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Sample records for large porous plga

  1. NanoCipro Encapsulation in Monodisperse Large Porous PLGA Microparticles

    PubMed Central

    Arnold, Matthew M.; Gorman, Eric M.; Schieber, Loren J.; Munson, Eric J.; Berland, Cory

    2007-01-01

    Pulmonary drug delivery of controlled release formulations may provide an effective adjunct approach to orally delivered antibiotics for clearing persistent lung infections. Dry powder formulations for this indication should possess characteristics including; effective deposition to infected lung compartments, persistence at the infection site, and steady release of antibiotic. Large porous particles (∼10-15 μm) have demonstrated effective lung deposition and enhanced lung residence as a result of their large diameter and reduced clearance by macrophages in comparison to small microparticles (∼1-5 μm). In this report, Precision Particle Fabrication technology was used to create monodisperse large porous particles of poly(D,L-lactic-co-glycolic acid) (PLGA) utilizing oils as extractable porogens. After extraction, the resulting large porous PLGA particles exhibited a low density and a web-like or hollow interior depending on porogen concentration and type, respectively. Ciprofloxacin nanoparticles (nanoCipro) created by homogenization in dichloromethane, possessed a polymorph with a decreased melting temperature. Encapsulating nanoCipro in large porous PLGA particles resulted in a steady release of ciprofloxacin that was extended for larger particle diameters and for the solid particle morphology in comparison to large porous particles. The encapsulation efficiency of nanoCipro was quite low and factors impacting the entrapment of nanoparticles during particle formation were elucidated. A dry powder formulation with the potential to control particle deposition and sustain release to the lung was developed and insight to improve nanoparticle encapsulation is discussed. PMID:17604870

  2. Inhalable, large porous PLGA microparticles loaded with paclitaxel: preparation, in vitro and in vivo characterization.

    PubMed

    Alipour, Shohreh; Montaseri, Hashem; Tafaghodi, Mohsen

    2015-01-01

    Large porous particles (LPPs) could be used as a useful carrier for non-invasive delivery to the deep lung. Pulmonary delivery of paclitaxel-loaded LPPs (PTX-LPPs) can help to eliminate the highly complicated and harmful solvent used in PTX parenteral formulations. PTX-LPPs with mass median aerodynamic diameter (MMAD) of 5.74 ± 0.09 μm, high encapsulation efficiency and good aerosolisation properties were produced using ammonium bicarbonate as porogen. Cytotoxicity of PTX-LPPs on A549 and Calu-6 cell lines was comparable with Free-PTX. Endotracheal administration of PTX-LPPs in rats exhibited PTX plasma concentration in the therapeutic range which lasted 4-fold longer than i.v. injection. The bioavailability was measured as 51 ± 7.1%. The lung targeting efficiency (Te) of PTX-LPPs was 11.9-fold higher than i.v. administration. PTX-LPPs could deliver a higher PTX to lung with a non-toxic plasma level in a longer duration which shows their pulmonary delivery suitability. PMID:26415914

  3. Doxorubicin-loaded porous PLGA microparticles with surface attached TRAIL for the inhalation treatment of metastatic lung cancer.

    PubMed

    Kim, Insoo; Byeon, Hyeong Jun; Kim, Tae Hyung; Lee, Eun Seong; Oh, Kyung Taek; Shin, Beom Soo; Lee, Kang Choon; Youn, Yu Seok

    2013-09-01

    Inhalable highly porous large PLGA microparticles with incorporated doxorubicin and surface-attached with TRAIL (TRAIL/Dox PLGA MP) were fabricated using a w/o/w double emulsification method using ammonium bicarbonate as a gas-foaming agent for the treatment of lung cancer. The TRAIL/Dox PLGA MP produced were highly porous and 11.5 ± 0.4 μm in diameter, and the loading efficiencies of Dox and TRAIL were 86.5 ± 6.5% and 91.8 ± 2.4%, respectively. TRAIL and doxorubicin were gradually released by TRAIL/Dox PLGA over 7 days, and pulmonary administration resulted in the deposition of TRAIL/Dox PLGA MP in mouse lungs, and they remained in situ for up to a week. The anti-tumor efficacy of pulmonary administered TRAIL/Dox PLGA MP was evaluated in a BALB/c nu/nu mice mouse model of H226 cell metastasis. Tumors in H226-implanted mice treated with TRAIL/Dox PLGA MP were markedly smaller and fewer in number than mice treated with TRAIL or Dox PLGA MP alone. Furthermore, this improved performance was found to be due to the synergistic apoptotic effects of the two drugs. We believe that TRAIL/Dox PLGA MP offer a promise of a sustained-release, long-acting, inhalable anti-lung cancer agent. Furthermore, the synergism observed between TRAIL and doxorubicin suggests that the doxorubicin dosage could be substantially reduced and its side effects minimized. PMID:23755831

  4. Injectable and porous PLGA microspheres that form highly porous scaffolds at body temperature.

    PubMed

    Qutachi, Omar; Vetsch, Jolanda R; Gill, Daniel; Cox, Helen; Scurr, David J; Hofmann, Sandra; Müller, Ralph; Quirk, Robin A; Shakesheff, Kevin M; Rahman, Cheryl V

    2014-12-01

    Injectable scaffolds are of interest in the field of regenerative medicine because of their minimally invasive mode of delivery. For tissue repair applications, it is essential that such scaffolds have the mechanical properties, porosity and pore diameter to support the formation of new tissue. In the current study, porous poly(dl-lactic acid-co-glycolic acid) (PLGA) microspheres were fabricated with an average size of 84±24μm for use as injectable cell carriers. Treatment with ethanolic sodium hydroxide for 2min was observed to increase surface porosity without causing the microsphere structure to disintegrate. This surface treatment also enabled the microspheres to fuse together at 37°C to form scaffold structures. The average compressive strength of the scaffolds after 24h at 37°C was 0.9±0.1MPa, and the average Young's modulus was 9.4±1.2MPa. Scaffold porosity levels were 81.6% on average, with a mean pore diameter of 54±38μm. This study demonstrates a method for fabricating porous PLGA microspheres that form solid porous scaffolds at body temperature, creating an injectable system capable of supporting NIH-3T3 cell attachment and proliferation in vitro. PMID:25152354

  5. Injectable and porous PLGA microspheres that form highly porous scaffolds at body temperature

    PubMed Central

    Qutachi, Omar; Vetsch, Jolanda R.; Gill, Daniel; Cox, Helen; Scurr, David J.; Hofmann, Sandra; Müller, Ralph; Quirk, Robin A.; Shakesheff, Kevin M.; Rahman, Cheryl V.

    2014-01-01

    Injectable scaffolds are of interest in the field of regenerative medicine because of their minimally invasive mode of delivery. For tissue repair applications, it is essential that such scaffolds have the mechanical properties, porosity and pore diameter to support the formation of new tissue. In the current study, porous poly(dl-lactic acid-co-glycolic acid) (PLGA) microspheres were fabricated with an average size of 84 ± 24 μm for use as injectable cell carriers. Treatment with ethanolic sodium hydroxide for 2 min was observed to increase surface porosity without causing the microsphere structure to disintegrate. This surface treatment also enabled the microspheres to fuse together at 37 °C to form scaffold structures. The average compressive strength of the scaffolds after 24 h at 37 °C was 0.9 ± 0.1 MPa, and the average Young’s modulus was 9.4 ± 1.2 MPa. Scaffold porosity levels were 81.6% on average, with a mean pore diameter of 54 ± 38 μm. This study demonstrates a method for fabricating porous PLGA microspheres that form solid porous scaffolds at body temperature, creating an injectable system capable of supporting NIH-3T3 cell attachment and proliferation in vitro. PMID:25152354

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

    PubMed

    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. PMID:25234156

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

    PubMed

    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

  8. Porous silicon oxide-PLGA composite microspheres for sustained ocular delivery of daunorubicin

    PubMed Central

    Nan, Kaihui; Ma, Feiyan; Hou, Huiyuan; Freeman, William R.; Sailor, Michael J.; Cheng, Lingyun

    2014-01-01

    A water-soluble anthracycline antibiotic drug (daunorubicin, DNR) was loaded into oxidized porous silicon (pSiO2) microparticles and then encapsulated with a layer of polymer (poly lactide-co-glycolide, PLGA) to investigate their synergistic effects in control of DNR release. Similarly fabricated PLGA-DNR microspheres without pSiO2, and pSiO2 microparticles without PLGA were used as control particles. The composite microparticles synthesized by a solid-in-oil-in-water (S/O/W) emulsion method have mean diameters of 52.33±16.37 μm for PLGA-pSiO2_21/40-DNR and the mean diameter of 49.31±8.87 μm for PLGA-pSiO2_6/20-DNR. The mean size, 26.00±8 μm, of PLGA-DNR was significantly smaller, compared with the other two (p<0.0001). Optical microscopy revealed that PLGA-pSiO2-DNR microsphere contained multiple pSiO2 particles. In vitro release experiments determined that control PLGA-DNR microspheres completely released DNR within 38 days and control pSiO2-DNR microparticles (with no PLGA coating) released DNR within 14 days, while the PLGA-pSiO2-DNR microspheres released DNR for 74 days. Temporal release profiles of DNR from PLGA-pSiO2 composite particles indicated that both PLGA and pSiO2 contribute to the sustained release of the payload. The PLGA-pSiO2 composite displayed a more constant rate of DNR release than the pSiO2 control formulation, and it displayed a significantly slower release of DNR than either the PLGA or pSiO2 formulations. We conclude that this system may be useful in managing unwanted ocular proliferation when formulated with anti-proliferation compounds such as DNR. PMID:24793657

  9. Development of a porous PLGA-based scaffold for mastoid air cell regeneration

    PubMed Central

    Gould, Toby W. A.; Birchall, John P.; Mallick, Ali S.; Alliston, Tamara; Lustig, Lawrence R.; Shakesheff, Kevin M.

    2015-01-01

    Objective To develop a porous, biodegradable scaffold for mastoid air cell regeneration. Study Design In vitro development of a temperature-sensitive poly(DL-lactic acid-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) scaffold tailored for this application. Methods Human mastoid bone microstructure and porosity was investigated using micro-computed tomography. PLGA/PEG-alginate scaffolds were developed and scaffold porosity was assessed. Human bone marrow mesenchymal stem cells (hBM-MSCs) were cultured on the scaffolds in vitro. Scaffolds were loaded with ciprofloxacin and release of ciprofloxacin over time in vitro was assessed. Results Porosity of human mastoid bone was measured at 83% with an average pore size of 1.3mm. PLGA/PEG-alginate scaffold porosity ranged from 43–78% depending on the alginate bead content. hBM-MSCs proliferate on the scaffolds in vitro, and release of ciprofloxacin from the scaffolds was demonstrated over 7–10 weeks. Conclusion The PLGA/PEG-alginate scaffolds developed in this study demonstrate similar structural features to human mastoid bone, support cell growth and display sustained antibiotic release. These scaffolds may be of potential clinical use in mastoid air cell regeneration. Further in vivo studies to assess the suitability of PLGA/PEG-alginate scaffolds for this application are required. PMID:23670365

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

    PubMed

    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. PMID:24863192

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

    PubMed

    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

  12. Formulations for modulation of protein release from large-size PLGA microparticles for tissue engineering.

    PubMed

    Qodratnama, Roozbeh; Serino, Lorenzo Pio; Cox, Helen C; Qutachi, Omar; White, Lisa J

    2015-02-01

    In this study we present an approach to pre-program lysozyme release from large size (100-300 μm) poly(DL-lactic acid-co-glycolic acid) (PLGA) microparticles. This approach involved blending in-house synthesized triblock copolymers with a PLGA 85:15. In this work it is demonstrated that the lysozyme release rate and the total release are related to the mass of triblock copolymer present in polymer formulation. Two triblock copolymers (PLGA-PEG1500-PLGA and PLGA-PEG1000-PLGA) were synthesized and used in this study. In a like-for-like comparison, these two triblock copolymers appeared to have similar effects on the release of lysozyme. It was shown that blending resulted in the increase of the total lysozyme release and shortened the release period (70% release within 30 days). These results demonstrated that blending PLGA-PEG-PLGA triblock copolymer with PLGA 85:15 can be used as a method to pre-program protein release from microparticles. These microparticles with modulated protein release properties may be used to create microparticle-based tissue engineering constructs with pre-programmed release properties. PMID:25492193

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  15. An endothelial cultured condition medium embedded porous PLGA scaffold for the enhancement of mouse embryonic stem cell differentiation.

    PubMed

    Li, Ching-Wen; Pan, Wei-Ting; Ju, Jyh-Cherng; Wang, Gou-Jen

    2016-01-01

    In this study, we have developed a microporous poly(lactic-co-glycolic acid) (PLGA) scaffold that combines a continuous release property and a three-dimensional (3D) scaffolding technique for the precise and efficient formation of endothelial cell lineage from embryonic stem cells (ESCs). Eight PLGA scaffolds (14.29%, 16.67%, 20% and 25% concentrations of PLGA solutions) mixed with two crystal sizes of sodium chloride (NaCl) were fabricated by leaching. Then, vascular endothelial cell conditioned medium (ECCM) mixed with gelatin was embedded into the scaffold for culturing of mouse embryonic stem cells (mESCs). The 14.29% PLGA scaffolds fabricated using non-ground NaCl particles (NG-PLGA) and the 25% PLGA containing scaffolds fabricated using ground NaCl particles (G-PLGA) possessed minimum and maximum moisture content and bovine serum albumin (BSA) content properties, respectively. These two groups of scaffolds were used for future experiments in this study. Cell culture results demonstrated that the proposed porous scaffolds without growth factors were sufficient to induce mouse ESCs to differentiate into endothelial-like cells in the early culture stages, and combined with embedded ECCM could provide a long-term inducing system for ESC differentiation. PMID:27068738

  16. Preparation and properties of PLGA microspheres containing hydrophilic drugs by the SPG (shirasu porous glass) membrane emulsification technique.

    PubMed

    Ito, Fuminori; Honnami, Hiroyuki; Kawakami, Hiroyoshi; Kanamura, Kiyoshi; Makino, Kimiko

    2008-11-15

    In the present paper, monodisperse poly (lactide-co-glycolide) (PLGA) microspheres containing the hydrophilic model drug, blue dextran (BLD), were manufactured by the solvent evaporation method and the shirasu porous glass (SPG) membrane emulsification technique. In order to prepare PLGA microspheres with a higher drug loading efficiency by the membrane emulsification technique, the test of stability and productivity of the primary emulsion (w(1)/o emulsion) was preliminary examined by change species or concentration of the oil-soluble surfactant and the ratio of water and organic solvent. The primary emulsion (w(1)/o) composed of the BLD aqueous solution and dichloromethane (DCM) dissolved PLGA was prepared with the micro homogenizer. The secondary emulsion (w(1)/o/w(2)) was prepared by the SPG membrane emulsification technique. BLD/PLGA microspheres of various micro level sizes of 2.0-10 microm prepared by variation of pore size of the using SPG membrane. The highly monodisperse BLD/PLGA microspheres were also manufactured by added polyethylene glycol (PEG) into the water phase, as reported in a previous paper. The initial release rate of the drug from such microspheres controlled than the sample manufactured without an additive. PMID:18774278

  17. Development of porous PLGA/PEI1.8k biodegradable microspheres for the delivery of Mesenchymal Stem Cells (MSCs)

    PubMed Central

    Lee, Young Sook; Lim, Kwang Suk; Oh, Jung-Eun; Yun, Arum; Joo, Wan Seok; Kim, Hyun Soo; Yun, Chae-Ok; Kim, Sung Wan

    2015-01-01

    Multipotent mesenchymal stem cells (MSCs) promise a therapeutic alternative for many debilitating and incurable diseases. However, one of the major limitations for the therapeutic application of human MSC (hMSC) is the lengthy ex vivo expansion time for preparing a sufficient amount of cells due to the low engraftment rate after transplantation. To solve this conundrum, a porous biodegradable polymeric microsphere was investigated as a potential scaffold for the delivery of MSCs. The modified water/oil/water (W1/O/W2) double emulsion solvent evaporation method was used for the construction of porous microspheres. PEI1.8k was blended with Poly(lactic-co-glycolic acid) (PLGA) to enhance electrostatic cellular attachment to the microspheres. The porous PLGA/PEI1.8k (PPP) particles demonstrated an average particle size of 290 µm and an average pore size of 14.3 µm, providing a micro-carrier for the MSC delivery. PPP particles allowed for better attachment of rMSCs than nonporous PLGA/PEI1.8k (NPP) particles and non-porous (NP) and porous PLGA (PP) microspheres. rMSC successfully grew on the PPP particles for 2 weeks in vitro. Next, PPP particles loaded with 3 different amounts of hMSC showed increased in vivo engraftment rates and maintained the stemness characteristics of hMSC compared with hMSCs-alone group in rats 2 weeks after intramyocardial administration. These customized PPP particles for MSC delivery are a biodegradable and injectable scaffold that can be used for clinical applications. PMID:25575866

  18. Characterization of porous PLGA/PLA microparticles as a scaffold for three dimensional growth of breast cancer cells.

    PubMed

    Sahoo, Sanjeeb K; Panda, Amulya K; Labhasetwar, Vinod

    2005-01-01

    We have designed and evaluated biodegradable porous polymeric microparticles as a scaffold for cell growth. The hypothesis was that microparticles with optimized composition and properties would have better cell adhesion and hence cell growth into a tissue-like structure. Solvent-evaporation method was modified using sucrose as an additive to form large porous microparticles of poly(D,L-lactic-co-glycolic) (PLGA) and polylactide (PLA) polymers. Microparticles containing hydrophilic polymers (poly(vinyl alcohol) and chitosan) incorporated in their internal matrix structure were also formulated. Different formulations of microparticles were evaluated for physical properties, cell adhesion, and cell growth in culture. PLA microparticles containing poly(vinyl alcohol) (PVA) in the matrix structure (PLA-PVA) and treated with serum prior to cell seeding demonstrated better cell adhesion and cell growth than other formulations of microparticles. Cells were seen to grow into clumps, engulfing microparticles completely with time, and forming a 3-D tissue-like structure. Cell density of 1.5 x 10(6) cells per mg of microparticles was achieved in 9 days of culture, which was a 7-fold increase from the initial seeding cell density. The mechanism of better cell growth on PLA-PVA microparticles appears to be due to the PVA associated with the internal matrix structure of microparticles. These microparticles demonstrated better wetting in culture and also cell adhesion. In addition to tissue engineering applications, microparticles with cancer cells grown into a tissue-like structure in vitro can be potentially used as a model system for preclinical evaluation of the cytotoxic effect of anticancer agents. PMID:15762686

  19. Biomimetic Porous PLGA Scaffolds Incorporating Decellularized Extracellular Matrix for Kidney Tissue Regeneration.

    PubMed

    Lih, Eugene; Park, Ki Wan; Chun, So Young; Kim, Hyuncheol; Kwon, Tae Gyun; Joung, Yoon Ki; Han, Dong Keun

    2016-08-24

    Chronic kidney disease is now recognized as a major health problem, but current therapies including dialysis and renal replacement have many limitations. Consequently, biodegradable scaffolds to help repairing injured tissue are emerging as a promising approach in the field of kidney tissue engineering. Poly(lactic-co-glycolic acid) (PLGA) is a useful biomedical material, but its insufficient biocompatibility caused a reduction in cell behavior and function. In this work, we developed the kidney-derived extracellular matrix (ECM) incorporated PLGA scaffolds as a cell supporting material for kidney tissue regeneration. Biomimetic PLGA scaffolds (PLGA/ECM) with different ECM concentrations were prepared by an ice particle leaching method, and their physicochemical and mechanical properties were characterized through various analyses. The proliferation of renal cortical epithelial cells on the PLGA/ECM scaffolds increased with an increase in ECM concentrations (0.2, 1, 5, and 10%) in scaffolds. The PLGA scaffold containing 10% of ECM has been shown to be an effective matrix for the repair and reconstitution of glomerulus and blood vessels in partially nephrectomized mice in vivo, compared with only PLGA control. These results suggest that not only can the tissue-engineering techniques be an effective alternative method for treatment of kidney diseases, but also the ECM incorporated PLGA scaffolds could be promising materials for biomedical applications including tissue engineered scaffolds and biodegradable implants. PMID:27456613

  20. Controllable promotion of chondrocyte adhesion and growth on PVA hydrogels by controlled release of TGF-β1 from porous PLGA microspheres.

    PubMed

    Nie, Lei; Zhang, Guohua; Hou, Ruixia; Xu, Haiping; Li, Yaping; Fu, Jun

    2015-01-01

    Poly(vinyl alcohol) (PVA) hydrogels have been candidate materials for cartilage tissue engineering. However, the cell non-adhesive nature of PVA hydrogels has been a limit. In this paper, the cell adhesion and growth on PVA hydrogels were promoted by compositing with transform growth factor-β1 (TGF-β1) loaded porous poly(D,L-lactide-co-glycolide) (PLGA) microspheres. The porous microspheres were fabricated by a modified double emulsion method with bovine serum albumin (BSA) as porogen. The average pore size of microspheres was manipulated by changing the BSA/PLGA ratio. Such controllable porous structures effectively influenced the encapsulation efficiency (Eencaps) and release profile of TGF-β1. By compositing PVA hydrogels with such TGF-β1-loaded PLGA microspheres, chondrocyte adhesion and proliferation were significantly promoted in a controllable manner, as confirmed by fluorescent imaging and quantitative CCK-8 assay. That is, the chondrocyte proliferation was favored by using PLGA microspheres with high Eencaps of TGF-β1 or by increasing the PLGA microsphere content in the hydrogels. These results demonstrated a facile method to improve the cell adhesion and growth on the intrinsically cell non-adhesive PVA hydrogels, which may find applications in cartilage substitution. PMID:25437063

  1. Novel porous hydroxyapatite prepared by combining H2O2 foaming with PU sponge and modified with PLGA and bioactive glass.

    PubMed

    Huang, Xiao; Miao, Xigeng

    2007-04-01

    Porous hydroxyapatite (HA) scaffolds have been intensively studied and developed for bone tissue engineering, but their mechanical properties remain to be improved. The aim of this study is to prepare HA-based composite scaffolds that have a unique macroporous structure and special struts of a polymer/ceramic interpenetrating composite and a bioactive coating. A novel combination of a polyurethane (PU) foam method and a hydrogen peroxide (H(2)O( 2)) foaming method is used to fabricate the macroporous HA scaffolds. Micropores are present in the resulting porous HA ceramics after the unusual sintering of a common calcium phosphate cement and are infiltrated with the poly(D,L-lactic-co-glycolic acid) (PLGA) polymer. The internal surfaces of the macropores are further coated with a PLGA-bioactive glass composite coating. The porous composite scaffolds are characterized in terms of microstructure, mechanical properties, and bioactivity. It is found that the HA scaffolds fabricated by the combined method show high porosities of 61-65% and proper macropore sizes of 200-600 microm. The PLGA infiltration improved the compressive strengths of the scaffolds from 1.5-1.8 to 4.0-5.8 MPa. Furthermore, the bioactive glass-PLGA coating rendered a good bioactivity to the composites, evidenced by the formation of an apatite layer on the sample surfaces immersed in the simulated body fluid (SBF) for 5 days. The porous HA-based composites obtained from this study have suitable porous structures, proper mechanical properties, and a high bioactivity, and thus finds potential application as scaffolds for bone tissue engineering. PMID:16543281

  2. Combination of doxorubicin-based chemotherapy and polyethylenimine/p53 gene therapy for the treatment of lung cancer using porous PLGA microparticles.

    PubMed

    Shi, Xiaozheng; Li, Chunjie; Gao, Sai; Zhang, Lingfei; Han, Haobo; Zhang, Jianxu; Shi, Wei; Li, Quanshun

    2014-10-01

    In this study, porous PLGA microparticles for the co-delivery of doxorubicin and PEI25K/p53 were successfully prepared by the water-oil-water emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The porous microparticles were obtained with a mean diameter of 22.9±11.8μm as determined by laser scattering particle size analysis. The particles' surface porous morphology and distributions of doxorubicin and p53 were systematically characterized by scanning electron microscopy, flow cytometry, fluorescence microscopy and confocal laser scanning microscopy, revealing that doxorubicin and the plasmid were successfully co-encapsulated. Encapsulation efficiencies of 88.2±1.7% and 36.5±7.5% were achieved for doxorubicin and the plasmid, respectively, demonstrating that the porous structure did not adversely affect payload encapsulation. Microparticles harboring both doxorubicin and PEI25K/p53 exhibited enhanced tumor growth inhibition and apoptosis induction compared to those loaded with either agent alone in A549 human lung adenocarcinoma cells. Overall, the porous PLGA microparticles provide a promising anticancer delivery system for combined chemotherapy and gene therapy, and have great potential as a tool for sustained local drug delivery by inhalation. PMID:25082753

  3. Release of PLGA-encapsulated dexamethasone from microsphere loaded porous surfaces.

    PubMed

    Dawes, G J S; Fratila-Apachitei, L E; Necula, B S; Apachitei, I; Witkamp, G J; Duszczyk, J

    2010-01-01

    The aim of the present study was to investigate the morphology and function of a drug eluting metallic porous surface produced by the immobilization of poly lactide-co-glycolide microspheres bearing dexamethasone onto plasma electrolytically oxidized Ti-6Al-7Nb medical alloy. Spheres of 20 microm diameter were produced by an oil-in-water emulsion/solvent evaporation method and thermally immobilized onto titanium discs. The scanning electron microscopy investigations revealed that the size distribution and morphology of the attached spheres had not changed significantly. The drug release profiles following degradation in phosphate buffered saline for 1000 h showed that, upon immobilisation, the spheres maintained a sustained release, with a triphasic profile similar to the non-attached system. The only significant change was an increased release rate during the first 100 h. This difference was attributed to the effect of thermal attachment of the spheres to the surface. PMID:19669866

  4. Large Deformations of a Soft Porous Material

    NASA Astrophysics Data System (ADS)

    MacMinn, Christopher W.; Dufresne, Eric R.; Wettlaufer, John S.

    2016-04-01

    Compressing a porous material will decrease the volume of the pore space, driving fluid out. Similarly, injecting fluid into a porous material can expand the pore space, distorting the solid skeleton. This poromechanical coupling has applications ranging from cell and tissue mechanics to geomechanics and hydrogeology. The classical theory of linear poroelasticity captures this coupling by combining Darcy's law with Terzaghi's effective stress and linear elasticity in a linearized kinematic framework. Linear poroelasticity is a good model for very small deformations, but it becomes increasingly inappropriate for moderate to large deformations, which are common in the context of phenomena such as swelling and damage, and for soft materials such as gels and tissues. The well-known theory of large-deformation poroelasticity combines Darcy's law with Terzaghi's effective stress and nonlinear elasticity in a rigorous kinematic framework. This theory has been used extensively in biomechanics to model large elastic deformations in soft tissues and in geomechanics to model large elastoplastic deformations in soils. Here, we first provide an overview and discussion of this theory with an emphasis on the physics of poromechanical coupling. We present the large-deformation theory in an Eulerian framework to minimize the mathematical complexity, and we show how this nonlinear theory simplifies to linear poroelasticity under the assumption of small strain. We then compare the predictions of linear poroelasticity with those of large-deformation poroelasticity in the context of two uniaxial model problems: fluid outflow driven by an applied mechanical load (the consolidation problem) and compression driven by a steady fluid throughflow. We explore the steady and dynamical errors associated with the linear model in both situations, as well as the impact of introducing a deformation-dependent permeability. We show that the error in linear poroelasticity is due primarily to kinematic

  5. Size matters: effects of PLGA-microsphere size in injectable CPC/PLGA on bone formation.

    PubMed

    Liao, Hongbing; Félix Lanao, Rosa P; van den Beucken, Jeroen J J P; Zhou, Nuo; Both, Sanne K; Wolke, Joop G C; Jansen, John A

    2016-08-01

    The aim of this study was to evaluate the effect of PLGA microsphere dimensions on bone formation after injection of calcium phosphate cement (CPC)/PLGA in a guinea pig tibial intramedullarly model. To this end, injectable CPC/PLGA formulations were prepared using PLGA microspheres with either a small (~25 µm) or large (~100 µm) diameter, which were incorporated at a 20:80 ratio (wt%) within apatite CPC. Both CPC/PLGA formulations were injected into a marrow-ablated tibial intramedullary cavity and, after an implantation period of 12 weeks, histology and histomorphometry were used to address bone formation. The results demonstrated bone ingrowth throughout the entire scaffold material for both CPC/PLGA formulations upon PLGA microsphere degradation. More importantly, bone formation within the CPC matrix was > two-fold higher for CPC-PLGA with 25 µm PLGA microspheres. Additionally, the pattern of bone and marrow formation showed distinct differences related to PLGA microsphere dimension. In general, this study demonstrates that PLGA microsphere dimensions of ~25 µm, leading to pores of ~25 µm within CPC, are sufficient for bone ingrowth and allow substantial bone formation. Further, the results demonstrate that PLGA microsphere dimensions provide a tool to control bone formation for injectable CPC/PLGA bone substitutes. Copyright © 2013 John Wiley & Sons, Ltd. PMID:24170734

  6. Engineering gas-foamed large porous particles for efficient local delivery of macromolecules to the lung.

    PubMed

    Ungaro, Francesca; Giovino, Concetta; Coletta, Ciro; Sorrentino, Raffaella; Miro, Agnese; Quaglia, Fabiana

    2010-09-11

    Gas-foamed large porous particles (gfLPP) based on poly(lactic-co-glycolic) acid (PLGA) have been recently suggested as potential carriers for pulmonary drug delivery. In this work, we attempt to engineer gfLPP for efficient local delivery of macromolecules in the lungs. Particles were fabricated by the double emulsion-solvent evaporation technique using ammonium bicarbonate as porogen. To improve particle technological properties, two lipid aid excipients, namely dipalmitoylphosphatidylcholine (DPPC) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), were tested. Preliminary technological studies performed on unloaded gfLPP showed that the addition of an appropriate amount of NH(4)(HCO(3)), which spontaneously produces CO(2) and NH(3) during solvent evaporation, is essential to achieve a homogeneous population of highly porous particles with optimal aerodynamic properties. Then, the effect of the presence of DPPC or DOTAP upon the properties of gfLPP containing a model hydrophilic macromolecule, rhodamine B isothiocyanate-dextran (Rhod-dex), was assessed. We found that in the case of hydrophilic macromolecules unable to interact with PLGA end-groups, such as Rhod-dex, excipient addition is essential to increase the amount of drug entrapped within gfLPP, being as high as 80% only for DPPC- or DOTAP-engineered gfLPP. Also Rhod-dex release profile from gfLPP was strongly affected by excipient addition in the initial formulation, with lipid-engineered gfLPP allowing for a more prolonged release of Rhod-dex as compared to excipient-free gfLPP. A further modulation of Rhod-dex initial release rate could be achieved when DOTAP was used, likely due to the electrostatic interactions occurring between macromolecule and cationic phospholipid. Conceiving the developed gfLPP for drug inhalation, DPPC- and DOTAP-engineered gfLPP displayed optimal MMAD(exp) values falling within the range 6.1-7.6 microm and very low geometric standard deviations (GSD) varying between 1.2 and

  7. Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance.

    PubMed

    Zhu, Huijun; Chen, Hongbo; Zeng, Xiaowei; Wang, Zhongyuan; Zhang, Xudong; Wu, Yanping; Gao, Yongfeng; Zhang, Jinxie; Liu, Kewei; Liu, Ranyi; Cai, Lintao; Mei, Lin; Feng, Si-Shen

    2014-02-01

    We report a strategy to make use of poly(lactic-co-glycolic acid) nanoparticle (PLGA NPs) for co-delivery of docetaxel (DTX) as a model anticancer drug together with vitamin E TPGS. The latter plays a dual role as a pore-forming agent in the nanoparticles that may result in smaller particle size, higher drug encapsulation efficiency and faster drug release, and also as a bioactive agent that could inhibit P-glycoprotein to overcome multi-drug resistance of the cancer cells, The DTX-loaded PLGA NPs of 0, 10, 20 and 40% TPGS were prepared by the nanoprecipitation method and then characterized for their size and size distribution, surface morphology, physical status and encapsulation efficiency of the drug in the NPs. All four NPs were found of size ranged 100-120 nm and EE ranged 85-95% at drug loading level around 10%. The in vitro evaluation showed that the 48 h IC50 values of the free DTX and the DTX-loaded PLGA NPs of 0, 10, 20% TPGS were 2.619 and 0.474, 0.040, 0.009 μg/mL respectively, which means that the PLGA NPs formulation could be 5.57 fold effective than the free DTX and that the DTX-loaded PLGA NPs of 10 or 20% TPGS further be 11.85 and 52.7 fold effective than the DTX-loaded PLGA NPs of no TPGS (therefore, 66.0 and 284 fold effective than the free DTX). Xenograft tumor model and immunohistological staining analysis further confirmed the advantages of the strategy of co-delivery of anticancer drugs with TPGS by PLGA NPs. PMID:24360574

  8. Dynamic compression combined with SOX-9 overexpression in rabbit adipose-derived mesenchymal stem cells cultured in a three-dimensional gradual porous PLGA composite scaffold upregulates HIF-1α expression.

