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Sample records for random plga fibers

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

    Science.gov (United States)

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

    2016-12-01

    During the last few decades, considerable research on diabetic wound healing strategies has been performed, but complete diabetic wound healing remains an unsolved problem, which constitutes an enormous biomedical burden. Herein, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber matrices loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) are fabricated by coaxial electrospinning. HA/PLGA-E core/shell fiber matrices are composed of randomly-oriented sub-micrometer fibers and have a 3D porous network structure. EGCG is uniformly dispersed in the shell and sustainedly released from the matrices in a stepwise manner by controlled diffusion and PLGA degradation over four weeks. EGCG does not adversely affect the thermomechanical properties of HA/PLGA-E matrices. The number of human dermal fibroblasts attached on HA/PLGA-E matrices is appreciably higher than that on HA/PLGA counterparts, while their proliferation is steadily retained on HA/PLGA-E matrices. The wound healing activity of HA/PLGA-E matrices is evaluated in streptozotocin-induced diabetic rats. After two weeks of surgical treatment, the wound areas are significantly reduced by the coverage with HA/PLGA-E matrices resulting from enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or HA/PLGA. In conclusion, the HA/PLGA-E matrices can be potentially exploited to craft strategies for the acceleration of diabetic wound healing and skin regeneration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Poly(lactic-co-glycolic.acid) (PLGA) and PLGA/gelatin random nanofibrous scaffolds embedded with different amounts of mesoporous silica nanoparticles (MSNPs) were fabricated using electrospinning method. To evaluate the effects of nanoparticles on the scaffolds, physical, chemical, and mechanical...... 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 nano fibers matrix increases the weight loss percentage of PLGA-based samples, whereas it decreases the weight loss...

  3. Hybrid Randomly Electrospun Poly(lactic-co-glycolic acid):Poly(ethylene oxide) (PLGA:PEO) Fibrous Scaffolds Enhancing Myoblast Differentiation and Alignment.

    Science.gov (United States)

    Evrova, Olivera; Hosseini, Vahid; Milleret, Vincent; Palazzolo, Gemma; Zenobi-Wong, Marcy; Sulser, Tullio; Buschmann, Johanna; Eberli, Daniel

    2016-11-23

    Cellular responses are regulated by their microenvironments, and engineered synthetic scaffolds can offer control over different microenvironment properties. This important relationship can be used as a tool to manipulate cell fate and cell responses for different biomedical applications. We show for the first time in this study how blending of poly(ethylene oxide) (PEO) to poly(lactic-co-glycolic acid) (PLGA) fibers to yield hybrid scaffolds changes the physical and mechanical properties of PLGA fibrous scaffolds and in turn affects cellular response. For this purpose we employed electrospinning to create fibrous scaffolds mimicking the basic structural properties of the native extracellular matrix. We introduced PEO to PLGA electrospun fibers by spinning a blend of PLGA:PEO polymer solutions in different ratios. PEO served as a sacrificial component within the fibers upon hydration, leading to pore formation in the fibers, fiber twisting, increased scaffold disintegration, and hydrophilicity, decreased Young's modulus, and significantly improved strain at break of initially electrospun scaffolds. We observed that the blended PLGA:PEO fibrous scaffolds supported myoblast adhesion and proliferation and resulted in increased myotube formation and self-alignment, when compared to PLGA-only scaffolds, even though the scaffolds were randomly oriented. The 50:50 PLGA:PEO blended scaffold showed the most promising results in terms of mechanical properties, myotube formation, and alignment, suggesting an optimal microenvironment for myoblast differentiation from the PLGA:PEO blends tested. The explored approach for tuning fiber properties can easily extend to other polymeric scaffolds and provides a valuable tool to engineer fibrillar microenvironments for several biomedical applications.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-09-01

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

  5. Relationships between mechanical properties and drug release from electrospun fibers of PCL and PLGA blends.

    Science.gov (United States)

    Chou, Shih-Feng; Woodrow, Kim A

    2017-01-01

    Electrospun nanofibers have the potential to achieve high drug loading and the ability to sustain drug release. Mechanical properties of the drug-incorporated fibers suggest the importance of drug-polymer interactions. In this study, we investigated the mechanical properties of electrospun polycaprolactone (PCL) and poly (D,L-lactic-co-glycolic) acid (PLGA) fibers at various blend ratios in the presence and absence of a small molecule hydrophilic drug, tenofovir (TFV). Young׳s modulus of the blend fibers showed dependence on PLGA content and the addition of the drug. At a PCL/PLGA (20/80) composition, Young׳s modulus and tensile strength were independent of drug loading up to 40wt% due to offsetting effects from drug-polymer interactions. In vitro drug release studies suggested that release of TFV significantly decreased fiber mechanical properties. In addition, mechanically stretched fibers displayed a faster release rate as compared to the non-stretched fibers. Finally, drug partition in the blend fibers was estimated using a mechanical model and then experimentally confirmed with a composite of individually stacked fiber meshes. This work provides scientific understanding on the dependence of drug release and drug loading on the mechanical properties of drug-eluting fibers. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-01

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

  7. Physical or Chemical Aging of PLGA Electrospun Fibers Related to its Sequence Distribution

    Science.gov (United States)

    Xu, Shanshan; Wang, Chenhong; Xiao, Bin; Han, Charles

    Biodegradable aliphatic polyesters such as poly(lactic-co-glycolic acid) (PLGA) have been studied for decades and widely used in life sciences. However, the major problems encountered in time-controlled drug delivery, stress maintenance, aging and degradation of this kind of copolymer are lack of stability, which are relied on both molecular weight distribution and sequence distribution. Based on commonly used ring-opening polymerization, PLGA with different sequence distribution was synthesized by controlling the transesterfication. Detailed investigations on electrospun PLGA fibers were carried out to identify the major factor of physical aging or chemical aging. With stretched polymer chains in electrospun fibers, the physical aging could be obtained by both entropy relaxation and contraction of the fibrous membrane. Even under low humidity and low temperature far away from the glass transition temperature, the physical aging of polymer with broad sequence distribution can be intense. These previously unidentified properties can still be improved in regulated clinical application if approached from a different angle.

  8. Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications.

    Science.gov (United States)

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

    2009-09-01

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

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

    Science.gov (United States)

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

    2009-01-01

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

  10. In Vivo Biocompatibility of PLGA-Polyhexylthiophene Nanofiber Scaffolds in a Rat Model

    Directory of Open Access Journals (Sweden)

    Anuradha Subramanian

    2013-01-01

    Full Text Available Electroactive polymers have applications in tissue engineering as a physical template for cell adhesion and carry electrical signals to improve tissue regeneration. Present study demonstrated the biocompatibility and biodegradability of poly(lactide-co-glycolide-poly(3-hexylthiophene (PLGA-PHT blend electrospun scaffolds in a subcutaneous rat model. The biocompatibility of PLGA-undoped PHT, PLGA-doped PHT, and aligned PLGA-doped PHT nanofibers was evaluated and compared with random PLGA fibers. The animals were sacrificed at 2, 4, and 8 weeks; the surrounding tissue along with the implant was removed to evaluate biocompatibility and biodegradability by histologic analysis and GPC, respectively. Histology results demonstrated that all scaffolds except PLGA-undoped PHT showed decrease in inflammation over time. It was observed that the aligned PLGA-doped PHT fibers elicited moderate response at 2 weeks, which further reduced to a mild response over time with well-organized tissue structure and collagen deposition. The degradation of aligned nanofibers was found to be very slow when compared to random fibers. Further, there was no reduction in the molecular weight of undoped form of PHT throughout the study. These experiments revealed the biocompatibility and biodegradability of PLGA-PHT nanofibers that potentiate it to be used as a biomaterial for various applications.

  11. Effects of poly(lactic-co-glycolic acid) (PLGA) degradability on the apatite-forming capacity of electrospun PLGA/SiO(2)-CaO nonwoven composite fabrics.

    Science.gov (United States)

    Kim, In Ae; Rhee, Sang-Hoon

    2010-04-01

    We investigated the effects of poly(lactic-co-glycolic acid) (PLGA) degradability on the apatite-forming ability of electrospun PLGA/SiO(2)-CaO gel composite fabric. Two PLGA copolymer compositions with low and high degradability were used in experiments. A nonwoven polymer/ceramic composite fabric composed of randomly mixed microsized biodegradable PLGA fibers and nanosized bioactive SiO(2)-CaO gel fibers was prepared using a simultaneous electrospinning method. A 17 wt.% PLGA solution was prepared using 1,1,3,3-hexafluoro-2-propanol as a solvent, while the SiO(2)-CaO gel solution was prepared via a condensation reaction following hydrolysis of tetraethyl orthosilicate under acidic conditions. PLGA and SiO(2)-CaO gel solutions were spun simultaneously with two separate nozzles under electric fields of 1 and 2 kV/cm using two syringe pumps with flow rates of 7.5 and 5 mL/h, respectively. As controls, low and high degradable PLGA and SiO(2)-CaO gel nonwoven fabrics were also made by the same methods. The five nonwoven fabrics that were produced were exposed to simulated body fluid (SBF) for 1 week. SBF exposure resulted in the deposition of a layer of apatite crystals on the surfaces of both the SiO(2)-CaO gel and the low degradable PLGA/SiO(2)-CaO gel composite fabrics, but not on the low and high degradable PLGA or the high degradable PLGA/SiO(2)-CaO gel composite fabrics. The results are explained in terms of the acidity of the PLGA degradation products, which could have a direct influence on apatite dissolution.

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

    Directory of Open Access Journals (Sweden)

    Jae Baek Lee

    2015-01-01

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

  13. Axial shear modulus of a fiber-reinforced composite with random fiber cross-sections

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    S. K. Bose

    1982-01-01

    Full Text Available A study is made of the effective axial shear modulus of a fiber reinforced material with random fiber cross-sections so that the micromechanics is governed by stochastic differential equations. A coarse-graining procedure is adopted to investigate the macroscopic behavior of the material. This analysis leads to the formula for the effective axial shear modulus μ∗=μ1/{1−2c(μ2−μ1/(μ2+μ1},where μ1 and μ2 are the shear modulus of the matrix and fibers respectively and c is the concentration of the fibers less that 0.5. For c>0.5, the fiber and matrix moduli are to be interchanged and c is to be replaced by 1−c. The results of this study are compared with those of the theory of fibre reinforced materials. Finally, a numerical example is presented with graphical representation.

  14. Failure process in heterogeneous materials with randomly oriented fibers

    Science.gov (United States)

    Sbiaai, H.; Hader, A.; Bakir, R.; Achik, I.; Tarras, I.; Boughaleb, Y.

    2017-06-01

    Our aim in this study is to investigate the failure process in heterogeneous materials with randomly oriented fibers. In our proposed system, the fiber bundle model assumes that all the fibers are randomly oriented in all directions relative to the vertical one. Our calculations are performed in the framework of the local load-sharing rule, which states that the applied load of a broken fiber is redistributed only to its neighboring ones. The results show that this system presents a greater resistance than the classical one where the fibers are arranged parallel to the applied load. We found that the density of the broken fibers exhibited a power law and was linearly correlated with the applied load and temperature. However, the results show that the failure process of the considered system is characterized by an avalanche phenomenon with two different regimes. We also studied the crossover behavior of lifetime of the materials versus both applied load and temperature. We compared these results with those obtained from the classical model.

  15. Modeling fiber type grouping by a binary Markov random field

    NARCIS (Netherlands)

    Venema, H. W.

    1992-01-01

    A new approach to the quantification of fiber type grouping is presented, in which the distribution of histochemical type in a muscle cross section is regarded as a realization of a binary Markov random field (BMRF). Methods for the estimation of the parameters of this model are discussed. The first

  16. Mechanical Behavior of Homogeneous and Composite Random Fiber Networks

    Science.gov (United States)

    Shahsavari, Ali

    Random fiber networks are present in many biological and non-biological materials such as paper, cytoskeleton, and tissue scaffolds. Mechanical behavior of networks is controlled by the mechanical properties of the constituent fibers and the architecture of the network. To characterize these two main factors, different parameters such as fiber density, fiber length, average segment length, nature of the cross-links at the fiber intersections, ratio of bending to axial behavior of fibers have been considered. Random fiber networks are usually modeled by representing each fiber as a Timoshenko or an Euler-Bernoulli beam and each cross-link as either a welded or rotating joint. In this dissertation, the effect of these modeling options on the dependence of the overall linear network modulus on microstructural parameters is studied. It is concluded that Timoshenko beams can be used for the whole range of density and fiber stiffness parameters, while the Euler-Bernoulli model can be used only at relatively low densities. In the low density-low bending stiffness range, elastic strain energy is stored in the bending mode of the deformation, while in the other extreme range of parameters, the energy is stored predominantly in the axial and shear deformation modes. It is shown that both rotating and welded joint models give the same rules for scaling of the network modulus with different micromechanical parameters. The elastic modulus of sparsely cross-linked random fiber networks, i.e. networks in which the degree of cross-linking varies, is studied. The relationship between the micromechanical parameters - fiber density, fiber axial and bending stiffness, and degree of cross-linking - and the overall elastic modulus is presented in terms of a master curve. It is shown that the master plot with various degrees of cross-linking can be collapsed to a curve which is also valid for fully cross-linked networks. Random fiber networks in which fibers are bonded to each other are

  17. Micromechanical Modeling of Fiber-Reinforced Composites with Statistically Equivalent Random Fiber Distribution

    Directory of Open Access Journals (Sweden)

    Wenzhi Wang

    2016-07-01

    Full Text Available Modeling the random fiber distribution of a fiber-reinforced composite is of great importance for studying the progressive failure behavior of the material on the micro scale. In this paper, we develop a new algorithm for generating random representative volume elements (RVEs with statistical equivalent fiber distribution against the actual material microstructure. The realistic statistical data is utilized as inputs of the new method, which is archived through implementation of the probability equations. Extensive statistical analysis is conducted to examine the capability of the proposed method and to compare it with existing methods. It is found that the proposed method presents a good match with experimental results in all aspects including the nearest neighbor distance, nearest neighbor orientation, Ripley’s K function, and the radial distribution function. Finite element analysis is presented to predict the effective elastic properties of a carbon/epoxy composite, to validate the generated random representative volume elements, and to provide insights of the effect of fiber distribution on the elastic properties. The present algorithm is shown to be highly accurate and can be used to generate statistically equivalent RVEs for not only fiber-reinforced composites but also other materials such as foam materials and particle-reinforced composites.

  18. Effect of Fiber Crimp on the Elasticity of Random Fiber Networks With and Without Embedding Matrices.

    Science.gov (United States)

    Ban, Ehsan; Barocas, Victor H; Shephard, Mark S; Picu, Catalin R

    2016-04-01

    Fiber networks are assemblies of one-dimensional elements representative of materials with fibrous microstructures such as collagen networks and synthetic nonwovens. The mechanics of random fiber networks has been the focus of numerous studies. However, fiber crimp has been explicitly represented only in few cases. In the present work, the mechanics of cross-linked networks with crimped athermal fibers, with and without an embedding elastic matrix, is studied. The dependence of the effective network stiffness on the fraction of nonstraight fibers and the relative crimp amplitude (or tortuosity) is studied using finite element simulations of networks with sinusoidally curved fibers. A semi-analytic model is developed to predict the dependence of network modulus on the crimp amplitude and the bounds of the stiffness reduction associated with the presence of crimp. The transition from the linear to the nonlinear elastic response of the network is rendered more gradual by the presence of crimp, and the effect of crimp on the network tangent stiffness decreases as strain increases. If the network is embedded in an elastic matrix, the effect of crimp becomes negligible even for very small, biologically relevant matrix stiffness values. However, the distribution of the maximum principal stress in the matrix becomes broader in the presence of crimp relative to the similar system with straight fibers, which indicates an increased probability of matrix failure.

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

    Science.gov (United States)

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

  20. The rising power of random distributed feedback fiber laser

    Science.gov (United States)

    Zhou, Pu; Ye, Jun; Xu, Jiangming; Zhang, Hanwei; Huang, Long; Wu, Jian; Xiao, Hu; Leng, Jinyong

    2018-01-01

    Random distributed feedback fiber lasers (RDFFL) are now attracting more and more attentions for their unique cavity-free, mode-free and structural simplicity features and broadband application potentials in many fields, such as long distance sensing, speck free imaging, nonlinear frequency conversion as well as new pump source. In this talk, we will review the recent research progresses on high power RDFFLs. We have achieved (1) More than 400 W RDFFL with nearly Gaussian beam profile based on crucial employment of fiber mismatching architecture. (2) High power RDFFL with specialized optical property that include: high power narrow-band RDFFL, hundred-watt level linearly-polarized RDFFL, hundred-watt level high-order RDFFL. (3) Power enhancements of RDFFL to record kilowatt level are demonstrated with the aid of fiber master oscillator power amplifier (MOPA) with different pump schemes.

  1. The GDF5 mutant BB-1 enhances the bone formation induced by an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia.

    Science.gov (United States)

    Gunnella, Francesca; Kunisch, Elke; Maenz, Stefan; Horbert, Victoria; Xin, Long; Mika, Joerg; Borowski, Juliane; Bischoff, Sabine; Schubert, Harald; Sachse, Andre; Illerhaus, Bernhard; Günster, Jens; Bossert, Jörg; Jandt, Klaus D; Plöger, Frank; Kinne, Raimund W; Brinkmann, Olaf; Bungartz, Matthias

    2018-02-01

    Targeted delivery of osteoinductive bone morphogenetic proteins (eg, GDF5) in bioresorbable calcium phosphate cement (CPC), potentially suitable for vertebroplasty and kyphoplasty of osteoporotic vertebral fractures, may be required to counteract augmented local bone catabolism and to support complete bone regeneration. The biologically optimized GDF5 mutant BB-1 may represent an attractive drug candidate for this purpose. The aim of the current study was to test an injectable, poly(l-lactide-co-glycolide) acid (PLGA) fiber-reinforced, brushite-forming CPC containing low-dose BB-1 in a sheep lumbar osteopenia model. This is a prospective experimental animal study. Bone defects (diameter 5 mm) were generated in aged, osteopenic female sheep and were filled with fiber-reinforced CPC alone (L4; CPC+fibers) or with CPC containing different dosages of BB-1 (L5; CPC+fibers+BB-1; 5, 100, and 500 µg BB-1; n=6 each). The results were compared with those of untouched controls (L1). Three and 9 months after the operation, structural and functional effects of the CPC (±BB-1) were analyzed ex vivo by measuring (1) bone mineral density (BMD); (2) bone structure, that is, bone volume/total volume (BV/TV) (assessed by micro-CT and histomorphometry), trabecular thickness (Tb.Th), and trabecular number (Tb.N); (3) bone formation, that is, osteoid volume/bone volume (OV/BV), osteoid surface/bone surface (OS/BS), osteoid thickness, mineralizing surface/bone surface (MS/BS), mineral apposition rate, and bone formation rate/bone surface; (4) bone resorption, that is, eroded surface/bone surface; and (5) compressive strength. Compared with untouched controls (L1), CPC+fibers (L4) and/or CPC+fibers+BB-1 (L5) significantly improved all parameters of bone formation, bone resorption, and bone structure. These effects were observed at 3 and 9 months, but were less pronounced for some parameters at 9 months. Compared with CPC without BB-1, additional significant effects of BB-1 were

  2. Dietary Fiber Supplementation for Fecal Incontinence: A Randomized Clinical Trial

    Science.gov (United States)

    Bliss, Donna Z.; Savik, Kay; Jung, Hans-Joachim G.; Whitebird, Robin; Lowry, Ann; Sheng, Xioayan

    2014-01-01

    Dietary fiber supplements are used to manage fecal incontinence (FI), but little is known about the fiber type to recommend or the level of effectiveness of such supplements, which appear related to the fermentability of the fiber. The aim of this single-blind, randomized controlled trial was to compare the effects of three dietary fiber supplements (carboxymethylcellulose [CMC], gum arabic [GA], or psyllium) with differing levels of fermentability to a placebo in community-living individuals incontinent of loose/liquid feces. The primary outcome was FI frequency; secondary outcomes included FI amount and consistency, supplement intolerance, and quality of life (QoL). Possible mechanisms underlying supplement effects were also examined. After a 14-day baseline, 189 subjects consumed a placebo or 16g total fiber/day of one of the fiber supplements for 32 days. FI frequency significantly decreased after psyllium supplementation versus placebo, in both intent-to-treat and per-protocol mixed model analyses. CMC increased FI frequency. In intent-to-treat analysis, the number of FI episodes/week after supplementation was estimated to be 5.5 for Placebo, 2.5 for Psyllium, 4.3 for GA, and 6.2 for CMC. Only psyllium consumption resulted in a gel in feces. Supplement intolerance was low. QoL scores did not differ among groups. Patients with FI may experience a reduction in FI frequency after psyllium supplementation, and decreased FI frequency has been shown to be an important personal goal of treatment for patients with FI. Formation of a gel in feces appears to be a mechanism by which residual psyllium improved FI. PMID:25155992

  3. Dietary fiber supplementation for fecal incontinence: a randomized clinical trial.

    Science.gov (United States)

    Bliss, Donna Z; Savik, Kay; Jung, Hans-Joachim G; Whitebird, Robin; Lowry, Ann; Sheng, Xiaoyan

    2014-10-01

    Dietary fiber supplements are used to manage fecal incontinence (FI), but little is known about the fiber type to recommend or the level of effectiveness of such supplements, which appears related to the fermentability of the fiber. The aim of this single-blind, randomized controlled trial was to compare the effects of three dietary fiber supplements (carboxymethylcellulose [CMC], gum arabic [GA], or psyllium) with differing levels of fermentability to a placebo in community-living individuals incontinent of loose/liquid feces. The primary outcome was FI frequency; secondary outcomes included FI amount and consistency, supplement intolerance, and quality of life (QoL). Possible mechanisms underlying supplement effects were also examined. After a 14-day baseline, 189 subjects consumed a placebo or 16 g total fiber/day of one of the fiber supplements for 32 days. FI frequency significantly decreased after psyllium supplementation versus placebo, in both intent-to-treat and per-protocol mixed model analyses. CMC increased FI frequency. In intent-to-treat analysis, the number of FI episodes/week after supplementation was estimated to be 5.5 for Placebo, 2.5 for Psyllium, 4.3 for GA, and 6.2 for CMC. Only psyllium consumption resulted in a gel in feces. Supplement intolerance was low. QoL scores did not differ among groups. Patients with FI may experience a reduction in FI frequency after psyllium supplementation, and decreased FI frequency has been shown to be an important personal goal of treatment for patients with FI. Formation of a gel in feces appears to be a mechanism by which residual psyllium improved FI. © 2014 Wiley Periodicals, Inc.

  4. Moisture diffusivity in structure of random fractal fiber bed

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Fanglong, E-mail: zhufanglong_168@163.com [College of Textile, Zhongyuan University of Technology, Zhengzhou City (China); The Chinese People' s Armed Police Forces Academy, Langfan City (China); Zhou, Yu; Feng, Qianqian [College of Textile, Zhongyuan University of Technology, Zhengzhou City (China); Xia, Dehong [School of Mechanical Engineering, University of Science and Technology, Beijing (China)

    2013-11-08

    A theoretical expression related to effective moisture diffusivity to random fiber bed is derived by using fractal theory and considering both parallel and perpendicular channels to diffusion flow direction. In this Letter, macroporous structure of hydrophobic nonwoven material is investigated, and Knudsen diffusion and surface diffusion are neglected. The effective moisture diffusivity predicted by the present fractal model are compared with water vapor transfer rate (WVTR) experiment data and calculated values obtained from other theoretical models. This verifies the validity of the present fractal diffusivity of fibrous structural beds.

  5. Fabrication, characterization and in vitro drug release behavior of electrospun PLGA/chitosan nanofibrous scaffold

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Z.X.; Zheng, W.; Li, L. [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Zheng, Y.F., E-mail: yfzheng@pku.edu.cn [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Department of Advanced Materials and Nanotechnology, College of Engineering, Peking University, Beijing 100871 (China)

    2011-02-15

    Graphical abstract: The fenbufen loaded PLGA/chitosan nanofibrous scaffolds were fabricated by electrospinning. The hydrophilicity of nanofibrous scaffold was enhanced with the increase of chitosan content. The drug release also is accelerated with chitosan increasing because the higher hydrophilicity makes drug diffusing from scaffold more easily. Research highlights: {yields} The average diameter increased with the increase of chitosan content and then decreased. {yields} The release rate of fenbufen increased with the increase of chitosan. {yields} The aligned nanofibrous scaffold exhibits lower drug release rate. {yields} The drug release could be controlled by crosslinking in glutaraldehyde vapor. - Abstract: In this study both aligned and randomly oriented poly(D,L-lactide-co-glycolide) (PLGA)/chitosan nanofibrous scaffold have been prepared by electrospinning. The ratio of PLGA to chitosan was adjusted to get smooth nanofiber surface. Morphological characterization using scanning electron microscopy showed that the aligned nanofiber diameter distribution obtained by electrospinning of polymer blend increased with the increase of chitosan content which was similar to that of randomly oriented nanofibers. The release characteristic of model drug fenbufen (FBF) from the FBF-loaded aligned and randomly oriented PLGA and PLGA/chitosan nanofibrous scaffolds was investigated. The drug release rate increased with the increase of chitosan content because the addition of chitosan enhanced the hydrophilicity of the PLGA/chitosan composite scaffold. Moreover, for the aligned PLGA/chitosan nanofibrous scaffold the release rate was lower than that of randomly oriented PLGA/chitosan nanofibrous scaffold, which indicated that the nanofiber arrangement would influence the release behavior. In addition, crosslinking in glutaraldehyde vapor would decrease the burst release of FBF from FBF-loaded PLGA/chitosan nanofibrous scaffold with a PLGA/chitosan ratio less than 9/1, which

  6. Random copolyesters containing perylene bisimide: flexible films and fluorescent fibers.

    Science.gov (United States)

    Nisha, S Kumari; Asha, S K

    2014-08-13

    Random copolyesters of poly(l-lactic acid) (PLLA) and [poly(1,4-cyclohexylenedimethylene-1,4- cyclohexanedicarboxylate)] (PCCD) incorporating varying mol ratios of perylene bisimide (PBI) were developed via a high-temperature solution-blending approach. PCCD incorporating PBI was developed by melt polycondenzation followed by a polyester-polyester transesterification reaction between PCCD-PBI and PLLA. The polymers exhibited good solubility in common organic solvents and formed free-standing films, which showed bright red emission upon irradiation with ultraviolet radiation. A solid state fluorescence quantum yield of 10% was observed for this PBI based polyester, which was much higher than that reported in literature for PBI based polymers in the solid state (fluorescent nanofibers of these polymers were successfully constructed by electrospinning technique. A random copolyester incorporating donor based on oligo(p-pheneylenevinylene) (OPV) and PBI as acceptor chromophore was also synthesized and fluorescence microscopy images of the electrospun fibers of this polymer exhibited blue, green and red emission upon excitation at different wavelengths. The high temperature solution blending approach involving a high molecular weight polymer and a suitably functionalized π conjugated molecule described here is a unique method by which 1D nanostructures of a wide range of π-conjugated chromophores could be fabricated having strong fluorescence, with the scope of application in nanoscale optoelectronics, biological devices, as well as sensing.

  7. Common-cavity ytterbium/Raman random distributed feedback fiber laser

    Science.gov (United States)

    Wu, Han; Wang, Zinan; He, Qiheng; Sun, Wei; Rao, Yunjiang

    2017-06-01

    In this letter, a common-cavity random distributed feedback fiber laser which can generate both 1064 nm ytterbium-doped random lasing and 1115 nm ytterbium-Raman random lasing is proposed and experimentally demonstrated for the first time. The common cavity is based on the combination of the double-cladding ytterbium-doped fiber and the standard single mode fiber (SMF); a 1064 nm high-reflectivity fiber Bragg grating and the fiber flat-end are connected to the signal port of the pump combiner as the point reflectors. The generated 1064 nm random lasing can serve as the Raman pump in the SMF, thus 1115 nm random lasing could be stimulated with the hybrid ytterbium-Raman gain. The feedback for 1115 nm random lasing is the combination of flat-end fiber and random Rayleigh feedback. By controlling the value of flat-end fiber’s reflectivity to 0.002, stable 1.91 W of 1064 nm ytterbium-doped random lasing and 3.72 W of 1115 nm ytterbium-Raman random lasing are generated successively. This work could provide a simple and cost-effective way to generate high-power random lasing.

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

    NARCIS (Netherlands)

    Liao, H.; Lanao, R.P.; Beucken, J.J.J.P van den; Zhou, N.; Both, S.K.; Wolke, J.G.C.; Jansen, J.A.

    2016-01-01

    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

  9. 3D imaging of cell interactions with electrospun PLGA nanofiber membranes for bone regeneration.

    Science.gov (United States)

    Stachewicz, Urszula; Qiao, Tuya; Rawlinson, Simon C F; Almeida, Filipe Veiga; Li, Wei-Qi; Cattell, Michael; Barber, Asa H

    2015-11-01

    The interaction between resident cells and electrospun nanofibers is critical in determining resultant osteoblast proliferation and activity in orthopedic tissue scaffolds. The use of techniques to evaluate cell-nanofiber interactions is critical in understanding scaffold function, with visualization promising unparalleled access to spatial information on such interactions. 3D tomography exploiting focused ion beam (FIB)-scanning electron microscopy (SEM) was used to examine electrospun nanofiber scaffolds to understand the features responsible for (osteoblast-like MC3T3-E1 and UMR106) cell behavior and resultant scaffold function. 3D imaging of cell-nanofiber interactions within a range of electrospun poly(d,l-lactide-co-glycolide acid) (PLGA) nanofiber scaffold architectures indicated a coherent interface between osteoblasts and nanofiber surfaces, promoting osteoblast filopodia formation for successful cell growth. Coherent cell-nanofiber interfaces were demonstrated throughout a randomly organized and aligned nanofiber network. Gene expression of UMR106 cells grown on PLGA fibers did not deviate significantly from those grown on plastic, suggesting maintenance of phenotype. However, considerably lower expression of Ibsp and Alpl on PLGA fibers might indicate that these cells are still in the proliferative phase compared with a more differentiated cell on plastic. This work demonstrates the synergy between designing electrospun tissue scaffolds and providing comprehensive evaluation through high resolution imaging of resultant 3-dimensional cell growth within the scaffold. Membranes made from electrospun nanofibers are potentially excellent for promoting bone growth for next-generation tissue scaffolds. The effectiveness of an electrospun membrane is shown here using high resolution 3D imaging to visualize the interaction between cells and the nanofibers within the membrane. Nanofibers that are aligned in one direction control cell growth at the surface of the

  10. Calculation of the mean differential group delay of periodically spun, randomly birefringent fibers.

    Science.gov (United States)

    Galtarossa, Andrea; Griggio, Paola; Pizzinat, Anna; Palmieri, Luca

    2002-05-01

    Spinning is one of the most effective and well-known ways to reduce polarization mode dispersion of optical fibers. In spite of the popularity of spinning, a detailed theory of spin effects is still lacking. We report an analytical expression for the mean differential group delay of a randomly birefringent spun fiber. The result holds for any periodic spin function with a period shorter than the fiber's beat length.

  11. Development of Risperidone PLGA Microspheres

    Directory of Open Access Journals (Sweden)

    Susan D’Souza

    2014-01-01

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

  12. Variability of Fiber Elastic Moduli in Composite Random Fiber Networks Makes the Network Softer

    Science.gov (United States)

    Ban, Ehsan; Picu, Catalin

    2015-03-01

    Athermal fiber networks are assemblies of beams or trusses. They have been used to model mechanics of fibrous materials such as biopolymer gels and synthetic nonwovens. Elasticity of these networks has been studied in terms of various microstructural parameters such as the stiffness of their constituent fibers. In this work we investigate the elasticity of composite fiber networks made from fibers with moduli sampled from a distribution function. We use finite elements simulations to study networks made by 3D Voronoi and Delaunay tessellations. The resulting data collapse to power laws showing that variability in fiber stiffness makes fiber networks softer. We also support the findings by analytical arguments. Finally, we apply these results to a network with curved fibers to explain the dependence of the network's modulus on the variation of its structural parameters.

  13. Electrospun dye-doped fiber networks: lasing emission from randomly distributed cavities

    DEFF Research Database (Denmark)

    Krammer, Sarah; Vannahme, Christoph; Smith, Cameron

    2015-01-01

    Dye-doped polymer fiber networks fabricated with electrospinning exhibit comb-like laser emission. We identify randomly distributed ring resonators being responsible for lasing emission by making use of spatially resolved spectroscopy. Numerical simulations confirm this result quantitatively....

  14. Broadband supercontinuum light source seeded by random distributed feedback fiber laser

    Science.gov (United States)

    Ma, R.; Rao, Y. J.; Zhang, W. L.; Wu, H.; Zeng, X.

    2017-04-01

    A novel broadband light source based on supercontinuum (SC) generation seeded by random distributed feedback fiber laser (RFL) is proposed and demonstrated for the first time. A half-opened fiber cavity formed by FBG and TrueWave fiber is used to generate random lasing and SC simultaneously. Experimental results indicate that RFL can be used as an effective pump for generation of SC. SC with 20-dB bandwidth of >250 nm was obtained. Such a broadband SC light source seeded by RFL may pave a way to generate high power broadband RFLs for use in optical sensing and measurement.

  15. Numerical simulation of fibrous biomaterials with randomly distributed fiber network structure.

    Science.gov (United States)

    Jin, Tao; Stanciulescu, Ilinca

    2016-08-01

    This paper presents a computational framework to simulate the mechanical behavior of fibrous biomaterials with randomly distributed fiber networks. A random walk algorithm is implemented to generate the synthetic fiber network in 2D used in simulations. The embedded fiber approach is then adopted to model the fibers as embedded truss elements in the ground matrix, which is essentially equivalent to the affine fiber kinematics. The fiber-matrix interaction is partially considered in the sense that the two material components deform together, but no relative movement is considered. A variational approach is carried out to derive the element residual and stiffness matrices for finite element method (FEM), in which material and geometric nonlinearities are both included. Using a data structure proposed to record the network geometric information, the fiber network is directly incorporated into the FEM simulation without significantly increasing the computational cost. A mesh sensitivity analysis is conducted to show the influence of mesh size on various simulation results. The proposed method can be easily combined with Monte Carlo (MC) simulations to include the influence of the stochastic nature of the network and capture the material behavior in an average sense. The computational framework proposed in this work goes midway between homogenizing the fiber network into the surrounding matrix and accounting for the fully coupled fiber-matrix interaction at the segment length scale, and can be used to study the connection between the microscopic structure and the macro-mechanical behavior of fibrous biomaterials with a reasonable computational cost.

  16. High-power random distributed feedback fiber laser: From science to application

    Energy Technology Data Exchange (ETDEWEB)

    Du, Xueyuan [College of Optoelectronic Science and Engineering, National University of Defense Technology, Changsha 410073 (China); Naval Academy of Armament, Beijing 100161 (China); Zhang, Hanwei; Xiao, Hu; Ma, Pengfei; Wang, Xiaolin; Zhou, Pu; Liu, Zejin [College of Optoelectronic Science and Engineering, National University of Defense Technology, Changsha 410073 (China)

    2016-10-15

    A fiber laser based on random distributed feedback has attracted increasing attention in recent years, as it has become an important photonic device and has found wide applications in fiber communications or sensing. In this article, recent advances in high-power random distributed feedback fiber laser are reviewed, including the theoretical analyses, experimental approaches, discussion on the practical applications and outlook. It is found that a random distributed feedback fiber laser can not only act as an information photonics device, but also has the feasibility for high-efficiency/high-power generation, which makes it competitive with conventional high-power laser sources. In addition, high-power random distributed feedback fiber laser has been successfully applied for midinfrared lasing, frequency doubling to the visible and high-quality imaging. It is believed that the high-power random distributed feedback fiber laser could become a promising light source with simple and economic configurations. (copyright 2016 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  17. RGD peptide and graphene oxide co-functionalized PLGA nanofiber scaffolds for vascular tissue engineering.

    Science.gov (United States)

    Shin, Yong Cheol; Kim, Jeonghyo; Kim, Sung Eun; Song, Su-Jin; Hong, Suck Won; Oh, Jin-Woo; Lee, Jaebeom; Park, Jong-Chul; Hyon, Suong-Hyu; Han, Dong-Wook

    2017-06-01

    In recent years, much research has been suggested and examined for the development of tissue engineering scaffolds to promote cellular behaviors. In our study, RGD peptide and graphene oxide (GO) co-functionalized poly(lactide-co-glycolide, PLGA) (RGD-GO-PLGA) nanofiber mats were fabricated via electrospinning, and their physicochemical and thermal properties were characterized to explore their potential as biofunctional scaffolds for vascular tissue engineering. Scanning electron microscopy images revealed that the RGD-GO-PLGA nanofiber mats were readily fabricated and composed of random-oriented electrospun nanofibers with average diameter of 558 nm. The successful co-functionalization of RGD peptide and GO into the PLGA nanofibers was confirmed by Fourier-transform infrared spectroscopic analysis. Moreover, the surface hydrophilicity of the nanofiber mats was markedly increased by co-functionalizing with RGD peptide and GO. It was found that the mats were thermally stable under the cell culture condition. Furthermore, the initial attachment and proliferation of primarily cultured vascular smooth muscle cells (VSMCs) on the RGD-GO-PLGA nanofiber mats were evaluated. It was revealed that the RGD-GO-PLGA nanofiber mats can effectively promote the growth of VSMCs. In conclusion, our findings suggest that the RGD-GO-PLGA nanofiber mats can be promising candidates for tissue engineering scaffolds effective for the regeneration of vascular smooth muscle.

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

    Directory of Open Access Journals (Sweden)

    A.R. Rosa

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

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

    Science.gov (United States)

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

    2014-12-01

    Bioresorbable suture anchors and interference screws have certain benefits over equivalent titanium-alloy implants. However, there is a need for compositional improvement of currently used bioresorbable implants. We hypothesized that implants made of poly(l-lactide-co-glycolide) (PLGA) compounded with nanostructured particles of beta-tricalcium phosphate (β-TCP) would induce stronger osteointegration than implants made of PLGA compounded with microsized β-TCP particles. The experimental nanostructured self-reinforced PLGA (85L:15G)/β-TCP composite was made by high-energy ball-milling. Self-reinforced microsized PLGA (95L:5G)/β-TCP composite was prepared by melt-compounding. The composites were characterized by gas chromatography, Ubbelohde viscometry, scanning electron microscopy, laser diffractometry, and standard mechanical tests. Four groups of implants were prepared for the controlled laboratory study employing a minipig animal model. Implants in the first two groups were prepared from nanostructured and microsized PLGA/β-TCP composites respectively. Microroughened titanium-alloy (Ti6Al4V) implants served as positive intra-animal control, and pure PLGA implants as negative control. Cone-shaped implants were inserted in a random order unilaterally in the anterior cortex of the femoral shaft. Eight weeks after surgery, the mechanical strength of osteointegration of the implants was measured by a push-out test. The quality of new bone surrounding the implant was assessed by microcomputed tomography and histology. Implants made of nanostructured PLGA/β-TCP composite did not show improved mechanical osteointegration compared with the implants made of microsized PLGA/β-TCP composite. In the intra-animal comparison, the push-out force of two PLGA/β-TCP composites was 35-60% of that obtained with Ti6Al4V implants. The implant materials did not result in distinct differences in quality of new bone surrounding the implant. Copyright © 2014 Elsevier Ltd. All

  20. Modulus of elasticity of randomly and aligned polymeric scaffolds with fiber size dependency.

    Science.gov (United States)

    Wang, Jun; Yuan, Bo; Han, Ray P S

    2017-09-20

    The stiffness of a nano-fibrous scaffold is generally enhanced due to the size-dependency of the thin nanofibers contained in the scaffold. We proposed a model that incorporates size-dependency of single nanofibers to predict the scaffold effective modulus, in which the fibers' random or orientation distribution are considered. In the model the fiber segments between rigid fiber-fiber bonds can be stretching, shearing and bending. Using deformation energy equilibrium between sum of individual fibers and the plate of nano-fibrous scaffold, the scaffold effective modulus was derived explicitly. The model was verified via finite element analysis (FEA) and published experimental results. The parametric studies revealed that the fiber diameter is the dominant parameter to stiffen the scaffold beyond the fiber density and fiber aspect ratio when the fiber diameter is reduced below the onset value of size-dependencies. As a result, the scaffold stiffness can maintain its higher value and lower decrease rate because of the size-dependency with a decreasing diameter of the nanofiber as a result of biodegradation. This inspires the idea of selecting nanofibers near the onset value of size-dependency to obtain a controlled tuning of the scaffold stiffness in the design of novel nano-fibrous scaffolds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Fiber

    Science.gov (United States)

    ... fiber you get from the food. Fiber-rich foods offer health benefits when eaten raw or cooked. Alternative Names Diet - fiber; Roughage; Bulk; Constipation - fiber Patient Instructions Constipation - ...

  2. RANDOMIZED CLINICAL TRIAL: SOLUBLE/INSOLUBLE FIBER OR PSYLLIUM FOR CHRONIC CONSTIPATION

    Science.gov (United States)

    Erdogan, Askin; Rao, Satish; Thiruvaiyaru, Dharma; Lee, Yeong Yeh; Adame, Enrique Coss; Valestin, Jessica; O’Banion, Meagan

    2016-01-01

    SUMMARY Background Fiber supplements are useful, but whether a plum-derived mixed fiber that contains both soluble and insoluble fiber improves constipation is unknown. Aim We investigated the efficacy and tolerability of mixed fiber versus psyllium in a randomized double blind controlled trial. Methods Constipated patients (Rome III) received mixed fiber or psyllium, 5g bid, for 4 weeks. Daily symptoms and stool habit were assessed using stool diary. Subjects with ≥1 complete spontaneous bowel movement (CSBM)/week above baseline for ≥ 2/4 weeks were considered responders. Secondary outcome measures included stool consistency, bowel satisfaction, straining, gas, bloating, taste, dissolvability and Quality of Life (QOL). Results 72 subjects (MF=40; psyllium=32) were enrolled and 2 from psyllium group withdrew. The mean CSBM/week increased with both mixed fiber (ppsyllium (p=0.0002) without group difference. There were 30 (75%) responders with mixed fiber and 24 (75%) with psyllium (p=0.9). Stool consistency increased (p=0.04), straining (p=0.006), and bloating scores decreased (p=0.02) without group differences. Significantly more patients reported improvement in flatulence (53% vs. 25%, p=0.01) and felt that mixed fiber dissolved better (p=0.02) compared to psyllium. QOL improved (p=0.0125) with both treatments without group differences. Conclusions Mixed fiber and psyllium were equally efficacious in improving constipation and QOL. Mixed fiber was more effective in relieving flatulence, bloating and dissolved better. Mixed fiber is effective and well tolerated. Clinical Trial No: NCT01288508 PMID:27125883

  3. Dynamic critical behavior of failure and plastic deformation in the random fiber bundle model.

    Science.gov (United States)

    Pradhan, S; Bhattacharyya, P; Chakrabarti, B K

    2002-07-01

    The random fiber bundle (RFB) model, with the strength of the fibers distributed uniformly within a finite interval, is studied under the assumption of global load sharing among all unbroken fibers of the bundle. At any fixed value of the applied stress sigma (load per fiber initially present in the bundle), the fraction U(t)(sigma) of fibers that remain unbroken at successive time steps t is shown to follow simple recurrence relations. The model is found to have stable fixed point U*, filled (sigma) for applied stress in the range 0 point sigma = sigma(c), one finds strict power law decay (with time t) of the fraction of unbroken fibers U(t)(sigma(c)) (as t--> infinity). The avalanche size distribution for this mean-field dynamics of failure at sigma < sigma(c) has been studied. The elastic response of the RFB model has also been studied analytically for a specific probability distribution of fiber strengths, where the bundle shows plastic behavior before complete failure, following an initial linear response.

  4. Graphene based widely-tunable and singly-polarized pulse generation with random fiber lasers

    Science.gov (United States)

    Yao, B. C.; Rao, Y. J.; Wang, Z. N.; Wu, Y.; Zhou, J. H.; Wu, H.; Fan, M. Q.; Cao, X. L.; Zhang, W. L.; Chen, Y. F.; Li, Y. R.; Churkin, D.; Turitsyn, S.; Wong, C. W.

    2015-12-01

    Pulse generation often requires a stabilized cavity and its corresponding mode structure for initial phase-locking. Contrastingly, modeless cavity-free random lasers provide new possibilities for high quantum efficiency lasing that could potentially be widely tunable spectrally and temporally. Pulse generation in random lasers, however, has remained elusive since the discovery of modeless gain lasing. Here we report coherent pulse generation with modeless random lasers based on the unique polarization selectivity and broadband saturable absorption of monolayer graphene. Simultaneous temporal compression of cavity-free pulses are observed with such a polarization modulation, along with a broadly-tunable pulsewidth across two orders of magnitude down to 900 ps, a broadly-tunable repetition rate across three orders of magnitude up to 3 MHz, and a singly-polarized pulse train at 41 dB extinction ratio, about an order of magnitude larger than conventional pulsed fiber lasers. Moreover, our graphene-based pulse formation also demonstrates robust pulse-to-pulse stability and wide-wavelength operation due to the cavity-less feature. Such a graphene-based architecture not only provides a tunable pulsed random laser for fiber-optic sensing, speckle-free imaging, and laser-material processing, but also a new way for the non-random CW fiber lasers to generate widely tunable and singly-polarized pulses.

  5. Effect of SiC Nano powder on Multiaxial Woven and Chopped Randomly Oriented Flax/Sisal Fiber Reinforced composites

    Directory of Open Access Journals (Sweden)

    Kalagi Ganesh R.

    2018-01-01

    Full Text Available A study has been carried out to investigate effect of SiC Nano powder on tensile and impact properties of Multiaxial layers of Flax and Sisal fiber reinforced composites and randomly oriented chopped Flax and Sisal fiber reinforced composites. It has been observed that tensile strength and impact strength were improved using 6% of SiC Nanopowder into Multiaxial layer (+45º/-45º, 0º/90º of Flax and Sisal where as randomly oriented chopped Flax and Sisal fiber reinforced composites are improved in its stiffnes for the same composition of fiber, epoxy and SiC Nano powder. SEM Analysis are done to analyse the distribution of SiC in both Multiaxial layers of Flax and Sisal fiber reinforced composites and randomly oriented chopped Flax and Sisal fiber reinforced composites.

  6. High-power ultralong-wavelength Tm-doped silica fiber laser cladding-pumped with a random distributed feedback fiber laser

    OpenAIRE

    Xiaoxi Jin; Xueyuan Du; Xiong Wang; Pu Zhou; Hanwei Zhang; Xiaolin Wang; Zejin Liu

    2016-01-01

    We demonstrated a high-power ultralong-wavelength Tm-doped silica fiber laser operating at 2153?nm with the output power exceeding 18?W and the slope efficiency of 25.5%. A random distributed feedback fiber laser with the center wavelength of 1173?nm was employed as pump source of Tm-doped fiber laser for the first time. No amplified spontaneous emissions or parasitic oscillations were observed when the maximum output power reached, which indicates that employing 1173?nm random distributed fe...

  7. Surface modified PLGA/carbon nanofiber composite enhances articular chondrocyte functions

    Science.gov (United States)

    Park, Grace Eunseung

    cartilage. Specifically, these results suggest that the superficial zone, middle zone, and deep zone of cartilage should be composed of carbon nanofibers aligned parallel to the surface in PLGA, randomly oriented carbon nanofibers in PLGA, and carbon nanofibers aligned perpendicular to the surface in PLGA, respectively. Clearly, such scaffolds may ultimately enhance the efficacy of scaffolds used for articular cartilage repair.

  8. High-power ultralong-wavelength Tm-doped silica fiber laser cladding-pumped with a random distributed feedback fiber laser.

    Science.gov (United States)

    Jin, Xiaoxi; Du, Xueyuan; Wang, Xiong; Zhou, Pu; Zhang, Hanwei; Wang, Xiaolin; Liu, Zejin

    2016-07-15

    We demonstrated a high-power ultralong-wavelength Tm-doped silica fiber laser operating at 2153 nm with the output power exceeding 18 W and the slope efficiency of 25.5%. A random distributed feedback fiber laser with the center wavelength of 1173 nm was employed as pump source of Tm-doped fiber laser for the first time. No amplified spontaneous emissions or parasitic oscillations were observed when the maximum output power reached, which indicates that employing 1173 nm random distributed feedback fiber laser as pump laser is a feasible and promising scheme to achieve high-power emission of long-wavelength Tm-doped fiber laser. The output power of this Tm-doped fiber laser could be further improved by optimizing the length of active fiber, reflectivity of FBGs, increasing optical efficiency of pump laser and using better temperature management. We also compared the operation of 2153 nm Tm-doped fiber lasers pumped with 793 nm laser diodes, and the maximum output powers were limited to ~2 W by strong amplified spontaneous emission and parasitic oscillation in the range of 1900-2000 nm.

  9. Plga Nanoparticles and Polysorbate-80-Coated Plga Nanoparticles Increase in the Vitro Antioxiant Activity of Melatonin.

    Science.gov (United States)

    Martins, Leiziani Gnatkowski; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2017-07-19

    Melatonin is an endogen substance with several physiological functions, acting as an important antioxidant. Our objective was to prepare nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) coated with polysorbate 80 (PLGA-PS80) or uncoated (PLGA) nanoparticles containing melatonin (MLT) and evaluate their in vitro cytotoxicity over erythrocytes and in vitro antioxidant activity. Nanoparticles were obtained by an emulsion-solvent evaporation method and characterized by size, morphology, polydispersity index, zeta potential, encapsulation efficiency, thermal properties and in vitro drug release profile. The in vitro cytotoxicity over erythrocytes was assessed by hemolysis assay and in vitro antioxidant was carried out by colorimetric assay using the radical 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) (ABTS∙+). Mean size of the PLGA-PS80 and PLGA nanoparticles was 212 and 187 nm, and the encapsulation efficiency of MLT was 26 and 41%, respectively. Nanoparticles were spherical in shape and presented negative zeta potential. MLT was released from nanoparticles following second order model and PLGA-PS80 presented more prolonged MLT release. Cytotoxicity over erythrocytes was assessed and both nanoparticles containing MLT demonstrated lack of hemolysis. Scavenging activity over ABTS∙+ demonstrated both nanoparticles containing MLT were more efficient than free drug, and MLT-loaded PLGA nanoparticles presented the higher in vitro antioxidant activity. The study concluded that PLGA and PLGA-PS80 nanoparticles are promising carriers for MLT. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-03-12

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

  12. Modification and mechanical properties of electrospun blended fibermat of PLGA and siloxane-containing vaterite/PLLA hybrids for bone repair

    Directory of Open Access Journals (Sweden)

    2011-10-01

    Full Text Available Multi-syringe electrospinning has been successfully employed to produce a blended fibermat composed of poly(lactic-glycolic acid (PLGA fibers and a composite fiber for bone repair. The composite fiber, siloxane-containing vaterite (SiV/poly(L-lactic acid (PLLA, donated as SiPVH has the ability to release soluble silica species and calcium ions at a controlled rate. The SiPVH fibermats have demonstrated excellent bone regeneration ability in vivo at the front midline of the calvaria of rabbits. However, they are brittle and have low tensile strength resulting from the large particulate SiV (60 wt% content. In this study, co-electrospinning of PLGA with SiPVH was performed in the hope of achieving a blended fibermat with improved mechanical properties. The co-electrospun fibermats showed good homogeneous blending of the PLGA and SiPVH composite fibers that had excellent flexibility. The blended PLGA-SiPVH fibermats had significantly improved mechanical properties compared to the SiPVH fibermats, where more than 20 times higher elongation to failure was achieved on comparison to the SiPVH fibermat. As well as strength, high porosity and large pore size are vital for the migration of cells into the centre of the graft. This was accomplished by heating the PLGA-SiPVH fibermats at 110°C for a fixed time, which induced the softening and flow of PLGA towards the more stable SiPVH fibers. Heating had successfully produced PLGA-SIPVH fibermats with large open pores and inter-fused SiPVH fibers, which also had better tensile mechanical properties than the SiPVH fibermat.

