynamics and Activity

    Science.gov (United States)

    2016-10-27

    pathway Status: not yet published Diverse technologies, from catalyst coking to graphene synthesis , entail hydrocarbon dehydrogena- tion and...AFRL-AFOSR-UK-TR-2016-0037 Towards cluster-assembled materials of true monodispersity in size and chemical environment: Synthesis , Dynamics and...Towards cluster-assembled materials of true monodispersity in size and chemical environment: synthesis , dynamics and activity 5a.  CONTRACT NUMBER 5b

  16. Size reduction of cosolvent-infused microbubbles to form acoustically responsive monodisperse perfluorocarbon nanodroplets.

    Science.gov (United States)

    Seo, Minseok; Williams, Ross; Matsuura, Naomi

    2015-09-07

    Perfluorocarbon (PFC) nanodroplet agents are exciting new biomaterials that can be remotely vapourized by ultrasound or light to change into micron-scale gas bubbles in situ. After PFC nanodroplet vapourization, the micron-scale gas bubble can interact strongly with ultrasound radiation, such that the bubbles can be used for cancer imaging and therapy. For these phase-change agents to be useful, however, PFC nanodroplets must be produced in the range of 100 to 400 nm in diameter with high size control and monodispersity, restrictions that remain a challenge. Here, we address this challenge by taking advantage of the size control offered by microfluidics, in combination with the size reduction provided by cosolvent-infused PFC bubbles through both condensation and cosolvent dissolution. In this approach, PFC bubbles with a high percentage of cosolvent (in this study, diethyl ether, DEE) are produced using microfluidics at a temperature above the boiling point. After synthesis, these bubbles become much smaller through both condensation of the gas into liquid droplets and from dissolution of the DEE into the continuous phase. This approach demonstrates that monodisperse, cosolvent-incorporated PFC bubbles can directly form monodisperse PFC nanodroplets a factor of 24 times smaller than the precursor bubbles. We also demonstrate that these nanoscale droplets can be converted to echogenic microbubbles after exposure to ultrasound, showing that these PFC nanodroplets are viable for the in situ production of ultrasound contrast agents. We show that this system can overcome the minimum droplet size limit of standard microfluidics, and is a powerful new tool for generating monodisperse, PFC phase-change ultrasound contrast agents for treating and imaging cancer.

  17. Aerosol-Assisted Synthesis of Monodisperse Single-Crystalline α-Cristobalite Nanospheres

    OpenAIRE

    Jiang, Xingmao; Bao, Lihong; Cheng, Yung-Sung; Dunphy, Darren R.; Li, Xiaodong; Brinker, C. Jeffrey

    2011-01-01

    Monodisperse single-crystalline α-cristobalite nanospheres have been synthesized by hydrocarbon-pyrolysis-induced carbon deposition on amorphous silica aerosol nanoparticles, devitrification of the coated silica at high temperature, and subsequent carbon removal by oxidation. The nanosphere size can be well controlled by tuning the size of the colloidal silica precursor. Uniform, high-purity nanocrystalline α-cristobalite is important for catalysis, nanocomposites, advanced polishing, and und...

  18. On sufficient stability conditions of the Couette — Poiseuille flow of monodisperse mixture

    Science.gov (United States)

    Popov, D. I.; Sagalakov, A. M.; Nikitenko, N. G.

    2011-06-01

    The stability of the Couette — Poiseuille flow of a monodisperse mixture is considered. Sufficient stability conditions are derived. Results of the computation of the spectrum are presented. A considerable stabilization of the flow with particles admixture to small disturbances is observed. It is found that the regions of instability generation may have complex geometry. The influence of the main velocity profile and admixture parameters on the stability conditions is considered.

  19. Enhancement of magnetic coercivity and macroscopic quantum tunneling in monodispersed Co/CoO cluster assemblies

    OpenAIRE

    Peng, D. L.; Sumiyama, Kenji; Hihara, Takehiko; Yamamuro, S.; ヒハラ, タケヒコ; スミヤマ, ケンジ; 日原, 岳彦; 隅山, 兼治; Hihara, T.; Sumiyama, K.

    1999-01-01

    Magnetic properties have been measured for monodisperse-sized Co/CoO cluster assemblies prepared by a plasma-gas-condensation-type cluster beam deposition technique. The clear correlation obtained between exchange bias field and coercivity suggests the enhancement of uniaxial anisotropy owing to the exchange coupling between the ferromagnetic Co core and antiferromagnetic CoO shell, and magnetic disorder at the core-shell interface. A nonthermal magnetic relaxation observed below 8 K, being r...

  20. Aqueous dispersion of monodisperse magnetic iron oxide nanocrystals through phase transfer

    Energy Technology Data Exchange (ETDEWEB)

    Yu, William W [Department of Chemistry, Rice University, Houston, TX 77005 (United States); Chang, Emmanuel [Department of Bioengineering, Rice University, Houston, TX 77005 (United States); Sayes, Christie M [Department of Chemistry, Rice University, Houston, TX 77005 (United States); Drezek, Rebekah [Department of Bioengineering, Rice University, Houston, TX 77005 (United States); Colvin, Vicki L [Department of Chemistry, Rice University, Houston, TX 77005 (United States)

    2006-09-14

    A facile method was developed for completely transferring high quality monodisperse iron oxide nanocrystals from organic solvents to water. The as-prepared aqueous dispersions of iron oxide nanocrystals were extremely stable and could be functionalized for bioconjugation with biomolecules. These iron oxide nanocrystals showed negligible cytotoxicity to human breast cancer cells (SK-BR-3) and human dermal fibroblast cells. This method is general and versatile for many organic solvent-synthesized nanoparticles, including fluorescent semiconductor nanocrystals.

  1. Monodisperse spherical meso-macroporous silica particles: Synthesis and adsorption of biological macromolecules

    Science.gov (United States)

    Stovpiaga, E. Yu.; Grudinkin, S. A.; Kurdyukov, D. A.; Kukushkina, Yu. A.; Nashchekin, A. V.; Sokolov, V. V.; Yakovlev, D. R.; Golubev, V. G.

    2016-11-01

    Monodispersed spherical silica particles, including large mesopores (over 10 nm) and macropores (up to 100 nm) were obtained by chemical etching in an autoclave. A method for introducing globular protein myoglobin molecules into the pores is developed. The method of filling is based on a high adsorption capacity of the developed internal pore structure of the particles. The structure and adsorption properties of the materials are studied.

  2. Monodispersed bimetallic PdAg nanoparticles with twinned structures: Formation and enhancement for the methanol oxidation

    OpenAIRE

    Zhen Yin; Yining Zhang; Kai Chen; Jing Li; Wenjing Li; Pei Tang; Huabo Zhao; Qingjun Zhu; Xinhe Bao; Ding Ma

    2014-01-01

    Monodispersed bimetallic PdAg nanoparticles can be fabricated through the emulsion-assisted ethylene glycol (EG) ternary system. Different compositions of bimetallic PdAg nanoparticles, Pd80Ag20, Pd65Ag35 and Pd46Ag54 can be obtained via adjusting the reaction parameters. For the formation process of the bimetallic PdAg nanoparticles, there have two-stage growth processes: firstly, nucleation and growth of the primary nanoclusters; secondly, formation of the secondary nanoparticles with the s...

  3. In-site synthesis of monodisperse, oleylamine-capped Ag nanoparticles through microemulsion approach

    Science.gov (United States)

    Chen, Shun; Ju, Yanyun; Guo, Yi; Xiong, Chuanxi; Dong, Lijie

    2017-03-01

    Ag NPs were in-site synthesized through microemulsion method by reducing silver acetate with oleylamine-mediated at 70 °C with highly monodisperse and narrow size from 10 to 20 nm. The synthesis of Ag NPs was aided by oleylamine and the role of oleylamine was researched. This in-site synthesis approach to Ag NPs was reproducibility and high yield more than 80% with stable store about 6 months.

  4. One-pot polyol synthesis of highly monodisperse short green silver nanorods.

    Science.gov (United States)

    Patarroyo, Javier; Genç, Aziz; Arbiol, Jordi; Bastús, Neus G; Puntes, Victor

    2016-09-21

    Green silver nanorods (Ag NRs) of a low aspect ratio (2.8) have been produced in high yields via an optimized, simple, and robust one-pot polyol method in the presence of tannic acid, which favors the nucleation of decahedral seeds needed for the production of monodisperse Ag NRs. These Ag NRs were further used as sacrificial templates to produce Au hollow nanostructures via galvanic replacement reaction with HAuCl4 at room temperature.

  5. Effects of PVP on the preparation and growth mechanism of monodispersed Ni nanoparticles

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Monodispersed Ni nanoparticles were successfully prepared by chemical reduction with hydrazine hydrate in ethylene glycol.The effect of the amount of polyvinylpyrrolidone (PVP-K30) on the preparation of Ni nanoparticles was investigated.X-ray diffraction (XRD),transmission electron microscopy (TEM),and high resolution transmission electron microscopy (HRTEM) were employed to characterize the nickel particles are spherical in shape and are not agglomerated.A possible extensive mechanism of nickel nanoparticle formation has been suggested.

  6. A reproducible accelerated in vitro release testing method for PLGA microspheres.

    Science.gov (United States)

    Shen, Jie; Lee, Kyulim; Choi, Stephanie; Qu, Wen; Wang, Yan; Burgess, Diane J

    2016-02-10

    The objective of the present study was to develop a discriminatory and reproducible accelerated in vitro release method for long-acting PLGA microspheres with inner structure/porosity differences. Risperidone was chosen as a model drug. Qualitatively and quantitatively equivalent PLGA microspheres with different inner structure/porosity were obtained using different manufacturing processes. Physicochemical properties as well as degradation profiles of the prepared microspheres were investigated. Furthermore, in vitro release testing of the prepared risperidone microspheres was performed using the most common in vitro release methods (i.e., sample-and-separate and flow through) for this type of product. The obtained compositionally equivalent risperidone microspheres had similar drug loading but different inner structure/porosity. When microsphere particle size appeared similar, porous risperidone microspheres showed faster microsphere degradation and drug release compared with less porous microspheres. Both in vitro release methods investigated were able to differentiate risperidone microsphere formulations with differences in porosity under real-time (37 °C) and accelerated (45 °C) testing conditions. Notably, only the accelerated USP apparatus 4 method showed good reproducibility for highly porous risperidone microspheres. These results indicated that the accelerated USP apparatus 4 method is an appropriate fast quality control tool for long-acting PLGA microspheres (even with porous structures).

  7. Development of a novel AMX-loaded PLGA/zein microsphere for root canal disinfection

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, F F O [Capes Foundation, Ministry of Education of Brazil, Cx. Postal 365, BrasIlia DF 70359-970 (Brazil); Luzardo-Alvarez, A; Blanco-Mendez, J [Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, Campus Universitario Sur s/n, 15782, Santiago de Compostela (Spain); Perez-Estevez, A; Seoane-Prado, R, E-mail: franciscofabio.oliveira@rai.usc.e [Departament of Microbiology and Parasitology, Medical School, University of Santiago de Compostela, R/de San Francisco, s/n, 15782, Santiago de Compostela (Spain)

    2010-10-01

    The aim of this study was to develop polymeric biodegradable microspheres (MSs) of poly(d-l lactide-co-glycolide) (PLGA) and zein capable of delivering amoxicillin (AMX) at significant levels for root canal disinfection. PLGA/zein MSs were prepared using a spray-drying technique. The systems were characterized in terms of particle size, morphology, drug loading and in vitro release. Drug levels were reached to be effective during the intracanal dressing in between visits during the endodontic treatment. In vitro release studies were carried out to understand the release profile of the MSs. Antimicrobial activity of AMX was performed by antibiograms. Enterococcus faecalis was the bacteria selected due to its prevalence in endodontic failure. Drug microencapsulation yielded MSs with spherical morphology and an average particle size of between 5 and 38 {mu}m. Different drug-release patterns were obtained among the formulations. Release features related to the MSs were strongly dependent on drug nature as it was demonstrated by using a hydrophobic drug (indomethacin). Finally, AMX-loaded MSs were efficient against E faecalis as demonstrated by the antibiogram results. In conclusion, PLGA/zein MSs prepared by spray drying may be a useful drug delivery system for root canal disinfection.

  8. Release retardation of model protein on polyelectrolyte-coated PLGA nano- and microparticles.

    Directory of Open Access Journals (Sweden)

    Chandra Nugraha

    Full Text Available PEM capsules have been proposed for vehicles of drug microencapsulation, with the release triggered by pH, salt, magnetic field, or light. When built on another carrier encapsulating drugs, such as nanoparticles, it could provide additional release barrier to the releasing drug, providing further control to drug release. Although liposomes have received considerable attention with PEM coating for sustained drug release, similar results employing PEM built on poly(lactic-co-lycolic acid (PLGA particles is scant. In this work, we demonstrate that the build-up pH and polyelectrolyte pairs of PEM affect the release retardation of BSA from PLGA particles. PAH/PSS pair, the most commonly used polyelectrolyte pair, was used in comparison with PLL/DES. In addition, we also demonstrate that the release retardation effect of PEM-coated PLGA particles diminishes as the particle size increases. We attribute this to the diminishing relative thickness of the PEM coating with respect to the size of the particle as the particle size increases, reducing the diffusional resistance of the PEM.

  9. Construction of a PLGA based, targeted siRNA delivery system for treatment of osteoporosis.

    Science.gov (United States)

    Sezlev Bilecen, Deniz; Rodriguez-Cabello, Jose Carlos; Uludag, Hasan; Hasirci, Vasif

    2017-11-01

    Osteoporosis, a systemic skeletal disorder, occurs when bone turnover balance is disrupted. With the identification of the genes involved in the pathogenesis of the disease, studies on development of new treatments has intensified. Short interfering RNA (siRNA) is used to knockdown disease related gene expressions. Targeting siRNA in vivo is challenging. The maintenance of therapeutic plasma level is hampered by clearance of siRNA from the body. Targeted systems are useful in increasing the drug concentration at the target site and decreasing side effects. Aim of the present study was to develop an injectable siRNA delivery system to protect siRNA during systemic distribution and target the siRNA to bone tissue using a thermoresponsive, genetically engineered, elastin-like recombinamer (ELR), designed to interact with the mineral component of bone. The delivery system consisted of DNAoligo as a siRNA substitute complexed with the cationic polymer, polyethyleneimine (PEI), at N/P ratio of 20. The complex was encapsulated in poly(lactic acid-co-glycolic acid) (PLGA) nanocapsules. PLGA capsules were characterized by SEM, TEM and XPS. FTIR was used to show the preferential attachment of ELR to HAp. Encapsulation efficiency of the complex in PLGA nanocapsules was 48%. The release kinetics of the complex fits the Higuchi release kinetics.

  10. Statistical design for formulation optimization of hydrocortisone butyrate-loaded PLGA nanoparticles.

    Science.gov (United States)

    Yang, Xiaoyan; Patel, Sulabh; Sheng, Ye; Pal, Dhananjay; Mitra, Ashim K

    2014-06-01

    The aim of this investigation was to develop hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) with ideal encapsulation efficiency (EE), particle size, and drug loading (DL) under emulsion solvent evaporation technique utilizing various experimental statistical design modules. Experimental designs were used to investigate specific effects of independent variables during preparation of HB-loaded PLGA NP and corresponding responses in optimizing the formulation. Plackett-Burman design for independent variables was first conducted to prescreen various formulation and process variables during the development of NP. Selected primary variables were further optimized by central composite design. This process leads to an optimum formulation with desired EE, particle size, and DL. Contour plots and response surface curves display visual diagrammatic relationships between the experimental responses and input variables. The concentration of PLGA, drug, and polyvinyl alcohol and sonication time were the critical factors influencing the responses analyzed. Optimized formulation showed EE of 90.6%, particle size of 164.3 nm, and DL of 64.35%. This study demonstrates that statistical experimental design methodology can optimize the formulation and process variables to achieve favorable responses for HB-loaded NP.

  11. Release retardation of model protein on polyelectrolyte-coated PLGA nano- and microparticles.

    Science.gov (United States)

    Nugraha, Chandra; Bora, Meghali; Venkatraman, Subbu S

    2014-01-01

    PEM capsules have been proposed for vehicles of drug microencapsulation, with the release triggered by pH, salt, magnetic field, or light. When built on another carrier encapsulating drugs, such as nanoparticles, it could provide additional release barrier to the releasing drug, providing further control to drug release. Although liposomes have received considerable attention with PEM coating for sustained drug release, similar results employing PEM built on poly(lactic-co-lycolic acid) (PLGA) particles is scant. In this work, we demonstrate that the build-up pH and polyelectrolyte pairs of PEM affect the release retardation of BSA from PLGA particles. PAH/PSS pair, the most commonly used polyelectrolyte pair, was used in comparison with PLL/DES. In addition, we also demonstrate that the release retardation effect of PEM-coated PLGA particles diminishes as the particle size increases. We attribute this to the diminishing relative thickness of the PEM coating with respect to the size of the particle as the particle size increases, reducing the diffusional resistance of the PEM.

  12. PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

    Science.gov (United States)

    Halayqa, Mohammed; Domańska, Urszula

    2014-12-22

    In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  13. PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

    Directory of Open Access Journals (Sweden)

    Mohammed Halayqa

    2014-12-01

    Full Text Available In our study, poly(dl-lactide-co-glycolide (PLGA nanoparticles loaded with perphenazine (PPH and chlorpromazine hydrochloride (CPZ-HCl were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol (PVA concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4 by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

  14. Study of antimicrobial effects of vancomycin loaded PLGA nanoparticles against enterococcus clinical isolates.

    Science.gov (United States)

    Lotfipour, F; Abdollahi, S; Jelvehgari, M; Valizadeh, H; Hassan, M; Milani, M

    2014-07-01

    Researchers have demonstrated that antimicrobial agents in nanoparticle (NP) forms have better activities. Vancomycin (VCM), as a glycopeptide antibiotic with antimicrobial activity against gram positive bacteria, is poorly absorbed from the intestinal tract. Enterococcus is a genus of bacteria that became resistant to a wide range of antibiotics in last decades, and cause severe infections in hospitalized patients. This paper describes preparation of VCM--loaded poly (lactic-co-glycolic acid) (PLGA) NPs and compares the antimicrobial effects with drug solution against clinical Enterococcus isolates. VCM-loaded PLGA NPs were fabricated by W1/O/W2 solvent evaporation method. The comparison of obtained Minimum Inhibitory Concentration (MIC) values showed a significant decrease in the antimicrobial effect of VCM -loaded NPs. Results also indicated that the potency of the NPs against VCM resistant isolates of Enterococcus was less than VCM susceptible isolates. The reduced antimicrobial effect of formulated NPs in invitro condition is perhaps related to the strong electrostatic linkage between hydrophilic drug (VCM) and hydrophobic polymer (PLGA) that lead to the slow release of the antibiotic from polymeric NPs.

  15. PLGA-carbon nanotube conjugates for intercellular delivery of caspase-3 into osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Qingsu Cheng

    Full Text Available Cancer has arisen to be of the most prominent health care issues across the world in recent years. Doctors have used physiological intervention as well as chemical and radioactive therapeutics to treat cancer thus far. As an alternative to current methods, gene delivery systems with high efficiency, specificity, and safety that can reduce side effects such as necrosis of tissue are under development. Although viral vectors are highly efficient, concerns have arisen from the fact that viral vectors are sourced from lethal diseases. With this in mind, rod shaped nano-materials such as carbon nanotubes (CNTs have become an attractive option for drug delivery due to the enhanced permeability and retention effect in tumors as well as the ability to penetrate the cell membrane. Here, we successfully engineered poly (lactic-co-glycolic (PLGA functionalized CNTs to reduce toxicity concerns, provide attachment sites for pro-apoptotic protein caspase-3 (CP3, and tune the temporal release profile of CP3 within bone cancer cells. Our results showed that CP3 was able to attach to functionalized CNTs, forming CNT-PLGA-CP3 conjugates. We show this conjugate can efficiently transduce cells at dosages as low as 0.05 μg/ml and suppress cell proliferation up to a week with no further treatments. These results are essential to showing the capabilities of PLGA functionalized CNTs as a non-viral vector gene delivery technique to tune cell fate.

  16. Surface hydrophilicity of PLGA fibers governs in vitro mineralization and osteogenic differentiation.

    Science.gov (United States)

    Thomas, Minnah; Arora, Aditya; Katti, Dhirendra S

    2014-12-01

    Interfacial properties of biomaterials play an important role in governing their interaction with biological microenvironments. This work investigates the role of surface hydrophilicity of electrospun poly(lactide-co-glycolide) (PLGA) fibers in determining their biological response. For this, PLGA is blended with varying amounts of Pluronic®F-108 and electrospun to fabricate microfibers with varying surface hydrophilicity. The results of mineralization study in simulated body fluid (SBF) demonstrate a significant enhancement in mineralization with an increase in surface hydrophilicity. While presence of serum proteins in SBF reduces absolute mineral content, mineralization continues to be higher on samples with higher surface hydrophilicity. The results from in vitro cell culture studies demonstrate a marked improvement in mesenchymal stem cell-adhesion, elongation, proliferation, infiltration, osteogenic differentiation and matrix mineralization on hydrophilized fibers. Therefore, hydrophilized PLGA fibers are advantageous both in terms of mineralization and elicitation of favorable cell response. Since most of the polymeric materials being used in orthopedics are hydrophobic in nature, the results from this study have strong implications in the future design of interfaces of such hydrophobic materials. In addition, the work proposes a facile method for the modification of electrospun fibers of hydrophobic polymers by blending with a poloxamer for improved bone tissue regeneration.

  17. The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth: Different administration routes.

    Science.gov (United States)

    Fasehee, Hamidreza; Zarrinrad, Ghazaleh; Tavangar, Seyed Mohammad; Ghaffari, Seyed Hamidollah; Faghihi, Shahab

    2016-06-01

    The strong anticancer activity of disulfiram is hindered by its rapid degradation in blood system. A novel folate-receptor-targeted poly (lactide-co-glycolide) (PLGA)-polyethylene glycol (PEG) nanoparticle (NP) is developed for encapsulation and delivery of disulfiram into breast cancer tumor using passive (EPR effect) and active (folate receptor) targeting. The anticancer activity of disulfiram and its effect on caspase-3 activity and cell cycle are studied. The administration of encapsulated PLGA NPs using intra-peritoneal, intravenous and intra-tumor routes is investigated using animal model. Disulfiram shows strong cytotoxicity against MCF7 cell line. The activity of caspase-3 inhibited with disulfiram via dose dependent manner while the drug causes cell cycle arrest in G0/G1 and S phase time-dependently. The encapsulated disulfiram shows higher activity in apoptosis induction as compared to free drug. In nontoxic dose of encapsulated disulfiram, the highest and lowest efficacy of NPs in tumor growth inhibition is observed for intravenous injection and intraperitoneal injection. It is suggested that administration of disulfiram by targeted PLGA nanoparticles using intravenous injection would present an alternative therapeutic approach for solid tumor treatment.

  18. Preparation and characterization of Chinese yam polysaccharide PLGA nanoparticles and their immunological activity.

    Science.gov (United States)

    Luo, Li; Zheng, Sisi; Huang, Yifan; Qin, Tao; Xing, Jie; Niu, Yale; Bo, Ruonan; Liu, Zhenguang; Huang, Yee; Hu, Yuanliang; Liu, Jiaguo; Wu, Yi; Wang, Deyun

    2016-09-10

    This paper first provides that Chinese yam polysaccharide (CYP) is encapsulated by PLGA using a double emulsion solvent evaporation method and aims to screen the optimal preparation of CYP-PLGA nanoparticles (CYPP) using response surface methodology (RSM). The volume ratio of the internal water phase to the organic phase (W1:O), the volume ratio of the primary emulsion to the external water phase (PE:W2) and the concentration of Poloxamer 188 (F68) are deemed key variables for the encapsulation efficiency of CYPP. The results demonstrated that the data were accurately fitted into the RSM model. According to the RSM, the optimal scheme was a volume ratio of W1:O of 1:9, a volume ratio of PE: W2 of 1:10 and a concentration of F68 (W/V) of 0.7%. TEM and SEM images demonstrated that the nanoparticles had a spherical shape and smooth surface. The CYP and CYPP in vitro release studies demonstrated that the CYPP showed a release rate 53.41% lower than the release rate of CYP after 48h. The result of pro-proliferation and flow cytometry emerged that the CYPP were more effective compared with the free CYP and blank PLGA nanoparticles in promoting lymphocyte proliferation and triggering the transformation of T lymphocytes into Th cells.

  19. Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair.

    Science.gov (United States)

    Wang, Jianhua; Yang, Qiu; Cheng, Niangmei; Tao, Xiaojun; Zhang, Zhihua; Sun, Xiaomin; Zhang, Qiqing

    2016-04-01

    For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration.