    PubMed

    Chen, Xu; Li, Jianjun; Wang, Enbo; Zhao, Qun; Kong, Zhan; Yuan, Xiangnan

    2015-12-01

    There is considerable interest in how the fate of adipose-derived stem cells is determined. Physical stimuli play a crucial role in skeletogenesis and in cartilage repair and regeneration. In the present study, we investigated the comparative and interactive effects of dynamic compression and SRY-related high-mobility group box gene-9 (SOX-9) on chondrogenesis of rabbit adipose-derived stem cells in three-dimensional gradual porous PLGA (polylactic-co-glycolic acid) composite scaffolds. Articular cartilage is stratified into zones delineated by characteristic changes in cellular, matrix, and nutritive components. As a consequence, biochemical and biomechanical properties vary greatly between the different zones, giving the tissue its unique structure and, thus, the ability to cope with extreme loading. The effects on development of the cartilage were examined using a combination of computational modeling to predict alterations in biophysical stimuli, detailed morphometric analysis of 3D digital representations. In addition, early chondrogenic differentiation was assessed via real-time PCR of mRNA expression levels for bone- and cartilage-specific gene markers. Our findings define the important role of dynamic compression combined with SOX-9 overexpression during in vitro generation of tissue-engineering cartilage and suggest that a 3D gradual porous PLGA composite scaffold may benefit articular cartilage tissue engineering in cartilage regeneration for better force distribution. PMID:26123537

  9. Large Porous Particles for Sustained Release of a Decoy Oligonucelotide and Poly(ethylenimine): Potential for Combined Therapy of Chronic Pseudomonas aeruginosa Lung Infections.

    PubMed

    d'Angelo, Ivana; Perfetto, Brunella; Costabile, Gabriella; Ambrosini, Veronica; Caputo, Pina; Miro, Agnese; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Donnarumma, Giovanna; Quaglia, Fabiana; Ungaro, Francesca

    2016-05-01

    We have recently demonstrated that the specific inhibition of nuclear factor-κB by a decoy oligonucleotide (dec-ODN) delivered through inhalable large porous particles (LPP) made of poly(lactic-co-glycolic acid) (PLGA) may be highly beneficial for long-term treatment of lung inflammation. Nevertheless, besides chronic inflammation, multifunctional systems aimed to control also infection are required in chronic lung diseases, such as cystic fibrosis (CF). In this work, we tested the hypothesis that engineering PLGA-based LPP with branched poly(ethylenimine) (PEI) may improve LPP properties for pulmonary delivery of dec-ODN, with particular regard to the treatment of Pseudomonas aeruginosa lung infections. After getting insight into the role of PEI on the technological properties of PLGA-based LPP for delivery of dec-ODN, the putative synergistic effect of PEI free or PEI released from LPP on in vitro antimicrobial activity of tobramycin (Tb) and aztreonam (AZT) against P. aeruginosa was elucidated. Meanwhile, cytotoxicity studies on A549 cells were carried out. Results clearly demonstrate that the dry powders have promising aerosolization properties and afford a prolonged in vitro release of both dec-ODN and PEI. The encapsulation of PEI into LPP results in a 2-fold reduction of the minimum inhibitory concentration of AZT, while reducing the cytotoxic effect of PEI. Of note, the developed ODN/PLGA/PEI LPP persisted at lung at least for 14 days after intratracheal administration in rats where they can provide sustained and combined release of dec-ODN and PEI. dec-ODN will likely act as an anti-inflammatory drug, while PEI may enhance the therapeutic activity of inhaled antibiotics, which are commonly employed for the treatment of concomitant lung infections. PMID:27002689

  10. Transport of large particles in flow through porous media

    NASA Astrophysics Data System (ADS)

    Imdakm, A. O.; Sahimi, Muhammad

    1987-12-01

    There is considerable evidence indicating that significant reduction in the efficiency of many processes in porous media, such as enhancing oil recovery, heterogeneous chemical reactions, deep-bed filtration, gel permeation, and liquid chromatography, is due to the reduction in the permeability of the pore space. This reduction is due to the transport of particles, whose sizes are comparable with those of the pores, and the subsequent blocking of the pores by various mechanisms. In this paper we develop a novel Monte Carlo method for theoretical modeling of this phenomenon. Particles of various sizes are injected into the medium, and their migration in the flow field is modeled by a random walk whose transition porbability is proportional to the local pore fluxes. Pores are blocked and their flow capacity is reduced (or vanished) when large particles pass through them (and reduce their flow) or totally block them. The permeability of the medium can ultimately vanish and, therefore, this phenomenon is a percolation process. Various quantities of interest such as the variations of the permeability with process time and the distribution of pore-plugging times are computed. The critical exponent characterizing the vanishing of the permeability near the percolation threshold appears to be different from that of percolation conductivity. The agreement between our results and the available experimental data is excellent.

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

    PubMed

    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. PMID:23511808

  12. Pulmonary delivery of pyrazinamide-loaded large porous particles.

    PubMed

    Pham, Dinh-Duy; Grégoire, Nicolas; Couet, William; Gueutin, Claire; Fattal, Elias; Tsapis, Nicolas

    2015-08-01

    We have improved the aerodynamic properties of pyrazinamide loaded large porous particles (PZA-LPPs) designed for pulmonary delivery. To overcome the segregation of the different components occurring during the spray drying process and to obtain homogeneous LPPs, spray drying parameters were modified to decrease the drying speed. As a result, good aerodynamic properties for lung delivery were obtained with a fine particle fraction (FPF) of 40.1±1.0%, an alveolar fraction (AF) of 29.6±3.1%, a mass median aerodynamic diameter (MMADaer) of 4.1±0.2μm and a geometric standard deviation (GSD) of 2.16±0.16. Plasma and epithelial lining fluid (ELF) concentrations of pyrazinamide were evaluated after intratracheal insufflation of PZA-LPPs (4.22mgkg(-1)) into rats and compared to intravenous administration (iv) of a pyrazinamide solution (5.82mgkg(-1)). The in vivo pharmacokinetic evaluation of PZA-LPPs in rats reveals that intratracheal insufflation of PZA-LPPs leads to a rapid absorption in plasma with an absolute bioavailability of 66%. This proves that PZA-LPPs dissolve fast upon deposition and that PZA crosses efficiently the lung barrier to reach the systemic circulation. PZA concentrations were 1.28-fold higher in ELF after intratracheal administration than after iv administration and the ratio of ELF concentrations over plasma concentrations was 2-fold greater. Although these improvements are moderate, lung delivery of PZA appears an interesting alternative to oral delivery of the molecule and should now be tested in an infected animal model to evaluate its efficacy against Mycobacterium tuberculosis. PMID:26036447

  13. “Re-growth Etching” to Large-sized Porous Gold Nanostructures

    PubMed Central

    Li, Wenzheng; Kuai, Long; Chen, Lu; Geng, Baoyou

    2013-01-01

    A new method, named “re-growth etching”, which introduces a unique etchant “AuI”, has been developed to fabricate large-sized porous gold nanostructures. The size of nanostructures and the number of pores can be regulated by the molar ratio of Ag and Au in the precursor. We have evaluated their performance by a model reaction of the reduction of 4-nitrophenol. The catalytic property of porous Au from Ag67.6Au32.4 (Sample 3) is higher than those of other obtained products, which are mainly attributed to its hollows-interior, porous-exterior, and the large amount of Au. The method for the large-sized porous metal nanostructures has been established for the first time and shows the potential of this route to expand the scope of fabricating porous metal nanostructures. PMID:23921558

  14. Production of large-scale, freestanding vanadium pentoxide nanobelt porous structures.

    PubMed

    Yun, Yong Ju; Kim, Byung Hoon; Hong, Won G; Kim, Chang Hee; Kim, Yark Yeon; Jeong, Eun-ju; Jang, Won Ick; Yu, Han Young

    2012-03-01

    Large-scale, freestanding, porous structures of vanadium pentoxide nanobelts (VPNs) were successfully prepared using the template-free freeze-drying method. The porous and multi-layered VPN macrostructures are composed of randomly oriented long nanobelts (over 100 μm) and their side length can be controlled up to a few tens of centimetres. Also, the bulk density and surface area of these macrostructures are 3-5 mg cm(-3) and 40-80 m(2) g(-1), respectively, which are similar to those of the excellent adsorbents. In addition, the removal efficiency measurements of ammonia molecules revealed that the VPN porous structures can adsorb the ammonia molecules with the combinations of van der Waals forces and strong chemical bonding by functional groups on the VPN surface. PMID:22293666

  15. Production of large-scale, freestanding vanadium pentoxide nanobelt porous structures

    NASA Astrophysics Data System (ADS)

    Yun, Yong Ju; Kim, Byung Hoon; Hong, Won G.; Kim, Chang Hee; Kim, Yark Yeon; Jeong, Eun-Ju; Jang, Won Ick; Yu, Han Young

    2012-02-01

    Large-scale, freestanding, porous structures of vanadium pentoxide nanobelts (VPNs) were successfully prepared using the template-free freeze-drying method. The porous and multi-layered VPN macrostructures are composed of randomly oriented long nanobelts (over 100 μm) and their side length can be controlled up to a few tens of centimetres. Also, the bulk density and surface area of these macrostructures are 3-5 mg cm-3 and 40-80 m2 g-1, respectively, which are similar to those of the excellent adsorbents. In addition, the removal efficiency measurements of ammonia molecules revealed that the VPN porous structures can adsorb the ammonia molecules with the combinations of van der Waals forces and strong chemical bonding by functional groups on the VPN surface.

  16. Large photocurrents in GaN porous structures with a redshift of the photoabsorption edge

    NASA Astrophysics Data System (ADS)

    Sato, Taketomo; Kumazaki, Yusuke; Kida, Hirofumi; Watanabe, Akio; Yatabe, Zenji; Matsuda, Soichiro

    2016-01-01

    Photoresponse and photoabsorption properties of GaN porous structures were investigated by measuring photocurrent and spectroscopic photoabsorption under monochromatic light with various wavelengths. The measured photocurrents on the porous GaN electrodes were larger than those on the planar electrodes due to the unique features of the former electrode, such as large surface area and low photoreflectance properties. Moreover, the photocurrents were observed even under illumination with wavelength of 380 nm, corresponding to photon energy of 3.26 eV, which is 130 meV lower than the bandgap energy of bulk GaN. A potential simulation revealed that a high-electric field was induced at the pore tips due to modification of the potential in the porous structures. The observed redshift of the photoabsorption edge can be qualitatively explained by the Franz-Keldysh effect.

  17. Large-range Control of the Microstructures and Properties of Three-dimensional Porous Graphene

    PubMed Central

    Xie, Xiao; Zhou, Yilong; Bi, Hengchang; Yin, Kuibo; Wan, Shu; Sun, Litao

    2013-01-01

    Graphene-based three-dimensional porous macrostructures are believed of great importance in various applications, e.g. supercapacitors, photovoltaic cells, sensors and high-efficiency sorbents. However, to precisely control the microstructures and properties of this material to meet different application requirements in industrial practice remains challenging. We herein propose a facile and highly effective strategy for large-range tailoring the porous architecture and its properties by a modified freeze casting process. The pore sizes and wall thicknesses of the porous graphene can be gradually tuned by 80 times (from 10 to 800 μm) and 4000 times (from 20 nm to 80 μm), respectively. The property experiences the changing from hydrophilic to hydrophobic, with the Young's Modulus varying by 15 times. The fundamental principle of the porous microstructure evolution is discussed in detail. Our results demonstrate a very convenient and general protocol to finely tailor the structure and further benefit the various applications of porous graphene. PMID:23817081

  18. Large-Scale NMR Measurements in Porous Media

    NASA Astrophysics Data System (ADS)

    Legchenko, Anatoly; Vouillamoz, Jean-Michel

    2011-03-01

    The large-scale Nuclear Magnetic Resonance measurements in the Earth's magnetic field (Surface NMR method) is a geophysical technique that allows non-invasive investigations of water-saturated rocks. The measuring setup consists of a wire loop on the surface that is energized by one or two pulses of oscillating current. After the pulses are cut off, the free induction decay (FID) and/or the spin echo (SE) signal from groundwater could be measured. SNMR results are averaged over the investigated volume that depends on the loop size and typically varies from 20x20x20 to 100x100x100 cubic meters. The maximum depth of groundwater detection can vary from 45 to 150 m depending on measurement conditions, although an average depth of investigation is generally considered to be about 100 m. Our recent results show that combination of FID and SE allows rendering the SNMR less dependent on the geological conditions. Because of different scales, use of rock samples for calibration of the SNMR-estimate of the water content is difficult or impossible. Thus, for interpretation of experimental data we use a mathematical model that allows computing the theoretical signal generated by groundwater. The processing of SNMR data can provide the depth, thickness and water content of investigated aquifers. For improving accuracy of the SNMR results we use calibration based on borehole pumping test data. Based on the water content and the relaxation time provided by MRS it is possible to estimate the aquifer's hydrodynamic properties.

  19. A Feasibility Study on Operating Large Scale Compressed Air Energy Storage in Porous Formations

    NASA Astrophysics Data System (ADS)

    Wang, B.; Pfeiffer, W. T.; Li, D.; Bauer, S.

    2015-12-01

    Compressed air energy storage (CAES) in porous formations has been considered as one promising option of large scale energy storage for decades. This study, hereby, aims at analyzing the feasibility of operating large scale CAES in porous formations and evaluating the performance of underground porous gas reservoirs. To address these issues quantitatively, a hypothetic CAES scenario with a typical anticline structure in northern Germany was numerically simulated. Because of the rapid growth in photovoltaics, the period of extraction in a daily cycle was set to the early morning and the late afternoon in order to bypass the massive solar energy production around noon. The gas turbine scenario was defined referring to the specifications of the Huntorf CAES power plant. The numerical simulations involved two stages, i.e. initial fill and cyclic operation, and both were carried out using the Eclipse E300 simulator (Schlumberger). Pressure loss in the gas wells was post analyzed using an analytical solution. The exergy concept was applied to evaluate the potential energy amount stored in the specific porous formation. The simulation results show that porous formations prove to be a feasible solution of large scale CAES. The initial fill with shut-in periods determines the spatial distribution of the gas phase and helps to achieve higher gas saturation around the wells, and thus higher deliverability. The performance evaluation shows that the overall exergy flow of stored compressed air is also determined by the permeability, which directly affects the deliverability of the gas reservoir and thus the number of wells required.

  20. Advection Scheme for Phase-changing Porous Media Flow of Fluids with Large Density Ratio

    NASA Astrophysics Data System (ADS)

    Zhang, Duan; Padrino, Juan

    2015-11-01

    Many flows in a porous media involve phase changes between fluids with a large density ratio. For instance, in the water-steam phase change the density ratio is about 1000. These phase changes can be results of physical changes, or chemical reactions, such as fuel combustion in a porous media. Based on the mass conservation, the velocity ratio between the fluids is of the same order of the density ratio. As the result the controlling Courant number for the time step in a numerical simulation is determined by the high velocity and low density phase, leading to small time steps. In this work we introduce a numerical approximation to increase the time step by taking advantage of the large density ratio. We provide analytical error estimation for this approximate numerical scheme. Numerical examples show that using this approximation about 40-fold speedup can be achieved at the cost of a few percent error. Work partially supported by LDRD project of LANL.

  1. Formation of quasi-single crystalline porous ZnO nanostructures with a single large cavity

    NASA Astrophysics Data System (ADS)

    Cho, Seungho; Kim, Semi; Jung, Dae-Won; Lee, Kun-Hong

    2011-09-01

    We report a method for synthesizing quasi-single crystalline porous ZnO nanostructures containing a single large cavity. The microwave-assisted route consists of a short (about 2 min) temperature ramping stage (from room temperature to 120 °C) and a stage in which the temperature is maintained at 120 °C for 2 h. The structures produced by this route were 200-480 nm in diameter. The morphological yields of this method were very high. The temperature- and time-dependent evolution of the synthesized powders and the effects of an additive, vitamin C, were studied. Spherical amorphous/polycrystalline structures (70-170 nm in diameter), which appeared transitorily, may play a key role in the formation of the single crystalline porous hollow ZnO nanostructures. Studies and characterization of the nanostructures suggested a possible mechanism for formation of the quasi-single crystalline porous ZnO nanostructures with an interior space.We report a method for synthesizing quasi-single crystalline porous ZnO nanostructures containing a single large cavity. The microwave-assisted route consists of a short (about 2 min) temperature ramping stage (from room temperature to 120 °C) and a stage in which the temperature is maintained at 120 °C for 2 h. The structures produced by this route were 200-480 nm in diameter. The morphological yields of this method were very high. The temperature- and time-dependent evolution of the synthesized powders and the effects of an additive, vitamin C, were studied. Spherical amorphous/polycrystalline structures (70-170 nm in diameter), which appeared transitorily, may play a key role in the formation of the single crystalline porous hollow ZnO nanostructures. Studies and characterization of the nanostructures suggested a possible mechanism for formation of the quasi-single crystalline porous ZnO nanostructures with an interior space. Electronic supplementary information (ESI) available: TEM images and the corresponding SAED image of a Zn

  2. Development of Risperidone PLGA Microspheres

    PubMed Central

    D'Souza, Susan; Faraj, Jabar A.; Giovagnoli, Stefano; DeLuca, Patrick P.

    2014-01-01

    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. PMID:24616812

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

    PubMed

    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. PMID:20532635

  4. Biomimetic Hybrid Nanofiber Sheets Composed of RGD Peptide-Decorated PLGA as Cell-Adhesive Substrates

    PubMed Central

    Shin, Yong Cheol; Lee, Jong Ho; Kim, Min Jeong; Park, Ji Hoon; Kim, Sung Eun; Kim, Jin Su; Oh, Jin-Woo; Han, Dong-Wook

    2015-01-01

    In biomedical applications, there is a need for tissue engineering scaffolds to promote and control cellular behaviors, including adhesion, proliferation and differentiation. In particular, the initial adhesion of cells has a great influence on those cellular behaviors. In this study, we concentrate on developing cell-adhesive substrates applicable for tissue engineering scaffolds. The hybrid nanofiber sheets were prepared by electrospinning poly(lactic-co-glycolic acid) (PLGA) and M13 phage, which was genetically modified to enhance cell adhesion thru expressing RGD peptides on their surface. The RGD peptide is a specific motif of extracellular matrix (ECM) for integrin receptors of cells. RGD peptide-decorated PLGA (RGD-PLGA) nanofiber sheets were characterized by scanning electron microscopy, immunofluorescence staining, contact angle measurement and differential scanning calorimetry. In addition, the initial adhesion and proliferation of four different types of mammalian cells were determined in order to evaluate the potential of RGD-PLGA nanofiber sheets as cell-adhesive substrates. Our results showed that the hybrid nanofiber sheets have a three-dimensional porous structure comparable to the native ECM. Furthermore, the initial adhesion and proliferation of cells were significantly enhanced on RGD-PLGA sheets. These results suggest that biomimetic RGD-PLGA nanofiber sheets can be promising cell-adhesive substrates for application as tissue engineering scaffolds. PMID:26034884

  5. Electrospun aligned PLGA and PLGA/gelatin nanofibers embedded with silica nanoparticles for tissue engineering.

    PubMed

    Mehrasa, Mohammad; Asadollahi, Mohammad Ali; Ghaedi, Kamran; Salehi, Hossein; Arpanaei, Ayyoob

    2015-08-01

    Aligned poly lactic-co-glycolic acid (PLGA) and PLGA/gelatin nanofibrous scaffolds embedded with mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. The mean diameters of nanofibers were 641±24 nm for the pure PLGA scaffolds vs 418±85 nm and 267±58 nm for the PLGA/10 wt% MSNPs and the PLGA/gelatin/10 wt% MSNPs scaffolds, respectively. The contact angle measurement results (102°±6.7 for the pure PLGA scaffold vs 81°±6.8 and 18°±8.7 for the PLGA/10 wt% MSNPs and the PLGA/gelatin/10 wt% MSNPs scaffolds, respectively) revealed enhanced hydrophilicity of scaffolds upon incorporation of gelatin and MSNPs. Besides, embedding the scaffolds with MSNPs resulted in improved tensile mechanical properties. Cultivation of PC12 cells on the scaffolds demonstrated that introduction of MSNPs into PLGA and PLGA/gelatin matrices leads to the improved cell attachment and proliferation as well as long cellular processes. DAPI staining results indicated that cell proliferations on the PLGA/10 wt% MSNPs and the PLGA/gelatin/10 wt% MSNPs scaffolds were strikingly (nearly 2.5 and 3 folds, respectively) higher than that on the aligned pure PLGA scaffolds. These results suggest superior properties of silica nanoparticles-incorporated PLGA/gelatin eletrospun nanofibrous scaffolds for the stem cell culture and tissue engineering applications. PMID:26045092

  6. Assessment of PLGA-PEG-PLGA Copolymer Hydrogel for Sustained Drug Delivery in the Ear

    PubMed Central

    Feng, Liang; Ward, Jonette A.; Li, S. Kevin; Tolia, Gaurav; Hao, Jinsong; Choo, Daniel I.

    2014-01-01

    Temperature sensitive copolymer systems were previously studied using modified diffusion cells in vitro for intratympanic injection, and the PLGA-PEG-PLGA copolymer systems were found to provide sustained drug delivery for several days. The objectives of the present study were to assess the safety of PLGA-PEG-PLGA copolymers in intratympanic injection in guinea pigs in vivo and to determine the effects of additives glycerol and poloxamer in PLGA-PEG-PLGA upon drug release in the diffusion cells in vitro for sustained inner ear drug delivery. In the experiments, the safety of PLGA-PEG-PLGA copolymers to inner ear was evaluated using auditory brainstem response (ABR). The effects of the additives upon drug release from PLGA-PEG-PLGA hydrogel were investigated in the modified Franz diffusion cells in vitro with cidofovir as the model drug. The phase transition temperatures of the PLGA-PEG-PLGA copolymers in the presence of the additives were also determined. In the ABR safety study, the PLGA-PEG-PLGA copolymer alone did not affect hearing when delivered at 0.05-mL dose but caused hearing loss after 0.1-mL injection. In the drug release study, the incorporation of the bioadhesive additive, poloxamer, in the PLGA-PEG-PLGA formulations was found to decrease the rate of drug release whereas the increase in the concentration of the humectant additive, glycerol, provided the opposite effect. In summary, the PLGA-PEG-PLGA copolymer did not show toxicity to the inner ear at the 0.05-mL dose and could provide sustained release that could be controlled by using the additives for inner ear applications. PMID:24438444

  7. Random porous media flow on large 3-D grids: Numerics, performance, and application to homogenization

    SciTech Connect

    Ababou, R.

    1996-12-31

    Subsurface flow processes are inherently three-dimensional and heterogeneous over many scales. Taking this into account, for instance assuming random heterogeneity in 3-D space, puts heavy constraints on numerical models. An efficient numerical code has been developed for solving the porous media flow equations, appropriately generalized to account for 3-D, random-like heterogeneity. The code is based on implicit finite differences (or finite volumes), and uses specialized versions of pre-conditioned iterative solvers that take advantage of sparseness. With Diagonally Scaled Conjugate Gradients, in particular, large systems on the order of several million equations, with randomly variable coefficients, have been solved efficiently on Cray-2 and Cray-Y/MP8 machines, in serial mode as well as parallel mode (autotasking). The present work addresses, first, the numerical aspects and computational issues associated with detailed 3-D flow simulations, and secondly, presents a specific application related to the conductivity homogenization problem (identifying a macroscale conduction law, and an equivalent or effective conductivity). Analytical expressions of effective conductivities are compared with empirical values obtained from several large scale simulations conducted for single realizations of random porous media.

  8. Large-scale fabrication, 3D tomography, and lithium-ion battery application of porous silicon.

    PubMed

    Ge, Mingyuan; Lu, Yunhao; Ercius, Peter; Rong, Jiepeng; Fang, Xin; Mecklenburg, Matthew; Zhou, Chongwu

    2014-01-01

    Recently, silicon-based lithium-ion battery anodes have shown encouraging results, as they can offer high capacities and long cyclic lifetimes. The applications of this technology are largely impeded by the complicated and expensive approaches in producing Si with desired nanostructures. We report a cost-efficient method to produce nanoporous Si particles from metallurgical Si through ball-milling and inexpensive stain-etching. The porosity of porous Si is derived from particle's three-dimensional reconstructions by scanning transmission electron microscopy (STEM) tomography, which shows the particles' highly porous structure when etched under proper conditions. Nanoporous Si anodes with a reversible capacity of 2900 mAh/g was attained at a charging rate of 400 mA/g, and a stable capacity above 1100 mAh/g was retained for extended 600 cycles tested at 2000 mA/g. The synthetic route is low-cost and scalable for mass production, promising Si as a potential anode material for the next-generation lithium-ion batteries with enhanced capacity and energy density. PMID:24279924

  9. Bioinspired large-scale aligned porous materials assembled with dual temperature gradients

    PubMed Central

    Bai, Hao; Chen, Yuan; Delattre, Benjamin; Tomsia, Antoni P.; Ritchie, Robert O.

    2015-01-01

    Natural materials, such as bone, teeth, shells, and wood, exhibit outstanding properties despite being porous and made of weak constituents. Frequently, they represent a source of inspiration to design strong, tough, and lightweight materials. Although many techniques have been introduced to create such structures, a long-range order of the porosity as well as a precise control of the final architecture remain difficult to achieve. These limitations severely hinder the scale-up fabrication of layered structures aimed for larger applications. We report on a bidirectional freezing technique to successfully assemble ceramic particles into scaffolds with large-scale aligned, lamellar, porous, nacre-like structure and long-range order at the centimeter scale. This is achieved by modifying the cold finger with a polydimethylsiloxane (PDMS) wedge to control the nucleation and growth of ice crystals under dual temperature gradients. Our approach could provide an effective way of manufacturing novel bioinspired structural materials, in particular advanced materials such as composites, where a higher level of control over the structure is required. PMID:26824062

  10. Porous medium convection at large Rayleigh number: Studies of coherent structure, transport, and reduced dynamics

    NASA Astrophysics Data System (ADS)

    Wen, Baole

    Buoyancy-driven convection in fluid-saturated porous media is a key environmental and technological process, with applications ranging from carbon dioxide storage in terrestrial aquifers to the design of compact heat exchangers. Porous medium convection is also a paradigm for forced-dissipative infinite-dimensional dynamical systems, exhibiting spatiotemporally chaotic dynamics if not "true" turbulence. The objective of this dissertation research is to quantitatively characterize the dynamics and heat transport in two-dimensional horizontal and inclined porous medium convection between isothermal plane parallel boundaries at asymptotically large values of the Rayleigh number Ra by investigating the emergent, quasi-coherent flow. This investigation employs a complement of direct numerical simulations (DNS), secondary stability and dynamical systems theory, and variational analysis. The DNS confirm the remarkable tendency for the interior flow to self-organize into closely-spaced columnar plumes at sufficiently large Ra (up to Ra ≃ 105), with more complex spatiotemporal features being confined to boundary layers near the heated and cooled walls. The relatively simple form of the interior flow motivates investigation of unstable steady and time-periodic convective states at large Ra as a function of the domain aspect ratio L. To gain insight into the development of spatiotemporally chaotic convection, the (secondary) stability of these fully nonlinear states to small-amplitude disturbances is investigated using a spatial Floquet analysis. The results indicate that there exist two distinct modes of instability at large Ra: a bulk instability mode and a wall instability mode. The former usually is excited by long-wavelength disturbances and is generally much weaker than the latter. DNS, strategically initialized to investigate the fully nonlinear evolution of the most dangerous secondary instability modes, suggest that the (long time) mean inter-plume spacing in

  11. Strong infrared photoluminescence in highly porous layers of large faceted Si crystalline nanoparticles

    PubMed Central

    de Jong, E. M. L. D; Mannino, G.; Alberti, A.; Ruggeri, R.; Italia, M.; Zontone, F.; Chushkin, Y.; Pennisi, A. R.; Gregorkiewicz, T.; Faraci, G.

    2016-01-01

    Almost all physical processes in solids are influenced by phonons, but their effect is frequently overlooked. In this paper, we investigate the photoluminescence of large silicon nanoparticles (approximately 100 nm size, synthesized by chemical vapor deposition) in the visible to the infrared detection range. We find that upon increasing laser irradiance, an enormous photoluminescence emission band appears in the infrared. Its intensity exhibits a superlinear power dependence, increasing over four orders of magnitude in the investigated pump power range. Particles of different sizes as well as different shapes in porous layers are investigated. The results are discussed taking into account the efficient generation of phonons under high-power pumping, and the reduced capability, porosity dependent, of the silicon nanoparticles to exchange energy with each other and with the substrate. Our findings are relevant for heat management strategies in silicon. PMID:27216452

  12. Strong infrared photoluminescence in highly porous layers of large faceted Si crystalline nanoparticles.

    PubMed

    de Jong, E M L D; Mannino, G; Alberti, A; Ruggeri, R; Italia, M; Zontone, F; Chushkin, Y; Pennisi, A R; Gregorkiewicz, T; Faraci, G

    2016-01-01

    Almost all physical processes in solids are influenced by phonons, but their effect is frequently overlooked. In this paper, we investigate the photoluminescence of large silicon nanoparticles (approximately 100 nm size, synthesized by chemical vapor deposition) in the visible to the infrared detection range. We find that upon increasing laser irradiance, an enormous photoluminescence emission band appears in the infrared. Its intensity exhibits a superlinear power dependence, increasing over four orders of magnitude in the investigated pump power range. Particles of different sizes as well as different shapes in porous layers are investigated. The results are discussed taking into account the efficient generation of phonons under high-power pumping, and the reduced capability, porosity dependent, of the silicon nanoparticles to exchange energy with each other and with the substrate. Our findings are relevant for heat management strategies in silicon. PMID:27216452

  13. Strong infrared photoluminescence in highly porous layers of large faceted Si crystalline nanoparticles

    NASA Astrophysics Data System (ADS)

    de Jong, E. M. L. D.; Mannino, G.; Alberti, A.; Ruggeri, R.; Italia, M.; Zontone, F.; Chushkin, Y.; Pennisi, A. R.; Gregorkiewicz, T.; Faraci, G.

    2016-05-01

    Almost all physical processes in solids are influenced by phonons, but their effect is frequently overlooked. In this paper, we investigate the photoluminescence of large silicon nanoparticles (approximately 100 nm size, synthesized by chemical vapor deposition) in the visible to the infrared detection range. We find that upon increasing laser irradiance, an enormous photoluminescence emission band appears in the infrared. Its intensity exhibits a superlinear power dependence, increasing over four orders of magnitude in the investigated pump power range. Particles of different sizes as well as different shapes in porous layers are investigated. The results are discussed taking into account the efficient generation of phonons under high-power pumping, and the reduced capability, porosity dependent, of the silicon nanoparticles to exchange energy with each other and with the substrate. Our findings are relevant for heat management strategies in silicon.

  14. Transport of iron oxide nanoparticles in saturated porous media: a large-scale 3D study

    NASA Astrophysics Data System (ADS)

    Velimirovic, Milica; Schmid, Doris; Micić, Vesna; Miyajima, Kumiko; Klaas, Norbert; Braun, Jürgen; Bosch, Julian; Meckenstock, Rainer; von der Kammer, Frank; Hofmann, Thilo

    2016-04-01

    Iron oxide nanoparticles (FeOxNp) have a high potential as electron acceptor for in situ microbial oxidation of a wide range of recalcitrant groundwater contaminants (Bosch et al., 2010). Tosco et al. (2012) reported on high colloidal stability of FeOxNp dispersed in water, their low deposition behavior, and consequently improved transport in column experiments compared to extensively studied zerovalent iron nanoparticles. However, determination of FeOxNp transport behavior at the field-relevant conditions has not been done before. The present work is aimed to evaluate different complementary methods for detection, quantification and transport characterization of FeOxNp in a large-scale three-dimensional (3D) model aquifer. Prior to that, batch-scale experiments were performed in order to elucidate the potential of the selected methods for direct and indirect characterization and detection of FeOxNp. Direct methods included measurements of particle size distribution, particle concentration, Fetot content and turbidity of the FeOxNp suspension. Indirect methods included measurements of particle zeta potential, as well as TOC content and pH of the FeOxNp suspension. The results of the batch experiments indicated that the most suitable approach for detecting and quantifying FeOxNp was measuring Fetot content and suspension turbidity, as well as particle size determined using dynamic light scattering principle. These complementary methods were further applied in a large-scale 3D study containing medium and coarse sand in order to 1) assess the transport of FeOxNp in saturated porous medium during injection (VFeOx = 6 m3, cparticle = 20 g/L, Qinj = 0.7 m3/h), and 2) illustrate their spatial distribution after injection. The outcomes of the large-scale 3D study confirmed that FeOxNp transport can be successfully investigated applying complementary methods. Monitoring data including Fetot content, turbidity and particle size showed the transport of particles towards the

  15. Large-deformation and high-strength amorphous porous carbon nanospheres.

    PubMed

    Yang, Weizhu; Mao, Shimin; Yang, Jia; Shang, Tao; Song, Hongguang; Mabon, James; Swiech, Wacek; Vance, John R; Yue, Zhufeng; Dillon, Shen J; Xu, Hangxun; Xu, Baoxing

    2016-01-01

    Carbon is one of the most important materials extensively used in industry and our daily life. Crystalline carbon materials such as carbon nanotubes and graphene possess ultrahigh strength and toughness. In contrast, amorphous carbon is known to be very brittle and can sustain little compressive deformation. Inspired by biological shells and honeycomb-like cellular structures in nature, we introduce a class of hybrid structural designs and demonstrate that amorphous porous carbon nanospheres with a thin outer shell can simultaneously achieve high strength and sustain large deformation. The amorphous carbon nanospheres were synthesized via a low-cost, scalable and structure-controllable ultrasonic spray pyrolysis approach using energetic carbon precursors. In situ compression experiments on individual nanospheres show that the amorphous carbon nanospheres with an optimized structure can sustain beyond 50% compressive strain. Both experiments and finite element analyses reveal that the buckling deformation of the outer spherical shell dominates the improvement of strength while the collapse of inner nanoscale pores driven by twisting, rotation, buckling and bending of pore walls contributes to the large deformation. PMID:27072412

  16. Large-deformation and high-strength amorphous porous carbon nanospheres

    NASA Astrophysics Data System (ADS)

    Yang, Weizhu; Mao, Shimin; Yang, Jia; Shang, Tao; Song, Hongguang; Mabon, James; Swiech, Wacek; Vance, John R.; Yue, Zhufeng; Dillon, Shen J.; Xu, Hangxun; Xu, Baoxing

    2016-04-01

    Carbon is one of the most important materials extensively used in industry and our daily life. Crystalline carbon materials such as carbon nanotubes and graphene possess ultrahigh strength and toughness. In contrast, amorphous carbon is known to be very brittle and can sustain little compressive deformation. Inspired by biological shells and honeycomb-like cellular structures in nature, we introduce a class of hybrid structural designs and demonstrate that amorphous porous carbon nanospheres with a thin outer shell can simultaneously achieve high strength and sustain large deformation. The amorphous carbon nanospheres were synthesized via a low-cost, scalable and structure-controllable ultrasonic spray pyrolysis approach using energetic carbon precursors. In situ compression experiments on individual nanospheres show that the amorphous carbon nanospheres with an optimized structure can sustain beyond 50% compressive strain. Both experiments and finite element analyses reveal that the buckling deformation of the outer spherical shell dominates the improvement of strength while the collapse of inner nanoscale pores driven by twisting, rotation, buckling and bending of pore walls contributes to the large deformation.