  13. Hyaluronic acid/poly(lactic-co-glycolic acid) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate as skin tissue engineering scaffolds.

    Science.gov (United States)

    Lee, Eun Ji; Lee, Jong Ho; Jin, Linhua; Jin, Oh Seong; Shin, Yong Cheol; Sang, Jin Oh; Lee, Jaebeom; Hyon, Suong-Hyu; Han, Dong-Wook

    2014-11-01

    In this study, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber meshes loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) for application to tissue engineering scaffolds for skin regeneration were prepared via coaxial electrospinning. Physicochemical properties of HA/PLGA-E core/shell fiber meshes were characterized by SEM, Raman spectroscopy, contact angle, EGCG release profiling and in vitro degradation. Biomechanical properties of HA/PLGA-E meshes were also investigated by a tensile strength test. SEM images showed that HA/PLGA-E fiber meshes had a three-dimensional interconnected pore structure with an average fiber diameter of about 1270 nm. Raman spectra revealed that EGCG was uniformly dispersed in the PLGA shell of meshes. HA/PLGA-E meshes showed sustained EGCG release patterns by controlled diffusion and PLGA degradation over 4 weeks. EGCG loading did not adversely affect the tensile strength and elastic modulus of HA/PLGA meshes, while increased their hydrophilicity and surface energy. Attachment of human dermal fibroblasts on HA/PLGA-E meshes was appreciably increased and their proliferation was steadily retained during the culture period. These results suggest that HA/PLGA-E core/shell fiber meshes can be potentially used as scaffolds supporting skin regeneration.

  14. PLGA/alginate composite microspheres for hydrophilic protein delivery

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-01

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

  15. Fabrication and preliminary study of a biomimetic tri-layer tubular graft based on fibers and fiber yarns for vascular tissue engineering.

    Science.gov (United States)

    Wu, Tong; Zhang, Jialing; Wang, Yuanfei; Li, Dandan; Sun, Binbin; El-Hamshary, Hany; Yin, Meng; Mo, Xiumei

    2018-01-01

    Designing a biomimetic and functional tissue-engineered vascular graft has been urgently needed for repairing and regenerating defected vascular tissues. Utilizing a multi-layered vascular scaffold is commonly considered an effective way, because multi-layered scaffolds can easily simulate the structure and function of natural blood vessels. Herein, we developed a novel tri-layer tubular graft consisted of Poly(L-lactide-co-caprolactone)/collagen (PLCL/COL) fibers and Poly(lactide-co-glycolide)/silk fibroin (PLGA/SF) yarns via a three-step electrospinning method. The tri-layer vascular graft consisted of PLCL/COL aligned fibers in inner layer, PLGA/SF yarns in middle layer, and PLCL/COL random fibers in outer layer. Each layer possessed tensile mechanical strength and elongation, and the entire tubular structure provided tensile and compressive supports. Furthermore, the human umbilical vein endothelial cells (HUVECs) and smooth muscle cells (SMCs) proliferated well on the materials. Fluorescence staining images demonstrated that the axially aligned PLCL/COL fibers prearranged endothelium morphology in lumen and the circumferential oriented PLGA/SF yarns regulated SMCs organization along the single yarns. The outside PLCL/COL random fibers performed as the fixed layer to hold the entire tubular structure. The in vivo results showed that the tri-layer vascular graft supported cell infiltration, scaffold biodegradation and abundant collagen production after subcutaneous implantation for 10weeks, revealing the optimal biocompatibility and tissue regenerative capability of the tri-layer graft. Therefore, the specially designed tri-layer vascular graft will be beneficial to vascular reconstruction. Copyright © 2017. Published by Elsevier B.V.

  16. Randomized controlled trial of dietary fiber for the prevention of radiation-induced gastrointestinal toxicity during pelvic radiotherapy.

    Science.gov (United States)

    Wedlake, Linda; Shaw, Clare; McNair, Helen; Lalji, Amyn; Mohammed, Kabir; Klopper, Tanya; Allan, Lindsey; Tait, Diana; Hawkins, Maria; Somaiah, Navita; Lalondrelle, Susan; Taylor, Alexandra; VanAs, Nicholas; Stewart, Alexandra; Essapen, Sharadah; Gage, Heather; Whelan, Kevin; Andreyev, H Jervoise N

    2017-09-01

    Background: Therapeutic radiotherapy is an important treatment of pelvic cancers. Historically, low-fiber diets have been recommended despite a lack of evidence and potentially beneficial mechanisms of fiber.Objective: This randomized controlled trial compared low-, habitual-, and high-fiber diets for the prevention of gastrointestinal toxicity in patients undergoing pelvic radiotherapy.Design: Patients were randomly assigned to low-fiber [≤10 g nonstarch polysaccharide (NSP)/d], habitual-fiber (control), or high-fiber (≥18 g NSP/d) diets and received individualized counseling at the start of radiotherapy to achieve these targets. The primary endpoint was the difference between groups in the change in the Inflammatory Bowel Disease Questionnaire-Bowel Subset (IBDQ-B) score between the starting and nadir (worst) score during treatment. Other measures included macronutrient intake, stool diaries, and fecal short-chain fatty acid concentrations.Results: Patients were randomly assigned to low-fiber (n = 55), habitual-fiber (n = 55), or high-fiber (n = 56) dietary advice. Fiber intakes were significantly different between groups (P fiber group (mean ± SD: -3.7 ± 12.8) than in the habitual-fiber group (-10.8 ± 13.5; P = 0.011). At 1-y postradiotherapy (n = 126) the difference in IBDQ-B scores between the high-fiber (+0.1 ± 14.5) and the habitual-fiber (-8.4 ± 13.3) groups was significant (P = 0.004). No significant differences were observed in stool frequency or form or in short-chain fatty acid concentrations. Significant reductions in energy, protein, and fat intake occurred in the low- and habitual-fiber groups only.Conclusions: Dietary advice to follow a high-fiber diet during pelvic radiotherapy resulted in reduced gastrointestinal toxicity both acutely and at 1 y compared with habitual-fiber intake. Restrictive, non-evidence-based advice to reduce fiber intake in this setting should be abandoned. This trial was registered at clinicaltrials.gov as NCT

  17. Long Period Gratings in Random Hole Optical Fibers for Refractive Index Sensing

    Directory of Open Access Journals (Sweden)

    Gary Pickrell

    2011-01-01

    Full Text Available We have demonstrated the fabrication of long period gratings in random hole optical fibers. The long period gratings are fabricated by a point-by-point technique using a CO2 laser. The gratings with a periodicity of 450 µm are fabricated and a maximum coupling efficiency of −9.81 dB has been achieved. Sensing of different refractive indices in the surrounding mediums is demonstrated by applying standard liquids with refractive indices from 1.400 to 1.440 to the long period grating.

  18. Recommended Minimum Test Requirements and Test Methods for Assessing Durability of Random-Glass-Fiber Composites

    Energy Technology Data Exchange (ETDEWEB)

    Battiste, R.L.; Corum, J.M.; Ren, W.; Ruggles, M.B.

    1999-06-01

    This report provides recommended minimum test requirements are suggested test methods for establishing the durability properties and characteristics of candidate random-glass-fiber polymeric composites for automotive structural applications. The recommendations and suggestions are based on experience and results developed at Oak Ridge National Laboratory (ORNL) under a US Department of Energy Advanced Automotive Materials project entitled ''Durability of Lightweight Composite Structures,'' which is closely coordinated with the Automotive Composites Consortium. The report is intended as an aid to suppliers offering new structural composites for automotive applications and to testing organizations that are called on to characterize the composites.

  19. Randomized clinical study comparing metallic and glass fiber post in restoration of endodontically treated teeth.

    Science.gov (United States)

    Gbadebo, Olaide S; Ajayi, Deborah M; Oyekunle, Oyekunle O Dosumu; Shaba, Peter O

    2014-01-01

    Post-retained crowns are indicated for endodontically treated teeth (ETT) with severely damaged coronal tissue. Metallic custom and prefabricated posts have been used over the years, however, due to unacceptable color, extreme rigidity and corrosion, fiber posts, which are flexible, aesthetically pleasing and have modulus of elasticity comparable with dentin were introduced. To compare clinical performance of metallic and glass fiber posts in restoration of ETT. 40 ETT requiring post retained restorations were included. These teeth were randomly allocated into 2 groups. Twenty teeth were restored using a glass fiber-reinforced post (FRP) and 20 others received stainless steel parapost (PP), each in combination with composite core buildups. Patients were observed at 1 and 6 months after post placement and cementation of porcelain fused to metal (PFM) crown. Marginal gap consideration, post retention, post fracture, root fracture, crown fracture, crown decementation and loss of restoration were part of the data recorded. All teeth were assessed clinically and radiographically. Fisher's exact test was used for categorical values while log-rank test was used for descriptive statistical analysis. One tooth in the PP group failed, secondary to decementation of the PFM crown giving a 2.5% overall failure while none in the FRP group failed. The survival rate of FRP was thus 100% while it was 97.5% in the PP group. This however was not statistically significant (log-rank test, P = 0.32). Glass FRPs performed better than the metallic post based on short-term clinical performance.

  20. Fiber

    Science.gov (United States)

    ... white toast. Lunch and Dinner: Make sandwiches with whole-grain breads (rye, oat, or wheat) instead of white. Make a fiber-rich sandwich with whole-grain bread, peanut butter, and bananas. Use whole-grain spaghetti ...

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  2. Mid-infrared optical parametric oscillator pumped by an amplified random fiber laser

    Science.gov (United States)

    Shang, Yaping; Shen, Meili; Wang, Peng; Li, Xiao; Xu, Xiaojun

    2017-01-01

    Recently, the concept of random fiber lasers has attracted a great deal of attention for its feature to generate incoherent light without a traditional laser resonator, which is free of mode competition and insure the stationary narrow-band continuous modeless spectrum. In this Letter, we reported the first, to the best of our knowledge, optical parametric oscillator (OPO) pumped by an amplified 1070 nm random fiber laser (RFL), in order to generate stationary mid-infrared (mid-IR) laser. The experiment realized a watt-level laser output in the mid-IR range and operated relatively stable. The use of the RFL seed source allowed us to take advantage of its respective stable time-domain characteristics. The beam profile, spectrum and time-domain properties of the signal light were measured to analyze the process of frequency down-conversion process under this new pumping condition. The results suggested that the near-infrared (near-IR) signal light `inherited' good beam performances from the pump light. Those would be benefit for further develop about optical parametric process based on different pumping circumstances.

  3. A micromechanical model of tension-softening and bridging toughening of short random fiber reinforced brittle matrix composites

    Science.gov (United States)

    Li, Victor C.; Wang, Youjiang; Backer, Stanley

    A MICROMECHANICAL model has been formulated for the post-cracking behavior of a brittle matrix composite reinforced with randomly distributed short fibers. This model incorporates the mechanics of pull-out of fibers which are inclined at an angle to the matrix crack plane and which undergo slip-weakening or slip-hardening during the pull-out process. In addition, the random location and orientation of fibers are accounted for. Comparisons of model predictions of post-cracking tension-softening behavior with experimental data appear to support the validity of the model. The model is used to examine the effects of fiber length, snubbing friction coefficient and interfacial bond behavior on composite post-cracking tensile properties. The scaling of the bridging fracture toughening with material parameters is discussed.

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

    DEFF Research Database (Denmark)

    Yang, Chiming; Plackett, David; Needham, David

    2009-01-01

    -loaded PHBV microspheres was increased by FA loading. After the initial burst release, FA was released from PLGA microspheres much slower compared to PHBV microspheres. A unique phase separation phenomenon of FA in PLGA but not in PHBV polymers was observed, driven by coalescence of liquid microdroplets...... of 1% (w/w) FA phase separated from PLGA polymer and formed distinct spherical FA-rich amorphous microdomains throughout the PLGA microsphere. For FA-loaded PLGA microspheres, encapsulation efficiency and cumulative release increased with initial drug loading. Similarly, cumulative release from FA...

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

    Directory of Open Access Journals (Sweden)

    Zhuo Ye

    2015-08-01

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

  6. Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jin-Hyung Shim

    2015-10-01

    Full Text Available This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid/β-tricalcium phosphate (PCL/PLGA/β-TCP membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. Implant surgery and guided bone regeneration were performed randomly in three groups (a no membrane group, a titanium membrane group, and a PCL/PLGA/β-TCP membrane group (n = 8 per group. Histological and histometric analyses were conducted to evaluate effects on bone regeneration and osseointegration. Using the results of mechanical testing; a PCL/PLGA/β-TCP ratio of 2:6:2 was selected. The new bone areas (% in buccal defects around implants were highest in the PCL/PLGA/β-TCP group and significantly higher than in the control group (p < 0.05. Bone-to-implant contact ratios (% were also significantly higher in the PCL/PLGA/β-TCP and titanium groups than in the control group (p < 0.05. When the guided bone regeneration procedure was performed using the PCL/PLGA/β-TCP membrane; new bone formation around the implant and osseointegration were not inferior to those of the non-resorbable pre-formed titanium mesh membrane.

  7. (PLGA) microspheres-encapsulated vaccine preparation against

    African Journals Online (AJOL)

    Study on the immunogencity of poly(D,L-lactide-coglycolide) (PLGA) microspheres-encapsulated vaccine preparation against Stenotrophomonas maltophilia infection ... of the immune group, the other two groups were not coated with S. maltophilia raising vaccination with inactivated Aeromonas group and the control group.

  8. Multiscale modeling of interwoven Kevlar fibers based on random walk to predict yarn structural response

    Science.gov (United States)

    Recchia, Stephen

    Kevlar is the most common high-end plastic filament yarn used in body armor, tire reinforcement, and wear resistant applications. Kevlar is a trade name for an aramid fiber. These are fibers in which the chain molecules are highly oriented along the fiber axis, so the strength of the chemical bond can be exploited. The bulk material is extruded into filaments that are bound together into yarn, which may be chorded with other materials as in car tires, woven into a fabric, or layered in an epoxy to make composite panels. The high tensile strength to low weight ratio makes this material ideal for designs that decrease weight and inertia, such as automobile tires, body panels, and body armor. For designs that use Kevlar, increasing the strength, or tenacity, to weight ratio would improve performance or reduce cost of all products that are based on this material. This thesis computationally and experimentally investigates the tenacity and stiffness of Kevlar yarns with varying twist ratios. The test boundary conditions were replicated with a geometrically accurate finite element model, resulting in a customized code that can reproduce tortuous filaments in a yarn was developed. The solid model geometry capturing filament tortuosity was implemented through a random walk method of axial geometry creation. A finite element analysis successfully recreated the yarn strength and stiffness dependency observed during the tests. The physics applied in the finite element model was reproduced in an analytical equation that was able to predict the failure strength and strain dependency of twist ratio. The analytical solution can be employed to optimize yarn design for high strength applications.

  9. Pseudo-random-bit-sequence phase modulation for reduced errors in a fiber optic gyroscope.

    Science.gov (United States)

    Chamoun, Jacob; Digonnet, Michel J F

    2016-12-15

    Low noise and drift in a laser-driven fiber optic gyroscope (FOG) are demonstrated by interrogating the sensor with a low-coherence laser. The laser coherence was reduced by broadening its optical spectrum using an external electro-optic phase modulator driven by either a sinusoidal or a pseudo-random bit sequence (PRBS) waveform. The noise reduction measured in a FOG driven by a modulated laser agrees with the calculations based on the broadened laser spectrum. Using PRBS modulation, the linewidth of a laser was broadened from 10 MHz to more than 10 GHz, leading to a measured FOG noise of only 0.00073  deg/√h and a drift of 0.023  deg/h. To the best of our knowledge, these are the lowest noise and drift reported in a laser-driven FOG, and this noise is below the requirement for the inertial navigation of aircraft.

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

    Science.gov (United States)

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

    2015-11-01

    Poly(lactic-co-glycolic acid) (PLGA) microspheres and PLGA/alginate composite microspheres were prepared by a novel double emulsion and solvent evaporation technique and loaded with bovine serum albumin (BSA) or rabbit anti-laminin antibody protein. The addition of alginate and the use of a surfactant during microsphere preparation increased the encapsulation efficiency and reduced the initial burst release of hydrophilic BSA. Confocal laser scanning microcopy (CLSM) of BSA-loaded PLGA/alginate composite microspheres showed that PLGA, alginate, and BSA were distributed throughout the depths of microspheres; no core/shell structure was observed. Scanning electron microscopy revealed that PLGA microspheres erode and degrade more quickly than PLGA/alginate composite microspheres. When loaded with anti-laminin antibody, the function of released antibody was well preserved in both PLGA and PLGA/alginate composite microspheres. The biocompatibility of PLGA and PLGA/alginate microspheres were examined using four types of cultured cell lines, representing different tissue types. Cell survival was variably affected by the inclusion of alginate in composite microspheres, possibly due to the sensitivity of different cell types to excess calcium that may be released from the calcium cross-linked alginate. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Hossam M Zawbaa

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

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

    Science.gov (United States)

    Zawbaa, Hossam M; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

    2016-01-01

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

  13. Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres—Focus on Feature Selection

    Science.gov (United States)

    Zawbaa, Hossam M.; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

    2016-01-01

    Poly-lactide-co-glycolide (PLGA) is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP), multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR). The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE) of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven. PMID:27315205

  14. Behavior of Random Hole Optical Fibers under Gamma Ray Irradiation and Its Potential Use in Radiation Sensing Applications

    Directory of Open Access Journals (Sweden)

    Anbo Wang

    2007-05-01

    Full Text Available Effects of radiation on sensing and data transmission components are of greatinterest in many applications including homeland security, nuclear power generation, andmilitary. A new type of microstructured optical fiber (MOF called the random hole opticalfiber (RHOF has been recently developed. The RHOFs can be made in many differentforms by varying the core size and the size and extent of porosity in the cladding region.The fibers used in this study possessed an outer diameter of 110 μm and a core ofapproximately 20 μm. The fiber structure contains thousands of air holes surrounding thecore with sizes ranging from less than 100 nm to a few μm. We present the first study ofthe behavior of RHOF under gamma irradiation. We also propose, for the first time to ourknowledge, an ionizing radiation sensor system based on scintillation light from ascintillator phosphor embedded within a holey optical fiber structure. The RHOF radiationresponse was compared to normal single mode and multimode commercial fibers(germanium doped core, pure silica cladding and to those of radiation resistant fibers (puresilica core with fluorine doped cladding fibers. The comparison was done by measuringradiation-induced absorption (RIA in all fiber samples at the 1550 nm wavelength window(1545 ± 25 nm. The study was carried out under a high-intensity gamma ray field from a 60Co source (with an exposure rate of 4x104 rad/hr at an Oak Ridge National Laboratory gamma ray irradiation facility. Linear behavior, at dose values less than 106 rad, was observed in all fiber samples except in the pure silica core fluorine doped cladding fiber which showed RIA saturation at 0.01 dB. RHOF samples demonstrated low RIA (0.02 and 0.005 dB compared to standard germanium doped core pure silica cladding (SMF and MMF fibers. Results also showed the possibility of post-fabrication treatment to improve the radiation resistance of the RHOF fibers.

  15. Spatial distribution of fiber types in skeletal muscle: test for a random distribution

    NARCIS (Netherlands)

    Venema, H. W.

    1988-01-01

    A statistical test is introduced for the assessment of fiber type grouping based on the number of neighboring fibers of different histochemical type. It is conceptually simple and can be applied to regular and irregular fiber patterns alike. One important feature of this test is that it has more

  16. The effect of viscous soluble fiber on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Khan, K; Jovanovski, E; Ho, H V T; Marques, A C R; Zurbau, A; Mejia, S B; Sievenpiper, J L; Vuksan, V

    2018-01-01

    Dietary fiber intake, especially viscous soluble fiber, has been established as a means to reduce cardiometabolic risk factors. Whether this is true for blood pressure remains controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of viscous soluble fiber supplementation on blood pressure and quantify the effect of individual fibers. MEDLINE, Embase, and Cochrane databases were searched. We included RCTs of ≥4-weeks in duration assessing viscous fiber supplementation from five types: β-glucan from oats and barley, guar gum, konjac, pectin and psyllium, on systolic blood pressure (SBP) and diastolic blood pressure (DBP). Study data were pooled using the generic inverse variance method with random effects models and expressed as mean differences (MD) with 95% confidence intervals (CIs). Twenty-two (N = 1430) and twenty-one RCTs (N = 1343) were included in the final analysis for SBP and DBP, respectively. Viscous fiber reduced SBP (MD = -1.59 mmHg [95% CI: -2.72,-0.46]) and DBP (MD = -0.39 mmHg [95% CI: -0.76,-0.01]) at a median dose of 8.7 g/day (1.45-30 g/day) over a median follow-up of 7-weeks. Substantial heterogeneity in SBP (I2 = 72%, P fiber types, SBP reductions were observed only for supplementation using psyllium fiber (MD = -2.39 mmHg [95% CI: -4.62,-0.17]). Viscous soluble fiber has an overall lowering effect on SBP and DBP. Inclusion of viscous fiber to habitual diets may have additional value in reducing CVD risk via improvement in blood pressure. ClinicalTrials.gov identifier-NCT02670967. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  17. Psyllium fiber vs. placebo in early treatment after STARR for obstructed defecation: a randomized double-blind clinical trial.

    Science.gov (United States)

    Gabrielli, Francesco; Macchini, Daniele; Guttadauro, Angelo; Frassani, Silvia; Bertolini, Aimone; Giussani, Cristina; DE Simone, Matilde; Cioffi, Ugo

    2016-04-01

    Previous Literature has never evaluated the effectiveness of fiber intake after surgery for obstructed defecation in improving residual constipation and defecation urgency. From May 2010 to June 2011, 65 patients were randomly assigned to either the active group (N.=32) or placebo group (N.=33) receiving 3.5 g/day of pure Psyllium fiber or inert compound respectively. During the 6-month follow-up score systems were evaluated: Longo's Obstructed Defecation Syndrome Score, Cleveland Constipation Score; Wexner incontinence Score and Visual Analogic Scale. We also recorded the incidence of postoperative defecation urgency. Active group reported less constipation at 1 week (ODS: 6.25±3.55 vs. 11.94±4.99, PPsyllium fiber improves early and 6 month results after stapled transanal rectal resection, both in terms of residual constipation and fecal incontinence. It also reduces postoperative defecation urgency.

  18. Surface Plasmon Resonance Temperature Sensor Based on Photonic Crystal Fibers Randomly Filled with Silver Nanowires

    Directory of Open Access Journals (Sweden)

    Nannan Luan

    2014-08-01

    Full Text Available We propose a temperature sensor design based on surface plasmon resonances (SPRs supported by filling the holes of a six-hole photonic crystal fiber (PCF with a silver nanowire. A liquid mixture (ethanol and chloroform with a large thermo-optic coefficient is filled into the PCF holes as sensing medium. The filled silver nanowires can support resonance peaks and the peak will shift when temperature variations induce changes in the refractive indices of the mixture. By measuring the peak shift, the temperature change can be detected. The resonance peak is extremely sensitive to temperature because the refractive index of the filled mixture is close to that of the PCF material. Our numerical results indicate that a temperature sensitivity as high as 4 nm/K can be achieved and that the most sensitive range of the sensor can be tuned by changing the volume ratios of ethanol and chloroform. Moreover, the maximal sensitivity is relatively stable with random filled nanowires, which will be very convenient for the sensor fabrication.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    solvents were tested to dissolve two PLGA grades (50 KDa-RG755, 100 KDa-RG750). The viscoelasticity, surface tension, and evaporation rate of the PLGA solutions were characterized prior to the electrospinning process. The resulting electrospun nanofibers were characterized with respect to the morphology...

  20. Soluble fibers from psyllium improve glycemic response and body weight among diabetes type 2 patients (randomized control trial).

    Science.gov (United States)

    Abutair, Ayman S; Naser, Ihab A; Hamed, Amin T

    2016-10-12

    Water-soluble dietary fibers intake may help control blood glucose and body weight. The objective of the study was to determine whether soluble fiber supplementation from psyllium improves glycemic control indicators and body weight in type 2 diabetic patients. Forty type 2 diabetes patients, non-smoker, aged >35 years were stratified to different strata according to sex, age, body mass index (BMI) and fasting blood sugar level (FBS) and randomly assigned into two groups; The intervention group which consists of 20 participants was on soluble fiber (10.5 g daily), and the control group which consist of 20 participants continued on their regular diet for eight weeks duration. After 8 weeks of intervention, soluble fiber supplementation showed significant reduction in the intervention group in BMI (p < 0.001) when compared with the control group. Moreover, water soluble fiber supplementation proven to improve FBS (163 to 119 mg/dl), HbA1c (8.5 to 7.5 %), insulin level (27.9 to 19.7 μIU/mL), C-peptide (5.8 to 3.8 ng/ml), HOMA.IR (11.3 to 5.8) and HOMA-β % (103 to 141 %). The reduction in glycemic response was enhanced by combining soluble fiber to the normal diet. Consumption of foods containing moderate amounts of these fibers may improve glucose metabolism and lipid profile in type 2 diabetes patients. Current Controlled Trials PHRC/HC/28/15 .

  1. Characterisation, cytotoxicity and apoptosis studies of methotrexate-loaded PLGA and PLGA-PEG nanoparticles.

    Science.gov (United States)

    Afshari, Majid; Derakhshandeh, Katayoun; Hosseinzadeh, Leila

    2014-01-01

    Methotrexate (MTX) widely used in the treatments of various types of malignancies, but high toxicity and short plasma half-life have limited its use. This study was aimed at developing a polymeric drug delivery system for improving the therapeutic index of this potent drug. To achieve these goals, PLGA and PLGA-PEG nanoparticles were prepared using the emulsification-solvent diffusion technique and were optimized for particle size and entrapment efficiency. The optimum loaded nanoparticles were evaluated by cytotoxicity and their ability to induce apoptosis compared to free drug by examining of caspase-3 activity. The results showed that optimized particles were 182 ± 14 nm and 258 ± 10 nm in size for PLGA-PEG and PLGA nanoparticles, respectively, with an entrapment efficiency of more than 51%. The cytotoxicity experiment showed that the nanoparticles were more effective than pure MTX and increase the activity of caspase-3 in MCF7 and AGS and A549 cell lines.

  2. Characterization of composites fabricated from discontinuous random carbon fiber thermoplastic matrix sheets produced by a paper making process

    Science.gov (United States)

    Ducote, Martin Paul, Jr.

    In this thesis, a papermaking process was used to create two randomly oriented, high performance composite material systems. The primary objective of this was to discover the flexural properties of both composite systems and compare those to reported results from other studies. In addition, the process was evaluated for producing quality, randomly oriented composite panels. Thermoplastic polymers have the toughness and necessary strength to be alternatives to thermosets, but with the promise of lower cycle times and increased recyclability. The wet-lay papermaking process used in this study produces a quality, randomly oriented thermoplastic composite at low cycle times and simple production. The materials chosen represent high performance thermoplastics and carbon fibers. Short chopped carbon fiber filled Nylon 6,6 and PEEK composites were created at varying fiber volume fractions. Ten nylon based panels and five PEEK based panels were subjected to 4-point flexural testing. In several of the nylon-based panels, flexural testing was done in multiple direction to verify the in-plane isotropy of the final composite. The flexural strength performance of both systems showed promise when compared to equivalent products currently available. The flexural modulus results were less than expected and further research should be done into possibly causes. Overall, this research gives good insight into two high performance engineering composites and should aid in continued work.

  3. Quantum correlation of fiber-based telecom-band photon pairs through standard loss and random media.

    Science.gov (United States)

    Sua, Yong Meng; Malowicki, John; Lee, Kim Fook

    2014-08-15

    We study quantum correlation and interference of fiber-based telecom-band photon pairs with one photon of the pair experiencing multiple scattering in a random medium. We measure joint probability of two-photon detection for signal photon in a normal channel and idler photon in a channel, which is subjected to two independent conditions: standard loss (neutral density filter) and random media. We observe that both conditions degrade the correlation of signal and idler photons, and depolarization of the idler photon in random medium can enhance two-photon interference at certain relative polarization angles. Our theoretical calculation on two-photon polarization correlation and interference as a function of mean free path is in agreement with our experiment data. We conclude that quantum correlation of a polarization-entangled photon pair is better preserved than a polarization-correlated photon pair as one photon of the pair scatters through a random medium.

  4. Surface characteristics of PLA and PLGA films

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-12-30

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

  5. Randomized controlled clinical pilot trial of titanium vs. glass fiber prefabricated posts: preliminary results after up to 3 years.

    Science.gov (United States)

    Naumann, Michael; Sterzenbac, Guido; Alexandra, Franke; Dietrich, Thomas

    2007-01-01

    This randomized parallel-group clinical pilot study aimed to compare the clinical outcome of prefabricated rigid titanium to glass fiber endodontic posts when luted with self-adhesive universal resin cement. Ninety-eight patients in need of postendodontic restoration were assessed for eligibility. Ninety-one patients met the selection criteria and were randomized and allocated to 2 intervention groups. Forty-five participants were treated using a titanium post and 46 participants received a glass fiber post, each in combination with composite core buildups for postendodontic restoration. All posts had a diameter of 1.4 mm and a length of 13 mm and were cemented 8 mm within the root canal with self-adhesive universal resin cement. A circumferential ferrule of 2 mm was always provided. Surgical crown lengthening was necessary in 13 cases. Patients were observed in intervals of 3, 6, 12, 24, and 36 months after post placement. After 24 to 36 months (mean +/- SD: 27.9 +/- 5.6) of observation following post placement, 1 tooth was extracted because of changes of the prosthetic treatment plan. No failures were observed among the 88 patients with follow-up data. Both titanium and glass fiber reinforced composite posts result in successful treatment outcomes after 2 years. The material combination used seems to be appropriate in the short term for cementing endodontic posts, irrespective of the post material.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-02-01

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

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

    National Research Council Canada - National Science Library

    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...

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

    Science.gov (United States)

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

    2015-09-01

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

  9. A PLGA–PEG–PLGA Thermosensitive Gel Enabling Sustained Delivery of Ropivacaine Hydrochloride for Postoperative Pain Relief

    National Research Council Canada - National Science Library

    Fu, Xudong; Zeng, Huilin; Guo, Jiaping; Liu, Hong; Shi, Zhen; Chen, Huhai; Li, Dezong; Xie, Xiangyang; Kuang, Changchun

    2017-01-01

    .... In the current work, we used a poly(lactic-co-glycolic acid) (PLGA)–polyethylene glycol (PEG)–PLGA (PLGA–PEG–PLGA) temperature-sensitive gel to deliver a local anesthetic, ropivacaine hydrochloride...

  10. Nanoparticles of Poly(Lactide-Co-Glycolide-d-a-Tocopheryl Polyethylene Glycol 1000 Succinate Random Copolymer for Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Zheng Yi

    2010-01-01

    Full Text Available Abstract Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS by ring-opening polymerization using stannous octoate as catalyst. The obtained random copolymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded nanoparticles made of PLGA-TPGS copolymer were prepared by a modified solvent extraction/evaporation method. The nanoparticles were then characterized by various state-of-the-art techniques. The results revealed that the size of PLGA-TPGS nanoparticles was around 250 nm. The docetaxel-loaded PLGA-TPGS nanoparticles could achieve much faster drug release in comparison with PLGA nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa. The results also indicated that PLGA-TPGS-based nanoparticles were biocompatible, and the docetaxel-loaded PLGA-TPGS nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for PLGA-TPGS nanoparticles was in time- and concentration-dependent manner. In conclusion, PLGA-TPGS random copolymer could be acted as a novel and promising biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.

  11. Antimicrobial Properties and Cytocompatibility of PLGA/Ag Nanocomposites

    Directory of Open Access Journals (Sweden)

    Mariangela Scavone

    2016-01-01

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

  12. The Twister laser fiber degradation and tissue ablation capability during 980-nm high-power diode laser ablation of the prostate. A randomized study versus the standard side-firing fiber.

    Science.gov (United States)

    Shaker, Hassan; Alokda, Alsayed; Mahmoud, Hisham

    2012-09-01

    The objective of this work is to test the ablation capability and fiber degradation of the novel Twister fibers (TW), in both the large (LTW) and the standard (STW) sizes, against the standard side-firing (SF) fiber in a clinical setting during the treatment of BPH patients using the 980-nm high-power diode laser (HPDL). One hundred and twenty BPH patients treated with HPDL (Ceralase300, Biolitec AG, Jena, Germany) were randomized to receive treatment by one of the three fibers. Operative time corrected to tissue volume, laser treatment time, and laser energy were measured. Ablation rate was calculated as follows: the decrease of the prostate volume after 6 months/laser time. The fibers' resistance to degradation was defined by the laser energy needed to degrade the fiber completely. Preoperative prostate volume of 76 ± 38, 70 ± 39, and 88 ± 49 cc decreased by 49 ± 16, 51 ± 20, and 63 ± 16% for the SF, STW, and LTW fibers, respectively. This difference was highly significant when the LTW was compared to the other two fibers (p < 0.001). Prostate volume reduction post-operatively within each group as compared to the pre-operative volume was highly significant (p < 0.001). The ablation rate was highest in LTW, being 1.31 ± 0.59, 1.09 ± 0.51, and 1.54 ± 0.44 cc/min for the SF, STW, and LTW fibers, respectively. The LTW fiber resisted degradation more than the other fibers and the STW more than the SF fiber (p < 0.001). This study demonstrates the higher ablation efficiency and resistance to degradation of the LTW fiber as compared to the STW and SF fibers. The STW fiber has a similar ablation rate of the SF fiber but resists degradation better.

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

    National Research Council Canada - National Science Library

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

    2010-01-01

    .... 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...

  14. Two-dimensional coherent random laser in photonic crystal fiber with dye-doped nematic liquid crystal.

    Science.gov (United States)

    Nagai, Yusuke; Shao-Chieh, Chen; Kajikawa, Kotaro

    2017-11-10

    A random laser of a photonic crystal fiber (PCF) with holes filled with laser dye-doped nematic liquid crystal (NLC) is reported. When the excitation polarization was along the PCF axis, the measured laser threshold was 80  μJ/mm(2) per pulse, which is much lower than the previously reported random laser of PCF filled with laser dye-doped organic solvent. This low threshold is due to the high refractive index of the NLC, which produces a greater scattering efficiency. In contrast, when the excitation polarization is perpendicular to the PCF axis, the threshold was much higher or the laser oscillation was absent. This is because of the lower refractive index of the NLC for the perpendicular polarization. The laser oscillation was absent in the isotropic phase because of a low fluorescence efficiency at high temperatures.

  15. Plasma glucose and insulin responses after consumption of breakfasts with different sources of soluble fiber in type 2 diabetes patients: a randomized crossover clinical trial.

    Science.gov (United States)

    de Carvalho, Cláudia M; de Paula, Tatiana P; Viana, Luciana V; Machado, Vitória Mt; de Almeida, Jussara C; Azevedo, Mirela J

    2017-11-01

    Background: The amount and quality of carbohydrates are important determinants of plasma glucose after meals. Regarding fiber content, it is unclear whether the intake of soluble fibers from foods or supplements has an equally beneficial effect on lowering postprandial glucose.Objective: The aim of our study was to compare the acute effect of soluble fiber intake from foods or supplements after a common meal on postprandial plasma glucose and plasma insulin in patients with type 2 diabetes (T2D).Design: A randomized crossover clinical trial was conducted in patients with T2D. Patients consumed isocaloric breakfasts (mean ± SD: 369.8 ± 9.4 kcal) with high amounts of fiber from diet food sources (total fiber: 9.7 g; soluble fiber: 5.4 g), high amounts of soluble fiber from guar gum supplement (total fiber: 9.1 g; soluble fiber: 5.4 g), and normal amounts of fiber (total fiber: 2.4 g; soluble fiber: 0.8 g). Primary outcomes were postprandial plasma glucose and insulin (0-180 min). Data were analyzed by repeated measures ANOVA and post hoc Bonferroni test.Results: A total of 19 patients [aged 65.8 ± 7.3 y; median (IQR), 10 (5-9) y of T2D duration; glycated hemoglobin 7.0% ± 0.8%; body mass index (in kg/m2) 28.2 ± 2.9] completed 57 meal tests. After breakfast, the incremental area under the curve (iAUC) for plasma glucose [mg/dL · min; mean (95% CI)] did not differ between high fiber from diet (HFD) [7861 (6257, 9465)] and high fiber from supplement (HFS) [7847 (5605, 10,090)] (P = 1.00) and both were lower than usual fiber (UF) [9527 (7549, 11,504)] (P = 0.014 and P = 0.037, respectively). iAUCs [μIU/mL · min; mean (95% CI)] did not differ (P = 0.877): HFD [3781 (2513, 5050)], HFS [4006 (2711, 5302), and UF [4315 (3027, 5603)].Conclusions: Higher fiber intake was associated with lower postprandial glucose at breakfast, and the intake of soluble fiber from food and supplement had a similar effect in patients with T2D. This trial was registered at clinicaltrials

  16. Preparation, Physicochemical Characterization and Anti-fungal Evaluation of Nystatin-Loaded PLGA-Glucosamine Nanoparticles.

    Science.gov (United States)

    Mohammadi, Ghobad; Shakeri, Amineh; Fattahi, Ali; Mohammadi, Pardis; Mikaeili, Ali; Aliabadi, Alireza; Adibkia, Khosro

    2017-02-01

    Nystatin loaded PLGA and PLGA-Glucosamine nanoparticles were formulated. PLGA were functionalized with Glucosamine (PLGA-GlcN) to enhance the adhesion of nanoparticles to Candida Albicans (C.albicans) cell walls. Quasi-emulsion solvent diffusion method was employed using PLGA and PLGA-GlcN with various drug-polymer ratios for the preparation of nanoparticles. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency and release properties. DSC, SEM, XRPD, 1H-NMR, and FT-IR were performed to analyze the physicochemical properties of the nanoparticles. Antifungal activity of the nanoparticles was evaluated by determination of MICs against C.albicans. The spectra of 1H-NMR and FT-IR analysis ensured GlcN functionalization on PLGA nanoparticles. SEM characterization confirmed that particles were in the nanosize range and the particle size for PLGA and PLGA-GlcN nanoparticles were in the range of 108.63 ± 4.5 to 168.8 ± 5.65 nm and 208.76 ± 16.85 nm, respectively. DSC and XRPD analysis ensured reduction of the drug crystallinity in the nanoparticles. PLGA-GlcN nanoparticles exhibit higher antifungal activity than PLGA nanoparticles. PLGA-GlcN nanoparticles showed more antifungal activity with appropriate physicochemical properties than pure Nystatin and PLGA nanoparticles.

  17. Fiber intake and glycemic control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Silva, Flávia M; Kramer, Caroline K; de Almeida, Jussara C; Steemburgo, Thais; Gross, Jorge Luiz; Azevedo, Mirela J

    2013-12-01

    This systematic review with meta-analysis of randomized controlled trials (RCT) aimed to analyze the effect of fiber intake on glycemic control in patients with type 2 diabetes. Databases were searched up to November 2012 using the following medical subject headings: diabetes, fiber, and randomized controlled trial. Absolute changes in glycated hemoglobin and fasting plasma glucose were reported as differences between baseline and end-of-study measures. Pooled estimates were obtained using random-effects models. Of the 22,046 articles initially identified, 11 (13 comparisons; range of duration, 8-24 weeks) fulfilled the inclusion criteria, providing data from 605 patients. High-fiber diets, including diets with foods rich in fiber (up to 42.5 g/day; four studies) or supplements containing soluble fiber (up to 15.0 g/day; nine studies), reduced absolute values of glycated hemoglobin by 0.55% (95% CI -0.96 to -0.13) and fasting plasma glucose by 9.97 mg/dL (95% CI -18.16 to -1.78). In conclusion, increased fiber intake improved glycemic control, indicating it should be considered as an adjunctive tool in the treatment of patients with type 2 diabetes. © 2013 International Life Sciences Institute.

  18. Fracture resistance of short, randomly oriented, glass fiber-reinforced composite premolar crowns.

    Science.gov (United States)

    Garoushi, Sufyan; Vallittu, Pekka K; Lassila, Lippo V J

    2007-09-01

    The aim of this work was to determine the static load-bearing capacity of posterior composite crowns made of experimental composite resin (FC) with short fiber fillers and a semi-interpenetrating polymer network (IPN) matrix. In addition, we wanted to investigate how load-bearing capacity of surface composite resins was affected by substructures of fiber-reinforced composite (FRC) and FC, and by different curing systems. Five groups of crowns were fabricated (n=6). The crowns were either polymerized with a hand-light curing unit (LCU) or cured in a vacuum curing device (VLC) before they were statically loaded at a speed of 1mm min(-1) until fracture. Failure modes were visually examined. Data were analyzed using ANOVA. ANOVA revealed that crowns made from the FC had a statistically significant higher load-bearing capacity than the control PFC composite. Crowns with FRC substructure and PFC covering gave force values of 348N (LCU) and 1199N (VLC), respectively, which were lower than the values of FC composite. No statistically significant difference was found between crowns made from plain FC composite and those made from FC composite with a surface layer of PFC (P=0.892 and 1.00). Restorations made from short glass fiber-containing composite resin with IPN-polymer matrix showed better load bearing capacity than those made with either plain PFC or PFC reinforced with FRC substructure.

  19. HDL-mimetic PLGA nanoparticle to target atherosclerosis plaque macrophages.

    Science.gov (United States)

    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

    2015-03-18

    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.

  20. Stabilization of tetanus toxoid encapsulated in PLGA microspheres.

    Science.gov (United States)

    Jiang, Wenlei; Schwendeman, Steven P

    2008-01-01

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

  1. Improved cellular uptake of chitosan-modified PLGA nanospheres by A549 cells.

    Science.gov (United States)

    Tahara, Kohei; Sakai, Takeshi; Yamamoto, Hiromitsu; Takeuchi, Hirofumi; Hirashima, Naohide; Kawashima, Yoshiaki

    2009-12-01

    The authors have previously developed poly(DL-lactic-co-glycolic acid) (PLGA) nanospheres (NSs) as a nanoparticulate drug carrier for pulmonary administration. The present study demonstrates that chitosan (CS)-modified PLGA NSs (CS-PLGA NSs) are preferentially taken up by human lung adenocarcinoma cells (A549). PLGA NSs prepared using a water-oil-water emulsion solvent evaporation method were surface-modified by adsorption of CS. The physicochemical parameters of PLGA NS, including average size and surface charge, were measured to identify which parameter influenced cellular uptake of PLGA NS. Uptake was confirmed using fluorescence spectrophotometry and was visualized in A549 cells with confocal laser scanning microscopy (CLSM). The cytotoxicities of non- and CS-PLGA NS systems were compared in vitro by MTS assay. Cellular uptake of PLGA NS increased with decreasing diameter to the submicron level and with CS-mediated surface modification. Cellular uptake of PLGA NS was energy dependent, as shown by a reduction in uptake at lower incubation temperatures and in hypertonic growth medium used as an inhibitor of clathrin-coated pit endocytosis. CS-PLGA NSs were taken up by A549 cells in an energy-dependent manner, suggesting a clathrin-mediated endocytic process. CS-PLGA NS demonstrated low cytotoxicity, similar to non-PLGA NS.

  2. Soy fiber improves weight loss and lipid profile in overweight and obese adults: a randomized controlled trial.

    Science.gov (United States)

    Hu, Xiaojie; Gao, Jinlong; Zhang, Qianyuan; Fu, Yuanqing; Li, Kelei; Zhu, Shankuan; Li, Duo

    2013-12-01

    Studies have suggested that food rich in dietary fiber may facilitate body weight loss, lower total and LDL-cholesterol levels, and reduce body fat. This study examined the effects of soy fiber (SF) on body weight, body composition, and blood lipids in overweight and obese participants. Thirty-nine overweight and obese college adults (19-39 years of age) were randomly assigned to consume control biscuits or biscuits supplemented with SF for their breakfast for 12 wk (approximately 100 g/day). There were significant differences in changes on body weight, BMI, and LDL-cholesterol (LDL-C) between the two groups after 12-wk intervention (p weight, BMI, waist circumference, diastolic blood pressure, serum levels of total cholesterol, LDL-C, and glucose, body fat, and trunk fat of participants in SF group were observed significantly after 12 wk. SF had favorable effects on body weight, BMI, and fasting LDL-C levels in overweight and obese adults. These effects may be beneficial in antiobesity and the improvement of hyperlipidemia and hypertension (ClinicalTrials.gov registration number-NCT01802840). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The effects of functional fiber on postprandial glycemia, energy intake, satiety, palatability and gastrointestinal wellbeing: a randomized crossover trial

    NARCIS (Netherlands)

    Yuan, J.Y.F.; Smeele, R.J.M.; Harington, K.D.; Loon, van F.M.; Wanders, A.J.; Venn, B.J.

    2014-01-01

    Background: Fiber intakes in developed countries are generally below those recommended by relevant authorities. Given that many people consume fiber-depleted refined-grain products, adding functional fiber will help to increase fiber intakes. The objective of the study was to determine metabolic and

  4. Surface modification of electrospun PLGA scaffold with collagen for bioengineered skin substitutes

    Energy Technology Data Exchange (ETDEWEB)

    Sadeghi, A.R., E-mail: sadeghi_av@ymail.com [Materials Research Group, Iranian Academic Center for Education, Culture and Research, (ACECR), Mashhad Branch, Mashhad (Iran, Islamic Republic of); Nokhasteh, S. [Materials Research Group, Iranian Academic Center for Education, Culture and Research, (ACECR), Mashhad Branch, Mashhad (Iran, Islamic Republic of); Molavi, A.M. [Materials Research Group, Iranian Academic Center for Education, Culture and Research, (ACECR), Mashhad Branch, Mashhad (Iran, Islamic Republic of); Materials Engineering Department, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Khorsand-Ghayeni, M. [Materials Research Group, Iranian Academic Center for Education, Culture and Research, (ACECR), Mashhad Branch, Mashhad (Iran, Islamic Republic of); Naderi-Meshkin, H. [Stem Cell and Regenerative Medicine Research Department, Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad Branch, Mashhad (Iran, Islamic Republic of); Mahdizadeh, A. [Nanotechnology Institute, University of Sistan and Baluchestan, Zahedan (Iran, Islamic Republic of)

    2016-09-01

    In skin tissue engineering, surface feature of the scaffolds plays an important role in cell adhesion and proliferation. In this study, non-woven fibrous substrate based on poly (lactic-co-glycolic acid) (PLGA) (75/25) were hydrolyzed in various concentrations of NaOH (0.05 N, 0.1 N, 0.3 N) to increase carboxyl and hydroxyl groups on the fiber surfaces. These functional groups were activated by EDC/NHS to create chemical bonding with collagen. To improve bioactivity, the activated substrates were coated with a collagen solution (2 mg/ml) and cross-linking was carried out using the EDC/NHS in MES buffer. The effectiveness of the method was evaluated by contact angle measurements, porosimetry, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), tensile and degradation tests as well as in vitro cell attachment and cytotoxicity assays. Cell culture results of human dermal fibroblasts (HDF) and keratinocytes cell line (HaCat) revealed that the cells could attach to the scaffold. Further investigation with MTT assay showed that the cell proliferation of HaCat significantly increases with collagen coating. It seems that sufficient stability of collagen on the surface due to proper chemical bonding and cross-linking has increased the bioactivity of surface remarkably which can be promising for bioengineered skin applications. - Highlights: • Surface activation was carried out by hydrolysis of PLGA fibers. • To improve bioactivity, the activated samples were coated with a collagen solution. • Functional groups were activated by EDC/NHS to create chemical bonding with collagen. • Cross-linking of collagen was carried out using EDC/NHS in MES buffer. • The coated samples exhibited better adhesion and proliferation of epidermal cells.

  5. Fiber-rich diet with brown rice improves endothelial function in type 2 diabetes mellitus: A randomized controlled trial.

    Science.gov (United States)

    Kondo, Keiko; Morino, Katsutaro; Nishio, Yoshihiko; Ishikado, Atsushi; Arima, Hisatomi; Nakao, Keiko; Nakagawa, Fumiyuki; Nikami, Fumio; Sekine, Osamu; Nemoto, Ken-Ichi; Suwa, Makoto; Matsumoto, Motonobu; Miura, Katsuyuki; Makino, Taketoshi; Ugi, Satoshi; Maegawa, Hiroshi

    2017-01-01

    A fiber-rich diet has a cardioprotective effect, but the mechanism for this remains unclear. We hypothesized that a fiber-rich diet with brown rice improves endothelial function in patients with type 2 diabetes mellitus. Twenty-eight patients with type 2 diabetes mellitus at a single general hospital in Japan were randomly assigned to a brown rice (n = 14) or white rice (n = 14) diet and were followed for 8 weeks. The primary outcome was changes in endothelial function determined from flow debt repayment by reactive hyperemia using strain-gauge plethysmography in the fasting state. Secondary outcomes were changes in HbA1c, postprandial glucose excursions, and markers of oxidative stress and inflammation. The area under the curve for glucose after ingesting 250 kcal of assigned rice was compared between baseline (T0) and at the end of the intervention (T1) to estimate glucose excursions in each group. Improvement in endothelial function, assessed by fasting flow debt repayment (20.4% vs. -5.8%, p = 0.004), was significantly greater in the brown rice diet group than the white rice diet group, although the between-group difference in change of fiber intake was small (5.6 g/day vs. -1.2 g/day, pdiet group compared with the white rice diet group (0.01 μg/L vs. -0.04 μg/L, p = 0.063). The area under the curve for glucose was subtly but consistently lower in the brown rice diet group (T0: 21.4 mmol/L*h vs. 24.0 mmol/L*h, p = 0.043, T1: 20.4 mmol/L*h vs. 23.3 mmol/L*h, p = 0.046) without changes in HbA1c. Intervention with a fiber-rich diet with brown rice effectively improved endothelial function, without changes in HbA1c levels, possibly through reducing glucose excursions.