  20. Development and physicochemical characterization of copper complexes-loaded PLGA nanoparticles.

    Science.gov (United States)

    Courant, T; Roullin, V G; Cadiou, C; Delavoie, F; Molinari, M; Andry, M C; Chuburu, F

    2009-09-11

    PLGA nanoparticles were prepared via a modified W/O/W emulsion solvent diffusion process, in which all formulation components were fully biocompatible and biodegradable. Different independent processing parameters were systematically studied. Nanoparticles were characterized by DLS (particle size, polydispersity, zeta-potential) and TEM/AFM (surface morphology). An optimized formulation was used to encapsulate copper complexes of cyclen and DOTA as potential PET imaging agents. Results showed that the predominant formulation factors appeared to be the lactide-to-glycolide (L:G) ratio of PLGA, the nature of the diffusion phase, and the presence of hydroxyl ions in the first-emulsion aqueous phase. By regulating those 3 parameters, PLGA nanoparticles were prepared with very good preparation yields (>95%), a size less than 200 nm and a polydispersity index less than 0.1. TEM pictures showed nanoparticles with a narrow size distribution, a spherical shape and a smooth surface. The optimized formulation allowed to encapsulate Cu-cyclen and Cu-DOTA complexes with an encapsulation efficiency between 20% and 25%.

  1. Gelsolin Amyloidogenesis Is Effectively Modulated by Curcumin and Emetine Conjugated PLGA Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Ankit Srivastava

    Full Text Available Small molecule based therapeutic intervention of amyloids has been limited by their low solubility and poor pharmacokinetic characteristics. We report here, the use of water soluble poly lactic-co-glycolic acid (PLGA-encapsulated curcumin and emetine nanoparticles (Cm-NPs and Em-NPs, respectively, as potential modulators of gelsolin amyloidogenesis. Using the amyloid-specific dye Thioflavin T (ThT as an indicator along with electron microscopic imaging we show that the presence of Cm-NPs augmented amyloid formation in gelsolin by skipping the pre-fibrillar assemblies, while Em-NPs induced non-fibrillar aggregates. These two types of aggregates differed in their morphologies, surface hydrophobicity and secondary structural signatures, confirming that they followed distinct pathways. In spite of differences, both these aggregates displayed reduced toxicity against SH-SY5Y human neuroblastoma cells as compared to control gelsolin amyloids. We conclude that the cytotoxicity of gelsolin amyloids can be reduced by either stalling or accelerating its fibrillation process. In addition, Cm-NPs increased the fibrillar bulk while Em-NPs defibrillated the pre-formed gelsolin amyloids. Moreover, amyloid modulation happened at a much lower concentration and at a faster rate by the PLGA encapsulated compounds as compared to their free forms. Thus, besides improving pharmacokinetic and biocompatible properties of curcumin and emetine, PLGA conjugation elevates the therapeutic potential of both small molecules against amyloid fibrillation and toxicity.

  2. Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats

    Directory of Open Access Journals (Sweden)

    Changxing Wang

    2017-03-01

    Full Text Available Background/Aims: Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI. This study investigated the potential for poly (lactic-co-glycolic acid (PLGA complex inoculated with olfactory ensheathing cells (OECs to treat spinal cord injury in a rat model. Methods: OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR p75. The Basso, Beattie, and Bresnahan (BBB score, together with an inclined plane (IP test were used to detect functional recovery. Nissl staining along with the luxol fast blue (LFB staining were independently employed to illustrate morphological alterations. More so, immunofluorescence labeling of the glial fibrillary acidic protein (GFAP and the microtubule-associated protein-2 (MAP-2, representing astrocytes and neurons respectively, were investigated at time points of weeks 2 and 8 post-operation. Results: The findings showed enhanced locomotor recovery, axon myelination and better protected neurons post SCI when compared with either PLGA or untreated groups (P < 0.05. Conclusion: PLGA complexes inoculated with OECs improve locomotor functional recovery in transected spinal cord injured rat models, which is most likely due to the fact it is conducive to a relatively benevolent microenvironment, has nerve protective effects, as well as the ability to enhance remyelination, via a promotion of cell differentiation and inhibition of astrocyte formation.

  3. Electrospun PLGA/gelatin fibrous tubes for the application of biodegradable intestinal stent in rat model.

    Science.gov (United States)

    Son, So-Ra; Franco, Rose-Ann; Bae, Sang-Ho; Min, Young-Ki; Lee, Byong-Taek

    2013-08-01

    A biodegradable fibrous tube was fabricated by electrospinning method using a combination of Poly(lactic-co-glycolic acid) (PLGA) and gelatin dissolved in trifluoroethanol (TFE). Different ratios of the two polymers (PLGA/Gelatin: 1/9, 3/7, 5/5) were used for electrospinning to determine the optimum condition appropriate for intestinal stent application. Fiber morphology was visualized and analyzed using a scanning electron microscope (SEM). Characterizations of physical properties were done according to its tensile strength, surface hydrophilicity, swelling ability, and biodegradability. Biocompatibility of the scaffolds was investigated in vitro using IEC-18 (Rat intestinal epithelial cell). Cell proliferation was quantified using MTT assay and cell adhesion behavior was visualized by SEM and confocal laser scanning microscope. PLGA/Gelatin (5/5) was determined to have adequate material properties and sufficient in vitro biocompatibility. This was then implanted in a male Sprague-Dawley rat for 14 days to determine in vivo behavior of the sample. Histological examination on the intestinal tissue surrounding the graft showed normal morphology comparable to non-implanted intestine.

  4. Characterization of lysosome-destabilizing DOPE/PLGA nanoparticles designed for cytoplasmic drug release.

    Science.gov (United States)

    Chhabra, Resham; Grabrucker, Andreas M; Veratti, Patrizia; Belletti, Daniela; Boeckers, Tobias M; Vandelli, Maria Angela; Forni, Flavio; Tosi, Giovanni; Ruozi, Barbara

    2014-08-25

    Polymeric nanoparticles (NPs) offer a promising approach for therapeutic intracellular delivery of proteins, conventionally hampered by short half-lives, instability and immunogenicity. Remarkably, NPs uptake occurs via endocytic internalization leading to NPs content's release within lysosomes. To overcome lysosomal degradation and achieve NPs and/or loaded proteins release into cytosol, we propose the formulation of hybrid NPs by adding 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) as pH sensitive component in the formulation of poly-lactide-co-glycolide (PLGA) NPs. Hybrid NPs, featured by different DOPE/PLGA ratios, were characterized in terms of structure, stability and lipid organization within the polymeric matrix. Experiments on NIH cells and rat primary neuronal cultures highlighted the safety profile of hybrid NPs. Moreover, after internalization, NPs are able to transiently destabilize the integrity of lysosomes in which they are taken up, speeding their escape and favoring cytoplasmatic localization. Thus, these DOPE/PLGA-NPs configure themselves as promising carriers for intracellular protein delivery.

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

    Science.gov (United States)

    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.

  6. Interpenetrating Polymer Network Hydrogels Based on VP/MMA Gel and PLGA Diacrylate Macromers

    Science.gov (United States)

    Lee, J. Hannah; Radzi, Zamri; Swan, Marc; Bucknall, David; Czernuszka, Jan

    2010-03-01

    Hydrogels have been widely used in biomedical applications due to their biocompatibility, similar physical properties to human tissue and appropriate mechanical properties. A thorough understanding of their swelling behavior is necessary to be able to choose the most suitable hydrogel and to applying it optimally. The long term goal of our research is to develop hydrogel systems with controllable swelling behavior for medical/surgical use. For this purpose, interpenetrating polymer network (IPN) hydrogels have been prepared based on the N-vinyl-2-pyrrolidone (VP)/methyl methacrylate (MMA) copolymeric gel and poly(DL-lactic-co-glycolic acid) (PLGA) diacrylate macromers as well as semi-IPN VP/MMA and PLGA hydrogels. The thermal, morphological, mechanical and physical properties of the hydrogels have been characterized and the potential for surgical use verified. This presentation will concentrate on the studies of the swelling kinetics and equilibrium swelling ratios of the hydrogels. In addition, very recent results will be presented on how additions of PLGA can be used to manipulate the swelling behavior of the hydrogel system.

  7. Peripheral nerve regeneration within an asymmetrically porous PLGA/Pluronic F127 nerve guide conduit.

    Science.gov (United States)

    Oh, Se Heang; Kim, Jun Ho; Song, Kyu Sang; Jeon, Byeong Hwa; Yoon, Jin Hwan; Seo, Tae Beom; Namgung, Uk; Lee, Il Woo; Lee, Jin Ho

    2008-04-01

    Asymmetrically porous tubes with selective permeability and hydrophilicity as nerve guide conduits (NGCs) were fabricated using poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127 by a modified immersion precipitation method. The inner surface of the tube had nano-size pores ( approximately 50nm) which can effectively prevent from fibrous tissue infiltration but permeate nutrients and retain neurotrophic factors, while the outer surface had micro-size pores ( approximately 50microm) which can allow vascular ingrowth for effective supply of nutrients into the tube. From the animal study using a rat model, the hydrophilized PLGA/F127 (3wt%) tube showed better nerve regeneration behavior than the control silicone or hydrophobic PLGA tubes, as investigated by immunohistochemical observation (by fluorescent microscopy with anti-neurofilament staining), histological observations (by light microscopy with toluidine blue staining and transmission electron microscopy), and electrophysiological evaluation (by compound muscle action potential measurement). This is probably owing to the effective permeation of nutrients and prevention of fibrous scar tissue invasion as well as the good mechanical strength of the tube to maintain a stable support structure for the nerve regeneration.

  8. Studies on Monodispersed Microspheres of Zinc Sulfide Doped with Mn2+

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In this paper, zinc acetate, manganese acetate and thiacetamide are used as raw materials to successfully synthesize monodispersed ZnS:Mn2+ microspheres by using hydrothermal method and taking P123 surfactant as a template. The products were characterized by XRD, STEM,FT-IR and N2 adsorption-desorption. And the results show that the diameter of this microsphere is 1.0 μm or so, which is larger than that of ZnS microsphere without Mn2+ doping, and it has monodispersion, smooth surface and uniform size. The doping of Mn2+ does not obviously change the structure of monodispersed ZnS microsphere. The photoluminescence peak lies in a wide band ranging from 450 to 650 nm, and the microspheres emit orange light;with the increase of Mn2+concentration, fluorescence intensity of ZnS:Mn2+ microsphere changes, and when the mole ratio of Mn2+:Zn2+is 0.3:1, the fluorescence intensity is the strongest.

  9. Monodispersity of recombinant Cre recombinase correlates with its effectiveness in vivo

    Directory of Open Access Journals (Sweden)

    Edenhofer Frank

    2009-09-01

    Full Text Available Abstract Background Cre recombinase is a common reagent used for the in vivo on/off switching of the expression of target genes flanked by loxP sites. In particular, recombinant TAT-Cre fusion constructs purified from bacteria have been used to promote the cell uptake of the enzyme. However, the recovery of active TAT-Cre remains a demanding process and its specific activity varies significantly among batches, making difficult data comparison. Results We noticed a strong correlation between recombinase activity and enzyme monodispersity. The existence of such correlation enabled us to indirectly monitor the TAT-Cre recombinase activity during the multi-step purification process by measuring its monodispersity, a parameter detectable by means of a spectrofluorimetric assay that allows the calculation of the Aggregation Index (AI in an easy and rapid way. AI values were recorded after each purification passage to identify the critical steps and to choose optimal alternatives for chromatographic conditions, desalting procedures, and protocols for bacterial endotoxin removal. Furthermore, the effect of metal ions and temperature on TAT-Cre aggregation and inactivation was characterized in vitro. Finally, we optimized the enzyme delivery protocol in vivo by following the accumulation tuning of the reporter protein β-catenin. Conclusion A rational purification protocol for TAT-Cre has been developed by choosing the options that minimize the enzyme aggregation. Our data suggest that AI measurement should support the optimization of any protocol aiming at the recovery of monodispersed protein.

  10. Existence of isostatic, maximally random jammed monodisperse hard-disk packings.

    Science.gov (United States)

    Atkinson, Steven; Stillinger, Frank H; Torquato, Salvatore

    2014-12-30

    We generate jammed packings of monodisperse circular hard-disks in two dimensions using the Torquato-Jiao sequential linear programming algorithm. The packings display a wide diversity of packing fractions, average coordination numbers, and order as measured by standard scalar order metrics. This geometric-structure approach enables us to show the existence of relatively large maximally random jammed (MRJ) packings with exactly isostatic jammed backbones and a packing fraction (including rattlers) of [Formula: see text]. By contrast, the concept of random close packing (RCP) that identifies the most probable packings as the most disordered misleadingly identifies highly ordered disk packings as RCP in 2D. Fundamental structural descriptors such as the pair correlation function, structure factor, and Voronoi statistics show a strong contrast between the MRJ state and the typical hyperstatic, polycrystalline packings with [Formula: see text] that are more commonly obtained using standard packing protocols. Establishing that the MRJ state for monodisperse hard disks is isostatic and qualitatively distinct from commonly observed polycrystalline packings contradicts conventional wisdom that such a disordered, isostatic packing does not exist due to a lack of geometrical frustration and sheds light on the nature of disorder. This prompts the question of whether an algorithm may be designed that is strongly biased toward generating the monodisperse disk MRJ state.

  11. Synthesis of monodisperse silver nanoparticles for ink-jet printed flexible electronics

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Zhiliang; Zhang Xingye; Xin Zhiqing; Deng Mengmeng; Wen Yongqiang; Song Yanlin, E-mail: zhangxy@iccas.ac.cn, E-mail: ylsong@iccas.ac.cn [Beijing National Laboratory for Molecular Sciences (BNLMS), Key Lab of Organic Solids, Laboratory of New Materials, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China)

    2011-10-21

    In this study, monodisperse silver nanoparticles were synthesized with a new reduction system consisting of adipoyl hydrazide and dextrose at ambient temperature. By this facile and rapid approach, high concentration monodisperse silver nanoparticles were obtained on a large scale at low protectant/AgNO{sub 3} mass ratio which was highly beneficial to low cost and high conductivity. Based on the synthesized monodisperse silver nanoparticles, conductive inks were prepared with water, ethanol and ethylene glycol as solvents, and were expected to be more environmentally friendly. A series of electrocircuits were fabricated by ink-jet printing silver nanoparticle ink on paper substrate with a commercial printer, and they had low resistivity in the range of 9.18 x 10{sup -8}-8.76 x 10{sup -8} {Omega} m after thermal treatment at 160 {sup 0}C for 30 min, which was about five times that of bulk silver (1.586 x 10{sup -8} {Omega} m). Moreover, a radio frequency identification (RFID) antenna was fabricated by ink-jet printing, and 6 m wireless identification was realized after an Alien higgs-3 chip was mounted on the printed antenna by the flip-chip method. These flexible electrocircuits produced by ink-jet printing would have enormous potential for low cost electrodes and sensor devices.

  12. Synthesis of monodisperse silver nanoparticles for ink-jet printed flexible electronics.

    Science.gov (United States)

    Zhang, Zhiliang; Zhang, Xingye; Xin, Zhiqing; Deng, Mengmeng; Wen, Yongqiang; Song, Yanlin

    2011-10-21

    In this study, monodisperse silver nanoparticles were synthesized with a new reduction system consisting of adipoyl hydrazide and dextrose at ambient temperature. By this facile and rapid approach, high concentration monodisperse silver nanoparticles were obtained on a large scale at low protectant/AgNO(3) mass ratio which was highly beneficial to low cost and high conductivity. Based on the synthesized monodisperse silver nanoparticles, conductive inks were prepared with water, ethanol and ethylene glycol as solvents, and were expected to be more environmentally friendly. A series of electrocircuits were fabricated by ink-jet printing silver nanoparticle ink on paper substrate with a commercial printer, and they had low resistivity in the range of 9.18 × 10( - 8)-8.76 × 10( - 8) Ω m after thermal treatment at 160 °C for 30 min, which was about five times that of bulk silver (1.586 × 10( - 8) Ω m). Moreover, a radio frequency identification (RFID) antenna was fabricated by ink-jet printing, and 6 m wireless identification was realized after an Alien higgs-3 chip was mounted on the printed antenna by the flip-chip method. These flexible electrocircuits produced by ink-jet printing would have enormous potential for low cost electrodes and sensor devices.

  13. Enhanced antitumor activity in A431 cells via encapsulation of 20(R)-ginsenoside Rg3 in PLGA nanoparticles.

    Science.gov (United States)

    Zhang, Shaozhi; Liu, Jiwei; Ge, Baojian; Du, Meiling; Fu, Li; Fu, Yushan; Yan, Qiu

    2017-10-01

    The objective of this study is to investigate the encapsulation of 20(R)-ginsenoside Rg3 (20(R)-Rg3) using polylactic-co-glycolic acid (PLGA) and promotion for its antitumor activity. Preparation and evaluation of the antitumor efficacy of 20(R)-Rg3-loaded PLGA nanoparticles were the first reported. The data will be helpful to apply 20(R)-Rg3 efficiently and broadly in new drug form development and clinical cancer treatment. The nanoparticles were prepared using emulsion and solvent evaporation methods. The uniform particle size and good dispersion were further confirmed by scanning electron microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to detect cell proliferation after 20(R)-Rg3-loaded PLGA nanoparticles treatment. Western blotting and immunofluorescent staining were used for observation of key proteins related with proliferation and apoptosis. Cell cycle and apoptosis were analyzed by flow cytometer technology. The results showed that the size of 20(R)-Rg3-loaded PLGA was 97.5 nm in diameter, and zeta potential was -28 mV detected by Malvern particle size analyzer. The encapsulation efficiency was 97.5%, and drug loading was 70.2% measured by high-performance liquid chromatography. The in vitro study showed that the encapsulated 20(R)-Rg3 was consecutively released and the release ratio reached to the highest value (19.36%) at the time point of 96 h. The encapsulated 20(R)-Rg3 significantly inhibited the proliferation and induced apoptosis in A431 cancer cells compared with the unencapsulated 20(R)-Rg3, control and PLGA alone. 20(R)-Rg3-loaded PLGA nanoparticles was well prepared and characterized. The antitumor activity was increased after PLGA encapsulation. The data will be beneficial to the development of new dosage forms of 20(R)-Rg3 and extensive application.

  14. A biomimetic approach to active self-microencapsulation of proteins in PLGA.

    Science.gov (United States)

    Shah, Ronak B; Schwendeman, Steven P

    2014-12-28

    A biomimetic approach to organic solvent-free microencapsulation of proteins based on the self-healing capacity of poly (DL)-lactic-co-glycolic acid (PLGA) microspheres containing glycosaminoglycan-like biopolymers (BPs), was examined. To screen BPs, aqueous solutions of BP [high molecular weight dextran sulfate (HDS), low molecular weight dextran sulfate (LDS), chondroitin sulfate (CS), heparin (HP), hyaluronic acid (HA), chitosan (CH)] and model protein lysozyme (LYZ) were combined in different molar and mass ratios, at 37 °C and pH7. The BP-PLGA microspheres (20-63 μm) were prepared by a double water-oil-water emulsion method with a range of BP content, and trehalose and MgCO3 to control microclimate pH and to create percolating pores for protein. Biomimetic active self-encapsulation (ASE) of proteins [LYZ, vascular endothelial growth factor165 (VEGF) and fibroblast growth factor (FgF-20)] was accomplished by incubating blank BP-PLGA microspheres in low concentration protein solutions at ~24 °C, for 48 h. Pore closure was induced at 42.5 °C under mild agitation for 42h. Formulation parameters of BP-PLGA microspheres and loading conditions were studied to optimize protein loading and subsequent release. LDS and HP were found to bind >95% LYZ at BP:LYZ>0.125 w/w, whereas HDS and CS bound >80% LYZ at BP:LYZ of 0.25-1 and 2% w/w of LYZ). Sulfated BP-PLGA microspheres were capable of loading LYZ (~2-7% w/w), VEGF (~4% w/w), and FgF-20 (~2% w/w) with high efficiency. Protein loading was found to be dependent on the loading solution concentration, with higher protein loading obtained at higher loading solution concentration within the range investigated. Loading also increased with content of sulfated BP in microspheres. Release kinetics of proteins was evaluated in-vitro with complete release media replacement. Rate and extent of release were found to depend upon volume of release (with non-sink conditions observed 90% of protein being enzymatically active. Nearly

  15. Evaluating the Use of Monocytes with a Degradable Polyurethane for Vascular Tissue Regeneration

    Science.gov (United States)

    Battiston, Kyle Giovanni

    Monocytes are one of the first cell types present following the implantation of a biomaterial or tissue engineered construct. Depending on the monocyte activation state supported by the biomaterial, monocytes and their derived macrophages (MDMs) can act as positive contributors to tissue regeneration and wound healing, or conversely promote a chronic inflammatory response that leads to fibrous encapsulation and implant rejection. A degradable polar hydrophobic iconic polyurethane (D-PHI) has been shown to reduce pro-inflammatory monocyte/macrophage response compared to tissue culture polystyrene (TCPS), a substrate routinely used for in vitro culture of cells, as well as poly(lactide- co-glycolide) (PLGA), a standard synthetic biodegradable biomaterial in the tissue engineering field. D-PHI has also shown properties suitable for use in a vascular tissue engineering context. In order to understand the mechanism through which D-PHI attenuates pro-inflammatory monocyte response, this thesis investigated the ability of D-PHI to modulate interactions with adsorbed serum proteins and the properties of D-PHI that were important for this activity. D-PHI was shown to regulate protein adsorption in a manner that produced divergent monocyte responses compared to TCPS and PLGA when coated with the serum proteins alpha2-macroglobulin or immunoglobulin G (IgG). In the case of IgG, D-PHI was shown to reduce pro-inflammatory binding site exposure as a function of the material's polar, hydrophobic, and ionic character. Due to the favourable monocyte activation state supported by D-PHI, and the importance of monocytes/macrophages in regulating the response of tissue-specific cell types in vivo, the ability of a D-PHI-stimulated monocyte/macrophage activation state to contribute to modulating the response of vascular smooth muscle cells (VSMCs) in a vascular tissue engineering context was investigated. D-PHI- stimulated monocytes promoted VSMC growth and migration through biomolecule

  16. Evaluation of Changes in Morphology and Function of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (HiPSC-CMs Cultured on an Aligned-Nanofiber Cardiac Patch.

    Directory of Open Access Journals (Sweden)

    Mahmood Khan

    Full Text Available Dilated cardiomyopathy is a major cause of progressive heart failure. Utilization of stem cell therapy offers a potential means of regenerating viable cardiac tissue. However, a major obstacle to stem cell therapy is the delivery and survival of implanted stem cells in the ischemic heart. To address this issue, we have developed a biomimetic aligned nanofibrous cardiac patch and characterized the alignment and function of human inducible pluripotent stem cell derived cardiomyocytes (hiPSC-CMs cultured on this cardiac patch. This hiPSC-CMs seeded patch was compared with hiPSC-CMs cultured on standard flat cell culture plates.hiPSC-CMs were cultured on; 1 a highly aligned polylactide-co-glycolide (PLGA nanofiber scaffold (~50 microns thick and 2 on a standard flat culture plate. Scanning electron microscopy (SEM was used to determine alignment of PLGA nanofibers and orientation of the cells on the respective surfaces. Analysis of gap junctions (Connexin-43 was performed by confocal imaging in both the groups. Calcium cycling and patch-clamp technique were performed to measure calcium transients and electrical coupling properties of cardiomyocytes.SEM demonstrated >90% alignment of the nanofibers in the patch which is similar to the extracellular matrix of decellularized rat myocardium. Confocal imaging of the cardiomyocytes demonstrated symmetrical alignment in the same direction on the aligned nanofiber patch in sharp contrast to the random appearance of cardiomyocytes cultured on a tissue culture plate. The hiPSC-CMs cultured on aligned nanofiber cardiac patches showed more efficient calcium cycling compared with cells cultured on standard flat surface culture plates. Quantification of mRNA with qRT-PCR confirmed that these cardiomyocytes expressed α-actinin, troponin-T and connexin-43 in-vitro.Overall, our results demonstrated changes in morphology and function of human induced pluripotent derived cardiomyocytes cultured in an anisotropic

  17. Sequential delivery of chlorhexidine acetate and bFGF from PLGA-glycol chitosan core-shell microspheres.

    Science.gov (United States)

    Chen, Ming-Mao; Cao, Huan; Liu, Yuan-Yuan; Liu, Yan; Song, Fei-Fei; Chen, Jing-Di; Zhang, Qi-Qing; Yang, Wen-Zhi

    2017-03-01

    Wound treatment should meet the challenge both of preventing infection and promoting wound healing. To design a sequential delivery system for wound healing, PLGA-glycol chitosan (GC) core-shell microspheres containing chlorhexidine acetate (CHA) at the GC shell and bFGF in the core of PLGA microspheres were fabricated using emulsion-solvent evaporation method. SEM showed that the microspheres were all spherical in shape with a smooth surface. The average size of PLGA-GC microspheres increased due to the GC coating on the surface. The results of release profiles and fluorescence images indicated that PLGA-GC microspheres had an ability to deliver drugs in sequence. The CHA was rapidly released, whereas the proteins presented a sustained release. The release behavior could be modulated by changing the GC amount. Antibacterial assay and cell proliferation tests suggested that the released CHA and bFGF retained their antimicrobial activity and bioactivity during preparation. The microspheres exhibited non-cytotoxicity against 3T3 cells and had a good biocompatibility. These results demonstrated that PLGA-GC core-shell microspheres could be a promising controlled release system of delivering drugs and proteins in sequence for wound healing.