  17. Large-deformation and high-strength amorphous porous carbon nanospheres

    PubMed Central

    Yang, Weizhu; Mao, Shimin; Yang, Jia; Shang, Tao; Song, Hongguang; Mabon, James; Swiech, Wacek; Vance, John R.; Yue, Zhufeng; Dillon, Shen J.; Xu, Hangxun; Xu, Baoxing

    2016-01-01

    Carbon is one of the most important materials extensively used in industry and our daily life. Crystalline carbon materials such as carbon nanotubes and graphene possess ultrahigh strength and toughness. In contrast, amorphous carbon is known to be very brittle and can sustain little compressive deformation. Inspired by biological shells and honeycomb-like cellular structures in nature, we introduce a class of hybrid structural designs and demonstrate that amorphous porous carbon nanospheres with a thin outer shell can simultaneously achieve high strength and sustain large deformation. The amorphous carbon nanospheres were synthesized via a low-cost, scalable and structure-controllable ultrasonic spray pyrolysis approach using energetic carbon precursors. In situ compression experiments on individual nanospheres show that the amorphous carbon nanospheres with an optimized structure can sustain beyond 50% compressive strain. Both experiments and finite element analyses reveal that the buckling deformation of the outer spherical shell dominates the improvement of strength while the collapse of inner nanoscale pores driven by twisting, rotation, buckling and bending of pore walls contributes to the large deformation. PMID:27072412

  18. Efficient Chemotherapy of Rat Glioblastoma Using Doxorubicin-Loaded PLGA Nanoparticles with Different Stabilizers

    PubMed Central

    Wohlfart, Stefanie; Khalansky, Alexander S.; Gelperina, Svetlana; Maksimenko, Olga; Bernreuther, Christian; Glatzel, Markus; Kreuter, Jörg

    2011-01-01

    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. PMID:21573151

  19. Exploring the dark side of MTT viability assay of cells cultured onto electrospun PLGA-based composite nanofibrous scaffolding materials.

    PubMed

    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. PMID:21647502

  20. Analysis of porosity distribution of large-scale porous media and their reconstruction by Langevin equation.

    PubMed

    Jafari, G Reza; Sahimi, Muhammad; Rasaei, M Reza; Tabar, M Reza Rahimi

    2011-02-01

    Several methods have been developed in the past for analyzing the porosity and other types of well logs for large-scale porous media, such as oil reservoirs, as well as their permeability distributions. We developed a method for analyzing the porosity logs ϕ(h) (where h is the depth) and similar data that are often nonstationary stochastic series. In this method one first generates a new stationary series based on the original data, and then analyzes the resulting series. It is shown that the series based on the successive increments of the log y(h)=ϕ(h+δh)-ϕ(h) is a stationary and Markov process, characterized by a Markov length scale h(M). The coefficients of the Kramers-Moyal expansion for the conditional probability density function (PDF) P(y,h|y(0),h(0)) are then computed. The resulting PDFs satisfy a Fokker-Planck (FP) equation, which is equivalent to a Langevin equation for y(h) that provides probabilistic predictions for the porosity logs. We also show that the Hurst exponent H of the self-affine distributions, which have been used in the past to describe the porosity logs, is directly linked to the drift and diffusion coefficients that we compute for the FP equation. Also computed are the level-crossing probabilities that provide insight into identifying the high or low values of the porosity beyond the depth interval in which the data have been measured. PMID:21405908

  1. Porous capsules with a large number of active sites: nucleation/growth under confined conditions.

    PubMed

    Garai, Somenath; Rubčić, Mirta; Bögge, Hartmut; Gouzerh, Pierre; Müller, Achim

    2015-03-01

    This work deals with the generation of large numbers of active sites and with ensuing nucleation/ growth processes on the inside wall of the cavity of porous nanocapsules of the type (pentagon)12(linker)30≡{(Mo(VI))Mo(VI)5}12{Mo(V)2(ligand)}30. A first example refers to sulfur dioxide capture through displacement of acetate ligands, while the grafted sulfite ligands are able to trap {MoO3H}(+) units thereby forming unusual {(O2SO)3MoO3H}(5-) assemblies. A second example relates to the generation of open coordination sites through release of carbon dioxide upon mild acidification of a carbonate-type capsule. When the reaction is performed in the presence of heptamolybdate ions, MoO4(2-) ions enter the cavity where they bind to the inside wall while forming new types of polyoxomolybdate architectures, thereby extending the molybdenum oxide skeleton of the capsule. Parallels can be drawn with Mo-storage proteins and supported MoO3 catalysts, making the results relevant to molybdenum biochemistry and to catalysis. PMID:25653204

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

    PubMed

    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. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25628059

  3. Bone regeneration using a freeze-dried 3D gradient-structured scaffold incorporating OIC-A006-loaded PLGA microspheres based on β-TCP/PLGA.

    PubMed

    Lin, Liulan; Gao, Haitao; Dong, Yangyang

    2015-01-01

    To reveal the latent capacity of the growth factor-like low-molecular-weight material OIC-A006 in tissue regeneration, it is essential to design a porous scaffold in order to concurrently accommodate cells and drug release in a controlled manner. Consequently, we fabricated poly (L-lactide-co-glycolide) (PLGA)-based microspheres with an OIC-A006-loaded gradient-structured β-TCP/PLGA scaffold by freeze-drying which could then be used for drug delivery and bone regeneration. The OIC-A006-loaded β-TCP/PLGA scaffold consisted of two parts which loaded different doses of OIC-A006 (6.25 μM, outside; 12.5 μM, inside). The porosity, compressive strength, SEM, degradation, and cumulative amount of drug release in vitro were characterized. Furthermore, we confirmed the incorporation of OIC-A006 into the PLGA-based microspheres within the scaffolds using UV-spectrophotometry, and the amount of drug remaining in the scaffold was maintained by 10 % for up to 28 days. The drug release was slower in the normal-structured drug-loaded scaffold. The OIC-A006 released action from the OIC-A006-loaded β-TCP/PLGA scaffold with ideal therapeutic prospects in tissue regeneration. In vitro cell culture results showed that this gradient-structured composite scaffold can induce the adhesion and proliferation of rat bone marrow stromal cells towards osteoblasts. These results showed that the newly developed OIC-A006-loaded scaffolds with gradient structure can be potentially applied to bone regeneration in clinical applications. PMID:25577209

  4. Enhanced mechanical performance and biological evaluation of a PLGA coated β-TCP composite scaffold for load-bearing applications

    PubMed Central

    Kang, Yunqing; Scully, Allison; Young, Daniel A; Kim, Sungwoo; Tsao, Helen; Sen, Milan; Yang, Yunzhi

    2011-01-01

    Porous β-tricalcium phosphate (β-TCP) has been used for bone repair and replacement in clinics due to its excellent biocompatibility, osteoconductivity, and biodegradability. However, the application of β-TCP has been limited by its brittleness. Here, we demonstrated that an interconnected porous β-TCP scaffold infiltrated with a thin layer of poly (lactic-co-glycolic acid) (PLGA) polymer showed improved mechanical performance compared to an uncoated β-TCP scaffold while retaining its excellent interconnectivity and biocompatibility. The infiltration of PLGA significantly increased the compressive strength of β-TCP scaffolds from 2.90 MPa to 4.19 MPa, bending strength from 1.46 MPa to 2.41 MPa, and toughness from 0.17 MPa to 1.44 MPa, while retaining an interconnected porous structure with a porosity of 80.65%. These remarkable improvements in the mechanical properties of PLGA-coated β-TCP scaffolds are due to the combination of the systematic coating of struts, interpenetrating structural characteristics, and crack bridging. The in vitro biological evaluation demonstrated that rat bone marrow stromal cells (rBMSCs) adhered well, proliferated, and expressed alkaline phosphatase (ALP) activity on both the PLGA-coated β-TCP and the β-TCP. These results suggest a new strategy for fabricating interconnected macroporous scaffolds with significantly enhanced mechanical strength for potential load-bearing bone tissue regeneration. PMID:21892228

  5. Initial Development and Characterization of PLGA Nanospheres Containing Ropivacaine

    PubMed Central

    Moraes, Carolina Morales; de Matos, Angélica Prado; de Lima, Renata; Rosa, André Henrique; de Paula, Eneida

    2008-01-01

    Local anesthetics are able to induce pain relief by binding to the sodium channels of excitable membranes, blocking the influx of sodium ions and the propagation of the nervous impulse. Ropivacaine (RVC) is an amino amide, enantiomerically pure, local anesthetic largely used in surgical procedures, which present physico-chemical and therapeutic properties similar to those of bupivacaine but decreased toxicity and motor blockade. The present work focuses on the preparation and characterization of nanospheres containing RVC; 0.25% and 0.50% RVC were incorporated in poly(d,l-lactide-co-glycolide (PLGA) 50:50) nanospheres (PLGA-NS), prepared by the nanoprecipitation method. Characterization of the nanospheres was conducted through the measurement of pH, particle size, and zeta potential. The pH of the nanoparticle system with RVC was 6.58. The average diameters of the RVC-containing nanospheres was 162.7 ± 1.5 nm, and their zeta potentials were negative, with values of about −10.81 ± 1.16 mV, which promoted good stabilization of the particles in solution. The cytotoxicity experiments show that RVC-loaded PLGA-NS generate a less toxic formulation as compared with plain RVC. Since this polymer drug-delivery system can effectively generate an even less toxic RVC formulation, this study is fundamental due to its characterization of a potentially novel pharmaceutical form for the treatment of pain with RVC. PMID:19669531

  6. On the blow-up rate of large solutions for a porous media logistic equation on radial domain

    NASA Astrophysics Data System (ADS)

    Feng, Peng

    2007-05-01

    In this paper we establish the exact blow-up rate of the large solutions of a porous media logistic equation. We consider the carrying capacity function with a general decay rate at the boundary instead of the usual cases when it can be approximated by a distant function. Obtaining the accurate blow-up rate allows us to establish the uniqueness result. Our result covers all previous results on the ball domain and can be further adapted in a more general domain.

  7. Effects of designed PLLA and 50:50PLGA scaffold architectures on bone formation in vivo

    PubMed Central

    Saito, Eiji; Liao, Elly E.; Hu, Wei-Wen; Krebsbach, Paul H.; Hollister, Scott J.

    2015-01-01

    Biodegradable porous scaffolds have been investigated as an alternative approach to current metal, ceramic, and polymer bone graft substitutes for lost or damaged bone tissues. Although there have been many studies investigating the effects of scaffold architecture on bone formation, many of these scaffolds were fabricated using conventional methods, such as salt leaching and phase separation, and were constructed without designed architecture. To study the effects of both designed architecture and material on bone formation, we designed and fabricated three types of porous scaffold architecture from two biodegradable materials, poly (L-lactic acid) (PLLA) and 50:50Poly (lactic-co-glycolic acid) (PLGA) using image based design and indirect solid freeform fabrication techniques, seeded them with bone morphogenic protein-7 transduced human gingival fibroblasts and implanted them subcutaneously into mice for 4 and 8 weeks. Micro-computed tomography data confirmed that the fabricated porous scaffolds replicated the designed architectures. Histological analysis revealed that the 50:50PLGA scaffolds degraded and did not maintain their architecture after 4 weeks. The PLLA scaffolds maintained their architecture at both time points and showed improved bone ingrowth which followed the internal architecture of the scaffolds. Mechanical properties of both PLLA and 50:50PLGA scaffolds decreased, but PLLA scaffolds maintained greater mechanical properties than 50:50PLGA after implantation. The increase of mineralized tissue helped to support mechanical properties of bone tissue and scaffold constructs from 4 to 8 weeks. The results indicated the importance of choice of scaffold materials and computationally designed scaffolds to control tissue formation and mechanical properties for desired bone tissue regeneration. PMID:22162220

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

    PubMed

    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. PMID:25175212

  9. Formulation of pyrazinamide-loaded large porous particles for the pulmonary route: avoiding crystal growth using excipients.

    PubMed

    Pham, Dinh-Duy; Fattal, Elias; Ghermani, Noureddine; Guiblin, Nicolas; Tsapis, Nicolas

    2013-10-01

    We have designed a novel formulation of pyrazinamide (PZA), an antitubercular drug within large porous particles intended for deep lung delivery. By simply spray-drying PZA, we have obtained crystalline particles of the δ polymorph of PZA that were unstable and not adapted for lung administration. Several excipients were added to the formulation to obtain stable large porous particles with a median size above 5 μm and a low tap density. Although a combination of leucine and ammonium bicarbonate (AB) allowed to reduce tap density and to increase particle size, these excipients were not sufficient to prevent crystallization and promote stability. The addition of hyaluronic acid (HA) in combination with dipalmitoylphosphatidylcholine (DPPC) allowed to obtain stable partially crystalline spherical particles adapted for deep lung delivery. The optimized formulation obtained by spray-drying 0.9 g/L PZA, 0.6g/L leucine, 0.2g/L HA, 0.3g/L DPPC and 2g/L AB in a mixture of ethanol-water (70/30, v/v) possesses a median size of 5.8 ± 0.1 μm and a tap density around 0.09 ± 0.01 g/cm(3). The estimated aerodynamic diameter is around 1.75 μm and the powder is stable for more than 4 weeks of storage. PMID:23603099

  10. A hybrid computational approach for the interactions between river flow and porous sediment bed covered with large roughness elements

    NASA Astrophysics Data System (ADS)

    Liu, X.

    2013-12-01

    In many natural and human-impacted rivers, the porous sediment beds are either fully or partially covered by large roughness elements, such as gravels and boulders. The existence of these large roughness elements, which are in direct contact with the turbulent river flow, changes the dynamics of mass and momentum transfer across the river bed. It also impacts the overall hydraulics in the river channel and over time, indirectly influences the geomorphological evolution of the system. Ideally, one should resolve each of these large roughness elements in a computational fluid model. This approach is apparently not feasible due to the prohibitive computational cost. Considering a typical river bed with armoring, the distribution of sediment sizes usually shows significant vertical variations. Computationally, it poses great challenge to resolve all the size scales. Similar multiscale problem exists in the much broader porous media flow field. To cope with this, we propose a hybrid computational approach where the large surface roughness elements are resolved using immersed boundary method and sediment layers below (usually finer) are modeled by adding extra drag terms in momentum equations. Large roughness elements are digitized using a 3D laser scanner. They are put into the computational domain using the collision detection and rigid body dynamics algorithms which guarantees realistic and physically-correct spatial arrangement of the surface elements. Simulation examples have shown the effectiveness of the hybrid approach which captures the effect of the surface roughness on the turbulent flow as well as the hyporheic flow pattern in and out of the bed.

  11. Peptide/protein vaccine delivery system based on PLGA particles.

    PubMed

    Allahyari, Mojgan; Mohit, Elham

    2016-03-01

    Due to the excellent safety profile of poly (D,L-lactide-co-glycolide) (PLGA) particles in human, and their biodegradability, many studies have focused on the application of PLGA particles as a controlled-release vaccine delivery system. Antigenic proteins/peptides can be encapsulated into or adsorbed to the surface of PLGA particles. The gradual release of loaded antigens from PLGA particles is necessary for the induction of efficient immunity. Various factors can influence protein release rates from PLGA particles, which can be defined intrinsic features of the polymer, particle characteristics as well as protein and environmental related factors. The use of PLGA particles encapsulating antigens of different diseases such as hepatitis B, tuberculosis, chlamydia, malaria, leishmania, toxoplasma and allergy antigens will be described herein. The co-delivery of antigens and immunostimulants (IS) with PLGA particles can prevent the systemic adverse effects of immunopotentiators and activate both dendritic cells (DCs) and natural killer (NKs) cells, consequently enhancing the therapeutic efficacy of antigen-loaded PLGA particles. We will review co-delivery of different TLR ligands with antigens in various models, highlighting the specific strengths and weaknesses of the system. Strategies to enhance the immunotherapeutic effect of DC-based vaccine using PLGA particles can be designed to target DCs by functionalized PLGA particle encapsulating siRNAs of suppressive gene, and disease specific antigens. Finally, specific examples of cellular targeting where decorating the surface of PLGA particles target orally administrated vaccine to M-cells will be highlighted. PMID:26513024

  12. Possibility for the development of cosmetics with PLGA nanospheres.

    PubMed

    Ito, Fuminori; Takahashi, Tadahito; Kanamura, Kiyoshi; Kawakami, Hiroyoshi

    2013-05-01

    The optimized preparation of Poly-(lactide-co-glycolic acid) (PLGA) nanospheres containing ubiquinone (UQ) for cosmetic products was pursued. By investigating various conditions for the preparation of UQ/PLGA nanospheres such as the molecular weight of PLGA, PLGA concentration, and UQ concentration, UQ/PLGA nanospheres with increased stability and slower drug release at a higher drug loading efficiency were prepared. Permeation tests on the prepared nanospheres using iontophoresis via electric dermal administration on membrane filters (200 nm pore size) and hairless mouse skin samples were also carried out. After iontophoresis, the nanospheres choked the membrane filter and remained on the horny layer of the hairless mouse skin, even after washing. Therefore, the prepared UQ/PLGA nanospheres and the established iontophoresis technique with the PLGA nanospheres in the present study can be applied to the future development of cosmetics. PMID:22725249

  13. Porous silicon Bloch surface and sub-surface wave structure for simultaneous detection of small and large molecules

    NASA Astrophysics Data System (ADS)

    Rodriguez, Gilberto A.; Lonai, John D.; Mernaugh, Raymond L.; Weiss, Sharon M.

    2014-08-01

    A porous silicon (PSi) Bloch surface wave (BSW) and Bloch sub-surface wave (BSSW) composite biosensor is designed and used for the size-selective detection of both small and large molecules. The BSW/BSSW structure consists of a periodic stack of high and low refractive index PSi layers and a reduced optical thickness surface layer that gives rise to a BSW with an evanescent tail that extends above the surface to enable the detection of large surface-bound molecules. Small molecules were detected in the sensor by the BSSW, which is a large electric field intensity spatially localized to a desired region of the Bragg mirror and is generated by the implementation of a step or gradient refractive index profile within the Bragg mirror. The step and gradient BSW/BSSW sensors are designed to maximize both resonance reflectance intensity and sensitivity to large molecules. Size-selective detection of large molecules including latex nanospheres and the M13KO7 bacteriophage as well as small chemical linker molecules is reported.

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

    PubMed

    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. PMID:26249587

  15. Enhancing the in vitro anti-cancer efficacy of artesunate by loading into poly-D,L-lactide-co-glycolide (PLGA) nanoparticles.

    PubMed

    Nguyen, Hanh Thuy; Tran, Tuan Hiep; Kim, Jong Oh; Yong, Chul Soon; Nguyen, Chien Ngoc

    2015-01-01

    Artesunate (ART)-a well-known anti-malarial agent is also known to have potential anti-proliferative activities but its instability, poor aqueous solubility, and lack of relevant studies have limited its application as an effective anti-cancer drug. To overcome these problems, ART was loaded in poly (lactic-co-glycolic) acid (PLGA) nanoparticles using oil/water emulsion evaporation method. PLGA nanoparticles with small particle size and high entrapment efficiency were obtained. The PLGA nanoparticles were optimized by evaluating the effects of several formulation parameters on physicochemical properties of nanoparticles. The in vitro cytotoxicity of blank PLGA, free ART, and ART-PLGA on 3 human cancer cell lines viz. A549, SCC-7, and MCF-7 was conducted using MTT assay. The particles showed nanometric size (~170 nm), large entrapment efficiency (up to 83.4%), and excellent stability (evaluated for 1 month) after lyophilization with 5% mannitol. ART was dispersed inside particle core allowing a sustained release up to 48 h. The in vitro cytotoxicity results demonstrated strong activity of ART against cancer cell lines. The ART-PLGA formulation significantly reduced cell viability than the free ART. The formulation of ART loaded PLGA nanoparticles supported a potential application of ART as an anticancer agent. PMID:24968925

  16. Exogenous phytoestrogenic molecule icaritin incorporated into a porous scaffold for enhancing bone defect repair.

    PubMed

    Wang, Xin-Luan; Xie, Xin-Hui; Zhang, Ge; Chen, Shi-Hui; Yao, Dong; He, Kai; Wang, Xiao-Hong; Yao, Xin-Sheng; Leng, Yang; Fung, Kwok-Pui; Leung, Kwok-Sui; Qin, Ling

    2013-01-01

    This study was designed to develop a bioactive scaffold to enhance bone defect repair in steroid-associated osteonecrosis (SAON). Icaritin, a metabolite of the herb Epimedium, has been identified as an angiogenic and osteogenic phytomolecule. Icaritin was homogenized into poly lactic-co-glycolic acid/tricalcium phosphate (PLGA/TCP) to form an icaritin-releasing porous composite scaffold (PLGA/TCP/icaritin) by fine-spinning technology. In vitro, high performance liquid chromatography was used to determine the release of icaritin during degradation of PLGA/TCP/icaritin. The osteogenic effects of PLGA/TCP/icaritin were evaluated using rat bone marrow mesenchymal stem cells (BMSCs). In vivo, the osteogenic effect of PLGA/TCP/icaritin was determined within a bone tunnel after core decompression in SAON rabbits and angiography within scaffolds was examined in rabbit muscle pouch model. In vitro study confirmed the sustainable release of icaritin from PLGA/TCP/icaritin with the bioactive scaffold promoting the proliferation and osteoblastic differentiation of rat BMSCs. In vivo study showed that PLGA/TCP/icaritin significantly promoted new bone formation within the bone defect after core decompression in SAON rabbits and enhanced neovascularization in the rabbit muscle pouch experiment. In conclusion, PLGA/TCP/icaritin is an innovative local delivery system that demonstrates sustainable release of osteogenic phytomolecule icaritin enhancing bone repair in an SAON rabbit model. The supplement of scaffold materials with bioactive phytomolecule(s) might improve treatment efficiency in challenging orthopedic conditions. PMID:22807243

  17. Influence of PEI as a Core Modifying Agent on PLGA Microspheres of PGE1, A Pulmonary Selective Vasodilator

    PubMed Central

    Gupta, Vivek; Ahsan, Fakhrul

    2011-01-01

    This study tests the hypothesis that large porous poly (lactic-co-glycolic acid) (PLGA) microparticles modified with polyethyleneimine (PEI) are viable carriers for pulmonary delivery of prostaglandin E1 (PGE1) used in the treatment of pulmonary arterial hypertension (PAH), a pulmonary vascular disorder. The particles were prepared by a double-emulsion solvent evaporation method with PEI-25 kDa in the internal aqueous phase to produce an osmotic pressure gradient. Polyvinyl alcohol (PVA) was used for external coating of the particles. The particles were examined for morphology, size, aerodynamic diameter, surface area, pore volume and in-vitro release profiles. Particles with optimal properties for inhalation were tested for in-vivo pulmonary absorption, metabolic stability in rat lung homogenates, and acute toxicity in rat bronchoalveolar lavage fluid and respiratory epithelial cells, Calu-3. The micromeritic data indicated that the PEI-modified particles of PGE1 are optimal for inhalation. Incorporation of PEI in the formulations resulted in an increased entrapment efficiency–83.26±3.04% for particles with 1% PVA and 95.48±0.46% for particles with 2% PVA. The amount of cumulative drug released into the simulated interstitial lung fluid was between 50.8±0.76% and 55.36±0.06%. A remarkable extension of the circulation half-life up to 6.0–6.5 hours was observed when the formulations were administered via the lungs. The metabolic stability and toxicity studies showed that the optimized formulations were stable at physiological conditions and relatively safe to the lungs and respiratory epithelium. Overall, this study demonstrates that large porous inhalable polymeric microparticles can be a feasible option for non-invasive and controlled release of PGE1 for treatment of PAH. PMID:21530623

  18. Quantitative multi-agent models for simulating protein release from PLGA bioerodible nano- and microspheres.

    PubMed

    Barat, Ana; Crane, Martin; Ruskin, Heather J

    2008-09-29

    Using poly(lactide-co-glycolide) (PLGA) particles for drug encapsulation and delivery has recently gained considerable popularity for a number of reasons. An advantage in one sense, but a drawback of PLGA use in another, is that drug delivery systems made of this material can provide a wide range of dissolution profiles, due to their internal structure and properties related to particles' manufacture. The advantages of enriching particulate drug design experimentation with computer models, are evident with simulations used to predict and optimize design, as well as indicate choice of best manufacturing parameters. In the present work, we seek to understand the phenomena observed for PLGA micro- and nanospheres, through Cellular Automata (CA) agent-based Monte Carlo (MC) models. Systems are studied both over large temporal scales (capturing slow erosion of PLGA) and for various spatial configurations (capturing initial as well as dynamic morphology). The major strength of this multi-agent approach is to observe dissolution directly, by monitoring the emergent behaviour: the dissolution profile manifested, as a sphere erodes. Different problematic aspects of the modelling process are discussed in details in this paper. The models were tested on experimental data from literature, demonstrating very good performance. Quantitative discussion is provided throughout the text in order to make a demonstration of the use in practice of the proposed model. PMID:18436414

  19. Strong and Tough Mineralized PLGA Nanofibers for Tendon-to-bone Scaffolds

    PubMed Central

    Kolluru, Pavan V.; Lipner, Justin; Liu, Wenying; Xia, Younan; Thomopoulos, Stavros; Genin, Guy M.; Chasiotis, Ioannis

    2013-01-01

    Engineering complex tissues such as the tendon-to-bone insertion sites require a strong and tough biomimetic material system that incorporates both mineralized and unmineralized tissues with different strengths and stiffnesses. However, increasing strength without degrading toughness is a fundamental challenge in materials science. Here, we demonstrate a promising nanofibrous polymer-hydroxyapatite system in which, a continuous fibrous network must function as a scaffold for both mineralized and unmineralized tissues. It is shown that the high toughness of this material system could be maintained without compromising on the strength with the addition of hydroxyapatite mineral. Individual electrospun poly(lactide-co-glycolide) (PLGA) nanofibers demonstrated outstanding strain-hardening behavior and ductility when stretched uniaxially, even in the presence of surface mineralization. This highly desirable hardening behavior which results in simultaneous nanofiber strengthening and toughening was shown to depend on the initial cross-sectional morphology of the PLGA nanofibers. For pristine PLGA nanofibers, it was shown that ellipsoidal cross-sections provide the largest increase in fiber strength by almost 200% compared to bulk PLGA. This exceptional strength accompanied by 100% elongation was shown to be retained for thin and strongly bonded conformal mineral coatings, which were preserved on the nanofiber surface even for such very large extensions. PMID:23933048

  20. Calcium phosphate cement scaffolds with PLGA fibers.

    PubMed

    Vasconcellos, Letícia Araújo; dos Santos, Luís Alberto

    2013-04-01

    The use of calcium phosphate-based biomaterials has revolutionized current orthopedics and dentistry in repairing damaged parts of the skeletal system. Among those biomaterials, the cement made of hydraulic grip calcium phosphate has attracted great interest due to its biocompatibility and hardening "in situ". However, these cements have low mechanical strength compared with the bones of the human body. In the present work, we have studied the attainment of calcium phosphate cement powders and their addition to poly (co-glycolide) (PLGA) fibers to increase mechanical properties of those cements. We have used a new method that obtains fibers by dripping different reagents. PLGA fibers were frozen after lyophilized. With this new method, which was patented, it was possible to obtain fibers and reinforcing matrix which furthered the increase of mechanical properties, thus allowing the attainment of more resistant materials. The obtained materials were used in the construction of composites and scaffolds for tissue growth, keeping a higher mechanical integrity. PMID:23827539

  1. Bone Regeneration from PLGA Micro-Nanoparticles.

    PubMed

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    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. PMID:26509156

  2. Bone Regeneration from PLGA Micro-Nanoparticles

    PubMed Central

    Ortega-Oller, Inmaculada; Padial-Molina, Miguel; Galindo-Moreno, Pablo; O'Valle, Francisco; Jódar-Reyes, Ana Belén; Peula-García, Jose Manuel

    2015-01-01

    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. PMID:26509156

  3. Large-eddy simulations of turbulent reacting flows in a chamber with gaseous ethylene injecting through the porous wall

    SciTech Connect

    Liou, T.M.; Lien, W.Y.; Hwang, P.W. . Dept of Power Mechanical Engineering)

    1994-12-01

    Large-eddy simulations were performed to study the turbulent reacting flows in a simulated solid-fuel combustion chamber. The time-dependent axisymmetric compressible conservation equations were solved directly without using subgrid-scale turbulence models. The combustion process considered was a one-step, irreversible, and infinitely fast chemical reaction and the pyrolizing solid fuel was simulated by gaseous ethylene injected through a porous wall for a practical range of fuel blowing velocity encountered in solid-fuel combustion chambers for the first time. The numerical code used the finite-volume technique which involved alternating in time the second-order, explicit MacCormack's and Godunov's methods. Characteristic-based boundary conditions were applied on inflow and outflow boundaries, which allow outlet boundary conditions to be nonzero gradients, and in turn, a practical length of computational domain to be realized. The effects of combustion on the large-scale unsteady flow structure and the mean flameholder recirculation zone were documented in terms of the density contours, vorticity dynamics, streamlines, mean-velocity vector fields, temperature profiles, flame position, and fuel blowing velocity. A comparison of the distributions of instantaneous and mean mass fractions of reactants shows that the present method appropriately reveals the effects of large-scale turbulent motions on combustion. Furthermore, the present large-eddy simulations have achieved a significant improvement in predicting the mean effective reattachment length over the previous calculations incorporating with turbulence models. The physical insight regarding the decrease of the mean effective reattachment length with combustion was also addressed.

  4. Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance

    PubMed Central

    Khalid, Syed; Cao, Chuanbao; Wang, Lin; Zhu, Youqi

    2016-01-01

    Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric & symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric & symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm−2 & 19.1 Wh Kg−1 and 194 mF cm−2 & 4.5 Wh Kg−1 (based on total mass loading of 6.25 & 6.0 mg) respectively at current density of 1 mA cm−2. The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices. PMID:26936283

  5. Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance

    NASA Astrophysics Data System (ADS)

    Khalid, Syed; Cao, Chuanbao; Wang, Lin; Zhu, Youqi

    2016-03-01

    Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric & symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric & symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm-2 & 19.1 Wh Kg-1 and 194 mF cm-2 & 4.5 Wh Kg-1 (based on total mass loading of 6.25 & 6.0 mg) respectively at current density of 1 mA cm-2. The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices.

  6. Microwave Assisted Synthesis of Porous NiCo2O4 Microspheres: Application as High Performance Asymmetric and Symmetric Supercapacitors with Large Areal Capacitance.

    PubMed

    Khalid, Syed; Cao, Chuanbao; Wang, Lin; Zhu, Youqi

    2016-01-01

    Large areal capacitance is essentially required to integrate the energy storage devices at the microscale electronic appliances. Energy storage devices based on metal oxides are mostly fabricated with low mass loading per unit area which demonstrated low areal capacitance. It is still a challenge to fabricate supercapacitor devices of porous metal oxides with large areal capacitance. Herein we report microwave method followed by a pyrolysis of the as-prepared precursor is used to synthesize porous nickel cobaltite microspheres. Porous NiCo2O4 microspheres are capable to deliver large areal capacitance due to their high specific surface area and small crystallite size. The facile strategy is successfully demonstrated to fabricate aqueous-based asymmetric &symmetric supercapacitor devices of porous NiCo2O4 microspheres with high mass loading of electroactive materials. The asymmetric &symmetric devices exhibit maximum areal capacitance and energy density of 380 mF cm(-2) &19.1 Wh Kg(-1) and 194 mF cm(-2) &4.5 Wh Kg(-1) (based on total mass loading of 6.25 &6.0 mg) respectively at current density of 1 mA cm(-2). The successful fabrication of symmetric device also indicates that NiCo2O4 can also be used as the negative electrode material for futuristic asymmetric devices. PMID:26936283

  7. Large scale flow visualization and anemometry applied to lab-on-a-chip models of porous media.

    PubMed

    Paiola, Johan; Auradou, Harold; Bodiguel, Hugues

    2016-08-01

    The following is a report on an experimental technique that allows one to quantify and map the velocity field with very high resolution and simple equipment in large 2D devices. Illumination through a grid is proposed to reinforce the contrast in the images and allow one to detect seeded particles that are pixel-sized or even smaller. The velocimetry technique that we have reported is based on the auto-correlation functions of the pixel intensity, which we have shown are directly related to the magnitude of the local average velocity. The characteristic time involved in the decorrelation of the signal is proportional to the tracer size and inversely proportional to the average velocity. We have reported on a detailed discussion about the optimization of relevant involved parameters, the spatial resolution and the accuracy of the method. The technique is then applied to a model porous medium made of a random channel network. We show that it is highly efficient to determine the magnitude of the flow in each of the channels of the network, opening the door to the fundamental study of the flows of complex fluids. The latter is illustrated with a yield stress fluid, in which the flow becomes highly heterogeneous at small flow rates. PMID:27349888

  8. Porous polymer monoliths with large surface area and functional groups prepared via copolymerization of protected functional monomers and hypercrosslinking.