  6. Interaction of PLGA and trimethyl chitosan modified PLGA nanoparticles with mixed anionic/zwitterionic phospholipid bilayers studied using molecular dynamics simulations

    Science.gov (United States)

    Novak, Brian; Astete, Carlos; Sabliov, Cristina; Moldovan, Dorel

    2012-02-01

    Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable polymer. Nanoparticles of PLGA are commonly used for drug delivery applications. The interaction of the nanoparticles with the cell membrane may influence the rate of their uptake by cells. Both PLGA and cell membranes are negatively charged, so adding positively charged polymers such as trimethyl chitosan (TMC) which adheres to the PLGA particles improves their cellular uptake. The interaction of 3 nm PLGA and TMC-modified-PLGA nanoparticles with lipid bilayers composed of mixtures of phosphatidylcholine and phosphatidylserine lipids was studied using molecular dynamics simulations. The free energy profiles as function of nanoparticles position along the normal direction to the bilayers were calculated, the distribution of phosphatidylserine lipids as a function of distance of the particle from the bilayer was calculated, and the time scale for particle motion in the directions parallel to the bilayer surface was estimated.

  7. Engineering of lipid-coated PLGA nanoparticles with a tunable payload of diagnostically active nanocrystals for medical imaging.

    Science.gov (United States)

    Mieszawska, Aneta J; Gianella, Anita; Cormode, David P; Zhao, Yiming; Meijerink, Andries; Langer, Robert; Farokhzad, Omid C; Fayad, Zahi A; Mulder, Willem J M

    2012-06-14

    Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles that incorporate high payloads of nanocrystals into their core for tunable bioimaging features. We accomplished this through esterification reactions of PLGA to generate polymers modified with nanocrystals. The PLGA nanoparticles formed from modified PLGA polymers that were functionalized with either gold nanocrystals or quantum dots exhibited favorable features for computed tomography and optical imaging, respectively.

  8. Effect of dietary fiber on circulating C-reactive protein in overweight and obese adults: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Jiao, Jun; Xu, Jia-Ying; Zhang, Weiguo; Han, Shufen; Qin, Li-Qiang

    2015-02-01

    Previous studies suggested that dietary fiber intake may have a lowing effect on circulating C-reactive protein (CRP) level, a sensitive marker of inflammation, in overweight/obese adults with inconsistent results. A literature search was performed in April 2014 for related randomized controlled trials (RCTs) and meta-analysis was conducted. Meta-analysis including 14 RCTs showed that intervention with dietary fiber or fiber-rich food, compared with control, produced a slight, but significant reduction of 0.37 mg/L (95% CI -0.74, 0) in circulating CRP level among this population. Subgroup analyses showed that such a significant reduction was only observed after combining studies where the total fiber intake was 8 g/d higher in the intervention group than in the control group. No obvious heterogeneity and publication bias were found in the meta-analysis. In conclusion, this meta-analysis provides evidence that dietary fiber or food naturally rich in fiber has beneficial effects on circulating CRP level in overweight/obese adults.

  9. Concentrated oat β-glucan, a fermentable fiber, lowers serum cholesterol in hypercholesterolemic adults in a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Fulcher R Gary

    2007-03-01

    Full Text Available Abstract Background Soluble fibers lower serum lipids, but are difficult to incorporate into products acceptable to consumers. We investigated the physiological effects of a concentrated oat β-glucan on cardiovascular disease (CVD endpoints in human subjects. We also compared the fermentability of concentrated oat β-glucan with inulin and guar gum in a model intestinal fermentation system. Methods Seventy-five hypercholesterolemic men and women were randomly assigned to one of two treatments: 6 grams/day concentrated oat β-glucan or 6 grams/day dextrose (control. Fasting blood samples were collected at baseline, week 3, and week 6 and analyzed for total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, insulin, homocysteine and C-reactive protein (CRP. To estimate colonic fermentability, 0.5 g concentrated oat β-glucan was incubated in a batch model intestinal fermentation system, using human fecal inoculum to provide representative microflora. Fecal donors were not involved with the β-glucan feeding trial. Inulin and guar gum were also incubated in separate serum bottles for comparison. Results Oat β-glucan produced significant reduction from baseline in total cholesterol (-0.3 ± 0.1 mmol/L and LDL cholesterol (-0.3 ± 0.1 mmol/L, and the reduction in LDL cholesterol were significantly greater than in the control group (p = 0.03. Concentrated oat β-glucan was a fermentable fiber and produced total SCFA and acetate concentrations similar to inulin and guar gum. Concentrated oat β-glucan produced the highest concentrations of butyrate at 4, 8, and 12 hours. Conclusion Six grams concentrated oat β-glucan per day for six weeks significantly reduced total and LDL cholesterol in subjects with elevated cholesterol, and the LDL cholesterol reduction was greater than the change in the control group. Based on a model intestinal fermentation, this oat β-glucan was fermentable, producing higher amounts of butyrate than other

  10. Nanoporous Calcium Silicate and PLGA Biocomposite for Bone Repair

    Directory of Open Access Journals (Sweden)

    Jiacan Su

    2010-01-01

    Full Text Available Nanoporous calcium silicate (n-CS with high surface area was synthesized using the mixed surfactants of EO20PO70EO20 (polyethylene oxide20(polypropylene oxide70(polyethylene oxide20, P123 and hexadecyltrimethyl ammonium bromide (CTAB as templates, and its composite with poly(lactic acid-co-glycolic acid (PLGA were fabricated. The results showed that the n-CS/PLGA composite (n-CPC with 20 wt% n-CS could induce a dense and continuous layer of apatite on its surface after soaking in simulated body fluid (SBF for 1 week, suggesting the excellent in vitro bioactivity. The n-CPC could promote cell attachment on its surfaces. In addition, the proliferation ratio of MG63 cells on n-CPC was significantly higher than PLGA; the results demonstrated that n-CPC had excellent cytocompatibility. We prepared n-CPC scaffolds that contained open and interconnected macropores ranging in size from 200 to 500 μm. The n-CPC scaffolds were implanted in femur bone defect of rabbits, and the in vivo biocompatibility and osteogenicity of the scaffolds were investigated. The results indicated that n-CPC scaffolds exhibited good biocompatibility, degradability, and osteogenesis in vivo. Collectively, these results suggested that the incorporation of n-CS in PLGA produced biocomposites with improved bioactivity and biocompatibility.

  11. Psyllium Fiber Reduces Abdominal Pain in Children With Irritable Bowel Syndrome in a Randomized, Double-Blind Trial.

    Science.gov (United States)

    Shulman, Robert J; Hollister, Emily B; Cain, Kevin; Czyzewski, Danita I; Self, Mariella M; Weidler, Erica M; Devaraj, Sridevi; Luna, Ruth Ann; Versalovic, James; Heitkemper, Margaret

    2017-05-01

    We sought to determine the efficacy of psyllium fiber treatment on abdominal pain and stool patterns in children with irritable bowel syndrome (IBS). We evaluated effects on breath hydrogen and methane production, gut permeability, and microbiome composition. We also investigated whether psychological characteristics of children or parents affected the response to treatment. We performed a randomized, double-blind trial of 103 children (mean age, 13 ± 3 y) with IBS seen at primary or tertiary care settings. After 2 weeks on their habitual diet, children began an 8-day diet excluding carbohydrates thought to cause symptoms of IBS. Children with ≥75% improvement in abdominal pain were excluded (n = 17). Children were assigned randomly to groups given psyllium (n = 37) or placebo (maltodextrin, n = 47) for 6 weeks. Two-week pain and stool diaries were compared at baseline and during the final 2 weeks of treatment. We assessed breath hydrogen and methane production, intestinal permeability, and the composition of the microbiome before and after administration of psyllium or placebo. Psychological characteristics of children were measured at baseline. Children in the psyllium group had a greater reduction in the mean number of pain episodes than children in the placebo group (mean reduction of 8.2 ± 1.2 after receiving psyllium vs mean reduction of 4.1 ± 1.3 after receiving placebo; P = .03); the level of pain intensity did not differ between the groups. Psychological characteristics were not associated with response. At the end of the study period, the percentage of stools that were normal (Bristol scale scores, 3-5), breath hydrogen or methane production, intestinal permeability, and microbiome composition were similar between groups. Psyllium fiber reduced the number of abdominal pain episodes in children with IBS, independent of psychological factors. Psyllium did not alter breath hydrogen or methane production, gut permeability, or microbiome composition

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

    Directory of Open Access Journals (Sweden)

    Francesca Selmin

    2015-01-01

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

  13. Bone augmentation using a highly porous PLGA/β-TCP scaffold containing fibroblast growth factor-2.

    Science.gov (United States)

    Yoshida, T; Miyaji, H; Otani, K; Inoue, K; Nakane, K; Nishimura, H; Ibara, A; Shimada, A; Ogawa, K; Nishida, E; Sugaya, T; Sun, L; Fugetsu, B; Kawanami, M

    2015-04-01

    Beta-tricalcium phosphate (β-TCP), a bio-absorbable ceramic, facilitates bone conductivity. We constructed a highly porous three-dimensional scaffold, using β-TCP, for bone tissue engineering and coated it with co-poly lactic acid/glycolic acid (PLGA) to improve the mechanical strength and biological performance. The aim of this study was to examine the effect of implantation of the PLGA/β-TCP scaffold loaded with fibroblast growth factor-2 (FGF-2) on bone augmentation. The β-TCP scaffold was fabricated by the replica method using polyurethane foam, then coated with PLGA. The PLGA/β-TCP scaffold was characterized by scanning electron miscroscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction, compressive testing, cell culture and a subcutaneous implant test. Subsequently, a bone-forming test was performed using 52 rats. The β-TCP scaffold, PLGA-coated scaffold, and β-TCP and PLGA-coated scaffolds loaded with FGF-2, were implanted into rat cranial bone. Histological observations were made at 10 and 35 d postsurgery. SEM and TEM observations showed a thin PLGA layer on the β-TCP particles after coating. High porosity (> 90%) of the scaffold was exhibited after PLGA coating, and the compressive strength of the PLGA/β-TCP scaffold was six-fold greater than that of the noncoated scaffold. Good biocompatibility of the PLGA/β-TCP scaffold was found in the culture and implant tests. Histological samples obtained following implantation of PLGA/β-TCP scaffold loaded with FGF-2 showed significant bone augmentation. The PLGA coating improved the mechanical strength of β-TCP scaffolds while maintaining high porosity and tissue compatibility. PLGA/β-TCP scaffolds, in combination with FGF-2, are bioeffective for bone augmentation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Fabrication of mineralized electrospun PLGA and PLGA/gelatin nanofibers and their potential in bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Z.X. [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Li, H.F. [Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871 (China); Sun, Z.Z. [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Zheng, W., E-mail: zhengwei@hrbeu.edu.cn [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Zheng, Y.F., E-mail: yfzheng@pku.edu.cn [Center for Biomedical Materials and Engineering, Harbin Engineering University, Harbin 150001 (China); Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871 (China)

    2013-03-01

    Surface mineralization is an effective method to produce calcium phosphate apatite coating on the surface of bone tissue scaffold which could create an osteophilic environment similar to the natural extracellular matrix for bone cells. In this study, we prepared mineralized poly(D,L-lactide-co-glycolide) (PLGA) and PLGA/gelatin electrospun nanofibers via depositing calcium phosphate apatite coating on the surface of these nanofibers to fabricate bone tissue engineering scaffolds by concentrated simulated body fluid method, supersaturated calcification solution method and alternate soaking method. The apatite products were characterized by the scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), and X-ray diffractometry (XRD) methods. A large amount of calcium phosphate apatite composed of dicalcium phosphate dihydrate (DCPD), hydroxyapatite (HA) and octacalcium phosphate (OCP) was deposited on the surface of resulting nanofibers in short times via three mineralizing methods. A larger amount of calcium phosphate was deposited on the surface of PLGA/gelatin nanofibers rather than PLGA nanofibers because gelatin acted as nucleation center for the formation of calcium phosphate. The cell culture experiments revealed that the difference of morphology and components of calcium phosphate apatite did not show much influence on the cell adhesion, proliferation and activity. - Highlights: Black-Right-Pointing-Pointer Ca-P phases were coated on PLGA/gelatin electrospun nanofiber membranes within 3 h. Black-Right-Pointing-Pointer Ca-P coatings prepared by 3 methods exhibited different structures and components. Black-Right-Pointing-Pointer The Ca-P coating weight increase depends on the apatite nucleation velocity. Black-Right-Pointing-Pointer Surface hydrophilicity enhanced the velocity and quantity of apatite nucleation. Black-Right-Pointing-Pointer The resulting Ca-P apatite coatings exhibit good biocompatibility to MG63 cells.

  15. Cocoa, hazelnuts, sterols and soluble fiber cream reduces lipids and inflammation biomarkers in hypertensive patients: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Rosa Solà

    Full Text Available Cocoa, mixed with other food ingredients, intake can have beneficial effects on cardiovascular disease (CVD biomarkers. We compared the effects of 4 cocoa cream products on some of these biomarkers.In this multi-centered, randomized, controlled, double-blind, parallel trial, volunteers (n = 113; age range: 43-65 years who were pre-hypertensive, stage-1 hypertensive and hypercholesterolemic received one of 4 cocoa cream products (13 g/unit; 1 g cocoa/unit, 6 units/d; 465 Kcal/d added to a low saturated fat diet for 4 weeks. The groups were: A (n = 28, cocoa cream considered as control; B (n = 28, cocoa+hazelnut cream (30 g/d hazelnuts; C (n = 30, cocoa+hazelnuts+phytosterols (2 g/d; and D (n = 27, cocoa+hazelnuts+phytosterols+soluble fiber (20 g/d the patented "LMN product". Primary outcome measures were BP, LDL-c, apolipoprotein B-100 (Apo B, ApoB/ApoA ratio, oxidized LDL (oxLDL and high-sensitive C-reactive protein (hsCRP determined at baseline and post-cocoa cream product intake. Statistical analysis used was ANCOVA or mixed models (in case of repeated measurements, with baseline observation included as a covariate. After 4 weeks, compared to product A, product C reduced LDL-c by 11.2%, Apo B by 8.1% and ApoB/ApoA ratio by 7.8% (P = 0.01. LMN decreased LDL-c by 9.2%, Apo B-100 by 8.5%, ApoB/ApoA ratio by 10.5%, hsCRP by 33.4% and oxLDL by 5.9% (P = 0.01. Surprisingly, even "control" product A reduced systolic BP (-7.89 mmHg; 95%CI: -11.45 to -4.3 and diastolic BP (-5.54 mmHg; 95%CI: -7.79 to -3.29. The BP reductions were similar with the other 3 products. Limitations of the study are that the trial period was relatively short and that a better "BP control" product would have been preferable.The creams (particularly the LMN have anti-inflammatory and antioxidant effects in addition to lowering LDL-c, Apo B and ApoB/ApoA ratio. Thus, the soluble fiber effects amplified with sterols (as contained in the cocoa creams provide new dietary

  16. A Cluster Randomized Controlled Trial to Reduce Childhood Diarrhea Using Hollow Fiber Water Filter and/or Hygiene–Sanitation Educational Interventions

    OpenAIRE

    Lindquist, Erik D.; George, C. M.; Perin, Jamie; Neiswender de Calani, Karen J.; Norman, W. Ray; Davis, Thomas P.; Perry, Henry

    2014-01-01

    Safe domestic potable water supplies are urgently needed to reduce childhood diarrheal disease. In periurban neighborhoods in Cochabamba, Bolivia, we conducted a cluster randomized controlled trial to evaluate the efficacy of a household-level hollow fiber filter and/or behavior change communication (BCC) on water, sanitation, and hygiene (WASH) to reduce the diarrheal disease in children less than 5 years of age. In total, 952 households were followed for a period of 12 weeks post-distributi...

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

    OpenAIRE

    Ma YR; Zhao XY; Li J; Shen Q

    2012-01-01

    Yiran Ma, Xinyi Zhao, Jian Li, Qi ShenSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai, ChinaAbstract: The aim of this research was to increase the oral bioavailability of daidzein by the formulations of poly(lactic-co-glycolic) acid (PLGA) nanoparticles loaded with daidzein. Amongst the various traditional and novel techniques of preparing daidzein-loaded PLGA nanoparticles, daidzein-loaded phospholipid complexes PLGA nanoparticles and daidzein-loaded cyclodextrin inclusion comple...

  18. Statistical Design for Formulation Optimization of Hydrocortisone Butyrate-Loaded PLGA Nanoparticles

    National Research Council Canada - National Science Library

    Yang, Xiaoyan; Patel, Sulabh; Sheng, Ye; Pal, Dhananjay; Mitra, Ashim K

    2014-01-01

    .... Experimental designs were used to investigate specific effects of independent variables during preparation of HB-loaded PLGA NP and corresponding responses in optimizing the formulation. Plackett...

  19. Random or selective neuroanatomical connectivity. Study of the distribution of fibers over two populations of identified interneurons in cerebral cortex

    NARCIS (Netherlands)

    Vinkenoog, M.; van den Oever, M.C.; Uylings, H.B.M.; Wouterlood, F.G.

    2005-01-01

    We present a neuroanatomical tracing method in a stereological approach to study the proportional distribution of fibers of a particular projection over two chemically different populations of neurons. The fiber projection from the presubiculum to the medial division of the entorhinal cortex of the

  20. Loperamide Versus Psyllium Fiber for Treatment of Fecal Incontinence: The Fecal Incontinence Prescription (Rx) Management (FIRM) Randomized Clinical Trial.

    Science.gov (United States)

    Markland, Alayne D; Burgio, Kathryn L; Whitehead, William E; Richter, Holly E; Wilcox, C Mel; Redden, David T; Beasley, Timothy M; Goode, Patricia S

    2015-10-01

    Fecal incontinence is a devastating condition with few US Food and Drug Administration-approved pharmacologic treatment options. Loperamide and psyllium, both first-line treatments, have different mechanisms of action without any comparative data. The purpose of this study was to examine the effectiveness and tolerability of loperamide compared with psyllium for reducing fecal incontinence. We hypothesized that psyllium fiber supplementation would be more effective than loperamide for reducing fecal incontinence episodes and have fewer adverse effects. We conducted a randomized, double-blind, placebo-controlled crossover trial comparing loperamide (followed by psyllium) with psyllium (followed by loperamide). Our sites included outpatient clinics within a Veterans Affairs medical center and university affiliate. Participants included community-dwelling adults (n = 80) with at least 1 fecal incontinent episode on a 7-day bowel diary. Participants received either daily loperamide (plus placebo psyllium powder) or psyllium powder (plus loperamide placebo) for 4 weeks. After a 2-week washout, participants crossed over to 4 weeks of alternate treatment. The primary outcome was the number of fecal incontinence episodes from 7-day bowel diaries. Secondary outcomes included symptom severity, quality of life, and tolerability. Mean age was 60.7 ± 10.1 years; 68% were men. After determining nonsignificant carryover effects, combined analyses showed no differences between the loperamide and psyllium groups for reducing fecal incontinent episodes, symptom severity, or quality of life. Within each group, both loperamide and psyllium reduced fecal incontinent episodes and improved symptom severity and quality of life. Constipation occurred in 29% of participants for loperamide vs 10% for psyllium. Limitations include the washout period length and dropout rate after crossing over to the second intervention. Both loperamide and psyllium improve fecal incontinence. Loperamide was

  1. 3D printing PLGA: a quantitative examination of the effects of polymer composition and printing parameters on print resolution.

    Science.gov (United States)

    Guo, Ting; Holzberg, Timothy R; Lim, Casey G; Gao, Feng; Gargava, Ankit; Trachtenberg, Jordan E; Mikos, Antonios G; Fisher, John P

    2017-04-12

    In the past few decades, 3D printing has played a significant role in fabricating scaffolds with consistent, complex structure that meet patient-specific needs in future clinical applications. Although many studies have contributed to this emerging field of additive manufacturing, which includes material development and computer-aided scaffold design, current quantitative analyses do not correlate material properties, printing parameters, and printing outcomes to a great extent. A model that correlates these properties has tremendous potential to standardize 3D printing for tissue engineering and biomaterial science. In this study, we printed poly(lactic-co-glycolic acid) (PLGA) utilizing a direct melt extrusion technique without additional ingredients. We investigated PLGA with various lactic acid:glycolic acid (LA:GA) molecular weight ratios and end caps to demonstrate the dependence of the extrusion process on the polymer composition. Micro-computed tomography was then used to evaluate printed scaffolds containing different LA:GA ratios, composed of different fiber patterns, and processed under different printing conditions. We built a statistical model to reveal the correlation and predominant factors that determine printing precision. Our model showed a strong linear relationship between the actual and predicted precision under different combinations of printing conditions and material compositions. This quantitative examination establishes a significant foreground to 3D print biomaterials following a systematic fabrication procedure. Additionally, our proposed statistical models can be applied to couple specific biomaterials and 3D printing applications for patient implants with particular requirements.

  2. Biological Properties of Low-Toxic PLGA and PLGA/PHB Fibrous Nanocomposite Scaffolds for Osseous Tissue Regeneration. Evaluation of Potential Bioactivity

    Directory of Open Access Journals (Sweden)

    Boguslawa Żywicka

    2017-10-01

    Full Text Available Abstracts: The aim of the study was to evaluate the biocompatibility and bioactivity of two new prototype implants for bone tissue regeneration made from biodegradable fibrous materials. The first is a newly developed poly(l-lactide-co-glycolide, (PLGA, and the second is a blend of PLGA with synthetic poly([R,S]-3-hydroxybutyrate (PLGA/PHB. The implant prototypes comprise PLGA or PLGA/PHB nonwoven fabrics with designed pore structures to create the best conditions for cell proliferation. The bioactivity of the proposed implants was enhanced by introducing a hydroxyapatite material and a biologically active agent, namely, growth factor IGF1, encapsulated in calcium alginate microspheres. To assess the biocompatibility and bioactivity, allergenic tests and an assessment of the local reaction of bone tissue after implantation were performed. Comparative studies of local tissue response after implantation into trochanters for a period of 12 months were performed on New Zealand rabbits. Based on the results of the in vivo evaluation of the allergenic effects and the local tissue reaction 12 months after implantation, it was concluded that the two implant prototypes, PLGA + IGF1 and PLGA/PHB + IGF1, were characterized by high biocompatibility with the soft and bone tissues of the tested animals.

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

    Directory of Open Access Journals (Sweden)

    Krucińska Izabella

    2014-06-01

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

  4. Engineering of lipid-coated PLGA nanoparticles with a tunable payload of diagnostically active nanocrystals for medical imaging

    NARCIS (Netherlands)

    Mieszawska, A.J.; Gianella, A.; Cormode, D.P.; Zhao, Y.; Meijerink, A.; Langer, R.; Farokhzad, O.C.; Fayad, Z.A.; Mulder, W J M

    2012-01-01

    Polylactic-co-glycolic acid (PLGA) based nanoparticles are biocompatible and biodegradable and therefore have been extensively investigated as therapeutic carriers. Here, we engineered diagnostically active PLGA nanoparticles that incorporate high payloads of nanocrystals into their core for tunable

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

    Science.gov (United States)

    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.

  6. Voronoi polygons and self-consistent technique used to compute the airflow resistivity of randomly placed fibers in glass wool

    DEFF Research Database (Denmark)

    Tarnow, Viggo

    2002-01-01

    Sound in glass wool propagates mainly in the air between glass fibers. For sound waves considered here, the distance between fibers is much smaller than the wavelength. Therefore, the sound velocity and attenuation can be computed from an effective mass density and compressibility. For simple...... harmonic waves at low frequencies, the effective mass density is determined by the friction between air and fibers. The friction is described by the airflow resistivity, which depends on frequency, but for frequencies below 1000 Hz in glass wool with density 15–30 kg/m3, the resistivity to airflow...

  7. Evaluation of the biocompatibility of calcium phosphate cement/PLGA microparticle composites.

    NARCIS (Netherlands)

    Link, D.P.; Dolder, J. van den; Beucken, J.J.J.P van den; Cuijpers, V.M.J.I.; Wolke, J.G.C.; Mikos, A.G.; Jansen, J.A.

    2008-01-01

    In this study, the biocompatibility of a calcium phosphate (CaP) cement incorporating poly (D,L-lactic-co-glycolic acid) (PLGA) microparticles was evaluated in a subcutaneous implantation model in rats. Short-term biocompatibility was assessed using pure CaP discs and CaP discs incorporating PLGA

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Cristian Vilos

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

  11. Effect of a low-glycemic index or a high-cereal fiber diet on type 2 diabetes: a randomized trial.

    Science.gov (United States)

    Jenkins, David J A; Kendall, Cyril W C; McKeown-Eyssen, Gail; Josse, Robert G; Silverberg, Jay; Booth, Gillian L; Vidgen, Edward; Josse, Andrea R; Nguyen, Tri H; Corrigan, Sorcha; Banach, Monica S; Ares, Sophie; Mitchell, Sandy; Emam, Azadeh; Augustin, Livia S A; Parker, Tina L; Leiter, Lawrence A

    2008-12-17

    Clinical trials using antihyperglycemic medications to improve glycemic control have not demonstrated the anticipated cardiovascular benefits. Low-glycemic index diets may improve both glycemic control and cardiovascular risk factors for patients with type 2 diabetes but debate over their effectiveness continues due to trial limitations. To test the effects of low-glycemic index diets on glycemic control and cardiovascular risk factors in patients with type 2 diabetes. A randomized, parallel study design at a Canadian university hospital research center of 210 participants with type 2 diabetes treated with antihyperglycemic medications who were recruited by newspaper advertisement and randomly assigned to receive 1 of 2 diet treatments each for 6 months between September 16, 2004, and May 22, 2007. High-cereal fiber or low-glycemic index dietary advice. Absolute change in glycated hemoglobin A(1c) (HbA(1c)), with fasting blood glucose and cardiovascular disease risk factors as secondary measures. In the intention-to-treat analysis, HbA(1c) decreased by -0.18% absolute HbA(1c) units (95% confidence interval [CI], -0.29% to -0.07%) in the high-cereal fiber diet compared with -0.50% absolute HbA(1c) units (95% CI, -0.61% to -0.39%) in the low-glycemic index diet (P fiber diet (P = .005). The reduction in dietary glycemic index related positively to the reduction in HbA(1c) concentration (r = 0.35, P diabetes, 6-month treatment with a low-glycemic index diet resulted in moderately lower HbA(1c) levels compared with a high-cereal fiber diet. Trial Registration clinicaltrials.gov identifier: NCT00438698.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-01

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

  13. Low temperature gamma sterilization of a bioresorbable polymer, PLGA

    Science.gov (United States)

    Davison, Lisa; Themistou, Efrosyni; Buchanan, Fraser; Cunningham, Eoin

    2018-02-01

    Medical devices destined for insertion into the body must be sterilised before implantation to prevent infection or other complications. Emerging biomaterials, for example bioresorbable polymers, can experience changes in their properties due to standard industrial sterilization processes. Gamma irradiation is one of the most reliable, large scale sterilization methods, however it can induce chain scission, cross-linking or oxidation reactions in polymers. sterilization at low temperature or in an inert atmosphere has been reported to reduce the negative effects of gamma irradiation. The aim of this study was to investigate the impact of low temperature sterilization (at -80 °C) when compared to sterilization at ambient temperature (25 °C) both in inert atmospheric conditions of nitrogen gas, on poly(lactide co-glycolide) (PLGA). PLGA was irradiated at -80 and 25 °C at 40 kGy in a nitrogen atmosphere. Samples were characterised using differential scanning calorimetry (DSC), tensile test, Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). The results showed that the molecular weight was significantly reduced as was the glass transition temperature, an indication of chain scission. FTIR showed small changes in chemical structure in the methyl and carbonyl groups after irradiation. Glass transition temperature was significantly different between irradiation at -80 °C and irradiation at 25 °C, however this was a difference of only 1 °C. Ultimately, the results indicate that the sterilization temperature used does not affect PLGA when carried out in a nitrogen atmosphere.

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

    Science.gov (United States)

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

    2015-08-01

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

  15. Investigation on the ion pair amphiphiles and their in vitro release of amantadine drug based on PLGA-PEG-PLGA gel

    Science.gov (United States)

    Yang, Xiaoxia; Ji, Xiaoqing; Shi, Chunhuan; Liu, Jing; Wang, Haiyang; Luan, Yuxia

    2014-12-01

    The amantadine drug and oleic acid surfactant are used to form amantadine-based ion pair amphiphiles based on proton transfer reaction between the drug and the surfactant molecules. The ion pair amphiphiles are characterized by 1H-nuclear magnetic resonance, Fourier transform infrared spectroscopy, and X-ray diffraction. Self-assembly properties of amantadine-based ion pair amphiphiles are studied by surface tension determination, transmission electron microscopy, zeta potential, and dynamic light scattering. The aggregation behavior studies indicate that the as-prepared ion pair amphiphiles can self-assemble into vesicles with the size of 200-300 nm in aqueous solution. The drug release results show that the amantadine release rate could be well controlled by incorporating the amantadine-based ion pair vesicles in poly (lactic-co-glycolic acid)-poly (ethylene glycol)-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer hydrogel. The drug release from the AT-OA vesicle-loaded PLGA-PEG-PLGA hydrogel is significantly inhibited in comparison with the AT-loaded PLGA-PEG-PLGA hydrogel. The present work thus demonstrates that the vesicle-loaded hydrogel is a good candidate for the drug delivery system with long-term controlled drug release behavior.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-08-15

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

  17. Surface functionalisation of PLGA nanoparticles for gene silencing

    DEFF Research Database (Denmark)

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

    2010-01-01

    This work presents a method for decorating the surface of poly (lactide-co-glycolide) (PLGA) nanoparticles with polyethyleneimine (PEI) utilising a cetyl derivative to improve surface functionalisation and siRNA delivery. Sub-micron particles were produced by an emulsion-diffusion method using...... microscopy and flow cytometry to bind and mediate siRNA delivery into the human osteosarcoma cell line U2OS and the murine macrophage cell line J774.1. Specific reduction in the anti-apoptotic oncogene BCL-w in U2OS cells was achieved with particles containing cetylated-PEI (53%) with no cellular toxicity...

  18. Acute fiber supplementation with inulin-type fructans curbs appetite sensations: a randomized, double-blind, placebo-controlled study

    OpenAIRE

    Salmean, Younis A.

    2017-01-01

    ABSTRACT Background:?Research points to a benefit of inulin fiber on appetite and weight regulation but results remain mixed.?Objectives:?To test the impact of 16 g/d of Inulin-type fructans (ITFs) on appetite and food intake in acute settings. Design: Forty college age females received either a fiber drink with 16 g of ITFs in 330 ml water or placebo. On the 8th?day of the study, appetite sensations were assessed using visual analogue scale (VAS) along with food intake. Repeated-measures ANO...

  19. A randomized, prospective, comparison study of a mixture of acacia fiber, psyllium fiber, and fructose vs polyethylene glycol 3350 with electrolytes for the treatment of chronic functional constipation in childhood.

    Science.gov (United States)

    Quitadamo, Paolo; Coccorullo, Paola; Giannetti, Eleonora; Romano, Claudio; Chiaro, Andrea; Campanozzi, Angelo; Poli, Emanuela; Cucchiara, Salvatore; Di Nardo, Giovanni; Staiano, Annamaria

    2012-10-01

    To compare the effectiveness of a mixture of acacia fiber, psyllium fiber, and fructose (AFPFF) with polyethylene glycol 3350 combined with electrolytes (PEG+E) in the treatment of children with chronic functional constipation (CFC); and to evaluate the safety and effectiveness of AFPFF in the treatment of children with CFC. This was a randomized, open label, prospective, controlled, parallel-group study involving 100 children (M/F: 38/62; mean age ± SD: 6.5 ± 2.7 years) who were diagnosed with CFC according to the Rome III Criteria. Children were randomly divided into 2 groups: 50 children received AFPFF (16.8 g daily) and 50 children received PEG+E (0.5 g/kg daily) for 8 weeks. Primary outcome measures were frequency of bowel movements, stool consistency, fecal incontinence, and improvement of other associated gastrointestinal symptoms. Safety was assessed with evaluation of clinical adverse effects and growth measurements. Compliance rates were 72% for AFPFF and 96% for PEG+E. A significant improvement of constipation was seen in both groups. After 8 weeks, 77.8% of children treated with AFPFF and 83% of children treated with PEG+E had improved (P = .788). Neither PEG+E nor AFPFF caused any clinically significant side effects during the entire course of the study period. In this randomized study, we did not find any significant difference between the efficacy of AFPFF and PEG+E in the treatment of children with CFC. Both medications were proved to be safe for CFC treatment, but PEG+E was better accepted by children. Copyright © 2012 Mosby, Inc. All rights reserved.

  20. Microencapsulation of inorganic nanocrystals into PLGA microsphere vaccines enables their intracellular localization in dendritic cells by electron and fluorescence microscopy.

    Science.gov (United States)

    Schliehe, Christopher; Schliehe, Constanze; Thiry, Marc; Tromsdorf, Ulrich I; Hentschel, Joachim; Weller, Horst; Groettrup, Marcus

    2011-05-10

    Biodegradable poly-(D,L-lactide-co-glycolide) microspheres (PLGA-MS) are approved as a drug delivery system in humans and represent a promising antigen delivery device for immunotherapy against cancer. Immune responses following PLGA-MS vaccination require cross-presentation of encapsulated antigen by professional antigen presenting cells (APCs). While the potential of PLGA-MS as vaccine formulations is well established, the intracellular pathway of cross-presentation following phagocytosis of PLGA-MS is still under debate. A part of the controversy stems from the difficulty in unambiguously identifying PLGA-MS within cells. Here we show a novel strategy for the efficient encapsulation of inorganic nanocrystals (NCs) into PLGA-MS as a tool to study their intracellular localization. We microencapsulated NCs as an electron dense marker to study the intracellular localization of PLGA-MS by transmission electron microscopy (TEM) and as fluorescent labels for confocal laser scanning microscopy. Using this method, we found PLGA-MS to be rapidly taken up by dendritic cells and macrophages. Co-localization with the lysosomal marker LAMP1 showed a lysosomal storage of PLGA-MS for over two days after uptake, long after the initiation of cross-presentation had occurred. Our data argue against an escape of PLGA-MS from the endosome as has previously been suggested as a mechanism to facilitate cross-presentation of PLGA-MS encapsulated antigen. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Psyllium fiber reduces abdominal pain in children with irritable bowel syndrome in a randomized, double-blind trial

    Science.gov (United States)

    We sought to determine the efficacy of psyllium fiber treatment on abdominal pain and stool patterns in children with irritable bowel syndrome (IBS). We evaluated effects on breath hydrogen and methane production, gut permeability, and microbiome composition. We also investigated whether psychologic...

  2. Acute fiber supplementation with inulin-type fructans curbs appetite sensations: a randomized, double-blind, placebo-controlled study

    Science.gov (United States)

    Salmean, Younis A.

    2017-01-01

    ABSTRACT Background: Research points to a benefit of inulin fiber on appetite and weight regulation but results remain mixed. Objectives: To test the impact of 16 g/d of Inulin-type fructans (ITFs) on appetite and food intake in acute settings. Design: Forty college age females received either a fiber drink with 16 g of ITFs in 330 ml water or placebo. On the 8th day of the study, appetite sensations were assessed using visual analogue scale (VAS) along with food intake. Repeated-measures ANOVA were performed comparing VAS ratings during test day. Energy consumption was compared using paired t-tests. Significance was determined at p<0.05. Results: On the 8th day, the fiber group reported lower ratings for hunger, desire to eat, and prospective food consumption with significantly higher ratings for satisfaction and fullness. Subsequently, the fiber group consumed 21% less kcal from food at lunch (453 ± 47 kcal) compared to controls (571 ± 39 kcal) (p<0.05). Conclusions: Consuming 16 g/d of ITFs in the morning for 7 days, and after an overnight fast, curbed appetite sensations and helped reduce food intake during lunch meal. These findings highlight the potential of using ITFs in weight management. Future studies should explore ITFs long term benefits. PMID:28747861

  3. Therapeutic effect of adipose-derived stem cells and BDNF-immobilized PLGA membrane in a rat model of cavernous nerve injury.

    Science.gov (United States)

    Piao, Shuyu; Kim, In Gul; Lee, Ji Young; Hong, Sung Hoo; Kim, Sae Woong; Hwang, Tae-Kon; Oh, Se Heang; Lee, Jin Ho; Ra, Jeong Chan; Lee, Ji Youl

    2012-08-01

    Cavernous nerve injury is the main reason for post-prostatectomy erectile dysfunction (ED). Stem cell and neuroprotection therapy are promising therapeutic strategy for ED. To evaluate the therapeutic efficacy of adipose-derived stem cells (ADSCs) and brain-derived neurotrophic factor (BDNF) immobilized Poly-Lactic-Co-Glycolic (PLGA) membrane on the cavernous nerve in a rat model of post-prostatectomy ED. Methods.  Rats were randomly divided into five groups: normal group, bilateral cavernous nerve crush injury (BCNI) group, ADSC (BCNI group with ADSCs on cavernous nerve) group, BDNF-membrane (BCNI group with BDNF/PLGA membrane on cavernous nerve) group, and ADSC/BDNF-membrane (BCNI group with ADSCs covered with BDNF/PLGA membrane on cavernous nerve) group. BDNF was controlled-released for a period of 4 weeks in a BDNF/PLGA porous membrane system. Four weeks after the operation, erectile function was assessed by detecting the ratio of intra-cavernous pressure (ICP)/mean arterial pressure (MAP). Smooth muscle and collagen content were determined by Masson's trichrome staining. Neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve was detected by immunostaining. Phospho-endothelial nitric oxide synthase (eNOS) protein expression and cyclic guanosine monophosphate (cGMP) level of the corpus cavernosum were quantified by Western blotting and cGMP assay, respectively. In the ADSC/BDNF-membrane group, erectile function was significantly elevated, compared with the BCNI and other treated groups. ADSC/BDNF-membrane treatment significantly increased smooth muscle/collagen ratio, nNOS content, phospho-eNOS protein expression, and cGMP level, compared with the BCNI and other treated groups. ADSCs with BDNF-membrane on the cavernous nerve can improve erectile function in a rat model of post-prostatectomy ED, which may be used as a novel therapy for post-prostatectomy ED. © 2012 International Society for Sexual Medicine.

  4. High-birefringent photonic crystal fiber

    DEFF Research Database (Denmark)

    Libori, Stig E. Barkou; Broeng, Jes; Knudsen, Erik

    2001-01-01

    A highly birefringent photonic crystal fiber design is analysed. Birefringence up to 10-3 is found. Random fluctuations in the cladding design are analysed, and the fiber is found to be a feasible polarization maintaining fiber.......A highly birefringent photonic crystal fiber design is analysed. Birefringence up to 10-3 is found. Random fluctuations in the cladding design are analysed, and the fiber is found to be a feasible polarization maintaining fiber....

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

    Science.gov (United States)

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

    2010-12-01

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

  6. Adsorption of plasma proteins on uncoated PLGA nanoparticles.

    Science.gov (United States)

    Sempf, Karim; Arrey, Tabiwang; Gelperina, Svetlana; Schorge, Tobias; Meyer, Björn; Karas, Michael; Kreuter, Jörg

    2013-09-01

    The biodistribution of nanoparticles is significantly influenced by their interaction with plasma proteins. In order to optimize and possibly monitor the delivery of drugs bound to nanoparticles across the blood-brain barrier (BBB), the protein adsorption pattern of uncoated poly(lactic-co-glycolic acid) (PLGA) nanoparticles after their incubation in human plasma was studied by mass spectrometry. After washing of the particles with water, the proteins were directly digested on the nanoparticle surface using trypsin and then analyzed by nLC MALDI-TOF/TOF. Up to now, the standard method for investigation into the plasma protein adsorption to the particles was 2D gel electrophoresis (2D-PAGE), in certain cases followed by mass spectrometry. The non-gel-based method proposed in the present study provides novel insights into the protein corona surrounding the nanoparticles. The proteins adsorbed on the PLGA nanoparticles after incubation that gave the best signal in terms of quality (high MASCOT score) in human plasma were apolipoprotein E, vitronectin, histidine-rich glycoprotein and kininogen-1. These proteins also are constituents of HDL. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Controlled Release of Lysozyme from Double-Walled Poly(Lactide-Co-Glycolide (PLGA Microspheres

    Directory of Open Access Journals (Sweden)

    Rezaul H. Ansary

    2017-10-01

    Full Text Available Double-walled microspheres based on poly(lactide-co-glycolide (PLGA are potential delivery systems for reducing a very high initial burst release of encapsulated protein and peptide drugs. In this study, double-walled microspheres made of glucose core, hydroxyl-terminated poly(lactide-co-glycolide (Glu-PLGA, and carboxyl-terminated PLGA were fabricated using a modified water-in-oil-in-oil-in-water (w1/o/o/w2 emulsion solvent evaporation technique for the controlled release of a model protein, lysozyme. Microspheres size, morphology, encapsulation efficiency, lysozyme in vitro release profiles, bioactivity, and structural integrity, were evaluated. Scanning electron microscopy (SEM images revealed that double-walled microspheres comprising of Glu-PLGA and PLGA with a mass ratio of 1:1 have a spherical shape and smooth surfaces. A statistically significant increase in the encapsulation efficiency (82.52% ± 3.28% was achieved when 1% (w/v polyvinyl alcohol (PVA and 2.5% (w/v trehalose were incorporated in the internal and external aqueous phase, respectively, during emulsification. Double-walled microspheres prepared together with excipients (PVA and trehalose showed a better control release of lysozyme. The released lysozyme was fully bioactive, and its structural integrity was slightly affected during microspheres fabrication and in vitro release studies. Therefore, double-walled microspheres made of Glu-PLGA and PLGA together with excipients (PVA and trehalose provide a controlled and sustained release for lysozyme.

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

    Directory of Open Access Journals (Sweden)

    Marxa Figueiredo

    2012-01-01

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

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

    Science.gov (United States)

    Zhang, Lijuan; Webster, Thomas J

    2013-01-01

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

  10. Preparation, physicochemical properties and biocompatibility of PBLG/PLGA/bioglass composite scaffolds.

    Science.gov (United States)

    Cui, Ning; Qian, Junmin; Wang, Jinlei; Ji, Chuanlei; Xu, Weijun; Wang, Hongjie

    2017-02-01

    In this study, novel poly(γ-benzyl l-glutamate)/poly(lactic-co-glycolic acid)/bioglass (PBLG/PLGA/BG) composite scaffolds with different weight ratios were fabricated using a negative NaCl-templating method. The morphology, compression modulus and degradation kinetics of the scaffolds were characterized. The results showed that the PBLG/PLGA/BG composite scaffolds with a weight ratio of 5:5:1, namely PBLG5PLGA5BG composite scaffolds, displayed a pore size range of 50-500μm, high compressive modulus (566.6±8.8kPa), suitable glass transition temperature (46.8±0.2°C) and low degradation rate (>8weeks). The in vitro biocompatibility of the scaffolds was evaluated with MC3T3-E1 cells by live-dead staining, MTT and ALP activity assays. The obtained results indicated that the PBLG5PLGA5BG composite scaffolds were more conducive to the adhesion, proliferation and osteoblastic differentiation of MC3T3-E1 cells than PBLG and PBLG/PLGA composite scaffolds. The in vivo biocompatibility of the scaffolds was evaluated in both SD rat subcutaneous model and rabbit tibia defect model. The results of H&E, Masson's trichrome and CD34 staining assays demonstrated that the PBLG5PLGA5BG composite scaffolds allowed the ingrowth of tissue and microvessels more effectively than PBLG/PLGA composite scaffolds. The results of digital radiography confirmed that the PBLG5PLGA5BG composite scaffolds significantly improved in vivo osteogenesis. Collectively, the PBLG5PLGA5BG composite scaffolds could be a promising candidate for tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

    Sixty percent of implant-supported dental prostheses require bone grafting to enhance bone quantity and quality prior to implant placement. We have developed a metallic magnesium particle/PLGA composite scaffold to overcome the limitations of currently used dental bone grafting materials. This is the first report of porous metallic magnesium/PLGA scaffolds synthesized using a solvent casting, salt leaching method. We found that incorporation of varying amounts of magnesium into the PLGA scaffolds increased the compressive strength and modulus, as well as provided a porous structure suitable for cell infiltration, as measured by mercury intrusion porosimetry. Additionally, combining basic-degrading magnesium with acidic-degrading PLGA led to an overall pH buffering effect and long-term release of magnesium over the course of a 10-week degradation assay, as measured with inductively coupled plasma-atomic emission spectroscopy. Using an indirect proliferation assay adapted from ISO 10993:5, it was found that extracts of medium from degrading magnesium/PLGA scaffolds increased bone marrow stromal cell proliferation in vitro, a phenomenon observed by other groups investigating magnesium's impact on cells. Finally, magnesium/PLGA scaffold biocompatibility was assessed in a canine socket preservation model. Micro-computed tomography and histological analysis showed the magnesium/PLGA scaffolds to be safer and more effective at preserving bone height than empty controls. Three-dimensional magnesium/PLGA composite scaffolds show promise for dental socket preservation and also, potentially, orthopedic bone regeneration. These scaffolds could decrease inflammation observed with clinically used PLGA devices, as well as enhance osteogenesis, as observed with previously studied magnesium devices. Copyright © 2014. Published by Elsevier Ltd.

  13. Development of dry powder inhaler containing tadalafil-loaded PLGA nanoparticles.

    Science.gov (United States)

    Varshosaz, Jaleh; Taymouri, Somayeh; Hamishehkar, Hamed; Vatankhah, Razieh; Yaghubi, Shadi

    2017-06-01

    Inhalable dry powders containing poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were developed for the delivery of tadalafil (TAD) for treatment of life-treating pulmonary arterial hypertension. Taguchi design was employed to evaluate the effects of different formulation variables on the physicochemical characteristics of PLGA-NPs prepared using emulsion solvent evaporation method. Inhalable PLGA-NPs of TAD were successfully prepared by co-spray drying the PLGA-NPs with inert carriers. Physicochemical characteristics and in vitro deposition of the aerosolized drug were also evaluated. The optimized formulation was prepared using 7.5 mg of PLGA, 2.5 mg of TAD, sonication time of 6 min and 2% polyvinyl alcohol (PVA) as the stabilizer. The optimized aqueous/oil phase ratio for PLGA-NPs preparation was 10:1. Polymer/drug ratio was the most effective parameter on the release efficiency. Encapsulation efficiency, zeta potential and particle size of PLGA-NPs were more affected by aqueous/organic phase ratio. The spray dried powders containing PLGA-NPs had a mass median aerodynamic diameter (MMAD) in the range of 1.4-2.8 μm that was suitable for TAD delivery to the deep region of lung. The presence of L- leucine in mannitol containing formulations decreased the interparticulate forces between particles and increased significantly the process yield and fine particle fraction (FPF). The results indicated that prepared dry powders containing TAD-loaded PLGA-NPs were suitable for inhalation and has the potential for the treatment of pulmonary arterial hypertension.

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

    Science.gov (United States)

    Zhao, Kai; Li, Wei; Huang, Tingting; Luo, Xiaomei; Chen, Gang; Zhang, Yang; Guo, Chen; Dai, Chunxiao; Jin, Zheng; Zhao, Yan; Cui, Hongyu; Wang, Yunfeng

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kai Zhao

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

  16. Effects of isolated soluble fiber supplementation on body weight, glycemia, and insulinemia in adults with overweight and obesity: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Thompson, Sharon V; Hannon, Bridget A; An, Ruopeng; Holscher, Hannah D

    2017-12-01

    Background: There is strong epidemiologic evidence that dietary fiber intake is protective against overweight and obesity; however, results of intervention studies have been mixed. Soluble fiber beneficially affects metabolism, and fiber supplementation may be a feasible approach to improve body composition and glycemia in adults with overweight and obesity.Objective: We evaluated randomized controlled trials (RCTs) of isolated soluble fiber supplementation in overweight and obese adults on outcomes related to weight management [body mass index (BMI; in kg/m2), body weight, percentage of body fat, and waist circumference] and glucose and insulin metabolism (homeostasis model assessment of insulin resistance and fasting insulin) through a systematic review and meta-analysis.Design: We searched PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and Cochrane Library databases. Eligible studies were RCTs that compared isolated soluble fiber with placebo treatments without energy-restriction protocols. Random-effects models were used to estimate pooled effect sizes and 95% CIs. Meta-regressions were performed to assess outcomes in relation to the intervention duration, fiber dose, and fiber type. Publication bias was assessed via Begg's and Egger's tests and funnel plot inspection.Results: Findings from 12 RCTs (n = 609 participants) from 2 to 17 wk of duration are summarized in this review. Soluble fiber supplementation reduced BMI by 0.84 (95% CI: -1.35, -0.32; P = 0.001), body weight by 2.52 kg (95% CI: -4.25, -0.79 kg; P = 0.004), body fat by 0.41% (95% CI: -0.58%, -0.24%; P soluble fiber supplementation improves anthropometric and metabolic outcomes in overweight and obese adults, thereby indicating that supplementation may improve fiber intake and health in these individuals. However, the interpretation of these findings warrants caution because of the considerable between-study heterogeneity. This trial was registered at

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

    Science.gov (United States)

    Makadia, Hirenkumar K.; Siegel, Steven J.

    2011-01-01

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

  18. Biological Properties of Low-Toxicity PLGA and PLGA/PHB Fibrous Nanocomposite Implants for Osseous Tissue Regeneration. Part I: Evaluation of Potential Biotoxicity

    Directory of Open Access Journals (Sweden)

    Izabella Krucińska

    2017-11-01

    Full Text Available In response to the demand for new implant materials characterized by high biocompatibility and bioresorption, two prototypes of fibrous nanocomposite implants for osseous tissue regeneration made of a newly developed blend of poly(l-lactide-co-glycolide (PLGA and syntheticpoly([R,S]-3-hydroxybutyrate, PLGA/PHB, have been developed and fabricated. Afibre-forming copolymer of glycolide and l-lactide (PLGA was obtained by a unique method of synthesis carried out in blocksusing Zr(AcAc4 as an initiator. The prototypes of the implants are composed of three layers of PLGA or PLGA/PHB, nonwoven fabrics with a pore structure designed to provide the best conditions for the cell proliferation. The bioactivity of the proposed implants has been imparted by introducing a hydroxyapatite material and IGF1, a growth factor. The developed prototypes of implants have been subjected to a set of in vitro and in vivobiocompatibility tests: in vitro cytotoxic effect, in vitro genotoxicity and systemic toxicity. Rabbitsshowed no signs of negative reactionafter implantation of the experimental implant prototypes.