  18. Perfluorocarbon-Encapsulated PLGA-PEG Emulsions as Enhancement Agents for Highly Efficient Reoxygenation to Cell and Organism.

    Science.gov (United States)

    Yao, Yanjie; Zhang, Minmin; Liu, Tian; Zhou, Juan; Gao, Yuan; Wen, Zhengfeng; Guan, Jun; Zhu, Jun; Lin, Zhaofen; He, Dannong

    2015-08-26

    Perfluorocarbon (PFC), a kind of oxygen carrier, is encapsulated in PLGA-PEG to prepare a PLGA-PEG/PFC emulsion for highly efficient reoxygenation to cell and organism. HCT 116 cells are used as a model cell, whose viability has a significant enhancement after reoxygenation with PLGA-PEG/PFC emulsion because of the sufficient and timely oxygen supply. Meanwhile, hypoxia-reoxygenation injury will happen along with cell hypoxia-reoxygenation treatment, which is reflected by increasing reactive oxygen species (ROS) in cells. However, the integration of intracellular ROS and cell viability implies that the degree of hypoxia-reoxygenation injury is sublethal to HCT116 cells when the concentration of PLGA-PEG/PFC emulsion is lower than 0.2 mg/mL. Furthermore, the change of the expression level of hypoxia-inducible factor-1α (HIF-1α) is similar to that of cell viability during reoxygenation, which suggests that HIF-1α or its downstream proteins may make a significant contribution to cell viability. In vivo oxygen supply is assessed in rats through pulmonary delivery, which shows that PLGA-PEG/PFC emulsion can supply oxygen to rats and improve rats' lung ventilation.

  19. Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2015-01-01

    Full Text Available Erythropoietin (EPO has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide (PLGA microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery.

  20. Localized and sustained delivery of erythropoietin from PLGA microspheres promotes functional recovery and nerve regeneration in peripheral nerve injury.

    Science.gov (United States)

    Zhang, Wei; Gao, Yuan; Zhou, Yan; Liu, Jianheng; Zhang, Licheng; Long, Anhua; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery.

  1. RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang Seok; Hong, Suck Won; Han, Dong Wook; Kim, Chun Tae; Oh, Jin Woo [Pusan National University, Busan (Korea, Republic of)

    2015-01-15

    Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic-co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

  2. The Study on Biocompatibility of Porous nHA/PLGA Composite Scaffolds for Tissue Engineering with Rabbit Chondrocytes In Vitro

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2013-01-01

    Full Text Available Objective. To examine the biocompatibility of a novel nanohydroxyapatite/poly[lactic-co-glycolic acid] (nHA/PLGA composite and evaluate its feasibility as a scaffold for cartilage tissue engineering. Methods. Chondrocytes of fetal rabbit were cultured with nHA/PLGA scaffold in vitro and the cell viability was assessed by MTT assay first. Cells adhering to nHA/PLGA scaffold were then observed by inverted microscope and scanning electron microscope (SEM. The cell cycle profile was analyzed by flow cytometry. Results. The viability of the chondrocytes on the scaffold was not affected by nHA/PLGA comparing with the control group as it was shown by MTT assay. Cells on the surface and in the pores of the scaffold increased in a time-dependent manner. Results obtained from flow cytometry showed that there was no significant difference in cell cycle profiles between the coculture group and control (P>0.05. Conclusion. The porous nHA/PLGA composite scaffold is a biocompatible and good kind of scaffold for cartilage tissue engineering.

  3. A three-layered nano-carbonated hydroxyapatite/collagen/PLGA composite membrane for guided tissue regeneration.

    Science.gov (United States)

    Liao, Susan; Wang, Wei; Uo, Motohiro; Ohkawa, Shoji; Akasaka, Tsukasa; Tamura, Kazuchika; Cui, Fuzhai; Watari, Fumio

    2005-12-01

    Functional graded materials (FGM) provided us one new concept for guided tissue regeneration (GTR) membrane design with graded component and graded structure where one face of the membrane is porous thereby allowing cell growth thereon and the opposite face of the membrane is smooth, thereby inhibiting cell adhesion in periodontal therapy. The goal of the present study was to develop a three-layered graded membrane, with one face of 8% nano-carbonated hydroxyapatite/collagen/poly(lactic-co-glycolic acid) (nCHAC/PLGA) porous membrane, the opposite face of pure PLGA non-porous membrane, the middle layer of 4% nCHAC/PLGA as the transition through layer-by-layer casting method. Then the three layers were combined well with each other with flexibility and enough high mechanical strength as membrane because the three layers all contained PLGA polymer that can be easily used for practical medical application. This high biocompatibility and osteoconductivity of this biodegraded composite membrane was enhanced by the nCHAC addition, for the same component and nano-level crystal size with natural bone tissue. The osteoblastic MC3T3-E1 cells were cultured on the three-layered composite membrane, the primary result shows the positive response compared with pure PLGA membrane.

  4. cRGD conjugated mPEG-PLGA-PLL nanoparticles for SGC-7901 gastric cancer cells-targeted Delivery of fluorouracil.

    Science.gov (United States)

    Liu, Peifeng; Wang, Hongbin; Wang, Qi; Sun, Ying; Shen, Ming; Zhu, Mingjie; Wan, Zhiyong; Duan, Yourong

    2012-06-01

    The main purpose of this study was to evaluate the targeting effect of cyclic arginine-glycine-aspartic peptide (cRGD)-modified monomethoxy (polyethylene glycol)-poly (D, L-lactide-co-glycolide)-poly (L-lysine) nanoparticles (mPEG-PLGA-PLL-cRGD NPs) for gastric cancer SGC-7901 cells. We prepared the 5-Fulorouracil (5Fu)-loaded mPEG-PLGA-PLL-cRGD (5Fu/mPEG-PLGA-PLL-cRGD) NPs that had an average particle size of 180 nm and a zeta potential 2.77 mV. The results of cytotoxicity demonstrated the mPEG-PLGA-PLL-cRGD NPs showed the ignorable cytotoxicity and the 5Fu/mPEG-PLGA-PLL-cRGD NPs could significantly enhance the cytotoxicity of 5Fu. In vitro drug release experiments showed that the release of drug was effectively prolonged and sustained. The results of confocal laser scanning microscope (CLSM) and flow cytometer analysis demonstrated that the fluorescence intensity of the SGC-7901 gastric cancer cells treated with Rb/mPEG-PLGA-PLL-cRGD NPs was significantly higher than that treated with Rb, this suggested that Rb/mPEG-PLGA-PLL-cRGD NPs could effectively be internalized by SGC-7901 gastric cancer cells. In summary, the above experimental results illustrate that mPEG-PLGA-PLL-cRGD NPs have great potential to be used as an effective delivery carriers.

  5. 多肽修饰聚合物PLGA-[ASP-PEG]对骨髓基质细胞黏附特性的影响%Characteristics of MSCs Adhesion to Polypeptides Modified Surface Polymer PLGA-[ASP-PEG

    Institute of Scientific and Technical Information of China (English)

    杨大志; 郑启新; 郭晓东; 郝杰; 宋玉林

    2007-01-01

    探讨在PLGA-[ASP-PEG]表面进行多肽改性后,对骨髓基质细胞在其表面黏附力的影响.在骨支架材料PLGA-[ASP-PEG]表面固定多肽GRGDSPC,用微吸管吸吮法测定骨髓基质细胞不同的时间段在骨支架材料表面的黏附力,并进行扫描电镜观察.结果表明:骨髓基质细胞接种在二种支架材料上4 h时,PLGA-[ASP-PEG]表面黏附力为172.78±15.23 N,多肽改性的PLGA-[SP-PEG]细胞黏附力209.47±92.59 N,二者无明显差异;在12 h,多肽改性的PLGA-[ASP-PEG]黏附力576.23±165.74 N, PLGA-[ASP-PEG] 黏附力为261.84±100.09 N,前者表面细胞黏附力明显强于后者(P<0.01);在24 h时,二种材料表面的细胞黏附力无明显差异(P>0.05).扫描电镜观察结果为多肽改性支架材料上表面黏附的细胞数明显多于未改性材料表面黏附的细胞数.在生物材料表面结合多肽可以增强细胞在材料表面的黏附力,从而改善生物材料生物相容性.

  6. A Comparison between the cytotoxic effects of pure curcumin and curcumin-loaded PLGA-PEG nanoparticles on the MCF-7 human breast cancer cell line.

    Science.gov (United States)

    Tabatabaei Mirakabad, Fatemeh Sadat; Akbarzadeh, Abolfazl; Milani, Morteza; Zarghami, Nosratollah; Taheri-Anganeh, Mortaza; Zeighamian, Vahideh; Badrzadeh, Fariba; Rahmati-Yamchi, Mohammad

    2016-01-01

    Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women worldwide. Herbal medicines have tremendous potential as promising agents for the treatment of cancer. Curcumin is a natural polyphenol which has many anticancer effects. Because of its low aqueous solubility, low bioavailability, and quick degradation and metabolism, curcumin was released using PLGA-PEG nanoparticles. Herein, the efficiency of pure curcumin and curcumin-loaded PLGA-PEG in MCF-7 human breast cancer cell lines was studied. (1)H NMR, FT-IR and SEM demonstrated PLGA-PEG structure and curcumin loaded on nanoparticles. Subsequently, the cytotoxic effects of free curcumin and curcumin-loaded PLGA-PEG were determined via an MTT assay. Our study confirmed that curcumin-loaded PLGA-PEG has more cytotoxic effects on the MCF-7 breast cancer cell line and could be exploited as a potential source for developing novel drugs against breast cancer.

  7. cRGD-functionalized mPEG-PLGA-PLL nanoparticles for imaging and therapy of breast cancer.

    Science.gov (United States)

    Liu, Peifeng; Qin, Liubin; Wang, Qi; Sun, Ying; Zhu, Mingjie; Shen, Ming; Duan, Yourong

    2012-10-01

    Cyclic peptide (arginine-glycine-aspartic-glutamic-valine acid, cRGD)-modified monomethoxy (polyethylene glycol)-poly (D,L-lactide-co-glycolide)-poly (L-lysine) nanoparticles (mPEG-PLGA-PLL-cRGD NPs) with antitumor drug Mitoxantrone (DHAQ) or fluorescence agent Rhodamine B (Rb) encapsulated in their interior were prepared. The remarkable features of the mPEG-PLGA-PLL-cRGD NPs are the effective improvement for the cytotoxicity and uptake of the cell in vitro, and the significant enhancement of delivery ability for DHAQ or Rb in vivo. As a consequence, an excellent therapeutic efficiency for cancer is obtained, demonstrating the mPEG-PLGA-PLL-cRGD NPs play a key role in enhancing cancer therapeutic efficiency. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  8. An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering

    Science.gov (United States)

    Gentile, Piergiorgio; Chiono, Valeria; Carmagnola, Irene; Hatton, Paul V.

    2014-01-01

    Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function. PMID:24590126

  9. A Fractional Factorial Design to Study the Effect of Process Variables on the Preparation of Hyaluronidase Loaded PLGA Nanoparticles

    Directory of Open Access Journals (Sweden)

    K. Narayanan

    2014-01-01

    Full Text Available The present study was initiated to understand the effect of PLGA concentration, PVA concentration, internal-external phase ratio, homogenization speed, and homogenization time on mean particle size, zeta potential, and percentage drug encapsulation using fractional factorial design. Using PLGA (50-50 as the carrier, hyaluronidase loaded PLGA nanoparticles were prepared using double emulsion solvent evaporation technique. The particle size was analyzed by dynamic light scattering technique and protein content by Lowry method. The study showed that homogenization speed as an independent variable had maximum effect on particle size and zeta potential. Internal-external phase volume ratio had maximum effect on drug encapsulation. Mean particle size also had high dependency on the combined effect of PVA concentration and phase volume ratio. Using fractional factorial design particle size of <400 nm, zeta potential of <−30 mV, and percentage encapsulation of 15–18% were achieved.

  10. Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells.

    Science.gov (United States)

    Costa, Marcilia P; Feitosa, Anderson C S; Oliveira, Fátima C E; Cavalcanti, Bruno C; da Silva, Eufrânio N; Dias, Gleiston G; Sales, Francisco A M; Sousa, Bruno L; Barroso-Neto, Ito L; Pessoa, Cláudia; Caetano, Ewerton W S; Di Fiore, Stefano; Fischer, Rainer; Ladeira, Luiz O; Freire, Valder N

    2016-07-02

    Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NβL on PLGA. Finally, the cytotoxic activity of NβL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

  11. 姜黄素PLGA-TPGS纳米粒的制备和质量评价%Preparation and quality evaluation of Curcumin-loaded PLGA-TPGS Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    孙辉; 高萌; 蒋妮; 鲍旭; 李磊; 李镇; 田燕

    2013-01-01

    目的 制备姜黄素乳酸羟基乙酸共聚物-水溶性维生素E纳米粒(CM-PLGA-TPGS-NPs,简称CPTN)并评价其质量.方法 用自制的PLGA-TPGS为载体材料,采用超声乳化-溶剂挥发法制备CPTN,通过粒径、Zeta电位、载药量、包封率和体外释放度控制其质量.采用RP-HPLC法,色谱柱为KROMASIL柱(4.6 mm×250 mm,5 μm),用乙腈-2%冰醋酸溶液(58:42)为流动相,检测波长为430 nm.结果 自制CPTN的平均粒径为(197.9±6.2)nm,Zeta电位为(-22.3±1.8)mV,载药量为(13.2±0.9)%和包封率为(79.3±1.6)%.体外姜黄素在含0.5%十二烷基硫酸钠的磷酸盐缓冲液(pH7.4)中呈两相释放,30 d时累积释放率为91.3%.结论 CPTN质量稳定可控,体外试验显示具有明显的缓释作用.

  12. Seed mediated synthesis of highly mono-dispersed gold nanoparticles in the presence of hydroquinone

    Science.gov (United States)

    Kumar, Dhiraj; Mutreja, Isha; Sykes, Peter

    2016-09-01

    Gold nanoparticles (AuNPs) are being studied for several biomedical applications, including drug delivery, biomedical imaging, contrast agents and tumor targeting. The synthesis of nanoparticles with a narrow size distribution is critical for these applications. We report the synthesis of highly mono-dispersed AuNPs by a seed mediated approach, in the presence of tri-sodium citrate and hydroquinone (HQ). AuNPs with an average size of 18 nm were used for the synthesis of highly mono-dispersed nanocrystals of an average size 40 nm, 60 nm, 80 nm and ˜100 nm; but the protocol is not limited to these sizes. The colloidal gold was subjected to UV-vis absorbance spectroscopy, showing a red shift in lambda max wavelength, peaks at 518.47 nm, 526.37 nm, 535.73 nm, 546.03 nm and 556.50 nm for AuNPs seed (18 nm), 40 nm, 60 nm, 80 nm and ˜100 nm respectively. The analysis was consistent with dynamic light scattering and electron microscopy. Hydrodynamic diameters measured were 17.6 nm, 40.8 nm, 59.8 nm, 74.1 nm, and 91.4 nm (size by dynamic light scattering—volume %); with an average poly dispersity index value of 0.088, suggesting mono-dispersity in the size distribution, which was also confirmed by transmission electron microscopy analysis. The advantage of a seed mediated approach is a multi-step growth of nanoparticle size that enables us to control the number of nanoparticles in the suspension, for size ranging from 24.5 nm to 95.8 nm. In addition, the HQ-based synthesis of colloidal nanocrystals allowed control of the particle size and size distribution by tailoring either the number of seeds, amount of gold precursor or reducing agent (HQ) in the final reaction mixture.

  13. Microfluidic separation of satellite droplets as the basis of a monodispersed micron and submicron emulsification system.

    Science.gov (United States)

    Tan, Yung-Chieh; Lee, Abraham Phillip

    2005-10-01

    Emulsions are widely used to produce sol-gel, drugs, synthetic materials, and food products. Recent advancements in microfluidic droplet emulsion technology has enabled the precise sampling and processing of small volumes of fluids (picoliter to femtoliter) by the controlled viscous shearing in microchannels. However the generation of monodispersed droplets smaller than 1 microm without surfactants has been difficult to achieve. Normally, the generation of satellite droplets along with parent droplets is undesirable and makes it difficult to control volume and purity of samples in droplets. In this paper, however, several methods are presented to passively filter out satellite droplets from the generation of parent droplets and use these satellite droplets as the source for monodispersed production of submicron emulsions. A passive satellite droplet filtration system and a dynamic satellite droplet separation system are demonstrated. Satellite droplets are filtered from parent droplets with a two-layer channel geometry. This design allows the creation and collection of droplets that are less than 100 nm in diameter. In the dynamic separation system, satellite droplets of defined sizes can be selectively separated into different collecting zones. The separation of the satellite droplets into different collecting zones correlates with the cross channel position of the satellite droplets during the breakup of the liquid thread. The delay time for droplets to switch between the different alternating collecting zones is nominally 1 min and is proportional to the ratio of the oil shear flows. With our droplet generation system, monodispersed satellite droplets with an average radius of 2.23 +/- 0.11 microm, and bidispersed secondary and tertiary satellite droplets with radii of 1.55 +/- 0.07 microm and 372 +/- 46 nm respectively, have been dynamically separated and collected.

  14. Seed mediated synthesis of highly mono-dispersed gold nanoparticles in the presence of hydroquinone.

    Science.gov (United States)

    Kumar, Dhiraj; Mutreja, Isha; Sykes, Peter

    2016-09-02

    Gold nanoparticles (AuNPs) are being studied for several biomedical applications, including drug delivery, biomedical imaging, contrast agents and tumor targeting. The synthesis of nanoparticles with a narrow size distribution is critical for these applications. We report the synthesis of highly mono-dispersed AuNPs by a seed mediated approach, in the presence of tri-sodium citrate and hydroquinone (HQ). AuNPs with an average size of 18 nm were used for the synthesis of highly mono-dispersed nanocrystals of an average size 40 nm, 60 nm, 80 nm and ∼100 nm; but the protocol is not limited to these sizes. The colloidal gold was subjected to UV-vis absorbance spectroscopy, showing a red shift in lambda max wavelength, peaks at 518.47 nm, 526.37 nm, 535.73 nm, 546.03 nm and 556.50 nm for AuNPs seed (18 nm), 40 nm, 60 nm, 80 nm and ∼100 nm respectively. The analysis was consistent with dynamic light scattering and electron microscopy. Hydrodynamic diameters measured were 17.6 nm, 40.8 nm, 59.8 nm, 74.1 nm, and 91.4 nm (size by dynamic light scattering-volume %); with an average poly dispersity index value of 0.088, suggesting mono-dispersity in the size distribution, which was also confirmed by transmission electron microscopy analysis. The advantage of a seed mediated approach is a multi-step growth of nanoparticle size that enables us to control the number of nanoparticles in the suspension, for size ranging from 24.5 nm to 95.8 nm. In addition, the HQ-based synthesis of colloidal nanocrystals allowed control of the particle size and size distribution by tailoring either the number of seeds, amount of gold precursor or reducing agent (HQ) in the final reaction mixture.

  15. In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hao-Xuan [Department of Orthopedics, Shandong University Qilu Hospital, Jinan, Shandong (China); Zhang, Xiu-Ping [School of Public Health, Fudan University, Shanghai (China); Xiao, Gui-Yong [School of Materials Science and Engineering, Shandong University, Jinan, Shandong (China); Key Laboratory for Liquid–Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan, Shandong (China); Hou, Yong; Cheng, Lei; Si, Meng; Wang, Shuai-Shuai [Department of Orthopedics, Shandong University Qilu Hospital, Jinan, Shandong (China); Li, Yu-Hua, E-mail: qiluyuhua@126.com [Department of Orthopedics, Shandong University Qilu Hospital, Jinan, Shandong (China); Nie, Lin, E-mail: hoho05@126.com [Department of Orthopedics, Shandong University Qilu Hospital, Jinan, Shandong (China)

    2016-03-01

    Avascular necrosis of the femoral head (ANFH) is difficult to treat due to high pressure and hypoxia, and reduced levels of growth factors such as bone morphogenetic protein (BMP), and vascular endothelial growth factor (VEGF). We generated a novel calcium phosphate (CPC) composite scaffold, which contains BMP-VEGF-loaded poly-lactic-co-glycolic acid (PLGA) microspheres (BMP-VEGF-PLGA-CPC). The BMP-VEGF-loaded microspheres have an encapsulation efficiency of 89.15% for BMP, and 78.55% for VEGF. The BMP-VEGF-PLGA-CPC scaffold also demonstrated a porosity of 62% with interconnected porous structures, and pore sizes of 219 μm and compressive strength of 6.60 MPa. Additionally, bone marrow mesenchymal stem cells (BMSCs) were seeded on scaffolds in vitro. Further characterization showed that the BMP-VEGF-PLGA-CPC scaffolds were biocompatible and enhanced osteogenesis and angiogenesis in vitro. Using a rabbit model of ANFH, BMP-VEGF-PLGA-CPC scaffolds were implanted into the bone tunnels of core decompression in the femoral head for 6 and 12 weeks. Radiographic and histological analysis demonstrated that the BMP-VEGF-PLGA-CPC scaffolds exhibited good biocompatibility, and osteogenic and angiogenic activity in vivo. These results indicate that the BMP-VEGF-PLGA-CPC scaffold may improve the therapeutic effect of core decompression surgery and be used as a treatment for ANFH. - Highlights: • BMP-VEGF-PLGA-CPC scaffolds were biocompatible and enhanced osteogenesis and angiogenesis in vitro. • BMP-VEGF-PLGA-CPC scaffolds exhibited good biocompatibility, and osteogenic and angiogenic activity in vivo. • BMP-VEGF-PLGA-CPC scaffolds provided a new approach for the treatment of avascular necrosis of the femoral head (ANFH).

  16. Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

    Science.gov (United States)

    Chang, N-J; Lam, C-F; Lin, C-C; Chen, W-L; Li, C-F; Lin, Y-T; Yeh, M-L

    2013-10-01

    Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  17. Prediction of dexamethasone release from PLGA microspheres prepared with polymer blends using a design of experiment approach.

    Science.gov (United States)

    Gu, Bing; Burgess, Diane J

    2015-11-10

    Hydrophobic drug release from poly (lactic-co-glycolic acid) (PLGA) microspheres typically exhibits a tri-phasic profile with a burst release phase followed by a lag phase and a secondary release phase. High burst release can be associated with adverse effects and the efficacy of the formulation cannot be ensured during a long lag phase. Accordingly, the development of a long-acting microsphere product requires optimization of all drug release phases. The purpose of the current study was to investigate whether a blend of low and high molecular weight polymers can be used to reduce the burst release and eliminate/minimize the lag phase. A single emulsion solvent evaporation method was used to prepare microspheres using blends of two PLGA polymers (PLGA5050 (25 kDa) and PLGA9010 (113 kDa)). A central composite design approach was applied to investigate the effect of formulation composition on dexamethasone release from these microspheres. Mathematical models obtained from this design of experiments study were utilized to generate a design space with maximized microsphere drug loading and reduced burst release. Specifically, a drug loading close to 15% can be achieved and a burst release less than 10% when a composition of 80% PLGA9010 and 90 mg of dexamethasone is used. In order to better describe the lag phase, a heat map was generated based on dexamethasone release from the PLGA microsphere/PVA hydrogel composite coatings. Using the heat map an optimized formulation with minimum lag phase was selected. The microspheres were also characterized for particle size/size distribution, thermal properties and morphology. The particle size was demonstrated to be related to the polymer concentration and the ratio of the two polymers but not to the dexamethasone concentration.

  18. Ultrasound-stimulated peripheral nerve regeneration within asymmetrically porous PLGA/Pluronic F127 nerve guide conduit.