    PubMed

    Maya, Fernando; Svec, Frantisek

    2013-11-22

    A new approach to the preparation of porous polymer monoliths possessing both large surface area and functional groups has been developed. The chloromethyl groups of poly(styrene-co-4-acetoxystyrene-co-vinylbenzyl chloride-co-divinylbenzene) monolith enable post-polymerization hypercrosslinking catalyzed by ferric chloride in dichloroethane leading to a multitude of small pores thus enhancing the surface area. The acetoxy functionalities are easily deprotected using hydrazine to produce polar phenolic hydroxyl groups, which would be difficult to obtain by direct copolymerization of hydroxyl-containing monomers. The hypercrosslinking and deprotection reactions as well as their sequence were studied in detail with bulk polymer monoliths containing up to 50% 4-acetoxystyrene and its progress monitored by infrared spectrometry and nitrogen adsorption/desorption measurements. No significant difference was found for both possible successions. All monoliths were also prepared in a capillary column format, then deprotected and hypercrosslinked. Capillary columns were tested for the separation of small molecules using reversed phase and normal phase chromatographic modes. For polymer monoliths containing 50% deprotected 4-acetoxystyrene, column efficiencies of 40,000 plates/m for benzene in reversed phase mode and 31,800 plates/m for nitrobenzene in normal phase mode, were obtained. The percentage of hydroxyl groups in the monoliths enables modulation of polarity of the stationary phase. They also represent functionalities that are potentially suitable for further modifications and formation of new types of stationary phases for liquid chromatography. PMID:23910448

  9. Hierarchically-Porous Carbon Derived from a Large-Scale Iron-based Organometallic Complex for Versatile Energy Storage.

    PubMed

    Fan, Chao-Ying; Li, Huan-Huan; Wang, Hai-Feng; Sun, Hai-Zhu; Wu, Xing-Long; Zhang, Jing-Ping

    2016-06-22

    Inspired by the preparation of the hierarchically-porous carbon (HPC) derived from metal organic frameworks (MOFs) for energy storage, in this work, a simple iron-based metal- organic complex (MOC), which was simpler and cheaper compared with the MOF, was selected to achieve versatile energy storage. The intertwined 1 D nanospindles and enriched-oxygen doping of the HPC was obtained after one-step carbonization of the MOC. When employed in lithium-ion batteries, the HPC exhibited reversible capacity of 778 mA h g(-1) after 60 cycles at 50 mA g(-1) . Moreover, the HPC maintained a capacity of 188 mA h g(-1) after 400 cycles at 100 mA g(-1) as the anode material in a sodium-ion battery. In addition, the HPC served as the cathode matrix for evaluation of a lithium-sulfur battery. The general preparation process of the HPC is commercial, which is responsible for the large-scale production for its practical application. PMID:27219476

  10. Controlling the degradation kinetics of porous iron by poly(lactic-co-glycolic acid) infiltration for use as temporary medical implants

    PubMed Central

    Yusop, Abdul Hakim Md; Daud, Nurizzati Mohd; Nur, Hadi; Kadir, Mohammed Rafiq Abdul; Hermawan, Hendra

    2015-01-01

    Iron and its alloy have been proposed as biodegradable metals for temporary medical implants. However, the formation of iron oxide and iron phosphate on their surface slows down their degradation kinetics in both in vitro and in vivo scenarios. This work presents new approach to tailor degradation behavior of iron by incorporating biodegradable polymers into the metal. Porous pure iron (PPI) was vacuum infiltrated by poly(lactic-co-glycolic acid) (PLGA) to form fully dense PLGA-infiltrated porous iron (PIPI) and dip coated into the PLGA to form partially dense PLGA-coated porous iron (PCPI). Results showed that compressive strength and toughness of the PIPI and PCPI were higher compared to PPI. A strong interfacial interaction was developed between the PLGA layer and the iron surface. Degradation rate of PIPI and PCPI was higher than that of PPI due to the effect of PLGA hydrolysis. The fast degradation of PIPI did not affect the viability of human fibroblast cells. Finally, this work discusses a degradation mechanism for PIPI and the effect of PLGA incorporation in accelerating the degradation of iron. PMID:26057073

  11. Controlling the degradation kinetics of porous iron by poly(lactic-co-glycolic acid) infiltration for use as temporary medical implants

    NASA Astrophysics Data System (ADS)

    Yusop, Abdul Hakim Md; Daud, Nurizzati Mohd; Nur, Hadi; Kadir, Mohammed Rafiq Abdul; Hermawan, Hendra

    2015-06-01

    Iron and its alloy have been proposed as biodegradable metals for temporary medical implants. However, the formation of iron oxide and iron phosphate on their surface slows down their degradation kinetics in both in vitro and in vivo scenarios. This work presents new approach to tailor degradation behavior of iron by incorporating biodegradable polymers into the metal. Porous pure iron (PPI) was vacuum infiltrated by poly(lactic-co-glycolic acid) (PLGA) to form fully dense PLGA-infiltrated porous iron (PIPI) and dip coated into the PLGA to form partially dense PLGA-coated porous iron (PCPI). Results showed that compressive strength and toughness of the PIPI and PCPI were higher compared to PPI. A strong interfacial interaction was developed between the PLGA layer and the iron surface. Degradation rate of PIPI and PCPI was higher than that of PPI due to the effect of PLGA hydrolysis. The fast degradation of PIPI did not affect the viability of human fibroblast cells. Finally, this work discusses a degradation mechanism for PIPI and the effect of PLGA incorporation in accelerating the degradation of iron.

  12. Controlling the degradation kinetics of porous iron by poly(lactic-co-glycolic acid) infiltration for use as temporary medical implants.

    PubMed

    Yusop, Abdul Hakim Md; Daud, Nurizzati Mohd; Nur, Hadi; Kadir, Mohammed Rafiq Abdul; Hermawan, Hendra

    2015-01-01

    Iron and its alloy have been proposed as biodegradable metals for temporary medical implants. However, the formation of iron oxide and iron phosphate on their surface slows down their degradation kinetics in both in vitro and in vivo scenarios. This work presents new approach to tailor degradation behavior of iron by incorporating biodegradable polymers into the metal. Porous pure iron (PPI) was vacuum infiltrated by poly(lactic-co-glycolic acid) (PLGA) to form fully dense PLGA-infiltrated porous iron (PIPI) and dip coated into the PLGA to form partially dense PLGA-coated porous iron (PCPI). Results showed that compressive strength and toughness of the PIPI and PCPI were higher compared to PPI. A strong interfacial interaction was developed between the PLGA layer and the iron surface. Degradation rate of PIPI and PCPI was higher than that of PPI due to the effect of PLGA hydrolysis. The fast degradation of PIPI did not affect the viability of human fibroblast cells. Finally, this work discusses a degradation mechanism for PIPI and the effect of PLGA incorporation in accelerating the degradation of iron. PMID:26057073

  13. Highly Ordered Porous Anodic Alumina with Large Diameter Pores Fabricated by an Improved Two-Step Anodization Approach.

    PubMed

    Li, Xiaohong; Ni, Siyu; Zhou, Xingping

    2015-02-01

    The aim of this study is to prepare highly ordered porous anodic alumina (PAA) with large pore sizes (> 200 nm) by an improved two-step anodization approach which combines the first hard anodization in oxalic acid-water-ethanol system and second mild anodization in phosphoric acid-water-ethanol system. The surface morphology and elemental composition of PAA are characterized by field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectrometer (EDS). The effects of matching of two-step anodizing voltages on the regularity of pore arrangement is evaluated and discussed. Moreover, the pore formation mechanism is also discussed. The results show that the nanopore arrays on all the PAA samples are in a highly regular arrangement and the pore size is adjustable in the range of 200-300 nm. EDS analysis suggests that the main elements of the as-prepared PAA are oxygen, aluminum and a small amount of phosphorus. Furthermore, the voltage in the first anodization must match well with that in the second anodization, which has significant influence on the PAA regularity. The addition of ethanol to the electrolytes effectively accelerates the diffusion of the heat that evolves from the sample, and decreases the steady current to keep the steady growth of PAA film. The improved two-step anodization approach in this study breaks through the restriction of small pore size in oxalic acid and overcomes the drawbacks of irregular pore morphology in phosphoric acid, and is an efficient way to fabricate large diameter ordered PAA. PMID:26353721

  14. Large surface area ordered porous carbons via nanocasting zeolite 10X and high performance for hydrogen storage application.

    PubMed

    Cai, Jinjun; Li, Liangjun; Lv, Xiaoxia; Yang, Chunpeng; Zhao, Xuebo

    2014-01-01

    We report the preparation of ordered porous carbons for the first time via nanocasting zeolite 10X with an aim to evaluate their potential application for hydrogen storage. The synthesized carbons exhibit large Brunauer-Emmett-Teller surface areas in the 1300-3331 m(2)/g range and pore volumes up to 1.94 cm(3)/g with a pore size centered at 1.2 nm. The effects of different synthesis processes with pyrolysis temperature varied in the 600-800 °C range on the surface areas, and pore structures of carbons were explored. During the carbonization process, carbons derived from the liquid-gas two-step routes at around 700 °C are nongraphitic and retain the particle morphology of 10X zeolite, whereas the higher pyrolysis temperature results in some graphitic domains and hollow-shell morphologies. In contrast, carbons derived from the direct acetylene infiltration process have some incident nanoribbon or nanofiber morphologies. A considerable hydrogen storage capacity of 6.1 wt % at 77 K and 20 bar was attained for the carbon with the surface area up to 3331 m(2)/g, one of the top-ranked capacities ever observed for large surface area adsorbents, demonstrating their potential uses for compacting gaseous fuels of hydrogen. The hydrogen capacity is comparable to those of previously reported values on other kinds of carbon-based materials and highly dependent on the surface area and micropore volume of carbons related to the optimum pore size, therefore providing guidance for the further search of nanoporous materials for hydrogen storage. PMID:24344972

  15. Incorporation of sol-gel bioactive glass into PLGA improves mechanical properties and bioactivity of composite scaffolds and results in their osteoinductive properties.

    PubMed

    Filipowska, J; Pawlik, J; Cholewa-Kowalska, K; Tylko, G; Pamula, E; Niedzwiedzki, L; Szuta, M; Laczka, M; Osyczka, A M

    2014-12-01

    In this study, 3D porous bioactive composite scaffolds were produced and evaluated for their physico-chemical and biological properties. Polymer poly-L-lactide-co-glycolide (PLGA) matrix scaffolds were modified with sol-gel-derived bioactive glasses (SBGs) of CaO-SiO2-P2O5 systems. We hypothesized that SBG incorporation into PLGA matrix would improve the chemical and biological activity of composite materials as well as their mechanical properties. We applied two bioactive glasses, designated as S2 or A2, differing in the content of SiO2 and CaO (i.e. 80 mol% SiO2, 16 mol% CaO for S2 and 40 mol% SiO2, 52 mol% CaO for A2). The composites were characterized for their porosity, bioactivity, microstructure and mechanical properties. The osteoinductive properties of these composites were evaluated in human bone marrow stromal cell (hBMSC) cultures grown in either standard growth medium or treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) or dexamethasone (Dex). After incubation in simulated body fluid, calcium phosphate precipitates formed inside the pores of both A2-PLGA and S2-PLGA scaffolds. The compressive strength of the latter was increased slightly compared to PLGA. Both composites promoted superior hBMSC attachment to the material surface and stimulated the expression of several osteogenic markers in hBMSC compared to cells grown on unmodified PLGA. There were also marked differences in the response of hBMSC to composite scaffolds, depending on chemical compositions of the scaffolds and culture treatments. Compared to silica-rich S2-PLGA, hBMSC grown on calcium-rich A2-PLGA were overall less responsive to rhBMP-2 or Dex and the osteoinductive properties of these A2-PLGA scaffolds seemed partially dependent on their ability to induce BMP signaling in untreated hBMSC. Thus, beyond the ability of currently studied composites to enhance hBMSC osteogenesis, it may become possible to modulate the osteogenic response of hBMSC, depending on the

  16. Poly(lactide-co-glycolide) porous scaffolds for tissue engineering and regenerative medicine

    PubMed Central

    Pan, Zhen; Ding, Jiandong

    2012-01-01

    Porous scaffolds fabricated from biocompatible and biodegradable polymers play vital roles in tissue engineering and regenerative medicine. Among various scaffold matrix materials, poly(lactide-co-glycolide) (PLGA) is a very popular and an important biodegradable polyester owing to its tunable degradation rates, good mechanical properties and processibility, etc. This review highlights the progress on PLGA scaffolds. In the latest decade, some facile fabrication approaches at room temperature were put forward; more appropriate pore structures were designed and achieved; the mechanical properties were investigated both for dry and wet scaffolds; a long time biodegradation of the PLGA scaffold was observed and a three-stage model was established; even the effects of pore size and porosity on in vitro biodegradation were revealed; the PLGA scaffolds have also been implanted into animals, and some tissues have been regenerated in vivo after loading cells including stem cells. PMID:23741612

  17. Factors affecting the loading efficiency of water-soluble drugs in PLGA microspheres.

    PubMed

    Ito, Fuminori; Fujimori, Hiroyuki; Makino, Kimiko

    2008-01-15

    Poly(lactide-co-glycolide), PLGA, microspheres containing blue dextran as a hydrophilic model drug were prepared by a solvent evaporation method from w/o/w emulsions using a micro homogenizer. Effects of surfactant concentration in oil phase, stirring time period and stirring rate in the preparation procedure of primary emulsion (w/o) upon drug-loading efficiency were evaluated. Stirring rate during preparation of primary emulsion and surfactant concentration in oil phase affected drug-loading efficiency and the particle size of primary emulsion. Microspheres having the higher drug-loading efficiency were obtained when size differences between the primary emulsions and the secondary ones were large. That is, when the diameter of the primary emulsion is much smaller than that of the secondary emulsion, PLGA microspheres with high-loading efficiency of blue dextran were obtained. PMID:17719753

  18. Perturbation solutions for a micropolar fluid flow in a semi-infinite expanding or contracting pipe with large injection or suction through porous wall

    NASA Astrophysics Data System (ADS)

    Si, Xinhui; Yuan, Lili; Cao, Limei; Zheng, Liancun; Shen, Yanan; Li, Lin

    2016-07-01

    We investigate an unsteady incompressible laminar micropolar flow in a semi-infinite porous pipe with large injection or suction through a deforming pipe wall. Using suitable similarity transformations, the governing partial differential are transformed into a coupled nonlinear singular boundary value problem. For large injection, the asymptotic solutions are constructed using the Lighthill method, which eliminates singularity of solution in the high order derivative. For large suction, a series expansion matching method is used. Analytical solutions are validated against the numerical solutions obtained by Bvp4c.

  19. Surface characteristics of PLA and PLGA films

    NASA Astrophysics Data System (ADS)

    Paragkumar N, Thanki; Edith, Dellacherie; Six, Jean-Luc

    2006-12-01

    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 ˜15 μm 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.

  20. In vitro degradation and release characteristics of spin coated thin films of PLGA with a “breath figure” morphology

    PubMed Central

    Ponnusamy, Thiruselvam; Lawson, Louise B.; Freytag, Lucy C.; Blake, Diane A.; Ayyala, Ramesh S.; John, Vijay T.

    2012-01-01

    Poly (lactic-co-glycolic acid) (PLGA) coatings on implant materials are widely used in controlled drug delivery applications. Typically, such coatings are made with non-porous films. Here, we have synthesized a thin PLGA film coating with a highly ordered microporous structure using a simple and inexpensive water templating “breath figure” technique. A single stage process combining spin coating and breath figure process was used to obtain drug incorporated porous thin films. The films were characterized by scanning electron microscope (SEM) to observe the surface and bulk features of porosity and also, degradation pattern of the films. Moreover, the effect of addition of small amount of poly (ethylene glycol) (PEG) into PLGA was characterized. SEM analysis revealed an ordered array of ~2 µm sized pores on the surface with the average film thickness measured to be 20 µm. The incorporation of hydrophilic poly (ethylene glycol) (PEG) enhances pore structure uniformity and facilitates ingress of water into the structure. A five week in vitro degradation study showed a gradual deterioration of the breath figure pores. During the course of degradation, the surface pore structure deteriorates to initially flatten the surface. This is followed by the formation of new pinprick pores that eventually grow into a macroporous film prior to film breakup. Salicylic acid (highly water soluble) and Ibuprofen (sparingly water soluble) were chosen as model drug compounds to characterize release rates, which are higher in films of the breath figure morphology rather than in non-porous films. The results are of significance in the design of biodegradable films used as coatings to modulate delivery. PMID:23507805

  1. Resolving the Effects of Aperture and Volume Restriction of the Flow by Semi-Porous Barriers Using Large-Eddy Simulations

    NASA Astrophysics Data System (ADS)

    Chatziefstratiou, Efthalia K.; Velissariou, Vasilia; Bohrer, Gil

    2014-09-01

    The Regional Atmospheric Modelling System (RAMS)-based Forest Large-Eddy Simulation (RAFLES) model is used to simulate the effects of large rectangular prism-shaped semi-porous barriers of varying densities under neutrally buoyant conditions. RAFLES model resolves flows inside and above forested canopies and other semi-porous barriers, and it accounts for barrier-induced drag on the flow and surface flux exchange between the barrier and the air. Unlike most other models, RAFLES model also accounts for the barrier-induced volume and aperture restriction via a modified version of the cut-cell coordinate system. We explicitly tested the effects of the numerical representation of volume restriction, independent of the effects of the drag, by comparing drag-only simulations (where we prescribed neither volume nor aperture restrictions to the flow), restriction-only simulations (where we prescribed no drag), and control simulations where both drag and volume plus aperture restrictions were included. Previous modelling and empirical work have revealed the development of important areas of increased uplift upwind of forward-facing steps, and recirculation zones downwind of backward-facing steps. Our simulations show that representation of the effects of the volume and aperture restriction due to the presence of semi-porous barriers leads to differences in the strengths and locations of increased-updraft and recirculation zones, and the length and strength of impact and adjustment zones when compared to simulation solutions with a drag-only representation. These are mostly driven by differences to the momentum budget of the streamwise wind velocity by resolved turbulence and pressure gradient fields around the front and back edges of the barrier. We propose that volume plus aperture restriction is an important component of the flow system in semi-porous environments such as forests and cities and should be considered by large-eddy simulation (LES).

  2. Mechanistic studies for monodisperse exenatide-loaded PLGA microspheres prepared by different methods based on SPG membrane emulsification.

    PubMed

    Qi, Feng; Wu, Jie; Yang, Tingyuan; Ma, Guanghui; Su, Zhiguo

    2014-10-01

    Poly(DL-lactic-co-glycolic acid) (PLGA) microspheres have been widely prepared by many methods, including solvent evaporation, solvent extraction and the co-solvent method. However, very few studies have compared the properties of microspheres fabricated by these methods. This is partly because the broad size distribution of the resultant particles severely complicates the analysis and affects the reliability of the comparison. To this end, uniform-sized PLGA microspheres have been prepared by Shirasu porous glass premix membrane emulsification and used to encapsulate exenatide, a drug for treating Type 2 diabetes. Based on this technique, the influences on the properties of microspheres fabricated by the aforementioned three methods were intensively investigated, including in vitro release, degradation and pharmacology. We found that these microspheres presented totally different release behaviors in vitro and in vivo, but exhibited a similar trend of PLGA degradation. Moreover, the internal structural evolution visually demonstrated these release behaviors. We selected for further examination the microsphere prepared by solvent evaporation because of its constant release rate, and explored its pharmacodynamics, histology, etc., in more detail. This microsphere when injected once showed equivalent efficacy to that of twice-daily injections of exenatide with no inflammatory response. PMID:24952071

  3. Cellular uptake, antioxidant and antiproliferative activity of entrapped α-tocopherol and γ-tocotrienol in poly (lactic-co-glycolic) acid (PLGA) and chitosan covered PLGA nanoparticles (PLGA-Chi).

    PubMed

    Alqahtani, Saeed; Simon, Lacey; Astete, Carlos E; Alayoubi, Alaadin; Sylvester, Paul W; Nazzal, Sami; Shen, Yixiao; Xu, Zhimin; Kaddoumi, Amal; Sabliov, Cristina M

    2015-05-01

    The aim of this study was to formulate and characterize α-tocopherol (α-T) and tocotrienol-rich fraction (TRF) entrapped in poly (lactide-co-glycolide) (PLGA) and chitosan covered PLGA (PLGA-Chi) based nanoparticles. The resultant nanoparticles were characterized and the effect of nanoparticles entrapment on the cellular uptake, antioxidant, and antiproliferative activity of α-T and TRF were tested. In vitro uptake studies in Caco2 cells showed that PLGA and PLGA-Chi nanoparticles displayed a greater enhancement in the cellular uptake of α-T and TRF when compared with the control without causing toxicity to the cells (p<0.0001). Furthermore, the cellular internalization of both PLGA and PLGA-Chi nanoparticles labeled with FITC was investigated by fluorescence microscopy; both types of nanoparticles were able to get internalized into the cells with reasonable amounts. However, PLGA-Chi nanoparticles showed significantly higher (3.5-fold) cellular uptake compared to PLGA nanoparticles. The antioxidant activity studies demonstrated that entrapment of α-T and TRF in PLGA and PLGA-Chi nanoparticles exhibited greater ability in inhibiting cholesterol oxidation at 48 h compared to the control. In vitro antiproliferative studies confirmed marked cytotoxicity of TRF on MCF-7 and MDA-MB-231 cell lines when delivered by PLGA and PLGA-Chi nanoparticles after 48 h incubation compared to control. In summary, PLGA and PLGA-Chi nanoparticles may be considered as an attractive and promising approach to enhance the bioavailability and activity of poorly water soluble compounds such as α-tocopherol and tocotrienols. PMID:25622049

  4. Size-Dependent Effect of Prochloraz-Loaded mPEG-PLGA Micro- and Nanoparticles.

    PubMed

    Zhang, Jiakun; Zhao, Caiyan; Liu, Yajing; Cao, Lidong; Wu, Yan; Huang, Qiliang

    2016-06-01

    As a controlled release formulation, polymer-based pesticide particle, provide an effective approach to achieve the target crop sites of increasing the pesticide utilization and reducing side effects. The particle size impacts on the dispersibility, pesticide loading content, control effect, etc. It is essential to investigate size-dependent effect. Hence, size-dependent effect of polymer-based pesticide particle was studied systematically in this paper. The biodegradable mPEG-PLGA copolymer with suitable molecular weight (45 KDa) was selected as carrier. Prochloraz-loaded mPEG-PLGA particles with different sizes (190.7 nm, 708.8 nm and 3980.0 nm) were constructed by emulsion/solvent evaporation method based on the same carrier. With the constant mass ratio of copolymer/prochloraz, as the particle size became large, the prochloraz loading content increased, and prochloraz released speed decreased. All prochloraz-loaded particles showed a sustained-release process and sustained impact against the Fusarium graminearum. Among the prochloraz-loaded mPEG-PLGA particles, the 190.7 nm particles exhibited the best germicidal efficacy in two weeks. Hence, the smaller size particles hold a better control efficacy in short time. PMID:27427695

  5. Immunogenicity of single-dose diphtheria vaccines based on PLA/PLGA microspheres in guinea pigs.

    PubMed

    Johansen, P; Moon, L; Tamber, H; Merkle, H P; Gander, B; Sesardic, D

    1999-09-01

    Biodegradable polyester microspheres (MS) have shown potential for single-dose vaccines. This study examined the immunogenicity of diphtheria toxoid (Dtxd) microencapsulated in different types of poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) MS prepared by the methods of spray-drying and coacervation. We investigated the influence of polymer type (PLGA 50:50 of low M(w); PLA of high M(w); end-group stearylated PLAs of low M(w)) and co-encapsulated excipients (BSA and/or trehalose) on Dtxd content, in vitro release and immunogenicity in guinea pigs. The co-encapsulated trehalose lowered the Dtxd entrapment efficiency in the spray-dried particles from 75 to 56%, whereas albumin alone had no effect in the spray-drying, but improved the encapsulation in the coacervation process. With the hydrophobic, end-group stearylated PLAs, Dtxd could only be encapsulated in the presence of albumin. Guinea pigs immunised with Dtxd-MS made with the relatively hydrophilic PLGA 50:50 exhibited specific and sustained antibody responses over 40 weeks, comparable to the responses to alum-adjuvanted toxoid. In contrast, undetectable or very low antibody responses were determined after immunisation with MS made with hydrophobic polymers. Surprisingly, large (15-60 microm) and small (1-5 microm) MS gave comparable primary antibody responses. In conclusion, the data presented confirm the feasibility of MS vaccines to induce strong, long-lasting protective antibody responses after a single immunisation. PMID:10506644

  6. Reconstructing jaw defects with MSCs and PLGA-encapsulated growth factors.

    PubMed

    Tee, Boon Ching; Desai, Kashappa Goud H; Kennedy, Kelly S; Sonnichsen, Brittany; Kim, Do-Gyoon; Fields, Henry W; Mallery, Susan R; Schwendeman, Steven P; Sun, Zongyang

    2016-01-01

    Cell and growth factor-based tissue engineering has shown great potentials for skeletal regeneration. This study tested its feasibility in reconstructing large mandibular defects and compared the efficacy of varied construction materials and sealing methods. Bilateral mandibular critical-size (5-cm(3)) defects were created on six 4-month-old domestic pigs, and grafted with β-tricalcium phosphate (βTCP) only (Group-A), βTCP with autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) (Group-B), and βTCP with BM-MSCs and biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres containing bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) (Group-C). The buccal sides of Groups-B/-C were either sealed by fibrin sealant or by a biodegradable PLGA barrier membrane before soft-tissue closure. Computed tomography (CT), microCT and histology analyses were performed 12 weeks postoperatively. In vitro data demonstrated that BM-MSCs, with MSC properties confirmed, remained vital after integration with βTCP; and PLGA microspheres exhibited an initial burst followed by slow and continuous release of growth factors over a period of 28 days. In vivo data demonstrated that Group-B/-C sites had significantly greater gap obliteration, higher tissue mineral densities and more residual βTCP granules (p<0.05, Kruskal-Wallis tests). Qualitatively, Group-B/-C defect sites had started remodeling while Group-A sites were mainly forming new bone to bridge the gaps. Furthermore, βTCP degradation was not mediated by macrophages or osteoclasts, and was significantly slowed down by sealing the defects with barrier membrane. Combined, these data present a promising formulation composed of βTCP granules, autologous MSCs, controlled-release growth factors and biodegradable PLGA barrier membrane for the reconstruction of critical-size mandibular defects. PMID:27398152

  7. Reconstructing jaw defects with MSCs and PLGA-encapsulated growth factors

    PubMed Central

    Tee, Boon Ching; Desai, Kashappa Goud H; Kennedy, Kelly S; Sonnichsen, Brittany; Kim, Do-Gyoon; Fields, Henry W; Mallery, Susan R; Schwendeman, Steven P; Sun, Zongyang

    2016-01-01

    Cell and growth factor-based tissue engineering has shown great potentials for skeletal regeneration. This study tested its feasibility in reconstructing large mandibular defects and compared the efficacy of varied construction materials and sealing methods. Bilateral mandibular critical-size (5-cm3) defects were created on six 4-month-old domestic pigs, and grafted with β-tricalcium phosphate (βTCP) only (Group-A), βTCP with autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) (Group-B), and βTCP with BM-MSCs and biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres containing bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) (Group-C). The buccal sides of Groups-B/-C were either sealed by fibrin sealant or by a biodegradable PLGA barrier membrane before soft-tissue closure. Computed tomography (CT), microCT and histology analyses were performed 12 weeks postoperatively. In vitro data demonstrated that BM-MSCs, with MSC properties confirmed, remained vital after integration with βTCP; and PLGA microspheres exhibited an initial burst followed by slow and continuous release of growth factors over a period of 28 days. In vivo data demonstrated that Group-B/-C sites had significantly greater gap obliteration, higher tissue mineral densities and more residual βTCP granules (p<0.05, Kruskal-Wallis tests). Qualitatively, Group-B/-C defect sites had started remodeling while Group-A sites were mainly forming new bone to bridge the gaps. Furthermore, βTCP degradation was not mediated by macrophages or osteoclasts, and was significantly slowed down by sealing the defects with barrier membrane. Combined, these data present a promising formulation composed of βTCP granules, autologous MSCs, controlled-release growth factors and biodegradable PLGA barrier membrane for the reconstruction of critical-size mandibular defects. PMID:27398152

  8. Use of microseismicity for determining the structure of the fracture network of large-scale porous media

    NASA Astrophysics Data System (ADS)

    Tafti, Tayeb A.; Sahimi, Muhammad; Aminzadeh, Fred; Sammis, Charles G.

    2013-03-01

    We show that microseismic events—earthquakes with small magnitudes—can be fruitfully used to gain insight into the properties of the fracture network of large-scale porous media, such as oil, gas, and geothermal reservoirs. As an example, we analyze extensive data for the Geysers geothermal field in northeast California. Injection of cold water into the reservoir to produce steam leads to microseismic events. It is demonstrated that the analysis can also lead to insight into whether the fractures are of tectonic type or induced by injection of cold water. To demonstrate this we estimate, using the catalogue of the microseismic events, the fractal dimension Df of the spatial distribution of hypocenters of the events in three seismic clusters associated with the injection of cold water into the field, as well as the b values in the Gutenberg-Richter frequency-magnitude distribution. The fractal dimensions are all in a narrow range centered around Df≃2.57±0.06, comparable to the measured fractal dimension of fracture sets in the greywacke reservoir rock. For most cases the b values are about b≃1.3±0.1, consistent with the Aki relation, Df=2b. Both Df and b are significantly higher than those commonly observed for regional tectonic seismicity or aftershock sequences for which Df≈2 and b≈1 are typical. Our results do not imply that no tectonic triggering exists in the reservoir, but rather that the overpressure allows the activation of less favorably oriented fractures that produce an increase in both b and Df. The estimate Df≈2 for tectonic seismicity has been interpreted as indicating that most tectonic events occur on the subset of near-vertical faults—because they have lower normal stress—or that they occur on the backbone of the fracture and fault network, the multiply connected part of the network that enables finite shear strain. Our results lend support to the latter. The results that the entire fracture network, and not just its backbone, is

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

    NASA Astrophysics Data System (ADS)

    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.

  10. Biomimetic mucin modified PLGA nanoparticles for enhanced blood compatibility.

    PubMed

    Thasneem, Y M; Rekha, M R; Sajeesh, S; Sharma, Chandra P

    2013-11-01

    Efforts to develop long circulating polymeric nanoparticles have propelled many strategies in nanoparticle surface modification to bypass immune surveillance and systemic clearance. In this context, our present study reports on the preparation and evaluation of mucin functionalized poly lactic-co-glycolic acid (PLGA) nanoparticles as hemocompatible, cell penetrating nanoparticulate drug delivery system. Amino groups of mucin were conjugated to the terminal carboxylic acid groups on PLGA to be followed by nanoparticle synthesis via standard solvent evaporation technique. Detailed in vitro experiments were performed to illustrate the significance of alternating copolymer structured mucin modified PLGA nanoparticles in terms of enhanced hemocompatibility and cellular uptake. Mucylation proved promising in controlling PLGA nanoparticle- interaction with plasma proteins (opsonins) and blood components via hemolysis, thrombogenecity and complement activation. Besides hemocompatibility, the modified and unmodified nanoparticles were also found to be cytocompatible with L929 and C6 cell lines. The fluorescent and confocal image analysis evaluated the extent of cellular uptake of nanoparticles into C6 cells. Specifically the combination of stealth properties and cellular internalization capacity of mucin modified PLGA nanoparticle (PLGA-Mucin) lead us to propose it as a safe, efficient and multifunctional nanoplatform for disease specific intravenous drug delivery applications as far as in vitro experiments are concerned. PMID:23978287

  11. Systemic delivery to central nervous system by engineered PLGA nanoparticles.

    PubMed

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  12. Systemic delivery to central nervous system by engineered PLGA nanoparticles

    PubMed Central

    Cai, Qiang; Wang, Long; Deng, Gang; Liu, Junhui; Chen, Qianxue; Chen, Zhibiao

    2016-01-01

    Neurological disorders are an important global public health problem, but pharmaceutical treatments are limited due to drug access to the central nervous system being restricted by the blood-brain barrier (BBB). Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are one of the most promising drug and gene delivery systems for crossing the BBB. While these systems offer great promise, PLGA NPs also have some intrinsic drawbacks and require further engineering for clinical and research applications. Multiple strategies have been developed for using PLGA NPs to deliver compounds across the BBB. We classify these strategies into three categories according to the adaptations made to the PLGA NPs (1) to facilitate travel from the injection site (pre-transcytosis strategies); (2) to enhance passage across the brain endothelial cells (BBB transcytosis strategies) and (3) to achieve targeting of the impaired nervous system cells (post-transcytosis strategies). PLGA NPs modified according to these three strategies are denoted first, second, and third generation NPs, respectively. We believe that fusing these three strategies to engineer multifunctional PLGA NPs is the only way to achieve translational applications. PMID:27158367

  13. Magnetic hyperthermia efficiency and (1)H-NMR relaxation properties of iron oxide/paclitaxel-loaded PLGA nanoparticles.

    PubMed

    Ruggiero, Maria R; Crich, Simonetta Geninatti; Sieni, Elisabetta; Sgarbossa, Paolo; Forzan, Michele; Cavallari, Eleonora; Stefania, Rachele; Dughiero, Fabrizio; Aime, Silvio

    2016-07-15

    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 (1)H 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. PMID:27265726

  14. Magnetic hyperthermia efficiency and 1H-NMR relaxation properties of iron oxide/paclitaxel-loaded PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    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.