  19. Amplitude-modulated fiber-ring laser

    DEFF Research Database (Denmark)

    Caputo, J. G.; Clausen, Carl A. Balslev; Sørensen, Mads Peter

    2000-01-01

    Soliton pulses generated by a fiber-ring laser are investigated by numerical simulation and perturbation methods. The mathematical modeling is based on the nonlinear Schrödinger equation with perturbative terms. We show that active mode locking with an amplitude modulator leads to a self-starting......Soliton pulses generated by a fiber-ring laser are investigated by numerical simulation and perturbation methods. The mathematical modeling is based on the nonlinear Schrödinger equation with perturbative terms. We show that active mode locking with an amplitude modulator leads to a self......-starting of stable solitonic pulses from small random noise, provided the modulation depth is small. The perturbative analysis leads to a nonlinear coupled return map for the amplitude, phase, and position of the soliton pulses circulating in the fiber-ring laser. We established the validity of this approach...

  20. Degradable PLGA Scaffolds with Basic Fibroblast Growth Factor: Experimental Studies in Myocardial Revascularization

    OpenAIRE

    Wang, Ying; Liu, Xiao-Cheng; Zhao, Jian; Kong, Xiang-Rong; Shi, Rong-Fang; Zhao, Xiao-Bin; Song, Cun-Xian; Liu, Tian-Jun; Lu, Feng

    2009-01-01

    Our goal was to investigate the efficacy of degradable poly(D,L-lactic-coglycolic acid) (PLGA) scaffolds loaded with basic fibroblast growth factor (bFGF) in inducing cardiac neovascularization, increasing perfusion, and improving cardiac function.

  1. Fabrication of Core-Shell PLGA-Chitosan Microparticles Using Electrospinning: Effects of Polymer Concentration

    National Research Council Canada - National Science Library

    Nguyen Thi Hiep; Nguyen Dai Hai; Vo Van Toi

    2017-01-01

    ...(lactic-co-glycolic acid) and chitosan (PLGA-CS MPs) using electrospinning. The challenge of using electrospinning is that it has many parameters which change product outcome if any single parameter is changed...

  2. In vitro study on tamsulosin release kinetics from biodegradable PLGA in situ implants

    National Research Council Canada - National Science Library

    Elias-Al-Mamun, Md; Khan, Humaira Afreen; Dewan, Irin; Jalil, Reza-Ul

    2009-01-01

    The objective of this study was to evaluate the effect of drug loading and the effect of excipients on the release pattern of tamsulosin tydrochloride from in situ PLGA implants formed in vitro in gelatin gel...

  3. Gastrointestinal tolerance and plasma status of carotenoids, EPA and DHA with a fiber-enriched tube feed in hospitalized patients initiated on tube nutrition: Randomized controlled trial.

    Science.gov (United States)

    Jakobsen, L H; Wirth, R; Smoliner, C; Klebach, M; Hofman, Z; Kondrup, J

    2017-04-01

    During the first days of tube feeding (TF) gastrointestinal (GI) complications are common and administration of sufficient nutrition is a challenge. Not all standard nutritionally complete formulas contain dietary fiber, fish oil or carotenoids, key dietary nutrients for health and wellbeing. The aim of this study was to investigate the effects of a fiber, fish oil and carotenoid enriched TF formula on diarrhea, constipation and nutrient bioavailability. A multi-center randomized, double-blind, controlled, parallel trial compared the effects of a dietary fiber, fish oil and carotenoid-enriched TF formula (test) with an isocaloric non-enriched formula (control) in 51 patients requiring initiation of TF. Incidence of diarrhea and constipation (based on stool frequency and consistency) was recorded daily. Plasma status of EPA, DHA and carotenoids was measured after 7 days. The incidence of diarrhea was lower in patients receiving the test formula compared with the control group (19% vs. 48%, p = 0.034). EPA and DHA status (% of total plasma phospholipids) was higher after 7 days in test compared with control group (EPA: p = 0.002, DHA: p = 0.082). Plasma carotenoid levels were higher after 7 days in the test group compared with control group (lutein: p = 0.024, α-carotene: p = 0.005, lycopene: p = 0.020, β-carotene: p = 0.054). This study suggests that the nutrient-enriched TF formula tested might have a positive effect on GI tolerance with less diarrhea incidence and significantly improved EPA, DHA and carotenoid plasma levels during the initiation of TF in hospitalized patients who are at risk of diarrhea and low nutrient status. This trial was registered at trialregister.nl; registration number 2924. Copyright © 2016. Published by Elsevier Ltd.

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

    Directory of Open Access Journals (Sweden)

    Stefanie Wohlfart

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

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

    Science.gov (United States)

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

    2015-06-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

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

    Directory of Open Access Journals (Sweden)

    Dustin L Cooper

    Full Text Available 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.

  8. Mannan-Modified PLGA Nanoparticles for Targeted Gene Delivery

    Directory of Open Access Journals (Sweden)

    Fansheng Kong

    2012-01-01

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

  9. Randomized crossover study assessing oropharyngeal leak pressure and fiber optic positioning : Laryngeal Mask Airway Supreme™ versus Laryngeal Tube LTS II™ size 2 in non-paralyzed anesthetized children.

    Science.gov (United States)

    Gasteiger, L; Ofner, S; Stögermüller, B; Ziegler, B; Brimacombe, J; Keller, C

    2016-08-01

    As there are currently no data available comparing the practicability of the laryngeal mask airway (LMA) Supreme™ size 2 versus the laryngeal tube LTS II™ size 2 in children, this trial was conducted to quantify the differences between these two airway devices concerning leak pressure and fiber optic-controlled positioning in non-paralyzed, anesthetized pediatric patients. A total of 56 children aged 1-6 years and weighing between 11 and 23 kg were enrolled in the study. Anesthesia was intravenously induced according to local standards using fentanyl and propofol. After induction of anesthesia both airway devices were inserted consecutively in accordance with the randomization protocol. The mean oropharyngeal leak pressure was significantly higher for the LTS II™ (33±8 cmH2O) than for the LMA Supreme™ (21±7 cmH2O, p insertion (55Supreme LMA vs. 43LTSII, p insertion time (25 s Supreme LMA vs. 34 s LTSII, p laryngeal tube LTS II™. We conclude that oropharyngeal leak pressure, fiber optic position, first attempt insertion success rate and bloodstaining differed between the LMA Supreme™ and the LTS II™ in children.

  10. Comparison of early enteral nutrition in severe acute pancreatitis with prebiotic fiber supplementation versus standard enteral solution: A prospective randomized double-blind study

    Science.gov (United States)

    Karakan, Tarkan; Ergun, Meltem; Dogan, Ibrahim; Cindoruk, Mehmet; Unal, Selahattin

    2007-01-01

    AIM: To compare the beneficial effects of early enteral nutrition (EN) with prebiotic fiber supplementation in patients with severe acute pancreatitis (AP). METHODS: Thirty consecutive patients with severe AP, who required stoppage of oral feeding for 48 h, were randomly assigned to nasojejunal EN with or without prebiotics. APACHE II score, Balthazar’s CT score and CRP were assessed daily during the study period. RESULTS: The median duration of hospital stay was shorter in the study group [10 ± 4 (8-14) d vs 15 ± 6 (7-26) d] (P 0.05). Deaths occurred in 6 patients (20%), 2 in the study group and 4 in the control group. The mean duration of APACHE II normalization (APACHE II score < 8) was shorter in the study group than in the control group (4 ± 2 d vs 6.5 ± 3 d, P < 0.05). The mean duration of CRP normalization was also shorter in the study group than in the control group (7 ± 2 d vs 10 ± 3 d, P < 0.05). CONCLUSION: Nasojejunal EN with prebiotic fiber supplementation in severe AP improves hospital stay, duration nutrition therapy, acute phase response and overall complications compared to standard EN therapy. PMID:17569144

  11. PEG-PLGA electrospun nanofibrous membranes loaded with Au@Fe2O3 nanoparticles for drug delivery applications

    Science.gov (United States)

    Spadaro, Salvatore; Santoro, Marco; Barreca, Francesco; Scala, Angela; Grimato, Simona; Neri, Fortunato; Fazio, Enza

    2018-02-01

    A PEGylated-PLGA random nanofibrous membrane loaded with gold and iron oxide nanoparticles and with silibinin was prepared by electrospinning deposition. The nanofibrous membrane can be remotely controlled and activated by a laser light or magnetic field to release biological agents on demand. The nanosystems were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, and thermogravimetric analyses. The drug loading efficiency and drug content percentages were determined by UV-vis optical absorption spectroscopy. The nanofibrous membrane irradiated by a relatively low-intensity laser or stimulated by a magnetic field showed sustained silibinin release for at least 60 h, without the burst effect. The proposed low-cost electrospinning procedure is capable of assembling, via a one-step procedure, a stimuli-responsive drug-loaded nanosystem with metallic nanoparticles to be externally activated for controlled drug delivery.

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

    Science.gov (United States)

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

    2015-05-29

    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.

  13. Crystallinity control of apatite through Ca-EDTA complexes and porous composites with PLGA.

    Science.gov (United States)

    Mochizuki, Chihiro; Sasaki, Yuji; Hara, Hiroki; Sato, Mitsunobu; Hayakawa, Tohru; Yang, Fei; Hu, Xixue; Shen, Hong; Wang, Shenguo

    2009-07-01

    Apatite compounds with different levels of crystallinity were prepared using Ca-EDTA complexes. Ca-deficient hydroxyapatite (CDHA) with low crystallinity was synthesized by ultrasonic stirring of a mixture of Ca-EDTA complex, phosphoric acid, and ammonium hydroxide in hydrogen peroxide aqueous solution. Mixtures of carbonate hydroxyapatite (HA) and CDHA with higher crystallinity were also prepared from a solution involving the same complex. The porous composites with lower or higher crystallinity apatite with a copolymer of poly(L-lactide-co-glycilide)(70/30) (PLGA(70/30)) were fabricated by a solution-casting/particles leaching method. The apatites and porous composites were characterized, and it was found that the degradation of composites of apatite with a low level of crystallinity was fastest in phosphate-bufferd saline (PBS) solution compared with other apatite composites with higher levels of crystallinity; however, the rate was smaller than that of PLGA alone. Plasma treatment influenced the degradation of composites in PBS and apatite precipitation in simulated body fluid (SBF). Hydroxyapatite deposition on the PLGA composite with the low crystallinity occurred six times faster than that on PLGA alone after immersion in SBF. The incorporation of apatite into the PLGA matrix did not cause any adverse effects on cell attachment in an assay employing human gingival fibroblasts. This study suggested that the current apatite and PLGA porous composite will be a promising scaffold material for tissue engineering. (c) 2008 Wiley Periodicals, Inc.

  14. Curdlan-Conjugated PLGA Nanoparticles Possess Macrophage Stimulant Activity and Drug Delivery Capabilities.

    Science.gov (United States)

    Tukulula, Matshawandile; Hayeshi, Rose; Fonteh, Pascaline; Meyer, Debra; Ndamase, Abongile; Madziva, Michael T; Khumalo, Vincent; Labuschagne, Philip; Lubuschagne, Philip; Naicker, Brendon; Swai, Hulda; Dube, Admire

    2015-08-01

    There is significant interest in the application of nanoparticles to deliver immunostimulatory signals to cells. We hypothesized that curdlan (immune stimulating polymer) could be conjugated to PLGA and nanoparticles from this copolymer would possess immunostimulatory activity, be non-cytotoxic and function as an effective sustained drug release system. Carbodiimide chemistry was employed to conjugate curdlan to PLGA. The conjugate (C-PLGA) was characterized using (1)H and (13)C NMR, FTIR, DSC and TGA. Nanoparticles were synthesized using an emulsion-solvent evaporation technique. Immunostimulatory activity was characterized in THP-1 derived macrophages. MTT assay and real-time impedance measurements were used to characterize polymer and nanoparticle toxicity and uptake in macrophages. Drug delivery capability was assessed across Caco-2 cells using rifampicin as a model drug. Spectral characterization confirmed successful synthesis of C-PLGA. C-PLGA nanoparticles enhanced phosphorylated ERK production in macrophages indicating cell stimulation. Nanoparticles provided slow release of rifampicin across Caco-2 cells. Polymers but not nanoparticles altered the adhesion profiles of the macrophages. Impedance measurements suggested Ca(2+) dependent uptake of nanoparticles by the macrophages. PLGA nanoparticles with macrophage stimulating and sustained drug delivery capabilities have been prepared. These nanoparticles can be used to stimulate macrophages and concurrently deliver drug in infectious disease therapy.

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

    Directory of Open Access Journals (Sweden)

    Shalil Khanal

    2016-08-01

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

  16. PLGA, PLGA-TMC and TMC-TPP nanoparticles differentially modulate the outcome of nasal vaccination by inducing tolerance or enhancing humoral immunity.

    Science.gov (United States)

    Keijzer, Chantal; Slütter, Bram; van der Zee, Ruurd; Jiskoot, Wim; van Eden, Willem; Broere, Femke

    2011-01-01

    Development of vaccines in autoimmune diseases has received wide attention over the last decade. However, many vaccines showed limited clinical efficacy. To enhance vaccine efficacy in infectious diseases, biocompatible and biodegradable polymeric nanoparticles have gained interest as antigen delivery systems. We investigated in mice whether antigen-encapsulated PLGA (poly-lactic-co-glycolic acid), PLGA-TMC (N-trimethyl chitosan) or TMC-TPP (tri-polyphosphate) nanoparticles can also be used to modulate the immunological outcome after nasal vaccination. These three nanoparticles enhanced the antigen presentation by dendritic cells, as shown by increased in vitro and in vivo CD4(+) T-cell proliferation. However, only nasal PLGA nanoparticles were found to induce an immunoregulatory response as shown by enhanced Foxp3 expression in the nasopharynx associated lymphoid tissue and cervical lymph nodes. Nasal administration of OVA-containing PLGA particle resulted in functional suppression of an OVA-specific Th-1 mediated delayed-type hypersensitivity reaction, while TMC-TPP nanoparticles induced humoral immunity, which coincided with the enhanced generation of OVA-specific B-cells in the cervical lymph nodes. Intranasal treatment with Hsp70-mB29a peptide-loaded PLGA nanoparticles suppressed proteoglycan-induced arthritis, leading to a significant reduction of disease. We have uncovered a role for PLGA nanoparticles to enhance CD4(+) T-cell mediated immunomodulation after nasal application. The exploitation of this differential regulation of nanoparticles to modulate nasal immune responses can lead to innovative vaccine development for prophylactic or therapeutic vaccination in infectious or autoimmune diseases.

  17. Comparison of high protein and high fiber weight-loss diets in women with risk factors for the metabolic syndrome: a randomized trial

    Directory of Open Access Journals (Sweden)

    Williams Sheila M

    2011-04-01

    Full Text Available Abstract Background Studies have suggested that moderately high protein diets may be more appropriate than conventional low-fat high carbohydrate diets for individuals at risk of developing the metabolic syndrome and type 2 diabetes. However in most such studies sources of dietary carbohydrate may not have been appropriate and protein intakes may have been excessively high. Thus, in a proof-of-concept study we compared two relatively low-fat weight loss diets - one high in protein and the other high in fiber-rich, minimally processed cereals and legumes - to determine whether a relatively high protein diet has the potential to confer greater benefits. Methods Eighty-three overweight or obese women, 18-65 years, were randomized to either a moderately high protein (30% protein, 40% carbohydrate diet (HP or to a high fiber, relatively high carbohydrate (50% carbohydrate, > 35 g total dietary fiber, 20% protein diet (HFib for 8 weeks. Energy intakes were reduced by 2000 - 4000 kJ per day in order to achieve weight loss of between 0.5 and 1 kg per week. Results Participants on both diets lost weight (HP: -4.5 kg [95% confidence interval (CI:-3.7, -5.4 kg] and HFib: -3.3 kg [95% CI: -4.2, -2.4 kg], and reduced total body fat (HP: -4.0 kg [5% CI:-4.6, -3.4 kg] and HFib: -2.5 kg [95% CI: -3.5, -1.6 kg], and waist circumference (HP: -5.4 cm [95% CI: -6.3, -4.5 cm] and HFib: -4.7 cm [95% CI: -5.8, -3.6 cm], as well as total and LDL cholesterol, triglycerides, fasting plasma glucose and blood pressure. However participants on HP lost more body weight (-1.3 kg [95% CI: -2.5, -0.1 kg; p = 0.039] and total body fat (-1.3 kg [95% CI: -2.4, -0.1; p = 0.029]. Diastolic blood pressure decreased more on HP (-3.7 mm Hg [95% CI: -6.2, -1.1; p = 0.005]. Conclusions A realistic high protein weight-reducing diet was associated with greater fat loss and lower blood pressure when compared with a high carbohydrate, high fiber diet in high risk overweight and obese women.

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

    Science.gov (United States)

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

    2011-05-01

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

  19. Hydroxypropyltrimethyl Ammonium Chloride Chitosan Functionalized-PLGA Electrospun Fibrous Membranes as Antibacterial Wound Dressing: In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Shengbing Yang

    2017-12-01

    Full Text Available A novel poly(lactic-co-glycolic acid (PLGA-hydroxypropyltrimethyl ammonium chloride chitosan (HACC composite nanofiber wound dressing was prepared through electrospinning and the entrapment-graft technique as an antibacterial dressing for cutaneous wound healing. HACC with 30% degrees of substitution (DS was immobilized onto the surface of PLGA membranes via the reaction between carboxyl groups in PLGA after alkali treatment and the reactive groups (–NH2 in HACC molecules. The naked PLGA and chitosan graft PLGA (PLGA-CS membranes served as controls. The surface immobilization was characterized by scanning electron microscopy (SEM, atomic force microscopy (AFM, Fourier transform infrared (FTIR, thermogravimetric analysis (TGA and energy dispersive X-ray spectrometry (EDX. The morphology studies showed that the membranes remain uniform after the immobilization process. The effects of the surface modification by HACC and CS on the biological properties of the membranes were also investigated. Compared with PLGA and PLGA-CS, PLGA-HACC exhibited more effective antibacterial activity towards both Gram-positive (S. aureus and Gram-negative (P. aeruginosa bacteria. The newly developed fibrous membranes were evaluated in vitro for their cytotoxicity using human dermal fibroblasts (HDFs and human keratinocytes (HaCaTs and in vivo using a wound healing mice model. It was revealed that PLGA-HACC fibrous membranes exhibited favorable cytocompatibility and significantly stimulated adhesion, spreading and proliferation of HDFs and HaCaTs. PLGA-HACC exhibited excellent wound healing efficacy, which was confirmed using a full thickness excision wound model in S. aureus-infected mice. The experimental results in this work suggest that PLGA-HACC is a strong candidate for use as a therapeutic biomaterial in the treatment of infected wounds.

  20. A comparative evaluation of the effect of polymer chemistry and fiber orientation on mesenchymal stem cell differentiation.

    Science.gov (United States)

    Rowland, David C L; Aquilina, Thomas; Klein, Andrei; Hakimi, Osnat; Alexis-Mouthuy, Pierre; Carr, Andrew J; Snelling, Sarah J B

    2016-11-01

    Bioengineered tissue scaffolds in combination with cells hold great promise for tissue regeneration. The aim of this study was to determine how the chemistry and fiber orientation of engineered scaffolds affect the differentiation of mesenchymal stem cells (MSCs). Adipogenic, chondrogenic, and osteogenic differentiation on aligned and randomly orientated electrospun scaffolds of Poly (lactic-co-glycolic) acid (PLGA) and Polydioxanone (PDO) were compared. MSCs were seeded onto scaffolds and cultured for 14 days under adipogenic-, chondrogenic-, or osteogenic-inducing conditions. Cell viability was assessed by alamarBlue metabolic activity assays and gene expression was determined by qRT-PCR. Cell-scaffold interactions were visualized using fluorescence and scanning electron microscopy. Cells grew in response to scaffold fiber orientation and cell viability, cell coverage, and gene expression analysis showed that PDO supports greater multilineage differentiation of MSCs. An aligned PDO scaffold supports highest adipogenic and osteogenic differentiation whereas fiber orientation did not have a consistent effect on chondrogenesis. Electrospun scaffolds, selected on the basis of fiber chemistry and alignment parameters could provide great therapeutic potential for restoration of fat, cartilage, and bone tissue. This study supports the continued investigation of an electrospun PDO scaffold for tissue repair and regeneration and highlights the potential of optimizing fiber orientation for improved utility. © 2016 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2843-2853, 2016. © 2016 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

  1. Efficient production of retroviruses using PLGA/bPEI-DNA nanoparticles and application for reprogramming somatic cells.

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    Eun Jin Seo

    Full Text Available Reprogramming of somatic cells to pluripotent cells requires the introduction of factors driving fate switches. Viral delivery has been the most efficient method for generation of induced pluripotent stem cells. Transfection, which precedes virus production, is a commonly-used process for delivery of nucleic acids into cells. The aim of this study is to evaluate the efficiency of PLGA/ bPEI nanoparticles in transfection and virus production. Using a modified method of producing PLGA nanoparticles, PLGA/bPEI-DNA nanoparticles were examined for transfection efficiency and virus production yield in comparison with PLGA-DNA, bPEI-DNA nanoparticles or liposome-DNA complexes. After testing various ratios of PLGA, bPEI, and DNA, the ratio of 6:3:1 (PLGA:bPEI:DNA, w/w/w was determined to be optimal, with acceptable cellular toxicity. PLGA/bPEI-DNA (6:3:1 nanoparticles showed superior transfection efficiency, especially in multiple gene transfection, and viral yield when compared with liposome-DNA complexes. The culture supernatants of HEK293FT cells transfected with PLGA/bPEI-DNA of viral constructs containing reprogramming factors (Oct4, Sox2, Klf4, or c-Myc successfully and more efficiently generated induced pluripotent stem cell colonies from mouse embryonic fibroblasts. These results strongly suggest that PLGA/bPEI-DNA nanoparticles can provide significant advantages in studying the effect of multiple factor delivery such as in reprogramming or direct conversion of cell fate.

  2. Cartilage repair using mesenchymal stem cell (MSC) sheet and MSCs-loaded bilayer PLGA scaffold in a rabbit model.

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    Qi, Yiying; Du, Yi; Li, Weixu; Dai, Xuesong; Zhao, Tengfei; Yan, Weiqi

    2014-06-01

    The integration of regenerated cartilage with surrounding native cartilage is a major challenge for the success of cartilage tissue-engineering strategies. The purpose of this study is to investigate whether incorporation of the power of mesenchymal stem cell (MSC) sheet to MSCs-loaded bilayer poly-(lactic-co-glycolic acid) (PLGA) scaffolds can improve the integration and repair of cartilage defects in a rabbit model. Rabbit bone marrow-derived MSCs were cultured and formed cell sheet. Full-thickness cylindrical osteochondral defects (4 mm in diameter, 3 mm in depth) were created in the patellar groove of 18 New Zealand white rabbits and the osteochondral defects were treated with PLGA scaffold (n = 6), PLGA/MSCs (n = 6) or MSC sheet-encapsulated PLGA/MSCs (n = 6). After 6 and 12 weeks, the integration and tissue response were evaluated histologically. The MSC sheet-encapsulated PLGA/MCSs group showed significantly more amounts of hyaline cartilage and higher histological scores than PLGA/MSCs group and PLGA group (P MSC sheet-encapsulated PLGA/MCSs group showed the best integration between the repaired cartilage and surrounding normal cartilage and subchondral bone compared to other two groups. The novel method of incorporation of MSC sheet to PLGA/MCSs could enhance the ability of cartilage regeneration and integration between repair cartilage and the surrounding cartilage. Transplantation of autologous MSC sheet combined with traditional strategies or cartilage debris might provide therapeutic opportunities for improving cartilage regeneration and integration in humans.

  3. Effects of vitamin D on retinal nerve fiber layer in vitamin D deficient patients with optic neuritis: Preliminary findings of a randomized, placebo-controlled trial

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    Mehri Salari

    2015-01-01

    Full Text Available Background: There is accumulating evidence for a possible protective role of vitamin D in the development and disease course of multiple sclerosis. Whether vitamin D is also effective in treating patients with optic neuritis (ON is not known. The aim of this study was to evaluate the effect of oral vitamin D on the thickness of retinal nerve fiber layer (RNFL in vitamin D deficient patients with ON by optical coherence tomography. Materials and Methods: A Phase II placebo-controlled randomized clinical trial conducted between July 2011 and November 2012 included 52 patients with confirmed unilateral ON aged 15-38 years and low serum 25-hydroxyvitamin D levels. The main outcome measures were changes in thickness of RNFL and macula 6 months after treatment. Patients were randomly allocated to receive 6 months of treatment with adding either 50,000 IU/week vitamin D or placebo. Results: In the 27 patients treated with vitamin D, the mean (standard deviation [SD] thickness of RNFL decreased from 111.3 (18.9 μm at baseline to 91.4 (13.3 at the end of study period (P 0.05. Average thickness of RNFL at the end of trial did not differ between groups. Conclusion: Adding vitamin D to routine disease therapy had no significant effect on the thickness of RNFL or macula in patients with ON. This trial is registered on www.clinicaltrials.gov (ID NCT01465893.

  4. Safety, Tolerance, and Enhanced Efficacy of a Bioavailable Formulation of Curcumin With Fenugreek Dietary Fiber on Occupational Stress: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

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    Pandaran Sudheeran, Subash; Jacob, Della; Natinga Mulakal, Johannah; Gopinathan Nair, Gopakumar; Maliakel, Abhilash; Maliakel, Balu; Kuttan, Ramadasan; Im, Krishnakumar

    2016-06-01

    Drug delivery systems capable of delivering free (unconjugated) curcuminoids is of great therapeutic significance, since the absorption of bioactive and permeable form plays a key factor in mediating the efficacy of a substance which undergoes rapid biotransformation. Considering the recent understanding on the relatively high bioactivities and blood-brain-barrier permeability of free curcuminoids over their conjugated metabolites, the present human study investigated the safety, antioxidant efficacy, and bioavailability of CurQfen (curcumagalactomannoside [CGM]), a food-grade formulation of natural curcumin with fenugreek dietary fiber that has shown to possess improved blood-brain-barrier permeability and tissue distribution in rats. In this randomized double-blinded and placebo-controlled trial, 60 subjects experiencing occupational stress-related anxiety and fatigue were randomized to receive CGM, standard curcumin, and placebo for 30 days (500 mg twice daily). The study demonstrated the safety, tolerance, and enhanced efficacy of CGM in comparison with unformulated standard curcumin. A significant improvement in the quality of life (P comparison of the free curcuminoids bioavailability after a single-dose (500 mg once per day) and repeated-dose (500 mg twice daily for 30 days) oral administration revealed enhanced absorption and improved pharmacokinetics of CGM upon both single- (30.7-fold) and repeated-dose (39.1-fold) administrations.

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

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

    2015-10-20

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

  6. Fiber webs

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    Roger M. Rowell; James S. Han; Von L. Byrd

    2005-01-01

    Wood fibers can be used to produce a wide variety of low-density three-dimensional webs, mats, and fiber-molded products. Short wood fibers blended with long fibers can be formed into flexible fiber mats, which can be made by physical entanglement, nonwoven needling, or thermoplastic fiber melt matrix technologies. The most common types of flexible mats are carded, air...

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

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    Sharma Akhilesh

    2009-12-01

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

  8. Using PVA and TPGS as combined emulsifier in nanoprecipitation method improves characteristics and anticancer activity of ibuprofen loaded PLGA nanoparticles.

    Science.gov (United States)

    Sahin, A; Spiroux, F; Guedon, I; Arslan, F B; Sarcan, E T; Ozkan, T; Colak, N; Yuksel, S; Ozdemir, S; Ozdemir, B; Akbas, S; Ultav, G; Aktas, Y; Capan, Y

    2017-09-01

    In the preparation of nanoparticles (NPs) by the nanoprecipitation method, emulsifiers play a key role for NPs' characteristics. The present study aimed to investigate the combined emulsifier effect on ibuprofen loaded poly(lactic-co-glycolic acid) (PLGA) NPs' characteristics and anticancer activity. Ibuprofen loaded PLGA NPs were prepared by nanoprecipitation using different concentrations of PVA (poly(vinyl alcohol)) or PVA-TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) combination as emulsifier. It was found that encapsulation efficiencies of NPs varied between 17.9 and 41.9 % and the highest encapsulation efficiency was obtained with 0.5% PVA + 0.1% TPGS (coded as PLGA PVA/TPGS NPs). PLGA PVA/TPGS NPs were characterized and compared with PLGA PVA NPs, which was obtained by 0.5% PVA alone. Polydispersity index of PLGA PVA/TPGS and PLGA PVA NPs were found to be 0.08 and 0.15, respectively. Incorporation of TPGS with PVA slightly decreased the initial ibuprofen release. Transmission electron microscopy analyses demonstrated a nearly uniform particle size distribution and spherical particle shape of the PLGA PVA/TPGS NPs. Additionally, PLGA PVA/TPGS NPs were significantly more cytotoxic than PLGA PVA NPs on the MCF-7 (human breast adenocarcinoma cells) and Caco-2 (human epithelial colorectal adenocarcinoma) cells (p0.05). In conclusion, these results indicated that using a combination of TPGS and PVA as an emulsifier in nanoprecipitation could be a promising approach for preparing ibuprofen loaded PLGA NPs because of their improved characteristics and anticancer activity.

  9. Activated carbon fibers/poly(lactic-co-glycolic) acid composite scaffolds: Preparation and characterizations

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Yanni [State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620 (China); College of Materials Science and Engineering, Donghua University, Shanghai 201620 (China); Han, Hao [College of Materials Science and Engineering, Donghua University, Shanghai 201620 (China); Bayer Material Science China Co., Ltd, Shanghai 200120 (China); Quan, Haiyu; Zang, Yongju; Wang, Ning; Ren, Guizhi [College of Materials Science and Engineering, Donghua University, Shanghai 201620 (China); Xing, Melcolm [Department of Mechanical Engineering, Faculty of Engineering and Department of Biochemistry and Genetics, Faculty of Medicine P.I., Manitoba Institute of Child Health, University of Manitoba, Winnipeg, Manitoba (Canada); Wu, Qilin, E-mail: wql@dhu.edu.cn [State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620 (China); College of Materials Science and Engineering, Donghua University, Shanghai 201620 (China)

    2014-10-01

    The present work is a first trial to introduce activated carbon fibers (ACF) with high adsorption capacity into poly(lactic-co-glycolic) acid (PLGA), resulting in a novel kind of scaffolds for tissue engineering applications. ACF, prepared via high-temperature processing of carbon fibers, are considered to possess bioactivity and biocompatibility. The ACF/PLGA composite scaffolds are prepared by solvent casting/particulate leaching method. Increments in both pore quantity and quality over the surface of ACF as well as a robust combination between ACF and PLGA matrix are observed via scanning electron microscopy (SEM). The high adsorption capacity of ACF is confirmed by methylene blue solution absorbency test. The surfaces of ACF are affiliated with many hydrophilic groups and characterized by Fourier transform infrared spectroscopy. Furthermore, the SEM images show that cells possess a favorable spreading morphology on the ACF/PLGA scaffolds. Besides, vivo experiments are also carried out to evaluate the histocompatibility of the composite scaffolds. The results show that ACF have the potential to become one of the most promising materials in biological fields. - Highlights: • ACF with strong adsorption capacity and porous structure for enhanced surface area • The incorporation of ACF promoting the porosity of composite scaffolds • The composite scaffolds having no side effect on cell adhesion and proliferation • The composite scaffolds presenting good biocompatibility in vivo.

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

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    Zulaikha A. Busari

    2017-09-01

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

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

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    Antonietta Vilella

    2015-06-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2014-11-01

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

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

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    Li Tang

    2012-01-01

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

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

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    F. A Langroodi

    2016-01-01

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

  15. Feasibility of drug delivery to the eye's posterior segment by topical instillation of PLGA nanoparticles

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    Kohei Tahara

    2017-07-01

    Full Text Available We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide (PLGA nanoparticles (NPs. Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan (CS and glycol chitosan (GCS, which are mucoadhesive polymers, and polysorbate 80 (P80 were used as surface modifiers, and have been reported to increase the association of NPs with cells. Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal, non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation.

  16. Targeted delivery of antibiotics to intracellular chlamydial infections using PLGA nanoparticles.

    Science.gov (United States)

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

    2011-09-01

    Chlamydia trachomatis and Chlamydia 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2015-02-01

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

  18. In vitro release profiles of PLGA core-shell composite particles loaded with theophylline and budesonide.

    Science.gov (United States)

    Yeh, Hsi-Wei; Chen, Da-Ren

    2017-08-07

    We investigated the effects of drug loading location, matrix material and shell thickness on the in vitro release of combinational drugs from core-shell PLGA (i.e., poly(lactic-co-glycolic acid)) particles. Budesonide and Theophylline were selected as highly hydrophobic and hydrophilic model drugs, respectively. The dual-capillary electrospray (ES) technique, operated at the cone-jet mode, was used to produce samples of drug-loaded core-shell composite particles with selected overall sizes, polymer materials, and shell thicknesses. Theophylline and Budesonide were loaded at different locations in a PLGA composite particle. This study illustrated how the aforementioned factors affect the release rates of Budesonide and Theophylline loaded in core-shell PLGA composites. We further identified that core-shell composite particles with both model drugs loaded in the core and with matrix PLGA polymers of low molecular weights and low LA/GA ratios are the best formulation for the sustained release of highly hydrophilic and hydrophobic active pharmaceutical ingredients from PLGA composite particles. The formulation strategy obtained in this study can be in principle generalized for biopharmaceutical applications in fixed-dose combination therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

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

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

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    Sho Koda

    2017-01-01

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

  1. Controlled delivery of aspirin: effect of aspirin on polymer degradation and in vitro release from PLGA based phase sensitive systems.

    Science.gov (United States)

    Tang, Yu; Singh, Jagdish

    2008-06-05

    The objective of this study was to develop poly (d,l-lactide-co-glycolide) (PLGA) based injectable phase sensitive in situ gel forming delivery system for controlled delivery of aspirin, and to characterize the effect of drug/polymer interaction on the in vitro release of aspirin and polymer degradation. Aspirin was dissolved into PLGA solution in 1-methyl-2-pyrrolidone. Poly(ethylene glycol)400 was used as plasticizer to reduce initial burst release. The solution formulation was injected into aqueous release medium to form a gel depot. Released samples were withdrawn periodically and assayed for aspirin content by high performance liquid chromatography. The effect of aspirin on the degradation of PLGA matrix was evaluated using Proton Nuclear Magnetic Resonance and Gel Permeation Chromatography. PLGA based in situ gel forming formulations controlled the in vitro release of aspirin for 7 days only. Analysis of PLGA matrix residuals revealed that PLGA in aspirin loaded formulations exhibited a significantly (pdegradation compared to blank formulations. These findings suggest that aspirin causes an unusually faster degradation of PLGA. Such faster degradation of PLGA has not been noticed for any other drugs reported in the literature.

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-08-01

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

  5. Differentiation behavior of iPS cells cultured on PLGA with osteoinduction medium.

    Science.gov (United States)

    Tokita, Reiko; Nakajima, Kei; Inoue, Kenji; Al-Wahabi, Akram; Ser-Od, Tungalag; Matsuzaka, Kenichi; Inoue, Takashi

    2017-01-31

    In the present report, we have generated osteoblast-like cells derived from mouse induced-pluripotent stem (iPS) cells on PLGA with osteoinduction medium in vitro and in vivo. The cell culture period was 2 weeks. At 2 weeks, mRNA level of type I collagen was significantly higher than at 1 week. Osteocalcin mRNA level at 2 weeks was tendency to increase compared with at 1 week. And the cells cultured on PLGA were positive for immunofluorescent staining of osteocalcin and alizarin red S staining. The scaffold and osteogenic-like cells induced in vitro were implanted subcutaneously into SCID mice. In resected teratoma, hard tissues resembling bone were observed mixed with other tissues on the scaffold. The sum of these findings suggests that PLGA does not disturb the osteogenesis of iPS cells.

  6. A Cluster Randomized Controlled Trial to Reduce Childhood Diarrhea Using Hollow Fiber Water Filter and/or Hygiene–Sanitation Educational Interventions

    Science.gov (United States)

    Lindquist, Erik D.; George, C. M.; Perin, Jamie; Neiswender de Calani, Karen J.; Norman, W. Ray; Davis, Thomas P.; Perry, Henry

    2014-01-01

    Safe domestic potable water supplies are urgently needed to reduce childhood diarrheal disease. In periurban neighborhoods in Cochabamba, Bolivia, we conducted a cluster randomized controlled trial to evaluate the efficacy of a household-level hollow fiber filter and/or behavior change communication (BCC) on water, sanitation, and hygiene (WASH) to reduce the diarrheal disease in children less than 5 years of age. In total, 952 households were followed for a period of 12 weeks post-distribution of the study interventions. Households using Sawyer PointONE filters had significantly less diarrheal disease compared with the control arm during the intervention period, which was shown by diarrheal prevalence ratios of 0.21 (95% confidence interval [95% CI] = 0.15–0.30) for the filter arm and 0.27 (95% CI = 0.22–0.34) for the filter and WASH BCC arm. A non-significant reduction in diarrhea prevalence was reported in the WASH BCC study arm households (0.71, 95% CI = 0.59–0.86). PMID:24865680

  7. A cluster randomized controlled trial to reduce childhood diarrhea using hollow fiber water filter and/or hygiene-sanitation educational interventions.

    Science.gov (United States)

    Lindquist, Erik D; George, C M; Perin, Jamie; Neiswender de Calani, Karen J; Norman, W Ray; Davis, Thomas P; Perry, Henry

    2014-07-01

    Safe domestic potable water supplies are urgently needed to reduce childhood diarrheal disease. In periurban neighborhoods in Cochabamba, Bolivia, we conducted a cluster randomized controlled trial to evaluate the efficacy of a household-level hollow fiber filter and/or behavior change communication (BCC) on water, sanitation, and hygiene (WASH) to reduce the diarrheal disease in children less than 5 years of age. In total, 952 households were followed for a period of 12 weeks post-distribution of the study interventions. Households using Sawyer PointONE filters had significantly less diarrheal disease compared with the control arm during the intervention period, which was shown by diarrheal prevalence ratios of 0.21 (95% confidence interval [95% CI] = 0.15-0.30) for the filter arm and 0.27 (95% CI = 0.22-0.34) for the filter and WASH BCC arm. A non-significant reduction in diarrhea prevalence was reported in the WASH BCC study arm households (0.71, 95% CI = 0.59-0.86). © The American Society of Tropical Medicine and Hygiene.

  8. Natural fibers

    Science.gov (United States)

    Craig M. Clemons; Daniel F. Caulfield

    2005-01-01

    The term “natural fibers” covers a broad range of vegetable, animal, and mineral fibers. However, in the composites industry, it usually refers to wood fiber and agrobased bast, leaf, seed, and stem fibers. These fibers often contribute greatly to the structural performance of the plant and, when used in plastic composites, can provide significant reinforcement. Below...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-15

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

  10. 3-month parenteral PLGA microsphere formulations of risperidone: Fabrication, characterization and neuropharmacological assessments.

    Science.gov (United States)

    Chaurasia, Sundeep; Mounika, Kuchukuntla; Bakshi, Vasudha; Prasad, Vure

    2017-06-01

    The study aims at formulation and characterization of three months parenteral risperidone loaded polymeric microspheres (p-RLPMs) as a sustained delivery system and established their in vitro and in vivo assessments. The p-RLPMs formulations were prepared by solvent extraction and diffusion method. The optimized p-RLPMs (batch R PLGA -1) formulation demonstrated favorable different physicochemical properties such as mean particle size (104±5.34μm), percent porosity (44.56±3.11%) and percent drug loading (38.42±2.67%). The physical state characterization, Fourier transformed infrared spectroscopy analysis showed no changes in the chemical structure of risperidone (RPD) in the batch R PLGA -1 formulation and differential scanning calorimetry study confirmed, pure RPD retained its crystallinity in the batch R PLGA -1 formulation. The SEM micrographs of the all p-RLPMs formulations revealed the irregular shapes and indentations. The GC/MS results showed that the residual organic solvent content in the batch R PLGA -1 formulation was below the limits. Pharmacokinetic parameters revealed that optimized R PLGA -1 formulation exhibited an initial burst followed by an excellent sustained release as compared to pure RPD as well as other formulations. Furthermore, in vivo studies of the batch, R PLGA -1 formulation showed an antipsychotic effect that was significantly prolonged over that of pure RPD solution for up to 72h with fewer extrapyramidal side effects. Thus, results of this study prove the suitability of using poly(lactic-co-glycolic acid) copolymer to develop sustained release p-RLPMs formulations that can tailor in vivo behavior and enhance the pharmacological effectiveness of the RPD. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

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

    Science.gov (United States)

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

    2016-03-01

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

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

    Science.gov (United States)

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

    2013-01-01

    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. 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. 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. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-15

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-12-15

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

  18. Biotin decorated PLGA nanoparticles containing SN-38 designed for cancer therapy.

    Science.gov (United States)

    Mehdizadeh, Mozhdeh; Rouhani, Hasti; Sepehri, Nima; Varshochian, Reyhaneh; Ghahremani, Mohammad Hossein; Amini, Mohsen; Gharghabi, Mehdi; Ostad, Seyed Nasser; Atyabi, Fatemeh; Baharian, Azin; Dinarvand, Rassoul

    2017-05-01

    Active targeted chemotherapy is expected to provide more specific delivery of cytotoxic drugs to the tumor cells and hence reducing the side effects on healthy tissues. Due to the over expression of biotin receptors on cancerous cells as a result of further requirement for rapid proliferations, biotin can be a good candidate as a targeting agent. In this study, biotin decorated PLGA nanoparticles (NPs) containing SN-38 were prepared and in vitro studies were evaluated for their improved anti-cancer properties. In conclusion, biotin targeted PLGA NPs containing SN-38 showed preferential anticancer properties against tumor cells with biotin receptor over expression.

  19. Effect of n-HA with different surface-modified on the properties of n-HA/PLGA composite

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Liuyun, E-mail: jlytxg@163.com [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Xiong Chengdong; Chen Dongliang [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Jiang Lixin [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Graduated School of Chinese Academy of Sciences, Beijing 100039 (China); Pang Xiubing [Zhejiang Apeloa Medical Technology Co. Ltd, Jinhua 322118 (China)

    2012-10-15

    Graphical abstract: The bend strength of n-HA/PLGA composite with the unmodified n-HA becomes lower than that of PLGA. However, when n-HA was modified by different methods, the bend strength of g-n-HA/PLGA composites gets a little increase than PLGA, and the g3-n-HA/PLGA shows the highest bend strength at 3% g3-n-HA loading amount in weight, reached 162 MPa, which was 24.4% higher than that of pure PLGA. Highlights: Black-Right-Pointing-Pointer A new surface modification method for n-HA of combining stearic acid with surface-grafting L-lactic was adopted. Black-Right-Pointing-Pointer Three different surface modification methods for n-HA were compared in detail. Black-Right-Pointing-Pointer The new surface modification method was the most ideal method in this study. Black-Right-Pointing-Pointer The g3-n-HA/PLGA composite had the highest bending strength, which would be potential to be used as bone fracture internal fixation materials. - Abstract: Three different surface modification methods for nano-hydroxyapatite (n-HA) of stearic acid, grafted with L-lactide, combining stearic acid and surface-grafting L-lactic were adopted, respectively. The surface modification reaction and the effect of different methods were evaluated by Fourier transformation infrared (FTIR), X-ray photoelectron spectra (XPS), thermal gravimetric analysis (TGA), transmission electron microscopy (TEM). The results showed that n-HA surfaces were all successful modified, and the modification method of combining stearic acid and surface-grafting L-lactic had the greatest grafting amount and the best dispersion among the three modification methods. Then, the n-HA with three different surface modification and unmodified n-HA were introduced into PLGA, respectively, and a serials of n-HA/PLGA composites with 3% n-HA amount in weight were prepared by solution mixing, and the properties of n-HA/PLGA composites were also investigated by electromechanical universal tester and scanning electron

  20. Raman fiber lasers

    CERN Document Server

    2017-01-01

    This book serves as a comprehensive, up-to-date reference about this cutting-edge laser technology and its many new and interesting developments. Various aspects and trends of Raman fiber lasers are described in detail by experts in their fields. Raman fiber lasers have progressed quickly in the past decade, and have emerged as a versatile laser technology for generating high power light sources covering a spectral range from visible to mid-infrared. The technology is already being applied in the fields of telecommunication, astronomy, cold atom physics, laser spectroscopy, environmental sensing, and laser medicine. This book covers various topics relating to Raman fiber laser research, including power scaling, cladding and diode pumping, cascade Raman shifting, single frequency operation and power amplification, mid-infrared laser generation, specialty optical fibers, and random distributed feedback Raman fiber lasers. The book will appeal to scientists, students, and technicians seeking to understand the re...

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

    Science.gov (United States)

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

    2012-06-01

    The use of degradable composite materials in orthopedics remains a field of intense research due to their ability to support new bone formation and degrade in a controlled manner, broadening their use for orthopedic applications. Poly (lactide-co-glycolide) acid (PLGA), a degradable biopolymer, is now a popular material for different orthopedic applications and is proposed for use in tissue engineering scaffolds either alone or combined with bioactive ceramics. Interference screws composed of calcium phosphates and PLGA are readily available in the market. However, some reports highlight problems of screw migration or aseptic cyst formation following screw degradation. In order to understand these phenomena and to help to improve implant formulation, we have evaluated the effects of PLGA degradation products: lactic acid and glycolic acid on human osteoblasts in vitro. Cell proliferation, differentiation, and matrix mineralization, important for bone healing were studied. It was found that the toxicity of polymer degradation products under buffering conditions was limited to high concentrations. However, non-toxic concentrations led to a decrease in cell proliferation, rapid cell differentiation, and mineralization failure. Calcium, whilst stimulating cell proliferation was not able to overcome the negative effects of high concentrations of lactic and glycolic acids on osteoblasts. These effects help to explain recently reported clinical failures of calcium phosphate/PLGA composites, but further in vitro analyses are needed to mimic the dynamic situation which occurs in the body by, for example, culture of osteoblasts with materials that have been pre-degraded to different extents and thus be able to relate these findings to the degradation studies that have been performed previously. Copyright © 2011 Orthopaedic Research Society.

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

    Directory of Open Access Journals (Sweden)

    Jun Jia

    2012-01-01

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

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

    Science.gov (United States)

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

    2013-05-01

    Bone defect repair is challenging in orthopaedic clinics. For treatment of large bone defects, bone grafting remains the method of choice for the majority of surgeons, as it fills spaces and provides support to enhance biological bone repair. As therapeutic agents are desirable for enhancing bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier, incorporating a phytomolecule icaritin (ICT), i.e., a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high-dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of these bioactive scaffolds with slow release of osteogenic ICT, the authors established a 12 mm ulnar bone defect model in rabbits. X-ray and high-resolution peripheral quantitative computed tomography results at weeks 2, 4 and 8 post-surgery showed more newly formed bone within bone defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized bone in PLGA/TCP/ICT groups, especially in the PLGA/TCP/MICT group, with correspondingly more new vessel ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with the proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Effects of Cactus Fiber on the Excretion of Dietary Fat in Healthy Subjects: A Double Blind, Randomized, Placebo-Controlled, Crossover Clinical Investigation

    Directory of Open Access Journals (Sweden)

    Ralf Uebelhack, MD, PhD

    2014-12-01

    Conclusions: Cactus fiber has been shown to significantly promote fecal fat excretion in healthy adults. The results of our study support the hypothesis that cactus fiber helps in reducing body weight by binding to dietary fat and increasing its excretion, thus reducing dietary fat available for absorption. ClinicalTrials.gov identifier: NCT01590667.

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

    CSIR Research Space (South Africa)

    Semete, B

    2010-10-01

    Full Text Available distribution and retention following oral administration of PLGA particles was analyzed for 7 days. After 7 days, the particles remained detectable in the brain, heart, kidney, liver, lungs, and spleen. The results show that a mean percentage (40...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-03-15

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

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

    Science.gov (United States)

    Manabe, Noriyoshi; Kirikoshi, Ryota; Takahashi, Ohgi

    2015-03-31

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

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

    Science.gov (United States)

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

    2016-01-01

    With the aim to explore a membrane system with appropriate degradation rate and excellent cell-occlusiveness for guided tissue regeneration (GTR), a series of poly(D, L-lactic acid) (PDLLA)/poly(D, L-lactic-co-glycolic acid) (PLGA) (100/0, 70/30, 50/50, 30/70, 0/100, w/w) composite membranes were fabricated via electrospinning. The fabricated membranes were evaluated by morphological characterization, water contact angle measurement and tensile test. In vitro degradation was characterized in terms of the weight loss and the morphological change. Moreover, in vitro cytologic research revealed that PDLLA/PLGA composite membranes could efficiently inhibit the infiltration of 293 T cells. Finally, subcutaneous implant test on SD rat in vivo showed that PDLLA/PLGA (70/30, 50/50) composite membranes could function well as a physical barrier to prevent cellular infiltration within 13 weeks. These results suggested that electrospun PDLLA/PLGA (50/50) composite membranes could serve as a promising barrier membrane for guided tissue regeneration due to suitable biodegradability, preferable mechanical properties and excellent cellular shielding effects. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

    2013-03-01

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

  10. Mechanical evaluation of implanted calcium phosphate cement incorporated with PLGA microparticles.

    NARCIS (Netherlands)

    Link, D.P.; Dolder, J. van den; Jurgens, W.J.; Wolke, J.G.C.; Jansen, J.A.

    2006-01-01

    In this study, the mechanical properties of an implanted calcium phosphate (CaP) cement incorporated with 20wt% poly (dl-lactic-co-glycolic acid) (PLGA) microparticles were investigated in a rat cranial defect. After 2, 4 and 8 weeks of implantation, implants were evaluated mechanically (push-out

  11. In vitro characterisation of PLGA nanoparticles encapsulating rifampicin and isoniazid - Towards IVIVC

    CSIR Research Space (South Africa)

    Booysen, L

    2010-09-01

    Full Text Available circulation of the nanoparticles4. The objective of the current study was to determine the effect that PLGA (coated/ uncoated with PEG/Pluronic F127) nanoencapsulation of rifampicin (RIF) and isoniazid (INH) has on plasma protein binding of these drugs...

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

    CSIR Research Space (South Africa)

    Semete, B

    2012-03-01

    Full Text Available of surface coating with various concentrations of polymeric surfactants (PEG and Pluronics F127) on the in vitro protein binding as well as the tissue biodistribution, post oral administration, of PLGA nanoparticles. The in vitro protein binding varied...