    Science.gov (United States)

    Park, Sang Chul; Oh, Se Heang; Seo, Tae Beom; Namgung, Uk; Kim, Jin Man; Lee, Jin Ho

    2010-08-01

    Recently, we developed a novel method to fabricate a nerve guide conduit (NGC) with asymmetrical pore structure and hydrophilicity using poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127 by a modified immersion precipitation method. From the animal study using a rat model (sciatic nerve defect of rat), we recognized that the unique PLGA/Pluronic F127 tube provided good environments for nerve regeneration. In this study, we applied low-intensity pulsed ultrasound as a simple and noninvasive stimulus at the PLGA/F127 NGC-implanted site transcutaneously in rats to investigate the feasibility of ultrasound for the enhanced nerve regeneration through the tube. The nerve regeneration behaviors within the ultrasound-stimulated PLGA/Pluronic F127 NGCs were compared with the NGCs without the ultrasound treatment as well as normal nerve by histological and immunohistochemical observations. It was observed that the PLGA/Pluronic F127 tube-implanted group applied with the ultrasound had more rapid nerve regeneration behavior (approximately 0.71 mm/day) than the tube-implanted group without the ultrasound treatment (approximately 0.48 mm/day). The ultrasound-treated tube group also showed greater neural tissue area as well as larger axon diameter and thicker myelin sheath than the tube group without the ultrasound treatment, indicating better nerve regeneration. The better nerve regeneration behavior in the our NGC/ultrasound system may be caused by the synergistic effect of the asymmetrically porous PLGA/Pluronic F127 tube with unique properties (selective permeability, hydrophilicity, and structural stability, which can provide good environment for nerve regeneration) and physical stimulus (stimulation of the Schwann cells and activation of the neurotrophic factors).

  19. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Wenjia Guo

    2015-10-01

    Full Text Available The purpose of this study was to develop a PLGA microspheres-based donepezil (DP formulation which was expected to sustain release of DP for one week with high encapsulation efficiency (EE. DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared successfully with average diameter of 30 µm, drug loading of 15.92 ± 0.31% and EE up to 78.79 ± 2.56%. Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface. Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres. The Tg of PLGA was increased with the addition of DP. The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model, which suggested the diffusion governing release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained. The results suggest the potential use of DP microspheres for treatment of Alzheimer's disease over long periods.

  20. Layering PLGA-based electrospun membranes and cell sheets for engineering cartilage-bone transition.

    Science.gov (United States)

    Mouthuy, P-A; El-Sherbini, Y; Cui, Z; Ye, H

    2016-04-01

    It is now widely acknowledged that implants that have been designed with an effort towards reconstructing the transition between tissues might improve their functionality and integration in vivo. This paper contributes to the development of improved treatment for articular cartilage repair by exploring the potential of the combination of electrospinning technology and cell sheet engineering to create cartilage tissue. Poly(lactic-co-glycolic acid) (PLGA) was used to create the electrospun membranes. The focus being on the cartilage-bone transition, collagen type I and hydroxyapatite (HA) were also added to the scaffolds to increase the histological biocompatibility. Human mesenchymal stem cells (hMSCs) were cultured in thermoresponsive dishes to allow non-enzymatic removal of an intact cell layer after reaching confluence. The tissue constructs were created by layering electrospun membranes with sheets of hMSCs and were cultured under chondrogenic conditions for up to 21 days. High viability was found to be maintained in the multilayered construct. Under chondrogenic conditions, reverse-transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry have shown high expression levels of collagen type X, a form of collagen typically found in the calcified zone of articular cartilage, suggesting an induction of chondrocyte hypertrophy in the PLGA-based scaffolds. To conclude, this paper suggests that layering electrospun scaffolds and cell sheets is an efficient approach for the engineering of tissue transitions, and in particular the cartilage-bone transition. The use of PLGA-based scaffold might be particularly useful for the bone-cartilage reconstruction, since the differentiated tissue constructs seem to show characteristics of calcified cartilage. Copyright © 2013 John Wiley & Sons, Ltd.

  1. Approximate Bayesian computation for estimating number concentrations of monodisperse nanoparticles in suspension by optical microscopy

    Science.gov (United States)

    Röding, Magnus; Zagato, Elisa; Remaut, Katrien; Braeckmans, Kevin

    2016-06-01

    We present an approximate Bayesian computation scheme for estimating number concentrations of monodisperse diffusing nanoparticles in suspension by optical particle tracking microscopy. The method is based on the probability distribution of the time spent by a particle inside a detection region. We validate the method on suspensions of well-controlled reference particles. We illustrate its usefulness with an application in gene therapy, applying the method to estimate number concentrations of plasmid DNA molecules and the average number of DNA molecules complexed with liposomal drug delivery particles.

  2. Memory effects in metal-oxide-semiconductor capacitors incorporating dispensed highly monodisperse 1 nm silicon nanoparticles

    Science.gov (United States)

    Nayfeh, Osama M.; Antoniadis, Dimitri A.; Mantey, Kevin; Nayfeh, Munir H.

    2007-04-01

    Metal-oxide-semiconductor capacitors containing various densities of ex situ produced, colloidal, highly monodisperse, spherical, 1nm silicon nanoparticles were fabricated and evaluated for potential use as charge storage elements in future nonvolatile memory devices. The capacitance-voltage characteristics are well behaved and agree with similarly fabricated zero-nanoparticle control samples and with an ideal simulation. Unlike larger particle systems, the demonstrated memory effect exhibits effectively pure hole storage. The nature of charging, hole type versus electron type may be understood in terms of the characteristics of ultrasmall silicon nanoparticles: large energy gap, large charging energy, and consequently a small electron affinity.

  3. The Synthesis, Characterization and Catalytic Reaction Studies of Monodisperse Platinum Nanoparticles in Mesoporous Oxide Materials

    Energy Technology Data Exchange (ETDEWEB)

    Rioux, Robert M. [Univ. of California, Berkeley, CA (United States)

    2006-01-01

    A catalyst design program was implemented in which Pt nanoparticles, either of monodisperse size and/or shape were synthesized, characterized and studied in a number of hydrocarbon conversion reactions. The novel preparation of these materials enables exquisite control over their physical and chemical properties that could be controlled (and therefore rationally tuned) during synthesis. The ability to synthesize rather than prepare catalysts followed by thorough characterization enable accurate structure-function relationships to be elucidated. This thesis emphasizes all three aspects of catalyst design: synthesis, characterization and reactivity studies. The precise control of metal nanoparticle size, surface structure and composition may enable the development of highly active and selective heterogeneous catalysts.

  4. Synthesis of 3-D ordered macroporous silicate using the template formed from monodispersed polystyrene latex

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Based on the template formed from monodispersed polystyrene (PS) latex, a modified fast sol-gel process was employed to synthesize a three-dimensional ( 3-D ) ordered macroporous silica material after removing the template by calcination at high temperature. It was indicated that there existed highly ordered packed pores within the whole silica material by SEM morphology observation. It was also found that the pores were interconnected. The pore size could be controlled mainly by varying the particle size of the latex ranging from 101 to 102 nm. The formation process of the ordered pores was also preliminarily discussed.

  5. A Facile Synthesis of Monodisperse Au Nanoparticles and Their Catalysis of CO Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Sheng [ORNL; Peng, Sheng [Brown University; Lee, Youngmin [Brown University; Wang, Chao [Brown University; Yin, Hongfeng [ORNL; Sun, Shouheng [ORNL

    2008-01-01

    Monodisperse Au nanoparticles (NPs) have been synthesized at room temperature via a burst nucleation of Au upon injection of the reducing agent t-butylamine-borane complex into a 1, 2, 3, 4-tetrahydronaphthalene solution of HAuCl{sub 4} {center_dot} 3H{sub 2}O in the presence of oleylamine. The as-synthesized Au NPs show size-dependent surface plasmonic properties between 520 and 530 nm. They adopt an icosahedral shape and are polycrystalline with multiple-twinned structures. When deposited on a graphitized porous carbon support, the NPs are highly active for CO oxidation, showing 100% CO conversion at -45 C.

  6. Shape-dependent electrocatalytic activity of monodispersed palladium nanocrystals toward formic acid oxidation.

    Science.gov (United States)

    Zhang, Xuwei; Yin, Huajie; Wang, Jinfeng; Chang, Lin; Gao, Yan; Liu, Wei; Tang, Zhiyong

    2013-09-21

    The catalytic activity of different-shaped and monodispersed palladium nanocrystals, including cubes, octahedra and rhombic dodecahedra, toward the electrochemical oxidation of formic acid has been systematically evaluated in both HClO4 and H2SO4 solutions. Notably, the cubic palladium nanocrystals wholly exposed with {100} facets exhibit the highest activity, while the rhombic dodecahedra with {110} facets show the lowest electrocatalytic performance. Furthermore, compared with HClO4 electrolyte, the catalytic activity is found to be obviously lower in H2SO4 solution likely due to the competitive adsorption of SO4(2-) ions and formic acid on the surface of Pd nanocrystals.

  7. Surface-assembled poly(I:C) on PEGylated PLGA microspheres as vaccine adjuvant: APC activation and bystander cell stimulation.

    Science.gov (United States)

    Hafner, Annina M; Corthésy, Blaise; Textor, Marcus; Merkle, Hans P

    2016-11-30

    Biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres are potential vehicles to deliver antigens for vaccination. Because they lack the full capacity to activate professional antigen presenting cells (APCs), combination with an immunostimulatory adjuvant may be considered. A candidate is the synthetic TLR3 ligand polyriboinosinic acid-polyribocytidylic acid, poly(I:C), which drives cell-mediated immunity. However, poly(I:C) has also been linked to the pathogenesis of autoimmunity, as affected by widespread stimulation of non-hematopoietic bystander cells. To address this aspect, we propose to minimize the poly(I:C) dose as well as to control the stimulation of non-immune bystander cells by poly(I:C). To facilitate the maturation of APCs with minimal poly(I:C) doses, we surface-assembled poly(I:C) onto PLGA microspheres. The microspheres' surface was further modified by poly(ethylene glycol) (PEG) coronas with varying PEG-densities. PLGA microspheres loaded with tetanus toxoid (tt) as model antigen were manufactured by microextrusion-based solvent extraction. The negatively charged PLGA(tt) microspheres were coated with polycationic poly(l-lysine) (PLL) polymers, either PLL itself or PEG-grafted PLL (PLL-g-PEG) with varying grafting ratios (g=2.2 and g=10.1). Stable surface assembly of poly(I:C) was achieved by subsequent incubation of polymer-coated PLGA microspheres with aqueous poly(I:C) solutions. We evaluated the immunostimulatory potential of such PLGA(tt) microsphere formulations on monocyte-derived dendritic cells (MoDCs) as well as human foreskin fibroblasts (HFFs) as model for non-hematopoietic bystander cells. Formulations with surface-assembled poly(I:C) readily activated MoDCs with respect to the expression of maturation-related surface markers, proinflammatory cytokine secretion and directed migration. When surface-assembled, poly(I:C) enhanced its immunostimulatory activity by more than one order of magnitude as compared to free poly

  8. Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kedong, E-mail: kedongsong@dlut.edu.cn [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Liu, Yingchao [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Macedo, Hugo M. [Biological Systems Engineering Laboratory, Department of Chemical Engineering, Department of Chemical Engineering, South Kensington Campus, London SW7 2AZ (United Kingdom); Jiang, Lili; Li, Chao; Mei, Guanyu [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Liu, Tianqing, E-mail: liutq@dlut.edu.cn [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China)

    2013-04-01

    Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27–55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99 ± 2.51) %, (89.66 ± 0.66) % and (73.77 ± 3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24 ± 0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44 ± 1.81) × 10{sup −2} mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a

  9. In vitro characterisation of PLGA nanoparticles encapsulating rifampicin and isoniazid - Towards IVIVC

    CSIR Research Space (South Africa)

    Booysen, L

    2010-09-01

    Full Text Available , 561-573 (2006). 5. s. stolnik et al. The effect of surface coverage and conformation of poly(ethylene oxide) (PEO) chains of poloxamer 407 on the biological fate of model colloidal drug carriers, 1514 BIocHIMIcA Et BIoPHYsIcA ActA (BBA) - BIo... nanoparticles of 1% PEG or 1% Pluronics-F127, these formulations were fluorescently labelled with rhodamine 6G and orally administered to mice at 4 mg particles in 0.2 ml sterile saline by oral gavage. the biodistribution of uncoated PLGA nanoparticles...

  10. Phase separation behavior of fusidic acid and rifampicin in PLGA microspheres.

    Science.gov (United States)

    Gilchrist, Samuel E; Rickard, Deborah L; Letchford, Kevin; Needham, David; Burt, Helen M

    2012-05-01

    The purpose of this study was to characterize the phase separation behavior of fusidic acid (FA) and rifampicin (RIF) in poly(d,l-lactic acid-co-glycolic acid) (PLGA) using a model microsphere formulation. To accomplish this, microspheres containing 20% FA with 0%, 5%, 10%, 20%, and 30% RIF and 20% RIF with 30%, 20% 10%, 5%, and 0% FA were prepared by solvent evaporation. Drug-polymer and drug-drug compatibility and miscibility were characterized using laser confocal microscopy, Raman spectroscopy, XRPD, DSC, and real-time video recordings of single-microsphere formation. The encapsulation of FA and RIF alone, or in combination, results in a liquid-liquid phase separation of solvent-and-drug-rich microdomains that are excluded from the polymer bulk during microsphere hardening, resulting in amorphous spherical drug-rich domains within the polymer bulk and on the microsphere surface. FA and RIF phase separate from PLGA at relative droplet volumes of 0.311 ± 0.014 and 0.194 ± 0.000, respectively, predictive of the incompatibility of each drug and PLGA. When coloaded, FA and RIF phase separate in a single event at the relative droplet volume 0.251 ± 0.002, intermediate between each of the monoloaded formulations and dependent on the relative contribution of FA or RIF. The release of FA and RIF from phase-separated microspheres was characterized exclusively by a burst release and was dependent on the phase exclusion of surface drug-rich domains. Phase separation results in coalescence of drug-rich microdroplets and polymer phase exclusion, and it is dependent on the compatibility between FA and RIF and PLGA. FA and RIF are mutually miscible in all proportions as an amorphous glass, and they phase separate from the polymer as such. These drug-rich domains were excluded to the surface of the microspheres, and subsequent release of both drugs from the microspheres was rapid and reflected this surface location.

  11. The preosteoblast response of electrospinning PLGA/PCL nanofibers: effects of biomimetic architecture and collagen I

    Directory of Open Access Journals (Sweden)

    Qian YZ

    2016-08-01

    Full Text Available Yunzhu Qian,1,2 Hanbang Chen,1 Yang Xu,1 Jianxin Yang,2 Xuefeng Zhou,3 Feimin Zhang,1 Ning Gu3 1Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 2Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou, 3School of Biological Science and Medical Engineering, Southeast University, Nanjing, People’s Republic of China Abstract: Constructing biomimetic structure and incorporating bioactive molecules is an effective strategy to achieve a more favorable cell response. To explore the effect of electrospinning (ES nanofibrous architecture and collagen I (COL I-incorporated modification on tuning osteoblast response, a resorbable membrane composed of poly(lactic-co-glycolic acid/poly(caprolactone (PLGA/PCL; 7:3 w/w was developed via ES. COL I was blended into PLGA/PCL solution to prepare composite ES membrane. Notably, relatively better cell response was delivered by the bioactive ES-based membrane which was fabricated by modification of 3,4-dihydroxyphenylalanine and COL I. After investigation by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle measurement, and mechanical test, polyporous three-dimensional nanofibrous structure with low tensile force and the successful integration of COL I was obtained by the ES method. Compared with traditional PLGA/PCL membrane, the surface hydrophilicity of collagen-incorporated membranes was largely enhanced. The behavior of mouse preosteoblast MC3T3-E1 cell infiltration and proliferation on membranes was studied at 24 and 48 hours. The negative control was fabricated by solvent casting. Evaluation of cell adhesion and morphology demonstrated that all the ES membranes were more favorable for promoting the cell adhesion and spreading than the casting membrane. Cell Counting Kit-8 assays revealed that biomimetic architecture, surface topography, and bioactive properties of membranes were favorable for cell

  12. Bonelike/PLGA hybrid materials for bone regeneration : preparation route and physicochemical characterisation

    OpenAIRE

    Oliveira, Joaquim M.; Miyazaki, T; Lopes, M A; Ohtsuki, C.; Santos,J.D.

    2005-01-01

    Bonelike R /PLGA hybrid materials have been developed using γ -MPS as silane-coupling agent between the inorganic and organic phases for controlled drug delivery applications. Silanization showed to be more effective when cyclohexane was used as a non-polar solvent (nP method) due to a chemical interaction between Bonelike R and the silane film, while by using a 95/5 (V/V) methanol/water as a polar solvent (P method), a much thinner film was achieved. Functional groups of PL...

  13. In situ Gelation of Monodisperse Alginate Hydrogel in Microfluidic Channel Based on Mass Transfer of Calcium Ions

    Energy Technology Data Exchange (ETDEWEB)

    Song, YoungShin; Lee, Chang-Soo [Chungnam National University, Daejeon (Korea, Republic of)

    2014-10-15

    A microfluidic method for the in situ production of monodispersed alginate hydrogels using biocompatible polymer gelation by crosslinker mass transfer is described. Gelation of the hydrogel was achieved in situ by the dispersed calcium ion in the microfluidic device. The capillary number (Ca) and the flow rate of the disperse phase which are important operating parameters mainly influenced the formation of three distinctive flow regions, such as dripping, jetting, and unstable dripping. Under the formation of dripping region, monodispersed alginate hydrogels having a narrow size distribution (C.V=2.71%) were produced in the microfluidic device and the size of the hydrogels, ranging from 30 to 60 µm, could be easily controlled by varying the flow rate, viscosity, and interfacial tension. This simple microfluidic method for the production of monodisperse alginate hydrogels shows strong potential for use in delivery systems of foods, cosmetics, inks, and drugs, and spherical alginate hydrogels which have biocompatibility will be applied to cell transplantation.

  14. Chlamydia trachomatis recombinant MOMP encapsulated in PLGA nanoparticles triggers primarily T helper 1 cellular and antibody immune responses in mice: a desirable candidate nanovaccine

    Directory of Open Access Journals (Sweden)

    Fairley SJ

    2013-05-01

    Full Text Available Stacie J Fairley, Shree R Singh, Abebayehu N Yilma, Alain B Waffo, Praseetha Subbarayan, Saurabh Dixit, Murtada A Taha, Chino D Cambridge, Vida A Dennis Center for NanoBiotechnology Research, Alabama State University, Montgomery, AL, USA Abstract: We recently demonstrated by in vitro experiments that PLGA (poly D, L-lactide-co-glycolide potentiates T helper 1 (Th1 immune responses induced by a peptide derived from the recombinant major outer membrane protein (rMOMP of Chlamydia trachomatis, and may be a promising vaccine delivery system. Herein we evaluated the immune-potentiating potential of PLGA by encapsulating the full-length rMOMP (PLGA-rMOMP, characterizing it in vitro, and investigating its immunogenicity in vivo. Our hypothesis was that PLGA-rMOMP triggers Th1 immune responses in mice, which are desirable prerequisites for a C. trachomatis candidate nanovaccine. Physical-structural characterizations of PLGA-rMOMP revealed its size (approximately 272 nm, zeta potential (−14.30 mV, apparent spherical smooth morphology, and continuous slow release pattern. PLGA potentiated the ability of encapsulated rMOMP to trigger production of cytokines and chemokines by mouse J774 macrophages. Flow cytometric analyses revealed that spleen cells from BALB/c mice immunized with PLGA-rMOMP had elevated numbers of CD4+ and CD8+ T cell subsets, and secreted more rMOMP-specific interferon-gamma (Th1 and interleukin (IL-12p40 (Th1/Th17 than IL-4 and IL-10 (Th2 cytokines. PLGA-rMOMP-immunized mice produced higher serum immunoglobulin (IgG and IgG2a (Th1 than IgG1 (Th2 rMOMP-specific antibodies. Notably, sera from PLGA-rMOMP-immunized mice had a 64-fold higher Th1 than Th2 antibody titer, whereas mice immunized with rMOMP in Freund's adjuvant had only a four-fold higher Th1 than Th2 antibody titer, suggesting primarily induction of a Th1 antibody response in PLGA-rMOMP-immunized mice. Our data underscore PLGA as an effective delivery system for a C

  15. Facile Synthesis of Mono-Dispersed Polystyrene (PS/Ag Composite Microspheres via Modified Chemical Reduction

    Directory of Open Access Journals (Sweden)

    Wen Zhu

    2013-12-01

    Full Text Available A modified method based on in situ chemical reduction was developed to prepare mono-dispersed polystyrene/silver (PS/Ag composite microspheres. In this approach; mono-dispersed PS microspheres were synthesized through dispersion polymerization using poly-vinylpyrrolidone (PVP as a dispersant at first. Then, poly-dopamine (PDA was fabricated to functionally modify the surfaces of PS microspheres. With the addition of [Ag(NH32]+ to the PS dispersion, [Ag(NH32]+ complex ions were absorbed and reduced to silver nanoparticles on the surfaces of PS-PDA microspheres to form PS/Ag composite microspheres. PVP acted both as a solvent of the metallic precursor and as a reducing agent. PDA also acted both as a chemical protocol to immobilize the silver nanoparticles at the PS surface and as a reducing agent. Therefore, no additional reducing agents were needed. The resulting composite microspheres were characterized by TEM, field emission scanning electron microscopy (FESEM, energy-dispersive X-ray spectroscopy (EDS, XRD, UV-Vis and surface-enhanced Raman spectroscopy (SERS. The results showed that Ag nanoparticles (NPs were homogeneously immobilized onto the PS microspheres’ surface in the presence of PDA and PVP. PS/Ag composite microspheres were well formed with a uniform and compact shell layer and were adjustable in terms of their optical property.

  16. Preparation of monodisperse, superparamagnetic, luminescent, and multifunctional PGMA microspheres with amino-groups

    Institute of Scientific and Technical Information of China (English)

    WANG WeiCai; ZHANG Qi; ZHANG BingBo; LI DeNa; DONG XiaoQing; ZHANG Lei; CHANG Jin

    2008-01-01

    Micron-sized, monodisperse, superparamagnetic, luminescent composite poly(glycidyl methacrylate) (PGMA) microspheres with functional amino-groups were successfully synthesized in this study. The process of preparation was as follows: preparation of monodisperse poly(glycidyl methacrylate) mi-crospheres by dispersion polymerization method; modification of poly(glycidyl methacrylate) micro-spheres with ethylene diamine to form amino-groups; impregnation of iron ions (Fe2+ and Fe3+) inside the microspheres and subsequently precipitating them with ammonium hydroxide to form magnetite (Fe3O,4>) nanoparticles within the polymer microspheres; infusion of CdSe/CdS core-shell quantum dots (QDs) into magnetic polymer microspheres. Scanning electron microscopy (SEM) was used to char-acterize surface morphology and size distribution of composite microspheres. The average size of mi-crospheres was 1.42μm with a size variation of 3.8%, The composite microspheres were bright enough and easily observed using a conventional fluorescence microscope, The composite microspheres were easily separated from solution by magnetic decantation using a permanent magnet. The new multi-functional composite microspheres are promising to be used in a variety of bioanalytical assays in-volving luminescence detection and magnetic separation.

  17. Microwave Synthesized Monodisperse CdS Spheres of Different Size and Color for Solar Cell Applications

    Directory of Open Access Journals (Sweden)

    Carlos A. Rodríguez-Castañeda

    2015-01-01

    Full Text Available Monodisperse CdS spheres of size of 40 to 140 nm were obtained by microwave heating from basic solutions. It is observed that larger CdS spheres were formed at lower solution pH (8.4–8.8 and smaller ones at higher solution pH (10.8–11.3. The color of CdS products changed with solution pH and reaction temperature; those synthesized at lower pH and temperature were of green-yellow color, whereas those formed at higher pH and temperature were of orange-yellow color. A good photovoltage was observed in CdS:poly(3-hexylthiophene solar cells with spherical CdS particles. This is due to the good dispersion of CdS nanoparticles in P3HT solution that led to a large interface area between the organic and inorganic semiconductors. Higher photocurrent density was obtained in green-yellow CdS particles of lower defect density. The efficient microwave chemistry accelerated the hydrolysis of thiourea in pH lower than 9 and produced monodisperse spherical CdS nanoparticles suitable for solar cell applications.

  18. Monodisperse polyvinylpyrrolidone-coated CoFe2O4 nanoparticles: Synthesis, characterization and cytotoxicity study

    Science.gov (United States)

    Wang, Guangshuo; Ma, Yingying; Mu, Jingbo; Zhang, Zhixiao; Zhang, Xiaoliang; Zhang, Lina; Che, Hongwei; Bai, Yongmei; Hou, Junxian; Xie, Hailong

    2016-03-01

    In this study, monodisperse cobalt ferrite (CoFe2O4) nanoparticles were prepared successfully with various additions of polyvinylpyrrolidone (PVP) by sonochemical method, in which PVP served as a stabilizer and dispersant. The effects and roles of PVP on the morphology, microstructure and magnetic properties of the obtained CoFe2O4 were investigated in detail by X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS) and superconducting quantum interference device (SQUID). It was found that PVP-coated CoFe2O4 showed relatively well dispersion with narrow size distribution. The field-dependent magnetization curves indicated superparamagnetic behavior of PVP-coated CoFe2O4 with moderate saturation magnetization and hydrophilic character at room temperature. More importantly, the in vitro cytotoxicity testing exhibited negligible cytotoxicity of as-prepared PVP-CoFe2O4 even at the concentration as high as 150 μg/mL after 24 h treatment. Considering the superparamagnetic properties, hydrophilic character and negligible cytotoxicity, the monodisperse CoFe2O4 nanoparticles hold great potential in a variety of biomedical applications.