  15. Synthesis of porous graphene/activated carbon composite with high packing density and large specific surface area for supercapacitor electrode material

    NASA Astrophysics Data System (ADS)

    Zheng, Chao; Zhou, Xufeng; Cao, Hailiang; Wang, Guohua; Liu, Zhaoping

    2014-07-01

    A simple method has been developed to prepare graphene/activated carbon (AC) nanosheet composite as high-performance electrode material for supercapacitor. Glucose solution containing dispersed graphite oxide (GO) sheets is hydrothermally carbonized to form a brown char-like intermediate product, and finally converts to porous nanosheet composite by two-step chemical activation using KOH. In this composite, a layer of porous AC coats on graphene to from wrinkled nanosheet structure, with length of several micrometers and thickness of tens of nanometer. The composite has a relatively high packing density of ˜0.3 g cm-3 and large specific surface area of 2106 m2 g-1, as well as containing plenty of mesopores. It exhibits specific capacitance up to 210 F g-1 in aqueous electrolyte and 103 F g-1 in organic electrolyte, respectively, and the specific capacitance decreases by only 5.3% after 5000 cycles. These results indicate that the porous graphene/AC nanosheet composite prepared by hydrothermal carbonization and chemical activation can be applied for high performance supercapacitors.

  16. Stem Cells Grown in Osteogenic Medium on PLGA, PLGA/HA, and Titanium Scaffolds for Surgical Applications

    PubMed Central

    Asti, Annalia; Gastaldi, Giulia; Dorati, Rossella; Saino, Enrica; Conti, Bice; Visai, Livia; Benazzo, Francesco

    2010-01-01

    Pluripotent adipose tissue-derived stem cells (hASCs) can differentiate into various mesodermal cell types such as osteoblasts, chondroblasts, and myoblasts. We isolated hASCs from subcutaneous adipose tissue during orthopaedic surgery and induced the osteogenic differentiation for 28 days on three different synthetic scaffolds such as polylactide-co-glycolide (PLGA), polylactide-co-glycolide/hydroxyapatite (PLGA/HA), and trabecular titanium scaffolds (Ti6Al4V). Pore size can influence certain criteria such as cell attachment, infiltration, and vascularization. The aim of this study was to investigate the performance of PLGA and PLGA/HA scaffolds with a higher porosity, ranging between 75% and 84%, with respect to Ti scaffolds but with smaller pore size, seeded with hASCs to develop a model that could be used in the treatment of bone defects and fractures. Osteogenesis was assessed by ELISA quantitation of extracellular matrix protein expression, von Kossa staining, X-ray microanalysis, and scanning electron microscopy. The higher amount of protein matrix on the Ti scaffold with respect to PLGA and PLGA/HA leads to the conclusion that not only the type of material but the structure significantly affects cell proliferation. PMID:21234383

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

    PubMed

    Mehrasa, Mohammad; Asadollahi, Mohammad Ali; Nasri-Nasrabadi, Bijan; Ghaedi, Kamran; Salehi, Hossein; Dolatshahi-Pirouz, Alireza; Arpanaei, Ayyoob

    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±68nm for the pure PLGA scaffolds vs 832±70, 764±80, and 486±64 for the PLGA/gelatin, PLGA/10wt% MSNPs, and the PLGA/gelatin/10wt% 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. PMID:27207035

  18. Seeing is believing, PLGA microsphere degradation revealed in PLGA microsphere/PVA hydrogel composites.

    PubMed

    Gu, Bing; Sun, Xuanhao; Papadimitrakopoulos, Fotios; Burgess, Diane J

    2016-04-28

    The aim of this study was to understand the polymer degradation and drug release mechanism from PLGA microspheres embedded in a PVA hydrogel. Two types of microspheres were prepared with different molecular weight PLGA polymers (approximately 25 and 7kDa) to achieve different drug release profiles, with a 9-day lag phase and without a lag phase, respectively. The kinetics of water uptake into the microspheres coincided with the drug release profiles for both formulations. For the 25kDa microspheres, minimal water uptake was observed in the early part of the lag phase followed by substantial water uptake at the later stages and in the drug release phase. For the 7kDa microspheres, water uptake occurred simultaneously with drug release. Water uptake was approximately 2-3 times that of the initial microsphere weight for both formulations. The internal structure of the PLGA microspheres was evaluated using low temperature scanning electron microscopy (cryo-SEM). Burst drug release occurred followed by pore forming from the exterior to the core of both microspheres. A well-defined hydrogel/microsphere interface was observed. For the 25kDa microspheres, internal pore formation and swelling occurred before the second drug release phase. The surface layer of the microspheres remained intact whereas swelling, and degradation of the core continued throughout the drug release period. In addition, microsphere swelling reduced glucose transport through the coatings in PBS media and this was considered to be a as a consequence of the increased thickness of the coatings. The combination of the swelling and microdialysis results provides a fresh understanding on the competing processes affecting molecular transport of bioanalytes (i.e. glucose) through these composite coatings during prolonged exposure in PBS. PMID:26965956

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

    NASA Astrophysics Data System (ADS)

    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

  20. High-speed growth and photoluminescence of porous anodic alumina films with controllable interpore distances over a large range

    NASA Astrophysics Data System (ADS)

    Li, Y. B.; Zheng, M. J.; Ma, L.

    2007-08-01

    Highly ordered porous anodic alumina (PAA) films are fabricated with high efficiency by stable high-field anodization in oxalic acid/ethanol/water electrolytes at 100-180V and sulfuric acid/oxalic acid/ethanol/water electrolytes at 30-80V, giving interpore distances in the range of 225-450nm and 70-140nm, respectively. The photoluminescence of PAA films prepared by high-field anodization shows remarkable redshift of the peak position and decrease of the intensity compared to that of PAA films formed by conventional low-field anodization.

  1. In vivo biocompatibility of the PLGA microparticles in parotid gland

    PubMed Central

    Cantín, Mario; Miranda, Patricio; Suazo Galdames, Iván; Zavando, Daniela; Arenas, Patricia; Velásquez, Luis; Vilos, Cristian

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) microparticles are used in various disorders for the controlled or sustained release of drugs, with the management of salivary gland pathologies possible using this technology. There is no record of the response to such microparticles in the glandular parenchyma. The purpose of this study was to assess the morphological changes in the parotid gland when injected with a single dose of PLGA microparticles. We used 12 adult female Sprague Dawley rats (Rattus norvegicus) that were injected into their right parotid gland with sterile vehicle solution (G1, n=4), 0.5 mg PLGA microparticles (G2, n=4), and 0.75 mg PLGA microparticles (G3, n=4); the microparticles were dissolved in a sterile vehicle solution. The intercalar and striated ducts lumen, the thickness of the acini and the histology aspect in terms of the parenchyma organization, cell morphology of acini and duct system, the presence of polymeric residues, and inflammatory response were determined at 14 days post-injection. The administration of the compound in a single dose modified some of the morphometric parameters of parenchyma (intercalar duct lumen and thickness of the glandular acini) but did not induce tissue inflammatory response, despite the visible presence of polymer waste. This suggests that PLGA microparticles are biocompatible with the parotid tissue, making it possible to use intraglandular controlled drug administration. PMID:24228103

  2. Combined photothermal therapy and chemotherapy in cancer using HER-2 targeted PLGA nanoparticles

    NASA Astrophysics Data System (ADS)

    McGoron, Anthony J.; Srinivasan, Supriya; Lei, Tingjun; Tang, Yuan; Manchanda, Romila

    2013-02-01

    We previously reported on the synergistic effects of hyperthermia and chemotherapy using doxorubicin (DOX) and Indocyanine Green (ICG). In a previous study we also explored the potential use of simultaneous entrapment of optical/imaging and chemotherapeutic agents into PLGA nanoparticles. The aim of the present study is to further decorate their surface with tumor specific monoclonal antibodies in order to achieve simultaneous therapy and diagnosis in a targeted manner. Thus, ICG was selected as an imaging agent due to its wide clinical applications and since it can also serve as hyperthermia agent. DOX was selected as the chemotherapeutic agent since it is used clinically for a large spectrum of tumors.

  3. Porous silicon gettering

    SciTech Connect

    Tsuo, Y.S.; Menna, P.; Al-Jassim, M.

    1995-08-01

    We have studied a novel extrinsic gettering method that utilizes the very large surface areas, produced by porous silicon etch on both front and back surfaces of the silicon wafer, as gettering sites. In this method, a simple and low-cost chemical etching is used to generate the porous silicon layers. Then, a high-flux solar furnace (HFSF) is used to provide high-temperature annealing and the required injection of silicon interstitials. The gettering sites, along with the gettered impurities, can be easily removed at the end the process. The porous silicon removal process consists of oxidizing the porous silicon near the end the gettering process followed by sample immersion in HF acid. Each porous silicon gettering process removes up to about 10 {mu}m of wafer thickness. This gettering process can be repeated so that the desired purity level is obtained.

  4. Planar monolithic porous polymer layers functionalized with gold nanoparticles as large-area substrates for sensitive surface-enhanced Raman scattering sensing of bacteria.

    PubMed

    Cao, Yao; Lv, Mingyang; Xu, Haijun; Svec, Frantisek; Tan, Tianwei; Lv, Yongqin

    2015-10-01

    For the first time, large-area surface-enhanced Raman scattering sensing active substrates using porous polymer monolithic layers have been successfully prepared. Our approach includes a simple photoinitiated polymerization process using glycidyl methacrylate and ethylene dimethacrylate in a glass mold, followed by a chemical reaction of the epoxy functionalities leading to thiols, and the attachment of preformed gold nanoparticles. We demonstrated that this very simple process produced uniform and reproducible large area surfaces that significantly enhance sensitivity of Raman spectroscopy. Experiments were also carried out that confirmed preferential adsorption of living bacteria Escherichia coli from a very dilute solution on the surface of the monolithic layer, and immediate detection of the captured microorganisms using the SERS spectrum. PMID:26481994

  5. Microencapsulation of curcumin in PLGA microcapsules by coaxial flow focusing

    NASA Astrophysics Data System (ADS)

    Lei, Fan; Si, Ting; Luo, Xisheng; Xu, Ronald X.

    2014-03-01

    Curcumin-loaded PLGA microcapsules are fabricated by a liquid-driving coaxial flow focusing device. In the process, a stable coaxial cone-jet configuration is formed under the action of a coflowing liquid stream and the coaxial liquid jet eventually breaks up into microcapsules because of flow instability. This process can be well controlled by adjusting the flow rates of three phases including the driving PVA water solution, the outer PLGA ethyl acetate solution and the inner curcumin propylene glycol solution. Confocal and SEM imaging methods clearly indicate the core-shell structure of the resultant microcapsules. The encapsulation rate of curcumin in PLGA is measured to be more than 70%, which is much higher than the tranditional methods such as emulsion. The size distribution of resultant microcapsules under different conditions is presented and compared. An in vitro release simulation platform is further developed to verify the feasibility and reliability of the method.

  6. A novel strategy for the preparation of porous microspheres and its application in peptide drug loading.

    PubMed

    Wei, Yi; Wang, Yuxia; Zhang, Huixia; Zhou, Weiqing; Ma, Guanghui

    2016-09-15

    A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens. PMID:27285778

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

    PubMed Central

    Tavanai, Hossein; Hilborn, Jöns; Donzel-Gargand, Olivier; Leifer, Klaus; 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. PMID:24689041

  8. Oral Delivery of DMAB-Modified Docetaxel-Loaded PLGA-TPGS Nanoparticles for Cancer Chemotherapy

    NASA Astrophysics Data System (ADS)

    Chen, Hongbo; Zheng, Yi; Tian, Ge; Tian, Yan; Zeng, Xiaowei; Liu, Gan; Liu, Kexin; Li, Lei; Li, Zhen; Mei, Lin; Huang, Laiqiang

    2011-12-01

    Three types of nanoparticle formulation from biodegradable PLGA-TPGS random copolymer were developed in this research for oral administration of anticancer drugs, which include DMAB-modified PLGA nanoparticles, unmodified PLGA-TPGS nanoparticles and DMAB-modified PLGA-TPGS nanoparticles. Firstly, the PLGA-TPGS random copolymer was synthesized and characterized. DMAB was used to increase retention time at the cell surface, thus increasing the chances of particle uptake and improving oral drug bioavailability. Nanoparticles were found to be of spherical shape with an average particle diameter of around 250 nm. The surface charge of PLGA-TPGS nanoparticles was changed to positive after DMAB modification. The results also showed that the DMAB-modified PLGA-TPGS nanoparticles have significantly higher level of the cellular uptake than that of DMAB-modified PLGA nanoparticles and unmodified PLGA-TPGS nanoparticles. In vitro, cytotoxicity experiment showed advantages of the DMAB-modified PLGA-TPGS nanoparticle formulation over commercial Taxotere® in terms of cytotoxicity against MCF-7 cells. In conclusion, oral chemotherapy by DMAB-modified PLGA-TPGS nanoparticle formulation is an attractive and promising treatment option for patients.

  9. Development of a methacrylate-terminated PLGA copolymer for potential use in craniomaxillofacial fracture plates.

    PubMed

    Upson, Sarah J; Partridge, Simon W; Tcacencu, Ion; Fulton, David A; Corbett, Ian; German, Matthew J; Dalgarno, Kenneth W

    2016-12-01

    We synthesised methacrylate-terminated PLGA (HT-PLGA, 85:15 LA:GA, 169kDa), for potential use as an adhesively attached craniomaxillofacial fracture fixation plate. The in vitro degradation of molecular weight, pH and flexural modulus were measured over 6weeks storage in PBS at 37°C, with commercially available high (225kDa, H-PLGA) and low (116kDa, L-PLGA) molecular weight 85:15 PLGAs used as comparators. Molecular weights of the materials reduced over 6weeks, HT-PLGA by 48%, H-PLGA by 23% and L-PLGA by 81%. HT-PLGA and H-PLGA exhibited a near constant pH (7.35) and had average flexural moduli in excess of 6GPa when produced, similar to that of the mandible. After 1week storage both exhibited a significant reduction in average modulus, however, from weeks 1-6 no further significant changes were observed, the average modulus never dropped significantly below 5.5GPa. In contrast, the L-PLGA caused a pH drop to below 7.3 by week 6 and an average modulus drop to 0.6 from an initial 4.6GPa. Cell culture using rat bone marrow stromal cells, revealed all materials were cytocompatible and exhibited no osteogenic potential. We conclude that our functionalised PLGA retains mechanical properties which are suitable for use in craniofacial fixation plates. PMID:27612737

  10. Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres.

    PubMed

    Song, Kedong; Liu, Yingchao; Macedo, Hugo M; Jiang, Lili; Li, Chao; Mei, Guanyu; Liu, Tianqing

    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(-2) mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a promising technique

  11. Preparation of insulin-loaded PLA/PLGA microcapsules by a novel membrane emulsification method and its release in vitro.

    PubMed

    Liu, Rong; Huang, Shan-Shan; Wan, Yin-Hua; Ma, Guang-Hui; Su, Zhi-Guo

    2006-08-01

    Uniform-sized biodegradable PLA/PLGA microcapsules loading recombinant human insulin (rhI) were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and a double emulsion-evaporation method. An aqueous phase containing rhI was used as the inner water phase (w1), and PLA/PLGA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene, which was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion was permeated through the uniform pores of a SPG membrane into an outer water phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. The solid polymer microcapsules were obtained by simply evaporating solvent from droplets. Various factors of the preparation process influencing the drug encapsulation efficiency and the drug cumulative release were investigated systemically. The results indicated that the drug encapsulation efficiency and the cumulative release were affected by the PLA/PLGA ratio, NaCl concentration in outer water phase, the inner water phase volume, rhI-loading amount, pH-value in outer water phase and the size of microcapsules. By optimizing the preparation process, the drug encapsulation efficiency was high up to 91.82%. The unique advantage of preparing drug-loaded microcapsules by membrane emulsification technique is that the size of microcapsules can be controlled accurately, and thus the drug cumulative release profile can be adjusted just by changing the size of microcapsules. Moreover, much higher encapsulation efficiency can be obtained when compared with the conventional mechanical stirring method. PMID:16814994

  12. Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles.

    PubMed

    Yeredla, Nitish; Kojima, Taisuke; Yang, Yi; Takayama, Shuichi; Kanapathipillai, Mathumai

    2016-01-01

    Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations. PMID:27279329

  13. Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles

    NASA Astrophysics Data System (ADS)

    Yeredla, Nitish; Kojima, Taisuke; Yang, Yi; Takayama, Shuichi; Kanapathipillai, Mathumai

    2016-06-01

    Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations.

  14. PLGA nanofibers improves the antitumoral effect of daunorubicin.

    PubMed

    Guimarães, Pedro P G; Oliveira, Michele F; Gomes, Alinne D M; Gontijo, Sávio M L; Cortés, Maria E; Campos, Paula P; Viana, Celso T R; Andrade, Silvia P; Sinisterra, Rubén D

    2015-12-01

    The objective of this study was to evaluate the in vivo anti-inflammatory angiogenesis activity and in vitro cytotoxicity on normal and cancer cell models of a drug delivery system consisting of poly(lactic-co-glycolic acid) nanofibers loaded with daunorubicin (PLGA-DNR) that were fabricated using an electrospinning process. The PLGA-DNR nanofibers were also characterized by thermogravimetric analysis (TGA), differential thermal analysis (DTA) and differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and confocal fluorescence microscopy. In vitro release of DNR from the nanofibers and its corresponding mechanism were also evaluated. Sixty-five percent of the DNR was released in an initial burst over 8h, and by 1224 h, eighty-five percent of the DNR had been released. The Higuchi model yielded the best fit to the DNR release profile over the first 8h, and the corresponding data from 24 to 1224 h could be modeled using zero-order kinetics. The PLGA-DNR nanofibers exhibited a higher cytotoxicity to A431 cells than free DNR but a cytotoxicity similar to free DNR against fibroblast cells. A higher antiangiogenic effect of PLGA nanofibers was observed in the in vivo data when compared to free DNR, and no inflammatory potential was observed for the nanofibers. PMID:26402423

  15. Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles

    PubMed Central

    Yeredla, Nitish; Kojima, Taisuke; Yang, Yi; Takayama, Shuichi; Kanapathipillai, Mathumai

    2016-01-01

    Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations. PMID:27279329

  16. The preosteoblast response of electrospinning PLGA/PCL nanofibers: effects of biomimetic architecture and collagen I.

    PubMed

    Qian, Yunzhu; Chen, Hanbang; Xu, Yang; Yang, Jianxin; Zhou, Xuefeng; Zhang, Feimin; Gu, Ning

    2016-01-01

    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 growth. Analysis of β1 integrin expression level by immunofluorescence indicated that such biomimetic architecture, especially COL I-grafted surface, plays a key role in cell adhesion and proliferation. The real-time polymerase chain reaction suggested that both surface topography and bioactive properties could facilitate the cell adhesion. The combined effect of biomimetic architecture with enhanced

  17. The preosteoblast response of electrospinning PLGA/PCL nanofibers: effects of biomimetic architecture and collagen I

    PubMed Central

    Qian, Yunzhu; Chen, Hanbang; Xu, Yang; Yang, Jianxin; Zhou, Xuefeng; Zhang, Feimin; Gu, Ning

    2016-01-01

    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 growth. Analysis of β1 integrin expression level by immunofluorescence indicated that such biomimetic architecture, especially COL I-grafted surface, plays a key role in cell adhesion and proliferation. The real-time polymerase chain reaction suggested that both surface topography and bioactive properties could facilitate the cell adhesion. The combined effect of biomimetic architecture with enhanced

  18. Enhanced photoluminescence of porous silicon nanoparticles coated by bioresorbable polymers

    NASA Astrophysics Data System (ADS)

    Gongalsky, Maxim B.; Kharin, Alexander Yu; Osminkina, Liubov A.; Timoshenko, Victor Yu; Jeong, Jinyoung; Lee, Han; Chung, Bong Hyun

    2012-08-01

    A significant enhancement of the photoluminescence (PL) efficiency is observed for aqueous suspensions of porous silicon nanoparticles (PSiNPs) coated by bioresorbable polymers, i.e., polylactic-co-glycolic acid (PLGA) and polyvinyl alcohol (PVA). PSiNPs with average size about 100 nm prepared by mechanical grinding of electrochemically etched porous silicon were dispersed in water to prepare the stable suspension. The inner hydrophobic PLGA layer prevents the PSiNPs from the dissolution in water, while the outer PVA layer makes the PSiNPs hydrophilic. The PL quantum yield of PLGA/PVA-coated PSiNPs was found to increase by three times for 2 weeks of the storage in water. The observed effect is explained by taking into account both suppression of the dissolution of PSiNPs in water and a process of the passivation of nonradiative defects in PSiNPs. The obtained results are interesting in view of the potential applications of PSiNPs in bioimaging.

  19. Manufacture of porous biodegradable polymer conduits by an extrusion process for guided tissue regeneration

    NASA Technical Reports Server (NTRS)

    Widmer, M. S.; Gupta, P. K.; Lu, L.; Meszlenyi, R. K.; Evans, G. R.; Brandt, K.; Savel, T.; Gurlek, A.; Patrick, C. W. Jr; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

    1998-01-01

    We have fabricated porous, biodegradable tubular conduits for guided tissue regeneration using a combined solvent casting and extrusion technique. The biodegradable polymers used in this study were poly(DL-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). A polymer/salt composite was first prepared by a solvent casting process. After drying, the composite was extruded to form a tubular construct. The salt particles in the construct were then leached out leaving a conduit with an open-pore structure. PLGA was studied as a model polymer to analyze the effects of salt weight fraction, salt particle size, and processing temperature on porosity and pore size of the extruded conduits. The porosity and pore size were found to increase with increasing salt weight fraction. Increasing the salt particle size increased the pore diameter but did not affect the porosity. High extrusion temperatures decreased the pore diameter without altering the porosity. Greater decrease in molecular weight was observed for conduits manufactured at higher temperatures. The mechanical properties of both PLGA and PLLA conduits were tested after degradation in vitro for up to 8 weeks. The modulus and failure strength of PLLA conduits were approximately 10 times higher than those of PLGA conduits. Failure strain was similar for both conduits. After degradation for 8 weeks, the molecular weights of the PLGA and PLLA conduits decreased to 38% and 43% of the initial values, respectively. However, both conduits maintained their shape and did not collapse. The PLGA also remained amorphous throughout the time course, while the crystallinity of PLLA increased from 5.2% to 11.5%. The potential of seeding the conduits with cells for transplantation or with biodegradable polymer microparticles for drug delivery was also tested with dyed microspheres. These porous tubular structures hold great promise for the regeneration of tissues which require tubular scaffolds such as peripheral nerve

  20. Histological evaluation of osteogenesis of 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds in a rabbit model.

    PubMed

    Ge, Zigang; Tian, Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo, Jin Fei; Cao, Tong

    2009-04-01

    Utilizing a suitable combination of lactide and glycolide in a copolymer would optimize the degradation rate of a scaffold upon implantation in situ. Moreover, 3D printing technology enables customizing the shape of the scaffold to biometric data from CT and MRI scans. A previous in vitro study has shown that novel 3D-printed poly-lactic-co-glycolic acid (PLGA) scaffolds had good biocompatibility and mechanical properties comparable with human cancellous bone, while they could support proliferation and osteogenic differentiation of osteoblasts. Based on the previous study, this study evaluated PLGA scaffolds for bone regeneration within a rabbit model. The scaffolds were implanted at two sites on the same animal, within the periosteum and within bi-cortical bone defects on the iliac crest. Subsequently, the efficacy of bone regeneration within the implanted scaffolds was evaluated at 4, 12 and 24 weeks post-surgery through histological analysis. In both the intra-periosteum and iliac bone defect models, the implanted scaffolds facilitated new bone tissue formation and maturation over the time course of 24 weeks, even though there was initially observed to be little tissue ingrowth within the scaffolds at 4 weeks post-surgery. Hence, the 3D-printed porous PLGA scaffolds investigated in this study displayed good biocompatibility and are osteoconductive in both the intra-periosteum and iliac bone defect models. PMID:19208943

  1. Novel DiR and SPIO nanoparticles embedded PEG-PLGA nanobubbles as a multimodalimaging contrast agent.

    PubMed

    Luo, Binhua; Zhang, Huajie; Liu, Xuhan; Rao, Rong; Wu, Yun; Liu, Wei

    2015-01-01

    Fluorescence dye DiR and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in PEG-PLGA nanobubbles (DiR-SPIO-NBs) were produced using double emulsion method on a membrane of Shirasu porous glass (SPG). The nanobubbles encapsulated with DiR and SPIONs had a liquid core (perfluoropentane) and a PEG-PLGA shell. DiR-SPIO-NBs showed biocompatibility based on MTT cytotoxicity and hemolysis studies. The PFP encapsulated in the nanobubbles experienced phase transition under ultrasonic irradation. Nanobubbles dispersed well in saline over 3 months, and the relaxivity was 127.9 mM(-1)s(-1), suggesting that it could be used as a contrast agent in MRI. The MR and fluorescence images in vivo demonstrated that the signal intensity in the spleen and liver was significantly enhanced with the treatment of nanobubbles. In addition, results of ultrasound images suggested that the nanobubbles had persistent contrast ability. In conclusion, nanobubbles could be utilized as an US/MRI/fluorescence contrast agent. PMID:26406092

  2. Preparation and properties of PLGA nanofiber membranes reinforced with cellulose nanocrystals.

    PubMed

    Mo, Yunfei; Guo, Rui; Liu, Jianghui; Lan, Yong; Zhang, Yi; Xue, Wei; Zhang, Yuanming

    2015-08-01

    Although extensively used in the fields of drug-carrier and tissue engineering, the biocompatibility and mechanical properties of polylactide-polyglycolide (PLGA) nanofiber membranes still limit their applications. The objective of this study was to improve their utility by introducing cellulose nanocrystals (CNCs) into PLGA nanofiber membranes. PLGA and PLGA/CNC composite nanofiber membranes were prepared via electrospinning, and the morphology and thermodynamic and mechanical properties of these nanofiber membranes were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). The cytocompatibility and cellular responses of the nanofiber membranes were also studied by WST-1 assay, SEM, and confocal laser scanning microscopy (CLSM). Incorporation of CNCs (1, 3, 5, and 7 wt.%) increased the average fiber diameter of the prepared nanofiber membranes from 100 nm (neat PLGA) to ∼400 nm (PLGA/7 wt.% CNC) and improved the thermal stability of the nanofiber membranes. Among the PLGA/CNC composite nanofiber membranes, those loaded with 7 wt.% CNC nanofiber membranes had the best mechanical properties, which were similar to those of human skin. Cell culture results showed that the PLGA/CNC composite nanofiber membranes had better cytocompatibility and facilitated fibroblast adhesion, spreading, and proliferation compared with neat PLGA nanofiber membranes. These preliminary results suggest that PLGA/CNC composite nanofiber membranes are promising new materials for the field of skin tissue engineering. PMID:26047881

  3. Development of sulfadiazine-decorated PLGA nanoparticles loaded with 5-fluorouracil and cell viability.

    PubMed

    Guimarães, Pedro Pires Goulart; Oliveira, Sheila Rodrigues; de Castro Rodrigues, Gabrielle; Gontijo, Savio Morato Lacerda; Lula, Ivana Silva; Cortés, Maria Esperanza; Denadai, Ângelo Márcio Leite; Sinisterra, Rubén Dario

    2015-01-01

    The aim of this work was to synthesize sulfadiazine-poly(lactide-co-glycolide) (SUL-PLGA) nanoparticles (NPs) for the efficient delivery of 5-fluorouracil to cancer cells. The SUL-PLGA conjugation was assessed using FTIR, 1H-NMR, 13C-NMR, elemental analysis and TG and DTA analysis. The SUL-PLGA NPs were characterized using transmission and scanning electron microscopy and dynamic light scattering. Additionally, the zeta potential, drug content, and in vitro 5-FU release were evaluated. We found that for the SUL-PLGA NPs, Dh = 114.0 nm, ZP = -32.1 mV and the encapsulation efficiency was 49%. The 5-FU was released for up to 7 days from the NPs. Cytotoxicity evaluations of 5-FU-loaded NPs (5-FU-SUL-PLGA and 5-FU-PLGA) on two cancer cell lines (Caco-2, A431) and two normal cell lines (fibroblast, osteoblast) were compared. Higher cytotoxicity of 5-FU-SUL-PLGA NPs were found to both cancer cell lines when compared to normal cell lines, demonstrating that the presence of SUL could significantly enhance the cytotoxicity of the 5-FU-SUL-PLGA NPs when compared with 5-FU-PLGA NPs. Thus, the development of 5-FU-SUL-PLGA NPs to cancer cells is a promising strategy for the 5-FU antitumor formulation in the future. PMID:25580685

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

    PubMed Central

    Selmin, Francesca; Puoci, Francesco; Parisi, Ortensia I.; Franzé, Silvia; Musazzi, Umberto M.; Cilurzo, Francesco

    2015-01-01

    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. PMID:25569163

  5. Effect of copolymer composition on the physicochemical characteristics, in vitro stability, and biodistribution of PLGA-mPEG nanoparticles.

    PubMed

    Avgoustakis, K; Beletsi, A; Panagi, Z; Klepetsanis, P; Livaniou, E; Evangelatos, G; Ithakissios, D S

    2003-06-18

    The physicochemical properties, the colloidal stability in vitro and the biodistribution properties in mice of different PLGA-mPEG nanoparticle compositions were investigated. The nanoparticles were prepared by a precipitation-solvent evaporation technique. The physical characteristics and the colloidal stability of the PLGA-mPEG nanoparticles were significantly influenced by the composition of the PLGA-mPEG copolymer used to prepare the nanoparticles. PLGA-mPEG nanoparticles prepared from copolymers having relatively high mPEG/PLGA ratios were smaller and less stable than those prepared from copolymers having relatively low mPEG/PLGA ratios. All PLGA-mPEG nanoparticle compositions exhibited prolonged residence in blood, compared to the conventional PLGA nanoparticles. The composition of the PLGA-mPEG copolymer affected significantly the blood residence time and the biodistribution of the PLGA-mPEG nanoparticles in liver, spleen and bones. The in vivo behavior of the different PLGA-mPEG nanoparticle compositions did not appear to correlate with their in vitro stability. Optimum mPEG/PLGA ratios appeared to exist leading to long blood circulation times of the PLGA-mPEG nanoparticles. This may be associated with the effects of the mPEG/PLGA ratio on the density of PEG on the surface of the nanoparticles and on the size of the nanoparticles. PMID:12787641

  6. PLGA microdevices for retinoids sustained release produced by supercritical emulsion extraction: continuous versus batch operation layouts.

    PubMed

    Porta, Giovanna Della; Campardelli, Roberta; Falco, Nunzia; Reverchon, Ernesto

    2011-10-01

    Retinyl acetate (RA) was selected as a model compound to be entrapped in poly(lactic-co-glycolic)acid (PLGA) microspheres using supercritical emulsion extraction (SEE). Several oil-in-water emulsions prepared using acetone and aqueous glycerol (80% glycerol, 20% water) were processed using supercritical carbon dioxide (SC-CO2 ) to extract the oily phase and to induce microspheres formation. The characteristics of the microspheres obtained by conventional liquid emulsion extraction and SEE were also compared: SEE produced spherical and free flowing microspheres, whereas the conventional liquid-liquid extraction showed large intraparticles aggregation. Emulsion extraction by SC-CO2 technology was tested using two different operation layouts: batch (SEE-B) and continuous (SEE-C). SEE-C was performed using a packed tower to produce emulsion/SC-CO2 contact in countercurrent mode, allowing higher microsphere recovery and process efficiencies. Operating at 80 bar and 36°C, SEE-C produced PLGA/RA microspheres with mean sizes between 3.3 and 4.5 μm with an excellent encapsulation efficiency of 80%-90%. Almost all the drug was released in about 6 days when charged at 2.7% (w/w), whereas only 40% and 10% of RA were released in the same period of time when the charge was 5.2% and 8.8% (w/w), respectively. Release kinetics constants calculated from the experimental data, using a mathematical model, were also proposed and discussed. PMID:21638283

  7. Formulation and in vitro/in vivo evaluation of terbutaline sulphate incorporated in PLGA (25/75) and L-PLA microspheres.

    PubMed

    Selek, H; Sahin, S; Ercan, M T; Sargon, M; Hincal, A A; Kas, H S

    2003-01-01

    Terbutaline sulphate (TBS) is widely used in the treatment of bronchial asthma, chronic bronchitis and emphysema. Because of its short biological half life and dosing schedule, a long acting TBS formulation is required to improve patient compliance. The objective of this study was to develop a TBS containing biodegradable microsphere formulation. Poly(D,L-lactide-co-glycolide) (PLGA) and poly(L-lactic acid) (L-PLA) were chosen as matrix materials. A solvent evaporation method was used for preparation of microspheres. Surface morphology, particle size distribution and encapsulation efficiency were investigated. In vitro release studies were performed in pH 7.4 phosphate buffer. In vitro distribution of microspheres were studied in the Swiss albino male mice. All microspheres were spherical in shape and had a porous surface with mean diameters of 9-21 microm. The encapsulation efficiency was influenced by the polymer type, but not the molecular weight. About 90% of the initial amount was trapped in PLGA microspheres, and the remainder was on the surface. In the case of L-PLA, 50% of the total drug was associated with the surface of microspheres. The In vitro release pattern was biphasic characterized by an initial burst phase followed by a slower phase. The L-PLA microspheres released approximately 92% of the initial payload in 72 h. On the other hand, TBS release was increased with an increase in the molecular weight of PLGA. Biodistribution of L-PLA microspheres was characterized by an initially high uptake (35%) by the lungs. All these results suggest that L-PLA and PLGA microspheres have the potential to be used for passive lung targeting. PMID:12554379

  8. Large-area one-step assembly of three-dimensional porous metal micro/nanocages by ethanol-assisted femtosecond laser irradiation for enhanced antireflection and hydrophobicity.