  13. PLGA-Based Microparticles for the Sustained Release of BMP-2

    Directory of Open Access Journals (Sweden)

    Maria A. Woodruff

    2011-03-01

    Full Text Available The development of growth factor delivery strategies to circumvent the burst release phenomenon prevalent in most current systems has driven research towards encapsulating molecules in resorbable polymer matrices. For these polymer release techniques to be efficacious in a clinical setting, several key points need to be addressed. This present study has investigated the encapsulation of the growth factor, BMP-2 within PLGA/PLGA-PEG-PLGA microparticles. Morphology, size distribution, encapsulation efficiency and release kinetics were investigated and we have demonstrated a sustained release of bioactive BMP-2. Furthermore, biocompatibility of the PLGA microparticles was established and released BMP-2 was shown to promote the differentiation of MC3T3-E1 cells towards the osteogenic lineage to a greater extent than osteogenic supplements (as early as day 10 in culture, as determined using alkaline phosphatase and alizarin red assays. This study showcases a potential BMP-2 delivery system which may now be translated into more complex delivery systems, such as 3D, mechanically robust scaffolds for bone tissue regeneration applications.

  14. Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers

    Science.gov (United States)

    Xiong, Yi; Zhu, Ji-Xiang; Fang, Zheng-Yu; Zeng, Cheng-Guang; Zhang, Chao; Qi, Guo-Long; Li, Man-Hui; Zhang, Wei; Quan, Da-Ping; Wan, Jun

    2012-01-01

    Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury. PMID:22619535

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

    Directory of Open Access Journals (Sweden)

    Anila Mathew

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

  16. New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles.

    Science.gov (United States)

    Zou, Weiwei; Cao, Guangqing; Xi, Yanwei; Zhang, Na

    2009-01-01

    Local delivery of antiproliferative drugs encapsulated in biodegradable nanoparticles has shown promise as an experimental strategy for preventing vascular restenosis development. The general aim of this work was to develop polymeric nanoparticle carriers with bioadhesive properties, and to evaluate its adjuvant potential for local, intramural delivery of rapamycin for inhibition of restenosis. The bioadhesive rapamycin-loaded PLGA nanoparticles were obtained by applying carbopol 940 of different concentrations as stabilizer and bioadhesive agent. The resultant nanoparticles were characterized concerning physicochemical properties such as morphology, particle size, zeta potential, entrapment efficiency, drug loading, drug release in vitro, stability in vitro as well as the arterial uptake and retention ability in an ex-vivo model. The results revealed that carbopol could serve as a better stabilizer in the preparation of rapamycin-loaded PLGA nanoparticles compared with PVA, and the physicochemical characteristics of the obtained PLGA nanoparticles were affected by the concentration of carbopol. Furthermore, it was found that carbopol could impart the nanoparticles with bioadhesive properties, improving the rentention and uptake of nanoparticles in the arterial wall, benefiting the nanoparticles for efficient localization of therapeutic agents in restenosis site. Cell viability assay results showed that blank PLGA-carbopol nanoparticles exhibited low toxicity and excellent biocompatibility and rapamycin-loaded nanoparticles with a smaller particle size (carbopol stabilized bioadhesive nanoparticles against restenosis in vivo.

  17. High-throughput screening of PLGA thin films utilizing hydrophobic fluorescent dyes for hydrophobic drug compounds.

    Science.gov (United States)

    Steele, Terry W J; Huang, Charlotte L; Kumar, Saranya; Widjaja, Effendi; Chiang Boey, Freddy Yin; Loo, Joachim S C; Venkatraman, Subbu S

    2011-10-01

    Hydrophobic, antirestenotic drugs such as paclitaxel (PCTX) and rapamycin are often incorporated into thin film coatings for local delivery using implantable medical devices and polymers such as drug-eluting stents and balloons. Selecting the optimum coating formulation through screening the release profile of these drugs in thin films is time consuming and labor intensive. We describe here a high-throughput assay utilizing three model hydrophobic fluorescent compounds: fluorescein diacetate (FDAc), coumarin-6, and rhodamine 6G that were incorporated into poly(d,l-lactide-co-glycolide) (PLGA) and PLGA-polyethylene glycol films. Raman microscopy determined the hydrophobic fluorescent dye distribution within the PLGA thin films in comparison with that of PCTX. Their subsequent release was screened in a high-throughput assay and directly compared with HPLC quantification of PCTX release. It was observed that PCTX controlled-release kinetics could be mimicked by a hydrophobic dye that had similar octanol-water partition coefficient values and homogeneous dissolution in a PLGA matrix as the drug. In particular, FDAc was found to be the optimal hydrophobic dye at modeling the burst release as well as the total amount of PCTX released over a period of 30 days. Copyright © 2011 Wiley-Liss, Inc.

  18. Self-neutralizing PLGA/magnesium composites as novel biomaterials for tissue engineering.

    Science.gov (United States)

    Xu, Thomas O; Kim, Hyun Sung; Stahl, Tyler; Nukavarapu, Syam Prasad

    2018-01-24

    Controlling acidic degradation of biodegradable polyesters remains a major challenge when used them as biomaterials in biomedical devices. This work presents a simple strategy of developing polyester composites with biodegradable magnesium metal or alloys. PLGA films with compositions of 1, 3, 5, and 10 wt% Mg were simply produced using the solvent-casting method, which resulted in composite films with near uniform Mg metal/alloy particle dispersion. Degradation study of the composite films showed that all compositions higher than 1 wt% Mg were able to extend the duration of degradation, and buffer acidic pH resulting from PLGA degradation. PLGA-5Wt% Mg composition in sink condition is found to show near-neutral degradation pattern. Magnesium addition also showed improved mechanical characteristics in terms of the tensile modulus and strength. In vitro experiments conducted by seeding PLGA-5 wt% Mg composite films with MC3T3-E1 preosteoblast cells demonstrated increased ALP expression, and cellular mineralization. The established new biodegradable polymer-metal system provides a useful biomaterial platform with a wide range of applications in biomedical device development and scaffold-based tissue engineering. © 2018 IOP Publishing Ltd.

  19. PLGA Ethionamide Nanoparticles for Pulmonary Delivery: Development and in vivo evaluation of dry powder inhaler.

    Science.gov (United States)

    Debnath, Sujit Kumar; Saisivam, Srinivasan; Omri, Abdelwahab

    2017-10-25

    PLGA (50:50) nanoparticles were prepared to sustain the release of Ethionamide in order to decrease the dose and dosing frequency. It further modified in the form of dry powder inhaler to make suitable for pulmonary administration and increase drug residency in lungs. Ethionamide loaded PLGA nanoparticles were prepared by solvent evaporation method. Freeze dried nanoparticles and anhydrous inhalable grade lactose were mixed manually using geometrical dilution process to modify the nanoparticles in the form of dry powder inhaler. Animal study was conducted to correlate between in-vivo and in-vitro. PLGA nanoparticles showed initial burst release followed by zero order release up to 95.17±3.59% in 24h. Aerodynamic particle size of optimized dry powder inhaler was found as 1.79μm. There was no significant aggregation of dry powder inhaler during 6 months of stability study. Area under the concentration-time curve from 0h to infinity (AUC0(-∞)) signifies the prolong residency of ETH in body compartment, revealed from animal study. PLGA 50:50 coated nanoparticles released Ethionamide for the period of 24h in simulated lungs fluid. Correlation between in-vitro dissolution and in-vivo study was established after performing animal study. Prepared dry powder inhaler maintained Ethionamide concentration above minimum inhibitory concentration for more than 12h after single dose administration. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Wan, Feng; Yang, Mingshi

    2016-01-01

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

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

    Science.gov (United States)

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

    2012-11-01

    Liposomes and polymers are widely used drug carriers for controlled release since they offer many advantages like increased treatment effectiveness, reduced toxicity and are of biodegradable nature. In this work, anticancer drug-loaded PLGA-lecithin-PEG nanoparticles (NPs) were synthesized and were functionalized with AS1411 anti-nucleolin aptamers for site-specific targeting against tumor cells which over expresses nucleolin receptors. The particles were characterized by transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS). The drug-loading efficiency, encapsulation efficiency and in vitro drug release studies were conducted using UV spectroscopy. Cytotoxicity studies were carried out in two different cancer cell lines, MCF-7 and GI-1 cells and two different normal cells, L929 cells and HMEC cells. Confocal microscopy and flowcytometry confirmed the cellular uptake of particles and targeted drug delivery. The morphology analysis of the NPs proved that the particles were smooth and spherical in shape with a size ranging from 60 to 110 nm. Drug-loading studies indicated that under the same drug loading, the aptamer-targeted NPs show enhanced cancer killing effect compared to the corresponding non-targeted NPs. In addition, the PLGA-lecithin-PEG NPs exhibited high encapsulation efficiency and superior sustained drug release than the drug loaded in plain PLGA NPs. The results confirmed that AS1411 aptamer-PLGA-lecithin-PEG NPs are potential carrier candidates for differential targeted drug delivery. Copyright © 2012 Wiley Periodicals, Inc.

  2. From micelles to fibers: balancing self-assembling and random coiling domains in pH-responsive silk-collagen-like protein-based polymers.

    Science.gov (United States)

    Beun, Lennart H; Storm, Ingeborg M; Werten, Marc W T; de Wolf, Frits A; Cohen Stuart, Martien A; de Vries, Renko

    2014-09-08

    We study the self-assembly of genetically engineered protein-based triblock copolymers consisting of a central pH-responsive silk-like middle block (S(H)n, where S(H) is a silk-like octapeptide, (GA)3GH and n is the number of repeats) flanked by hydrophilic random coil outer blocks (C2). Our previous work has already shown that triblocks with very long midblocks (n = 48) self-assemble into long, stiff protein filaments at pH values where the middle blocks are uncharged. Here we investigate the self-assembly behavior of the triblock copolymers for a range of midblock lengths, n = 8, 16, 24, 48. Upon charge neutralization of S(H)n by adjusting the pH, we find that C2S(H)8C2 and C2S(H)16C2 form spherical micelles, whereas both C2S(H)24C2 and C2S(H)48C2 form protein filaments with a characteristic beta-roll secondary structure of the silk midblocks. Hydrogels formed by C2S(H)48C2 are much stronger and form much faster than those formed by C2S(H)24C2. Enzymatic digestion of much of the hydrophilic outer blocks is used to show that with much of the hydrophilic outer blocks removed, all silk-midblocks are capable of self-assembling into stiff protein filaments. In that case, reduction of the steric repulsion by the hydrophilic outer blocks also leads to extensive fiber bundling. Our results highlight the opposing roles of the hydrophilic outer blocks and central silk-like midblocks in driving protein filament formation. They provide crucial information for future designs of triblock protein-based polymers that form stiff filaments with controlled bundling, that could mimick properties of collagen in the extracellular matrix.

  3. An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: a randomized, controlled trial.

    Science.gov (United States)

    Seidner, Douglas L; Lashner, Bret A; Brzezinski, Aaron; Banks, Phillip L C; Goldblum, John; Fiocchi, Claudio; Katz, Jeffry; Lichtenstein, Gary R; Anton, Peter A; Kam, Lori Y; Garleb, Keith A; Demichele, Stephen J

    2005-04-01

    N-3 fatty acids from fish oil, antioxidants, and short-chain fatty acids (SCFAs) produced during the fermentation of soluble fiber may attenuate inflammation associated with ulcerative colitis (UC). We assessed the efficacy of a nutritionally balanced oral supplement enriched with fish oil, fructooligosaccharides, gum arabic, vitamin E, vitamin C, and selenium on disease activity and medication use in adults with mild to moderate UC. A total of 121 patients with UC and a disease activity index (DAI) from 3-9 on a 12-point scale were block randomized for extent of disease and smoking status. In addition to their usual diet, patients consumed 18 oz of the oral supplement or a carbohydrate-based placebo formula each day for 6 months. Clinical and histologic responses were assessed at 3 and 6 months or at the final visit. A change in average prednisone use between groups was tested by using a linear mixed-effects model. Eighty-six patients completed the study. Baseline characteristics were not different between groups except for a higher total DAI score in the oral supplement group (7.3 +/- 1.3; n = 36) compared with the placebo group (6.2 +/- 2.0; n = 50) ( P < .05). Both groups showed significant and similar degree of improvement at 6 months in DAI (-2.5 for oral supplement and -2.8 for placebo) and histologic index (-1.9 for oral supplement vs. -2.0 for placebo). Both intent-to-treat and completed patients given oral supplement had a significantly greater rate of decrease in the dose of prednisone required to control clinical symptoms over 6 months as compared with the placebo group ( P < .001). The improvement in clinical response combined with a decreased requirement for corticosteroids suggest that this enriched oral supplement can be a useful adjuvant therapy in patients with UC.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-05-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique...... during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes....

  6. Fiber biology

    Science.gov (United States)

    Cotton fiber cells arising from seed epidermis is the most important agricultural textile commodity in the world. To produce fully mature fibers, approximately two months of fiber developmental process are required. The timing of four distinctive fiber development stages consisting of initiation, ...

  7. Effect of n-HA content on the isothermal crystallization, morphology and mechanical property of n-HA/PLGA composites

    Energy Technology Data Exchange (ETDEWEB)

    Liuyun, Jiang, E-mail: jlytxg@163.com [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Chengdong, Xiong [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Lixin, Jiang [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China); Graduated School of Chinese Academy of Sciences, Beijing 100039 (China); Dongliang, Chen; Qing, Li [Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041 (China)

    2013-03-15

    Graphical abstract: Effect of n-HA content on the isothermal crystallization, morphology and mechanical property of n-HA/PLGA composites was studied in details. The results showed that the addition of higher content of g-n-HA was favorable to promote the crystallization better in g-n-HA/PLGA composites, but it could also cause more agglomeration in PLGA matrix, as a result of worse mechanical properties, and the addition content of 3 wt% g-n-HA to PLGA matrix was an appropriate proportion, which had the highest bending strength among these g-n-HA/PLGA composites, and it might be potential to be used in biomedical fields in future. Highlights: ► The effect of n-HA content on the n-HA/PLGA composites was studied in detail. ► Isothermal crystallization, microstructure and mechanical property were studied. ► The relation between n-HA content and properties of n-HA/PLGA composite was found. ► An appropriate proportion of n-HA in n-HA/PLGA composite was obtained. - Abstract: A serials of g-n-HA/PLGA composites with surface-modified g-n-HA of 1%, 3%, 6%, 10% and 15% in weight were prepared by solution mixing. The isothermal crystallization, morphology and mechanical property of g-n-HA/PLGA composites were investigated by differential scanning calorimeter (DSC), scanning electron microscope (SEM) and electromechanical universal tester. The results showed that Avrami equation was suitable for describing the isothermal crystallization process in this system, and the crystallization rate of g-n-HA/PLGA composites containing more than 3 wt% g-n-HA was basically accord with the relational expression of T{sub 110} {sub °C} > T{sub 105°C} > T{sub 115°C} > T{sub 120°C}. Moreover, at the same Tc, crystallization rate was greatly enhanced with the increasing of g-n-HA acting as nucleate. However, the addition of higher content of g-n-HA would cause more agglomeration in PLGA matrix, so that the mechanical properties of g-n-HA/PLGA composites would gradually decrease. In

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-15

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

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

    Science.gov (United States)

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

    2013-10-01

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

  10. Micro-Flow Imaging as a quantitative tool to assess size and agglomeration of PLGA microparticles.

    Science.gov (United States)

    van Beers, Miranda M C; Slooten, Cees; Meulenaar, Jelte; Sediq, Ahmad S; Verrijk, Ruud; Jiskoot, Wim

    2017-08-01

    The purpose of this study was to explore the potential of flow imaging microscopy to measure particle size and agglomeration of poly(lactic-co-glycolic acid) (PLGA) microparticles. The particle size distribution of pharmaceutical PLGA microparticle products is routinely determined with laser diffraction. In our study, we performed a unique side-by-side comparison between MFI 5100 (flow imaging microscopy) and Mastersizer 2000 (laser diffraction) for the particle size analysis of two commercial PLGA microparticle products, i.e., Risperdal Consta and Sandostatin LAR. Both techniques gave similar results regarding the number and volume percentage of the main particle population (28-220μm for Risperdal Consta; 16-124μm for Sandostatin LAR). MFI additionally detected a 'fines' population (<28μm for Risperdal Consta; <16μm for Sandostatin LAR), which was overlooked by Mastersizer. Moreover, MFI was able to split the main population into 'monospheres' and 'agglomerates' based on particle morphology, and count the number of particles in each sub-population. Finally, we presented how MFI can be applied in process development of risperidone PLGA microparticles and to monitor the physical stability of Sandostatin LAR. These case studies showed that MFI provides insight into the effect of different process steps on the number, size and morphology of fines, monospheres and agglomerates as well as the extent of microparticle agglomeration after reconstitution. This can be particularly important for the suspendability, injectability and release kinetics of PLGA microparticles. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Mandiwana, Vusani; Kalombo, Lonji; Venter, Kobus; Sathekge, Mike; Grobler, Anne; Zeevaart, Jan Rijn

    2015-09-01

    Developing nanoparticulate delivery systems that will allow easy movement and localization of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly( d, l-lactide- co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([153Sm]Sm2O3) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive 153Sm-loaded-PLGA nanoparticles. The nanoparticles were characterized for size, zeta potential, and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The 153Sm-loaded-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The zeta potential ranged between 5 and 20 mV. The [153Sm]Sm2O3 loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles. While the IV injected [153Sm]Sm2O3-loaded PLGA nanoparticles exhibited the highest localization of nanoparticles in the spleen (8.63 %ID/g) and liver (3.07 %ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen. From the biodistribution data obtained, it is clear that polymeric nanoscale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2017-05-10

    The aim of this study was to evaluate the impact of the addition of small amounts of hydrophilic polymers (Poloxamer 188 and PEO 200kDa) to PLGA-based implants loaded with prilocaine. Special emphasis was placed on the importance of the type of preparation technique: direct compression of milled drug-polymer powder blends versus compression of drug loaded microparticles (prepared by spray-drying). The implants were thoroughly characterized before and upon exposure to phosphate buffer pH7.4, e.g. using optical and scanning electron microscopy, X-ray diffraction, DSC and GPC. Interestingly, the addition of Poloxamer/PEO to the PLGA implants had opposite effects on the resulting drug release kinetics, depending on the type of preparation method: in the case of implants prepared by compression of milled drug-polymer powder blends, drug release was accelerated, whereas it was slowed down when the implants were prepared by compression of drug loaded PLGA microparticles. These phenomena could be explained by the swelling/disintegration behavior of the implants upon exposure to the release medium. Systems consisting of compressed microparticles remained intact and autocatalytic effects were of major importance. The presence of a hydrophilic polymer facilitated water penetration into these devices, slowing down PLGA degradation and drug release. In contrast, implants consisting of compressed drug-polymer powder blends rapidly (at least partially) disintegrated and autocatalysis was much less important. In these cases, the addition of a hydrophilic polymer facilitated ester bond cleavage, leading to accelerated PLGA degradation and drug release. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2015-05-01

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

  15. Fiber Amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten

    2017-01-01

    The chapter provides a discussion of optical fiber amplifiers and through three sections provides a detailed treatment of three types of optical fiber amplifiers, erbium doped fiber amplifiers (EDFA), Raman amplifiers, and parametric amplifiers. Each section comprises the fundamentals including...... the basic physics and relevant in-depth theoretical modeling, amplifiers characteristics and performance data as a function of specific operation parameters. Typical applications in fiber optic communication systems and the improvement achievable through the use of fiber amplifiers are illustrated....

  16. Low-Loss Fiber Waveguides.

    Science.gov (United States)

    1980-10-01

    quality. Ion exchange will be attempted using liquid (e.g., HBr ) and gas phase chemistry on extruded KRS-5 fiber. The fiber developed, both clad and...glasses, mechanisms which give rise td these fluctuations include: density variations resulting from the frozen-in, random variations in dielectric

  17. Carbon Fiber Reinforced Polymer with Shredded Fibers: Quasi-Isotropic Material Properties and Antenna Performance

    OpenAIRE

    Gerald Artner; Gentner, Philipp K.; Johann Nicolics; Mecklenbräuker, Christoph F.

    2017-01-01

    A carbon fiber reinforced polymer (CFRP) laminate, with the top layer consisting of shredded fibers, is proposed and manufactured. The shredded fibers are aligned randomly on the surface to achieve a more isotropic conductivity, as is desired in antenna applications. Moreover, fiber shreds can be recycled from carbon fiber composites. Conductivity, permittivity, and permeability are obtained with the Nicolson-Ross-Weir method from material samples measured inside rectangular waveguides in the...

  18. Design and optimization of PLGA microparticles for controlled and local delivery of Neuregulin-1 in traumatic spinal cord injury.

    Science.gov (United States)

    Santhosh, Kallivalappil T; Alizadeh, Arsalan; Karimi-Abdolrezaee, Soheila

    2017-09-10

    Spinal cord injury (SCI) results in significant tissue damage that underlies functional impairments. Pharmacological interventions to confer neuroprotection and promote cell replacement are essential for SCI repair. We previously reported that Neuregulin-1 (Nrg-1) is acutely and permanently downregulated after SCI. Nrg-1 is a critical growth factor for differentiation of neural precursor cells (NPCs) into myelinating oligodendrocytes. We showed that intrathecal delivery of Nrg-1 enhances oligodendrocyte replacement following SCI. While an effective delivery system, intrathecal and systemic administration of growth factors with diverse biological targets may pose adverse off-target effects. Here, we have developed and optimized an injectable biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles system for sustained and prolonged intraspinal delivery of Nrg-1 in SCI. Recombinant human Nrg-1β1 peptide was encapsulated into PLGA microparticles. Optimal Nrg-1 release rate and duration were achieved by manipulating the porosity and size of PLGA particles. Our in vitro analysis showed a direct correlation between particle size and porosity with Nrg-1 release rate, while Nrg-1 loading efficiency in PLGA microparticles was inversely correlated with particle porosity. In SCI, local intraspinal injection of PLGA-Nrg-1 microparticles maintained significantly higher tissue levels of Nrg-1 for a long-term duration compared to Nrg-1 delivered intrathecally by osmotic pumps. Bioactivity of Nrg-1 in PLGA microparticles was verified by promoting oligodendrocyte differentiation of NPCs in vitro, and preservation of oligodendrocytes and axons in SCI. PLGA-Nrg-1 also attenuated neuroinflammation and glial scarring following SCI. We show, for the first time, the feasibility, efficacy and safety of PLGA microparticle system for local and controlled administration of Nrg-1 in SCI. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Starch-entrapped microsphere fibers improve bowel habit but do not exhibit prebiotic capacity in those with unsatisfactory bowel habits: a phase I, randomized, double-blind, controlled human trial.

    Science.gov (United States)

    Rasmussen, Heather E; Hamaker, Bruce; Rajan, Kumar B; Mutlu, Ece; Green, Stefan J; Brown, Michael; Kaur, Amandeep; Keshavarzian, Ali

    2017-08-01

    Approximately one-third of individuals in the United States experience unsatisfactory bowel habits, and dietary intake, especially one low in fiber, could be partly responsible. We hypothesized that intake of a fermentable fiber (starch-entrapped microspheres, SM) that has a delayed, slow fermentation profile in vitro would improve bowel habit while exhibiting prebiotic capacity in those with self-described unsatisfactory bowel habits, all with minimal adverse effects. A total of 43 healthy volunteers completed a 3-month, double-blind, parallel-arm randomized clinical trial to assess the ability of a daily dose (9 or 12 g) of SM vs psyllium (12 g) to improve bowel habit, including stool consistency and frequency, and modify gut milieu through changes in stool microbiota and short-chain fatty acids while remaining tolerable through minimal gastrointestinal symptoms. All outcomes were compared before and after fiber treatment. Stool frequency significantly improved (P=.0003) in all groups after 3 months, but stool consistency improved only in both SM groups compared with psyllium. In addition, all groups self-reported a similar improvement in overall bowel habit with fiber intake. Both SM and psyllium resulted in minimal changes in microbiota composition and short-chain fatty acid concentrations. The present study suggests that supplementation with a delayed and slow-fermenting fiber in vitro may improve bowel habit in those with constipation, but further investigation is warranted to determine capacity to alter microbiota and fermentation profiles in humans. This trial was registered at ClinicalTrials.gov as NCT01210625. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Zhi-Cai Xing

    2012-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-06-15

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

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

    Science.gov (United States)

    Wan, Feng; Bohr, Adam; Maltesen, Morten Jonas; Bjerregaard, Simon; Foged, Camilla; Rantanen, Jukka; Yang, Mingshi

    2013-04-01

    It is imperative to understand the particle formation mechanisms when designing advanced nano/microparticulate drug delivery systems. We investigated how the solvent power and volatility influence the texture and surface chemistry of celecoxib-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles prepared by spray-drying. Binary mixtures of acetone and methanol at different molar ratios were applied to dissolve celecoxib and PLGA prior to spray-drying. The resulting microparticles were characterized with respect to morphology, texture, surface chemistry, solid state properties and drug release profile. The evaporation profiles of the feed solutions were investigated using thermogravimetric analysis (TGA). Spherical PLGA microparticles were obtained, irrespectively of the solvent composition. The particle size and surface chemistry were highly dependent on the solvent power of the feed solution. An obvious burst release was observed for the microparticles prepared by the feed solutions with the highest amount of poor solvent for PLGA. TGA analysis revealed distinct drying kinetics for the binary mixtures. The particle formation process is mainly governed by the PLGA precipitation rate, which is solvent-dependent, and the migration rate of celecoxib molecules during drying. The texture and surface chemistry of the spray-dried PLGA microparticles can therefore be tailored by adjusting the solvent composition.

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

    Science.gov (United States)

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

    2016-11-15

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

  4. Health Benefits of Fiber Fermentation.

    Science.gov (United States)

    Dahl, Wendy J; Agro, Nicole C; Eliasson, Åsa M; Mialki, Kaley L; Olivera, Joseph D; Rusch, Carley T; Young, Carly N

    2017-02-01

    Although fiber is well recognized for its effect on laxation, increasing evidence supports the role of fiber in the prevention and treatment of chronic disease. The aim of this review is to provide an overview of the health benefits of fiber and its fermentation, and describe how the products of fermentation may influence disease risk and treatment. Higher fiber intakes are associated with decreased risk of cardiovascular disease, type 2 diabetes, and some forms of cancer. Fiber may also have a role in lowering blood pressure and in preventing obesity by limiting weight gain. Fiber is effective in managing blood glucose in type 2 diabetes, useful for weight loss, and may provide therapeutic adjunctive roles in kidney and liver disease. In addition, higher fiber diets are not contraindicated in inflammatory bowel disease or irritable bowel syndrome and may provide some benefit. Common to the associations with disease reduction is fermentation of fiber and its potential to modulate microbiota and its activities and inflammation, specifically the production of anti-inflammatory short chain fatty acids, primarily from saccharolytic fermentation, versus the deleterious products of proteolytic activity. Because fiber intake is inversely associated with all-cause mortality, mechanisms by which fiber may reduce chronic disease risk and provide therapeutic benefit to those with chronic disease need further elucidation and large, randomized controlled trials are needed to confirm causality.Teaching Points• Strong evidence supports the association between higher fiber diets and reduced risk of cardiovascular disease, type 2 diabetes, and some forms of cancer.• Higher fiber intakes are associated with lower body weight and body mass index, and some types of fiber may facilitate weight loss.• Fiber is recommended as an adjunctive medical nutritional therapy for type 2 diabetes, chronic kidney disease, and certain liver diseases.• Fermentation and the resulting shifts in

  5. Effects of gamma-irradiation on PLGA microspheres loaded with thienorphine.

    Science.gov (United States)

    Yang, Yang; Gao, Yongliang; Mei, Xingguo

    2011-09-01

    Ionizing radiation can be used as a drug sterilization technique, provided that the drug itself is not modified and that no toxic products are produced; moreover, if the irradiated product is a drug delivery system, its drug release characteristics must not be significantly altered by radiation. The aim of this work was to study the effects of sterilization by ionizing radiation on PLGA microspheres, containing thienorphine. Thienorphine PLGA microspheres were prepared by the O/W solvent evaporation method and characterized by HPLC, SEM and laser particle size analysis. Our experimental results showed that gamma-rays did not alter the drug content, and did not modify the kinetics of drug release from microspheres. Moreover, no significant changes in the shape and in the size distribution of microspheres were found after irradiation. In conclusion, the sterilization method is adequate because microspheres not underwent any change after exposition to gamma-irradiation.

  6. Effect of Injection Molding Melt Temperatures on PLGA Craniofacial Plate Properties during In Vitro Degradation

    Directory of Open Access Journals (Sweden)

    Liliane Pimenta de Melo

    2017-01-01

    Full Text Available The purpose of this article is to present mechanical and physicochemical properties during in vitro degradation of PLGA material as craniofacial plates based on different values of injection molded temperatures. Injection molded plates were submitted to in vitro degradation in a thermostat bath at 37 ± 1°C by 16 weeks. The material was removed after 15, 30, 60, and 120 days; then bending stiffness, crystallinity, molecular weights, and viscoelasticity were studied. A significant decrease of molecular weight and mechanical properties over time and a difference in FT-IR after 60 days showed faster degradation of the material in the geometry studied. DSC analysis confirmed that the crystallization occurred, especially in higher melt temperature condition. DMA analysis suggests a greater contribution of the viscous component of higher temperature than lower temperature in thermomechanical behavior. The results suggest that physical-mechanical properties of PLGA plates among degradation differ per injection molding temperatures.

  7. Dietary Fiber

    Science.gov (United States)

    Fiber is a substance in plants. Dietary fiber is the kind you eat. It's a type of carbohydrate. You may also see it listed on a food label as soluble ... types have important health benefits. Good sources of dietary fiber include Whole grains Nuts and seeds Fruit and ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-04-01

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

  9. Mechanical characterization of fiber reinforced Polymer Concrete

    OpenAIRE

    Reis,João Marciano Laredo dos

    2005-01-01

    A comparative study between epoxy Polymer Concrete plain, reinforced with carbon and glass fibers and commercial concrete mixes was made. The fibers are 6 mm long and the fiber content was 2% and 1%, respectively, in mass. Compressive tests were performed at room temperature and load vs. displacement curves were plotted up to failure. The carbon and glass fibers reinforcement were randomly dispersed into the matrix of polymer concrete. An increase in compressive properties was observed as fun...

  10. PLGA-carbon nanotube conjugates for intercellular delivery of caspase-3 into osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Qingsu Cheng

    Full Text Available Cancer has arisen to be of the most prominent health care issues across the world in recent years. Doctors have used physiological intervention as well as chemical and radioactive therapeutics to treat cancer thus far. As an alternative to current methods, gene delivery systems with high efficiency, specificity, and safety that can reduce side effects such as necrosis of tissue are under development. Although viral vectors are highly efficient, concerns have arisen from the fact that viral vectors are sourced from lethal diseases. With this in mind, rod shaped nano-materials such as carbon nanotubes (CNTs have become an attractive option for drug delivery due to the enhanced permeability and retention effect in tumors as well as the ability to penetrate the cell membrane. Here, we successfully engineered poly (lactic-co-glycolic (PLGA functionalized CNTs to reduce toxicity concerns, provide attachment sites for pro-apoptotic protein caspase-3 (CP3, and tune the temporal release profile of CP3 within bone cancer cells. Our results showed that CP3 was able to attach to functionalized CNTs, forming CNT-PLGA-CP3 conjugates. We show this conjugate can efficiently transduce cells at dosages as low as 0.05 μg/ml and suppress cell proliferation up to a week with no further treatments. These results are essential to showing the capabilities of PLGA functionalized CNTs as a non-viral vector gene delivery technique to tune cell fate.

  11. Development of a novel AMX-loaded PLGA/zein microsphere for root canal disinfection

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, F F O [Capes Foundation, Ministry of Education of Brazil, Cx. Postal 365, BrasIlia DF 70359-970 (Brazil); Luzardo-Alvarez, A; Blanco-Mendez, J [Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, Campus Universitario Sur s/n, 15782, Santiago de Compostela (Spain); Perez-Estevez, A; Seoane-Prado, R, E-mail: franciscofabio.oliveira@rai.usc.e [Departament of Microbiology and Parasitology, Medical School, University of Santiago de Compostela, R/de San Francisco, s/n, 15782, Santiago de Compostela (Spain)

    2010-10-01

    The aim of this study was to develop polymeric biodegradable microspheres (MSs) of poly(d-l lactide-co-glycolide) (PLGA) and zein capable of delivering amoxicillin (AMX) at significant levels for root canal disinfection. PLGA/zein MSs were prepared using a spray-drying technique. The systems were characterized in terms of particle size, morphology, drug loading and in vitro release. Drug levels were reached to be effective during the intracanal dressing in between visits during the endodontic treatment. In vitro release studies were carried out to understand the release profile of the MSs. Antimicrobial activity of AMX was performed by antibiograms. Enterococcus faecalis was the bacteria selected due to its prevalence in endodontic failure. Drug microencapsulation yielded MSs with spherical morphology and an average particle size of between 5 and 38 {mu}m. Different drug-release patterns were obtained among the formulations. Release features related to the MSs were strongly dependent on drug nature as it was demonstrated by using a hydrophobic drug (indomethacin). Finally, AMX-loaded MSs were efficient against E faecalis as demonstrated by the antibiogram results. In conclusion, PLGA/zein MSs prepared by spray drying may be a useful drug delivery system for root canal disinfection.

  12. Gelsolin Amyloidogenesis Is Effectively Modulated by Curcumin and Emetine Conjugated PLGA Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Ankit Srivastava

    Full Text Available Small molecule based therapeutic intervention of amyloids has been limited by their low solubility and poor pharmacokinetic characteristics. We report here, the use of water soluble poly lactic-co-glycolic acid (PLGA-encapsulated curcumin and emetine nanoparticles (Cm-NPs and Em-NPs, respectively, as potential modulators of gelsolin amyloidogenesis. Using the amyloid-specific dye Thioflavin T (ThT as an indicator along with electron microscopic imaging we show that the presence of Cm-NPs augmented amyloid formation in gelsolin by skipping the pre-fibrillar assemblies, while Em-NPs induced non-fibrillar aggregates. These two types of aggregates differed in their morphologies, surface hydrophobicity and secondary structural signatures, confirming that they followed distinct pathways. In spite of differences, both these aggregates displayed reduced toxicity against SH-SY5Y human neuroblastoma cells as compared to control gelsolin amyloids. We conclude that the cytotoxicity of gelsolin amyloids can be reduced by either stalling or accelerating its fibrillation process. In addition, Cm-NPs increased the fibrillar bulk while Em-NPs defibrillated the pre-formed gelsolin amyloids. Moreover, amyloid modulation happened at a much lower concentration and at a faster rate by the PLGA encapsulated compounds as compared to their free forms. Thus, besides improving pharmacokinetic and biocompatible properties of curcumin and emetine, PLGA conjugation elevates the therapeutic potential of both small molecules against amyloid fibrillation and toxicity.

  13. Peripheral nerve regeneration within an asymmetrically porous PLGA/Pluronic F127 nerve guide conduit.

    Science.gov (United States)

    Oh, Se Heang; Kim, Jun Ho; Song, Kyu Sang; Jeon, Byeong Hwa; Yoon, Jin Hwan; Seo, Tae Beom; Namgung, Uk; Lee, Il Woo; Lee, Jin Ho

    2008-04-01

    Asymmetrically porous tubes with selective permeability and hydrophilicity as nerve guide conduits (NGCs) were fabricated using poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127 by a modified immersion precipitation method. The inner surface of the tube had nano-size pores ( approximately 50nm) which can effectively prevent from fibrous tissue infiltration but permeate nutrients and retain neurotrophic factors, while the outer surface had micro-size pores ( approximately 50microm) which can allow vascular ingrowth for effective supply of nutrients into the tube. From the animal study using a rat model, the hydrophilized PLGA/F127 (3wt%) tube showed better nerve regeneration behavior than the control silicone or hydrophobic PLGA tubes, as investigated by immunohistochemical observation (by fluorescent microscopy with anti-neurofilament staining), histological observations (by light microscopy with toluidine blue staining and transmission electron microscopy), and electrophysiological evaluation (by compound muscle action potential measurement). This is probably owing to the effective permeation of nutrients and prevention of fibrous scar tissue invasion as well as the good mechanical strength of the tube to maintain a stable support structure for the nerve regeneration.

  14. Formulation and in vitro interaction of rhodamine-B loaded PLGA nanoparticles with cardiac myocytes.

    Directory of Open Access Journals (Sweden)

    Antranik Jonderian

    2016-12-01

    Full Text Available This study aims to characterize rhodamine B (Rh B loaded poly(D,L-lactide-co-glycolide (PLGA nanoparticles (NPs and their interactions with cardiac myocytes. PLGA NPs were formulated using single emulsion solvent evaporation technique. The influence of varying parameters such as the stabilizer concentration, the sonication time, and the organic to aqueous ratio were investigated. The diameter, the dispersity, the encapsulation efficiency and the zeta potential of the optimized nanoparticles were about 184 nm, 0.19, 40% and -21.7 mV respectively. In vitro release showed that 29% of the Rh B was released within the first 8 hours. Scanning electron microscopy (SEM measurements performed on the optimized nanoparticles showed smooth surface and spherical shapes. No significant cytotoxic or apoptotic effects were observed on fetal cardiac myocytes after 24 and 48 hours of exposure with concentrations up to 200 µg/mL. The kinetic of the intracellular uptake was confirmed by confocal microscopy and cells took up PLGA NPs within the first hours. Interestingly, our data show an increase in the nanoparticles’ uptake with time of exposure. Taken together, we demonstrate for the first time that the designed NPs can be used as potential probes for drug delivery in cardiac myocytes.

  15. Surface characterisation of bioadhesive PLGA/chitosan microparticles produced by supercritical fluid technology.

    Science.gov (United States)

    Casettari, Luca; Castagnino, Enzo; Stolnik, Snjezana; Lewis, Andrew; Howdle, Steven M; Illum, Lisbeth

    2011-07-01

    Novel biodegradable and mucoadhesive PLGA/chitosan microparticles with the potential for use as a controlled release gastroretentive system were manufactured using supercritical CO(2) (scCO(2)) by the Particle Gas Saturated System (PGSS) technique (also called CriticalMix(TM)). Microparticles were produced from PLGA with the addition of mPEG and chitosan in the absence of organic solvents, surfactants and crosslinkers using the PGSS technique. Microparticle formulations were morphologically characterized by scanning electron microscope; particle size distribution was measured using laser diffraction. Microparticle surface was analyzed using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) to evaluate the presence of chitosan on the surface. Mucoadhesiveness of the microparticles was evaluated in vitro using a mucin assay employing two different kinds of mucin (Mucin type III and I-S) with different degrees of sialic acid contents, 0.5-1.5% and 9-17%, respectively. The two analytical surface techniques (XPS and ToF-SIMS) demonstrated the presence of the chitosan on the surface of the particles (polymer composition of the microparticles. The interaction between the mucin solutions and the PLGA/chitosan microparticles increased significantly with an increasing concentration of mucin and chitosan. The strong interaction of mucin with the chitosan present on the surface of the particles suggests a potential use of the mucoadhesive carriers for gastroretentive and oral controlled drug release.

  16. Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 delivery.

    Science.gov (United States)

    Nie, Hemin; Soh, Beng Wee; Fu, Yin-Chih; Wang, Chi-Hwa

    2008-01-01

    A protein loaded three-dimensional scaffold can be used for protein delivery and bone tissue regeneration. The main objective of this project was to develop recombinant human bone morphogenetic protein-2 (rhBMP-2) loaded poly(D,L-lactide-co-glycolide)/hydroxylapatite (PLGA/HAp) composite fibrous scaffolds through a promising fabrication technique, electrospinning. In vitro release of BMP-2 from these scaffolds, and the attachment ability and viability of marrow derived messenchymal stem cells (MSCs) in the presence of the scaffolds were investigated. The PLGA/HAp composite scaffolds developed in this study exhibit good morphology and it was observed that HAp nanoparticles were homogeneously dispersed inside PLGA matrix within the scaffold. The composite scaffolds allowed sustained (2-8 weeks) release of BMP-2 whose release rate was accelerated with increasing HAp content. It was also shown that BMP-2 protein successfully maintained its integrity and natural conformations after undergoing the process of electrospinning. Cell culture experiments showed that the encapsulation of HAp could enhance cell attachment to scaffolds and lower cytotoxicity. (c) 2007 Wiley Periodicals, Inc.

  17. Injectable PLGA based Colloidal Gels for Zero-order Dexamethasone Release in Cranial Defects

    Science.gov (United States)

    Wang, Qun; Wang, Jinxi; Lu, Qinghua; Detamore, Michael S.; Berkland, Cory

    2010-01-01

    Bone fillers have emerged as an alternative to the invasive surgery often required to repair skeletal defects. Achieving controlled release from these materials is desired for accelerating healing. Here, oppositely-charged Poly (d,l-lactic-co-glycolic acid) (PLGA) nanoparticles were used to create a cohesive colloidal gel as an injectable drug-loaded filler to promote healing in bone defects. The colloid self-assembled through electrostatic forces resulting in a stable 3-D network that may be extruded or molded to the desired shape. The colloidal gel demonstrated shear-thinning behavior due to the disruption of interparticle interactions as the applied shear force was increased. Once the external force was removed, the cohesive property of the colloidal gel was recovered. Similar reversibility and shear-thinning behavior were also observed in colloidal gels loaded with dexamethasone. Near zero-order dexamethasone release was observed over two months when the drug was encapsulated in PLGA nanoparticles and simply blending the drug with the colloidal gel showed similar kinetics for one month. Surgical placement was facilitated by the pseudoplastic material properties and in vivo observations demonstrated that the PLGA colloidal gels stimulated osteoconductive bone formation in rat cranial bone defects. PMID:20303585

  18. Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats

    Directory of Open Access Journals (Sweden)

    Changxing Wang

    2017-03-01

    Full Text Available Background/Aims: Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI. This study investigated the potential for poly (lactic-co-glycolic acid (PLGA complex inoculated with olfactory ensheathing cells (OECs to treat spinal cord injury in a rat model. Methods: OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR p75. The Basso, Beattie, and Bresnahan (BBB score, together with an inclined plane (IP test were used to detect functional recovery. Nissl staining along with the luxol fast blue (LFB staining were independently employed to illustrate morphological alterations. More so, immunofluorescence labeling of the glial fibrillary acidic protein (GFAP and the microtubule-associated protein-2 (MAP-2, representing astrocytes and neurons respectively, were investigated at time points of weeks 2 and 8 post-operation. Results: The findings showed enhanced locomotor recovery, axon myelination and better protected neurons post SCI when compared with either PLGA or untreated groups (P < 0.05. Conclusion: PLGA complexes inoculated with OECs improve locomotor functional recovery in transected spinal cord injured rat models, which is most likely due to the fact it is conducive to a relatively benevolent microenvironment, has nerve protective effects, as well as the ability to enhance remyelination, via a promotion of cell differentiation and inhibition of astrocyte formation.

  19. PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery.

    Science.gov (United States)

    Das, Sreemanti; Khuda-Bukhsh, Anisur Rahman

    2016-08-01

    Current treatment methods for melanoma have some limitations such as less target-specific action, severe side effects and resistance to drugs. Significant progress has been made in exploring novel drug delivery systems based on suitable biochemical mechanisms using nanoparticles ranging from 10 to 400 nm for drug delivery and imaging, utilizing their enhanced penetration and retention properties. Poly-lactide-co-glycolide (PLGA), a copolymer of poly-lactic acid and poly-glycolic acid, provides an ideally suited performance-based design for better penetration into skin cells, thereby having a greater potential for the treatment of melanoma. Moreover, encapsulation protects the drug from deactivation by biological reactions and interactions with biomolecules, ensuring successful delivery and bioavailability for effective treatment. Controlled and sustained delivery of drugs across the skin barrier that otherwise prohibits entry of larger molecules can be successfully made with adequately stable biocompatible nanocarriers such as PLGA for taking drugs through the small cutaneous pores permitting targeted deposition and prolonged drug action. PLGA is now being extensively used in photodynamic therapy and targeted therapy through modulation of signal proteins and drug-DNA interactions. Recent advances made on these nanomedicines and their advantages in the treatment of skin melanoma are highlighted and discussed in this review.

  20. PLGA-loaded nanomedicines in melanoma treatment: Future prospect for efficient drug delivery

    Directory of Open Access Journals (Sweden)

    Sreemanti Das

    2016-01-01

    Full Text Available Current treatment methods for melanoma have some limitations such as less target-specific action, severe side effects and resistance to drugs. Significant progress has been made in exploring novel drug delivery systems based on suitable biochemical mechanisms using nanoparticles ranging from 10 to 400 nm for drug delivery and imaging, utilizing their enhanced penetration and retention properties. Poly-lactide-co-glycolide (PLGA, a copolymer of poly-lactic acid and poly-glycolic acid, provides an ideally suited performance-based design for better penetration into skin cells, thereby having a greater potential for the treatment of melanoma. Moreover, encapsulation protects the drug from deactivation by biological reactions and interactions with biomolecules, ensuring successful delivery and bioavailability for effective treatment. Controlled and sustained delivery of drugs across the skin barrier that otherwise prohibits entry of larger molecules can be successfully made with adequately stable biocompatible nanocarriers such as PLGA for taking drugs through the small cutaneous pores permitting targeted deposition and prolonged drug action. PLGA is now being extensively used in photodynamic therapy and targeted therapy through modulation of signal proteins and drug-DNA interactions. Recent advances made on these nanomedicines and their advantages in the treatment of skin melanoma are highlighted and discussed in this review.

  1. Water Fibers

    CERN Document Server

    Douvidzon, Mark L; Martin, Leopoldo L; Carmon, Tal

    2016-01-01

    Fibers constitute the backbone of modern communication and are used in laser surgeries; fibers also genarate coherent X-ray, guided-sound and supercontinuum. In contrast, fibers for capillary oscillations, which are unique to liquids, were rarely considered in optofluidics. Here we fabricate fibers by water bridging an optical tapered-coupler to a microlensed coupler. Our water fibers are held in air and their length can be longer than a millimeter. These hybrid fibers co-confine two important oscillations in nature: capillary- and electromagnetic-. We optically record vibrations in the water fiber, including an audio-rate fundamental and its 3 overtones in a harmonic series, that one can hear in soundtracks attached. Transforming Micro-Electro-Mechanical-Systems [MEMS] to Micro-Electro-Capillary-Systems [MECS], boosts the device softness by a million to accordingly improve its response to minute forces. Furthermore, MECS are compatible with water, which is a most important liquid in our world.

  2. PLGA-based gene delivering nanoparticle enhance suppression effect of miRNA in HePG2 cells

    Directory of Open Access Journals (Sweden)

    Liang Gao

    2011-01-01

    Full Text Available Abstract The biggest challenge in the field of gene therapy is how to effectively deliver target genes to special cells. This study aimed to develop a new type of poly(D,L-lactide-co-glycolide (PLGA-based nanoparticles for gene delivery, which are capable of overcoming the disadvantages of polyethylenimine (PEI- or cationic liposome-based gene carrier, such as the cytotoxicity induced by excess positive charge, as well as the aggregation on the cell surface. The PLGA-based nanoparticles presented in this study were synthesized by emulsion evaporation method and characterized by transmission electron microscopy, dynamic light scattering, and energy dispersive spectroscopy. The size of PLGA/PEI nanoparticles in phosphate-buffered saline (PBS was about 60 nm at the optimal charge ratio. Without observable aggregation, the nanoparticles showed a better monodispersity. The PLGA-based nanoparticles were used as vector carrier for miRNA transfection in HepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity in HepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex shows better serum compatibility than commercial liposome. PLGA nanocomplexes obviously accumulate in tumor cells after transfection, which indicate that the complexes contribute to cellular uptake of pDNA and pronouncedly enhance the treatment effect of miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.

  3. Enhanced antitumor activity in A431 cells via encapsulation of 20(R)-ginsenoside Rg3 in PLGA nanoparticles.

    Science.gov (United States)

    Zhang, Shaozhi; Liu, Jiwei; Ge, Baojian; Du, Meiling; Fu, Li; Fu, Yushan; Yan, Qiu

    2017-10-01

    The objective of this study is to investigate the encapsulation of 20(R)-ginsenoside Rg3 (20(R)-Rg3) using polylactic-co-glycolic acid (PLGA) and promotion for its antitumor activity. Preparation and evaluation of the antitumor efficacy of 20(R)-Rg3-loaded PLGA nanoparticles were the first reported. The data will be helpful to apply 20(R)-Rg3 efficiently and broadly in new drug form development and clinical cancer treatment. The nanoparticles were prepared using emulsion and solvent evaporation methods. The uniform particle size and good dispersion were further confirmed by scanning electron microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to detect cell proliferation after 20(R)-Rg3-loaded PLGA nanoparticles treatment. Western blotting and immunofluorescent staining were used for observation of key proteins related with proliferation and apoptosis. Cell cycle and apoptosis were analyzed by flow cytometer technology. The results showed that the size of 20(R)-Rg3-loaded PLGA was 97.5 nm in diameter, and zeta potential was -28 mV detected by Malvern particle size analyzer. The encapsulation efficiency was 97.5%, and drug loading was 70.2% measured by high-performance liquid chromatography. The in vitro study showed that the encapsulated 20(R)-Rg3 was consecutively released and the release ratio reached to the highest value (19.36%) at the time point of 96 h. The encapsulated 20(R)-Rg3 significantly inhibited the proliferation and induced apoptosis in A431 cancer cells compared with the unencapsulated 20(R)-Rg3, control and PLGA alone. 20(R)-Rg3-loaded PLGA nanoparticles was well prepared and characterized. The antitumor activity was increased after PLGA encapsulation. The data will be beneficial to the development of new dosage forms of 20(R)-Rg3 and extensive application.

  4. PLGA-based gene delivering nanoparticle enhance suppression effect of miRNA in HePG2 cells

    Science.gov (United States)

    Feng Liang, Gao; Zhu, Yan Liang; Sun, Bo; Hu, Fei Hu; Tian, Tian; Li, Shu Chun; Xiao, Zhong Dang

    2011-07-01

    The biggest challenge in the field of gene therapy is how to effectively deliver target genes to special cells. This study aimed to develop a new type of poly( D, L-lactide-co-glycolide) (PLGA)-based nanoparticles for gene delivery, which are capable of overcoming the disadvantages of polyethylenimine (PEI)- or cationic liposome-based gene carrier, such as the cytotoxicity induced by excess positive charge, as well as the aggregation on the cell surface. The PLGA-based nanoparticles presented in this study were synthesized by emulsion evaporation method and characterized by transmission electron microscopy, dynamic light scattering, and energy dispersive spectroscopy. The size of PLGA/PEI nanoparticles in phosphate-buffered saline (PBS) was about 60 nm at the optimal charge ratio. Without observable aggregation, the nanoparticles showed a better monodispersity. The PLGA-based nanoparticles were used as vector carrier for miRNA transfection in HepG2 cells. It exhibited a higher transfection efficiency and lower cytotoxicity in HepG2 cells compared to the PEI/DNA complex. The N/P ratio (ratio of the polymer nitrogen to the DNA phosphate) 6 of the PLGA/PEI/DNA nanocomplex displays the best property among various N/P proportions, yielding similar transfection efficiency when compared to Lipofectamine/DNA lipoplexes. Moreover, nanocomplex shows better serum compatibility than commercial liposome. PLGA nanocomplexes obviously accumulate in tumor cells after transfection, which indicate that the complexes contribute to cellular uptake of pDNA and pronouncedly enhance the treatment effect of miR-26a by inducing cell cycle arrest. Therefore, these results demonstrate that PLGA/PEI nanoparticles are promising non-viral vectors for gene delivery.