  19. DMSO as a solvent/ligand to monodisperse CdS spherical nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Kaijun [China Pharmaceutical University, Physical Chemistry Lab, School of Science (China); Han, Qiaofeng, E-mail: hanqiaofeng@njust.edu.cn [Nanjing University of Science and Technology, Key Laboratory for Soft Chemistry and Functional Materials, Ministry of Education (China)

    2016-01-15

    Monodisperse CdS nanospheres assembled by small nanoparticles were prepared using dimethyl sulfoxide (DMSO) as a solvent through several routes including thermolysis of xanthate, the reaction of cadmium acetate (Cd(CH{sub 3}CO{sub 2}){sub 2}) with thiourea, and interfacial reaction of CS{sub 2} and Cd(CH{sub 3}CO{sub 2}){sub 2}/DMSO. The corresponding products possessed the particle sizes ranging from around 35 to 45 nm, 63 to 73 nm, and 240 to 280 nm, respectively. These products presented uniform spherical morphology, which provide insights into the effect of DMSO on CdS morphology. DMSO, as an aprotic and polar solvent, possesses unique properties. The oxygen and sulfur atoms in DMSO can coordinate to metal ions on nanoparticles surface, and the high polarity of DMSO is favorable to fast reaction, nucleation, growth, and Ostwald ripening, forming monodisperse nanospheres with narrow size distribution. The influence of CdS size on its photocatalytic activity was evaluated using Rhodamine B (RhB) as a model compound under visible light irradiation.

  20. Preparation of monodisperse magnetic polymer microspheres by swelling and thermolysis technique.

    Science.gov (United States)

    Yang, Chengli; Shao, Qian; He, Jie; Jiang, Biwang

    2010-04-06

    A novel process for the preparation of monodisperse magnetic polymer microspheres by uniquely combining swelling and thermolysis technique was reported. The monodisperse polystyrene microspheres were first prepared by dispersion polymerization and swelled in chloroform. Then, ferric oleate was dispersed in chloroform as a precursor and impregnated into the swollen polymer microspheres. Subsequently, the iron oxide nanoparticles were formed within the polymer matrix by thermal decomposition of ferric oleate. The morphology, inner structure, and magnetic properties of the magnetic polymer microspheres were studied with a field emission scanning electron microscope (SEM), transmission electron microscope (TEM), and superconducting quantum interference device (SQUID) magnetometer. The results showed that the average diameter of the magnetic polymer microspheres was 5.1 microm with a standard deviation of 0.106, and the magnetic polymer microspheres with saturation magnetization of 12.6 emu/g exhibited distinct superparamagnetic characteristics at room temperature. More interestingly, the magnetite nanoparticles with a spinel structure are evenly distributed over the whole area of the polymer microspheres. These magnetic polymer microspheres have potential applications in biotechnology.

  1. Random-close packing limits for monodisperse and polydisperse hard spheres.

    Science.gov (United States)

    Baranau, Vasili; Tallarek, Ulrich

    2014-06-07

    We investigate how the densities of inherent structures, which we refer to as the closest jammed configurations, are distributed for packings of 10(4) frictionless hard spheres. A computational algorithm is introduced to generate closest jammed configurations and determine corresponding densities. Closest jamming densities for monodisperse packings generated with high compression rates using Lubachevsky-Stillinger and force-biased algorithms are distributed in a narrow density range from φ = 0.634-0.636 to φ≈ 0.64; closest jamming densities for monodisperse packings generated with low compression rates converge to φ≈ 0.65 and grow rapidly when crystallization starts with very low compression rates. We interpret φ≈ 0.64 as the random-close packing (RCP) limit and φ≈ 0.65 as a lower bound of the glass close packing (GCP) limit, whereas φ = 0.634-0.636 is attributed to another characteristic (lowest typical, LT) density φLT. The three characteristic densities φLT, φRCP, and φGCP are determined for polydisperse packings with log-normal sphere radii distributions.

  2. Preparation and Characterization of Gd3+-doped Monodisperse TiO2 Hollow Microsphere

    Institute of Scientific and Technical Information of China (English)

    JI; Feng; SHANG; Pengbo; ZHENG; Yuying

    2015-01-01

    Gd3+-doped monodisperse TiO2 hollow microspheres with various molar ratios of Gd3+/TBOT were synthesized via a novel process, which involved the preparation of SiO2 templates, deposition of Gd3+-doped TiO2 by sol-gel, SiO2 coating, heat treatment to induce crystallization of TiO2, and finally etching away the inner SiO2 templates and outer SiO2 layers. The synthesized samples were characterized by transmission electron microscopy(TEM), scanning electron microscopy(SEM), X-ray diffraction(XRD), diffuse reflection spectroscopy(DRS), specific surface area measurement(BET) and X-ray photoelectron spectroscopy(XPS), respectively. The photocatalytic activity of Gd3+-doped samples was evaluated via photocatalytic degradation of Methyl orange under UV irradiation. The results show that the SiO2 layers prevent aggregation of TiO2 hollow microspheresand improve the thermal stability of the synthesized samples. Also, the photocatalytic activity of monodisperse TiO2 hollow microspheres can be enhanced at the optimal molar ration of Gd3+/TBOT of 0.7%.

  3. Shape-dependent electrocatalytic activity of monodispersed palladium nanocrystals toward formic acid oxidation

    Science.gov (United States)

    Zhang, Xuwei; Yin, Huajie; Wang, Jinfeng; Chang, Lin; Gao, Yan; Liu, Wei; Tang, Zhiyong

    2013-08-01

    The catalytic activity of different-shaped and monodispersed palladium nanocrystals, including cubes, octahedra and rhombic dodecahedra, toward the electrochemical oxidation of formic acid has been systematically evaluated in both HClO4 and H2SO4 solutions. Notably, the cubic palladium nanocrystals wholly exposed with {100} facets exhibit the highest activity, while the rhombic dodecahedra with {110} facets show the lowest electrocatalytic performance. Furthermore, compared with HClO4 electrolyte, the catalytic activity is found to be obviously lower in H2SO4 solution likely due to the competitive adsorption of SO42- ions and formic acid on the surface of Pd nanocrystals.The catalytic activity of different-shaped and monodispersed palladium nanocrystals, including cubes, octahedra and rhombic dodecahedra, toward the electrochemical oxidation of formic acid has been systematically evaluated in both HClO4 and H2SO4 solutions. Notably, the cubic palladium nanocrystals wholly exposed with {100} facets exhibit the highest activity, while the rhombic dodecahedra with {110} facets show the lowest electrocatalytic performance. Furthermore, compared with HClO4 electrolyte, the catalytic activity is found to be obviously lower in H2SO4 solution likely due to the competitive adsorption of SO42- ions and formic acid on the surface of Pd nanocrystals. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr03100d

  4. Coalescence of functional gold and monodisperse silver nanoparticles mediated by black Panax ginseng Meyer root extract

    Science.gov (United States)

    Wang, Dandan; Markus, Josua; Kim, Yeon-Ju; Wang, Chao; Jiménez Pérez, Zuly Elizabeth; Ahn, Sungeun; Aceituno, Verónica Castro; Mathiyalagan, Ramya; Yang, Deok Chun

    2016-01-01

    A rapid biological synthesis of multifunctional gold nanoparticle (AuNp) and monodisperse silver nanoparticle (AgNp) was achieved by an aqueous extract of black Panax ginseng Meyer root. The physicochemical transformation into black ginseng (BG) greatly enhanced the pharmacological activities of white ginseng and its minor ginsenoside content. The optimal temperature conditions and kinetics of bioreduction were investigated. Formation of BG-AuNps and BG-AgNps was verified by ultraviolet–visible spectrophotometry at 548 and 412 nm, respectively. The biosynthesized BG-AgNps were spherical and monodisperse with narrow distribution, while BG-AuNps were icosahedral-shaped and moderately polydisperse. Synthesized nanoparticles exhibited long-term stability in buffers of pH 7.0–8.0 and biological media (5% bovine serum albumin) at an ambient temperature and at 37°C. BG-AgNps showed effective antibacterial activity against Escherichia coli and Staphylococcus aureus. BG-AuNps and BG-AgNps demonstrated increased scavenging activity against 2,2-diphenyl-1-picrylhydrazyl free radicals. In addition, BG-AuNps and BG-AgNps were nontoxic to HaCaT and MCF-7 cells; the latter showed no cytotoxicity at concentrations lower than 10 µg/mL. At higher concentrations, BG-AgNps exhibited apparent apoptotic activity in MCF-7 breast cancer cell line through reactive oxygen species generation and nuclear fragmentation. PMID:28008248

  5. Development of monodispersed and functional magnetic polymeric liposomes via simple liposome method

    Energy Technology Data Exchange (ETDEWEB)

    Liang Xiaofei; Wang Hanjie [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China); Jiang Xinguo [Fudan University, School of Pharmacy (China); Chang Jin, E-mail: jinchang@tju.edu.c [Tianjin University and Tianjin Key Laboratory of Composites and Functional Materials, Institute of Nanobiotechnology, School of Materials Science and Engineering (China)

    2010-06-15

    We are reporting a simple and rapid method to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by octadecyl quaternized carboxymethyl chitosan (OQCMC) and cholesterol. The whole process is only about 25 min with simple thin-film dispersion and solvent evaporation method. Hydrophilic magnetic nanoparticles (LM) and hydrophobic magnetic nanoparticles (BM) can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. A model hydrophobic drug indomethacin can be successfully filled in MCPL with high drug loading capacity 22%. MCPL encapsulating BM also showed strong DNA (pEGFP) binding ability. Drug-loaded MCPL have a long and controlled sustained release profile by changing the number of polymeric lipid layer. These functional MCPL nanospheres can be allowed to serve as ideal candidates for many biomedical applications.Graphical AbstractA simple and rapid liposome method was reported to prepare superparamagnetic, controlled size, and monodispersed magnetic cationic polymeric liposomes (MCPL) by polymeric surfactant, octadecyl quaternized carboxymethyl chitosan (OQCMC), and cholesterol. Hydrophilic Fe{sub 3}O{sub 4} ferrofluid and hydrophobic magnetic nanoparticles can be encapsulated into these cationic polymeric liposomes, simultaneously or respectively. Hydrophobic drug indomethacin can be encapsulated into this MCPL with high encapsulating efficiency and with controlled release profile by changing the number of polymeric lipid layer.

  6. Fabrication of monodispersive nanoscale alginate–chitosan core–shell particulate systems for controlled release studies

    Energy Technology Data Exchange (ETDEWEB)

    Körpe, Didem Aksoy; Malekghasemi, Soheil; Aydın, Uğur; Duman, Memed, E-mail: memedduman@gmail.com [Hacettepe University, Institute of Science, Nanotechnology and Nanomedicine Division (Turkey)

    2014-12-15

    Biopolymers such as chitosan and alginate are widely used for controlled drug delivery systems. The present work aimed to develop a new protocol for preparation of monodisperse alginate-coated chitosan nanoparticles at nanoscale. Modifications of preparation protocol contain changing the pH of polymer solutions and adding extra centrifugation steps into the procedure. While chitosan nanoparticles were synthesized by ionic gelation method, they were coated with alginate by electrostatic interaction. The size, morphology, charge, and structural characterization of prepared core–shell nanoparticulated system were performed by AFM, Zeta sizer, and FTIR. BSA and DOX were loaded as test biomolecules to core and shell part of the nanoparticle, respectively. Release profiles of BSA and DOX were determined by spectrophotometry. The sizes of both chitosan and alginate-coated chitosan nanoparticles which were prepared by modified protocol were measured to be 50 ± 10 and 60 ± 3 nm, respectively. After loading BSA and DOX, the average size of the particles increased to 80 ± 7 nm. Moreover, while the zeta potential of chitosan nanoparticles was positive value, the value was inverted to negative after alginate coating. Release profile measurements of BSA and DOX were determined during 57 and 2 days, respectively. Our results demonstrated that monodisperse alginate-coated nanoparticles were synthesized and loaded successfully using our modified protocol.

  7. Fabrication of monodispersive nanoscale alginate-chitosan core-shell particulate systems for controlled release studies

    Science.gov (United States)

    Körpe, Didem Aksoy; Malekghasemi, Soheil; Aydın, Uğur; Duman, Memed

    2014-12-01

    Biopolymers such as chitosan and alginate are widely used for controlled drug delivery systems. The present work aimed to develop a new protocol for preparation of monodisperse alginate-coated chitosan nanoparticles at nanoscale. Modifications of preparation protocol contain changing the pH of polymer solutions and adding extra centrifugation steps into the procedure. While chitosan nanoparticles were synthesized by ionic gelation method, they were coated with alginate by electrostatic interaction. The size, morphology, charge, and structural characterization of prepared core-shell nanoparticulated system were performed by AFM, Zeta sizer, and FTIR. BSA and DOX were loaded as test biomolecules to core and shell part of the nanoparticle, respectively. Release profiles of BSA and DOX were determined by spectrophotometry. The sizes of both chitosan and alginate-coated chitosan nanoparticles which were prepared by modified protocol were measured to be 50 ± 10 and 60 ± 3 nm, respectively. After loading BSA and DOX, the average size of the particles increased to 80 ± 7 nm. Moreover, while the zeta potential of chitosan nanoparticles was positive value, the value was inverted to negative after alginate coating. Release profile measurements of BSA and DOX were determined during 57 and 2 days, respectively. Our results demonstrated that monodisperse alginate-coated nanoparticles were synthesized and loaded successfully using our modified protocol.

  8. Small silicon, big opportunities: the development and future of colloidally-stable monodisperse silicon nanocrystals.

    Science.gov (United States)

    Mastronardi, Melanie L; Henderson, Eric J; Puzzo, Daniel P; Ozin, Geoffrey A

    2012-11-14

    Nanomaterials are becoming increasingly widespread in consumer technologies, but there is global concern about the toxicity of nanomaterials to humans and the environment as they move rapidly from the research laboratory to the market place. With this in mind, it makes sense to intensify the nanochemistry community's global research effort on the synthesis and study of nanoparticles that are purportedly "green". One potentially green nanoparticle that seems to be a most promising candidate in this context is silicon, whose appealing optical, optoelectronic, photonic, and biomedical attributes are recently gaining much attention. In this paper, we outline some of our recent contributions to the development of the growing field of silicon nanocrystals (ncSi) in order to stress the importance of continued study of ncSi as a green alternative to the archetypal semiconductor nanocrystals like CdSe, InAs, and PbS. While a variety of developments in synthetic methods, characterization techniques, and applications have been reported in recent years, the ability to prepare colloidally-stable monodisperse ncSi samples may prove to have the largest impact on the field, as it opens the door to study and access the tunable size-dependent properties of ncSi. Here, we summarize our recent contributions in size-separation methods to achieve monodisperse samples, the characterization of size-dependant property trends, the development of ncSi applications, and their potential impact on the promising future of ncSi.

  9. An alternative route towards monodisperse CdS quantum dots for hybrid solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Cao, Fengfeng; Wang, Hao [College of Physics, Optoelectronics and Energy and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006 (China); Xia, Zhouhui [Institute of Functional Nano and Soft Materials, Soochow University, Suzhou 215123 (China); Dai, Xiao; Cong, Shan [College of Physics, Optoelectronics and Energy and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006 (China); Dong, Chao [Department of Chemistry and Biology, University of New Mexico, ABQ 87120 (United States); Sun, Baoquan [Institute of Functional Nano and Soft Materials, Soochow University, Suzhou 215123 (China); Lou, Yanhui, E-mail: yhlou@suda.edu.cn [College of Physics, Optoelectronics and Energy and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006 (China); Sun, Yinghui; Zhao, Jie [College of Physics, Optoelectronics and Energy and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006 (China); Zou, Guifu, E-mail: zouguifu@suda.edu.cn [College of Physics, Optoelectronics and Energy and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006 (China)

    2015-01-15

    Monodisperse CdS quantum dots (QDs) are synthesized by thermal decomposition of organic complexes in the system of the cost-effective commercial 0{sup #} diesel at 200 °C. The prepared CdS QDs have a good dispersion and high crystallization. When the CdS QDs are doped into the blends of poly(3-hexylthiophene) (P3HT) and 1-(3-methoxycarbonyl)-propyl-1-phenyl-(6, 6)C61 (PCBM) for hybrid solar cells (HSCs), the HSCs achieve about 25% increase of power conversion efficiency in comparison to the reference device without the CdS QDs. The improvement of the cell performance mainly attributes to the increased short-circuit current density arising from the absorption enhancement in the wavelength range of 350–550 nm by introducing the synthesized CdS QDs into the P3HT: PCBM active layer. - Highlights: • Monodisperse CdS quantum dots. • A cost-effective route to synthesize crystalline CdS quantum dots. • CdS quantum dots based hybrid solar cells with power conversion efficiency enhancement.

  10. Low temperature synthesis of monodispersed YAG:Eu crystallites by hydrothermal method

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Mengmeng [Shanghai Institute of Ceramics, Chinese Academy of Sciences, No. 1295 Dingxi Road, Shanghai, 200050 (China); University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 (China); Zhang, Zhijun, E-mail: zhangzhijun@shu.edu.cn [School of Materials Science and Engineering, Shanghai University, No. 99 Shangda Road, Shanghai, 200072 (China); Zhao, Jingtai, E-mail: jtzhao@shu.edu.cn [School of Materials Science and Engineering, Shanghai University, No. 99 Shangda Road, Shanghai, 200072 (China); Zhang, Jiazhi [Shanghai Institute of Ceramics, Chinese Academy of Sciences, No. 1295 Dingxi Road, Shanghai, 200050 (China); University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049 (China); Liu, Zhiwei [Shanghai Institute of Ceramics, Chinese Academy of Sciences, No. 1295 Dingxi Road, Shanghai, 200050 (China)

    2015-10-25

    Single phase europium doped yttrium aluminum garnet (YAG:Eu) crystallites with good dispersity were successfully synthesized by a facile hydrothermal method at 300 °C for 24 h. The influences of the molar ratio of (Y + Eu) to Al (denoted by Ln/Al) in the raw material on the phase, morphology, crystallinity, local environment of Eu ions and photoluminescence properties were investigated. It was found that the monodispersed single phase YAG:Eu crystallites with terminating faces of {110} can be obtained when Ln/Al is 3:4. Eu ions in all the samples are trivalent regardless of Ln/Al, while the local environment of Eu ions is more symmetric when Ln/Al is 3:4. Moreover, the YAG:Eu crystallites obtained when Ln/Al is 3:4 exhibit improved crystallinity, which contributes to the enhanced luminescence intensity. - Highlights: • Single phase YAG:Eu was synthesized by the hydrothermal method at 300 °C. • The YAG:Eu crystallites are monodispersed and exhibit improved crystallinity. • The YAG:Eu crystallites exhibit improved luminescence intensity. • XAFS and VUV were used to investigate the local structure of Eu.

  11. Silicon-based megahertz ultrasonic nozzles for production of monodisperse micrometer-sized droplets.

    Science.gov (United States)

    Tsai, Shirley C; Cheng, Chih H; Wang, Ning; Song, Yu L; Lee, Ching T; Tsai, Chen S

    2009-09-01

    Monodisperse ethanol droplets 2.4 microm and water droplets 4.5 microm in diameter have been produced in ultrasonic atomization using 1.5- and 1.0-MHz microelectromechanical system (MEMS)-based silicon nozzles, respectively. The 1.5- and 1.0-MHz nozzles, each consisting of 3 Fourier horns in resonance, measured 1.20 cm x 0.15 cm x .11 cm and 1.79 cm x 0.21 cm x 0.11 cm, respectively, required electrical drive power as low as 0.25 W and could accommodate flow rates as high as 350 microl/min. As the liquid issues from the nozzle tip that vibrates longitudinally at the nozzle resonance frequency, a liquid film is maintained on the end face of the nozzle tip and standing capillary waves are formed on the free surface of the liquid film when the tip vibration amplitude exceeds a critical value due to Faraday instability. Temporal instability of the standing capillary waves, treated in terms of the unstable solutions (namely, time-dependant function with a positive Floquet exponent) to the corresponding Mathieu differential equation, is shown to be the underlying mechanism for atomization and production of such monodisperse droplets. The experimental results of nozzle resonance and atomization frequencies, droplet diameter, and critical vibration amplitude are all in excellent agreement with the predictions of the 3-D finite element simulation and the theory of Faraday instability responsible for atomization.

  12. Time Resolved Nucleation and Growth of Monodisperse FeOOH Nanoparticles Observed in situ

    Science.gov (United States)

    Legg, B. A.; Zhu, M.; Zhang, H.; Waychunas, G.; Banfield, J. F.

    2012-12-01

    The nucleation and growth of oxide minerals from aqueous solution is a poorly understood process. Complexities such as two-stage precipitation, phase transformation, and hydrolysis often inhibit simple interpretation. In this study, we track the thermally induced nucleation and growth of akaganeite (β-FeOOH) nanoparticles from FeCl3 solutions, using in situ time resolved small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM). Variations in reaction temperature (from 37 deg C to 80 deg C) and FeCl3 concentration (from 5 mM to 800 mM) produce systematic changes in nucleation rate, growth rate, particle size distribution, and aspect ratio. Low FeCl3 concentrations and high temperatures lead to formation of very small particles via rapid nucleation. (FeCl3 solutions are actually more supersaturated with respect to akaganeite when concentrations are low, due to the acid-base chemistry of ferric iron.) Increasing the FeCl3 concentration leads to large, highly monodisperse particles via size focused growth. Suspensions of highly monodisperse, elongated particles are found to self-organize into two dimensional colloidal crystals. The well-controlled growth processes in this system make it possible to conduct detailed kinetic modeling, and determine how both nucleation and growth rate respond to changes in the experimental conditions.

  13. Controlled synthesis of monodisperse gold nanorods with different aspect ratios in the presence of aromatic additives

    Science.gov (United States)

    Wang, Yun; Wang, Feihu; Guo, Yuan; Chen, Rongjun; Shen, Yuanyuan; Guo, Aijie; Liu, Jieying; Zhang, Xiao; Zhou, Dejian; Guo, Shengrong

    2014-12-01

    This paper reports the synthesis of monodisperse gold nanorods (GNRs) via a simple seeded growth approach in the presence of different aromatic additives, such as 7-bromo-3-hydroxy-2-naphthoic acid (7-BrHNA), 3-hydroxy-2-naphthoic acid (HNA), 5-bromosalicylic acid (5-BrSA), salicylic acid (SA), or phenol (PhOH). Effects of the aromatic additives and hydrochloric acid (HCl) on the structure and optical properties of the synthesized GNRs were investigated. The longitudinal surface plasmon resonance (LSPR) peak wavelength of the resulting GNRs was found to be dependent on the aromatic additive in the following sequence: 5-BrSA (778 nm) > 7-BrHNA (706 nm) > SA (688 nm) > HNA (676 nm) > PhOH (638 nm) without the addition of HCl, but this was changed to 7-BrHNA (920 nm) > SA (890 nm) > HNA (872 nm) > PhOH (858 nm) > 5-BrSA (816 nm) or 7-BrHNA (1,005 nm) > PhOH (995 nm) > SA (990 nm) > HNA (980 nm) > 5-BrSA (815 nm) with the addition of HCl or HNO3, respectively. The LSPR peak wavelength was increased with the increasing concentration of 7-BrHNA without HCl addition; however, there was a maximum LSPR peak wavelength when HCl was added. Interestingly, the LSPR peak wavelength was also increased with the amount of HCl added. The results presented here thus established a simple approach to synthesize monodisperse GNRs of different LSPR wavelengths.

  14. Monodisperse Au nanoparticles for selective electrocatalytic reduction of CO2 to CO.

    Science.gov (United States)

    Zhu, Wenlei; Michalsky, Ronald; Metin, Önder; Lv, Haifeng; Guo, Shaojun; Wright, Christopher J; Sun, Xiaolian; Peterson, Andrew A; Sun, Shouheng

    2013-11-13

    We report selective electrocatalytic reduction of carbon dioxide to carbon monoxide on gold nanoparticles (NPs) in 0.5 M KHCO3 at 25 °C. Among monodisperse 4, 6, 8, and 10 nm NPs tested, the 8 nm Au NPs show the maximum Faradaic efficiency (FE) (up to 90% at -0.67 V vs reversible hydrogen electrode, RHE). Density functional theory calculations suggest that more edge sites (active for CO evolution) than corner sites (active for the competitive H2 evolution reaction) on the Au NP surface facilitates the stabilization of the reduction intermediates, such as COOH*, and the formation of CO. This mechanism is further supported by the fact that Au NPs embedded in a matrix of butyl-3-methylimidazolium hexafluorophosphate for more efficient COOH* stabilization exhibit even higher reaction activity (3 A/g mass activity) and selectivity (97% FE) at -0.52 V (vs RHE). The work demonstrates the great potentials of using monodisperse Au NPs to optimize the available reaction intermediate binding sites for efficient and selective electrocatalytic reduction of CO2 to CO.