    PubMed

    Li, Guoqiang; Li, Jiawen; Zhang, Chenchu; Hu, Yanlei; Li, Xiaohong; Chu, Jiaru; Huang, Wenhao; Wu, Dong

    2015-01-14

    The capability to realize 2D-3D controllable metallic micro/nanostructures is of key importance for various fields such as plasmonics, electronics, bioscience, and chemistry due to unique properties such as electromagnetic field enhancement, catalysis, photoemission, and conductivity. However, most of the present techniques are limited to low-dimension (1D-2D), small area, or single function. Here we report the assembly of self-organized three-dimensional (3D) porous metal micro/nanocages arrays on nickel surface by ethanol-assisted femtosecond laser irradiation. The underlying formation mechanism was investigated by a series of femtosecond laser irradiation under exposure time from 5 to 30 ms. We also demonstrate the ability to control the size of micro/nanocage arrays from 0.8 to 2 μm by different laser pulse energy. This method features rapidness (∼10 min), simplicity (one-step process), and ease of large-area (4 cm(2) or more) fabrication. The 3D cagelike micro/nanostructures exhibit not only improved antireflection from 80% to 7% but also enhanced hydrophobicity from 98.5° to 142° without surface modification. This simple technique for 3D large-area controllable metal microstructures will find great potential applications in optoelectronics, physics, and chemistry. PMID:25473879

  9. Synthesis and Characterization of PLGA Shell Microcapsules Containing Aqueous Cores Prepared by Internal Phase Separation.

    PubMed

    Abulateefeh, Samer R; Alkilany, Alaaldin M

    2016-08-01

    The preparation of microcapsules consisting of poly(D,L-lactide-co-glycolide) (PLGA) polymer shell and aqueous core is a clear challenge and hence has been rarely addressed in literature. Herein, aqueous core-PLGA shell microcapsules have been prepared by internal phase separation from acetone-water in oil emulsion. The resulting microcapsules exhibited mean particle size of 1.1 ± 0.39 μm (PDI = 0.35) with spherical surface morphology and internal poly-nuclear core morphology as indicated by scanning electron microscopy (SEM). The incorporation of water molecules into PLGA microcapsules was confirmed by differential scanning calorimetry (DSC). Aqueous core-PLGA shell microcapsules and the corresponding conventional PLGA microspheres were prepared and loaded with risedronate sodium as a model drug. Interestingly, aqueous core-PLGA shell microcapsules illustrated 2.5-fold increase in drug encapsulation in comparison to the classical PLGA microspheres (i.e., 31.6 vs. 12.7%), while exhibiting sustained release behavior following diffusion-controlled Higuchi model. The reported method could be extrapolated to encapsulate other water soluble drugs and hydrophilic macromolecules into PLGA microcapsules, which should overcome various drawbacks correlated with conventional PLGA microspheres in terms of drug loading and release. PMID:26416284

  10. Heuristic modeling of macromolecule release from PLGA microspheres

    PubMed Central

    Szlęk, Jakub; Pacławski, Adam; Lau, Raymond; Jachowicz, Renata; Mendyk, Aleksander

    2013-01-01

    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 comparable predictability to the ANN model. PMID:24348037

  11. Heuristic modeling of macromolecule release from PLGA microspheres.

    PubMed

    Szlęk, Jakub; Pacławski, Adam; Lau, Raymond; Jachowicz, Renata; Mendyk, Aleksander

    2013-01-01

    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 comparable predictability to the ANN model. PMID:24348037

  12. Evaluation of a combined drug-delivery system for proteins assembled with polymeric nanoparticles and porous microspheres; characterization and protein integrity studies.

    PubMed

    Alcalá-Alcalá, Sergio; Benítez-Cardoza, Claudia G; Lima-Muñoz, Enrique J; Piñón-Segundo, Elizabeth; Quintanar-Guerrero, David

    2015-07-15

    This work presents an evaluation of the adsorption/infiltration process in relation to the loading of a model protein, α-amylase, into an assembled biodegradable polymeric system, free of organic solvents and made up of poly(D,L-lactide-co-glycolide) acid (PLGA). Systems were assembled in a friendly aqueous medium by adsorbing and infiltrating polymeric nanoparticles into porous microspheres. These assembled systems are able to load therapeutic amounts of the drug through adsorption of the protein onto the large surface area characteristic of polymeric nanoparticles. The subsequent infiltration of nanoparticles adsorbed with the protein into porous microspheres enabled the controlled release of the protein as a function of the amount of infiltrated nanoparticles, since the surface area available on the porous structure is saturated at different levels, thus modifying the protein release rate. Findings were confirmed by both the BET technique (N2 isotherms) and in vitro release studies. During the adsorption process, the pH of the medium plays an important role by creating an environment that favors adsorption between the surfaces of the micro- and nano-structures and the protein. Finally, assays of α-amylase activity using 2-chloro-4-nitrophenyl-α-D-maltotrioside (CNP-G3) as the substrate and the circular dichroism technique confirmed that when this new approach was used no conformational changes were observed in the protein after release. PMID:25936624

  13. HDL-Mimetic PLGA Nanoparticle To Target Atherosclerosis Plaque Macrophages

    PubMed Central

    Sanchez-Gaytan, Brenda L.; Fay, Francois; Lobatto, Mark E.; Tang, Jun; Ouimet, Mireille; Kim, YongTae; van der Staay, Susanne E. M.; van Rijs, Sarian M.; Priem, Bram; Zhang, Liangfang; Fisher, Edward A; Moore, Kathryn J.; Langer, Robert; Fayad, Zahi A.; Mulder, Willem J M

    2015-01-01

    High-density lipoprotein (HDL) is a natural nanoparticle that exhibits an intrinsic affinity for atherosclerotic plaque macrophages. Its natural targeting capability as well as the option to incorporate lipophilic payloads, e.g., imaging or therapeutic components, in both the hydrophobic core and the phospholipid corona make the HDL platform an attractive nanocarrier. To realize controlled release properties, we developed a hybrid polymer/HDL nanoparticle composed of a lipid/apolipoprotein coating that encapsulates a poly(lactic-co-glycolic acid) (PLGA) core. This novel HDL-like nanoparticle (PLGA–HDL) displayed natural HDL characteristics, including preferential uptake by macrophages and a good cholesterol efflux capacity, combined with a typical PLGA nanoparticle slow release profile. In vivo studies carried out with an ApoE knockout mouse model of atherosclerosis showed clear accumulation of PLGA–HDL nanoparticles in atherosclerotic plaques, which colocalized with plaque macrophages. This biomimetic platform integrates the targeting capacity of HDL biomimetic nanoparticles with the characteristic versatility of PLGA-based nanocarriers. PMID:25650634

  14. Electrospray synthesis and properties of hierarchically structured PLGA TIPS microspheres for use as controlled release technologies.

    PubMed

    Malik, Salman A; Ng, Wing H; Bowen, James; Tang, Justin; Gomez, Alessandro; Kenyon, Anthony J; Day, Richard M

    2016-04-01

    Microsphere-based controlled release technologies have been utilized for the long-term delivery of proteins, peptides and antibiotics, although their synthesis poses substantial challenges owing to formulation complexities, lack of scalability, and cost. To address these shortcomings, we used the electrospray process as a reproducible, synthesis technique to manufacture highly porous (>94%) microspheres while maintaining control over particle structure and size. Here we report a successful formulation recipe used to generate spherical poly(lactic-co-glycolic) acid (PLGA) microspheres using the electrospray (ES) coupled with a novel thermally induced phase separation (TIPS) process with a tailored Liquid Nitrogen (LN2) collection scheme. We show how size, shape and porosity of resulting microspheres can be controlled by judiciously varying electrospray processing parameters and we demonstrate examples in which the particle size (and porosity) affect release kinetics. The effect of electrospray treatment on the particles and their physicochemical properties are characterized by scanning electron microscopy, confocal Raman microscopy, thermogravimetric analysis and mercury intrusion porosimetry. The microspheres manufactured here have successfully demonstrated long-term delivery (i.e. 1week) of an active agent, enabling sustained release of a dye with minimal physical degradation and have verified the potential of scalable electrospray technologies for an innovative TIPS-based microsphere production protocol. PMID:26803601

  15. 'Breath figure' PLGA films as implant coatings for controlled drug release

    NASA Astrophysics Data System (ADS)

    Ponnusamy, Thiruselvam

    The breath figure method is a versatile and facile approach of generating ordered micro and nanoporous structures in polymeric materials. When a polymer solution (dissolved in a high vapor pressure organic solvent) is evaporated out in the presence of a moist air stream, the evaporative cooling effect causes the condensation and nucleation of water droplets onto the polymer solution surface. This leads to the formation of an imprinted porous structure upon removal of the residual solvent and water. The facile removal of the water droplet template leaving its structural imprint is a specifically appealing aspect of the breath figure film technology. The first part of the dissertation work involves the fabrication of drug loaded breath figure thin films and its utilization as a controlled drug release carrier and biomaterial scaffold. In a single fabrication step, single layer/multilayer porous thin films were designed and developed by combining the breath figure process and a modified spin or dip coating technique. Using biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) and poly (ethylene glycol) (PEG), drug loaded films were fabricated onto FDA approved medical devices (the Glaucoma drainage device and the Surgical hernia mesh). The porosity of the films is in the range of 2-4 microm as characterized by scanning electron microscope. The drug coated medical implants were characterized for their surface and bulk morphology, the degradation rate of the film, drug release rate and cell cytotoxicity. The results suggest that the use of breath figure morphologies in biodegradable polymer films adds an additional level of control to drug release. In comparison to non-porous films, the breath figure films showed an increased degradation and enhanced drug release. Furthermore, the porous nature of the film was investigated as a biomaterial scaffold to construct three dimensional in vitro tissue model systems. The breath figure film with interconnected

  16. Bacterial inhibition potential of 3D rapid-prototyped magnesium-based porous composite scaffolds–an in vitro efficacy study

    PubMed Central

    Ma, Rui; Lai, Yu-xiao; Li, Long; Tan, Hong-lue; Wang, Jia-li; Li, Ye; Tang, Ting-ting; Qin, Ling

    2015-01-01

    Bone infections are common in trauma-induced open fractures with bone defects. Therefore, developing anti-infection scaffolds for repairing bone defects is desirable. This study develoepd novel Mg-based porous composite scaffolds with a basal matrix composed of poly(lactic-co-glycolicacid) (PLGA) and tricalcium phosphate (TCP). A unique low-temperature rapid prototyping technology was used to fabricate the scaffolds, including PLGA/TCP (PT), PLGA/TCP/5%Mg (PT5M), PLGA/TCP/10%Mg (PT10M), and PLGA/TCP/15%Mg (PT15M). The bacterial adhesion and biofilm formation of Staphylococcus aureus were evaluated. The results indicated that the Mg-based scaffolds significantly inhibited bacterial adhesion and biofilm formation compared to PT, and the PT10M and PT15M exhibited significantly stronger anti-biofilm ability than PT5M. In vitro degratation tests revealed that the degradation of the Mg-based scaffolds caused an increase of pH, Mg2+ concentration and osmolality, and the increased pH may be one of the major contributing factors to the antibacterial function of the Mg-based scaffolds. Additionally, the PT15M exhibited an inhibitory effect on cell adhesion and proliferation of MC3T3-E1 cells. In conclusion, the PLGA/TCP/Mg scaffolds could inhibit bacterial adhesion and biofilm formation, and the PT10M scaffold was considered to be an effective composition with considerable antibacterial ability and good cytocompatibility. PMID:26346217

  17. N-trimethyl chitosan chloride-coated PLGA nanoparticles overcoming multiple barriers to oral insulin absorption.

    PubMed

    Sheng, Jianyong; Han, Limei; Qin, Jing; Ru, Ge; Li, Ruixiang; Wu, Lihong; Cui, Dongqi; Yang, Pei; He, Yuwei; Wang, Jianxin

    2015-07-22

    Although several strategies have been applied for oral insulin delivery to improve insulin bioavailability, little success has been achieved. To overcome multiple barriers to oral insulin absorption simultaneously, insulin-loaded N-trimethyl chitosan chloride (TMC)-coated polylactide-co-glycoside (PLGA) nanoparticles (Ins TMC-PLGA NPs) were formulated in our study. The Ins TMC-PLGA NPs were prepared using the double-emulsion solvent evaporation method and were characterized to determine their size (247.6 ± 7.2 nm), ζ-potential (45.2 ± 4.6 mV), insulin-loading capacity (7.8 ± 0.5%) and encapsulation efficiency (47.0 ± 2.9%). The stability and insulin release of the nanoparticles in enzyme-containing simulated gastrointestinal fluids suggested that the TMC-PLGA NPs could partially protect insulin from enzymatic degradation. Compared with unmodified PLGA NPs, the positively charged TMC-PLGA NPs could improve the mucus penetration of insulin in mucus-secreting HT29-MTX cells, the cellular uptake of insulin via clathrin- or adsorption-mediated endocytosis in Caco-2 cells and the permeation of insulin across a Caco-2 cell monolayer through tight junction opening. After oral administration in mice, the TMC-PLGA NPs moved more slowly through the gastrointestinal tract compared with unmodified PLGA NPs, indicating the mucoadhesive property of the nanoparticles after TMC coating. Additionally, in pharmacological studies in diabetic rats, orally administered Ins TMC-PLGA NPs produced a stronger hypoglycemic effect, with 2-fold higher relative pharmacological availability compared with unmodified NPs. In conclusion, oral insulin absorption is improved by TMC-PLGA NPs with the multiple absorption barriers overcome simultaneously. TMC-PLGA NPs may be a promising drug delivery system for oral administration of macromolecular therapeutics. PMID:26111015

  18. A facile green approach to prepare core-shell hybrid PLGA nanoparticles for resveratrol delivery.

    PubMed

    Kumar, Sandeep; Lather, Viney; Pandita, Deepti

    2016-03-01

    Green approach has revolutionized the area of nanoparticles (NPs) synthesis by virtue of eco and health friendly protocols. Advancing this further, the study proposes a captivating solvent free method for the preparation of green PLGA-oil nanohybrids (G-PONHs) using acrysol oil and encapsulation of resveratrol therein. G-PONHs were structurally similar to the standard PONHs, but had larger particle size of 375 nm. Avoidance of organic solvents resulted in the formation of smooth NPs which showed a considerable improvement in drug release profile and antioxidant properties. G-PONHs exhibited superior biocompatibility with normal Vero cells, while the cytotoxicity on breast cancer cells was moderate in comparison to standard NPs owing to their large size. The size of NPs was found to be a critical factor governing the amplitude of cytotoxicity. The comparative high stability of G-PONHs further favors the tremendous potential of this novel preparation method and delivery platform. PMID:26708438

  19. Porous silicon gettering

    SciTech Connect

    Tsuo, Y.S.; Menna, P.; Pitts, J.R.

    1996-05-01

    The authors have studied a novel extrinsic gettering method that uses the large surface areas produced by a porous-silicon etch as gettering sites. The annealing step of the gettering used a high-flux solar furnace. They found that a high density of photons during annealing enhanced the impurity diffusion to the gettering sites. The authors used metallurgical-grade Si (MG-Si) prepared by directional solidification casing as the starting material. They propose to use porous-silicon-gettered MG-Si as a low-cost epitaxial substrate for polycrystalline silicon thin-film growth.

  20. Concepts and practices used to develop functional PLGA-based nanoparticulate systems

    PubMed Central

    Sah, Hongkee; Thoma, Laura A; Desu, Hari R; Sah, Edel; Wood, George C

    2013-01-01

    The functionality of bare polylactide-co-glycolide (PLGA) nanoparticles is limited to drug depot or drug solubilization in their hard cores. They have inherent weaknesses as a drug-delivery system. For instance, when administered intravenously, the nanoparticles undergo rapid clearance from systemic circulation before reaching the site of action. Furthermore, plain PLGA nanoparticles cannot distinguish between different cell types. Recent research shows that surface functionalization of nanoparticles and development of new nanoparticulate dosage forms help overcome these delivery challenges and improve in vivo performance. Immense research efforts have propelled the development of diverse functional PLGA-based nanoparticulate delivery systems. Representative examples include PEGylated micelles/nanoparticles (PEG, polyethylene glycol), polyplexes, polymersomes, core-shell–type lipid-PLGA hybrids, cell-PLGA hybrids, receptor-specific ligand-PLGA conjugates, and theranostics. Each PLGA-based nanoparticulate dosage form has specific features that distinguish it from other nanoparticulate systems. This review focuses on fundamental concepts and practices that are used in the development of various functional nanoparticulate dosage forms. We describe how the attributes of these functional nanoparticulate forms might contribute to achievement of desired therapeutic effects that are not attainable using conventional therapies. Functional PLGA-based nanoparticulate systems are expected to deliver chemotherapeutic, diagnostic, and imaging agents in a highly selective and effective manner. PMID:23459088

  1. Tetraiodothyroacetic acid-conjugated PLGA nanoparticles: a nanomedicine approach to treat drug-resistant breast cancer

    PubMed Central

    Bharali, Dhruba J; Yalcin, Murat; Davis, Paul J; Mousa, Shaker A

    2013-01-01

    Aim The aim was to evaluate tetraiodothyroacetic acid (tetrac), a thyroid hormone analog of l-thyroxin, conjugated to poly(lactic-co-glycolic acid) nanoparticles (T-PLGA-NPs) both in vitro and in vivo for the treatment of drug-resistant breast cancer. Materials & methods The uptake of tetrac and T-PLGA-NPs in doxorubicin-resistant MCF7 (MCF7-Dx) cells was evaluated using confocal microscopy. Cell proliferation assays and a chick chorioallantoic membrane model of FGF2-induced angiogenesis were used to evaluate the anticancer effects of T-PLGA-NPs. In vivo efficacy was examined in a MCF7-Dx orthotopic tumor BALBc nude mouse model. Results T-PLGA-NPs were restricted from entering into the cell nucleus, and T-PLGA-NPs inhibited angiogenesis by 100% compared with 60% by free tetrac. T-PLGA-NPs enhanced inhibition of tumor-cell proliferation at a low-dose equivalent of free tetrac. In vivo treatment with either tetrac or T-PLGA-NPs resulted in a three- to five-fold inhibition of tumor weight. Conclusion T-PLGA-NPs have high potential as anticancer agents, with possible applications in the treatment of drug-resistant cancer. PMID:23448245

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

    PubMed Central

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

    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. PMID:27013917

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

    PubMed Central

    Vilos, Cristian; Velasquez, Luis A.; Rodas, Paula I.; Zepeda, Katherine; Bong, Soung-Jae; Herrera, Natalia; Cantin, Mario; Simon, Felipe; Constandil, Luis

    2015-01-01

    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. PMID:25915043

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

    NASA Astrophysics Data System (ADS)

    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.

  5. Gelatin/chitosan/hyaluronan scaffold integrated with PLGA microspheres for cartilage tissue engineering.

    PubMed

    Tan, Huaping; Wu, Jindan; Lao, Lihong; Gao, Changyou

    2009-01-01

    Poly(lactide-co-glycotide) (PLGA) microspheres integrated into gelatin/chitosan/hyaluronan scaffolds were fabricated by freeze-drying and crosslinking with 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide. The effects of the microspheres on porosity, density, compressive modulus, phosphate-buffered saline uptake ratio and weight loss of the scaffolds were evaluated. Generally, a scaffold with a higher PLGA content had a lower porosity and weight loss, and a medium uptake ratio, but a larger apparent density and compressive modulus. When the PLGA content was lower than 50%, the PLGA-integrated scaffolds had a similar pore size (approximately 200microm) as that of the control, and as much as 90% of their porosity could be preserved. In vitro chondrocyte culture in the 50% PLGA-integrated scaffold demonstrated that the cells could proliferate and secrete extracellular matrix at the same level as in the control gelatin/chitosan/hyaluronan scaffold. PMID:18723417

  6. A novel fractional crystallization route to porous TiO2-Fe2O3 composites: large scale preparation and high performances as a photocatalyst and Li-ion battery anode.

    PubMed

    Li, Li; Zhang, Jianbo; Zhu, Qingshan

    2016-02-21

    Meso/macroporous TiO2-Fe2O3 composite particles are prepared using naturally abundant ilmenite via a novel heat treatment induced fractional crystallization strategy in a fluidized bed. Fluid-bed roasting in oxidizing and reducing environments is carried out in order to realize the fractional crystallization of ilmenite. Subsequently, acid leaching is employed to remove most of the ferrous phase and form porous TiO2-Fe2O3 composites. The influences of the reaction parameters on the composition, structure and properties of the products are studied. It is found that the pore structure and composition of the porous TiO2-Fe2O3 composite particles can be controlled simply by controlling some parameters, such as the roasting time, temperature, precursor particle size, and post-roasting treatment. Photocatalytic and electrochemical cycling measurements show that the synergism of porous structures and the controlled doping of α-Fe2O3 endow the as-obtained products with excellent visible light photocatalytic activity and provide enhanced performance in lithium ion batteries. The composite porous particles thus obtained may have some promising applications in the fields of photocatalysts, electrode materials, absorbers, pigments etc. This work opens a new avenue for reasonable combination of cost-effective raw materials, a large scale fabricating process and fine control over the structure and composition in the design and preparation of functional materials. PMID:26743456

  7. Design of Controlled Release PLGA Microspheres for Hydrophobic Fenretinide.

    PubMed

    Zhang, Ying; Wischke, Christian; Mittal, Sachin; Mitra, Amitava; Schwendeman, Steven P

    2016-08-01

    Fenretinide, a chemotherapeutic agent for cancer, is water-insoluble and has a very low oral bioavailability. Hence, the objective was to deliver it as an injectable depot and improve the drug solubility and release behavior from poly(lactide-co-glycolide) (PLGA) microspheres by incorporating nonionic surfactants with fenretinide. Enhancement of drug solubilization was observed with Brij 35 or 98, Tween 20, and Pluronic F127, but not Pluronic F68. Co-incorporation of Brij 98 with fenretinide significantly changed the microsphere morphology and improved the fenretinide release profile. The most optimal microsphere formulation, with 20% Brij 98 as excipient, showed an initial in vitro burst around 20% and a sustained release over 28 days in a solubilizing release medium at 37 °C. The effect of addition of MgCO3, drug loading, and polymer blending on the release of fenretinide from PLGA microspheres was also investigated and observed to enhance the drug release. Two sustained release formulations, one incorporating 20% Brij 98 and the other incorporating 3% MgCO3 in the oil phase, were selected for dosing in Sprague-Dawley rats and compared to a single injection of an equivalent dose of fenretinide drug suspension. These two formulations were chosen due to their high encapsulation efficiency, high cumulative release, and desirable in vitro release profile. The drug suspension resulted in a higher initial release in rats compared to the polymeric formulations, however, sustained release was also observed beyond 2 weeks, which may be attributed to the physiological disposition of the drug in vivo. The two PLGA based test formulations provided the desired low initial burst of fenretinide followed by 4 weeks of in vivo sustained release. PMID:27144450

  8. Preparation and In-vitro Evaluation of Controlled Release PLGA Microparticles Containing Triptoreline.

    PubMed

    Mahboubian, Alireza; Hashemein, Seyyed Kazem; Moghadam, Shadi; Atyabi, Fatemeh; Dinarvand, Rassoul

    2010-01-01

    Triptoreline is a potent agonist of luteinizing hormone-releasing hormone, currently used in the treatment of prostatic cancer where therapy may be required over months or years. Frequent injection of drug decreases patients' compliance. The present study describes the formulation of a sustained release microparticulate drug delivery system containing triptoreline acetate, using poly (D,L lactide-co-glycolide) (PLGA). Biodegradable microspheres were prepared using 50 : 50 PLGA by a water in-oil-in-water (w/o/w) double emulsion-solvent evaporation procedure and characterized for drug content and drug release rate using the a HPLC method, particle size distribution using the laser diffraction method, and surface morphology using scanning electron microscopy and drug release rate. Effect of critical process parameters and formulation variables; i.e. volume of inner water phase, addition of NaCl to the outer aqueous phase (W2), addition of different types and amounts of emulsifying agents on microsphere characteristics; were investigated. Microspheres prepared were spherical with a smooth surface, but addition of poloxamer to the first emulsion produced microspheres with large pores. Size of microparticles was dependent on the type, as well as the amount of co-encapsulated surfactants. Increasing the inner water phase volume resulted in larger particles with a lower encapsulation efficiency. Low concentrations of Span 20 decreased triptoreline release rate, whereas the addition of poloxamer or high concentrations of Span 20 increased the drug release rateit. In conclusion, by selecting an appropriate level of the investigated parameters, spherical microparticles with encapsulation efficiencies higher than 90% and a prolonged triptoreline release over 45 days were obtained. PMID:24381601

  9. In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid) foams.

    PubMed

    Lu, L; Peter, S J; Lyman, M D; Lai, H L; Leite, S M; Tamada, J A; Uyama, S; Vacanti, J P; Langer, R; Mikos, A G

    2000-09-01

    This study investigated the in vitro degradation of porous poly(DL-lactic-co-glycolic acid) (PLGA) foams during a 20-week period in pH 7.4 phosphate-buffered saline (PBS) at 37 degrees C and their in vivo degradation following implantation in rat mesentery for up to 8 weeks. Three types of PLGA 85 : 15 and three types of 50 : 50 foams were fabricated using a solvent-casting, particulate-leaching technique. The two types had initial salt weight fraction of 80 and 90%, and a salt particle size of 106-150 microm, while the third type had 90% initial weight fraction of salt in the size range 0-53 microm. The porosities of the resulting foams were 0.82, 0.89, and 0.85 for PLGA 85 : 15, and 0.73, 0.87, and 0.84 for PLGA 50 : 50 foams, respectively. The corresponding median pore diameters were 30, 50, and 17 microm for PLGA 85: 15, and 19, 17, and 17 microm for PLGA 50 : 50. The in vitro and in vivo degradation kinetics of PLGA 85: 15 foams were independent of pore morphology with insignificant variation in foam weight, thickness, pore distribution, compressive creep behavior, and morphology during degradation. The in vitro foam half-lives based on the weight average molecular weight were 11.1 +/- 1.8 (80%, 106-150 microm), 12.0 +/- 2.0 (90%, 106-150 microm), and 11.6 +/- 1.3 (90%, 0-53 microm) weeks, similar to the corresponding values of 9.4 +/- 2.2, 14.3 +/- 1.5, and 13.7 +/- 3.3 weeks for in vivo degradation. In contrast, all PLGA 50 : 50 foams exhibited significant change in foam weight, water absorption, and pore distribution after 6-8 weeks of incubation with PBS. The in vitro foam half-lives were 3.3 +/- 0.3 (80%, 106-150 microm), 3.0 +/- 0.3 (90%, 106-150 microm), and 3.2 +/- 0.1 (90%, 0-53 microm) weeks, and the corresponding in vivo half-lives were 1.9 micro 0.1, 2.2 +/- 0.2, and 2.4 +/- 0.2 weeks. The significantly shorter half-lives of PLGA 50: 50 compared to 85: 15 foams indicated their faster degradation both in vitro and in vivo. In addition, PLGA 50: 50

  10. Evaluation of antibiotic releasing porous polymethylmethacrylate space maintainers in an infected composite tissue defect model.

    PubMed

    Spicer, Patrick P; Shah, Sarita R; Henslee, Allan M; Watson, Brendan M; Kinard, Lucas A; Kretlow, James D; Bevil, Kristin; Kattchee, Lauren; Bennett, George N; Demian, Nagi; Mende, Katrin; Murray, Clinton K; Jansen, John A; Wong, Mark E; Mikos, Antonios G; Kasper, F Kurtis

    2013-11-01

    This study evaluated the in vitro and in vivo performance of antibiotic-releasing porous polymethylmethacrylate (PMMA)-based space maintainers comprising a gelatin hydrogel porogen and a poly(dl-lactic-co-glycolic acid) (PLGA) particulate carrier for antibiotic delivery. Colistin was released in vitro from either gelatin or PLGA microparticle loaded PMMA constructs, with gelatin-loaded constructs releasing colistin over approximately 7 days and PLGA microparticle-loaded constructs releasing colistin for up to 8 weeks. Three formulations with either burst release or extended release at different doses were tested in a rabbit mandibular defect inoculated with Acinetobacter baumannii (2×10(7) colony forming units ml(-1)). In addition, one material control that released antibiotic but was not inoculated with A. baumannii was tested. A. baumannii was not detectable in any animal after 12 weeks on culture of the defect, saliva, or blood. Defects with high dose extended release implants had greater soft tissue healing compared with defects with burst release implants, with 8 of 10 animals showing healed mucosae compared with 2 of 10 respectively. Extended release of locally delivered colistin via a PLGA microparticle carrier improved soft tissue healing compared with implants with burst release of colistin from a gelatin carrier. PMID:23891810

  11. Hydrogels composed of cyclodextrin inclusion complexes with PLGA-PEG-PLGA triblock copolymers as drug delivery systems.

    PubMed

    Khodaverdi, Elham; Mirzazadeh Tekie, Farnaz Sadat; Hadizadeh, Farzin; Esmaeel, Haydar; Mohajeri, Seyed Ahmad; Sajadi Tabassi, Sayyed A; Zohuri, Gholamhossein

    2014-02-01

    Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA-PEGPLGA and α-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties. Naltrexone hydrochloride and vitamin B12 were loaded, and their release profiles were determined. PMID:24234803

  12. Synthesis of doxorubicin-PLGA loaded chitosan stabilized (Mn, Zn)Fe2O4 nanoparticles: Biological activity and pH-responsive drug release.

    PubMed

    Montha, Wararat; Maneeprakorn, Weerakanya; Buatong, Nattha; Tang, I-Ming; Pon-On, Weeraphat

    2016-02-01

    We have synthesized Mn1-xZnxFe2O4 ((Mn, Zn) ferrite) magnetic nanoparticles (MNPs) having radius of 25nm to act as platforms for delivering drugs. The Mn0.9Zn0.1Fe2O4 MNPs exhibit superparamagnetic behavior with large saturation magnetization (MS). They were encapsulated in polymer so that they can be developed into PLGA-coated chitosan stabilized (Mn, Zn) MNPs, i.e., DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 which can serve as an effective carrier of the anti-cancer drug doxorubicin (DOX) whose release would be controlled by the pH in the environment surrounding the cancer tumor. The structure of the as-prepared particles is of a magnetic core-encapsulated by polymer shell layer of around 50nm thick. At a pH of 4.0, the DOX release within the first 5h is fast (around 57%). It becomes slower (around 46% over the next 25h) when the pH is increased to 7.4. The DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 (for concentrations lower than 125μgmL(-1)) shows lower toxicity against HeLa cells using DOX only. When the DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 is increased to 250μgmL(-1), the DOX-PLGA@CS@Mn0.9Zn0.1Fe2O4 shows greater anti-cancer activity and has satisfactory therapeutic effect. The slow sustained release of the DOX by the drug loaded particles when they are in the physiological pH environment (7.4) of normal tissues and mild toxicity of DOX against cancer cell at low concentration point to the DOX loaded PLGA@CS@Mn0.9Zn0.1Fe2O4 being safely used for treating cancer. The higher dosage of DOX needed to kill the cancer cells will be released when the synthesized carriers are subject to the pH stimuli surrounding these cells. PMID:26652369

  13. Development of hematin conjugated PLGA nanoparticle for selective cancer targeting.

    PubMed

    Amin, Md Lutful; Kim, Dami; Kim, SeJin

    2016-08-25

    Targeted nanomedicine for cancer therapy has gained widespread popularity and is being extensively explored. Porphyrins have intrinsic tumor localizing ability and have been studied for photodynamic therapy. However, they have not been used as cancer targeting agents for nanomedicines. In this study, PLGA nanoparticles were formulated and an iron-containing blood porphyrin, hematin was conjugated to the surface of the nanoparticles to investigate selectivity towards cancer cell and cellular internalization. Hematin was previously shown to facilitate growth and proliferation of cancer cells. PLGA nanoparticles were characterized by FE-SEM, AFM, DLS, and Zeta potential analyzer. The conjugation of hematin was confirmed by FTIR. HeLa cells were used to study tumor selectivity and uptake. Hematin conjugated particles (ζ potential: -15.19mV) showed higher affinity towards the cancer cells than the control particles. The result indicated that the particles were internalized by heme carrier protein-1. Together these data suggest that hematin is a promising cancer targeting material for nanotherapeutics. PMID:27260086

  14. Transdermal iontophoresis of flufenamic acid loaded PLGA nanoparticles.

    PubMed

    Malinovskaja-Gomez, K; Labouta, H I; Schneider, M; Hirvonen, J; Laaksonen, T

    2016-06-30

    The objective of this study was to test in vitro a drug delivery system that combines nanoencapsulation and iontophoresis for the transdermal delivery of lipophilic model drug using poly(lactic-co-glycolic acid) (PLGA) as the carrier polymer. Negatively charged fluorescent nanoparticles loaded with negatively charged flufenamic acid were prepared. The colloidal properties of the particles were stable under iontophoretic current (constant, pulsed and alternating) profiles and in contact with skin barrier. The release of the drug from the particles was not affected by iontophoresis and remained always limited (≈50%), leading to significantly lower transdermal fluxes across human epidermis and full thickness porcine skin compared to respective free drug formulation. From nanoparticles, pulsed current profile resulted in comparable or higher fluxes compared to constant current profile although fluorescence imaging was not able to confirm deeper distribution of nanoparticles in skin. Based on our results, there is no clear advantage with respect to drug permeation from nanoencapsulating flufenamic acid into PLGA nanoparticles compared to free drug formulation, either in passive or iontophoretic delivery regimens. However, pulsed current iontophoresis could be an effective alternative instead of traditional constant current iontophoresis to enhance transdermal permeation of drugs from nanoencapsulated formulations. PMID:27131608

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

    PubMed Central

    Figueiredo, Marxa; Esenaliev, Rinat

    2012-01-01

    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. PMID:22506124

  16. PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

    PubMed

    Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; De Rosa, Enrica; Yazdi, Iman K; Liu, Xeuwu; Ferrari, Mauro; Tasciotti, Ennio

    2015-08-01

    In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(dl-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV's morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. The composites were fully characterized by optical microscopy, scanning electron microscopy, ζ potential, Fourier transform infrared spectroscopy, and thermogravimetric analysis-differential scanning calorimetry, and their release kinetics over 30 days. PLGA-MSV's biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the

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

    PubMed

    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. PMID:25241283

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

    PubMed Central

    2013-01-01

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

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed Central

    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

  1. Femtosecond laser ablation of highly oriented pyrolytic graphite: a green route for large-scale production of porous graphene and graphene quantum dots

    NASA Astrophysics Data System (ADS)

    Russo, Paola; Hu, Anming; Compagnini, Giuseppe; Duley, Walter W.; Zhou, Norman Y.