  5. Probiotic With or Without Fiber Controls Body Fat Mass, Associated With Serum Zonulin, in Overweight and Obese Adults—Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Lotta K. Stenman

    2016-11-01

    Discussion: This clinical trial demonstrates that a probiotic product with or without dietary fiber controls body fat mass. B420 and LU + B420 also reduced waist circumference and food intake, whereas LU alone had no effect on the measured outcomes.

  6. Fabricación de compuesto de matriz epoxi reforzado con fibras largas de henequén orientadas aleatoriamente//Fabrication of a composite with epoxy matrix and henequen fibers as reinforcement long and with random orientation

    Directory of Open Access Journals (Sweden)

    Angel A. Rodríguez Soto

    2015-05-01

    Full Text Available Se obtuvo el procedimiento para la fabricación de un material compuesto con matriz de epoxi reforzado con fibras de henequén largas orientadas aleatoriamente. Fueron diseñados y elaborados seis moldes de tipo caja para la fabricación por el método de prensado en frío. Se produjeron 37 placas con 0, 6, 9, 12, 16, 22, 26 y 28 % de fibras en relación másica. La inclusión de los refuerzos fue manual y los materiales fabricados se sometieron a un proceso de cura a 70 ºC por 24 horas. Los especímenes obtenidos presentaron buena calidad estando libres de defectos y asegurando la distribución correcta de las fibras. El método de fabricación es adecuado para placas con pequeñas y grandes cantidades de fibra.Palabras claves: plásticos reforzados con fibras (PRF, fibras vegetales, compuesto de matriz termoestable, moldeo por compresión en frío.______________________________________________________________________________AbstractIs presented a procedure for the fabrication of the composite material with epoxy as matrix reinforced with henequen fibers, long and random. Was designed and fabricated six molds of box type for the manufacture of the plates using cold pressing procedure. Was make 37 plates with 0, 6, 9, 12, 16, 22, 26 and 28 % of fiber´s inclusions in mass relation. The inclusion of the reinforcements was making manually and the obtained materials was submitted to a process of cure bellow 70ºC during 24 hours. The obtained specimens showed a good quality being free of defects and guarantee the correct distribution of the fibers. The fabrication method is de adequate for plates with small and large quantities of fiber.Key words: fiber reinforced plastics (FRP, natural fibers, composite with thermoset matrix, cold compression molded.

  7. A biomimetic approach to active self-microencapsulation of proteins in PLGA.

    Science.gov (United States)

    Shah, Ronak B; Schwendeman, Steven P

    2014-12-28

    A biomimetic approach to organic solvent-free microencapsulation of proteins based on the self-healing capacity of poly (DL)-lactic-co-glycolic acid (PLGA) microspheres containing glycosaminoglycan-like biopolymers (BPs), was examined. To screen BPs, aqueous solutions of BP [high molecular weight dextran sulfate (HDS), low molecular weight dextran sulfate (LDS), chondroitin sulfate (CS), heparin (HP), hyaluronic acid (HA), chitosan (CH)] and model protein lysozyme (LYZ) were combined in different molar and mass ratios, at 37 °C and pH7. The BP-PLGA microspheres (20-63 μm) were prepared by a double water-oil-water emulsion method with a range of BP content, and trehalose and MgCO3 to control microclimate pH and to create percolating pores for protein. Biomimetic active self-encapsulation (ASE) of proteins [LYZ, vascular endothelial growth factor165 (VEGF) and fibroblast growth factor (FgF-20)] was accomplished by incubating blank BP-PLGA microspheres in low concentration protein solutions at ~24 °C, for 48 h. Pore closure was induced at 42.5 °C under mild agitation for 42h. Formulation parameters of BP-PLGA microspheres and loading conditions were studied to optimize protein loading and subsequent release. LDS and HP were found to bind >95% LYZ at BP:LYZ>0.125 w/w, whereas HDS and CS bound >80% LYZ at BP:LYZ of 0.25-1 and 2% w/w of LYZ). Sulfated BP-PLGA microspheres were capable of loading LYZ (~2-7% w/w), VEGF (~4% w/w), and FgF-20 (~2% w/w) with high efficiency. Protein loading was found to be dependent on the loading solution concentration, with higher protein loading obtained at higher loading solution concentration within the range investigated. Loading also increased with content of sulfated BP in microspheres. Release kinetics of proteins was evaluated in-vitro with complete release media replacement. Rate and extent of release were found to depend upon volume of release (with non-sink conditions observed 90% of protein being enzymatically active. Nearly

  8. Enhanced cell proliferation and osteogenic differentiation in electrospun PLGA/hydroxyapatite nanofibre scaffolds incorporated with graphene oxide.

    Directory of Open Access Journals (Sweden)

    Chuan Fu

    Full Text Available One of the goals of bone tissue engineering is to mimic native ECM in architecture and function, creating scaffolds with excellent biocompatibility, osteoinductive ability and mechanical properties. The aim of this study was to fabricate nanofibrous matrices by electrospinning a blend of poly (L-lactic-co-glycolic acid (PLGA, hydroxyapatite (HA, and grapheme oxide (GO as a favourable platform for bone tissue engineering. The morphology, biocompatibility, mechanical properties, and biological activity of all nanofibrous matrices were compared. The data indicate that the hydrophilicity and protein adsorption rate of the fabricated matrices were significantly increased by blending with a small amount of HA and GO. Furthermore, GO significantly boosted the tensile strength of the nanofibrous matrices, and the PLGA/GO/HA nanofibrous matrices can serve as mechanically stable scaffolds for cell growth. For further test in vitro, MC3T3-E1 cells were cultured on the PLGA/HA/GO nanofbrous matrices to observe various cellular activities and cell mineralization. The results indicated that the PLGA/GO/HA nanofibrous matrices significantly enhanced adhesion, and proliferation in MCET3-E1 cells and functionally promoted alkaline phosphatase (ALP activity, the osteogenesis-related gene expression and mineral deposition. Therefore, the PLGA/HA/GO composite nanofibres are excellent and versatile scaffolds for applications in bone tissue regeneration.

  9. Scaffolds for bone tissue engineering fabricated from two different materials by the rapid prototyping technique: PCL versus PLGA.

    Science.gov (United States)

    Park, So Hee; Park, Dae Sung; Shin, Ji Won; Kang, Yun Gyeong; Kim, Hyung Keun; Yoon, Taek Rim; Shin, Jung-Woog

    2012-11-01

    Three dimensional tissue engineered scaffolds for the treatment of critical defect have been usually fabricated by salt leaching or gas forming technique. However, it is not easy for cells to penetrate the scaffolds due to the poor interconnectivity of pores. To overcome these current limitations we utilized a rapid prototyping (RP) technique for fabricating tissue engineered scaffolds to treat critical defects. The RP technique resulted in the uniform distribution and systematic connection of pores, which enabled cells to penetrate the scaffold. Two kinds of materials were used. They were poly(ε-caprolactone) (PCL) and poly(D, L-lactic-glycolic acid) (PLGA), where PCL is known to have longer degradation time than PLGA. In vitro tests supported the biocompatibility of the scaffolds. A 12-week animal study involving various examinations of rabbit tibias such as micro-CT and staining showed that both PCL and PLGA resulted in successful bone regeneration. As expected, PLGA degraded faster than PCL, and consequently the tissues generated in the PLGA group were less dense than those in the PCL group. We concluded that slower degradation is preferable in bone tissue engineering, especially when treating critical defects, as mechanical support is needed until full regeneration has occurred.

  10. Stabilization and encapsulation of recombinant human erythropoietin into PLGA microspheres using human serum albumin as a stabilizer.

    Science.gov (United States)

    He, Jintian; Feng, Meiyan; Zhou, Xianglian; Ma, Shufen; Jiang, Yang; Wang, Ying; Zhang, Hongxia

    2011-09-15

    The aim of this study was to prepare recombinant human erythropoietin (rhEPO) loaded poly(lactic-co-glycolic acid) (PLGA) microspheres using human serum albumin (HSA) as a stabilizer. Prior to encapsulation, the rhEPO-HSA mixture microparticles were fabricated using a modified freezing-induced phase separation method. The microparticles were subsequently encapsulated into PLGA microspheres. Process optimization revealed that the polymer concentration in the organic phase and the sodium chloride (NaCl) concentration in the outer water phase of the s/o/w emulsion played critical roles in determining the properties of the resultant microspheres. An in vitro release test showed that rhEPO was released from PLGA microspheres in a sustained manner up to 30 days. A single injection of rhEPO-loaded PLGA microspheres in Sprague-Dawley rats resulted in elevated hemoglobin and red blood cell concentrations for about 33 days. The stability of the rhEPO within the PLGA microspheres was systematically investigated by size-exclusion high-performance liquid chromatography (SEC-HPLC), SDS-PAGE, western blot and in vivo biological activity assay. The stability of rhEPO released from rhEPO-loaded microspheres was also examined by western blot. The results suggested that the integrity of rhEPO was successfully protected during the encapsulation process and the release period from polymeric matrices. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang Seok; Hong, Suck Won; Han, Dong Wook; Kim, Chun Tae; Oh, Jin Woo [Pusan National University, Busan (Korea, Republic of)

    2015-01-15

    Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic-co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

  12. RGD peptide-displaying M13 bacteriophage/PLGA nanofibers as cell-adhesive matrices for smooth muscle cells

    Science.gov (United States)

    Shin, Yong Cheol; Lee, Jong Ho; Jin, Oh Seong; Lee, Eun Ji; Jin, Lin Hua; Kim, Chang-Seok; Hong, Suck Won; Han, Dong-Wook; Kim, Chuntae; Oh, Jin-Woo

    2015-01-01

    Extracellular matrices (ECMs) are network structures that play an essential role in regulating cellular growth and differentiation. In this study, novel nanofibrous matrices were fabricated by electrospinning M13 bacteriophage and poly(lactic- co-glycolic acid) (PLGA) and were shown to be structurally and functionally similar to natural ECMs. A genetically-engineered M13 bacteriophage was constructed to display Arg-Gly-Asp (RGD) peptides on its surface. The physicochemical properties of RGD peptide-displaying M13 bacteriophage (RGD-M13 phage)/PLGA nanofibers were characterized by using scanning electron microscopy and Fourier-transform infrared spectroscopy. We used immunofluorescence staining to confirm that M13 bacteriophages were homogenously distributed in RGD-M13 phage/PLGA matrices. Furthermore, RGD-M13 phage/PLGA nanofibrous matrices, having excellent biocompatibility, can enhance the behaviors of vascular smooth muscle cells. This result suggests that RGD-M13 phage/PLGA nanofibrous matrices have potentials to serve as tissue engineering scaffolds.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  14. A high-glycemic index, low-fiber breakfast affects the postprandial plasma glucose, insulin, and ghrelin responses of patients with type 2 diabetes in a randomized clinical trial.

    Science.gov (United States)

    Silva, Flávia M; Kramer, Caroline K; Crispim, Daisy; Azevedo, Mirela J

    2015-04-01

    Meals with a low glycemic index (GI) and rich in fiber could be beneficial with regard to postprandial metabolic profile and satiety. The aim of this study was to investigate the effect of 4 breakfasts with a different GI and amount of fiber on postprandial plasma glucose, insulin, and appetite in patients with type 2 diabetes. This randomized 4-intervention crossover trial included 14 patients [7 men; ages 65.8 ± 5.2 y; glycated hemoglobin: 6.6 ± 0.9%; BMI (in kg/m(2)): 27.2 ± 3.1]. Dietary interventions were as follows: breakfasts with a high GI (60.4 ± 0.1%) and high fiber (6.0 ± 0.3 g) (HGI-HF), a high GI (60.9 ± 1.7%) and low fiber (2.5 ± 0.4 g) (HGI-LF), a low GI (37.7 ± 0.1%) and high fiber (6.2 ± 0.3 g) (LGI-HF), and a low GI (39.8 ± 1.3%) and low fiber (2.0 ± 0.1 g) (LGI-LF). Plasma glucose, insulin, and total ghrelin were evaluated postprandially (0-180 min). A visual analog scale was used to assess appetite. Data were analyzed by generalized estimating equations and post hoc least significant difference (LSD) tests. Data are reported as means ± SDs. The area under the curve (AUC) [mean (95% CI); P for LSD tests] for plasma glucose (mmol/L × min) was higher after patients consumed the HGI-LF breakfast [9.62 (8.39, 10.84)] than after the LGI-HF breakfast [8.95 (7.71, 10.18)] (P ≤ 0.05). Insulin AUC (μIU/mL × min) after patients consumed the HGI-LF meal [65.72 (38.24, 93.19)] was higher than after the HGI-HF meal [57.24 (32.44, 82.04)] (P ≤ 0.05). The other observed difference was higher insulin AUC after the consumption of the LGI-LF breakfast [61.54 (36.61, 86.48)] compared with the AUC after the LGI-HF breakfast [54.16 (31.43, 76.88)] (P ≤ 0.05). Plasma ghrelin decreased in comparison with baseline only after patients consumed the LGI-HF and LGI-LF breakfasts (P ≤ 0.05). Subjective satiety did not differ between breakfasts. Plasma glucose, insulin, and ghrelin responses were least favorable when patients with type 2 diabetes

  15. An Overview of Poly(lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering

    Science.gov (United States)

    Gentile, Piergiorgio; Chiono, Valeria; Carmagnola, Irene; Hatton, Paul V.

    2014-01-01

    Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function. PMID:24590126

  16. Graphene Oxide Hybridized nHAC/PLGA Scaffolds Facilitate the Proliferation of MC3T3-E1 Cells

    Science.gov (United States)

    Liang, Chunyong; Luo, Yongchao; Yang, Guodong; Xia, Dan; Liu, Lei; Zhang, Xiaomin; Wang, Hongshui

    2018-01-01

    Biodegradable porous biomaterial scaffolds play a critical role in bone regeneration. In this study, the porous nano-hydroxyapatite/collagen/poly(lactic-co-glycolic acid)/graphene oxide (nHAC/PLGA/GO) composite scaffolds containing different amount of GO were fabricated by freeze-drying method. The results show that the synthesized scaffolds possess a three-dimensional porous structure. GO slightly improves the hydrophilicity of the scaffolds and reinforces their mechanical strength. Young's modulus of the 1.5 wt% GO incorporated scaffold is greatly increased compared to the control sample. The in vitro experiments show that the nHAC/PLGA/GO (1.5 wt%) scaffolds significantly cell adhesion and proliferation of osteoblast cells (MC3T3-E1). This present study indicates that the nHAC/PLGA/GO scaffolds have excellent cytocompatibility and bone regeneration ability, thus it has high potential to be used as scaffolds in the field of bone tissue engineering.

  17. Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Marcilia P. Costa

    2016-07-01

    Full Text Available Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL in poly(d,l-lactide-co-glycolide (PLGA microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NβL on PLGA. Finally, the cytotoxic activity of NβL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

  18. A Fractional Factorial Design to Study the Effect of Process Variables on the Preparation of Hyaluronidase Loaded PLGA Nanoparticles

    Directory of Open Access Journals (Sweden)

    K. Narayanan

    2014-01-01

    Full Text Available The present study was initiated to understand the effect of PLGA concentration, PVA concentration, internal-external phase ratio, homogenization speed, and homogenization time on mean particle size, zeta potential, and percentage drug encapsulation using fractional factorial design. Using PLGA (50-50 as the carrier, hyaluronidase loaded PLGA nanoparticles were prepared using double emulsion solvent evaporation technique. The particle size was analyzed by dynamic light scattering technique and protein content by Lowry method. The study showed that homogenization speed as an independent variable had maximum effect on particle size and zeta potential. Internal-external phase volume ratio had maximum effect on drug encapsulation. Mean particle size also had high dependency on the combined effect of PVA concentration and phase volume ratio. Using fractional factorial design particle size of <400 nm, zeta potential of <−30 mV, and percentage encapsulation of 15–18% were achieved.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    ) microparticles prepared by spray-drying. METHODS: Binary mixtures of acetone and methanol at different molar ratios were applied to dissolve celecoxib and PLGA prior to spray-drying. The resulting microparticles were characterized with respect to morphology, texture, surface chemistry, solid state properties...... and drug release profile. The evaporation profiles of the feed solutions were investigated using thermogravimetric analysis (TGA). RESULTS: Spherical PLGA microparticles were obtained, irrespectively of the solvent composition. The particle size and surface chemistry were highly dependent on the solvent...... power of the feed solution. An obvious burst release was observed for the microparticles prepared by the feed solutions with the highest amount of poor solvent for PLGA. TGA analysis revealed distinct drying kinetics for the binary mixtures. CONCLUSIONS: The particle formation process is mainly governed...

  20. In vitro and in vivo evaluation of calcium phosphate composite scaffolds containing BMP-VEGF loaded PLGA microspheres for the treatment of avascular necrosis of the femoral head

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hao-Xuan [Department of Orthopedics, Shandong University Qilu Hospital, Jinan, Shandong (China); Zhang, Xiu-Ping [School of Public Health, Fudan University, Shanghai (China); Xiao, Gui-Yong [School of Materials Science and Engineering, Shandong University, Jinan, Shandong (China); Key Laboratory for Liquid–Solid Structural Evolution and Processing of Materials, Ministry of Education, Shandong University, Jinan, Shandong (China); Hou, Yong; Cheng, Lei; Si, Meng; Wang, Shuai-Shuai [Department of Orthopedics, Shandong University Qilu Hospital, Jinan, Shandong (China); Li, Yu-Hua, E-mail: qiluyuhua@126.com [Department of Orthopedics, Shandong University Qilu Hospital, Jinan, Shandong (China); Nie, Lin, E-mail: hoho05@126.com [Department of Orthopedics, Shandong University Qilu Hospital, Jinan, Shandong (China)

    2016-03-01

    Avascular necrosis of the femoral head (ANFH) is difficult to treat due to high pressure and hypoxia, and reduced levels of growth factors such as bone morphogenetic protein (BMP), and vascular endothelial growth factor (VEGF). We generated a novel calcium phosphate (CPC) composite scaffold, which contains BMP-VEGF-loaded poly-lactic-co-glycolic acid (PLGA) microspheres (BMP-VEGF-PLGA-CPC). The BMP-VEGF-loaded microspheres have an encapsulation efficiency of 89.15% for BMP, and 78.55% for VEGF. The BMP-VEGF-PLGA-CPC scaffold also demonstrated a porosity of 62% with interconnected porous structures, and pore sizes of 219 μm and compressive strength of 6.60 MPa. Additionally, bone marrow mesenchymal stem cells (BMSCs) were seeded on scaffolds in vitro. Further characterization showed that the BMP-VEGF-PLGA-CPC scaffolds were biocompatible and enhanced osteogenesis and angiogenesis in vitro. Using a rabbit model of ANFH, BMP-VEGF-PLGA-CPC scaffolds were implanted into the bone tunnels of core decompression in the femoral head for 6 and 12 weeks. Radiographic and histological analysis demonstrated that the BMP-VEGF-PLGA-CPC scaffolds exhibited good biocompatibility, and osteogenic and angiogenic activity in vivo. These results indicate that the BMP-VEGF-PLGA-CPC scaffold may improve the therapeutic effect of core decompression surgery and be used as a treatment for ANFH. - Highlights: • BMP-VEGF-PLGA-CPC scaffolds were biocompatible and enhanced osteogenesis and angiogenesis in vitro. • BMP-VEGF-PLGA-CPC scaffolds exhibited good biocompatibility, and osteogenic and angiogenic activity in vivo. • BMP-VEGF-PLGA-CPC scaffolds provided a new approach for the treatment of avascular necrosis of the femoral head (ANFH).

  1. New Polylactic Acid Composites Reinforced with Artichoke Fibers

    OpenAIRE

    Luigi Botta; Vincenzo Fiore; Tommaso Scalici; Antonino Valenza; Roberto Scaffaro

    2015-01-01

    In this work, artichoke fibers were used for the first time to prepare poly(lactic acid) (PLA)-based biocomposites. In particular, two PLA/artichoke composites with the same fiber loading (10% w/w) were prepared by the film-stacking method: the first one (UNID) reinforced with unidirectional long artichoke fibers, the second one (RANDOM) reinforced by randomly-oriented long artichoke fibers. Both composites were mechanically characterized in tensile mode by quasi-static and dynamic mechanica...

  2. Sustained delivery of rhBMP-2 via PLGA microspheres: cranial bone regeneration without heterotopic ossification or craniosynostosis

    Science.gov (United States)

    Wink, Jason D.; Gerety, Patrick A.; Sherif, Rami D.; Lim, Youngshin; A.Clarke, Nadya; Rajapakse, Chamith S.; Nah, Hyun-Duck; Taylor, Jesse A.

    2014-01-01

    Background Commercially available recombinant human bone morphogenetic protein 2 (rhBMP2) has demonstrated efficacy in bone regeneration, but not without significant side effects. In this study, we utilize rhBMP2 encapsulated in PLGA microspheres (PLGA-rhBMP2) placed in a rabbit cranial defect model to test whether low-dose, sustained, delivery can effectively induce bone regeneration. Methods rhBMP2 was encapsulated in 15% poly (lactic-co-glycolic acid), using a double emulsion, solvent extraction/evaporation technique, and its release kinetics and bioactivity were tested. Two critical-size defects (10mm) were created in the calvarium of New Zealand White rabbits (5-7 mos of age, M/F) and filled with a collagen scaffold containing one of four groups: 1) no implant, 2) collagen scaffold only, 3) PLGA-rhBMP2(0.1ug/implant), or 4) free rhBMP2 (0.1ug/implant). After 6 weeks, the rabbits were sacrificed and defects were analyzed by μCT, histology, and finite element analysis. Results RhBMP2 delivered via bioactive PLGA microspheres resulted in higher volumes and surface area coverage of new bone than an equal dose of free rhBMP2 by μCT and histology (p=0.025, 0.025). FEA indicated that the mechanical competence using the regional elastic modulus did not differ with rhBMP2 exposure (p=0.70). PLGA-rhBMP2 did not demonstrate heterotopic ossification, craniosynostosis, or seroma formation. Conclusions Sustained delivery via PLGA microspheres can significantly reduce the rhBMP2 dose required for de novo bone formation. Optimization of the delivery system may be a key to reduce the risk for recently reported rhBMP2 related adverse effects. Level of Evidence Animal Study PMID:24622573

  3. Antigen-specific killer polylactic-co-glycolic acid (PLGA) microspheres can prolong alloskin graft survival in a murine model.

    Science.gov (United States)

    Wang, Wei; Fang, Kun; Wang, Xiaobing; Li, Miaochen; Wu, You; Chen, Feng; Shahzad, Khawar Ali; Gu, Ning; Shen, Chuanlai

    2015-01-01

    The strategy of specifically depleting antigen-specific T cells can potentially be used for the treatment of allograft rejection and autoimmunity because it does not suppress the overall immune systems. In this study, we generated killer polylactic-co-glycolic acid (PLGA) microspheres by covalently coupling major histocompatibility complex (MHC) class I antigens and apoptosis-inducing anti-Fas monoclonal antibody (mAb) onto PLGA microspheres. A modified double-emulsion method was used for the preparation of cell-sized PLGA microspheres. H-2K(b)/peptide monomers were generated in-house and analyzed through flow cytometry. The killer PLGA microspheres were administered intravenously into BALB/c mice (H-2K(d)) that had previously been grafted with skin squares from C57BL/6 mice (H-2K(b)). Tumor cell challenge and third-party mixed lymphocyte culture were used to assess the general immune functions of host. The alloskin graft survival was prolonged by 4 days. The killer PLGA microspheres could specifically deplete the H-2K(b) alloantigen-reactive CD8(+) T cells that infiltrated into the alloskin graft but not CD4(+) T cells, without impairment of host overall immune function. Here, we initially report that PLGA microspheres, which have been widely used as medicine-delivering carriers, were used to prepare antigen-specific killer complexes and treat allograft rejection. Our data highlight the therapeutic potential of this biocompatible and biodegradable antigen-specific killer effector for the treatment of allograft rejection and autoimmune disease.

  4. Comparison of three different methods for effective introduction of platelet-rich plasma on PLGA woven mesh.

    Science.gov (United States)

    Lee, Ji-Hye; Nam, Jinwoo; Kim, Hee Joong; Yoo, Jeong Joon

    2015-03-11

    For successful tissue regeneration, effective cell delivery to defect site is very important. Various types of polymer biomaterials have been developed and applied for effective cell delivery. PLGA (poly lactic-co-glycolic acid), a synthetic polymer, is a commercially available and FDA approved material. Platelet-rich plasma (PRP) is an autologous growth factor cocktail containing various growth factors including PDGF, TGFβ-1 and BMPs, and has shown positive effects on cell behaviors. We hypothesized that PRP pretreatment on PLGA mesh using different methods would cause different patterns of platelet adhesion and stages which would modulate cell adhesion and proliferation on the PLGA mesh. In this study, we pretreated PRP on PLGA using three different methods including simple dripping (SD), dynamic oscillation (DO) and centrifugation (CE), then observed the amount of adhered platelets and their activation stage distribution. The highest amount of platelets was observed on CE mesh and calcium treated CE mesh. Moreover, calcium addition after PRP coating triggered dramatic activation of platelets which showed large and flat morphologies of platelets with rich fibrin networks. Human chondrocytes (hCs) and human bone marrow stromal cells (hBMSCs) were next cultured on PRP-pretreated PLGA meshes using different preparation methods. CE mesh showed a significant increase in the initial cell adhesion of hCs and proliferation of hBMSCs compared with SD and DO meshes. The results demonstrated that the centrifugation method can be considered as a promising coating method to introduce PRP on PLGA polymeric material which could improve cell-material interaction using a simple method.

  5. Graphene oxide-stimulated myogenic differentiation of C2C12 cells on PLGA/RGD peptide nanofiber matrices

    Science.gov (United States)

    Shin, Y. C.; Lee, J. H.; Kim, M. J.; Hong, S. W.; Oh, J.-W.; Kim, C.-S.; Kim, B.; Hyun, J. K.; Kim, Y.-J.; Han, D.-W.

    2015-07-01

    During the last decade, much attention has been paid to graphene-based nanomaterials because they are considered as potential candidates for biomedical applications such as scaffolds for tissue engineering and substrates for the differentiation of stem cells. Until now, electrospun matrices composed of various biodegradable copolymers have been extensively developed for tissue engineering and regeneration; however, their use in combination with graphene oxide (GO) is novel and challenging. In this study, nanofiber matrices composed of poly(lactic-co-glycolic acid, PLGA) and M13 phage with RGD peptide displayed on its surface (RGD peptide-M13 phage) were prepared as extracellular matrix (ECM)-mimicking substrates. RGD peptide is a tripeptide (Arg-Gly-Asp) found on ECM proteins that promotes various cellular behaviors. The physicochemical properties of PLGA and RGD peptide-M13 phage (PLGA/RGD peptide) nanofiber matrices were characterized by atomic force microscopy, Fourier-transform infrared spectroscopy and thermogravimetric analysis. In addition, the growth of C2C12 mouse myoblasts on the PLGA/RGD peptide matrices was examined by measuring the metabolic activity. Moreover, the differentiation of C2C12 mouse myoblasts on the matrices when treated with GO was evaluated. The cellular behaviors, including growth and differentiation of C2C12 mouse myoblasts, were substantially enhanced on the PLGA/RGD peptide nanofiber matrices when treated with GO. Overall, these findings suggest that the PLGA/RGD peptide nanofiber matrices can be used in combination with GO as a novel strategy for skeletal tissue regeneration.

  6. Effect of n-HA with different surface-modified on the properties of n-HA/PLGA composite

    Science.gov (United States)

    Liuyun, Jiang; Chengdong, Xiong; Dongliang, Chen; Lixin, Jiang; xiubing, Pang

    2012-10-01

    Three different surface modification methods for nano-hydroxyapatite (n-HA) of stearic acid, grafted with L-lactide, combining stearic acid and surface-grafting L-lactic were adopted, respectively. The surface modification reaction and the effect of different methods were evaluated by Fourier transformation infrared (FTIR), X-ray photoelectron spectra (XPS), thermal gravimetric analysis (TGA), transmission electron microscopy (TEM). The results showed that n-HA surfaces were all successful modified, and the modification method of combining stearic acid and surface-grafting L-lactic had the greatest grafting amount and the best dispersion among the three modification methods. Then, the n-HA with three different surface modification and unmodified n-HA were introduced into PLGA, respectively, and a serials of n-HA/PLGA composites with 3% n-HA amount in weight were prepared by solution mixing, and the properties of n-HA/PLGA composites were also investigated by electromechanical universal tester and scanning electron microscope(SEM), comparing with PLGA. The results showed that the n-HA/PLGA composite with the n-HA surface modified by combining stearic acid and surface-grafting L-lactic had the highest bending strength and the best dispersion and interfacial adhesion among the three different modification methods, suggesting the surface modification of combining stearic acid and surface-grafting L-lactic was the most ideal method in this study, which has a great deal of enhancement of bending strength than PLGA, and it would be potential to be used in the field of bone fracture internal fixation in future.

  7. Carboplatin loaded Surface modified PLGA nanoparticles: Optimization, characterization, and in vivo brain targeting studies.

    Science.gov (United States)

    Jose, S; Juna, B C; Cinu, T A; Jyoti, H; Aleykutty, N A

    2016-06-01

    The carboplatin (CP) loaded poly-lactide-co-glycolide (PLGA) nanoparticles (NPs) were formulated by modified solvent evaporation method. Its surface modification is done by 1% polysorbate80 (P80) to improve their entry into the brain after intraperitoneal administration (i.p) via receptor-mediated pathways. A formulation with maximum entrapment efficiency and minimal particle size was optimized by central composite design (CCD) based on mean particle size, and entrapment efficiencies as responses. The optimized formulation was characterized by mean particle size, entrapment efficiency, zeta potential, Fourier transform infrared (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) analysis. The surface modified NPs were analysed for mean particle, zeta potential, FTIR, and in vitro release studies. The spherical particles with mean particle size 161.9nm, 162.4nm and zeta potential value of -26.5, -23.9 were obtained for unmodified and surface modified NPs respectively. The in vitro release experiments of the surface modified PLGA NPs exhibited sustained release for more than 48h, which was in accordance with Higuchi's equation with Fickian diffusion-based release mechanism. The in vivo bio distribution of P80 coated CP loaded PLGA NPs was compared with CP solution, and CP loaded NPs, in adult wistar rats. In the brain, compared with CP solution, both types of NPs especially NPs coated with P80 increased the concentration of carboplatin by 3.27 fold. All these results suggest that the developed formulation may improve the targeted therapy for malignant brain tumors in future. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Wenjia Guo

    2015-10-01

    Full Text Available The purpose of this study was to develop a PLGA microspheres-based donepezil (DP formulation which was expected to sustain release of DP for one week with high encapsulation efficiency (EE. DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared successfully with average diameter of 30 µm, drug loading of 15.92 ± 0.31% and EE up to 78.79 ± 2.56%. Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface. Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres. The Tg of PLGA was increased with the addition of DP. The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model, which suggested the diffusion governing release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained. The results suggest the potential use of DP microspheres for treatment of Alzheimer's disease over long periods.

  9. A controlled, randomized, double-blind trial to evaluate the effect of a supplement of cocoa husk that is rich in dietary fiber on colonic transit in constipated pediatric patients.

    Science.gov (United States)

    Castillejo, Gemma; Bulló, Mònica; Anguera, Anna; Escribano, Joaquin; Salas-Salvadó, Jordi

    2006-09-01

    Although a diet that is rich in fiber is widely recommended for preventing and treating constipation, the efficacy of fiber supplements have not been tested sufficiently in children. Our aim with this pilot study was to evaluate if fiber supplementation is beneficial for the treatment of children with idiopathic chronic constipation. Using a parallel, randomized, double-blind, controlled trial, we conducted an interventional study to evaluate the efficacy of a supplement of cocoa husk rich in dietary fiber on intestinal transit time and other indices of constipation in children with constipation. After screening, the patients were randomly allocated to receive, for a period of 4 weeks, either a cocoa husk supplement or placebo plus standardized toilet training procedures. Before and after 4 weeks of treatment, we (1) performed anthropometry, a physical examination, and routine laboratory measurements, (2) determined total and segmental colonic transit time, (3) evaluated bowel movement habits and stool consistency using a diary, and (4) received a subjective evaluation from the parents regarding the efficacy of the treatment. The main variable for verifying the efficacy of the treatment was the total colonic transit time. Fifty-six chronically constipated children were randomly assigned into the study, but only 48 children completed it. These children, who were aged between 3 and 10 years, had a diagnosis of chronic idiopathic constipation. With respect to total, partial colon, and rectum transit time, there seemed to be a trend, although statistically nonsignificant, toward faster transit times in the cocoa husk group than in the placebo group. When we analyzed the evolution of the intestinal transit time throughout the study of children whose total basal intestinal transit time was > 50th percentile, significant differences were observed between the groups. The total transit time decreased by 45.4 +/- 38.4 hours in the cocoa husk group and by 8.7 +/- 28.9 hours

  10. Effect of the Freezing Step in the Stability and Bioactivity of Protein-Loaded PLGA Nanoparticles Upon Lyophilization

    DEFF Research Database (Denmark)

    Fonte, Pedro; Andrade, Fernanda; Azevedo, Cláudia

    2016-01-01

    PURPOSE: The freezing step in lyophilization is the most determinant for the quality of biopharmaceutics. Using insulin as model of therapeutic protein, our aim was to evaluate the freezing effect in the stability and bioactivity of insulin-loaded PLGA nanoparticles. The performance of trehalose....... The insulin structure maintenance was evident and close to 90%. Trehalose co-encapsulated insulin-loaded PLGA nanoparticles demonstrated enhanced hypoglycemic effect, comparatively to nanoparticles without cryoprotectant and added with trehalose, due to a superior insulin stabilization and bioactivity...

  11. Preparation and investigation of P28GST-loaded PLGA microparticles for immunomodulation of experimental colitis.

    Science.gov (United States)

    Thi, T H Hoang; Priemel, P A; Karrout, Y; Driss, V; Delbeke, M; Dendooven, A; Flament, M P; Capron, M; Siepmann, J

    2017-11-25

    The aim of this work was to prepare and characterize (in vitro and in vivo) PLGA-based microparticles loaded with an enzymatic protein derived from the helminth parasite Schistosoma haematobium: glutathione S-transferase P28GST (P28GST). This protein is not only a promising candidate vaccine against schistosomiasis, it also exhibits interesting immunomodulating effects, which can be helpful for the regulation of inflammatory diseases. Helminths express a regulatory role on intestinal inflammation, and immunization by P28GST has recently been shown to be as efficient as infection to reduce inflammation in a murine colitis model. As an alternative to the combination with a classical adjuvant, long acting P28GST microparticles were prepared in order to induce colitis prevention. PLGA was used as biodegradable and biocompatible matrix former, and a W/O/W emulsion/solvent extraction technique applied to prepare different types of microparticles. The effects of key formulation and processing parameters (e.g., the polymer molecular weight, drug loading, W/O/W phase volumes and stirring rates of the primary/secondary emulsions) on the systems' performance were studied. Microparticles providing about constant P28GST release during several weeks were selected and their effects in an experimental model of colitis evaluated. Mice received P28GST-loaded or P28GST-free PLGA microparticles (s.c.) on Day 0, and optionally also on Days 14 and 28. Colitis was induced on Day 35, the animals were sacrificed on Day 37. Interestingly, the Wallace score (being a measure of the severity of the inflammation) was significantly lower in mice treated with P28GST microparticles compared to placebo after 1 or 3 injections. As immunogenicity markers, increased anti-P28GST IgG levels were detected after three P28GST PLGA microparticle injections, but not in the control groups. Thus, the proposed microparticles offer an interesting potential for the preventive treatment of experimental colitis

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

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kedong, E-mail: kedongsong@dlut.edu.cn [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Liu, Yingchao [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Macedo, Hugo M. [Biological Systems Engineering Laboratory, Department of Chemical Engineering, Department of Chemical Engineering, South Kensington Campus, London SW7 2AZ (United Kingdom); Jiang, Lili; Li, Chao; Mei, Guanyu [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China); Liu, Tianqing, E-mail: liutq@dlut.edu.cn [Dalian R and D Center for Stem Cell and Tissue Engineering, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024 (China)

    2013-04-01

    Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27–55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99 ± 2.51) %, (89.66 ± 0.66) % and (73.77 ± 3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24 ± 0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44 ± 1.81) × 10{sup −2} mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a

  13. The effects of the combination of egg and fiber on appetite, glycemic response and food intake in normal weight adults - a randomized, controlled, crossover trial.

    Science.gov (United States)

    Bonnema, Angela L; Altschwager, Deena K; Thomas, William; Slavin, Joanne L

    2016-09-01

    This study evaluated appetite and glycemic effects of egg-based breakfasts, containing high and moderate protein (30 g protein and 20 g protein +7 g fiber, respectively) compared to a low-protein cereal breakfast (10 g protein) examined in healthy adults (N = 48; age 24 ± 1 yr; BMI 23 ± 1 kg/m(2); mean ± SE). Meals provided 390 kcal/serving and equal fat content. Food intake was measured at an ad libitum lunch meal and blood glucose response was measured. Visual analog scales (VAS) were used to assess hunger, satisfaction, fullness, and prospective food intake. The egg-based breakfast meal with high protein produced greater overall satiety (p glycemic response (p < 0.005) and food intake (p < 0.05) at subsequent meal (by 135 kcal and 69 kcal; effect sizes 0.44 and 0.23, respectively) compared to a cereal-based breakfast with low protein and fiber.

  14. A systematic review and meta-analysis of randomized controlled trials of the effect of konjac glucomannan, a viscous soluble fiber, on LDL cholesterol and the new lipid targets non-HDL cholesterol and apolipoprotein B.

    Science.gov (United States)

    Ho, Hoang Vi Thanh; Jovanovski, Elena; Zurbau, Andreea; Blanco Mejia, Sonia; Sievenpiper, John L; Au-Yeung, Fei; Jenkins, Alexandra L; Duvnjak, Lea; Leiter, Lawrence; Vuksan, Vladimir

    2017-05-01

    Background: Evidence from randomized controlled trials (RCTs) suggests the consumption of konjac glucomannan (KJM), a viscous soluble fiber, for improving LDL-cholesterol concentrations. It has also been suggested that the cholesterol-lowering potential of KJM may be greater than that of other fibers. However, trials have been relatively scarce and limited in sample size and duration, and the effect estimates have been inconsistent. The effect of KJM on new lipid targets of cardiovascular disease (CVD) risk is also unknown. Objective: This systematic review and meta-analysis aimed to assess the effect of KJM on LDL cholesterol, non-HDL cholesterol, and apolipoprotein B. Design: Medline, Embase, CINAHL, and the Cochrane Central databases were searched. We included RCTs with a follow-up of ≥3 wk that assessed the effect of KJM on LDL cholesterol, non-HDL cholesterol, or apolipoprotein B. Data were pooled by using the generic inverse-variance method with random-effects models and expressed as mean differences (MDs) with 95% CIs. Heterogeneity was assessed by the Cochran Q statistic and quantified by the I 2 statistic. Results: Twelve studies ( n = 370), 8 in adults and 4 in children, met the inclusion criteria. KJM significantly lowered LDL cholesterol (MD: -0.35 mmol/L; 95% CI: -0.46, -0.25 mmol/L) and non-HDL cholesterol (MD: -0.32 mmol/L; 95% CI: -0.46, -0.19 mmol/L). Data from 6 trials suggested no impact of KJM on apolipoprotein B. Conclusions: Our findings support the intake of ∼3 g KJM/d for reductions in LDL cholesterol and non-HDL cholesterol of 10% and 7%, respectively. The information may be of interest to health agencies in crafting future dietary recommendations related to reduction in CVD risk. This study was registered at clinicaltrials.gov as NCT02068248. © 2017 American Society for Nutrition.

  15. Optical Fibers

    Science.gov (United States)

    Ghatak, Ajoy; Thyagarajan, K.

    With the development of extremely low-loss optical fibers and their application to communication systems, a revolution has taken fiber glass place during the last 40 years. In 2001, using glass fibers as the transmission medium and lightwaves as carrier wave waves, information was transmitted at a rate more than 1 Tbit/s (which is roughly equivalent to transmission of about 15 million simultaneous telephone conversations) through one hair thin optical fiber. Experimental demonstration of transmission at the rate of 14 Tbit/s over a 160 km long single fiber was demonstrated in 2006, which is equivalent to sending 140 digital high definition movies in 1 s. Very recently record transmission of more than 100 Tbit/s over 165 km single mode fiber has been reported. These can be considered as extremely important technological achievements. In this chapter we will discuss the propagation characteristics of optical fibers with special applications to optical communication systems and also present some of the noncommunication applications such as sensing.

  16. Vacuum fiber-fiber coupler

    Science.gov (United States)

    Heinrici, Axel; Bjelajac, Goran; Jonkers, Jeroen; Jakobs, Stefan; Olschok, Simon; Reisgen, Uwe

    2017-02-01

    Research and development carried out by the ISF Welding and Joining Institute of RWTH Aachen University has proven that combining high power laser and low vacuum atmosphere provides a welding performance and quality, which is comparable to electron beam welding. The developed welding machines are still using a beam forming which takes place outside the vacuum and the focusing laser beam has to be introduced to the vacuum via a suitable window. This inflexible design spoils much of the flexibility of modern laser welding. With the target to bring a compact, lightweight flying optics with flexible laser transport fibers into vacuum chambers, a high power fiber-fiber coupler has been adapted by II-VI HIGHYAG that includes a reliable vacuum interface. The vacuum-fiber-fiber coupler (V-FFC) is tested with up to 16 kW sustained laser power and the design is flexible in terms of a wide variety of laser fiber plug systems and vacuum flanges. All that is needed to implement the V-FFC towards an existing or planned vacuum chamber is an aperture of at least 100 mm (4 inch) diameter with any type of vacuum or pressure flange. The V-FFC has a state-of-the-art safety interface which allows for fast fiber breakage detection for both fibers (as supported by fibers) by electric wire breakage and short circuit detection. Moreover, the System also provides connectors for cooling and electric signals for the laser beam optics inside the vacuum. The V-FFC has all necessary adjustment options for coupling the laser radiation to the receiving fiber.

  17. Electrically stimulated osteogenesis on Ti-PPy/PLGA constructs prepared by laser-assisted processes.

    Science.gov (United States)

    Paun, Irina Alexandra; Stokker-Cheregi, Flavian; Luculescu, Catalin Romeo; Acasandrei, Adriana Maria; Ion, Valentin; Zamfirescu, Marian; Mustaciosu, Cosmin Catalin; Mihailescu, Mona; Dinescu, Maria

    2015-10-01

    This work describes a versatile laser-based protocol for fabricating micro-patterned, electrically conductive titanium-polypyrrole/poly(lactic-co-glycolic)acid (Ti-PPy/PLGA) constructs for electrically stimulated (ES) osteogenesis. Ti supports were patterned using fs laser ablation in order to create high spatial resolution microstructures meant to provide mechanical resistance and physical cues for cell growth. Matrix Assisted Pulsed Laser Evaporation (MAPLE) was used to coat the patterned Ti supports with PPy/PLGA layers acting as biocompatible surfaces having chemical and electrical properties suitable for cell differentiation and mineralization. In vitro biological assays on osteoblast-like MG63 cells showed that the constructs maintained cell viability without cytotoxicity. At 24 h after cell seeding, electrical stimulation with currents of 200 μA was applied for 4 h. This treatment was shown to promote earlier onset of osteogenesis. More specifically, the alkaline phosphatase activity of the stimulated cultures reached the maximum before that of the non-stimulated ones, i.e. controls, indicating faster cell differentiation. Moreover, mineralization was found to occur at an earlier stage in the stimulated cultures, as compared to the controls, starting with Day 6 of cell culture. At later stages, calcium levels in the stimulated cultures were higher than those in control samples by about 70%, with Ca/P ratios similar to those of natural bone. In all, the laser-based protocol emerges as an efficient alternative to existing fabrication technologies. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. MAPLE deposition of PLGA:PEG films for controlled drug delivery: Influence of PEG molecular weight

    Science.gov (United States)

    Paun, Irina Alexandra; Moldovan, Antoniu; Luculescu, Catalin Romeo; Staicu, Angela; Dinescu, Maria

    2012-09-01

    Implantable devices consisting of indomethacin (INC) cores coated with poly(lactide-co-glycolide):polyethylene glycol films (i.e. PLGA:PEG films) deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) were produced. To predict their behavior after implantation inside the body, the implants were studied in vitro, in media similar with those encountered inside the body (phosphate buffered saline (PBS) pH 7.4 and blood). The influence of the molecular weight of PEG (i.e. low (1450 Da) versus high (10 kDa) molecular weights) on the characteristics of the implants was investigated, in terms of morphology, blood compatibility and kinetics of the drug release. The use of PEG of high molecular weight resulted in larger pores on the implants surfaces, enhanced blood compatibility of the implants and higher drug delivery rates. For both molecular weights PEGs, sustained release of INC was maintained over a three weeks interval. Theoretical fitting of the drug release data with Higuchi's model indicated that the INC was released mainly by diffusion, most probably through the pores formed in PLGA:PEG films during PBS immersion.

  19. Physico-chemical characterisation of PLGA nanoparticles after freeze-drying and storage.

    Science.gov (United States)

    Holzer, Melisande; Vogel, Vitali; Mäntele, Werner; Schwartz, Daniel; Haase, Winfried; Langer, Klaus

    2009-06-01

    Nanoparticles represent promising carriers for controlled drug delivery. Particle size and size distribution of the particles are important parameters for the in vivo behaviour after intravenous injection and have to be characterised precisely. In the present study, the influence of lyophilisation on the storage stability of poly(D,L lactic-co-glycolic acid) (PLGA) nanoparticles, formulated with several cryoprotective agents, was evaluated. Nanoparticles were prepared by a high pressure solvent evaporation method and freeze-dried in the presence of 1%, 2%, and 3% (m/v) sucrose, trehalose, and mannitol, respectively. Additionally, to all samples containing 3% of the excipients, L-arginine hydrochloride was added in concentrations of 2.1% or 8.4% (m/V). Dynamic light scattering (DLS), analytical ultracentrifugation and transmission electron microscopy (TEM) were used for particle characterisation before and after freeze-drying and subsequent reconstitution. In addition, glass transition temperatures were determined by differential scanning calorimetry (DSC), and the residual moisture of the lyophilisates was analysed by Karl Fischer titration. It was demonstrated that 1% sucrose or 2% trehalose were suitable to maintain particle integrity after reconstitution of lyophilised PLGA nanoparticles. The storage stability study over 3 months showed notable changes in mean particle size, size distribution, and residual moisture content, depending on the composition of the formulation.

  20. Fe3O4-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis.

    Science.gov (United States)

    Liu, Jia; Xu, Jie; Zhou, Jun; Zhang, Yu; Guo, Dajing; Wang, Zhigang

    2017-01-01

    Thrombotic disease is a great threat to human health, and early detection is particularly important. Magnetic resonance (MR) molecular imaging provides noninvasive imaging with the potential for early disease diagnosis. In this study, we developed Fe3O4-based poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface-modified with a cyclic Arg-Gly-Asp (cRGD) peptide as an MR contrast agent for the detection of thrombosis. The physical and chemical characteristics, biological toxicity, ability to target thrombi, and biodistribution of the NPs were studied. The Fe3O4-PLGA-cRGD NPs were constructed successfully, and hematologic and pathologic assays indicated no in vivo toxicity of the NPs. In a rat model of FeCl3-induced abdominal aorta thrombosis, the NPs readily and selectively accumulated on the surface of the thrombosis and under vascular endothelial cells ex vivo and in vivo. In the in vivo experiment, the biodistribution of the NPs suggested that the NPs might be internalized by the macrophages of the reticuloendothelial system in the liver and the spleen. The T2 signal decreased at the mural thrombus 10 min after injection and then gradually increased until 50 min. These results suggest that the NPs are suitable for in vivo molecular imaging of thrombosis under high shear stress conditions and represent a very promising MR contrast agent for sensitive and specific detection of thrombosis.

  1. Effect of Gamma Irradiation on Structural and Biological Properties of a PLGA-PEG-Hydroxyapatite Composite

    Science.gov (United States)

    Shahabi, Sima; Najafi, Farhood; Majdabadi, Abbas; Hooshmand, Tabassom; Haghbin Nazarpak, Masoumeh; Karimi, Batool

    2014-01-01

    Gamma irradiation is able to affect various structural and biological properties of biomaterials In this study, a composite of Hap/PLGA-PEG and their ingredients were submitted to gamma irradiation doses of 25 and 50 KGy. Various properties such as molecular weight (GPC), thermal behavior (DSC), wettability (contact angle), cell viability (MTT assay), and alkaline phosphatase activity were studied for the composites and each of their ingredients. The results showed a decrease in molecular weight of copolymer with no change in the glass transition and melting temperatures after gamma irradiation. In general gamma irradiation can increase the activation energy ΔH of the composites and their ingredients. While gamma irradiation had no effect on the wettability of copolymer samples, there was a significant decrease in contact angle of hydroxyapatite and composites with increase in gamma irradiation dose. This study showed an increase in biocompatibility of hydroxyapatite with gamma irradiation with no significant effect on cell viability in copolymer and composite samples. In spite of the fact that no change occurred in alkaline phosphatase activity of composite samples, results indicated a decrease in alkaline phosphatase activity in irradiated hydroxyapatites. These effects on the properties of PLGA-PEG-hydroxyapatite can enhance the composite application as a biomaterial. PMID:25574485

  2. PLGA-based microcarriers induce mesenchymal stem cell chondrogenesis and stimulate cartilage repair in osteoarthritis.

    Science.gov (United States)

    Morille, Marie; Toupet, Karine; Montero-Menei, Claudia N; Jorgensen, Christian; Noël, Danièle

    2016-05-01

    In the present study, we aimed at evaluating the ability of novel PLGA-P188-PLGA-based microspheres to induce the differentiation of mesenchymal stem/stromal cells (MSC) into chondrocytes. To this aim, we tested microspheres releasing TGFβ3 (PAM-T) in vitro and in situ, in a pathological osteoarthritic (OA) environment. We first evaluated the chondrogenic differentiation of human MSCs seeded onto PAM-T in vitro and confirmed the up-regulation of chondrogenic markers while the secretome of the cells was not changed by the 3D environment. We then injected human MSC seeded onto PAM-T in the knee joints of mice with collagenase-induced OA. After 6 weeks, histological analysis revealed that formation of a cartilage-like tissue occurred at the vicinity of PAM-T that was not observed when MSCs were seeded onto PAM. We also noticed that the endogenous articular cartilage was less degraded. The extent of cartilage protection was further analysed by confocal laser microscopy. When MSCs seeded onto PAM-T were injected early after OA induction, protection of cartilage against degradation was evidenced and this effect was associated to a higher survival of MSCs in presence of TGFβ3. This study points to the interest of using MSCs seeded onto PAM for cartilage repair and stimulation of endogenous cartilage regeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Spray drying of siRNA-containing PLGA nanoparticles intended for inhalation.