  15. Microfluidic fabrication of monodisperse polylactide microcapsules with tunable structures through rapid precipitation.

    Science.gov (United States)

    Watanabe, Takaichi; Kimura, Yukitaka; Ono, Tsutomu

    2013-11-19

    We describe a versatile and facile route to the continuous production of monodisperse polylactide (PLA) microcapsules with controllable structures. With the combination of microfluidic emulsification, solvent diffusion, and internal phase separation, uniform PLA microcapsules with a perfluorooctyl bromide (PFOB) core were successfully obtained by simply diluting monodisperse ethyl acetate (EA)-in-water emulsion with pure water. Rapid extraction of EA from the droplets into the aqueous phase enabled the solidification of the polymer droplets in a nonequilibrium state during internal phase separation between a concentrated PLA/EA phase and a PFOB phase. Higher-molecular-weight PLA generated structural complexity of the microcapsules, yielding core-shell microcapsules with covered with small PFOB droplets. Removal of the PFOB via freeze drying gave hollow microcapsules with dimpled surfaces. The core-shell ratios and the diameter of these microcapsules could be finely tuned by just adjusting the concentration of PFOB and flow rates on emulsification, respectively. These biocompatible microcapsules with controllable size and structures are potentially applicable in biomedical fields such as drug delivery carriers of many functional molecules.

  16. Linear theory on temporal instability of megahertz faraday waves for monodisperse microdroplet ejection.

    Science.gov (United States)

    Tsai, Shirley C; Tsai, Chen S

    2013-08-01

    A linear theory on temporal instability of megahertz Faraday waves for monodisperse microdroplet ejection based on mass conservation and linearized Navier-Stokes equations is presented using the most recently observed micrometer- sized droplet ejection from a millimeter-sized spherical water ball as a specific example. The theory is verified in the experiments utilizing silicon-based multiple-Fourier horn ultrasonic nozzles at megahertz frequency to facilitate temporal instability of the Faraday waves. Specifically, the linear theory not only correctly predicted the Faraday wave frequency and onset threshold of Faraday instability, the effect of viscosity, the dynamics of droplet ejection, but also established the first theoretical formula for the size of the ejected droplets, namely, the droplet diameter equals four-tenths of the Faraday wavelength involved. The high rate of increase in Faraday wave amplitude at megahertz drive frequency subsequent to onset threshold, together with enhanced excitation displacement on the nozzle end face, facilitated by the megahertz multiple Fourier horns in resonance, led to high-rate ejection of micrometer- sized monodisperse droplets (>10(7) droplets/s) at low electrical drive power (<;1 W) with short initiation time (<;0.05 s). This is in stark contrast to the Rayleigh-Plateau instability of a liquid jet, which ejects one droplet at a time. The measured diameters of the droplets ranging from 2.2 to 4.6 μm at 2 to 1 MHz drive frequency fall within the optimum particle size range for pulmonary drug delivery.

  17. Gentamicin loaded PLGA nanoparticles as local drug delivery system for the osteomyelitis treatment.

    Science.gov (United States)

    Posadowska, Urszula; Brzychczy-Włoch, Monika; Pamuła, Elżbieta

    2015-01-01

    Since there are more and more cases of multiresistance among microorganisms, rational use of antibiotics (especially their systemic vs. local application) is of great importance. Here we propose polymeric nanoparticles as locally applied gentamicin delivery system useful in osteomyelitis therapy. Gentamicin sulphate (GS) was encapsulated in the poly(lactide-co-glycolide) (PLGA 85:15) nanoparticles by double emulsification (water/oil/water, W1/O/W2). The nanoparticles were characterized by dynamic light scattering, laser electrophoresis and atomic force microscopy. UV-vis spectroscopy (O-phthaldialdehyde assay, OPA) and Kirby-Bauer tests were used to evaluate drug release and antimicrobial activity, respectively. Physicochemical characterization showed that size, shape and drug solubilization of the nanoparticles mainly depended on GS content and concentration of surface stabilizer (polyvinyl alcohol, PVA). Laser electrophoresis demonstrated negative value of zeta potential of the nanoparticles attributed to PLGA carboxyl end group presence. Drug release studies showed initial burst release followed by prolonged 35-day sustained gentamicin delivery. Agar-diffusion tests performed with pathogens causing osteomyelitis (Staphylococcus aureus and Staphylococcus epidermidis, both reference strains and clinical isolates) showed antibacterial activity of GS loaded nanoparticles (GS-NPs). It can be concluded that GS-NPs are a promising form of biomaterials useful in osteomyelitis therapy.

  18. Sophoridine-loaded PLGA microspheres for lung targeting: preparation, in vitro, and in vivo evaluation.

    Science.gov (United States)

    Wang, Wenping; Cai, Yaqin; Zhang, Guangxing; Liu, Yanhua; Sui, Hong; Park, Kinam; Wang, Hong

    2016-11-01

    Lung-targeting sophoridine-loaded poly(lactide-co-glycolide) (PLGA) microspheres were constructed by a simple oil-in-oil emulsion-solvent evaporation method. The obtained microspheres were systematically studied on their morphology, size distribution, drug loading, encapsulation efficiency, in vitro release profile, and biodistribution in rats. The drug-loaded microparticles showed as tiny spheres under SEM and had an average size of 17 μm with 90% of the microspheres ranging from 12 to 24 μm. The drug loading and encapsulation efficiency were 65% and 6.5%, respectively. The in vitro drug release behavior of microspheres exhibited an initial burst of 16.6% at 4 h and a sustained-release period of 14 days. Drug concentration in lung tissue of rats was 220.10 μg/g for microspheres and 6.77 μg/g for solution after intraveneous injection for 30 min, respectively. And the microsphere formulation showed a significantly higher drug level in lung tissue than in other major organs and blood samples for 12 days. These results demonstrated that the obtained PLGA microspheres could potentially improve the treatment efficacy of sophoridine against lung cancer.

  19. Fe3O4-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis

    Science.gov (United States)

    Liu, Jia; Xu, Jie; Zhou, Jun; Zhang, Yu; Guo, Dajing; Wang, Zhigang

    2017-01-01

    Thrombotic disease is a great threat to human health, and early detection is particularly important. Magnetic resonance (MR) molecular imaging provides noninvasive imaging with the potential for early disease diagnosis. In this study, we developed Fe3O4-based poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface-modified with a cyclic Arg-Gly-Asp (cRGD) peptide as an MR contrast agent for the detection of thrombosis. The physical and chemical characteristics, biological toxicity, ability to target thrombi, and biodistribution of the NPs were studied. The Fe3O4-PLGA-cRGD NPs were constructed successfully, and hematologic and pathologic assays indicated no in vivo toxicity of the NPs. In a rat model of FeCl3-induced abdominal aorta thrombosis, the NPs readily and selectively accumulated on the surface of the thrombosis and under vascular endothelial cells ex vivo and in vivo. In the in vivo experiment, the biodistribution of the NPs suggested that the NPs might be internalized by the macrophages of the reticuloendothelial system in the liver and the spleen. The T2 signal decreased at the mural thrombus 10 min after injection and then gradually increased until 50 min. These results suggest that the NPs are suitable for in vivo molecular imaging of thrombosis under high shear stress conditions and represent a very promising MR contrast agent for sensitive and specific detection of thrombosis. PMID:28223802

  20. Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy.

    Science.gov (United States)

    Fang, Kun; Song, Lina; Gu, Zhuxiao; Yang, Fang; Zhang, Yu; Gu, Ning

    2015-12-01

    Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.

  1. Effect of Gamma Irradiation on Structural and Biological Properties of a PLGA-PEG-Hydroxyapatite Composite

    Directory of Open Access Journals (Sweden)

    Sima Shahabi

    2014-01-01

    Full Text Available Gamma irradiation is able to affect various structural and biological properties of biomaterials In this study, a composite of Hap/PLGA-PEG and their ingredients were submitted to gamma irradiation doses of 25 and 50 KGy. Various properties such as molecular weight (GPC, thermal behavior (DSC, wettability (contact angle, cell viability (MTT assay, and alkaline phosphatase activity were studied for the composites and each of their ingredients. The results showed a decrease in molecular weight of copolymer with no change in the glass transition and melting temperatures after gamma irradiation. In general gamma irradiation can increase the activation energy ΔH of the composites and their ingredients. While gamma irradiation had no effect on the wettability of copolymer samples, there was a significant decrease in contact angle of hydroxyapatite and composites with increase in gamma irradiation dose. This study showed an increase in biocompatibility of hydroxyapatite with gamma irradiation with no significant effect on cell viability in copolymer and composite samples. In spite of the fact that no change occurred in alkaline phosphatase activity of composite samples, results indicated a decrease in alkaline phosphatase activity in irradiated hydroxyapatites. These effects on the properties of PLGA-PEG-hydroxyapatite can enhance the composite application as a biomaterial.

  2. Spray drying of siRNA-containing PLGA nanoparticles intended for inhalation.

    Science.gov (United States)

    Jensen, Ditte Marie Krohn; Cun, Dongmei; Maltesen, Morten Jonas; Frokjaer, Sven; Nielsen, Hanne Mørck; Foged, Camilla

    2010-02-25

    Local delivery of small interfering RNA (siRNA) to the lungs constitutes a promising new area in drug delivery. The present study evaluated parameters of importance for spray drying of siRNA-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) into nanocomposite microparticles intended for inhalation. The spray drying process was optimised using a statistical design of experiment and by evaluating powder characteristics upon systematic variation of the formulation parameters. Concentration, carbohydrate excipient (trehalose, lactose and mannitol) and the ratio of NP to excipient were varied to monitor the effects on moisture content, particle morphology, particle size and powder yield. The identified optimum conditions were applied for spray drying of siRNA-loaded nanocomposite microparticles, resulting in a product with a low water content (0.78% w/w) and an aerodynamic particle diameter considered suitable for inhalation. The use of mannitol in the formulation allowed a significantly lower moisture content than trehalose and lactose. The inclusion of 50% (w/w) or higher amounts of NPs resulted in a marked change in the surface morphology of the spray-dried particles. Importantly, the integrity and biological activity of the siRNA were preserved during the spray drying process. In conclusion, the present results show that spray drying is a suitable technique for producing nanocomposite microparticles comprising siRNA-containing PLGA NPs for potential use in inhalation therapy.

  3. Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.

    Science.gov (United States)

    Patel, Roshni S; Cho, Daniel Y; Tian, Cheng; Chang, Amy; Estrellas, Kenneth M; Lavin, Danya; Furtado, Stacia; Mathiowitz, Edith

    2012-01-01

    We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.

  4. Homogeneous PLGA-lipid nanoparticle as a promising oral vaccine delivery system for ovalbumin

    Directory of Open Access Journals (Sweden)

    Tongtong Ma

    2014-06-01

    Full Text Available In this study, a polymeric lipid nanoparticle (NP (simplified as Lipid NP was reported as a promising oral vaccine delivery system. The Lipid NPs composed of a hydrophobic polymeric poly(d,l-lactide-co-glycolide (PLGA core and a surface coating of lipid monolayer. Membrane emulsification technique was used to obtain uniform-sized Lipid NPs. Ovalbumin (OVA was used as a model vaccine. Compared with the pure PLGA NPs, the Lipid NPs achieved higher loading capacity (LC and entrapment efficiency (EE for the encapsulated OVA. An in vitro oral release profile showed that the OVA-Lipid NPs were with lower initial burst and could protect the loaded OVA from the harsh gastrointestinal (GI environment for a long time. In addition, a human microfold cell (M-cell transcytotic assay demonstrated that due to a lipid layer structure on the particle surface, the Lipid NPs showed higher affinity to the M-cells. Since the M-cell in the intestinal epithelium played an important role in particle transportation as well as intimately associated with the underlying immune cells, the OVA-Lipid NPs effectively induced mucosal and humoral immune responses.

  5. Enhanced transdermal permeability of estradiol using combination of PLGA nanoparticles system and iontophoresis.

    Science.gov (United States)

    Tomoda, Keishiro; Watanabe, Aya; Suzuki, Kenichi; Inagi, Toshio; Terada, Hiroshi; Makino, Kimiko

    2012-09-01

    Estradiol is a therapeutic agent for treatment of perimenopausal symptoms and osteoporosis. Conventional oral or intravenous administration of estradiol has many problems, such as, metabolization in gastrointestinal tract and liver, pain by using an injection needle, rapid increase of drug levels in blood and fast clearance with unwanted side effects including thrombosis, endometriosis and uterus carcinoma. The use of nanocarriers for transdermal delivery has been studied because of their ability to deliver therapeutic agents for long time with a controlled ratio, escaping from the first pass effect by liver. In this study, permeability of estradiol-loaded PLGA nanoparticles through rat skin was studied. Higher amount of estradiol was delivered through skin when estradiol was loaded in nanoparticles than estradiol was free molecules. Also, iontophoresis was applied to enhance the permeability of nanoparticles. When iontophoresis was applied, permeability of estradiol-loaded PLGA nanoparticles was much higher than that obtained by simple diffusion of them through skin, since they have negative surface charges. They were found to penetrate through follicles mainly. Also, enhanced permeability effect of estradiol by using nanoparticle system and iontophoresis were observed in vivo. The combination of charged nanoparticle system with iontophoresis is useful for effective transdermal delivery of therapeutic agents.

  6. Preparation of PLA and PLGA nanoparticles by binary organic solvent diffusion method

    Institute of Scientific and Technical Information of China (English)

    蒋新宇; 周春山; 唐课文

    2003-01-01

    The nanoparticles of polylactide (PLA) and poly(lactide-co-glycolide) (PLGA) were prepared by the bi-nary organic solvent diffusion method. The yield, particle size and size distribution of these nanoparticles wereevaluated. The yield of nanoparticles prepared by this method is over 90%, and the average size of the nanoparticlesis between 130-180 nm. In order to clarify the effect of the organic solvent used in the system on nanoparticle yieldand size, the cloud points of PLA and PLGA were examined by cloud point titration. The results indicate that theyields of nanoparticles increase with the increase of ethanol in the acetone solution and attain the maximum at thecloud point of ethanol, while the size of nanoparticles decreases with the increase of ethanol in the acetone solutionand attains the minimum at the cloud point of ethanol. The optimal composition ratio of binary organic solvents coin-cides to that near the cloud point and the optimal condition of binary organic solvents can be predicted.

  7. Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xiangru Wen

    Full Text Available Magnetic poly (D,L-lactide-co-glycolide (PLGA/lipid nanoparticles (MPLs were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol (DSPE-PEG-NH2, and magnetic nanoparticles (NPs, and then conjugated to trans-activating transcriptor (TAT peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES, naringin (NAR, and glutathione (GSH were encapsulated in MPLs with drug loading capacity (>10% and drug encapsulation efficiency (>90%. The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain.

  8. Optical tweezers based measurement of PLGA-NP interaction with prostate cancer cells

    Science.gov (United States)

    Blesener, Thea; Mondal, Argha; Menon, Jyothi U.; Nguyen, Kytai T.; Mohanty, Samarendra

    2013-02-01

    In order to quantify the binding capacities of polymeric, biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), conjugated with either R11 peptides or Folic Acid, the strength by detach from prostate cancer cells (PCCs) was measured via optical tweezers based measurements. Specific nanoparticle drug delivery eliminates the previously used diffuse, full-body application of potent cancer drugs by localizing drug delivery to malignant cells. Precise monitoring of NP position in the trap near the PCC membrane using a fluorescence imaging based method enabled calibration of the trap stiffness and subsequent force measurements. By defining the force with which the many diverse conjugates and coatings of different types of NPs bind the vast array of cancer cell types, chemotherapeutic drugs can be delivered in a specific manner with the optimal particle and corresponding conjugates. Further, and most significantly, the rupture force measurements will reveal whether or not targeted nanoparticles can overcome the force of blood attempting to pull the particle from designated cells. Our preliminary study revealed that the binding between PLGA-NPs and prostate cancer cells is enhanced by coating with folic acid or R11 peptides. These conjugates increase the force required to detach the particle thus allowing particles to overcome drag force of the blood in prostate capillary systems.

  9. Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jin-Hyung Shim

    2015-10-01

    Full Text Available This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid/β-tricalcium phosphate (PCL/PLGA/β-TCP membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. Implant surgery and guided bone regeneration were performed randomly in three groups (a no membrane group, a titanium membrane group, and a PCL/PLGA/β-TCP membrane group (n = 8 per group. Histological and histometric analyses were conducted to evaluate effects on bone regeneration and osseointegration. Using the results of mechanical testing; a PCL/PLGA/β-TCP ratio of 2:6:2 was selected. The new bone areas (% in buccal defects around implants were highest in the PCL/PLGA/β-TCP group and significantly higher than in the control group (p < 0.05. Bone-to-implant contact ratios (% were also significantly higher in the PCL/PLGA/β-TCP and titanium groups than in the control group (p < 0.05. When the guided bone regeneration procedure was performed using the PCL/PLGA/β-TCP membrane; new bone formation around the implant and osseointegration were not inferior to those of the non-resorbable pre-formed titanium mesh membrane.

  10. Therapeutic Use of 3β-[N-(N',N'-Dimethylaminoethane) Carbamoyl] Cholesterol-Modified PLGA Nanospheres as Gene Delivery Vehicles for Spinal Cord Injury.

    Science.gov (United States)

    Gwak, So-Jung; Yun, Yeomin; Yoon, Do Heum; Kim, Keung Nyun; Ha, Yoon

    2016-01-01

    Gene delivery holds therapeutic promise for the treatment of neurological diseases and spinal cord injury. Although several studies have investigated the use of non-viral vectors, such as polyethylenimine (PEI), their clinical value is limited by their cytotoxicity. Recently, biodegradable poly (lactide-co-glycolide) (PLGA) nanospheres have been explored as non-viral vectors. Here, we show that modification of PLGA nanospheres with 3β-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) enhances gene transfection efficiency. PLGA/DC-Chol nanospheres encapsulating DNA were prepared using a double emulsion-solvent evaporation method. PLGA/DC-Chol nanospheres were less cytotoxic than PEI both in vitro and in vivo. DC-Chol modification improved the uptake of nanospheres, thereby increasing their transfection efficiency in mouse neural stem cells in vitro and rat spinal cord in vivo. Also, transgene expression induced by PLGA nanospheres was higher and longer-lasting than that induced by PEI. In a rat model of spinal cord injury, PLGA/DC-Chol nanospheres loaded with vascular endothelial growth factor gene increased angiogenesis at the injury site, improved tissue regeneration, and resulted in better recovery of locomotor function. These results suggest that DC-Chol-modified PLGA nanospheres could serve as therapeutic gene delivery vehicles for spinal cord injury.

  11. mZD7349 peptide-conjugated PLGA nanoparticles directed against VCAM-1 for targeted delivery of simvastatin to restore dysfunctional HUVECs.

    Science.gov (United States)

    Imanparast, Fatemeh; Faramarzi, Mohammad Ali; Vatannejad, Akram; Paknejad, Maliheh; Deiham, Behnas; Kobarfard, Farzad; Amani, Amir; Doosti, Mahmood

    2017-02-02

    Endothelial dysfunction is initial and critical step of atherosclerosis. Impaired bioavailability of endothelial nitric oxide synthase (eNOS) is one of the main reasons of endothelial dysfunction. Improving bioavailability of eNOS by increasing its expression or activity using statins is an effective therapeutic strategy in restoring endothelial dysfunction. In this study, simvastatin (SIM) as a poorly water-soluble drug was loaded in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (SIM-PLGA-NPs). NPs were then conjugated with mZD7349 peptide (mZD7349-SIM-PLGA-NPs) and directed against vascular cell adhesion molecule 1 (VCAM-1). In vitro evaluation of the NPs for targeted delivery of SIM was performed on activated Human Umbilical Cord Vascular Endothelial Cells (HUVECs) by tumor necrosis factor alpha (TNF-α). Effect of mZD7349-SIM-PLGA-NPs and SIM-PLGA-NPs was compared on eNOS phosphorylation (ser-1177). Results of western blot showed SIM post-treatment increased significantly phosphor-eNOS (Ser1177) expression but no total eNOS expression. The study showed that mZD7349-SIM-PLGA-NPs have particle size, zeta potential value, polydispersity index (PDI) and encapsulation efficacy % of 233±18nm, -9.6±1.1mV, 0.59±0.066 and 69±17.3%, respectively. Also phosphor-eNOS (Ser1177) expression in activated HUVECs treated with mZD7349-SIM-PLGA-NPs was significantly (p<0.05) better than treated cells with SIM-PLGA-NPs. The results suggest that mZD7349-SIM-PLGA-NPs may be usable as an appropriate drug carrier for restoring endothelial dysfunction.

  12. Effect of PEG and water-soluble chitosan coating on moxifloxacin-loaded PLGA long-circulating nanoparticles.

    Science.gov (United States)

    Mustafa, Sanaul; Devi, V Kusum; Pai, Roopa S

    2017-02-01

    Moxifloxacin (MOX) is a Mycobacterium tuberculosis DNA gyrase inhibitor. Due to its intense hydrophilicity, MOX is cleared from the body within 24 h and required for repetitive doses which may then result in hepatotoxicity and acquisition of MOX resistant-TB, related with its use. To overcome the aforementioned limitations, the current study aimed to develop PLGA nanoparticles (PLGA NPs), to act as an efficient carrier for controlled delivery of MOX. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to MOX-PLGA NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was rose for surface modification of NPs. Surface modified NPs (MOX-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetic and in vivo biodistribution following oral administration were investigated. NP surface charge was closed to neutral +4.76 mV and significantly affected by the WSC coating. MOX-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long-drawn-out the blood circulation half-life with resultant reduced liver sequestration vis-à-vis MOX-PLGA NPs. The studies, therefore, indicate the successful formulation development of MOX-PEG-WSC NPs that showed sustained release behavior from nanoparticles which indicates low frequency of dosing.

  13. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    Science.gov (United States)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun

    2016-01-01

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly ( d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion-solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet-Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100-150 nm. We compared the antibacterial effects of PQTs against Escherichia coli ( E. coli) and Micrococcus tetragenus ( M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application.

  14. The Effect of Temozolomide/Poly(lactide-co-glycolide (PLGA/Nano-Hydroxyapatite Microspheres on Glioma U87 Cells Behavior

    Directory of Open Access Journals (Sweden)

    Anhua Wu

    2012-01-01

    Full Text Available In this study, we investigated the effects of temozolomide (TMZ/Poly (lactide-co-glycolide(PLGA/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the “Solid/Water/Oil” method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, αVβ3 integrin, was detected by the RT-PCR and Western blot method. It was found that the temozolomide/PLGA/nano-hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, αVβ3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano-hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma.

  15. Ebola Vaccination Using a DNA Vaccine Coated on PLGA-PLL/γPGA Nanoparticles Administered Using a Microneedle Patch.

    Science.gov (United States)

    Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R

    2017-01-01

    Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats.

    Science.gov (United States)

    Hamishehkar, Hamed; Emami, Jaber; Najafabadi, Abdolhossien Rouholamini; Gilani, Kambiz; Minaiyan, Mohsen; Hassanzadeh, Kambiz; Mahdavi, Hamid; Koohsoltani, Maryam; Nokhodchi, Ali

    2010-03-01

    The pulmonary route is an alternative route of administration for the systemic delivery of peptide and proteins with short-half lives. A long-acting formulation of insulin was prepared by encapsulation of protein into respirable, biodegradable microcapsules prepared by an oil in oil emulsification/solvent evaporation method. Insulin-loaded PLGA microcapsules prepared as a dry powder inhaler formulation were administered via the pulmonary route to diabetic rats and serum insulin and glucose concentrations were monitored. Control treatments consisted of respirable spray-dried insulin (RSDI) powder administered by intratracheal insufflation, insulin-loaded PLGA microcapsules and NPH (long-acting) insulin administered by subcutaneous (SC) administration. Pharmacokinetic analysis demonstrated that insulin administered in PLGA microcapsules illustrated a sustained release profile which resulted in a longer mean residence time, 4 and 5 fold longer than those after pulmonary administration of RSDI and SC injection of NPH insulin, respectively. Accordingly, the hypoglycemic profile followed a stable and sustained pattern which remained constant between 10 and 48 h. Results of the in vitro experiments were in good agreement with those of in vivo studies. Bronchoalveolar lavage fluid analysis indicated that microcapsules administration did not increase the activities of lactate dehydrogenase and total protein. However, histological examination of the lung tissue indicated a minor but detectable effect on the normal physiology of the rat lung. These findings suggest that the encapsulation of peptides and proteins into PLGA microcapsules technique could be a promising controlled delivery system for pulmonary administration.