    2014-01-01

    Porous graphene (PG) and graphene quantum dots (GQDs) are attracting attention due to their potential applications in photovoltaics, catalysis, and bio-related fields. We present a novel way for mass production of these promising materials. The femtosecond laser ablation of highly oriented pyrolytic graphite (HOPG) is employed for their synthesis. Porous graphene (PG) layers were found to float at the water-air interface, while graphene quantum dots (GQDs) were dispersed in the solution. The sheets consist of one to six stacked layers of spongy graphene, which form an irregular 3D porous structure that displays pores with an average size of 15-20 nm. Several characterization techniques have confirmed the porous nature of the collected layers. The analyses of the aqueous solution confirmed the presence of GQDs with dimensions of about 2-5 nm. It is found that the formation of both PG and GQDs depends on the fs-laser ablation energy. At laser fluences less than 12 J cm-2, no evidence of either PG or GQDs is detected. However, polyynes with six and eight carbon atoms per chain are found in the solution. For laser energies in the 20-30 J cm-2 range, these polyynes disappeared, while PG and GQDs were found at the water-air interface and in the solution, respectively. The origin of these materials can be explained based on the mechanisms for water breakdown and coal gasification. The absence of PG and GQDs, after the laser ablation of HOPG in liquid nitrogen, confirms the proposed mechanisms.Porous graphene (PG) and graphene quantum dots (GQDs) are attracting attention due to their potential applications in photovoltaics, catalysis, and bio-related fields. We present a novel way for mass production of these promising materials. The femtosecond laser ablation of highly oriented pyrolytic graphite (HOPG) is employed for their synthesis. Porous graphene (PG) layers were found to float at the water-air interface, while graphene quantum dots (GQDs) were dispersed in the

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

    PubMed

    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. PMID:23701139

  3. Release of a Wound-Healing Agent from PLGA Microspheres in a Thermosensitive Gel

    PubMed Central

    Machado, H. A.; Abercrombie, J. J.; You, T.; DeLuca, P. P.; Leung, K. P.

    2013-01-01

    The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4–7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant

  4. Porous bioactive materials

    NASA Astrophysics Data System (ADS)

    Zhang, Kai

    Bioactive materials chemically bond to tissues through the development of biologically active apatite. Porous structures in biomaterials are designed to enhance bioactivity, grow artificial tissues and achieve better integration with host tissues in the body. The goal of this research is to design, fabricate and characterize novel porous bioactive materials. 3D ordered macroporous bioactive glasses (3DOM-BGs, pore size: 200--1000 nm) were prepared using a sol-gel process and colloidal crystal templates. 3DOM-BGs are more bioactive and degradable than mesoporous (pore size <50 nm) sol-gel BGs in simulated body fluid (SBF). Apatite formation and 3DOM-BG degradation rates increased with the decrease of soaking ratio. Apatite induction time in SBF increased with 3DOM-BG calcination temperature (600--800°C). Apatite formation and 3DOMBG degradation were slightly enhanced for a phosphate containing composition. Large 3DOM-BG particles formed less apatite and degraded less completely as compared with small particles. An increase in macropore size slowed down 3DOM-BG degradation and apatite formation processes. After heating the converted apatite at a temperature higher than 700°C, highly crystalline hydroxyapatite and a minor tri-calcium phosphate phase formed. 3DOM-BGs have potential applications as bone/periodontal fillers, and drugs and biological factors delivery agents. Anchoring artificial soft tissues (e.g., cartilage) to native bone presents a challenge. Porous polymer/bioactive glass composites are candidate materials for engineering artificial soft tissue/bone interfaces. Porous composites consisting of polymer matrices (e.g., polysulfone, polylactide, and polyurethane) and bioactive glass particles were prepared by polymer phase separation techniques adapted to include ceramic particles. Composites (thickness: 200--500 mum) have asymmetric structures with dense top layers and porous structures beneath. Porous structures consist of large pores (>100 mum) in a

  5. Measurement of PLGA-NP interaction with single smooth muscle cells using optical tweezers

    NASA Astrophysics Data System (ADS)

    Gu, Ling; Mondal, Argha; Homayoni, Homa; Nguyen, Kytai; Mohanty, Samarendra

    2012-10-01

    For intervention of cardiovascular diseases, biodegradable and biocompatible, poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) are emerging as agents of choice for controlled and targeted drug delivery. Therefore development of PLGA-NP with optimal physico-chemical properties will allow efficient binding and thus delivery of drug to targeted cells under various patho-physiological conditions. The force kinetics and its dependence on size of the NPs will be crucial for designing the NPs. Since optical tweezers allow non-contact, highly sensitive force measurement with high spatial and temporal resolution, we utilized it for studying interaction forces between magnetic PLGA nanoparticles with smooth muscle cells (SMC). In order to investigate effect of size, interaction force for 200 to 1100nm PLGA NP was measured. For similar interaction duration, the force was found to be higher with increase in size. The rupture force was found to depend on time of interaction of SMC with NPs.

  6. Current advances in research and clinical applications of PLGA-based nanotechnology

    PubMed Central

    Lü, Jian-Ming; Wang, Xinwen; Marin-Muller, Christian; Wang, Hao; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2009-01-01

    Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases. PMID:19435455

  7. Fabrication of PLGA polymer microspheres for U. S. mediated gene delivery

    NASA Astrophysics Data System (ADS)

    Williamson, Rene G.; Saltzman, William M.; Brandsma, Janet L.

    2001-05-01

    The promises of gene therapy remain unfulfilled because of the lack of a safe and efficient method for transfecting DNA into cells. PLGA has been used as a vehicle for protein, drug, and gene delivery applications because of its biocompatibility and sustained release properties. PLGA polymer microspheres offer advantages of safety and the possibility of sustained intracytoplasmic delivery. The PLGA also protects the plasmid from degradation. Using the double-emulsion microsphere fabrication technique, a new DNA delivery vehicle, comprising of plasmid DNA and octafluoropropane gas encapsulated in PLGA polymer and PVA stabilizer (Sonospheres) was made. The encapsulated gas offers acoustic activity to the microspheres, which enables them to undergo cavitation in an acoustic field. The goal is to lead to increased DNA transfection when these Sonospheres are subjected to an acoustic field in the MHz frequency range. A summary of the fabrication methods and some initial in vitro studies will be presented.

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

    PubMed

    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. PMID:25794477

  9. Spinal cord injury repair by implantation of structured hyaluronic acid scaffold with PLGA microspheres in the rat.

    PubMed

    Wen, Yujun; Yu, Shukui; Wu, Yanhong; Ju, Rongkai; Wang, Hao; Liu, Yujun; Wang, Ying; Xu, Qunyuan

    2016-04-01

    In order to create an optimal microenvironment for neural regeneration in the lesion area after spinal cord injury (SCI), we fabricated a novel scaffold composed of a hyaluronic acid (HA) hydrogel with a longitudinal multi-tubular conformation. The scaffold was modified by binding with an anti-Nogo receptor antibody (antiNgR) and mixed further with poly(lactic-co-glycolic acid) (PLGA) microspheres containing brain-derived neurotrophic factor and vascular endothelial growth factor (HA+PLGA). In the rat, after implantation of this composite into an injured area created by a dorsal hemisection at T9-10 of the spinal cord, favorable effects were seen with regard to the promotion of spinal repair, including excellent integration of the implants with host tissue, inhibition of inflammation, and gliosis. In particular, large numbers of new blood vessels and regenerated nerve fibers were found within and around the implants. Simultaneously, the implanted rats exhibited improved locomotor recovery. Thus, this novel composite material might provide a suitable microenvironment for neural regeneration following SCI. PMID:26463048

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

    PubMed

    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. PMID:24375170

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

    PubMed

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

    2015-06-01

    Mucoadhesive poly (lactic-co-glycolic acid) (PLGA) nanoparticles having a modified shell-matrix derived from polyvinyl alcohol (PVA) and Carbopol (CP), a biodegradable polymer coating, to improve the adhesion and cell transfection properties were developed. The optimum formulations utilized a CP concentration in the range of 0.05-0.2%w/v, and were formed using modified emulsion-solvent evaporation technique. The resulting CP-PLGA nanoparticles were characterized in terms of their physical and chemical properties. The absorbed CP on the PLGA shell-matrix was found to affect the particle size and surface charge, with 0.05% CP giving rise to smooth spherical particles (0.05CP-PLGA) with the smallest size (285.90 nm), and strong negative surface charge (-25.70 mV). The introduction of CP results in an enhancement of the mucoadhesion between CP-PLGA nanoparticles and mucin particles. In vitro cell internalization studies highlighted the potential of 0.05CP-PLGA nanoparticles for transfection into SiHa cells, with uptake being time dependent. Additionally, cytotoxicity studies of CP-PLGA nanoparticles against SiHa cancer cells indicated that low concentrations of the nanoparticles were non-toxic to cells (cell viability >80%). From the various formulations studied, 0.05CP-PLGA nanoparticles proved to be the optimum model carrier having the required mucoadhesive profile and could be an alternative therapeutic efficacy carrier for targeted mucosal drug delivery systems with biodegradable polymer. PMID:25937384

  12. Mechanical properties and osteogenic potential of hydroxyapatite-PLGA-collagen biomaterial for bone regeneration.

    PubMed

    Bhuiyan, Didarul B; Middleton, John C; Tannenbaum, Rina; Wick, Timothy M

    2016-08-01

    A bone graft is a complicated structure that provides mechanical support and biological signals that regulate bone growth, reconstruction, and repair. A single-component material is inadequate to provide a suitable combination of structural support and biological stimuli to promote bone regeneration. Multicomponent composite biomaterials lack adequate bonding among the components to prevent phase separation after implantation. We have previously developed a novel multistep polymerization and fabrication process to construct a nano-hydroxyapatite-poly(D,L-lactide-co-glycolide)-collagen biomaterial (abbreviated nHAP-PLGA-collagen) with the components covalently bonded to each other. In the present study, the mechanical properties and osteogenic potential of nHAP-PLGA-collagen are characterized to assess the material's suitability to support bone regeneration. nHAP-PLGA-collagen films exhibit tensile strength very close to that of human cancellous bone. Human mesenchymal stem cells (hMSCs) are viable on 2D nHAP-PLGA-collagen films with a sevenfold increase in cell population after 7 days of culture. Over 5 weeks of culture, hMSCs deposit matrix and mineral consistent with osteogenic differentiation and bone formation. As a result of matrix deposition, nHAP-PLGA-collagen films cultured with hMSCs exhibit 48% higher tensile strength and fivefold higher moduli compared to nHAP-PLGA-collagen films without cells. More interestingly, secretion of matrix and minerals by differentiated hMSCs cultured on the nHAP-PLGA-collagen films for 5 weeks mitigates the loss of mechanical strength that accompanies PLGA hydrolysis. PMID:27120980

  13. Local delivery of controlled-release simvastatin/PLGA/HAp microspheres enhances bone repair

    PubMed Central

    Tai, I-Chun; Fu, Yin-Chih; Wang, Chih-Kuang; Chang, Je-Ken; Ho, Mei-Ling

    2013-01-01

    Statins are used clinically for reduction of cholesterol synthesis to prevent cardiovascular disease. Previous in vitro and in vivo studies have shown that statins stimulate bone formation. However, orally administered statins may be degraded during first-pass metabolism in the liver. This study aimed to prevent this degradation by developing a locally administered formulation of simvastatin that is encapsulated in poly(lactic-co-glycolic acid)/hydroxyapatite (SIM/PLGA/HAp) microspheres with controlled-release properties. The effect of this formulation of simvastatin on bone repair was tested using a mouse model of gap fracture bridging with a graft of necrotic bone. The simvastatin released over 12 days from 3 mg and 5 mg of SIM/PLGA/HAp was 0.03–1.6 μg/day and 0.05–2.6 μg/day, respectively. SIM/PLGA/HAp significantly stimulated callus formation around the repaired area and increased neovascularization and cell ingrowth in the grafted necrotic bone at week 2 after surgery. At week 4, both 3 mg and 5 mg of SIM/PLGA/HAp increased neovascularization, but only 5 mg SIM/PLGA/HAp enhanced cell ingrowth into the necrotic bone. The low dose of simvastatin released from SIM/PLGA/HAp enhanced initial callus formation, neovascularization, and cell ingrowth in the grafted bone, indicating that SIM/PLGA/HAp facilitates bone regeneration. We suggest that SIM/PLGA/HAp should be developed as an osteoinductive agent to treat osteonecrosis or in combination with an osteoconductive scaffold to treat severe bone defects. PMID:24143094

  14. Design and optimization of PLGA-based diclofenac loaded nanoparticles.

    PubMed

    Cooper, Dustin L; Harirforoosh, Sam

    2014-01-01

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

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

    PubMed Central

    Cooper, Dustin L.; Harirforoosh, Sam

    2014-01-01

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

  16. Antibiotic-releasing Porous Polymethylmethacrylate Constructs for Osseous Space Maintenance and Infection Control

    PubMed Central

    Shi, Meng; Kretlow, James D.; Nguyen, Anson; Young, Simon; Baggett, L. Scott; Wong, Mark E.; Kasper, F. Kurtis; Mikos, Antonios G.

    2010-01-01

    The use of a strategy involving space maintenance as the initial step of a two-stage regenerative medicine approach toward reconstructing significant bony or composite tissue defects in the craniofacial area, preserves the void volume of bony defects and could promote soft tissue healing prior to the subsequent definitive repair. One of the complications with a biomaterial-based space maintenance approach is local infection, which requires early, effective eradication, ideally through local antibiotic delivery. The purpose of this study is to develop a dual function implant material for maintaining osseous space and releasing an antibiotic to eliminate local infection in bony defects. Colistin, a polymyxin antibiotic, was chosen specifically to address infections with Acinetobacter species, the most common pathogen associated with combat-related traumatic craniofacial injuries. Porous polymethylmethacrylate (PMMA) constructs incorporating poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated by mixing a clinically used bone cement formulation of PMMA powder and methylmethacrylate liquid with a carboxymethylcellulose (CMC) hydrogel (40 or 50 wt%) to impart porosity and PLGA microspheres (10 or 15 wt%) loaded with colistin to control drug release. The PMMA/CMC/PLGA construct featured mild setting temperature, controllable surface/bulk porosity by incorporation of the CMC hydrogel, reasonably strong compressive properties, and continuous drug release over a period of 5 weeks with total drug release of 68.1-88.3%, depending on the weight percentage of CMC and PLGA incorporation. The concentration of released colistin was well above its reported minimum inhibitory concentration against susceptible species for 5 weeks. This study provides information on the composition parameters that enable viable porosity characteristics/drug release kinetics of the PMMA/CMC/PLGA construct for the initial space maintenance as part of a two-stage regenerative medicine

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

    PubMed

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

    2016-01-01

    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. PMID:27490577

  18. In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli

    2014-09-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.

  19. BMP-2 Grafted nHA/PLGA Hybrid Nanofiber Scaffold Stimulates Osteoblastic Cells Growth

    PubMed Central

    Haider, Adnan; Kim, Sukyoung; Huh, Man-Woo; Kang, Inn-Kyu

    2015-01-01

    Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/degenerated tissues or organs. Natural bone is a hierarchical structure, comprised of various cells having specific functions that are regulated by sophisticated mechanisms. However, the regulation of the normal functions in damaged or injured cells is disrupted. In order to address this problem, we attempted to artificially generate a scaffold for mimicking the characteristics of the extracellular matrix at the nanoscale level to trigger osteoblastic cell growth. For this purpose, we have chemically grafted bone morphogenetic protein (BMP-2) onto the surface of L-glutamic acid modified hydroxyapatite incorporated into the PLGA nanofiber matrix. After extensive characterization using various spectroscopic techniques, the BMP-g-nHA/PLGA hybrid nanofiber scaffolds were subjected to various in vitro cytocompatibility tests. The results indicated that BMP-2 on BMP-g-nHA/PLGA hybrid nanofiber scaffolds greatly stimulated osteoblastic cells growth, contrary to the nHA/PLGA and pristine PLGA nanofiber scaffold, which are used as control. These results suggest that BMP-g-nHA/PLGA hybrid nanofiber scaffold can be used as a nanodrug carrier for the controlled and targeted delivery of BMP-2, which will open new possibilities for enhancing bone tissue regeneration and will help in the treatment of various bone-related diseases in the future. PMID:26539477

  20. Phagostimulatory effect of uptake of PLGA microspheres loaded with rifampicin on alveolar macrophages.

    PubMed

    Hirota, Keiji; Hasegawa, Taizo; Nakajima, Takehisa; Makino, Kimiko; Terada, Hiroshi

    2011-10-15

    Our previous results on the phagocytic activity of alveolar macrophages (Mϕs) toward poly(lactic-co-glycolic) acid microspheres (PLGA MS) loaded with the anti-tuberculosis agent rifampicin (R-PLGA MS) suggest that the phagocytosis of R-PLGA MS enhances the phagocytic activity of Mϕ cells. To confirm this possibility, we examined the effect of phagocytosis of R-PLGA MS and polystyrene latex (PSL) MS on the phagocytic uptake of fluorescent PSL (F-PSL) MS by cells of the rat alveolar macrophage cell line NR8383 at 37°C. Phagocytic activity was examined in terms of the population of Mϕ cells that had phagocytosed MS (N(total)) and the total number of MS phagocytosed (n(total)) by counting the phagocytic Mϕ cells and the MS ingested in optical microscopic fields. Phagocytosis of R-PLGA MS enhanced about 1.5 times the values of N(total) and n(total) of the phagocytosis of F-PSL MS under the conditions where the phagocytosis of F-PSL MS did not attain the saturated level. In contrast, the phagocytosis of PSL MS did not enhance the phagocytic activity of Mϕ cells toward F-PSL MS. In conclusion, R-PLGA MS are favorable for drug delivery of anti-tuberculosis agents into alveolar Mϕs due to their ability to up-regulate the phagocytosis of MS. PMID:21700434

  1. Multifunctional Bi2S3/PLGA nanocapsule for combined HIFU/radiation therapy.

    PubMed

    Yao, Ming-hua; Ma, Ming; Chen, Yu; Jia, Xiao-qing; Xu, Guang; Xu, Hui-xiong; Chen, Hang-rong; Wu, Rong

    2014-09-01

    A multifunctional organic-inorganic hybrid nanocapsule based on Bi2S3-embedded poly (lactic-co-glycolic acid) (PLGA) nanocapsule has been elaborately designed to combine the merits of both polymeric shell structure and Bi2S3 nanoparticles. Hydrophobic Bi2S3 nanoparticles were successfully introduced into the PLGA nanocapsules via a facile and efficient water/oil/water (W/O/W) emulsion strategy. The elastic polymeric PLGA shell provides the excellent capability of ultrasound contrast imaging to the Bi2S3/PLGA. Meanwhile, the potential of these microcapsules to enhance the high intensity focused ultrasound (HIFU) therapy was demonstrated. Importantly, this research provided the first example of both in vitro and in vivo to demonstrate the radiosensitization effect of Bi2S3-embedded PLGA hybrid nanocapsules against prostate cancer under external X-ray irradiation. Thus, the successful integration of the Bi2S3 and PLGA nanocapsules provided an alternative strategy for the highly efficient ultrasound guided HIFU/RT synergistic therapy. PMID:24973300

  2. PLGA nanoparticle formulation of RK-33: an RNA helicase inhibitor against DDX3

    PubMed Central

    Bol, Guus Martinus; Khan, Raheela; van Voss, Marise Rosa Heerma; Tantravedi, Saritha; Korz, Dorian

    2016-01-01

    Background The DDX3 helicase inhibitor RK-33 is a newly developed anticancer agent that showed promising results in preclinical research (Bol et al. EMBO Mol Med, 7(5):648–649, 2015). However, due to the physicochemical and pharmacological characteristics of RK-33, we initiated development of alternative formulations of RK-33 by preparing sustained release nanoparticles that can be administered intravenously. Methods In this study, RK-33 was encapsulated in poly(lactic-co-glycolic acid) (PLGA), one of the most well-developed biodegradable polymers, using the emulsion solvent evaporation method. Results Hydrodynamic diameter of RK-33-PLGA nanoparticles was about 245 nm with a negative charge, and RK-33-PLGA nanoparticles had a payload of 1.4 % RK-33. RK-33 was released from the PLGA nanoparticles over 7 days (90 ± 5.7 % released by day 7) and exhibited cytotoxicity to human breast carcinoma MCF-7 cells in a time-dependent manner. Moreover, RK-33-PLGA nanoparticles were well tolerated, and systemic retention of RK-33 was markedly improved in normal mice. Conclusions PLGA nanoparticles have a potential as a parenteral formulation of RK-33. PMID:26330329

  3. BMP-2 Grafted nHA/PLGA Hybrid Nanofiber Scaffold Stimulates Osteoblastic Cells Growth.

    PubMed

    Haider, Adnan; Kim, Sukyoung; Huh, Man-Woo; Kang, Inn-Kyu

    2015-01-01

    Biomaterials play a pivotal role in regenerative medicine, which aims to regenerate and replace lost/degenerated tissues or organs. Natural bone is a hierarchical structure, comprised of various cells having specific functions that are regulated by sophisticated mechanisms. However, the regulation of the normal functions in damaged or injured cells is disrupted. In order to address this problem, we attempted to artificially generate a scaffold for mimicking the characteristics of the extracellular matrix at the nanoscale level to trigger osteoblastic cell growth. For this purpose, we have chemically grafted bone morphogenetic protein (BMP-2) onto the surface of L-glutamic acid modified hydroxyapatite incorporated into the PLGA nanofiber matrix. After extensive characterization using various spectroscopic techniques, the BMP-g-nHA/PLGA hybrid nanofiber scaffolds were subjected to various in vitro cytocompatibility tests. The results indicated that BMP-2 on BMP-g-nHA/PLGA hybrid nanofiber scaffolds greatly stimulated osteoblastic cells growth, contrary to the nHA/PLGA and pristine PLGA nanofiber scaffold, which are used as control. These results suggest that BMP-g-nHA/PLGA hybrid nanofiber scaffold can be used as a nanodrug carrier for the controlled and targeted delivery of BMP-2, which will open new possibilities for enhancing bone tissue regeneration and will help in the treatment of various bone-related diseases in the future. PMID:26539477

  4. Anticancer activity of bicalutamide-loaded PLGA nanoparticles in prostate cancers

    PubMed Central

    GUO, JUN; WU, SHU-HONG; REN, WEI-GUO; WANG, XIN-LI; YANG, AI-QING

    2015-01-01

    Prostate cancer is the most commonly diagnosed non-cutaneous malignancy in men in western and most developing countries. Bicalutamide (BLT) is an antineoplastic hormonal agent primarily used in the treatment of locally advanced and metastatic prostate cancers. In the present study, the aim was to develop a nanotechnology-based delivery system to target prostate cancer cells. This involved the development of a BLT-loaded poly(D,L-lactide-co-glycolide) PLGA (PLGA-BLT) nanoparticulate system in an attempt to improve the therapeutic efficacy of BLT in prostate cancer and to mitigate its toxicity. Nanosized particles with a uniform size distribution and spherical shape were developed. PLGA-BLT showed a pronounced cytotoxic effect on LNCaP and C4-2 cancer cells. The superior cell-killing effect of the nanoparticles may be attributable to their sustained drug-release characteristics and high cellular internalization. PLGA-BLT was also found to significantly inhibit colony formation in the two cell lines. Furthermore, the caspase-3 activity of PLGA-BLT treated cancer cells was enhanced, indicating the cell apoptosis-inducing potential of PLGA-BLT. Overall, these results suggest that nanotechnology-based formulations of BLT exhibit superior anticancer activity and have enormous potential in the treatment of prostate cancers. PMID:26668633

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

    PubMed Central

    Shin, Yong Cheol; Yang, Won Jun; Lee, Jong Ho; Oh, Jin-Woo; Kim, Tai Wan; Park, Jong-Chul; Hyon, Suong-Hyu; Han, Dong-Wook

    2014-01-01

    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 both scavenging reactive oxygen species and extending activated partial thromboplastin time. Macroscopic observation after 1 week of surgical treatment revealed that the antiadhesion efficacy of E-PLGA nanofiber membranes was significantly superior to those of untreated controls and pure PLGA equivalents, which was comparable to that of a commercial tissue-adhesion barrier. In conclusion, the E-PLGA hybrid nanofiber can be exploited to craft strategies for the prevention of postsurgical adhesions. PMID:25187710

  6. Biocompatibility and osteogenesis of calcium phosphate composite scaffolds containing simvastatin-loaded PLGA microspheres for bone tissue engineering.

    PubMed

    Zhang, Hao-Xuan; Xiao, Gui-Yong; Wang, Xia; Dong, Zhao-Gang; Ma, Zhi-Yong; Li, Lei; Li, Yu-Hua; Pan, Xin; Nie, Lin

    2015-10-01

    By utilizing a modified solid/oil/water (s/o/w) emulsion solvent evaporation technique, calcium phosphate composite scaffolds containing simvastatin-loaded PLGA microspheres (SIM-PLGA-CPC) were prepared in this study. We characterized the morphology, encapsulation efficiency and in vitro drug release of SIM-loaded PLGA microspheres as well as the macrostructure, pore size, porosity and mechanical strength of the scaffolds. Rabbit bone mesenchymal stem cells (BMSCs) were seeded onto SIM-PLGA-CPC scaffolds, and the proliferation, morphology, cell cycle and differentiation of BMSCs were investigated using the cell counting kit-8 (CCK-8) assay, scanning electron microscopy (SEM), flow cytometry, alkaline phosphatase (ALP) activity and alizarin red S staining, respectively. The results revealed that SIM-PLGA-CPC scaffolds were biocompatible and osteogenic in vitro. To determine the in vivo biocompatibility and osteogenesis of the scaffolds, both pure PLGA-CPC scaffolds and SIM-PLGA-CPC scaffolds were implanted in rabbit femoral condyles and microradiographically and histologically investigated. SIM-PLGA-CPC scaffolds exhibited good biocompatibility and could improve the efficiency of new bone formation. All these results suggested that the SIM-PLGA-CPC scaffolds fulfilled the basic requirements of bone tissue engineering scaffold and possessed application potentials in orthopedic surgery. PMID:25809455

  7. Active self-healing encapsulation of vaccine antigens in PLGA microspheres.

    PubMed

    Desai, Kashappa-Goud H; Schwendeman, Steven P

    2013-01-10

    Herein, we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly(lactic-co-glycolic acid) (PLGA) by simple mixing of preformed active self-microencapsulating (SM) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature (10-38 °C). Co-encapsulating protein-sorbing vaccine adjuvants and polymer plasticizers were used to "actively" load the protein in the polymer pores and facilitate polymer self-healing at a temperature>the hydrated polymer glass transition temperature, respectively. The microsphere formulation parameters and loading conditions to provide optimal active self-healing microencapsulation of vaccine antigens in PLGA was investigated. Active self-healing encapsulation of two antigens, ovalbumin and tetanus toxoid (TT), in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvants (aluminum hydroxide (Al(OH)₃) or calcium phosphate). Active loading of vaccine antigen in Al(OH)₃-PLGA microspheres was found to: a) increase with an increasing loading of Al(OH)₃ (0.88-3 wt.%) and addition of porosigen, b) decrease when the inner Al(OH)₃/trehalose phase to 1 mL outer oil phase and size of microspheres was respectively >0.2 mL and 63 μm, and c) change negligibly by PLGA concentration and initial incubation (loading) temperature. Encapsulation of protein sorbing Al(OH)₃ in PLGA microspheres resulted in suppression of self-healing of PLGA pores, which was then overcome by improving polymer chain mobility, which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA. Active self-healing microencapsulation of manufacturing process-labile TT in PLGA was found to: a) obviate micronization- and organic solvent-induced TT degradation, b) improve antigen loading (1.4-1.8 wt.% TT) and encapsulation efficiency (~97%), c) provide nearly homogeneous distribution and stabilization of antigen in polymer, and d

  8. Active self-healing encapsulation of vaccine antigens in PLGA microspheres

    PubMed Central

    Desai, Kashappa-Goud H.; Schwendeman, Steven P.

    2013-01-01

    Herein, we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly(lactic-co-glycolic acid) (PLGA) by simple mixing of preformed active self-microencapsulating (SM) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature (10-38 °C). Co-encapsulating protein-sorbing vaccine adjuvants and polymer plasticizers were used to “actively” load the protein in the polymer pores and facilitate polymer self-healing at temperature > hydrated polymer glass transition temperature, respectively. The microsphere formulation parameters and loading conditions to provide optimal active self-healing microencapsulation of vaccine antigen in PLGA was investigated. Active self-healing encapsulation of two vaccine antigens, ovalbumin and tetanus toxoid (TT), in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvant (aluminum hydroxide (Al(OH)3) or calcium phosphate). Active loading of vaccine antigen in Al(OH)3-PLGA microspheres was found to: a) increase proportionally with an increasing loading of Al(OH)3 (0.88-3 wt%) and addition of porosigen, b) decrease when the inner Al(OH)3/trehalose phase to 1 mL outer oil phase and size of microspheres was respectively > 0.2 mL and 63 μm, and c) change negligibly by PLGA concentration and initial incubation (loading) temperature. Encapsulation of protein sorbing Al(OH)3 in PLGA microspheres resulted in suppression of self-healing of PLGA pores, which was then overcome by improving polymer chain mobility, which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA. Active self-healing microencapsulation of manufacturing process-labile TT in PLGA was found to: a) obviate micronization- and organic solvent-induced TT degradation, b) improve antigen loading (1.4-1.8 wt% TT) and encapsulation efficiency (~ 97%), c) provide nearly homogeneous distribution and stabilization of antigen in polymer

  9. PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses.

    PubMed

    Ma, Wenxue; Chen, Mingshui; Kaushal, Sharmeela; McElroy, Michele; Zhang, Yu; Ozkan, Cengiz; Bouvet, Michael; Kruse, Carol; Grotjahn, Douglas; Ichim, Thomas; Minev, Boris

    2012-01-01

    The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-γ ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96(®) Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund's adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of -15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund's adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor CTL

  10. Tetracycline-grafted PLGA nanoparticles as bone-targeting drug delivery system

    PubMed Central

    Wang, Hua; Liu, Jun; Tao, Shan; Chai, Guihong; Wang, Jianwei; Hu, Fu-Qiang; Yuan, Hong

    2015-01-01

    Purpose Nanoparticles (NPs) that target bone tissue were developed using poly(lactic-co-glycolic acid) (PLGA) copolymers and tetracycline (TC)-based bone-targeting moieties. These NPs are expected to enable the transport of drugs, such as simvastatin (SIM), for the treatment of osteoporosis. Methods The molecular structures of TC–PLGA were validated by 1H-NMR, and the SIM-loaded NPs were prepared using the solvent emulsification method. The surface properties, cytotoxicity, cellular uptake, cell mineralization, bone targeting potential, and animal pharmacodynamics of the TC–PLGA NPs were evaluated and compared to those of PLGA NPs. Results It was confirmed that the average particle size of the NPs was approximately 220 nm. In phosphate-buffered saline (PBS, pH 7.4), the SIM-loaded NPs exhibited a cumulative release of up to 80% within 72 hours. An in vitro cell evaluation indicated that the NPs had an excellent cellular uptake capacity and showed great biocompatibility with MC3T3-E1 cells, thereby reducing the cytotoxic effects of SIM. The cell mineralization assay showed that the SIM-loaded NPs induced osteogenic differentiation and mineralized nodule formation in MC3T3-E1 cells, thereby achieving the same effect as SIM. Preliminary findings from in vitro and in vivo bone affinity assays indicated that the TC–PLGA NPs may display increased bone-targeting efficiency compared to PLGA NPs lacking a TC moiety. The use of SIM-loaded TC–PLGA NPs in treating osteoporosis was tested through animal pharmacodynamics analyses performed in ovariectomized rats, and the results suggested that the SIM-loaded TC–PLGA NPs can improve the curative effects of SIM on the recovery of bone mineral density compared to either SIM-loaded PLGA NPs or SIM alone. Conclusion Bone-targeting NPs, which were based on the conjugation of TC to PLGA copolymers, have the ability to target bone. These NPs may be developed as a delivery system for hydrophobic drugs, and they are expected to

  11. Bimodal porous gold opals for molecular sensing

    NASA Astrophysics Data System (ADS)

    Chae, Weon-Sik; Yu, Hyunung; Ham, Sung-Kyoung; Lee, Myung-Jin; Jung, Jin-Seung; Robinson, David B.