    Science.gov (United States)

    Jensen, Ditte Marie Krohn; Cun, Dongmei; Maltesen, Morten Jonas; Frokjaer, Sven; Nielsen, Hanne Mørck; Foged, Camilla

    2010-02-25

    Local delivery of small interfering RNA (siRNA) to the lungs constitutes a promising new area in drug delivery. The present study evaluated parameters of importance for spray drying of siRNA-loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) into nanocomposite microparticles intended for inhalation. The spray drying process was optimised using a statistical design of experiment and by evaluating powder characteristics upon systematic variation of the formulation parameters. Concentration, carbohydrate excipient (trehalose, lactose and mannitol) and the ratio of NP to excipient were varied to monitor the effects on moisture content, particle morphology, particle size and powder yield. The identified optimum conditions were applied for spray drying of siRNA-loaded nanocomposite microparticles, resulting in a product with a low water content (0.78% w/w) and an aerodynamic particle diameter considered suitable for inhalation. The use of mannitol in the formulation allowed a significantly lower moisture content than trehalose and lactose. The inclusion of 50% (w/w) or higher amounts of NPs resulted in a marked change in the surface morphology of the spray-dried particles. Importantly, the integrity and biological activity of the siRNA were preserved during the spray drying process. In conclusion, the present results show that spray drying is a suitable technique for producing nanocomposite microparticles comprising siRNA-containing PLGA NPs for potential use in inhalation therapy. Copyright 2009 Elsevier B.V. All rights reserved.

  4. PVA bio-nanocomposites: a new take-off using cellulose nanocrystals and PLGA nanoparticles.

    Science.gov (United States)

    Rescignano, N; Fortunati, E; Montesano, S; Emiliani, C; Kenny, J M; Martino, S; Armentano, I

    2014-01-01

    The formation of a new generation of hybrid bio-nanocomposites is reported: these are intended at modulating the mechanical, thermal and biocompatibility properties of the poly(vinyl alcohol) (PVA) by the combination of cellulose nanocrystals (CNC) and poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) loaded with bovine serum albumin fluorescein isothiocynate conjugate (FITC-BSA). CNC were synthesized from microcrystalline cellulose by hydrolysis, while PLGA nanoparticles were produced by a double emulsion with subsequent solvent evaporation. Firstly, binary bio-nanocomposites with different CNC amounts were developed in order to select the right content of CNC. Next, ternary PVA/CNC/NPs bio-nanocomposites were developed. The addition of CNC increased the elongation properties without compromising the other mechanical responses. Thermal analysis underlined the nucleation effect of the synergic presence of cellulose and nanoparticles. Remarkably, bio-nanocomposite films are suitable to vehiculate biopolymeric nanoparticles to adult bone marrow mesenchymal stem cells successfully, thus representing a new tool for drug delivery strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Humoral Immune Response Induced by PLGA Micro Particle Coupled Newcastle Disease Virus Vaccine in Chickens

    Directory of Open Access Journals (Sweden)

    Sanganagouda K

    2014-02-01

    Full Text Available This experiment was conducted for evaluating the humoral immune responses induced by Poly Lactide-co-Glycolide Acid (PLGA microspheres coupled inactivated Newcastle Disease Virus (NDV vaccine in comparison to an ‘in-house’ prepared inactivated and a live commercial vaccine. PLG microparticles containing inactivated NDV were prepared by a double emulsion technique based on solvent evaporation method. The size of the NDV coupled PLG microparticles was determined by Electron Microscopy. NDV coupled PLG microparticles were spherical having smooth surface, hollow core inside with no pores on the surface. The experiment was conducted in four groups of chickens (n=15. The encapsulation efficiency of NDV coupled PLG microparticles was determined by protein estimation and HA activity in elute. The mean (± SE size of PLG microspheres was found to be 2.409 ± 0.65 µm. The mean percent of encapsulation efficiency of PLG microspheres coupled to NDV was assessed based on the total protein content and HA activity in elute was found to be 8.03 ± 0.50 and 12.5 ± 0.00, respectively. In conclusion, the results of the experiment showed that PLGA coupled NDV vaccine elicited stronger and prolonged humoral immune response in chickens, in comparison to the other tested vaccines, as assessed by haemagglutination inhibition and enzyme linked immuno sorbent asaay titers.

  6. Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xiangru Wen

    Full Text Available Magnetic poly (D,L-lactide-co-glycolide (PLGA/lipid nanoparticles (MPLs were fabricated from PLGA, L-α-phosphatidylethanolamine (DOPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-amino (polyethylene glycol (DSPE-PEG-NH2, and magnetic nanoparticles (NPs, and then conjugated to trans-activating transcriptor (TAT peptide. The TAT-MPLs were designed to target the brain by magnetic guidance and TAT conjugation. The drugs hesperidin (HES, naringin (NAR, and glutathione (GSH were encapsulated in MPLs with drug loading capacity (>10% and drug encapsulation efficiency (>90%. The therapeutic efficacy of the drug-loaded TAT-MPLs in bEnd.3 cells was compared with that of drug-loaded MPLs. The cells accumulated higher levels of TAT-MPLs than MPLs. In addition, the accumulation of QD-loaded fluorescein isothiocyanate (FITC-labeled TAT-MPLs in bEnd.3 cells was dose and time dependent. Our results show that TAT-conjugated MPLs may function as an effective drug delivery system that crosses the blood brain barrier to the brain.

  7. Effect of Gamma Irradiation on Structural and Biological Properties of a PLGA-PEG-Hydroxyapatite Composite

    Directory of Open Access Journals (Sweden)

    Sima Shahabi

    2014-01-01

    Full Text Available Gamma irradiation is able to affect various structural and biological properties of biomaterials In this study, a composite of Hap/PLGA-PEG and their ingredients were submitted to gamma irradiation doses of 25 and 50 KGy. Various properties such as molecular weight (GPC, thermal behavior (DSC, wettability (contact angle, cell viability (MTT assay, and alkaline phosphatase activity were studied for the composites and each of their ingredients. The results showed a decrease in molecular weight of copolymer with no change in the glass transition and melting temperatures after gamma irradiation. In general gamma irradiation can increase the activation energy ΔH of the composites and their ingredients. While gamma irradiation had no effect on the wettability of copolymer samples, there was a significant decrease in contact angle of hydroxyapatite and composites with increase in gamma irradiation dose. This study showed an increase in biocompatibility of hydroxyapatite with gamma irradiation with no significant effect on cell viability in copolymer and composite samples. In spite of the fact that no change occurred in alkaline phosphatase activity of composite samples, results indicated a decrease in alkaline phosphatase activity in irradiated hydroxyapatites. These effects on the properties of PLGA-PEG-hydroxyapatite can enhance the composite application as a biomaterial.

  8. Encapsulation of lipophilic kiteplatin Pt(iv) prodrugs in PLGA-PEG micelles.

    Science.gov (United States)

    Margiotta, Nicola; Savino, Salvatore; Denora, Nunzio; Marzano, Cristina; Laquintana, Valentino; Cutrignelli, Annalisa; Hoeschele, James D; Gandin, Valentina; Natile, Giovanni

    2016-08-16

    Biodegradable, PEG-coated, nanoparticles (NPs) have gained therapeutic application as injectable colloidal systems for the controlled and site-specific release of drugs. In this paper, encapsulation in PLGA-PEG polymer NPs has been exploited to lower the toxicity and to increase the antitumor activity of kiteplatin ([PtCl2(cis-1,4-DACH)]). Kiteplatin contains an isomeric form of the diamine ligand present in oxaliplatin and proved to be particularly active against ovarian and colon cancers. To favor encapsulation of the platinum drug in the hydrophobic core of the polymeric micelles, Pt(iv) prodrugs having hydrophobic carboxylic ligands at the axial positions were used in place of hydrophilic Pt(ii) complexes (compounds 1-4). The size, size distribution, and zeta potential (ZP) were measured by dynamic light scattering (DLS) and laser Doppler velocimetry (LDV), and drug encapsulation efficiency (EE) correlated to the alkyl chain length of the different Pt(iv) prodrugs. The number of the Pt atoms per NP (in the range of 1.3-2.4 × 10(6)) is comparable to that of polysilsesquioxane-based NPs and higher than that found for other nanoparticle platforms. The platinum-loaded PLGA-PEG NPs, tested in vivo in a syngeneic murine solid tumor (LLC), had a higher antitumor effect and, most importantly, were markedly less toxic than kiteplatin.

  9. Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.

    Science.gov (United States)

    Patel, Roshni S; Cho, Daniel Y; Tian, Cheng; Chang, Amy; Estrellas, Kenneth M; Lavin, Danya; Furtado, Stacia; Mathiowitz, Edith

    2012-01-01

    We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.

  10. Comparative Efficacies of Collagen-Based 3D Printed PCL/PLGA/β-TCP Composite Block Bone Grafts and Biphasic Calcium Phosphate Bone Substitute for Bone Regeneration.

    Science.gov (United States)

    Hwang, Kyoung-Sub; Choi, Jae-Won; Kim, Jae-Hun; Chung, Ho Yun; Jin, Songwan; Shim, Jin-Hyung; Yun, Won-Soo; Jeong, Chang-Mo; Huh, Jung-Bo

    2017-04-17

    The purpose of this study was to compare bone regeneration and space maintaining ability of three-dimensional (3D) printed bone grafts with conventional biphasic calcium phosphate (BCP). After mixing polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA), and β-tricalcium phosphate (β-TCP) in a 4:4:2 ratio, PCL/PLGA/β-TCP particulate bone grafts were fabricated using 3D printing technology. Fabricated particulate bone grafts were mixed with atelocollagen to produce collagen-based PCL/PLGA/β-TCP composite block bone grafts. After formation of calvarial defects 8 mm in diameter, PCL/PLGA/β-TCP composite block bone grafts and BCP were implanted into bone defects of 32 rats. Although PCL/PLGA/β-TCP composite block bone grafts were not superior in bone regeneration ability compared to BCP, the results showed relatively similar performance. Furthermore, PCL/PLGA/β-TCP composite block bone grafts showed better ability to maintain bone defects and to support barrier membranes than BCP. Therefore, within the limitations of this study, PCL/PLGA/β-TCP composite block bone grafts could be considered as an alternative to synthetic bone grafts available for clinical use.

  11. From micelles to fibers: balancing self-assembling and random coiling domains in pH-responsive silk-collagen-like protein-based polymers

    NARCIS (Netherlands)

    Beun, L.H.; Storm, I.M.; Werten, M.W.T.; Wolf, de F.A.; Cohen Stuart, M.A.; Vries, de R.J.

    2014-01-01

    We study the self-assembly of genetically engineered protein-based triblock copolymers consisting of a central pH-responsive silk-like middle block (SHn, where SH is a silk-like octapeptide, (GA)3GH and n is the number of repeats) flanked by hydrophilic random coil outer blocks (C2). Our previous

  12. Preparation, Optimization and Toxicity Evaluation of (SPION-PLGA) ±PEG Nanoparticles Loaded with Gemcitabine as a Multifunctional Nanoparticle for Therapeutic and Diagnostic Applications.

    Science.gov (United States)

    Hamzian, Nima; Hashemi, Maryam; Ghorbani, Mahdi; Bahreyni Toosi, Mohammad Hossein; Ramezani, Mohammad

    2017-01-01

    The aim of this study was to develop a novel multifunctional nanoparticle, which encapsulates SPION and Gemcitabine in PLGA ± PEG to form multifunctional drug delivery system. For this aim, super paramagnetic iron oxide nanoparticles (SPIONs) were simultaneously synthesized and encapsulated with Gemcitabine (Gem) in PLGA ± PEG copolymers via W/O/W double emulsification method. Optimum size and encapsulation efficiency for radiosensitization, hyperthermia and diagnostic applications were considered and the preparation parameters systematically were investigated and physicochemical characteristics of optimized nanoparticle were studied. Then SPION-PLGA and PLGA-Gem nanoparticles were prepared with the same optimized parameters and the toxicity of these nanoparticles was compared with Gemcitabine in human breast cancer cell line (MCF-7). The optimum preparation parameters were obtained with Gem/polymer equal to 0.04, SPION/polymer equal to 0.8 and 1% sucrose per 20 mg of polymer. The hydrodynamic diameters of all nanoparticles were under 200 nm. Encapsulation efficiency was adjusted between 13.2% to 16.1% for Gemcitabine and 48.2% to 50.1% for SPION. In-vitro Gemcitabine release kinetics had controlled behavior. Enhancement ratios for PLGA-Gem and SPION-PLGA-Gem at concentration of nanoparticles equal to IC50 of Gemcitabine were 1.53 and 1.89 respectively. The statistical difference was significant (p-value = 0.006 for SPION-PLGA-Gem and p-value = 0.015 for PLGA-Gem compared with Gemcitabine). In conclusion, we have successfully developed a Gemcitabine loaded super paramagnetic PLGA-Iron Oxide multifunctional drag delivery system. Future work includes in-vitro and in-vivo investigation of radiosensitization and other application of these nanoparticles.

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

    Science.gov (United States)

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

    2016-07-01

    Magnetic iron oxide nanoparticles (Fe-NPs) can be exploited in biomedicine as agents for magnetic fluid hyperthermia (MFH) treatments and as contrast enhancers in magnetic resonance imaging. New, oleate-covered, iron oxide particles have been prepared either by co-precipitation or thermal decomposition methods and incorporated into poly(lactic-co-glycolic acid) nanoparticles (PLGA-Fe-NPs) to improve their biocompatibility and in vivo stability. Moreover, the PLGA-Fe-NPs have been loaded with paclitaxel to pursue an MFH-triggered drug release. Remarkably, it has been found that the nanoparticle formulations are characterized by peculiar 1H nuclear magnetic relaxation dispersion (NMRD) profiles that directly correlate with their heating potential when exposed to an alternating magnetic field. By prolonging the magnetic field exposure to 30 min, a significant drug release was observed for PLGA-Fe-NPs in the case of the larger-sized magnetic nanoparticles. Furthermore, the immobilization of lipophilic Fe-NPs in PLGA-NPs also made it possible to maintain Néel relaxation as the dominant relaxation contribution in the presence of large iron oxide cores (diameters of 15-20 nm), with the advantage of preserving their efficiency when they are entrapped in the intracellular environment. The results reported herein show that NMRD profiles are a useful tool for anticipating the heating capabilities of Fe-NPs designed for MFH applications.

  14. Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo

    Science.gov (United States)

    Liu, Hui; Lv, Peizhen; Zhu, Yongjia; Wu, Huayu; Zhang, Kun; Xu, Fuben; Zheng, Li; Zhao, Jinmin

    2017-01-01

    Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection. The results showed that SDS dramatically enhanced the proliferation and function of SCs. The underlying mechanism may be that SDS affects SCs growth through the modulation of neurotrophic factors (BDNF, GDNF and CNTF). 12 weeks after implantation with a 12 mm gap of sciatic nerve injury, SDS-PLGA/SCs achieved satisfying outcomes of nerve regeneration, as evidenced by morphological and functional improvements upon therapy by SDS, PLGA/SCs or direct suture group assessed by sciatic function index, nerve conduction assay, HE staining and immunohistochemical analysis. Our results demonstrated the significant role of introducing SDS into neural tissue engineering to promote nerve regeneration.

  15. In vitro and in vivo characterization of temoporfin-loaded PEGylated PLGA nanoparticles for use in photodynamic therapy

    NARCIS (Netherlands)

    Rojnik, Matija; Kocbek, Petra; Moret, Francesca; Compagnin, Chiara; Celotti, Lucia; Bovis, Melissa J.; Woodhams, Josephine H.; MacRobert, Alexander J.; Scheglmann, Dietrich; Helfrich, Wijnand; Verkaik, Marco J.; Papini, Emanuele; Reddi, Elena; Kos, Janko

    Aims: In this study we evaluated temoporfin-loaded polyethylene glycol (PEG) poly-(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) as a new formulation for potential use in cancer treatment. Materials & methods: NPs were characterized for their photophysical properties, temoporfin release,

  16. Folate Functionalized PLGA Nanoparticles Loaded with Plasmid pVAX1-NH36: Mathematical Analysis of Release

    Directory of Open Access Journals (Sweden)

    Cindy Alejandra Gutiérrez-Valenzuela

    2016-11-01

    Full Text Available Plasmid DNA (pVAX1-NH36 was encapsulated in nanoparticles of poly-dl-lactic-co-glycolic (PLGA functionalized with polyethylene glycol (PEG and folic acid (PLGA-PEG-FA without losing integrity. PLGA-PEG-FA nanoparticles loaded with pVAX1-NH36 (pDNA-NPs were prepared by using a double emulsification-solvent evaporation technique. PLGA-PEG-FA synthesis was verified by FT-IR and spectrophotometry methods. pVAX1-NH36 was replicated in Escherichia coli (E. coli cell cultures. Atomic force microscopy (AFM analysis confirmed pDNA-NPs size with an average diameter of 177–229 nm, depending on pVAX1-NH36 loading and zeta potentials were below −24 mV for all preparations. In vitro release studies confirmed a multiphase release profile for the duration of more than 30-days. Plasmid release kinetics were analyzed with a release model that considered simultaneous contributions of initial burst and degradation-relaxation of nanoparticles. Fitting of release model against experimental data presented excellent correlation. This mathematical analysis presents a novel approach to describe and predict the release of plasmid DNA from biodegradable nanoparticles.

  17. Effect of PEG and water-soluble chitosan coating on moxifloxacin-loaded PLGA long-circulating nanoparticles.

    Science.gov (United States)

    Mustafa, Sanaul; Devi, V Kusum; Pai, Roopa S

    2017-02-01

    Moxifloxacin (MOX) is a Mycobacterium tuberculosis DNA gyrase inhibitor. Due to its intense hydrophilicity, MOX is cleared from the body within 24 h and required for repetitive doses which may then result in hepatotoxicity and acquisition of MOX resistant-TB, related with its use. To overcome the aforementioned limitations, the current study aimed to develop PLGA nanoparticles (PLGA NPs), to act as an efficient carrier for controlled delivery of MOX. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG) to MOX-PLGA NPs and adsorption of water-soluble chitosan (WSC) (cationic deacetylated chitin) to particle surface, was rose for surface modification of NPs. Surface modified NPs (MOX-PEG-WSC NPs) were prepared to provide controlled delivery and circulate in the bloodstream for an extended period of time, thus minimizing dosing frequency. In vivo pharmacokinetic and in vivo biodistribution following oral administration were investigated. NP surface charge was closed to neutral +4.76 mV and significantly affected by the WSC coating. MOX-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long-drawn-out the blood circulation half-life with resultant reduced liver sequestration vis-à-vis MOX-PLGA NPs. The studies, therefore, indicate the successful formulation development of MOX-PEG-WSC NPs that showed sustained release behavior from nanoparticles which indicates low frequency of dosing.

  18. The Effect of Temozolomide/Poly(lactide-co-glycolide (PLGA/Nano-Hydroxyapatite Microspheres on Glioma U87 Cells Behavior

    Directory of Open Access Journals (Sweden)

    Anhua Wu

    2012-01-01

    Full Text Available In this study, we investigated the effects of temozolomide (TMZ/Poly (lactide-co-glycolide(PLGA/nano-hydroxyapatite microspheres on the behavior of U87 glioma cells. The microspheres were fabricated by the “Solid/Water/Oil” method, and they were characterized by using X-Ray diffraction, scanning electron microscopy and differential scanning calorimetry. The proliferation, apoptosis and invasion of glioma cells were evaluated by MTT, flow cytometry assay and Transwell assay. The presence of the key invasive gene, αVβ3 integrin, was detected by the RT-PCR and Western blot method. It was found that the temozolomide/PLGA/nano-hydroxyapatite microspheres have a significantly diminished initial burst of drug release, compared to the TMZ laden PLGA microspheres. Our results suggest they can significantly inhibit the proliferation and invasion of glioma cells, and induce their apoptosis. Additionally, αVβ3 integrin was also reduced by the microspheres. These data suggest that by inhibiting the biological behavior of glioma cells in vitro, the newly designed temozolomide/PLGA/nano-hydroxyapatite microspheres, as controlled drug release carriers, have promising potential in treating glioma.

  19. PLGA/Nano-ZnO Composite Particles for Use in Biomedical Applications: Preparation, Characterization, and Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Ana Stanković

    2016-01-01

    Full Text Available Copolymer poly (DL-lactide-co-glycolide (PLGA is extensively investigated for various biomedical applications such as controlled drug delivery or carriers in the tissue engineering. In addition, zinc oxide (ZnO is widely used in biomedicine especially for materials like dental composites, as a constituent of creams for the treatment of a variety of skin irritations, to enhance the antibacterial activity of different medicaments and so on. Uniform, spherical ZnO nanoparticles (nano-ZnO have been synthesized via microwave synthesis method. In addition to obtaining nano-ZnO, a further aim was to examine their immobilization in the PLGA polymer matrix (PLGA/nano-ZnO and this was done by a simple physicochemical solvent/nonsolvent method. The samples were characterized by X-ray diffraction, scanning electron microscopy, laser diffraction particle size analyzer, differential thermal analysis, and thermal gravimetric analysis. The synthesized PLGA/nano-ZnO particles are spherical, uniform, and with diameters below 1 µm. The influence of the different solvents and the drying methods during the synthesis was investigated too. The biocompatibility of the samples is discussed in terms of in vitro toxicity on human hepatoma HepG2 cells by application of MTT assay and the antimicrobial activity was evaluated by broth microdilution method against different groups of microorganisms (Gram-positive bacteria, Gram-negative bacteria, and yeast Candida albicans.

  20. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun, E-mail: weiywswzy@163.com [Anhui Agricultural University, School of Life Sciences (China)

    2016-01-15

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly (d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion–solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet–Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100–150 nm. We compared the antibacterial effects of PQTs against Escherichia coli (E. coli) and Micrococcus tetragenus (M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application.

  1. Antiproliferative activity of ferulic acid-encapsulated electrospun PLGA/PEO nanofibers against MCF-7 human breast carcinoma cells.

    Science.gov (United States)

    Vashisth, Priya; Sharma, Mohit; Nikhil, Kumar; Singh, Harmeet; Panwar, Richa; Pruthi, Parul A; Pruthi, Vikas

    2015-06-01

    Ferulic acid (FA) is a polyphenolic phytonutrient which possesses strong antiproliferative effect; however, it has limited therapeutic applications due to its physiochemical instability and low bioavailability at the tumor site. In present study, these shortcomings associated with FA were overcome by fabricating FA-encapsulated poly(D,L-lactide-co-glycolide)/polyethylene oxide (PLGA/PEO) blend nanofibers using electrospinning technique. FESEM and fluorescence microscopic analysis imitates the smooth morphology and even distribution of FA within the polymeric nanofibers at optimum 2 wt% concentration of FA. The average diameters were recorded to be 150 ± 47.4 and 200 ± 79 nm for PLGA/PEO and FA-encapsulated PLGA/PEO nanofibers, respectively. The encapsulation, compatibility, and physical state of FA within the nanofibers were further confirmed by FTIR, TGA and XRD analysis. In vitro drug delivery studies demonstrated initial burst liberation of FA within 24 h followed by a sustained release for the subsequent time. MTT assay revealed the effectiveness of FA-encapsulated nanofibers against human breast carcinoma cells (MCF-7) cells as compared to control. FESEM and fluorescence microscopic analysis further confirmed the apoptotic effect of FA-encapsulated PLGA/PEO nanofibers against MCF-7. These fabricated nanofibers hold enormous potential to be used as a therapeutic agent for various biomedical applications.

  2. Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

    Science.gov (United States)

    Sun, Dongdong; Li, Nuan; Zhang, Weiwei; Yang, Endong; Mou, Zhipeng; Zhao, Zhiwei; Liu, Haiping; Wang, Weiyun

    2016-01-01

    Nanotechnology-based approaches have tremendous potential for enhancing efficacy against infectious diseases. PLGA-based nanoparticles as drug delivery carrier have shown promising potential, owing to their sizes and related unique properties. This article aims to develop nanosized poly ( d, l-lactide-co-glycolide) PLGA nanoparticle formulation loaded with quercetin (QT). QT is an antioxidant and antibacterial compound isolated from Chinese traditional medicine with low skin permeability and extreme water insolubility. The quercetin-loaded PLGA nanoparticles (PQTs) were synthesized by emulsion-solvent evaporation method and stabilized by coating with poly (vinyl alcohol). The characteristics of PQTs were analyzed by Fourier transform infrared spectroscopy, Ultraviolet-Visible spectroscopy, scanning electron microscope, transmission electron microscopy, and atomic force microscopy, respectively. The PQTs showed a spherical shape with an average size of 100-150 nm. We compared the antibacterial effects of PQTs against Escherichia coli ( E. coli) and Micrococcus tetragenus ( M. tetragenus).The PQTs produced stronger antibacterial activity to E. coli than that to M. tetragenus through disrupting bacterial cell wall integrity. The antibacterial ratio was increased with the increasing dosages and incubation time. Next, we tested the in vivo antibacterial activity in mice. No noticeable organ damage was captured from H&E-staining organ slices, suggesting the promise of using PQTs for in vivo applications. The results of this study demonstrated the interaction between bacteria and PLGA-based nanoparticles, providing encouragement for conducting further investigations on properties and antimicrobial activity of the PQTs in clinical application.

  3. Osteoconductive Potential of Barrier NanoSiO2 PLGA Membranes Functionalized by Plasma Enhanced Chemical Vapour Deposition

    Directory of Open Access Journals (Sweden)

    Antonia Terriza

    2014-01-01

    Full Text Available The possibility of tailoring membrane surfaces with osteoconductive potential, in particular in biodegradable devices, to create modified biomaterials that stimulate osteoblast response should make them more suitable for clinical use, hopefully enhancing bone regeneration. Bioactive inorganic materials, such as silica, have been suggested to improve the bioactivity of synthetic biopolymers. An in vitro study on HOB human osteoblasts was performed to assess biocompatibility and bioactivity of SiO2 functionalized poly(lactide-co-glycolide (PLGA membranes, prior to clinical use. A 15 nm SiO2 layer was deposited by plasma enhanced chemical vapour deposition (PECVD, onto a resorbable PLGA membrane. Samples were characterized by X-ray photoelectron spectroscopy, atomic force microscopy, scanning electron microscopy, and infrared spectroscopy (FT-IR. HOB cells were seeded on sterilized test surfaces where cell morphology, spreading, actin cytoskeletal organization, and focal adhesion expression were assessed. As proved by the FT-IR analysis of samples, the deposition by PECVD of the SiO2 onto the PLGA membrane did not alter the composition and other characteristics of the organic membrane. A temporal and spatial reorganization of cytoskeleton and focal adhesions and morphological changes in response to SiO2 nanolayer were identified in our model. The novedous SiO2 deposition method is compatible with the standard sterilization protocols and reveals as a valuable tool to increase bioactivity of resorbable PLGA membranes.

  4. Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats.

    Science.gov (United States)

    Hamishehkar, Hamed; Emami, Jaber; Najafabadi, Abdolhossien Rouholamini; Gilani, Kambiz; Minaiyan, Mohsen; Hassanzadeh, Kambiz; Mahdavi, Hamid; Koohsoltani, Maryam; Nokhodchi, Ali

    2010-03-01

    The pulmonary route is an alternative route of administration for the systemic delivery of peptide and proteins with short-half lives. A long-acting formulation of insulin was prepared by encapsulation of protein into respirable, biodegradable microcapsules prepared by an oil in oil emulsification/solvent evaporation method. Insulin-loaded PLGA microcapsules prepared as a dry powder inhaler formulation were administered via the pulmonary route to diabetic rats and serum insulin and glucose concentrations were monitored. Control treatments consisted of respirable spray-dried insulin (RSDI) powder administered by intratracheal insufflation, insulin-loaded PLGA microcapsules and NPH (long-acting) insulin administered by subcutaneous (SC) administration. Pharmacokinetic analysis demonstrated that insulin administered in PLGA microcapsules illustrated a sustained release profile which resulted in a longer mean residence time, 4 and 5 fold longer than those after pulmonary administration of RSDI and SC injection of NPH insulin, respectively. Accordingly, the hypoglycemic profile followed a stable and sustained pattern which remained constant between 10 and 48 h. Results of the in vitro experiments were in good agreement with those of in vivo studies. Bronchoalveolar lavage fluid analysis indicated that microcapsules administration did not increase the activities of lactate dehydrogenase and total protein. However, histological examination of the lung tissue indicated a minor but detectable effect on the normal physiology of the rat lung. These findings suggest that the encapsulation of peptides and proteins into PLGA microcapsules technique could be a promising controlled delivery system for pulmonary administration. Copyright (c) 2010 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

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

    2016-11-01

    The interest in polymeric nanoparticles as imaging systems for biomedical applications has increased notably in the last decades. In this work, PLGA nanoparticles, prepared from nano-emulsion templating, have been used to prepare novel fluorescent imaging agents. Two model fluorescent dyes were chosen and dissolved in the oil phase of the nano-emulsions together with PLGA. Nano-emulsions were prepared by the phase inversion composition (PIC) low-energy method. Fluorescent dye-loaded nanoparticles were obtained by solvent evaporation of nano-emulsion templates. PLGA nanoparticles loaded with the fluorescent dyes showed hydrodynamic radii lower than 40nm; markedly lower than those reported in previous studies. The small nanoparticle size was attributed to the nano-emulsification strategy used. PLGA nanoparticles showed negative surface charge and enough stability to be used for biomedical imaging purposes. Encapsulation efficiencies were higher than 99%, which was also attributed to the nano-emulsification approach as well as to the low solubility of the dyes in the aqueous component. Release kinetics of both fluorescent dyes from the nanoparticle dispersions was pH-independent and sustained. These results indicate that the dyes could remain encapsulated enough time to reach any organ and that the decrease of the pH produced during cell internalization by the endocytic route would not affect their release. Therefore, it can be assumed that these nanoparticles are appropriate as systemic imaging agents. In addition, in vitro toxicity tests showed that nanoparticles are non-cytotoxic. Consequently, it can be concluded that the preparation of PLGA nanoparticles from nano-emulsion templating represents a very versatile technology that enables obtaining biocompatible, biodegradable and safe imaging agents suitable for biomedical purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB Stabilized Poly(Lactic-co-Glycolic Acid (PLGA Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Rebecca Gossmann

    Full Text Available Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid (PLGA is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB, in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA and polyethylene glycol (PEG modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to

  7. Development and characterisation of disulfiram-loaded PLGA nanoparticles for the treatment of non-small cell lung cancer.

    Science.gov (United States)

    Najlah, Mohammad; Ahmed, Zahima; Iqbal, Mohammed; Wang, Zhipeng; Tawari, Patrica; Wang, Weiguang; McConville, Christopher

    2017-03-01

    Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer in both men and women. A recent phase IIb study demonstrated that disulfiram (DSF) in combination with cisplatin and vinorelbine was well tolerated and prolonged the survival of patients with newly diagnosed NSCLC. However, DSF is rapidly (4min) metabolised in the bloodstream and it is this issue which is limiting its anticancer application in the clinic. We have recently demonstrated that a low dose of DSF-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles supplemented with oral Cu inhibited tumour growth and reduced metastasis in a xenograft mouse lung cancer model. Here we demonstrate the influence of PLGA polymer, stabilizer loading and molecular weight as well as sonication time on the characteristics, including DSF release and the cytotoxicity of 10% w/w DSF-loaded PLGA nanoparticles. The paper demonstrates that the choice of PLGA as no significance on the characteristics of the nanoparticles apart from their DSF release, which is due to the differing degradation rates of the polymers. However, increasing the loading and molecular weight of the stabilizer as well as the sonication time reduced the size of the nanoparticles, reduced their ability to protect the DSF from reacting with Cu and degrading in serum, while increasing their DSF release rate and cytotoxicity. Additionally, increasing the sonication time resulted in the premature degradation of the PLGA, which increased the permeability of the nanoparticles further decreasing their ability to protect DSF from reacting with Cu and degrading in serum, while increasing their DSF release rate and cytotoxicity. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles.

    Science.gov (United States)

    Gossmann, Rebecca; Langer, Klaus; Mulac, Dennis

    2015-01-01

    Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in literature, while especially nanoparticles with cationic properties show a promising increased cellular uptake. This is due to the electrostatic interaction between the cationic surface and the negatively charged lipid membrane of the cells. Even though several studies achieved the successful preparation of nanoparticles stabilized with the cationic surfactants such as didodecyldimethylammonium bromide (DMAB), in most cases insufficient attention was paid to a precise analytical characterization of the nanoparticle system. The aim of the present work was to overcome this deficit by presenting a new perspective in the formulation and characterization of DMAB-stabilized PLGA nanoparticles. Therefore these nanoparticles were carefully examined with regard to particle diameter, zeta potential, the effect of variation in stabilizer concentration, residual DMAB content, and electrolyte stability. Without any steric stabilization, the DMAB-modified nanoparticles were sensitive to typical electrolyte concentrations of biological environments due to compression of the electrical double layer in conjunction with a decrease in zeta potential. To handle this problem, the present study proposed two modifications to enable electrolyte stability. Both polyvinyl alcohol (PVA) and polyethylene glycol (PEG) modified DMAB-PLGA-nanoparticles were stable during electrolyte addition. Furthermore, in contrast to unmodified DMAB-PLGA-nanoparticles and free DMAB, such modifications led to a lower

  9. Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11.

    Science.gov (United States)

    Santos, Diego M; Carneiro, Marcia W; de Moura, Tatiana R; Fukutani, Kiyoshi; Clarencio, Jorge; Soto, Manuel; Espuelas, Socorro; Brodskyn, Claudia; Barral, Aldina; Barral-Netto, Manoel; de Oliveira, Camila I

    2012-01-01

    Vaccine development has been a priority in the fight against leishmaniases, which are vector-borne diseases caused by Leishmania protozoa. Among the different immunization strategies employed to date is inoculation of plasmid DNA coding for parasite antigens, which has a demonstrated ability to induce humoral and cellular immune responses. In this sense, inoculation of plasmid DNA encoding Leishmania kinetoplasmid membrane protein-11 (KMP-11) was able to confer protection against visceral leishmaniasis. However, recently the use of antigen delivery systems such as poly(lactic-co-glycolic acid) (PLGA) nanoparticles has also proven effective for eliciting protective immune responses. In the present work, we tested two immunization strategies with the goal of obtaining protection, in terms of lesion development and parasite load, against cutaneous leishmaniasis caused by L. braziliensis. One strategy involved immunization with plasmid DNA encoding L. infantum chagasi KMP-11. Alternatively, mice were primed with PLGA nanoparticles loaded with the recombinant plasmid DNA and boosted using PLGA nanoparticles loaded with recombinant KMP-11. Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti-inflammatory cytokines; mice receiving the recombinant PLGA nanoparticle formulations also demonstrated anti-KMP-11 IgG1 and IgG2a. Mice were then challenged with L. braziliensis, in the presence of sand fly saliva. Lesion development was not inhibited following either immunization strategy. However, immunization with PLGA nanoparticles resulted in a more prominent reduction in parasite load at the infection site when compared with immunization using plasmid DNA alone. This effect was associated with a local increase in interferon-gamma and in tumor necrosis factor-alpha. Both immunization strategies also resulted in a lower parasite load in the draining lymph nodes, albeit not significantly. Our results

  10. Enhanced encapsulation and bioavailability of breviscapine in PLGA microparticles by nanocrystal and water-soluble polymer template techniques.

    Science.gov (United States)

    Wang, Hong; Zhang, Guangxing; Ma, Xueqin; Liu, Yanhua; Feng, Jun; Park, Kinam; Wang, Wenping

    2017-06-01

    Poly (lactide-co-glycolide) (PLGA) microparticles are widely used for controlled drug delivery. Emulsion methods have been commonly used for preparation of PLGA microparticles, but they usually result in low loading capacity, especially for drugs with poor solubility in organic solvents. In the present study, the nanocrystal technology and a water-soluble polymer template method were used to fabricate nanocrystal-loaded microparticles with improved drug loading and encapsulation efficiency for prolonged delivery of breviscapine. Breviscapine nanocrystals were prepared using a precipitation-ultrasonication method and further loaded into PLGA microparticles by casting in a mold from a water-soluble polymer. The obtained disc-like particles were then characterized and compared with the spherical particles prepared by an emulsion-solvent evaporation method. X-ray powder diffraction (XRPD) and confocal laser scanning microscopy (CLSM) analysis confirmed a highly-dispersed state of breviscapine inside the microparticles. The drug form, loading percentage and fabrication techniques significantly affected the loading capacity and efficiency of breviscapine in PLGA microparticles, and their release performance as well. Drug loading was increased from 2.4% up to 15.3% when both nanocrystal and template methods were applied, and encapsulation efficiency increased from 48.5% to 91.9%. But loading efficiency was reduced as the drug loading was increased. All microparticles showed an initial burst release, and then a slow release period of 28days followed by an erosion-accelerated release phase, which provides a sustained delivery of breviscapine over a month. A relatively stable serum drug level for more than 30days was observed after intramuscular injection of microparticles in rats. Therefore, PLGA microparticles loaded with nanocrystals of poorly soluble drugs provided a promising approach for long-term therapeutic products characterized with preferable in vitro and in vivo

  11. A Novel High Mechanical Property PLGA Composite Matrix Loaded with Nanodiamond-Phospholipid Compound for Bone Tissue Engineering.

    Science.gov (United States)

    Zhang, Fan; Song, Qingxin; Huang, Xuan; Li, Fengning; Wang, Kun; Tang, Yixing; Hou, Canglong; Shen, Hongxing

    2016-01-20

    A potential bone tissue engineering material was produced from a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), loaded with nanodiamond phospholipid compound (NDPC) via physical mixing. On the basis of hydrophobic effects and physical absorption, we modified the original hydrophilic surface of the nanodiamond (NDs) with phospholipids to be amphipathic, forming a typical core-shell structure. The ND-phospholipid weight ratio was optimized to generate sample NDPC50 (i.e., ND-phospholipid weight ratio of 100:50), and NDPC50 was able to be dispersed in a PLGA matrix at up to 20 wt %. Compared to a pure PLGA matrix, the introduction of 10 wt % of NDPC (i.e., sample NDPC50-PF10) resulted in a significant improvement in the material's mechanical and surface properties, including a decrease in the water contact angle from 80 to 55°, an approximately 100% increase in the Young's modulus, and an approximate 550% increase in hardness, thus closely resembling that of human cortical bone. As a novel matrix supporting human osteoblast (hFOB1.19) growth, NDPC50-PFs with different amounts of NDPC50 demonstrated no negative effects on cell proliferation and osteogenic differentiation. Furthermore, we focused on the behaviors of NDPC-PFs implanted into mice for 8 weeks and found that NDPC-PFs induced acceptable immune response and can reduce the rapid biodegradation of PLGA matrix. Our results represent the first in vivo research on ND (or NDPC) as nanofillers in a polymer matrix for bone tissue engineering. The high mechanical properties, good in vitro and in vivo biocompatibility, and increased mineralization capability suggest that biodegradable PLGA composite matrices loaded with NDPC may potentially be useful for a variety of biomedical applications, especially bone tissue engineering.

  12. Mechanisms of in vivo release of triamcinolone acetonide from PLGA microspheres.

    Science.gov (United States)

    Doty, Amy C; Weinstein, David G; Hirota, Keiji; Olsen, Karl F; Ackermann, Rose; Wang, Yan; Choi, Stephanie; Schwendeman, Steven P

    2017-06-28

    Little is known about the underlying effects controlling in vitro-in vivo correlations (IVIVCs) for biodegradable controlled release microspheres. Most reports of IVIVCs that exist are empirical in nature, typically based on a mathematical relationship between in vitro and in vivo drug release, with the latter often estimated by deconvolution of pharmacokinetic data. In order to improve the ability of in vitro release tests to predict microsphere behavior in vivo and develop more meaningful IVIVCs, the in vivo release mechanisms need to be characterized. Here, two poly(lactic-co-glycolic acid) (PLGA) microsphere formulations encapsulating the model steroid triamcinolone acetonide (Tr-A) were implanted subcutaneously in rats by using a validated cage model, allowing for free fluid and cellular exchange and microsphere retrieval during release. Release kinetics, as well as mechanistic indicators of release such as hydrolysis and mass loss, was measured by direct analysis of the recovered microspheres. Release of Tr-A from both formulations was greatly accelerated in vivo compared to in vitro using agitated phosphate buffered saline +0.02% Tween 80 pH7.4, including rate of PLGA hydrolysis, mass loss and water uptake. Both microsphere formulations exhibited erosion-controlled release in vitro, indicated by similar polymer mass loss kinetics, but only one of the formulations (low molecular weight, free acid terminated) exhibited the same mechanism in vivo. The in vivo release of Tr-A from microspheres made of a higher molecular weight, ester end-capped PLGA displayed an osmotically induced/pore diffusion mechanism based on confocal micrographs of percolating pores in the polymer, not previously observed in vitro. This research indicates the need to fully understand the in vivo environment and how it causes drug release from biodegradable microspheres. This understanding can then be applied to develop in vitro release tests which better mimic this environment and cause

  13. Low-fiber diet

    Science.gov (United States)

    ... residue; Low-fiber diet; Fiber restricted diet; Crohn disease - low fiber diet; Ulcerative colitis - low fiber diet; ... pulp: Yellow squash (without seeds) Spinach Pumpkin Eggplant Potatoes, without skin Green beans Wax beans Asparagus Beets ...

  14. Soluble vs. insoluble fiber

    Science.gov (United States)

    Insoluble vs. soluble fiber; Fiber - soluble vs. insoluble ... There are 2 different types of fiber -- soluble and insoluble. Both are important for health, digestion, and preventing diseases. Soluble fiber attracts water and turns to gel during digestion. This slows ...

  15. PLGA nanoparticles for peptide receptor radionuclide therapy of neuroendocrine tumors: a novel approach towards reduction of renal radiation dose.

    Directory of Open Access Journals (Sweden)

    Geetanjali Arora

    Full Text Available BACKGROUND: Peptide receptor radionuclide therapy (PRRT, employed for treatment of neuroendocrine tumors (NETs is based on over-expression of Somatostatin Receptors (SSTRs on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, (177Lu-DOTATATE loaded PLGA nanoparticles (NPs were formulated in the present study, as a potential therapeutic model for NETs. METHODOLOGY AND FINDINGS: DOTATATE was labeled with Lutetium-177 ((177Lu (labeling efficiency 98%; R(f∼0.8. Polyethylene Glycol (PEG coated (177Lu-DOTATATE-PLGA NPs (50:50 and 75:25 formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated and 303.8±67.2 and 494.3±71.8 nm (coated for PLGA(50:50 and PLGA(75:25 respectively. Encapsulation efficiency (EE and In-vitro release kinetics for uncoated and coated NPs of PLGA (50:50 & 75:25 were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated and 65.385±5.67% & 58.495±5.35% (coated. NPs showed initial burst release between 16.64-21.65% with total 42.83-44.79% over 21 days. The release increased with coating to 20.4-23.95% initially and 60.97-69.12% over 21 days. In-vivo studies were done in rats injected with (177Lu-DOTATATE and (177Lu-DOTATATE-NP (uncoated and PEG-coated by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With (177Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated (177Lu-DOTATATE-NP. The high liver uptake with uncoated (177Lu-DOTATATE-NP (13.68±3.08% ID/g, reduced to 7.20±2.04%ID/g (p = 0.02 with PEG coating. CONCLUSION: PLGA NPs were easily formulated and modified for desired release properties. PLGA

  16. Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma

    Science.gov (United States)

    Arshad, Azeem; Yang, Bin; Bienemann, Alison S.; Barua, Neil U.; Wyatt, Marcella J.; Woolley, Max; Johnson, Dave E.; Edler, Karen J.; Gill, Steven S.

    2015-01-01

    We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas. PMID:26186224

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

    Science.gov (United States)

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

    2016-08-01

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

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

    DEFF Research Database (Denmark)

    Fonte, Pedro; Araújo, Francisca; Seabra, Vítor

    2015-01-01

    The purpose of this work was to evaluate the influence of the co-encapsulation of lyoprotectants with insulin into PLGA nanoparticles, on the stability of the protein and nanoparticles upon lyophilization. Different lyoprotectants were used, namely trehalose, glucose, sucrose, fructose and sorbitol...... formulations with externally added lyoprotectants, except trehalose, showed crystallinity. FTIR assessment showed that co-encapsulating lyoprotectants better preserved insulin structure upon lyophilization with a spectral area overlap of 82-87%, compared to only 72% in lyoprotectant absence. These results were...... confirmed by circular dichroism spectroscopy. Surprisingly, the simultaneous co-encapsulation and addition of lyoprotectants was detrimental to protein stabilization. The insulin in vitro release studies demonstrated that formulations with co-encapsulated trehalose, glucose, sucrose, fructose and sorbitol...

  19. Convection-Enhanced Delivery of Carboplatin PLGA Nanoparticles for the Treatment of Glioblastoma.

    Science.gov (United States)

    Arshad, Azeem; Yang, Bin; Bienemann, Alison S; Barua, Neil U; Wyatt, Marcella J; Woolley, Max; Johnson, Dave E; Edler, Karen J; Gill, Steven S

    2015-01-01

    We currently use Convection-Enhanced Delivery (CED) of the platinum-based drug, carboplatin as a novel treatment strategy for high grade glioblastoma in adults and children. Although initial results show promise, carboplatin is not specifically toxic to tumour cells and has been associated with neurotoxicity at high infused concentrations in pre-clinical studies. Our treatment strategy requires intermittent infusions due to rapid clearance of carboplatin from the brain. In this study, carboplatin was encapsulated in lactic acid-glycolic acid copolymer (PLGA) to develop a novel drug delivery system. Neuronal and tumour cytotoxicity were assessed in primary neuronal and glioblastoma cell cultures. Distribution, tissue clearance and toxicity of carboplatin nanoparticles following CED was assessed in rat and porcine models. Carboplatin nanoparticles conferred greater tumour cytotoxicity, reduced neuronal toxicity and prolonged tissue half-life. In conclusion, this drug delivery system has the potential to improve the prognosis for patients with glioblastomas.

  20. Mechanical characterization of fiber reinforced Polymer Concrete

    Directory of Open Access Journals (Sweden)

    João Marciano Laredo dos Reis

    2005-09-01

    Full Text Available A comparative study between epoxy Polymer Concrete plain, reinforced with carbon and glass fibers and commercial concrete mixes was made. The fibers are 6 mm long and the fiber content was 2% and 1%, respectively, in mass. Compressive tests were performed at room temperature and load vs. displacement curves were plotted up to failure. The carbon and glass fibers reinforcement were randomly dispersed into the matrix of polymer concrete. An increase in compressive properties was observed as function of reinforcement. The comparison also showed that Polymer Concrete, plain and reinforced, has a better performance than regular market concrete, suggesting that PC is a reliable alternative for construction industry.

  1. Antimicrobial efficacy of poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped cinnamon bark extract against Listeria monocytogenes and Salmonella typhimurium.

    Science.gov (United States)

    Hill, Laura E; Taylor, T Matthew; Gomes, Carmen

    2013-04-01

    Nanoencapsulation of active compounds using poly-(d,l-lactide-co-glycolide) (PLGA) is commonly used in the pharmaceutical industry for drug delivery and may have important applications in the food industry. Control of growth of foodborne bacteria with the goals of reducing the number of foodborne illness outbreaks, assuring consumers a safer food supply remains a priority in the food industry. Natural antimicrobials are an excellent way to eliminate pathogens without introducing chemical preservatives that consumers may find undesirable. Cinnamon bark extract (CBE) is an effective pathogen inhibitor isolated from cinnamon spice. PLGA nanoparticles containing CBE were produced using an emulsion-solvent evaporation method and characterized for size, polydispersity, morphology, entrapment efficiency, in vitro release and pathogen inhibition. PLGA with 2 different ratios of lactide to glycolide (65:35 and 50:50) were used to determine how polymer composition affected nanoparticle characteristics and antimicrobial potency. The size of the nanoparticles ranged from 144.77 to 166.65 nm and the entrapment efficiencies of CBE in 65:35 PLGA and 50:50 PLGA were 38.90% and 47.60%, respectively. The in vitro release profile at 35 °C showed an initial burst effect for both types of PLGA followed by a more gradual release of CBE from the polymer matrix. Both types of PLGA nanoparticles loaded with CBE were effective inhibitors of Salmonella enterica serovar Typhimurium and Listeria monocytogenes after 24 and 72 h at concentrations ranging from 224.42 to 549.23 μg/mL. The PLGA encapsulation improved delivery of hydrophobic antimicrobial to the pathogens in aqueous media. © 2013 Institute of Food Technologists®

  2. Hyaluronic acid-grafted PLGA nanoparticles for the sustained delivery of berberine chloride for an efficient suppression of Ehrlich ascites tumors.

    Science.gov (United States)

    Bhatnagar, Priyanka; Kumari, Manisha; Pahuja, Richa; Pant, A B; Shukla, Y; Kumar, Pradeep; Gupta, K C

    2018-02-13

    To promote the specific targeting and elimination of CD44-positive cancer cells, berberine chloride (BRB)-encapsulated hyaluronic acid-grafted poly(lactic-co-glycolic acid) copolymer (BRB-d(HA)-g-PLGA) nanoparticles (NPs) were prepared. The targeted action of these NPs was compared to non-targeted BRB-loaded PLGA NPs and bulk BRB. The in vitro studies demonstrated faster release of BRB and increased cytotoxicity of BRB-d(HA)-g-PLGA NPs in Hela and MCF-7 cells in comparison to BRB-PLGA NPs and bulk BRB. The uptake of BRB-d(HA)-g-PLGA NPs was increased in case of MCF-7 cells as compared to HeLa cells owing to the higher expression of CD44 receptors on MCF-7 cells. The CD44 receptor-mediated uptake of these NPs was confirmed through competitive inhibition experiments. The in vitro results were further validated in vivo in Ehrlich Ascites Carcinoma (EAC)-bearing mice. EAC-bearing mice were injected intravenously with these NPs and the results obtained were compared with that of BRB-PLGA NPs and bulk BRB. BRB-d(HA)-g-PLGA NPs were found to significantly enhance apoptosis, sub-G1 content, life span, mean survival time, and ROS levels in EAC cells with subsequent decrease in mitochondrial membrane potential and tumor burden ion tumor-bearing mice. Taking into account the findings of in vitro and in vivo studies, the enhanced and targeted anti-tumor activity of HA-grafted PLGA copolymer-encapsulated NPs of BRB cannot be negated. Therefore, HA-grafted nanoparticle-based delivery of BRB may offer a promising and improved alternative for anti-tumor therapy.