  17. Highly Stable PEGylated Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for the Effective Delivery of Docetaxel in Prostate Cancers

    Science.gov (United States)

    Cao, Long-Bin; Zeng, Sha; Zhao, Wei

    2016-06-01

    In the present study, a highly stable luteinizing-hormone-releasing hormone (LHRH)-conjugated PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles were developed for the successful treatment of prostate cancers. We have demonstrated that a unique combination of targeted drug delivery and controlled drug release is effective against prostate cancer therapy. The docetaxel (DTX)/PLGA-LHRH micelles possessed a uniform spherical shape with an average diameter of ~170 nm. The micelles exhibited a controlled drug release for up to 96 h which can minimize the non-specific systemic spread of toxic drugs during circulation while maximizing the efficiency of tumor-targeted drug delivery. The LHRH-conjugated micelles showed enhanced cellular uptake and exhibited significantly higher cytotoxicity against LNCaP cancer cells. We have showed that PLGA-LHRH induced greater caspase-3 activity indicating its superior apoptosis potential. Consistently, LHRH-conjugated micelles induced threefold and twofold higher G2/M phase arrest than compared to free DTX or PLGA NP-treated groups. Overall, results indicate that use of LHRH-conjugated nanocarriers may potentially be an effective nanocarrier to effectively treat prostate cancer.

  18. Osteoconductive Potential of Barrier NanoSiO2 PLGA Membranes Functionalized by Plasma Enhanced Chemical Vapour Deposition

    Directory of Open Access Journals (Sweden)

    Antonia Terriza

    2014-01-01

    Full Text Available The possibility of tailoring membrane surfaces with osteoconductive potential, in particular in biodegradable devices, to create modified biomaterials that stimulate osteoblast response should make them more suitable for clinical use, hopefully enhancing bone regeneration. Bioactive inorganic materials, such as silica, have been suggested to improve the bioactivity of synthetic biopolymers. An in vitro study on HOB human osteoblasts was performed to assess biocompatibility and bioactivity of SiO2 functionalized poly(lactide-co-glycolide (PLGA membranes, prior to clinical use. A 15 nm SiO2 layer was deposited by plasma enhanced chemical vapour deposition (PECVD, onto a resorbable PLGA membrane. Samples were characterized by X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and infrared spectroscopy (FT-IR. HOB cells were seeded on sterilized test surfaces where cell morphology, spreading, actin cytoskeletal organization, and focal adhesion expression were assessed. As proved by the FT-IR analysis of samples, the deposition by PECVD of the SiO2 onto the PLGA membrane did not alter the composition and other characteristics of the organic membrane. A temporal and spatial reorganization of cytoskeleton and focal adhesions and morphological changes in response to SiO2 nanolayer were identified in our model. The novedous SiO2 deposition method is compatible with the standard sterilization protocols and reveals as a valuable tool to increase bioactivity of resorbable PLGA membranes.

  19. A transferrin variant as the targeting ligand for polymeric nanoparticles incorporated in 3-D PLGA porous scaffolds.

    Science.gov (United States)

    Lopes, André M; Chen, Kevin Y; Kamei, Daniel T

    2017-04-01

    We have developed doxorubicin (DOX)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (DP) conjugated with polyethylene glycol (PEG) and transferrin (Tf) to form Tf-PEG-DPs (TPDPs), and incorporated these TPDPs into three-dimensional (3-D) PLGA porous scaffolds to form a controlled delivery system. To our knowledge, this represents the first use of a Tf variant (oxalate Tf) to improve the targeted delivery of drug-encapsulated nanoparticles (NPs) in PLGA scaffolds to PC3 prostate cancer cells. The PLGA scaffolds with TPDPs incorporated have been shown to release drugs for sustained delivery and provided a continuous release of DOX. The MTS assay was also performed to determine the potency of native and oxalate TPDPs, and a 3.0-fold decrease in IC50 values were observed between the native and oxalate TPDPs. The lower IC50 value for the oxalate version signifies greater potency compared to the native version, since a lower concentration of drug was required to achieve the same therapeutic effect. These results suggest that this technology has potential to become a new implantable polymeric device to improve the controlled and targeted drug delivery of Tf-conjugated NPs for cancer therapy.

  20. Formation of post-confluence structure in human parotid gland acinar cells on PLGA through regulation of E-cadherin.

    Science.gov (United States)

    Chan, Yen-Hui; Huang, Tsung-Wei; Chou, Ya-Shuan; Hsu, Sheng-Hao; Su, Wei-Fang; Lou, Pei-Jen; Young, Tai-Horng

    2012-01-01

    As a potential solution for patients to retrieve their lost salivary gland functions, tissue engineering of an auto-secretory device is profoundly needed. Under serum-free environment, primary human parotid gland acinar (PGAC) cells can be obtained. After reaching confluence, PGAC cells spontaneously form three-dimension (3D) cell aggregations, termed post-confluence structure (PCS), and change their behaviors. Poly (lactic-co-glycolic acid) (PLGA) has been widely used in the field of biomedical applications because of its biodegradable properties for desired functions. Nonetheless, the role of PLGA in facilitating PGAC cells to form PCS has seldom been explored to recover epithelial characteristics. In this study, PGAC cells were found to have a greater tendency to form PCS on PLGA than on tissue culture polystyrene (TCPS). By tracing cell migration paths and modulating E-cadherin activity with specific inhibitor or antibody, we demonstrated that the static force of homophilic interaction on surfaces of individual cells, but not the dynamics of cell migration, played a more important role in PCS formation. Thus, PLGA was successfully confirmed to support PGAC cells to form more PCS through the effects on enhancing E-cadherin expression, which is associated with FAK/ILK/Snail expression in PGAC cells. This result indicates that selective appropriate biomaterials may be potentially useful in generating 3D PCS on two-dimension (2D) substrate without fabricating a complex 3D scaffold.

  1. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun, E-mail: weiywswzy@163.com [Anhui Agricultural University, School of Life Sciences (China)

    2016-01-15

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly (d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion–solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet–Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100–150 nm. We compared the antibacterial effects of PQTs against Escherichia coli (E. coli) and Micrococcus tetragenus (M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application.

  2. Osteoconductive Potential of Barrier NanoSiO2 PLGA Membranes Functionalized by Plasma Enhanced Chemical Vapour Deposition

    Science.gov (United States)

    Terriza, Antonia; Vilches-Pérez, Jose I.; de la Orden, Emilio; Yubero, Francisco; Gonzalez-Caballero, Juan L.; González-Elipe, Agustin R.; Vilches, José; Salido, Mercedes

    2014-01-01

    The possibility of tailoring membrane surfaces with osteoconductive potential, in particular in biodegradable devices, to create modified biomaterials that stimulate osteoblast response should make them more suitable for clinical use, hopefully enhancing bone regeneration. Bioactive inorganic materials, such as silica, have been suggested to improve the bioactivity of synthetic biopolymers. An in vitro study on HOB human osteoblasts was performed to assess biocompatibility and bioactivity of SiO2 functionalized poly(lactide-co-glycolide) (PLGA) membranes, prior to clinical use. A 15 nm SiO2 layer was deposited by plasma enhanced chemical vapour deposition (PECVD), onto a resorbable PLGA membrane. Samples were characterized by X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and infrared spectroscopy (FT-IR). HOB cells were seeded on sterilized test surfaces where cell morphology, spreading, actin cytoskeletal organization, and focal adhesion expression were assessed. As proved by the FT-IR analysis of samples, the deposition by PECVD of the SiO2 onto the PLGA membrane did not alter the composition and other characteristics of the organic membrane. A temporal and spatial reorganization of cytoskeleton and focal adhesions and morphological changes in response to SiO2 nanolayer were identified in our model. The novedous SiO2 deposition method is compatible with the standard sterilization protocols and reveals as a valuable tool to increase bioactivity of resorbable PLGA membranes. PMID:24883304

  3. Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo

    Science.gov (United States)

    Liu, Hui; Lv, Peizhen; Zhu, Yongjia; Wu, Huayu; Zhang, Kun; Xu, Fuben; Zheng, Li; Zhao, Jinmin

    2017-01-01

    Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection. The results showed that SDS dramatically enhanced the proliferation and function of SCs. The underlying mechanism may be that SDS affects SCs growth through the modulation of neurotrophic factors (BDNF, GDNF and CNTF). 12 weeks after implantation with a 12 mm gap of sciatic nerve injury, SDS-PLGA/SCs achieved satisfying outcomes of nerve regeneration, as evidenced by morphological and functional improvements upon therapy by SDS, PLGA/SCs or direct suture group assessed by sciatic function index, nerve conduction assay, HE staining and immunohistochemical analysis. Our results demonstrated the significant role of introducing SDS into neural tissue engineering to promote nerve regeneration.

  4. Effect of pore sizes of PLGA scaffolds on mechanical properties and cell behaviour for nucleus pulposus regeneration in vivo.

    Science.gov (United States)

    Kim, Hye Yun; Kim, Ha Neul; Lee, So Jin; Song, Jeong Eun; Kwon, Soon Yong; Chung, Jin Wha; Lee, Dongwon; Khang, Gilson

    2017-01-01

    This study investigated the influence of pore sizes of poly(lactic-co-glycolic acid) (PLGA) scaffolds on the compressive strength of tissue-engineered biodiscs and selection of the best suitable pore size for cells to grow in vivo. PLGA scaffolds were fabricated by solvent casting/salt-leaching with pore sizes of 90-180, 180-250, 250-355 and 355-425 µm. Nucleus pulposus (NP) cells were seeded on PLGA scaffolds with various pore sizes. Each sample was harvested at each time point, after retrieval of PLGA scaffolds seeded with NP cells, which were implanted into subcutaneous spaces in nude mice at 4 and 6 weeks. MTT assay, glycosaminoglycan (GAG) assay, haematoxylin and eosin (H&E) staining, safranin O staining and immunohistochemistry (for collagen type II) were performed at each time point. As the pores became smaller, the value of the compressive strength of the scaffold was increased. The group of scaffolds with pore sizes of 90-250 µm showed better cell proliferation and ECM production. These results demonstrated that the compressive strength of the scaffold was improved while the scaffold had pore sizes in the range 90-250 µm and good cell interconnectivity. Suitable space in the scaffold for cell viability is a key factor for cell metabolism. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  5. Folate Functionalized PLGA Nanoparticles Loaded with Plasmid pVAX1-NH36: Mathematical Analysis of Release

    Directory of Open Access Journals (Sweden)

    Cindy Alejandra Gutiérrez-Valenzuela

    2016-11-01

    Full Text Available Plasmid DNA (pVAX1-NH36 was encapsulated in nanoparticles of poly-dl-lactic-co-glycolic (PLGA functionalized with polyethylene glycol (PEG and folic acid (PLGA-PEG-FA without losing integrity. PLGA-PEG-FA nanoparticles loaded with pVAX1-NH36 (pDNA-NPs were prepared by using a double emulsification-solvent evaporation technique. PLGA-PEG-FA synthesis was verified by FT-IR and spectrophotometry methods. pVAX1-NH36 was replicated in Escherichia coli (E. coli cell cultures. Atomic force microscopy (AFM analysis confirmed pDNA-NPs size with an average diameter of 177–229 nm, depending on pVAX1-NH36 loading and zeta potentials were below −24 mV for all preparations. In vitro release studies confirmed a multiphase release profile for the duration of more than 30-days. Plasmid release kinetics were analyzed with a release model that considered simultaneous contributions of initial burst and degradation-relaxation of nanoparticles. Fitting of release model against experimental data presented excellent correlation. This mathematical analysis presents a novel approach to describe and predict the release of plasmid DNA from biodegradable nanoparticles.

  6. PLGA/Nano-ZnO Composite Particles for Use in Biomedical Applications: Preparation, Characterization, and Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Ana Stanković

    2016-01-01

    Full Text Available Copolymer poly (DL-lactide-co-glycolide (PLGA is extensively investigated for various biomedical applications such as controlled drug delivery or carriers in the tissue engineering. In addition, zinc oxide (ZnO is widely used in biomedicine especially for materials like dental composites, as a constituent of creams for the treatment of a variety of skin irritations, to enhance the antibacterial activity of different medicaments and so on. Uniform, spherical ZnO nanoparticles (nano-ZnO have been synthesized via microwave synthesis method. In addition to obtaining nano-ZnO, a further aim was to examine their immobilization in the PLGA polymer matrix (PLGA/nano-ZnO and this was done by a simple physicochemical solvent/nonsolvent method. The samples were characterized by X-ray diffraction, scanning electron microscopy, laser diffraction particle size analyzer, differential thermal analysis, and thermal gravimetric analysis. The synthesized PLGA/nano-ZnO particles are spherical, uniform, and with diameters below 1 µm. The influence of the different solvents and the drying methods during the synthesis was investigated too. The biocompatibility of the samples is discussed in terms of in vitro toxicity on human hepatoma HepG2 cells by application of MTT assay and the antimicrobial activity was evaluated by broth microdilution method against different groups of microorganisms (Gram-positive bacteria, Gram-negative bacteria, and yeast Candida albicans.

  7. Magnetic hyperthermia efficiency and 1H-NMR relaxation properties of iron oxide/paclitaxel-loaded PLGA nanoparticles

    Science.gov (United States)

    Ruggiero, Maria R.; Geninatti Crich, Simonetta; Sieni, Elisabetta; Sgarbossa, Paolo; Forzan, Michele; Cavallari, Eleonora; Stefania, Rachele; Dughiero, Fabrizio; Aime, Silvio

    2016-07-01

    Magnetic iron oxide nanoparticles (Fe-NPs) can be exploited in biomedicine as agents for magnetic fluid hyperthermia (MFH) treatments and as contrast enhancers in magnetic resonance imaging. New, oleate-covered, iron oxide particles have been prepared either by co-precipitation or thermal decomposition methods and incorporated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-Fe-NPs) to improve their biocompatibility and in vivo stability. Moreover, the PLGA-Fe-NPs have been loaded with paclitaxel to pursue an MFH-triggered drug release. Remarkably, it has been found that the nanoparticle formulations are characterized by peculiar 1H nuclear magnetic relaxation dispersion (NMRD) profiles that directly correlate with their heating potential when exposed to an alternating magnetic field. By prolonging the magnetic field exposure to 30 min, a significant drug release was observed for PLGA-Fe-NPs in the case of the larger-sized magnetic nanoparticles. Furthermore, the immobilization of lipophilic Fe-NPs in PLGA-NPs also made it possible to maintain Néel relaxation as the dominant relaxation contribution in the presence of large iron oxide cores (diameters of 15-20 nm), with the advantage of preserving their efficiency when they are entrapped in the intracellular environment. The results reported herein show that NMRD profiles are a useful tool for anticipating the heating capabilities of Fe-NPs designed for MFH applications.

  8. PLGA nanoparticle encapsulation reduces toxicity while retaining the therapeutic efficacy of EtNBS-PDT in vitro

    Science.gov (United States)

    Hung, Hsin-I; Klein, Oliver J.; Peterson, Sam W.; Rokosh, Sarah R.; Osseiran, Sam; Nowell, Nicholas H.; Evans, Conor L.

    2016-01-01

    Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce “dark toxicity” through light-independent mechanisms. In this study, we evaluated the use of nanoparticle encapsulation to overcome this limitation. Interestingly, encapsulation of the compound within poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-EtNBS) was found to significantly reduce EtNBS dark toxicity while completely retaining the molecule’s cytotoxicity in both normoxic and hypoxic conditions. This dual effect can be attributed to the mechanism of release: EtNBS remains encapsulated until external light irradiation, which stimulates an oxygen-independent, radical-mediated process that degrades the PLGA nanoparticles and releases the molecule. As these PLGA-encapsulated EtNBS nanoparticles are capable of penetrating deeply into the hypoxic and acidic cores of 3D spheroid cultures, they may enable the safe and efficacious treatment of otherwise unresponsive tumour regions. PMID:27686626

  9. Enhanced encapsulation and bioavailability of breviscapine in PLGA microparticles by nanocrystal and water-soluble polymer template techniques.

    Science.gov (United States)

    Wang, Hong; Zhang, Guangxing; Ma, Xueqin; Liu, Yanhua; Feng, Jun; Park, Kinam; Wang, Wenping

    2017-03-02

    Poly (lactide-co-glycolide) (PLGA) microparticles are widely used for controlled drug delivery. Emulsion methods have been commonly used for preparation of PLGA microparticles, but they usually result in low loading capacity, especially for drugs with poor solubility in organic solvents. In the present study, the nanocrystal technology and a water-soluble polymer template method were used to fabricate nanocrystal-loaded microparticles with improved drug loading and encapsulation efficiency for prolonged delivery of breviscapine. Breviscapine nanocrystals were prepared using a precipitation-ultrasonication method and further loaded into PLGA microparticles by casting in a mold from a water-soluble polymer. The obtained disc-like particles were then characterized and compared with the spherical particles prepared by an emulsion-solvent evaporation method. X-ray powder diffraction (XRPD) and confocal laser scanning microscopy (CLSM) analysis confirmed a highly-dispersed state of breviscapine inside the microparticles. The drug form, loading percentage and fabrication techniques significantly affected the loading capacity and efficiency of breviscapine in PLGA microparticles, and their release performance as well. Drug loading was increased from 2.4 % up to 15.3 % when both nanocrystal and template methods were applied, and encapsulation efficiency increased from 48.5 % to 91.9 %. But loading efficiency was reduced as the drug loading was increased. All microparticles showed an initial burst release, and then a slow release period of 28 days followed by an erosion-accelerated release phase, which provides a sustained delivery of breviscapine over a month. A relatively stable serum drug level for more than 30 days was observed after intramuscular injection of microparticles in rats. Therefore, PLGA microparticles loaded with nanocrystals of poorly soluble drugs provided a promising approach for long-term therapeutic products characterized with preferable in vitro and in

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

    Science.gov (United States)

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

  11. A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering.

    Science.gov (United States)

    Zhang, Fan; Song, Qingxin; Huang, Xuan; Li, Fengning; Wang, Kun; Tang, Yixing; Hou, Canglong; Shen, Hongxing

    2016-01-20

    A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the material's mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Young's modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

  12. Exploring the dark side of MTT viability assay of cells cultured onto electrospun PLGA-based composite nanofibrous scaffolding materials.

    Science.gov (United States)

    Qi, Ruiling; Shen, Mingwu; Cao, Xueyan; Guo, Rui; Tian, Xuejiao; Yu, Jianyong; Shi, Xiangyang

    2011-07-21

    One major method used to evaluate the biocompatibility of porous tissue engineering scaffolding materials is MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The MTT cell viability assay is based on the absorbance of the dissolved MTT formazan crystals formed in living cells, which is proportional to the number of viable cells. Due to the strong dye sorption capability of porous scaffolding materials, we propose that the cell viability determined from the MTT assay is likely to give a false negative result. In this study, we aim to explore the effect of the adsorption of MTT formazan on the accuracy of the viability assay of cells cultured onto porous electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, HNTs (halloysite nanotubes)/PLGA, and CNTs (multiwalled carbon nanotubes)/PLGA composite nanofibrous mats. The morphology of electrospun nanofibers and L929 mouse fibroblasts cultured onto the nanofibrous scaffolds were observed using scanning electron microscopy. The viability of cells proliferated for 3 days was evaluated through the MTT assay. In the meantime, the adsorption of MTT formazan onto the same electrospun nanofibers was evaluated and the standard concentration-absorbance curve was obtained in order to quantify the contribution of the adsorbed MTT formazan during the MTT cell viability assay. We show that the PLGA, and the HNTs- or CNTs-doped PLGA nanofibers display appreciable MTT formazan dye sorption, corresponding to 35.6-50.2% deviation from the real cell viability assay data. The better dye sorption capability of the nanofibers leads to further deviation from the real cell viability. Our study gives a general insight into accurate MTT cytotoxicity assessment of various porous tissue engineering scaffolding materials, and may be applicable to other colorimetric assays for analyzing the biological properties of porous scaffolding materials.

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

    Directory of Open Access Journals (Sweden)

    Rebecca Gossmann

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

  14. Dynamics of polyelectrolyte adsorption and colloidal flocculation upon mixing studied using mono-dispersed polystyrene latex particles

    NARCIS (Netherlands)

    Feng, Lili; Cohen Stuart, Martien; Adachi, Yasuhisa

    2015-01-01

    The dynamic behavior of polyelectrolytes just after their encounter with the surface of bare colloidal particles is analyzed, using the flocculation properties of mono-dispersed polystyrene latex (PSL) particles. Applying a Standardized Colloid Mixing (SCM) approach, effects of ionic strength and

  15. Characteristic tunnel-type conductivity and magnetoresistance in a CoO-coated monodispersive Co cluster assembly

    OpenAIRE

    Peng, D. L.; Sumiyama, Kenji; Yamamuro, S.; Hihara, Takehiko; Konno, T. J.; ヒハラ, タケヒコ; スミヤマ, ケンジ; 隅山, 兼治; 日原, 岳彦; Sumiyama, K.; Hihara, T.

    1999-01-01

    We have studied electrical conductivity, σ, and magnetoresistance in a CoO-coated monodispersive Co cluster assembly fabricated by a plasma-gas-aggregation-type cluster beam deposition technique. The temperature dependence of σ is described in the form of log σ vs 1/T for 7

  16. Monodisperse embedded nanoparticles derived from an atomic metal-dispersed precursor of layered double hydroxide for architectured carbon nanotube formation

    DEFF Research Database (Denmark)

    Tian, Gui-Li; Zhao, Meng-Qiang; Zhang, Bingsen

    2014-01-01

    Monodisperse metal nanoparticles (NPs) with high activity and selectivity are among the most important catalytic materials. However, the intrinsic process to obtain well-dispersed metal NPs with tunable high density (ranging from 10(13) to 10(16) m(-2)) and thermal stability is not yet well under...

  17. Facile Hydrothermal Synthesis of Monodispersed MoS2 Ultrathin Nanosheets Assisted by Ionic Liquid Brij56

    Directory of Open Access Journals (Sweden)

    Guan-Qun Han

    2015-01-01

    Full Text Available Monodispersed MoS2 ultrathin nanosheets have been successfully fabricated by a facile hydrothermal process assisted by ionic liquid Brij56. The effect of Brij56 on the morphology and structure of MoS2 has been obviously observed. XRD shows that the as-prepared MoS2 assisted by Brij56 has the weak and broad peak of (002 planes, which implies the small size and well dispersed structure of MoS2 nanosheets. TEM and SEM images reveal that MoS2 ultrathin nanosheets have small size and few stacking layers with the adding of Brij56. HRTEM images prove that MoS2 appears to have a highly monodispersed morphology and to be monolayer ultrathin nanosheets with the length about 5–8 nm, which can provide more exposed rims and edges as active sites for hydrogen evolution reaction. Brij56 has played a crucial role in preparing monodispersed MoS2 ultrathin nanosheets as excellent electrocatalysts. The growth mechanism of monodispersed MoS2 has been discussed in detail.

  18. Annealing effect on the structural and optical properties of Cr/ -Cr2O3 monodispersed particles based solar absorbers

    CSIR Research Space (South Africa)

    Khamlich, S

    2013-01-01

    Full Text Available A cost-effective and environmentally friendly green chemical method, the so-called aqueous chemical growth (ACG) method, was used to deposit chromium/alpha-chromium(III) oxide, Cr/a-Cr2O3, monodispersed particles, for solar absorbers applications...

  19. Sustainable and scalable production of monodisperse and highly uniform colloidal carbonaceous spheres using sodium polyacrylate as the dispersant.

    Science.gov (United States)

    Gong, Yutong; Xie, Lei; Li, Haoran; Wang, Yong

    2014-10-28

    Monodisperse, uniform colloidal carbonaceous spheres were fabricated by the hydrothermal treatment of glucose with the help of a tiny amount of sodium polyacrylate (PAANa). This synthetic strategy is effective at high glucose concentration and for scale-up experiments. The sphere size can be easily tuned by the reaction time, temperature and glucose concentration.