    2013-11-01

    We have fabricated bimodal porous gold skeletons by double-templating routes using poly(styrene) colloidal opals as templates. The fabricated gold skeletons show a bimodal pore-size distribution, with small pores within spheres and large pores between spheres. The templated bimodal porous gold skeletons were applied in Raman scattering experiments to study sensing efficiency for probe molecules. We found that the bimodal porous gold skeletons showed obvious enhancement of Raman scattering signals versus that of the unimodal porous gold which only has interstitial pores of several hundred nanometers.

  12. Rifapentine-loaded PLGA microparticles for tuberculosis inhaled therapy: Preparation and in vitro aerosol characterization.

    PubMed

    Parumasivam, Thaigarajan; Leung, Sharon S Y; Quan, Diana Huynh; Triccas, Jamie A; Britton, Warwick J; Chan, Hak-Kim

    2016-06-10

    Inhaled delivery of drugs incorporated into poly (lactic-co-glycolic acid) (PLGA) microparticles allows a sustained lung concentration and encourages phagocytosis by alveolar macrophages that harboring Mycobacterium tuberculosis. However, limited data are available on the effects of physicochemical properties of PLGA, including the monomer ratio (lactide:glycide) and molecular weight (MW) on the aerosol performance, macrophage uptake, and toxicity profile. The present study aims to address this knowledge gap, using PLGAs with monomer ratios of 50:50, 75:25 and 85:15, MW ranged 24 - 240kDa and an anti-tuberculosis (TB) drug, rifapentine. The PLGA-rifapentine powders were produced through a solution spray drying technique. The particles were spherical with a smooth surface and a volume median diameter around 2μm (span ~2). When the powders were dispersed using an Osmohaler(®) at 100L/min for 2.4s, the fine particle fraction (FPFtotal, wt.% particles in aerosol <5μm relative to the total recovered drug mass) was ranged between 52 and 57%, with no significant difference between the formulations. This result suggests that the monomer ratio and MW are not crucial parameters for the aerosol performance of PLGA. The phagocytosis analysis was performed using Thp-1 monocyte-derived macrophages. The highest rate of uptake was observed in PLGA 85:15 followed by 75:25 and 50:50 with about 90%, 80% and 70%, respectively phagocytosis over 4h of exposure. Furthermore, the cytotoxicity analysis on Thp-1 and human lung adenocarcinoma epithelial cells demonstrated that PLGA concentration up to 1.5mg/mL, regardless of the monomer composition and MW, were non-toxic. In conclusion, the monomer ratio and MW are not crucial in determining the aerosol performance and cytotoxicity profile of PLGA however, the particles with high lactide composition have a superior tendency for macrophage uptake. PMID:27049049

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

    PubMed

    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. PMID:22088755

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

    PubMed

    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. PMID:27376895

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Preparation and Characterization of Novel PBAE/PLGA Polymer Blend Microparticles for DNA Vaccine Delivery

    PubMed Central

    Balashanmugam, Meenashi Vanathi; Nagarethinam, Sivagurunathan; Jagani, Hitesh; Josyula, Venkata Rao; Alrohaimi, Abdulmohsen; Udupa, Nayanabhirama

    2014-01-01

    Context. Poly(beta-amino ester) (PBAE) with its pH sensitiveness and Poly(lactic-co-glycolic acid) (PLGA) with huge DNA cargo capacity in combination prove to be highly efficient as DNA delivery system. Objective. To study the effectiveness of novel synthesized PBAE polymer with PLGA blend at different ratios in DNA vaccine delivery. Methods. In the present study, multifunctional polymer blend microparticles using a combination of PLGA and novel PBAE polymers A1 (bis(3-(propionyloxy)propyl)3,3′-(propane-1,3-diyl-bis(methylazanediyl))dipropanoate) and A2 (bis(4-(propionyloxy)butyl)3,3′-(ethane-1,2-diyl-bis(isopropylazanediyl))dipropanoate) at different ratios (85 : 15, 75 : 25, and 50 : 50) were prepared by double emulsion solvent removal method. The microparticles were characterized for cytotoxicity, transfection efficiency, and DNA encapsulation efficiency. Result. It was evident from results that among the microparticles prepared with PLGA/PBAE blend the PLGA : PBAE at 85 : 15 ratio was found to be more effective combination than the microparticles prepared with PLGA alone in terms of transfection efficiency and better DNA integrity. Microparticles made of PLGA and PBAE A1 at 85 : 15 ratio, respectively, were found to be less toxic when compared with microparticles prepared with A2 polymer. Conclusion. The results encourage the use of the synthesized PBAE polymer in combination with PLGA as an effective gene delivery system. PMID:25401137

  17. The effect of cross-linking on the microstructure, mechanical properties and biocompatibility of electrospun polycaprolactone-gelatin/PLGA-gelatin/PLGA-chitosan hybrid composite

    NASA Astrophysics Data System (ADS)

    Nguyen, Thi-Hiep; Lee, Byong-Taek

    2012-06-01

    In this study, multilayered scaffolds composed of polycaprolactone (PCL)-gelatin/poly(lactic-co-glycolic acid) (PLGA)-gelatin/PLGA-chitosan artificial blood vessels were fabricated using a double-ejection electrospinning system. The mixed fibers from individual materials were observed by scanning electron microscopy. The effects of the cross-linking process on the microstructure, mechanical properties and biocompatibility of the fibers were examined. The tensile stress and liquid strength of the cross-linked artificial blood vessels were 2.3 MPa and 340 mmHg, respectively, and were significantly higher than for the non-cross-linked vessel (2.0 MPa and 120 mmHg). The biocompatibility of the cross-linked artificial blood vessel scaffold was examined using the MTT assay and by evaluating cell attachment and cell proliferation. The cross-linked PCL-gelatin/PLGA-gelatin/PLGA-chitosan artificial blood vessel scaffold displayed excellent flexibility, was able to withstand high pressures and promoted cell growth; thus, this novel material holds great promise for eventual use in artificial blood vessels.

  18. 40 CFR 761.267 - Sampling non-porous surfaces.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Sampling non-porous surfaces. 761.267...) § 761.267 Sampling non-porous surfaces. (a) Sample large, nearly flat, non-porous surfaces by dividing the surface into roughly square portions approximately 2 meters on each side. Follow the procedures...

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Targeted Delivery of Antibiotics to Intracellular Chlamydial Infections using PLGA Nanoparticles

    PubMed Central

    Toti, Udaya S.; Guru, Bharath R.; Hali, Mirabela; McPharlin, Christopher; Wykes, Susan M.; Panyam, Jayanth; Whittum-Hudson, Judith A.

    2011-01-01

    Chlamydia trachomatis and C pneumoniae are intracellular bacterial pathogens that have been shown to cause, or are strongly associated with, diverse chronic diseases. Persistent infections by both organisms are refractory to antibiotic therapy. The lack of therapeutic efficacy results from the attenuated metabolic rate of persistently infecting chlamydiae in combination with the modest intracellular drug concentrations achievable by normal delivery of antibiotics to the inclusions within which chlamydiae reside in the host cell cytoplasm. In this research, we evaluated whether nanoparticles formulated using the biodegradable poly(d-L-lactide-co-glycolide) (PLGA) polymer can enhance the delivery of antibiotics to the chlamydial inclusion complexes. We initially studied the trafficking of PLGA nanoparticles in Chlamydia-infected cells. We then evaluated nanoparticles for the delivery of antibiotics to the inclusions. Intracellular trafficking studies show that PLGA nanoparticles efficiently concentrate in inclusions in both acutely and persistently infected cells. Further, encapsulation of rifampin and azithromycin antibiotics in PLGA nanoparticles enhanced the effectiveness of the antibiotics in reducing microbial burden. Combination of rifampin and azithromycin was more effective than the individual drugs. Overall, our studies show that PLGA nanoparticles can be effective carriers for targeted delivery of antibiotics to intracellular chlamydial infections. PMID:21652065

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

    PubMed

    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. PMID:26749322

  2. Development of new reverse micellar microencapsulation technique to load water-soluble drug into PLGA microspheres.

    PubMed

    Kim, Hyunjoo; Cho, Mihyun; Sah, Hongkee

    2005-03-01

    The objective of this study was to develop a new reverse micelle-based microencapsulation technique to load tetracycline hydrochloride into PLGA microspheres. To do so, a reverse micellar system was formulated to dissolve tetracycline hydrochloride and water in ethyl formate with the aid of cetyltrimethylammonium bromide. The resultant micellar solution was used to dissolve 0.3 to 0.75 g of PLGA, and microspheres were prepared following a modified solvent quenching technique. As a control experiment, the drug was encapsulated into PLGA microspheres via a conventional methylene chloride-based emulsion procedure. The microspheres were then characterized with regard to drug loading efficiency, their size distribution and morphology. The reverse micellar procedure led to the formation of free-flowing, spherical microspheres with the size mode of 88 microm. When PLGA microspheres were prepared following the conventional methylene chloride-based procedure, most of tetracycline hydrochloride leached to the aqueous external phase: A maximal loading efficiency observed our experimental conditions was below 5%. Their surfaces had numerous pores, while their internal architecture was honey-combed. In sharp contrast, the new reverse micellar encapsulation technique permitted the attainment of a maximal loading efficiency of 63.19 +/- 0.64%. Also, the microspheres had smooth and pore-free surfaces, and hollow cavities were absent from their internal matrices. The results of this study demonstrated that PLGA microspheres could be successfully prepared following the new reverse micellar encapsulation technique. PMID:15832828

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

    NASA Astrophysics Data System (ADS)

    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.

  4. Preformulation Studies of Bee Venom for the Preparation of Bee Venom-Loaded PLGA Particles.

    PubMed

    Park, Min-Ho; Kim, Ju-Heon; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Cho, Cheong-Weon

    2015-01-01

    It is known that allergic people was potentially vulnerable to bee venom (BV), which can induce an anaphylactic shock, eventually leading to death. Up until recently, this kind of allergy was treated only by venom immunotherapy (VIT) and its efficacy has been recognized worldwide. This treatment is practiced by subcutaneous injections that gradually increase the doses of the allergen. This is inconvenient for patients due to frequent injections. Poly (D,L-lactide-co-glycolide) (PLGA) has been broadly studied as a carrier for drug delivery systems (DDS) of proteins and peptides. PLGA particles usually induce a sustained release. In this study, the physicochemical properties of BV were examined prior to the preparation of BV-loaded PLGA nanoparticles NPs). The content of melittin, the main component of BV, was 53.3%. When protected from the light BV was stable at 4 °C in distilled water, during 8 weeks. BV-loaded PLGA particles were prepared using dichloromethane as the most suitable organic solvent and two min of ultrasonic emulsification time. This study has characterized the physicochemical properties of BV for the preparation BV-loaded PLGA NPs in order to design and optimize a suitable sustained release system in the future. PMID:26295219

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

    NASA Astrophysics Data System (ADS)

    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.

  6. Biodegradable polymer (PLGA) coatings featuring cinnamaldehyde and carvacrol mitigate biofilm formation.

    PubMed

    Zodrow, Katherine R; Schiffman, Jessica D; Elimelech, Menachem

    2012-10-01

    Biofilm-associated infections are one of the leading causes of death in the United States. Although infections may be treated with antibiotics, the overuse of antibiotics has led to the spread of antibiotic resistance. Many natural antimicrobial compounds derived from edible plants are safe for human use and target bacteria nonspecifically. Therefore, they may impair biofilm formation with less evolutionary pressure on pathogens. Here, we explore the use of two natural antimicrobial compounds, cinnamaldehyde (CA, from cinnamon) and carvacrol (CARV, from oregano), for biofilm prevention. We have fabricated and characterized films that incorporate CA and CARV into the biodegradable, FDA-approved polymer poly(lactic-co-glycolic acid), PLGA. The addition of CA and CARV to PLGA films not only adds antimicrobial activity but also changes the surface properties of the films, making them more hydrophilic and therefore more resistant to bacterial attachment. An addition of 0.1% CA to a PLGA film significantly impairs biofilm development by Staphylococcus aureus, and 0.1% CARV in PLGA significantly decreases biofilm formation by both Escherichia coli and S. aureus. Pseudomonas aeruginosa, which is less susceptible to CA and CARV, was not affected by the addition of 0.1% CA or CARV to the PLGA coatings; however, P. aeruginosa biofilm was significantly reduced by 1.0% CA. These results indicate that both CA and CARV could potentially be used in low concentrations as natural additives in polymer coatings for indwelling devices to delay colonization by bacteria. PMID:22937881

  7. Ozone Gas as a Benign Sterilization Treatment for PLGA Nanofiber Scaffolds.

    PubMed

    Rediguieri, Carolina Fracalossi; de Jesus Andreoli Pinto, Terezinha; Bou-Chacra, Nadia Araci; Galante, Raquel; de Araújo, Gabriel Lima Barros; do Nascimento Pedrosa, Tatiana; Maria-Engler, Silvya Stuchi; De Bank, Paul A

    2016-04-01

    The use of electrospun nanofibers for tissue engineering and regenerative medicine applications is a growing trend as they provide improved support for cell proliferation and survival due, in part, to their morphology mimicking that of the extracellular matrix. Sterilization is a critical step in the fabrication process of implantable biomaterial scaffolds for clinical use, but many of the existing methods used to date can negatively affect scaffold properties and performance. Poly(lactic-co-glycolic acid) (PLGA) has been widely used as a biodegradable polymer for 3D scaffolds and can be significantly affected by current sterilization techniques. The aim of this study was to investigate pulsed ozone gas as an alternative method for sterilizing PLGA nanofibers. The morphology, mechanical properties, physicochemical properties, and response of cells to PLGA nanofiber scaffolds were assessed following different degrees of ozone gas sterilization. This treatment killed Geobacillus stearothermophilus spores, the most common biological indicator used for validation of sterilization processes. In addition, the method preserved all of the characteristics of nonsterilized PLGA nanofibers at all degrees of sterilization tested. These findings suggest that ozone gas can be applied as an alternative method for sterilizing electrospun PLGA nanofiber scaffolds without detrimental effects. PMID:26757850

  8. Spectral and spatial characterization of protein loaded PLGA nanoparticles.

    PubMed

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

    2010-03-01

    The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess drug contents in poly(dl-lactide-co-glycolide) (PLGA) based nanoparticles of a model protein, cyclosporine A (CyA). A 6-factors 12-runs designed set of experiments with Plackett-Burman (PB) screening was applied in order to examine the effects of drug loading (X(1)), polymer loading (X(2)), emulsifier concentration (X(3)), stirring rate (X(4)), type of organic solvent (X(5)), and ratio of organic to aqueous phases' volumes (X(6)), on drug entrapment efficiency (EFF). After omitting the factors with nonsignificant influences on EFF, a reduced mathematical relationship, EFF = 48.34 + 7.3X(1) - 29.95X(3), was obtained to explain the effect of the significant factors on EFF. Using two different sets for calibration and validation, the developed NIR calibration model was able to assess CyA contents within the 12 PB formulations. NIR spectral imaging was capable of clearly distinguishing the 12 formulations, both qualitatively and quantitatively. A good correlation with a coefficient of 0.9727 was obtained for constructing a quantile-quantile plot for the actual drug loading percentage and the % standard deviation obtained for the drug loading prediction using the hyperspectral images. PMID:19774658

  9. Endocytosis of Nanomedicines: The Case of Glycopeptide Engineered PLGA Nanoparticles

    PubMed Central

    Vilella, Antonietta; Ruozi, Barbara; Belletti, Daniela; Pederzoli, Francesca; Galliani, Marianna; Semeghini, Valentina; Forni, Flavio; Zoli, Michele; Vandelli, Maria Angela; Tosi, Giovanni

    2015-01-01

    The success of nanomedicine as a new strategy for drug delivery and targeting prompted the interest in developing approaches toward basic and clinical neuroscience. Despite enormous advances on brain research, central nervous system (CNS) disorders remain the world’s leading cause of disability, in part due to the inability of the majority of drugs to reach the brain parenchyma. Many attempts to use nanomedicines as CNS drug delivery systems (DDS) were made; among the various non-invasive approaches, nanoparticulate carriers and, particularly, polymeric nanoparticles (NPs) seem to be the most interesting strategies. In particular, the ability of poly-lactide-co-glycolide NPs (PLGA-NPs) specifically engineered with a glycopeptide (g7), conferring to NPs’ ability to cross the blood brain barrier (BBB) in rodents at a concentration of up to 10% of the injected dose, was demonstrated in previous studies using different routes of administrations. Most of the evidence on NP uptake mechanisms reported in the literature about intracellular pathways and processes of cell entry is based on in vitro studies. Therefore, beside the particular attention devoted to increasing the knowledge of the rate of in vivo BBB crossing of nanocarriers, the subsequent exocytosis in the brain compartments, their fate and trafficking in the brain surely represent major topics in this field. PMID:26102358

  10. Thermogelling Biodegradable Polymers with Hydrophilic Backbones: PEG-g-PLGA

    SciTech Connect

    Jeong, Byeongmoon; Kibbey, Merinda R.; Birnbaum, Jerome C.; Won, You-Yeong; Gutowska, Anna

    2000-10-31

    The aqueous solutions of poly(ethylene glycol)grafted with poly(lactic acid-co-glycolic acid) flow freely at room temperature but form gels at higher temperature. The existence of micelles in water at low polymer concentration was confirmed by Cro-transmission electron microscopy and dye solubilization studies. The micellar diameter and critical micelle concentration are about 9 nm and 0.47 wt.% respectively. The critical gel concentration, above which a gel phase appears was 16 wt.% and sol-to-gel transition temperature was slightly affected by the concentration in the range of 16 {approx} 25 wt.%. At sol-to-gel transition, viscosity increased abruptly and C-NMR showed molecular motion of hydrophilic poly(lactic acid-co-glycolic acid) side-chains increased. The hydrogel of PEG-g-PLGA with hydrophilic backbones was transparent during degradation and remained a gel for one week, suggesting a promising material for short-term drug delivery.

  11. Enhanced Biological Functions of Human Mesenchymal Stem-Cell Aggregates Incorporating E-Cadherin-Modified PLGA Microparticles.

    PubMed

    Zhang, Yan; Mao, Hongli; Gao, Chao; Li, Suhua; Shuai, Qizhi; Xu, Jianbin; Xu, Ke; Cao, Lei; Lang, Ren; Gu, Zhongwei; Akaike, Toshihiro; Yang, Jun

    2016-08-01

    Mesenchymal stem cells (MSCs) have emerged as a promising source of multipotent cells for various cell-based therapies due to their unique properties, and formation of 3D MSC aggregates has been explored as a potential strategy to enhance therapeutic efficacy. In this study, poly(lactic-co-glycolic acid) (PLGA) microparticles modified with human E-cadherin fusion protein (hE-cad-PLGA microparticles) have been fabricated and integrated with human MSCs to form 3D cell aggregates. The results show that, compared with the plain PLGA, the hE-cad-PLGA microparticles distribute within the aggregates more evenly and further result in a more significant improvement of cellular proliferation and secretion of a series of bioactive factors due to the synergistic effects from the bioactive E-cadherin fragments and the PLGA microparticles. Meanwhile, the hE-cad-PLGA microparticles incorporated in the aggregates upregulate the phosphorylation of epidermal growth factor receptors and activate the AKT and ERK1/2 signaling pathways in the MSCs. Additionally, the E-cadherin/β-catenin cellular membrane complex in the MSCs is markedly stimulated by the hE-cad-PLGA microparticles. Therefore, engineering 3D cell aggregates with hE-cad-PLGA microparticles can be a promising method for ex vivo multipotent stem-cell expansion with enhanced biological functions and may offer a novel route to expand multipotent stem-cell-based clinical applications. PMID:27245478

  12. Neural Tissue as Porous Media

    SciTech Connect

    Basser, Peter J.

    2008-12-05

    The fields of MR in Porous Media and Neuroradiology have largely developed separately during the past two decades with little appreciation of the problems, challenges and methodologies of the other. However, this trend is clearly changing and possibilities for significant cross-fertilization and synergies are now being realized.

  13. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

    PubMed Central

    2014-01-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC. PMID:25232295

  14. In vitro performance of lipid-PLGA hybrid nanoparticles as an antigen delivery system: lipid composition matters

    NASA Astrophysics Data System (ADS)

    Hu, Yun; Ehrich, Marion; Fuhrman, Kristel; Zhang, Chenming

    2014-08-01

    Due to the many beneficial properties combined from both poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and liposomes, lipid-PLGA hybrid NPs have been intensively studied as cancer drug delivery systems, bio-imaging agent carriers, as well as antigen delivery vehicles. However, the impact of lipid composition on the performance of lipid-PLGA hybrid NPs as a delivery system has not been well investigated. In this study, the influence of lipid composition on the stability of the hybrid NPs and in vitro antigen release from NPs under different conditions was examined. The uptake of hybrid NPs with various surface charges by dendritic cells (DCs) was carefully studied. The results showed that PLGA NPs enveloped by a lipid shell with more positive surface charges could improve the stability of the hybrid NPs, enable better controlled release of antigens encapsulated in PLGA NPs, as well as enhance uptake of NPs by DC.

  15. Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

    NASA Astrophysics Data System (ADS)

    Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

    2015-03-01

    Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

  16. Magnetite loaded Polypeptide-PLGA multifunctional microbubbles for dual-mode US/MR imaging.

    PubMed

    Sun, Ying; Zhu, Yunkai; Huang, Can; Li, Rongxin; Chen, Yaqing; Duan, Yourong

    2016-01-01

    Magnetite loaded Polypeptide-PLGA multifunctional microbubbles (Fe3O4 /Polypeptide-PLGA MMBs) that show superparamagnetic properties were prepared by a modified double emulsion method and employed as imaging agent for dual-mode Ultrasound/Magnetic resonance (US/MR) imaging of prostatic cancer. The successful synthesis of MMBs was determined by Fourier Transform Infrared Spectrometer (FTIR), X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM), Atomic Absorption Spectroscopy (AAS) and vibrating sample magnetometer (VSM). The as-prepared MMBs had a diameter of 700 nm and were quite safe as confirmed by MTT assays. Prussian Blue Staining showed that targeted Fe3O4 /Polypeptide-PLGA MMBs enhanced the cellular uptake efficiency. In cell attachment study, adherence of MMBs was significantly higher to LNCaP cells compared with negative control PC3 cells. The in vitro results demonstrated that these MMBs could enhance both US and MR imaging of prostatic cancer. PMID:26647349

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

    PubMed Central

    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. PMID:26744842

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

    PubMed

    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. PMID:26744842

  19. Solute transport through a deforming porous medium

    NASA Astrophysics Data System (ADS)

    Peters, Glen P.; Smith, David W.

    2002-06-01

    Solute transport through a porous medium is typically modelled assuming the porous medium is rigid. However, many applications exist where the porous medium is deforming, including, municipal landfill liners, mine tailings dams, and land subsidence. In this paper, mass balance laws are used to derive the flow and transport equations for a deforming porous medium. The equations are derived in both spatial and material co-ordinate systems. Solute transport through an engineered landfill liner is used as an illustrative example to show the differences between the theory for a rigid porous medium, and small and large deformation analysis of a deforming porous medium. It is found that the large deformation model produces shorter solute breakthrough times, followed by the small deformation model, and then the rigid porous medium model. It is also found that it is important to include spatial and temporal void ratio variations in the large deformation analysis. It is shown that a non-linear large deformation model may greatly reduce the solute breakthrough time, compared to a standard transport analysis typically employed by environmental engineers.

  20. Electrospun PLGA fibers incorporated with functionalized biomolecules for cardiac tissue engineering.

    PubMed

    Yu, Jiashing; Lee, An-Rei; Lin, Wei-Han; Lin, Che-Wei; Wu, Yuan-Kun; Tsai, Wei-Bor

    2014-07-01

    Structural similarity of electrospun fibers (ESFs) to the native extracellular matrix provides great potential for the application of biofunctional ESFs in tissue engineering. This study aimed to synthesize biofunctionalized poly (L-lactide-co-glycolide) (PLGA) ESFs for investigating the potential for cardiac tissue engineering application. We developed a simple but novel strategy to incorporate adhesive peptides in PLGA ESFs. Two adhesive peptides derived from laminin, YIGSR, and RGD, were covalently conjugated to poly-L-lysine, and then mingled with PLGA solution for electrospinning. Peptides were uniformly distributed on the surface and in the interior of ESFs. PLGA ESFs incorporated with YIGSR or RGD or adsorbed with laminin significantly enhanced the adhesion of cardiomyocytes isolated from neonatal rats. Furthermore, the cells were found to adhere better on ESFs compared with flat substrates after 7 days of culture. Immunofluorescent staining of F-actin, vinculin, a-actinin, and N-cadherin indicated that cardiomyocytes adhered and formed striated α-actinin better on the laminin-coated ESFs and the YIGSR-incorporated ESFs compared with the RGD-incorporated ESFs. The expression of α-myosin heavy chain and β-tubulin on the YIGSR-incorporated ESFs was significantly higher compared with the expression level on PLGA and RGD-incorporated samples. Furthermore, the contraction of cardiomyocytes was faster and lasted longer on the laminin-coated ESFs and YIGSR-incorporated ESFs. The results suggest that aligned YIGSR-incorporated PLGA ESFs is a better candidate for the formation of cardiac patches. This study demonstrated the potential of using peptide-incorporated ESFs as designable-scaffold platform for tissue engineering. PMID:24471778

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

    PubMed Central

    Xiao, Xiaojun; Zeng, Xiaowei; Zhang, Xinxin; Ma, Li; Liu, Xiaoyu; Yu, Haiqiong; Mei, Lin; Liu, Zhigang

    2013-01-01

    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(OH)3 due to its superior efficacy, longer potency, and markedly fewer side effects. The rCmP-loaded PLGA nanoparticles developed herein offer a promising avenue for specific immunotherapy in allergic asthma. PMID:24376349

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Effects of Microemulsion Preparation Conditions on Drug Encapsulation Efficiency of PLGA Nanoparticles

    NASA Astrophysics Data System (ADS)

    Ng, Set Hui; Ooi, Ing Hong

    2011-12-01

    Emulsion solvent evaporation technique is widely used to prepare nanoparticles of many organic polymer drug carriers. The mechanism of nanoparticle generation by this technique involves oil-in-water (O/W) microemulsion formation followed by solvent evaporation. Various microemulsion preparation conditions can affect the encapsulation efficiency of drug in the nanoparticulate carrier. In this study, emulsifying speed, emulsifying temperature, and organic-to-aqueous phase ratio were varied and the resulting encapsulation efficiency of a model drug in Poly(Lactide-co-Glycolide) (PLGA) nanoparticles was determined. The organic phase containing PLGA and a model drug dissolved in chloroform was first dispersed in an aqueous solution containing 0.5 %(w/v) Poly(vinyl alcohol) (PVA), which was then homogenized at high speeds. The resulting O/W microemulsion was subsequently subjected to stirring at room temperature for four hours during which the solvent diffused and evaporated gradually. The fine white suspension was centrifuged and freeze-dried. The model drug loading in the PLGA nanoparticles was determined using UV spectrophotometry. Results showed that the encapsulation efficiency of a model drug, salicylic acid, ranged from 8.5% to 17% depending on the microemulsion preparation conditions. Under the same temperature (15 °C) and homogenization speed (19000 rpm) conditions studied, a relatively high organic-to-aqueous phase ratio (1:5) provided salicylic acid loaded PLGA nanoparticles with significantly higher drug encapsulation efficiency. In addition, under all microemulsion preparation conditions, PLGA nanoparticles obtained after solvent evaporation and freeze drying were spherical and aggregation between the nanoparticles was not observed under a high power microscope. This indicates that PLGA nanoparticles with desirable amount of drug and with anticipated size and shape can be realized by controlling emulsification process conditions.

  4. Hollow superparamagnetic PLGA/Fe 3O 4 composite microspheres for lysozyme adsorption

    NASA Astrophysics Data System (ADS)

    Yang, Qi; Wu, Yao; Lan, Fang; Ma, Shaohua; Xie, Liqin; He, Bin; Gu, Zhongwei

    2014-02-01

    Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe3O4 composite microspheres composed of an inner cavity, PLGA inner shell and Fe3O4 outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe3O4 nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 μm showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g-1) and high efficiency in lysozyme adsorption.

  5. Hollow superparamagnetic PLGA/Fe3O4 composite microspheres for lysozyme adsorption.

    PubMed

    Yang, Qi; Wu, Yao; Lan, Fang; Ma, Shaohua; Xie, Liqin; He, Bin; Gu, Zhongwei

    2014-02-28

    Uniform hollow superparamagnetic poly(lactic-co-glycolic acid) (PLGA)/Fe(3)O(4) composite microspheres composed of an inner cavity, PLGA inner shell and Fe(3)O(4) outer shell have been synthesized by a modified oil-in-water (O/W) emulsion-solvent evaporation method using Fe(3)O(4) nanoparticles as a particulate emulsifier. The obtained composite microspheres with an average diameter of 2.5 μm showed excellent monodispersity and stability in aqueous medium, strong magnetic responsiveness, high magnetite content (>68%), high saturation magnetization (58 emu g(-1)) and high efficiency in lysozyme adsorption. PMID:24492410

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

    PubMed Central

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

    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/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 this study

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

    NASA Astrophysics Data System (ADS)

    Kaur, Manpreet; Singh, Surinder; Mehta, Rajeev

    2014-12-01

    Swift heavy ions induced modification of thin films of blends of poly(lactide-co-glycolide) (PLGA) (50:50) with organically modified nanoclay (Cloisite® 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.

  8. PLA/PLGA nanoparticles for sustained release of docetaxel.

    PubMed

    Musumeci, T; Ventura, C A; Giannone, I; Ruozi, B; Montenegro, L; Pignatello, R; Puglisi, G

    2006-11-15

    This study investigates the potentiality of nanosphere colloidal suspensions as sustained release systems for intravenous administration of docetaxel (DTX). Nanospheres were prepared by solvent displacement method using polylactic acids (PLA) at different molecular weight and polylactic-co-glycolic (PLGA) as biodegradable matrices. The systems were characterized by light scattering analysis for their mean size, size distribution and zeta potential and by scanning electron microscopy (SEM) for surface morphology. The average diameters of the nanoparticles ranged from 100 to 200 nm. Negative zeta potential values were observed for all systems, particularly the nanospheres produced with the lowest molecular weight PLA showed a zeta potential value of -28mV. Differential scanning calorimetry analysis (DSC) suggested that DTX was molecularly dispersed in the polymeric matrices. A biphasic release of DTX was observed for all colloidal suspensions, after a burst effect in which about 50% (w/w) of the loaded drug was released a sustained release profile for about 10 days was observed. To evaluate the influence of the polymeric carrier on the interaction of DTX with biological membranes, we performed an in vitro study using lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) as a biomembrane model. DSC was used as a simple and not invasive technique of analysis. DTX produced a depression of DPPC pretransition peak, no variation of the main phase transition temperature and a significative increase of DeltaH value, showing a superficial penetration of the drug into DPPC bilayer. Kinetic experiments demonstrated that the release process of DTX form nanospheres is affected by the molecular weight of the employed polymers. PMID:16887303

  9. Impact of PEG and PEG-b-PAGE modified PLGA on nanoparticle formation, protein loading and release.

    PubMed

    Rietscher, René; Czaplewska, Justyna A; Majdanski, Tobias C; Gottschaldt, Michael; Schubert, Ulrich S; Schneider, Marc; Lehr, Claus-Michael

    2016-03-16

    The effect of modifying the well-established pharmaceutical polymer PLGA by different PEG-containing block-copolymers on the preparation of ovalbumin (OVA) loaded PLGA nanoparticles (NPs) was studied. The used polymers contained poly(d,l-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG) and poly(allyl glycidyl ether) (PAGE) as building blocks. The double emulsion technique yielded spherical NPs in the size range from 170 to 220 nm (PDI<0.15) for all the differently modified polymers, allowing to directly compare protein loading of and release. PEGylation is usually believed to increase the hydrophilic character of produced particles, favoring encapsulation of hydrophilic substances. However, in this study simple PEGylation of PLGA had only a slight effect on protein release. In contrast, incorporating a PAGE block between the PEG and PLGA units, also eventually enabling active targeting introducing a reactive group, led to a significantly higher loading (+25%) and release rate (+100%), compared to PLGA and PEG-b-PLGA NPs. PMID:26784983

  10. Hyaluronic Acid-Modified Cationic Lipid-PLGA Hybrid Nanoparticles as a Nanovaccine Induce Robust Humoral and Cellular Immune Responses.

    PubMed

    Liu, Lanxia; Cao, Fengqiang; Liu, Xiaoxuan; Wang, Hai; Zhang, Chao; Sun, Hongfan; Wang, Chun; Leng, Xigang; Song, Cunxian; Kong, Deling; Ma, Guilei

    2016-05-18

    Here, we investigated the use of hyaluronic acid (HA)-decorated cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles (HA-DOTAP-PLGA NPs) as vaccine delivery vehicles, which were originally developed for the cytosolic delivery of genes. Our results demonstrated that after the NPs uptake by dendritic cells (DCs), some of the antigens that were encapsulated in HA-DOTAP-PLGA NPs escaped to the cytosolic compartment, and whereas some of the antigens remained in the endosomal/lysosomal compartment, where both MHC-I and MHC-II antigen presentation occurred. Moreover, HA-DOTAP-PLGA NPs led to the up-regulation of MHC, costimulatory molecules, and cytokines. In vivo experiments further revealed that more powerful immune responses were induced from mice immunized with HA-DOTAP-PLGA NPs when compared with cationic lipid-PLGA nanoparticles and free ovalbumin (OVA); the responses included antigen-specific CD4(+) and CD8(+) T-cell responses, the production of antigen-specific IgG antibodies and the generation of memory CD4(+) and CD8(+) T cells. Overall, these data demonstrate the high potential of HA-DOTAP-PLGA NPs for use as vaccine delivery vehicles to elevate cellular and humoral immune responses. PMID:27088457