  20. Tf-PEG-PLL-PLGA nanoparticles enhanced chemosensitivity for hypoxia-responsive tumor cells

    Directory of Open Access Journals (Sweden)

    Liu P

    2016-08-01

    Full Text Available Ping Liu,1 Haijun Zhang,1 Xue Wu,1 Liting Guo,1 Fei Wang,1 Guohua Xia,2 Baoan Chen,1 HaiXiang Yin,3 Yonglu Wang,3 Xueming Li3 1Department of Hematology and Oncology, Key Department of Jiangsu Province, Zhongda Hospital, 2Department of Hematology and Oncology, Medical School of Southeast University, 3School of Pharmacy, Nanjing University of Technology, Nanjing, People’s Republic of China Abstract: Hypoxia is an inseparable component of the solid tumor as well as the bone marrow microenvironment. In this study, we investigated the effect of the novel polyethylene glycol (PEG-poly L-lysine (PLL-poly lactic-co-glycolic acid (PLGA based nanoparticles (NPs modified by transferrin (Tf loaded with daunorubicin (DNR (DNR-Tf-PEG-PLL-PLGA-NPs, abbreviated as DNR-Tf-NPs on leukemia cells (K562 under hypoxia. In vitro and in vivo tests to determine the effect of the enhanced chemosensitivity were evaluated using the immunofluorescence, flow cytometry, 3,-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-tetrazoliumbromide assay, Western blot analysis, histopathological examination, and immunohistochemistry analysis. Under hypoxia, K562 cells were hypoxia-responsive with the inhibitory concentration 50% (IC50 of DNR increased, resulting in chemotherapy insensitivity. By targeting the transferrin receptor (TfR on the surface of K562 cells, DNR-Tf-NPs led to an increased intracellular DNR level, enhancing drug sensitivity of K562 cells to DNR with a decreased IC50, even under hypoxia. We further detected the protein levels of hypoxia-inducible factor-1α (HIF-1α, Bcl-2, Bax, and caspase-3 in K562 cells. The results indicated that DNR-Tf-NPs downregulated HIF-1α and induced apoptosis to overcome hypoxia. In the xenograft model, injection of DNR-Tf-NPs significantly suppressed tumor growth, and the immunosignals of Ki67 in DNR-Tf-NPs group was significantly lower than the other groups. It was therefore concluded that DNR-Tf-NPs could be a promising candidate for

  1. Elastin-PLGA hybrid electrospun nanofiber scaffolds for salivary epithelial cell self-organization and polarization.

    Science.gov (United States)

    Foraida, Zahraa I; Kamaldinov, Tim; Nelson, Deirdre A; Larsen, Melinda; Castracane, James

    2017-08-08

    Development of electrospun nanofibers that mimic the structural, mechanical and biochemical properties of natural extracellular matrices (ECMs) is a promising approach for tissue regeneration. Electrospun fibers of synthetic polymers partially mimic the topography of the ECM, however, their high stiffness, poor hydrophilicity and lack of in vivo-like biochemical cues is not optimal for epithelial cell self-organization and function. In search of a biomimetic scaffold for salivary gland tissue regeneration, we investigated the potential of elastin, an ECM protein, to generate elastin hybrid nanofibers that have favorable physical and biochemical properties for regeneration of the salivary glands. Elastin was introduced to our previously developed poly-lactic-co-glycolic acid (PLGA) nanofiber scaffolds by two methods, blend electrospinning (EP-blend) and covalent conjugation (EP-covalent). Both methods for elastin incorporation into the nanofibers improved the wettability of the scaffolds while only blend electrospinning of elastin-PLGA nanofibers and not surface conjugation of elastin to PLGA fibers, conferred increased elasticity to the nanofibers measured by Young's modulus. After two days, only the blend electrospun nanofiber scaffolds facilitated epithelial cell self-organization into cell clusters, assessed with nuclear area and nearest neighbor distance measurements, leading to the apicobasal polarization of salivary gland epithelial cells after six days, which is vital for cell function. This study suggests that elastin electrospun nanofiber scaffolds have potential application in regenerative therapies for salivary glands and other epithelial organs. Regenerating the salivary glands by mimicking the extracellular matrix (ECM) is a promising approach for long term treatment of salivary gland damage. Despite their topographic similarity to the ECM, electrospun fibers of synthetic polymers lack the biochemical complexity, elasticity and hydrophilicity of the

  2. Lactobionic acid enhances mPEG-PLGA-PLL nanoparticles targeting to hepatocellular carcinoma cell Huh7%乳糖酸修饰mPEG-PLGA-PLL纳米粒靶向肝癌细胞Huh7的研究

    Institute of Scientific and Technical Information of China (English)

    孙彦明; 朱明洁; 王炳武; 孙颖; 刘培峰; 段友容

    2012-01-01

    背景与目的 去唾液酸糖蛋白受体(asialoglycoprotein receptor,ASGPR)是一种肝细胞特异性表达的膜表面蛋白,能够特异性地识别带有半乳糖残基的糖蛋白.乳糖酸含有半乳糖基团,可以作为靶向肝癌的特异性配基.该研究旨在探讨乳糖酸修饰的聚乙二醇/聚丙交酯-乙交酯/聚赖氨酸[methoxypoly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide)-b-poly(L-lysine)(mPEG-PLGA-PLL)纳米粒,mPEG-PLGA-PLL-GAL NPs)]对肝癌Huh7靶向效果,为构建新型的靶向肝癌的纳米递送系统提供实验数据.方法 MTT法确定Huh7细胞摄取mPEG-PLGA-PLL NPs与mPEG-PLGA-PLL-GAL NPs适当的浓度;通过激光共聚焦和荧光显微镜定性观察Huh7对罗丹明B标记的mPEG-PLGA-PLL NPs和mPEG-PLGA-PLL-GAL NPs的摄取;并采用流式细胞计数仪定量研究Huh7细胞对两者的摄取差别;尾静脉注射荷Huh7瘤裸鼠研究两者体内分布情况.结果 mPEG-PLGA-PLL NPs与mPEG-PLGA-PLL-GAL NPs的浓度在0.2 mg/mL时细胞存活率较高且对Huh7细胞的毒性较小.激光共聚焦断层扫描显示Huh7细胞可以较好地摄取mPEG-PLGA-PLL-GAL NPs,同时流式细胞仪定量显示mPEGPLGA-PLL-GAL NPs在Huh7细胞的分布较mPEG-PLGA-PLL NPs高40%(P<0.05).mPEG-PLGA-PLL NPs与mPEG-PLGAPLL-GAL NPs在移植瘤中的分布明显多于其他脏器,并且随时间的延长mPEG-PLGA-PLL-GAL NPs体现了更好的靶向效果.结论 体外与体内实验证明乳糖酸修饰的mPEG-PLGA-PLL NPs对肝癌细胞Huh7有很好的靶向效果,可为肝癌的靶向治疗提供较好的药物载体.%Background and purpose: It is a wonderful approach to deliver drugs to hepatocellular carcinoma cell by receptor-mediated targeting. The asialoglycoprotein receptor (ASGPR) specifically recognized by galactose moiety residue is a mainly expressing membrane protein on the surface of hepatocellular carcinoma cell. Methoxy-poly (ethylene glycol)-b-poly(D, L-lactide-co-glycolide)-b-poly(L-lysine) (mPEG-PLGA

  3. Synthesis of monodispersed silver nanoparticles using Hibiscus cannabinus leaf extract and its antimicrobial activity

    Science.gov (United States)

    Bindhu, M. R.; Umadevi, M.

    2013-01-01

    Synthesis of silver nanoparticles using leaf extract of Hibiscus cannabinus has been investigated. The influences of different concentration of H. cannabinus leaf extract, different metal ion concentration and different reaction time on the above cases on the synthesis of nanoparticles were evaluated. The synthesized nanoparticles were characterized using UV-vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Transmission Electron Microscopy (TEM). The prepared silver nanoparticles were monodispersed, spherical in shape with the average particle size of 9 nm and shows surface plasmon peak at 446 nm. The study also reveals that the ascorbic acid present in H. cannabinus leaf extract has been used as reducing agent. The prepared silver nanoparticle shows good antimicrobial activity against Escherichia coli, Proteus mirabilis and Shigella flexneri.

  4. Synthesis and characterization of monodispersed inorganic/organic core/shell microspheres with fluorescence

    Institute of Scientific and Technical Information of China (English)

    ZHANG Kai; HAN Kun; ZHANG Xuehai; YANG Bai

    2005-01-01

    @@ In recent years, the semiconductor nanocrystals (NCs) have attracted great interest due to their potentials in photonics, electronics, magnetics and catalysis, and the monodispersed organic or inorganic microspheres doped NCs display predominant characteristics in the fabrication and study for photonic crystals[1,2], and considerable effort has been devoted to the design and synthesis of CdTe NCs doped colloid with well fluorescence[3-8]. For example, CdTe NCs were fabricated on the surfaces of silica or polymer microspheres by the methods of layer-by-layer assembly, and CdTe NCs were also doped into inorganic or organic microspheres through sol-gel process or swell- ing.

  5. Synthesis of Monodisperse Walnut-Like SnO2 Spheres and Their Photocatalytic Performances

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2015-01-01

    Full Text Available Novel walnut-like SnO2 spheres have been synthesized using a one-step hydrothermal reaction with SnCl2·2H2O and KOH as raw materials. The morphology, microstructure, and optical properties of the products were characterized by X-ray powder diffraction (XRD, Raman spectrum, scanning electron microscopy (SEM, transmission electron microscopy (TEM, selected area electron diffraction (SAED, and ultraviolet-visible (UV-Vis absorption spectroscopy. The detailed studies revealed that these synthesized spheres are highly monodisperse and have a uniform size of approximately 250 nm. Photocatalytic activity of the prepared SnO2 spheres was evaluated by the degradation of methylene orange. The synthesized SnO2 spheres exhibited excellent photocatalytic degradation. In addition, a possible formation mechanism of the walnut-like nanostructures was proposed based on reaction time-dependent experiments.

  6. Sonochemical synthesis of monodispersed magnetite nanoparticles by using an ethanol-water mixed solvent.

    Science.gov (United States)

    Dang, Feng; Enomoto, Naoya; Hojo, Junichi; Enpuku, Keiji

    2009-06-01

    The magnetite nanoparticles were synthesized in an ethanol-water solution under ultrasonic irradiation from a Fe(OH)(2) precipitate. XRD, TEM, TG, IR, VSM and UV/vis absorption spectrum were used to characterize the magnetite nanoparticles. It was found that the formation of magnetite was accelerated in ethanol-water solution in the presence of ultrasonic irradiation, whereas, it was limited in ethanol-water solution under mechanical stirring. The monodispersibility of magnetite particles was improved significantly through the sonochemical synthesis in ethanol-water solution. The magnetic properties were improved for the samples synthesized under ultrasonic irradiation. This would be attributed to high Fe(2+) concentration in the magnetite cubic structure.

  7. Recent Progress in the Design of Monodisperse, Sequence-Defined Macromolecules.

    Science.gov (United States)

    Solleder, Susanne C; Schneider, Rebekka V; Wetzel, Katharina S; Boukis, Andreas C; Meier, Michael A R

    2017-05-01

    This review describes different synthetic strategies towards sequence-defined, monodisperse macromolecules, which are built up by iterative approaches and lead to linear non-natural polymer structures. The review is divided in three parts: solution phase-, solid phase-, and fluorous- and polymer-tethered approaches. Moreover, synthesis procedures leading to conjugated and non-conjugated macromolecules are considered and discussed in the respective sections. A major focus in the evaluation is the applicability of the different approaches in polymer chemistry. In this context, simple procedures for monomer and oligomer synthesis, overall yields, scalability, purity of the oligomers, and the achievable level of control (side-chains, backbone, stereochemistry) are important benchmarks. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. XAFS studies of monodisperse Au nanoclusters formation in the etching process

    Science.gov (United States)

    Yang, Lina; Huang, Ting; Liu, Wei; Bao, Jie; Huang, Yuanyuan; Cao, Yuanjie; Yao, Tao; Sun, Zhihu; Wei, Shiqiang

    2016-05-01

    Understanding the formation mechanism of gold nanoclusters is essential to the development of their synthetic chemistry. Here, by using x-ray absorption fine-structure (XAFS) spectroscopy, UV-Vis and MS spectra, the formation process of monodisperse Au13 nanoclusters is investigated. We find that a critical step involving the formation of smaller Au8-Au11 metastable intermediate clusters induced by the HCl + HSR etching of the polydisperse Aun precursor clusters occurs firstly. Then these intermediate species undergo a size-growth to Au13 cores, followed by a slow structure rearrangement to reach the final stable structure. This work enriches the understanding of cluster formation chemistry and may guide the way towards the design and the controllable synthesis of nanoclusters.

  9. Efficient thermolysis route to monodisperse Cu₂ZnSnS₄ nanocrystals with controlled shape and structure.

    Science.gov (United States)

    Zhang, Xiaoyan; Guo, Guobiao; Ji, Cheng; Huang, Kai; Zha, Chenyang; Wang, Yifeng; Shen, Liming; Gupta, Arunava; Bao, Ningzhong

    2014-05-28

    Monodisperse Cu2ZnSnS4 (CZTS) nanocrystals with tunable shape, crystalline phase, and composition are synthesized by efficient thermolysis of a single source precursor of mixed metal-oleate complexes in hot organic solvents with dissolved sulfur sources. Suitable tuning of the synthetic conditions and the Cu/(Zn + Sn) ratio of the precursor has enabled precise control of the crystalline phase in the form of kesterite, or a newly observed wurtzite structure. Nanocrystals with morphology in the form of spherical, rice-like, or rod-like shapes are obtained over a wide range of compositions (0.5 ≤ Cu/(Zn + Sn) ≤ 1.2). Both the final products and intermediates for each shape exhibit consistent composition and structure, indicating homogenous nucleation and growth of single-phase nanocrystals. Thin films prepared from colloidal nanocrystal suspensions display interesting shape-dependent photoresponse behavior under white light illumination from a solar simulator.

  10. Synthesis and characterization of monodisperse CdSe quantum dots in different organic solvents

    Institute of Scientific and Technical Information of China (English)

    He Rong; You Xiaogang; Tian Hongye; Gao Feng; Cui Daxiang; Gu Hongchen

    2006-01-01

    Nearly monodisperse CdSe quantum dots (QDs)have been prepared by a soft solution approach using air-stable reagents in different organic solvents.This scheme is a supplement to the conventional thermal decomposition of organometailic compounds at higher temperatures.CdSe nanocrystals of different sizes could be obtained by simply changing the solvent.This method is reproducible and simple and thus can be readily scaled up for industrial production.The reaction process was monitored by the temporal evolution of the UV-Vis absorption and room temperature photoluminensce spectra.The structures of the CdSe quantum dots were determined by X-ray powder diffraction (XRD) and transmission electron microscopy (TEM).The phase-transfer of oleic acid-stabilized CdSe nanocrystals into PBS buffer solutions was also studied for their potentials in biological applications.

  11. Straightforward and robust synthesis of monodisperse surface-functionalized gold nanoclusters

    Directory of Open Access Journals (Sweden)

    Silvia Varela-Aramburu

    2016-09-01

    Full Text Available Gold nanoclusters are small (1–3 nm nanoparticles with a high surface area that are useful for biomedical studies and drug delivery. The synthesis of small, surface-functionalized gold nanoclusters is greatly dependent on the reaction conditions. Here, we describe a straightforward, efficient and robust room temperature one-pot synthesis of 2 nm gold nanoclusters using thioglucose as a reducing and stabilizing agent, which was discovered by serendipity. The resultant monodisperse gold nanoclusters are more stable than those generated using some other common methods. The carboxylic acid contained in the stabilizing agent on the cluster surface serves as anchor for nanocluster functionalization. Alternatively, the addition of thiols serves to functionalize the nanoclusters. The resulting non-cytotoxic nanoclusters are taken up by cells and constitute a tuneable platform for biomedical applications including drug delivery.

  12. Shape-controlled synthesis of highly monodisperse and small size gold nanoparticles

    Institute of Scientific and Technical Information of China (English)

    FU YunZhi; DU YuKou; YANG Ping; LI JinRu; JIANG Long

    2007-01-01

    We describe here that fine control of nanoparticle shape and size can be achieved by systematic variation of experimental parameters in the seeded growth procedure in aqueous solution. Cubic and spherical gold nanoparticles are obtained respectively. In particularly, the Au cubes are highly monodisperse in 33±2 nm diameter. The experimental methods involve the preparation of Au seed particles and the subsequent addition of an appropriate quantity of Au seed solution to the aqueous growth solutions containing desired quantities of CTAB and ascorbic acid (AA). Here, AA is a weak reducing agent and CTAB is not only a stable agent for nanoparticles but also an inductive agent for leading increase in the face of nanoparticle. Ultraviolet visible spectroscopy (UV-vis), X-ray diffraction (XRD), transmission electron microscopy (TEM) are used to characterize the nanoparticles. The results show that the different size gold nanoparticles displayed high size homogenous distribution and formed mono-membrane at the air/solid interface.

  13. Straightforward and robust synthesis of monodisperse surface-functionalized gold nanoclusters

    Science.gov (United States)

    Varela-Aramburu, Silvia; Wirth, Richard; Lai, Chian-Hui; Orts-Gil, Guillermo

    2016-01-01

    Summary Gold nanoclusters are small (1–3 nm) nanoparticles with a high surface area that are useful for biomedical studies and drug delivery. The synthesis of small, surface-functionalized gold nanoclusters is greatly dependent on the reaction conditions. Here, we describe a straightforward, efficient and robust room temperature one-pot synthesis of 2 nm gold nanoclusters using thioglucose as a reducing and stabilizing agent, which was discovered by serendipity. The resultant monodisperse gold nanoclusters are more stable than those generated using some other common methods. The carboxylic acid contained in the stabilizing agent on the cluster surface serves as anchor for nanocluster functionalization. Alternatively, the addition of thiols serves to functionalize the nanoclusters. The resulting non-cytotoxic nanoclusters are taken up by cells and constitute a tuneable platform for biomedical applications including drug delivery. PMID:27826501

  14. One-Step Synthesis of Monodisperse In-Doped ZnO Nanocrystals

    Directory of Open Access Journals (Sweden)

    Wang QingLing

    2010-01-01

    Full Text Available Abstract A method for the synthesis of high quality indium-doped zinc oxide (In-doped ZnO nanocrystals was developed using a one-step ester elimination reaction based on alcoholysis of metal carboxylate salts. The resulting nearly monodisperse nanocrystals are well-crystallized with typically crystal structure identical to that of wurtzite type of ZnO. Structural, optical, and elemental analyses on the products indicate the incorporation of indium into the host ZnO lattices. The individual nanocrystals with cubic structures were observed in the 5% In–ZnO reaction, due to the relatively high reactivity of indium precursors. Our study would provide further insights for the growth of doped oxide nanocrystals, and deepen the understanding of doping process in colloidal nanocrystal syntheses.

  15. Two typical structure patterns in jammed monodisperse disk packings at high densities

    Science.gov (United States)

    Yuan, Ye; Jin, Weiwei; Liu, Lufeng; Li, Shuixiang

    2016-11-01

    We generate a large number of monodisperse disk packings in two dimensions via geometric-based packing algorithms including the relaxation algorithm and the Torquato-Jiao algorithm. Using the geometric-structure approach, a clear boundary of the geometrical feasible region in the order map is found which quite differs from that of the jammed region. For a certain packing density higher than 0.83, the crystalline degree varies in different packing samples. We find that the local hexatic order may increase in two fairly different ways as the system densifies. Therefore, two typical non-equilibrium jammed patterns, termed polycrystal and distorted crystal, are defined at high packing densities. Furthermore, their responses to isotropic compression are investigated using a compression-relaxation molecular dynamic protocol. The distorted crystal pattern is more stable than the polycrystal one with smaller displacements despite its low occurrence frequency. The results are helpful in understanding the structure and phase transition of disk packings.

  16. Formation and spectroscopic characterization of mono-dispersed CdSe nanocrystals

    Institute of Scientific and Technical Information of China (English)

    Miao Yan-Ming; Li Chao-Rong; Cao Li; Liu Rui-Bin; He Yu-Ping; Xie Si-Shen; Zou Bing-Suo

    2005-01-01

    In this article, mono-dispersed hexagonal structure CdSe nanocrystals with polyhedron shape were prepared by an open solvent thermal reaction. They show a discrete excitonic transition structure in the absorption spectra and the minimal photoluminescence (PL) peak full-width at half-maximum of 19nm. The PL quantum yield is about 60%. Transmission electron micrographs, high-resolution transmission electron micrographs, x-ray powder diffraction patterns, UV-vis absorption spectra and PL spectra were obtained for the as-prepared CdSe nanocrystals. The size of the CdSe nanocrystals can be tuned by changing the reaction temperature or time. Due to the improved synthesis method, a different growth mechanism of the CdSe nanocrystals is discussed.

  17. Direct Dry-Grinding Synthesis of Monodisperse Lipophilic CuS Nanoparticles.

    Science.gov (United States)

    Li, Yajuan; Scott, Julie; Chen, Yi-Tzai; Guo, Liangran; Zhao, Mingyang; Wang, Xiaodong; Lu, Wei

    2015-07-15

    Copper sulfide nanoparticles, effective absorbers of near-infrared light, are recently attracting broad interest as a photothermal coupling agent for cancer therapy. Lipophilic copper sulfide nanoparticles are preferred for high performance biomedical applications due to high tissue affinity. Synthesis of lipophilic copper sulfide nanoparticles requires complicated multi-step processes under severe conditions. Here, we describe a new synthetic process, developed by direct dry-grinding of copper(II) acetylacetonate with sulfur under ambient environment at low temperature. The formed CuS nanoparticles are of uniform size, ~10 nm in diameter, and are monodispersed in chloroform. Each covellite CuS nanocrystal surface is modified with oleylamine through hydrogen bonding between sulfur atoms and amine groups of oleylamine. The nanoparticles demonstrate near-infrared light absorption for photothermal applications. The synthetic methodology described here is more convenient and less extreme than previous methods, and should thus greatly facilitate the preparation of photothermal lipophilic copper sulfide nanomaterials for cancer therapy.

  18. Facile synthesis of monodisperse thermally immiscible Ag–Ni alloy nanoparticles at room temperature

    Indian Academy of Sciences (India)

    S Tabatabaei; S K Sadrnezhaad

    2014-10-01

    Ag and Ni are immiscible, mainly due to their large lattice mismatch. This paper reports on their nanoscale formation of solid solution at room temperature by simple reduction reactions which lead to the amorphous Ag–Ni alloy nanoparticles (ANPs) with mono-disperse distribution. Microscopic and spectroscopic studies confirmed dependence of the alloy composition on size of nanoparticles. In the presence of different ligands such as sodium citrate, polyvinyl alcohol and potassium carbonate a mixture of silver oxide and Ag–Ni ANPs was achieved. Stoichiometry of the Ag–Ni ANPs was also found to be strongly dependent on ligands of the reduction reaction and further study shows without any ligand 100% Ag–Ni ANPs was observed in the system. Using Tetrakis hydroxymethyl phosphonium chloride resulted in construction of near-uniform ANPs in the easily controllable conditions of the present alloying procedure. Nanoparticles having up to 65% Ni were observed for the first time in this research.

  19. Microwave Synthesis of Nearly Monodisperse Core/Multishell Quantum Dots with Cell Imaging Applications

    Directory of Open Access Journals (Sweden)

    Xu Hengyi

    2010-01-01

    Full Text Available Abstract We report in this article the microwave synthesis of relatively monodisperse, highly crystalline CdSe quantum dots (QDs overcoated with Cd0.5Zn0.5S/ZnS multishells. The as-prepared QDs exhibited narrow photoluminescence bandwidth as the consequence of homogeneous size distribution and uniform crystallinity, which was confirmed by transmission electron microscopy. A high photoluminescence quantum yield up to 80% was measured for the core/multishell nanocrystals. Finally, the resulting CdSe/Cd0.5Zn0.5S/ZnS core/multishell QDs have been successfully applied to the labeling and imaging of breast cancer cells (SK-BR3.

  20. Monodisperse core-shell particles composed of magnetite and dye-functionalized mesoporous silica

    Science.gov (United States)

    Eurov, D. A.; Kurdyukov, D. A.; Medvedev, A. V.; Kirilenko, D. A.; Yakovlev, D. R.; Golubev, V. G.

    2017-08-01

    Hybrid particles with a core-shell structure have been obtained in the form of monodisperse spherical mesoporous silica particles filled with magnetite and covered with a mesoporous silica shell functionalized with a luminescent dye. The particles have a small root-mean-square size deviation (at most 10%), possess a specific surface area and specific pore volume of up to 250 m2/g and 0.15 cm3/g, respectively, and exhibit visible luminescence peaked at a wavelength of 530 nm. The particles can be used in diagnostics of cancerous diseases, serving simultaneously for therapeutic (magnetic hyperthermia and targeted drug delivery) and diagnostic (contrast agent for magnetic-resonance tomography and luminescent marker) purposes.

  1. Hydrothermal synthesis of monodisperse α-Fe2O3 hexagonal platelets

    Institute of Scientific and Technical Information of China (English)

    Dengfeng Peng; Sadeh Beysen; Qiang Li; Yanfei Sun; Linyu Yang

    2010-01-01

    Uniformly sized α-Fe2O3 hexagonal platelets were synthesiz