  3. Comparative Efficacies of a 3D-Printed PCL/PLGA/β-TCP Membrane and a Titanium Membrane for Guided Bone Regeneration in Beagle Dogs

    OpenAIRE

    Jin-Hyung Shim; Joo-Yun Won; Su-Jin Sung; Dong-Hyuk Lim; Won-Soo Yun; Young-Chan Jeon; Jung-Bo Huh

    2015-01-01

    This study was conducted to evaluate the effects of a 3D-printed resorbable polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membrane on bone regeneration and osseointegration in areas surrounding implants and to compare results with those of a non-resorbable titanium mesh membrane. After preparation of PCL/PLGA/β-TCP membranes using extrusion-based 3D printing technology; mechanical tensile testing and in vitro cell proliferation testing were performed. ...

  4. UPEC biomimickry at the urothelial barrier: lectin-functionalized PLGA microparticles for improved intravesical chemotherapy.

    Science.gov (United States)

    Neutsch, Lukas; Wambacher, Michael; Wirth, Eva-Maria; Spijker, Sylvia; Kählig, Hanspeter; Wirth, Michael; Gabor, Franz

    2013-06-25

    The urgent demand for more potent treatment schedules in bladder cancer (BCa) therapy calls for a refinement of the intravesical administration modalities. However, progress on drug delivery systems tailored to the penetration-hostile urothelial barrier lags behind the advancements in comparable fields. This study reports on a multimodal, carrier-based delivery concept that combines biorecognitive targeting with modified release strategies for improved intravesical chemotherapy. The plant lectin wheat germ agglutinin (WGA) was immobilized on poly(lactide-co-glycolide) (PLGA) microparticles (MP) to induce stable cytoadhesion via cellular carbohydrate chains, similar to the specific attachment mechanism utilized by uropathogenic bacteria. A panel of DNA-selective chemotherapeutics with established track record in uro-oncology was screened for physicochemical compatibility with the polymeric carrier formulation. Critical limitations in encapsulation efficiency were found for mitomycin C (MMC), doxorubicin (DOX), and gemcitabine hydrochloride (GEM), despite multiparametric optimization of the preparation conditions. In contrast, the amphiphilic 4-(N)-stearoyl prodrug of gemcitabine (GEM-C18) exhibited excellent processability with PLGA. In vitro bioassays on 5637 human BCa cells showed that the enhanced cytoadhesion of WGA-GEM-C18-PGLA-MP traces back to the specific lectin/carbohydrate interaction, and is not easily disrupted by adverse environmental factors. Owing to several synergistic effects, the combined prodrug/targeting approach resulted in strong cytostatic response even when adjusting the exposure scheme to the confined temporal conditions of instillative treatment. Our results highlight the importance of fine-tuning both pharmacokinetic and pharmacologic parameters to gain adequate impact on urothelial cancer cells, and assign promising potential to glycan-targeted delivery concepts for the intravesical route. Copyright © 2013 Elsevier B.V. All rights

  5. Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles.

    Science.gov (United States)

    Panyam, Jayanth; Williams, Deborah; Dash, Alekha; Leslie-Pelecky, Diandra; Labhasetwar, Vinod

    2004-07-01

    Biodegradable nanoparticles formulated from poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) polymers are being extensively investigated for various drug delivery applications. In this study, we hypothesize that the solid-state solubility of hydrophobic drugs in polymers could influence their encapsulation and release from nanoparticles. Dexamethasone and flutamide were used as model hydrophobic drugs. A simple, semiquantitative method based on drug-polymer phase separation was developed to determine the solid-state drug-polymer solubility. Nanoparticles using PLGA/PLA polymers were formulated using an emulsion-solvent evaporation technique, and were characterized for size, drug loading, and in vitro release. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were used to determine the physical state of the encapsulated drug. Results demonstrated that the solid-state drug-polymer solubility depends on the polymer composition, molecular weight, and end-functional groups (ester or carboxyl) in polymer chains. Higher solid-state drug-polymer solubility resulted in higher drug encapsulation in nanoparticles, but followed an inverse correlation with the percent cumulative drug released. The XRD and DSC analyses demonstrated that the drug encapsulated in nanoparticles was present in the form of a molecular dispersion (dissolved state) in the polymer, whereas in microparticles, the drug was present in both molecular dispersion and crystalline forms. In conclusion, the solid-state drug-polymer solubility affects the nanoparticle characteristics, and thus could be used as an important preformulation parameter. Copyright 2004 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 93:1804-1814, 2004

  6. Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Doğan, Ayşegül; Demirci, Selami [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey); Bayir, Yasin [Department of Biochemistry, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Halici, Zekai [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karakus, Emre [Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum (Turkey); Aydin, Ali [Department of Orthopedics and Traumatology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Cadirci, Elif [Department of Pharmacology, Faculty of Pharmacy, Ataturk University, 25240, Erzurum (Turkey); Albayrak, Abdulmecit [Department of Pharmacology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Demirci, Elif [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Karaman, Adem [Department of Radiology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Ayan, Arif Kursat [Department of Nuclear Medicine, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Gundogdu, Cemal [Department of Pathology, Faculty of Medicine, Ataturk University, 25240, Erzurum (Turkey); Şahin, Fikrettin, E-mail: fsahin@yeditepe.edu.tr [Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University 34755 Istanbul (Turkey)

    2014-11-01

    Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. - Highlights: • Boron containing PLGA scaffolds were developed for bone tissue engineering. • Boron incorporation increased cell viability and mineralization of stem cells. • Boron containing scaffolds increased bone-related protein expression in vivo. • Implantation of stem cells on boron containing scaffolds improved bone healing.

  7. Hepatic toxicity caused by PLGA-microspheres containing usnic acid from the lichen C ladonia substellata (AHTI during pregnancy in Wistar rats

    Directory of Open Access Journals (Sweden)

    KETSIA S.N. MARINHO

    Full Text Available ABSTRACT This study aimed to evaluate the teratogenic and hepatotoxic potential of the usnic acid encapsulated into PLGA-microspheres. In total, 12 female Wistar rats in pregnancy were randomly distributed in the control group (n= 6 that received 1.0 mL of physiological solution and treatment group (n= 6 that received 25 mg/kg of encapsulated usnic acid by oral administration. All females were euthanized at day 20 of pregnancy and their fetuses were removed and analyzed. During the pregnancy was observed a reduction in weight gain. There was no difference in serum transaminases levels analyzed as well as any difference in liver weight in both groups. The histomorphometric analysis of the liver from the treatment group revealed an increase in number of hepatocytes and a decrease in nuclear area of these cells. Moreover, no alteration was observed in cell area of hepatocytes or number of Kupffer cells. The fetuses had an increase in total number of hepatocytes and a reduction in the amount of megakaryocytes. These results show the hepatotoxic potential of usnic acid during pregnancy. However, its toxicity can be minimized by encapsulation in microspheres.

  8. Poly aspartic acid peptide-linked PLGA based nanoscale particles: potential for bone-targeting drug delivery applications.

    Science.gov (United States)

    Jiang, Tao; Yu, Xiaohua; Carbone, Erica J; Nelson, Clarke; Kan, Ho Man; Lo, Kevin W-H

    2014-11-20

    Delivering drugs specifically to bone tissue is very challenging due to the architecture and structure of bone tissue. Poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) hold great promise for the delivery of therapeutics to bone tissue. The goal of the present research was to formulate a PLGA-based NP drug delivery system for bone tissue exclusively. Since poly-aspartic acids (poly-Asp) peptide sequence has been shown to bind to hydroxyapatite (HA), and has been suggested as a molecular tool for bone-targeting applications, we fabricated PLGA-based NPs linked with poly-Asp peptide sequence. Nanoparticles made of methoxy - poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged poly-Asp peptide was conjugated to the surface of the nanoparticles via the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the CC double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged poly-Asp peptide to PLGA NPs was confirmed by NMR analysis and fluorescent microscopy. The developed nanoparticle system is highly aqueous dispersible with an average particle size of ∼80 nm. In vitro binding analyses demonstrated that FITC-poly-Asp NPs were able to bind to HA gel as well as to mineralized matrices produced by human mesenchymal stem cells and mouse bone marrow stromal cells. Using a confocal microscopy technique, an ex vivo binding study of mouse major organ ground sections revealed that the FITC-poly-Asp NPs were able to bind specifically to the bone tissue. In addition, proliferation studies indicated that our FITC-poly-Asp NPs did not induce cytotoxicity to human osteoblast-like MG63 cell lines. Altogether, these promising results indicated that this nanoscale targeting system was able to bind to bone tissue specifically and might have a great

  9. A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering.

    Science.gov (United States)

    Boukari, Yamina; Qutachi, Omar; Scurr, David J; Morris, Andrew P; Doughty, Stephen W; Billa, Nashiru

    2017-11-01

    The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.

  10. Stimulating effect of graphene oxide on myogenesis of C2C12 myoblasts on RGD peptide-decorated PLGA nanofiber matrices.

    Science.gov (United States)

    Shin, Yong Cheol; Lee, Jong Ho; Kim, Min Jeong; Hong, Suck Won; Kim, Bongju; Hyun, Jung Keun; Choi, Yu Suk; Park, Jong-Chul; Han, Dong-Wook

    2015-01-01

    In the field of biomedical engineering, many studies have focused on the possible applications of graphene and related nanomaterials due to their potential for use as scaffolds, coating materials and delivery carriers. On the other hand, electrospun nanofiber matrices composed of diverse biocompatible polymers have attracted tremendous attention for tissue engineering and regenerative medicine. However, their combination is intriguing and still challenging. In the present study, we fabricated nanofiber matrices composed of M13 bacteriophage with RGD peptide displayed on its surface (RGD-M13 phage) and poly(lactic-co-glycolic acid, PLGA) and characterized their physicochemical properties. In addition, the effect of graphene oxide (GO) on the cellular behaviors of C2C12 myoblasts, which were cultured on PLGA decorated with RGD-M13 phage (RGD/PLGA) nanofiber matrices, was investigated. Our results revealed that the RGD/PLGA nanofiber matrices have suitable physicochemical properties as a tissue engineering scaffold and the growth of C2C12 myoblasts were significantly enhanced on the matrices. Moreover, the myogenic differentiation of C2C12 myoblasts was substantially stimulated when they were cultured on the RGD/PLGA matrices in the presence of GO. In conclusion, these findings propose that the combination of RGD/PLGA nanofiber matrices and GO can be used as a promising strategy for skeletal tissue engineering and regeneration.

  11. Stochastic phenomena in a fiber Raman amplifier

    CERN Document Server

    Kalashnikov, Vladimir; Ania-Castanón, Juan Diego; Jacobsen, Gunnar; Popov, Sergei

    2016-01-01

    The interplay of such cornerstones of modern nonlinear fiber optics as a nonlinearity, stochasticity and polarization leads to variety of the noise induced instabilities including polarization attraction and escape phenomena harnessing of which is a key to unlocking the fiber optic systems specifications required in high resolution spectroscopy, metrology, biomedicine and telecommunications. Here, by using direct stochastic modeling, the mapping of interplay of the Raman scattering-based nonlinearity, the random birefringence of a fiber, and the pump-to-signal intensity noise transfer has been done in terms of the fiber Raman amplifier parameters, namely polarization mode dispersion, the relative intensity noise of the pump laser, fiber length, and the signal power. The obtained results reveal conditions for emergence of the random birefringence-induced resonance-like enhancement of the gain fluctuations (stochastic anti-resonance) accompanied by pulse broadening and rare events in the form of low power outpu...

  12. Study of Optical Fiber Sensors for Cryogenic Temperature Measurements

    Directory of Open Access Journals (Sweden)

    Veronica De Miguel-Soto

    2017-11-01

    Full Text Available In this work, the performance of five different fiber optic sensors at cryogenic temperatures has been analyzed. A photonic crystal fiber Fabry-Pérot interferometer, two Sagnac interferometers, a commercial fiber Bragg grating (FBG, and a π-phase shifted fiber Bragg grating interrogated in a random distributed feedback fiber laser have been studied. Their sensitivities and resolutions as sensors for cryogenic temperatures have been compared regarding their advantages and disadvantages. Additionally, the results have been compared with the given by a commercial optical backscatter reflectometer that allowed for distributed temperature measurements of a single mode fiber.

  13. Fiber resources

    Science.gov (United States)

    P. J. Ince

    2004-01-01

    In economics, primary inputs or factors of production define the term ‘resources.’ Resources include land resources (plants, animals, and minerals), labor, capital, and entrepreneurship. Almost all pulp and paper fiber resources are plant materials obtained from trees or agricultural crops. These resources encompass plant materials harvested directly from the land (...

  14. Addition of Rye Bran and Pea Fiber to Pork Meatballs Enhances Subjective Satiety in Healthy Men, but Does Not Change Glycemic or Hormonal Responses: A Randomized Crossover Meal Test Study.

    Science.gov (United States)

    Kehlet, Ursula; Kofod, Josephine; Holst, Jens J; Ritz, Christian; Aaslyng, Margit D; Raben, Anne

    2017-09-01

    Background: The development of high-protein, fiber-rich foods targeting appetite control could be an efficient tool in obesity prevention. Objectives: We investigated whether ad libitum energy intake (EI), appetite, and metabolic markers in a meal context were affected by 1 ) fiber addition (rye bran and pea fiber) to pork meatballs, 2 ) the food matrix of the fiber (fiber meatballs compared with fiber bread), or 3 ) the protein source (animal compared with vegetable protein patties). Methods: In a crossover design, 40 healthy men [mean ± SD: body mass index (BMI; in kg/m 2 ), 22.2 ± 1.9; age, 23.3 ± 2.9 y] consumed 4 test meals: a low-fiber meal consisting of pork meatballs plus wheat bread (LF meal); pork meatballs plus fiber bread; fiber meatballs plus wheat bread, and vegetable patties with a natural fiber content plus wheat bread (∼3000 kJ; protein ∼18% of energy, carbohydrate ∼50% of energy, fat ∼30% of energy; 13 g fiber in the fiber meals). Ad libitum EI after 4 h was the primary endpoint. Moreover, appetite sensations and postprandial responses of glucose, insulin, glucagon-like peptide-1, peptide YY 3-36, and plasma amino acids were measured. Results: Ad libitum EI did not differ significantly between the meals. Satiety and fullness increased 11% and 13%, respectively, and hunger and prospective intake decreased 17% and 15%, respectively, after the meal of fiber meatballs plus wheat bread compared with the LF meal ( P Hormonal and metabolic responses did not differ between the meals. In general, plasma amino acid concentrations were higher after the fiber-rich meals than after the LF meal. Conclusions: Meals based on meatballs and bread with differences in the fiber content, food matrix of fiber, and protein source had similar effects on ad libitum EI in healthy men. However, fiber addition to pork meatballs favorably affected appetite sensations but without changes in hormonal and metabolic responses. Moreover, animal- and vegetable

  15. Fiber-reinforced sand strength and dilation characteristics

    Directory of Open Access Journals (Sweden)

    Hesham M. Eldesouky

    2016-06-01

    Full Text Available Randomly distributed fiber reinforcement is used to provide an isotropic increase in the sand shear strength. The previous studies were not consistent regarding the fibers effect on the volumetric change behavior of fiber-reinforced sand. In this paper, direct shear tests are conducted on 108 specimens to investigate the effects of the fibers content, relative density, normal stress and moisture content on the shear strength and volumetric change behaviors of fiber-reinforced sand. The study investigates also the possibility of using dry fiber-reinforced sand as an alternative to heavily compacted unreinforced moist sand. The results indicate that the fibers inclusion increases the shear strength and dilation of sand. Moisture suppresses the fibers effect on the peak and post-peak shear strengths, and dilation. Dry loose fiber-reinforced sand achieves the same shear strength of heavily compacted unreinforced moist sand, yet at more than double the horizontal displacement.

  16. Effect of Injection Molding Melt Temperatures on PLGA Craniofacial Plate Properties duringIn VitroDegradation.

    Science.gov (United States)

    de Melo, Liliane Pimenta; Salmoria, Gean Vitor; Fancello, Eduardo Alberto; Roesler, Carlos Rodrigo de Mello

    2017-01-01

    The purpose of this article is to present mechanical and physicochemical properties during in vitro degradation of PLGA material as craniofacial plates based on different values of injection molded temperatures. Injection molded plates were submitted to in vitro degradation in a thermostat bath at 37 ± 1°C by 16 weeks. The material was removed after 15, 30, 60, and 120 days; then bending stiffness, crystallinity, molecular weights, and viscoelasticity were studied. A significant decrease of molecular weight and mechanical properties over time and a difference in FT-IR after 60 days showed faster degradation of the material in the geometry studied. DSC analysis confirmed that the crystallization occurred, especially in higher melt temperature condition. DMA analysis suggests a greater contribution of the viscous component of higher temperature than lower temperature in thermomechanical behavior. The results suggest that physical-mechanical properties of PLGA plates among degradation differ per injection molding temperatures.

  17. Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies

    Science.gov (United States)

    Fornaguera, Cristina; Calderó, Gabriela; Mitjans, Montserrat; Vinardell, Maria Pilar; Solans, Conxita; Vauthier, Christine

    2015-03-01

    The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising alternative for delivery of drugs to specific cells. However, studies on their interaction with diverse blood components using different techniques are still lacking. Therefore, in the present work, the interaction of PLGA nanoparticles with blood components was described using different complementary techniques. The influence of different encapsulated compounds/functionalizing agents on these interactions was also reported. It is worth noting that all these techniques can be simply performed, without the need for highly sophisticated apparatus or skills. Moreover, their transference to industries and application of quality control could be easily performed. Serum albumin was adsorbed onto all types of tested nanoparticles. The saturation concentration was dependent on the nanoparticle size. In contrast, fibrinogen aggregation was dependent on nanoparticle surface charge. The complement activation was also influenced by the nanoparticle functionalization; the presence of a functionalizing agent increased complement activation, while the addition of an encapsulated compound only caused a slight increase. None of the nanoparticles influenced the coagulation cascade at low concentrations. However, at high concentrations, cationized nanoparticles did activate the coagulation cascade. Interactions of nanoparticles with erythrocytes did not reveal any hemolysis. Interactions of PLGA nanoparticles with blood proteins depended both on the nanoparticle properties and the protein studied. Independent of their loading/surface functionalization, PLGA nanoparticles did not influence the coagulation cascade and did not induce hemolysis of erythrocytes; they could be defined as safe concerning induction of embolization and cell lysis.The intravenous administration of poly(lactic-co-glycolic) acid (PLGA) nanoparticles has been widely reported as a promising

  18. Grooved PLGA films incorporated with RGD/YIGSR peptides for potential application on skeletal muscle tissue engineering.

    Science.gov (United States)

    Wang, Peng-Yuan; Wu, Tsung-Han; Tsai, Wei-Bor; Kuo, Wei-Hsuan; Wang, Meng-Jiy

    2013-10-01

    Alignment of myocytes or myotubes is critical for skeletal muscle tissue engineering. In this study, grooved PLGA films (800nm in width of ridge/groove and 600nm in depth) incorporated with RGD or YIGSR peptides were fabricated to evaluate its efficacy for skeletal muscle tissue engineering. The growth and differentiation of C2C12 myoblasts were enhanced by the presentation of RGD or YIGSR compared with the untreated PLGA control. On the other hand, cell morphology was guided by the grooved structure, i.e. alignment of myoblasts and myotubes with the direction of grooves. This study elucidates the effects of both surface biochemical and topographic cues on the proliferation and differentiation of C2C12 myoblasts on biodegradable polymer films. Combination of surface topography and peptide presentation has a great potential in designing scaffolds for skeletal muscle tissue engineering. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. PLGA-soya lecithin based micelles for enhanced delivery of methotrexate: Cellular uptake, cytotoxic and pharmacokinetic evidences.

    Science.gov (United States)

    Singh, Anupama; Thotakura, Nagarani; Kumar, Rajendra; Singh, Bhupinder; Sharma, Gajanand; Katare, Om Prakash; Raza, Kaisar

    2017-02-01

    Biocompatible and biodegradable polymers like PLGA have revolutionized the drug delivery approaches. However, poor drug loading and substantially high lipophilicity, pave a path for further tailing of this promising agent. In this regard, PLGA was feathered with biocompatible phospholipid and polymeric micelles were developed for delivery of Methotrexate (MTX) to cancer cells. The nanocarriers (114.6nm±5.5nm) enhanced the cytotoxicity of MTX by 2.13 folds on MDA-MB-231 cells. Confocal laser scanning microscopy confirmed the increased intracellular delivery. The carrier decreased the protein binding potential and enhanced the bioavailable fraction of MTX. Pharmacokinetic studies vouched substantial enhancement in AUC and bioresidence time, promising an ideal carrier to effectively deliver the drug to the site of action. The developed nanocarriers offer potential to deliver the drug in the interiors of cancer cells in an effective manner for improved therapeutic action. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Design and characterization of core-shell mPEG-PLGA composite microparticles for development of cell-scaffold constructs

    DEFF Research Database (Denmark)

    Wen, Yanhong; Gallego, Monica Ramos; Nielsen, Lene Feldskov

    2013-01-01

    Appropriate scaffolds capable of providing suitable biological and structural guidance are of great importance to generate cell-scaffold constructs for cell-based tissue engineering. The aim of the present study was to develop composite microparticles with a structure to provide functionality...... as a combined drug delivery/scaffold system. Composite microparticles were produced by incorporating either alginate/dermatan sulfate (Alg/DS) or alginate/chitosan/dermatan sulfate (Alg/CS/DS) particles in mPEG-PLGA microparticles using coaxial ultrasonic atomization. The encapsulation and distribution of Alg....../DS or Alg/CS/DS particles in the mPEG-PLGA microparticles were significantly dependent on the operating conditions, including the flow rate ratio (Qout/Qin) and the viscosity of the polymer solutions (Vout, Vin) between the outer and the inner feeding channels. The core-shell composite microparticles...

  1. Parallel Information Processing (Image Transmission Via Fiber Bundle and Multimode Fiber

    Science.gov (United States)

    Kukhtarev, Nicholai

    2003-01-01

    Growing demand for visual, user-friendly representation of information inspires search for the new methods of image transmission. Currently used in-series (sequential) methods of information processing are inherently slow and are designed mainly for transmission of one or two dimensional arrays of data. Conventional transmission of data by fibers requires many fibers with array of laser diodes and photodetectors. In practice, fiber bundles are also used for transmission of images. Image is formed on the fiber-optic bundle entrance surface and each fiber transmits the incident image to the exit surface. Since the fibers do not preserve phase, only 2D intensity distribution can be transmitted in this way. Each single mode fiber transmit only one pixel of an image. Multimode fibers may be also used, so that each mode represent different pixel element. Direct transmission of image through multimode fiber is hindered by the mode scrambling and phase randomization. To overcome these obstacles wavelength and time-division multiplexing have been used, with each pixel transmitted on a separate wavelength or time interval. Phase-conjugate techniques also was tested in, but only in the unpractical scheme when reconstructed image return back to the fiber input end. Another method of three-dimensional imaging over single mode fibers was demonstrated in, using laser light of reduced spatial coherence. Coherence encoding, needed for a transmission of images by this methods, was realized with grating interferometer or with the help of an acousto-optic deflector. We suggest simple practical holographic method of image transmission over single multimode fiber or over fiber bundle with coherent light using filtering by holographic optical elements. Originally this method was successfully tested for the single multimode fiber. In this research we have modified holographic method for transmission of laser illuminated images over commercially available fiber bundle (fiber endoscope, or

  2. Unidirectional high fiber content composites: Automatic 3D FE model generation and damage simulation

    DEFF Research Database (Denmark)

    Qing, Hai; Mishnaevsky, Leon

    2009-01-01

    A new method and a software code for the automatic generation of 3D micromechanical FE models of unidirectional long-fiber-reinforced composite (LFRC) with high fiber volume fraction with random fiber arrangement are presented. The fiber arrangement in the cross-section is generated through rando...

  3. Prevention of Oxidized Low Density Lipoprotein-Induced Endothelial Cell Injury by DA-PLGA-PEG-cRGD Nanoparticles Combined with Ultrasound.

    Science.gov (United States)

    Li, Zhaojun; Huang, Hui; Huang, Lili; Du, Lianfang; Sun, Ying; Duan, Yourong

    2017-04-13

    In general, atherosclerosis is considered to be a form of chronic inflammation. Dexamethasone has anti-inflammatory effects in atherosclerosis, but it was not considered for long-term administration on account of a poor pharmacokinetic profile and adverse side effects. Nanoparticles in which drugs can be dissolved, encapsulated, entrapped or chemically attached to the particle surface have abilities to incorporate dexamethasone and to be used as controlled or targeted drug delivery system. Long circulatory polymeric nanoparticles present as an assisting approach for controlled and targeted release of the encapsulated drug at the atherosclerotic site. Polymeric nanoparticles combined with ultrasound (US) are widely applied in cancer treatment due to their time applications, low cost, simplicity, and safety. However, there are few studies on atherosclerosis treatment using polymeric nanoparticles combined with US. In this study, targeted dexamethasone acetate (DA)-loaded poly (lactide-glycolide)-polyethylene glycol-cRGD (PLGA-PEG-cRGD) nanoparticles (DA-PLGA-PEG-cRGD NPs) were prepared by the emulsion-evaporation method using cRGD modified PLGA-PEG polymeric materials (PLGA-PEG-cRGD) prepared as the carrier. The average particle size of DA-PLGA-PEG-cRGD NPs was 221.6 ± 0.9 nm. Morphology of the nanoparticles was spherical and uniformly dispersed. In addition, the DA released profiles suggested that ultrasound could promote drug release from the nanocarriers and accelerate the rate of release. In vitro, the cellular uptake process of fluorescein isothiocyanate (FITC)@DA-PLGA-PEG-cRGD NPs combined with US into the damaged human umbilical vein endothelial cells (HUVECs) indicated that US promoted rapid intracellular uptake of FITC@DA- PLGA-PEG-cRGD NPs. The cell viability of DA-PLGA-PEG-cRGD NPs combined with US reached 91.9% ± 0.2%, which demonstrated that DA-PLGA-PEG-cRGD NPs combined with US had a positive therapeutic effect on damaged HUVECs. Overall, DA-PLGA

  4. Role Of Polymeric Excipients On Controlled Release Profile of Glipizide from PLGA and Eudragit RS 100 Nanoparticles

    OpenAIRE

    Naha, Pratap; Byrne, Hugh; Panda, Amulya

    2012-01-01

    Polylactic-co-glycolic acid (PLGA) 50:50 and Eudragit RS 100 nanoparticles entrapping glipizide along with excipients were prepared using single emulsion solvent evaporation method. The objective was to develop single oral dose glipizide nano particles for reducing blood sugar level in diabetes induced experimental animals. Incorporation of Polyethylene glycol (PEG) (0.5%), Hydroxypropyl methylcellulose (HPMC) (0.5%) and Tween 20 (0.5%) in the organic phase during particle formulation improve...

  5. [Experimental study of tissue-engineered bone constructed with simvastatin carried by PLGA/CPC and bone marrow stromal cells].

    Science.gov (United States)

    Han, Xiao-qian; Han, Xiao-qian; Dong, Zhi-heng; Yu, Xiang-ru; Guo, Chong-chong; Gu, Xu; Wu, Zhe

    2014-02-01

    To study the feasibility of tissue engineered bone constructed with simvastatin carried by PLGA/CPC and bone marrow stromal cells (BMSCs) and screen the effective drug loading of simvastatin. Solvent casting-particle leaching technology combined with the phase separation process was used to prepare the different concentrations (simvastatin mass: 0.1, 0.5, 1 mg) of simvastatin carried by PLGA/CPC composite scaffold materials. Scanning electron microscopy was used to observe the porosity and drug release curve was drawn; Alizarin red staining and type I collagen staining were applied to observe the effect of osteogenic medium and simvastatin on the role of BMSCs to the osteogenetic differentiation. The induced passage 3 cells after dil staining were mixed with the composite scaffold material to a complex. Scanning electron microscopy and laser confocal microscope were used to observe the adhesion on the complex. CCK-8 and alkaline phosphatase (ALP) were applied to observe the proliferation and differentiation. SPSS 18.0 software package was used for statistical analysis. The scaffold porosity was more than 90% with an average aperture of 200-300 μm. The drug released slowly. There was no obvious interpretation. Type I collagen showed positive expression. Alizarin red staining proofed the formation of mineralization nodules in group which was induced with the conditional medium and simvastatin. 0.5 mg group showed cells adhered to the inner surface of the scaffold material and could significantly promote the proliferation and differentiation of cells. Combination of simvastatin and osteogenic medium can effectively promote the differentiation of BMSCs. Simvastatin carried by PLGA/CPC scaffold materials is an ideal tissue engineering scaffold material. PLGA/CPC scaffold containing 0.5 mg simvastatin can effectively promote the proliferation and differentiation of BMSCs. Supported by Natural Science Foundation of Jilin Province (201215052).

  6. New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB) Stabilized Poly(Lactic-co-Glycolic Acid) (PLGA) Nanoparticles

    OpenAIRE

    Rebecca Gossmann; Klaus Langer; Dennis Mulac

    2015-01-01

    Over the last few decades the establishment of nanoparticles as suitable drug carriers with the transport of drugs across biological barriers such as the gastrointestinal barrier moved into the focus of many research groups. Besides drug transport such carrier systems are well suited for the protection of drugs against enzymatic and chemical degradation. The preparation of biocompatible and biodegradable nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) is intensively described in l...

  7. Biocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate Nanocomposites in Sheep.

    Science.gov (United States)

    Schneider, Oliver D; Mohn, Dirk; Fuhrer, Roland; Klein, Karina; Kämpf, Käthi; Nuss, Katja M R; Sidler, Michèle; Zlinszky, Katalin; von Rechenberg, Brigitte; Stark, Wendelin J

    2011-03-16

    The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects.

  8. Evaluation of Motor Neuron-Like Cell Differentiation of hEnSCs on Biodegradable PLGA Nanofiber Scaffolds.

    Science.gov (United States)

    Ebrahimi-Barough, Somayeh; Norouzi Javidan, Abbas; Saberi, Hoshangh; Joghataei, Mohammad Tghi; Rahbarghazi, Reza; Mirzaei, Esmaeil; Faghihi, Faezeh; Shirian, Sadegh; Ai, Armin; Ai, Jafar

    2015-12-01

    Human endometrium is a high-dynamic tissue that contains human endometrial stem cells (hEnSCs) which can be differentiated into a number of cell lineages. The differentiation of hEnSCs into many cell lineages such as osteoblast, adipocyte, and neural cells has been investigated previously. However, the differentiation of these stem cells into motor neuron-like cells has not been investigated yet. Different biochemical and topographical cues can affect the differentiation of stem cells into a specific cell. The aim of this study was to investigate the capability of hEnSCs to be differentiated into motor neuron-like cells under biochemical and topographical cues. The biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) electrospun nanofibrous scaffold was used as a topographical cue. Human EnSCs were cultured on the PLGA scaffold and tissue culture polystyrene (TCP), then differentiation of hEnSCs into motor neuron-like cells under induction media including retinoic acid (RA) and sonic hedgehog (Shh) were evaluated for 15 days. The proliferation rate of cells was assayed by using MTT assay. The morphology of cells was studied by scanning electron microscopy imaging, and the expression of motor neuron-specific markers by real-time PCR and immunocytochemistry. Results showed that survival and differentiation of hEnSCs into motor neuron-like cells on the PLGA scaffold were better than those on the TCP group. Taken together, the results suggest that differentiated hEnSCs on PLGA can provide a suitable, three-dimensional situation for neuronal survival and outgrowth for regeneration of the central nervous system, and these cells may be a potential candidate in cellular therapy for motor neuron diseases.

  9. Fiber tractography using machine learning.

    Science.gov (United States)

    Neher, Peter F; Côté, Marc-Alexandre; Houde, Jean-Christophe; Descoteaux, Maxime; Maier-Hein, Klaus H

    2017-09-01

    We present a fiber tractography approach based on a random forest classification and voting process, guiding each step of the streamline progression by directly processing raw diffusion-weighted signal intensities. For comparison to the state-of-the-art, i.e. tractography pipelines that rely on mathematical modeling, we performed a quantitative and qualitative evaluation with multiple phantom and in vivo experiments, including a comparison to the 96 submissions of the ISMRM tractography challenge 2015. The results demonstrate the vast potential of machine learning for fiber tractography. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Caffeic Acid Phenethyl Ester Loaded PLGA Nanoparticles: Effect of Various Process Parameters on Reaction Yield, Encapsulation Efficiency, and Particle Size

    Directory of Open Access Journals (Sweden)

    Serap Derman

    2015-01-01

    Full Text Available CAPE loaded PLGA nanoparticles were prepared using the oil in water (o/w single emulsion solvent evaporation methods. Five different processing parameters including initial CAPE amount, initial PLGA amount, PVA concentration in aqueous phase, PVA volume, and solvent type were screened systematically to improve encapsulation of hydrophobic CAPE molecule, simultaneously minimize particle size, and raise the reaction yield. Obtained results showed that the encapsulation efficiency of the nanoparticles significantly increased with the increase of the initial CAPE amount (p<0.05 and particle size (p<0.05. Furthermore, the particle size is significantly influenced by initial polymer amount (p<0.05 and surfactant concentration (p<0.05. By the optimization of process parameters, the nanoparticles produced 70±6% reaction yield, 89±3% encapsulation efficiency, -34.4±2.5 mV zeta potential, and 163±2 nm particle size with low polydispersity index 0.119±0.002. The particle size and surface morphology of optimized nanoparticles were studied and analyses showed that the nanoparticles have uniform size distribution, smooth surface, and spherical shape. Lyophilized nanoparticles with different CAPE and PLGA concentration in formulation were examined for in vitro release at physiological pH. Interestingly, the optimized nanoparticles showed a high (83.08% and sustained CAPE release (lasting for 16 days compared to nonoptimized nanoparticle.

  11. Fabrication of multi-layered biodegradable drug delivery device based on micro-structuring of PLGA polymers.

    Science.gov (United States)

    Ryu, Won Hyoung; Vyakarnam, Murty; Greco, Ralph S; Prinz, Fritz B; Fasching, Rainer J

    2007-12-01

    A programmable and biodegradable drug delivery device is desirable when a drug needs to be administered locally. While most local drug delivery devices made of biodegradable polymers relied on the degradation of the polymers, the degradation-based release control is often limited by the property of the polymers. Thus, we propose micro-geometry as an alternative measure of controlling drug release. The proposed devices consist of three functional layers: diffusion control layer via micro-orifices, diffusion layer, and drug reservoir layers. A micro-fabrication technology was used to shape an array of micro-orifices and micro-cavities in 85/15PLGA layers. A thin layer of fast degrading 50/50PLGA was placed as the diffusion layer between the 85/15PLGA layers to prevent any burst-type release. To modulate the release of the devices, the dimension and location of the micro-orifices were varied and the responding in vitro release response of tetracycline was monitored over 2 weeks. The release response to the different micro-geometry was prominent and further analyzed by FEM simulation. Comparison of the experiments to the simulated results identified that the variation of micro-geometry influenced also the volume-dependent degradation rate and induced the osmotic pressure.

  12. Robust, Responsive, and Targeted PLGA Anticancer Nanomedicines by Combination of Reductively Cleavable Surfactant and Covalent Hyaluronic Acid Coating.

    Science.gov (United States)

    Wu, Jintian; Zhang, Jian; Deng, Chao; Meng, Fenghua; Cheng, Ru; Zhong, Zhiyuan

    2017-02-01

    PLGA-based nanomedicines have enormous potential for targeted cancer therapy. To boost their stability, targetability, and intracellular drug release, here we developed novel multifunctional PLGA anticancer nanomedicines by combining a reductively cleavable surfactant (RCS), vitamin E-SS-oligo(methyl diglycol l-glutamate), with covalent hyaluronic acid (HA) coating. Reduction-sensitive HA-coated PLGA nanoparticles (rHPNPs) were obtained with small sizes of 55-61 nm and ζ potentials of -26.7 to -28.8 mV at 18.4-40.3 wt % RSC. rHPNPs were stable against dilution and 10% FBS while destabilized under reductive condition. The release studies revealed significantly accelerated docetaxel (DTX) release in the presence of 10 mM glutathione. DTX-rHPNPs exhibited potent and specific antitumor effect to CD44 + A549 lung cancer cells (IC50 = 0.52 μg DTX equiv/mL). The in vivo studies demonstrated that DTX-rHPNPs had an extended circulation time and greatly enhanced tolerance in mice. Strikingly, DTX-rHPNPs completely inhibited growth of orthotopic human A549-Luc lung tumor in mice, leading to a significantly improved survival rate and reduced adverse effect as compared to free DTX. This study highlights that advanced nanomedicines can be rationally designed by combining functional surfactants and surface coating.

  13. Topical delivery of urea encapsulated in biodegradable PLGA microparticles: O/W and W/O creams.

    Science.gov (United States)

    Haddadi, Azita; Aboofazeli, Reza; Erfan, Mohammad; Farboud, Effat Sadat

    2008-09-01

    This study describes the formulation and characterization of O/W and W/O creams containing urea-loaded microparticles prepared with poly (D, L-lactic-co-glycolic acid) (PLGA) in order to encapsulate and stabilize urea. The solvent evaporation method was used for preparing PLGA microparticles containing urea. The microparticles size was evaluated by laser light diffractometry. The resulting microparticles were then incorporated in O/W and W/O creams and stability and the release pattern from the creams was evaluated by UV-spectrophotometry. The particle size of PLGA microparticles was in the range of 1-5 microm and most microparticles had a particle size smaller than 3 microm. The encapsulation efficiency was calculated as 40.5% +/- 3.4. This study also examined release pattern of urea which varied among different formulations. The results showed that the release from O/W creams followed Higuchi kinetics while the release from W/O creams showed the zero order kinetics and the creams containing microparticulated urea had slower release than free urea creams.

  14. Characterization of Plasmid DNA Location within Chitosan/PLGA/pDNA Nanoparticle Complexes Designed for Gene Delivery

    Directory of Open Access Journals (Sweden)

    Hali Bordelon

    2011-01-01

    Full Text Available Poly(D,L-lactide-co-glycolide- (PLGA-chitosan nanoparticles are becoming an increasingly common choice for the delivery of nucleic acids to cells for various genetic manipulation techniques. These particles are biocompatible, with tunable size and surface properties, possessing an overall positive charge that promotes complex formation with negatively charged nucleic acids. This study examines properties of the PLGA-chitosan nanoparticle/plasmid DNA complex after formation. Specifically, the study aims to determine the optimal ratio of plasmid DNA:nanoparticles for nucleic acid delivery purposes and to elucidate the location of the pDNA within these complexes. Such characterization will be necessary for the adoption of these formulations in a clinical setting. The ability of PLGA-chitosan nanoparticles to form complexes with pDNA was evaluated by using the fluorescent intercalating due OliGreen to label free plasmid DNA. By monitoring the fluorescence at different plasmid: nanoparticle ratios, the ideal plasmid:nanoparticle ration for complete complexation of plasmid was determined to be 1:50. Surface-Enhanced Raman Spectroscopy and gel digest studies suggested that even at these optimal complexation ratios, a portion of the plasmid DNA was located on the outer complex surface. This knowledge will facilitate future investigations into the functionality of the system in vitro and in vivo.

  15. Curcumin conjugated with PLGA potentiates sustainability, anti-proliferative activity and apoptosis in human colon carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Bhargav N Waghela

    Full Text Available Curcumin, an ingredient of turmeric, exhibits a variety of biological activities such as anti-inflammatory, anti-atherosclerotic, anti-proliferative, anti-oxidant, anti-cancer and anti-metastatic. It is a highly pleiotropic molecule that inhibits cell proliferation and induces apoptosis in cancer cells. Despite its imperative biological activities, chemical instability, photo-instability and poor bioavailability limits its utilization as an effective therapeutic agent. Therefore, enhancing the bioavailability of curcumin may improve its therapeutic index for clinical setting. In the present study, we have conjugated curcumin with a biodegradable polymer Poly (D, L-lactic-co-glycolic acid and evaluated its apoptotic potential in human colon carcinoma cells (HCT 116. The results show that curcumin-PLGA conjugate efficiently inhibits cell proliferation and cell survival in human colon carcinoma cells as compared to native curcumin. Additionally, curcumin conjugated with PLGA shows improved cellular uptake and exhibits controlled release at physiological pH as compared to native curcumin. The curcumin-PLGA conjugate efficiently activates the cascade of caspases and promotes intrinsic apoptotic signaling. Thus, the results suggest that conjugation potentiates the sustainability, anti-proliferative and apoptotic activity of curcumin. This approach could be a promising strategy to improve the therapeutic index of cancer therapy.

  16. The Polyp Prevention Trial–Continued Follow-up Study: No Effect of a Low-Fat, High-Fiber, High-Fruit, and -Vegetable Diet on Adenoma Recurrence Eight Years after Randomization

    National Research Council Canada - National Science Library

    Elaine Lanza; Binbing Yu; Gwen Murphy; Paul S. Albert; Bette Caan; James R. Marshall; Peter Lance; Electra D. Paskett; Joel Weissfeld; Marty Slattery; Randall Burt; Frank Iber; Moshe Shike; James W. Kikendall; Brenda K. Brewer; Arthur Schatzkin

    2007-01-01

    .... Although intervention participants reported a significantly reduced intake of dietary fat, and increased fiber, fruit, and vegetable intakes, their risk of recurrent adenomas was not significantly...

  17. Collagen-coated polylactic-glycolic acid (PLGA) seeded with neural-differentiated human mesenchymal stem cells as a potential nerve conduit.

    Science.gov (United States)

    Sulong, Ahmad Fadzli; Hassan, Nur Hidayah; Hwei, Ng Min; Lokanathan, Yogeswaran; Naicker, Amaramalar Selvi; Abdullah, Shalimar; Yusof, Mohd Reusmaazran; Htwe, Ohnmar; Idrus, Ruszymah Bt Hj; Haflah, Nor Hazla Mohamed

    2014-01-01

    Autologous nerve grafts to bridge nerve gaps pose various drawbacks. Nerve tissue engineering to promote nerve regeneration using artificial neural conduits has emerged as a promising alternative. To develop an artificial nerve conduit using collagen-coated polylactic-glycolic acid (PLGA) and to analyse the survivability and propagating ability of the neuro-differentiated human mesenchymal stem cells in this conduit. The PLGA conduit was constructed by dip-molding method and coated with collagen by immersing the conduit in collagen bath. The ultra structure of the conduits were examined before they were seeded with neural-differentiated human mesenchymal stem cells (nMSC) and implanted sub-muscularly on nude mice thighs. The non-collagen-coated PLGA conduit seeded with nMSC and non-seeded non-collagen-coated PLGA conduit were also implanted for comparison purposes. The survivability and propagation ability of nMSC was studied by histological and immunohistochemical analysis. The collagen-coated conduits had a smooth inner wall and a highly porous outer wall. Conduits coated with collagen and seeded with nMSCs produced the most number of cells after 3 weeks. The best conduit based on the number of cells contained within it after 3 weeks was the collagen-coated PLGA conduit seeded with neuro-transdifferentiated cells. The collagen-coated PLGA conduit found to be suitable for attachment, survival and proliferation of the nMSC. Minimal cell infiltration was found in the implanted conduits where nearly all of the cells found in the cell seeded conduits are non-mouse origin and have neural cell markers, which exhibit the biocompatibility of the conduits. The collagen-coated PLGA conduit is biocompatible, non-cytotoxic and suitable for use as artificial nerve conduits.

  18. IgA and IgM protein primarily drive plasma corona-induced adhesion reduction of PLGA nanoparticles in human blood flow.

    Science.gov (United States)

    Sobczynski, Daniel J; Eniola-Adefeso, Omolola

    2017-06-01

    The high abundance of immunoglobulins (Igs) in the plasma protein corona on poly(lactic-co-glycolic) acid (PLGA)-based vascular-targeted carriers (VTCs) has previously been shown to reduce their adhesion to activated endothelial cells (aECs) in human blood flow. However, the relative role of individual Ig classes (e.g., IgG, IgA, and IgM) in causing adhesion reduction remains largely unknown. Here, we characterized the influence of specific Ig classes in prescribing the binding efficiency of PLGA nano-sized VTCs in blood flow. Specifically, we evaluated the flow adhesion to aECs of PLGA VTCs with systematic depletion of various Igs in their corona. Adhesion reduction was largely eliminated for PLGA VTCs when all Igs were removed from the corona. Furthermore, re-addition of IgA or IgM to the Igs-depleted corona reinstated the low adhesion of PLGA VTCs, as evidenced by ∼40-70% reduction relative to particles with an Igs-deficient corona. However, re-addition of a high concentration of IgG to the Igs-depleted corona did not cause significant adhesion reduction. Overall, the presented results reveal that PLGA VTC adhesion reduction in blood flows is primarily driven by high adsorption of IgA and IgM in the particle corona. Pre-coating of albumin on PLGA VTCs mitigated the extent of adhesion reduction in plasma for some donors but was largely ineffective in general. Overall, this work may shed light into effective control of protein corona composition, thereby enhancing VTC functionality in vivo for eventual clinical use.

  19. Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Zohreh Ebrahimnezhad

    2013-05-01

    Full Text Available Introduction: Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10, a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. Methods: The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Results: Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG- Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG- Fe3O4 than with free silibinin alone. Conclusion: The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG- Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.

  20. Combination of aligned PLGA/Gelatin electrospun sheets, native dental pulp extracellular matrix and treated dentin matrix as substrates for tooth root regeneration.

    Science.gov (United States)

    Chen, Gang; Chen, Jinlong; Yang, Bo; Li, Lei; Luo, Xiangyou; Zhang, Xuexin; Feng, Lian; Jiang, Zongting; Yu, Mei; Guo, Weihua; Tian, Weidong

    2015-06-01

    In tissue engineering, scaffold materials provide effective structural support to promote the repair of damaged tissues or organs through simulating the extracellular matrix (ECM) microenvironments for stem cells. This study hypothesized that simulating the ECM microenvironments of periodontium and dental pulp/dentin complexes would contribute to the regeneration of tooth root. Here, aligned PLGA/Gelatin electrospun sheet (APES), treated dentin matrix (TDM) and native dental pulp extracellular matrix (DPEM) were fabricated and combined into APES/TDM and DPEM/TDM for periodontium and dental pulp regeneration, respectively. This study firstly examined the physicochemical properties and biocompatibilities of both APES and DPEM in vitro, and further investigated the degradation of APES and revascularization of DPEM in vivo. Then, the potency of APES/TDM and DPEM/TDM in odontogenic induction was evaluated via co-culture with dental stem cells. Finally, we verified the periodontium and dental pulp/dentin complex regeneration in the jaw of miniature swine. Results showed that APES possessed aligned fiber orientation which guided cell proliferation while DPEM preserved the intrinsic fiber structure and ECM proteins. Importantly, both APES/TDM and DPEM/TDM facilitated the odontogenic differentiation of dental stem cells in vitro. Seeded with stem cells, the sandwich composites (APES/TDM/DPEM) generated tooth root-like tissues after being transplanted in porcine jaws for 12 w. In dental pulp/dentin complex-like tissues, columnar odontoblasts-like layer arranged along the interface between newly-formed predentin matrix and dental pulp-like tissues in which blood vessels could be found; in periodontium complex-like tissues, cellular cementum and periodontal ligament (PDL)-like tissues were generated on the TDM surface. Thus, above results suggest that APES and DPEM exhibiting appropriate physicochemical properties and well biocompatibilities, in accompany with TDM, could

  1. Mechanistic analysis of triamcinolone acetonide release from PLGA microspheres as a function of varying in vitro release conditions.

    Science.gov (United States)

    Doty, Amy C; Zhang, Ying; Weinstein, David G; Wang, Yan; Choi, Stephanie; Qu, Wen; Mittal, Sachin; Schwendeman, Steven P

    2017-04-01

    In vitro tests for controlled release PLGA microspheres in their current state often do not accurately predict in vivo performance of these products during formulation development. Here, we introduce a new mechanistic and multi-phase approach to more clearly understand in vitro-in vivo relationships, and describe the first "in vitro phase" with the model drug, triamcinolone acetonide (Tr-A). Two microsphere formulations encapsulating Tr-A were prepared from PLGAs of different molecular weights and end-capping (18kDa acid-capped and 54kDa ester-capped). In vitro release kinetics and the evidence for controlling mechanisms (i.e., erosion, diffusion, and water-mediated processes) were studied in four release media: PBST pH 7.4 (standard condition), PBST pH 6.5, PBS+1.0% triethyl citrate (TC), and HBST pH 7.4. The release mechanism in PBST was primarily polymer erosion-controlled as indicated by the similarity of release and mass loss kinetics. Release from the low MW PLGA was accelerated at low pH due to increased rate of hydrolysis and in the presence of the plasticizer TC due to slightly increased hydrolysis and much higher diffusion in the polymer matrix. TC also increased release from the high MW PLGA due to increased hydrolysis, erosion, and diffusion. This work demonstrates how in vitro conditions can be manipulated to change not only rates of drug release from PLGA microspheres but also the mechanism(s) by which release occurs. Follow-on studies in the next phases of this approach will utilize these results to compare the mechanistic data of the Tr-A/PLGA microsphere formulations developed here after recovery of microspheres in vivo. This new approach based on measuring mechanistic indicators of release in vitro and in vivo has the potential to design better, more predictive in vitro release tests for these formulations and potentially lead to mechanism-based in vitro-in vivo correlations. Copyright © 2016. Published by Elsevier B.V.

  2. Micromechanisms of damage in unidirectional fiber reinforced composites

    DEFF Research Database (Denmark)

    Mishnaevsky, Leon; Brøndsted, Povl

    2009-01-01

    Numerical micromechanical investigations of the mechanical behavior and damage evolution of glass fiber reinforced composites are presented. A program code for the automatic generation of 3D micromechanical unit cell models of composites with damageable elements is developed, and used...... in the numerical experiments. The effect of the statistical variability of fiber strengths, viscosity of the polymer matrix as well as the interaction between the damage processes in matrix, fibers and interface are investigated numerically. It is demonstrated that fibers with constant strength ensure higher...... strength of a composite at the pre-critical load, while the fibers with randomly distributed strengths lead to the higher strength of the composite at post-critical loads. In the case of randomly distributed fiber strengths, the damage growth in fibers seems to be almost independent from the crack length...

  3. PLGA-PEG-PLGA microspheres as a delivery vehicle for antisense oligonucleotides to CTGF: Implications on post-surgical peritoneal adhesion prevention

    Science.gov (United States)

    Azeke, John Imuetinyan-Jesu, Jr.

    , while both cytokines are over-expressed within the first day following injury, CTGF protein levels could not be correlated with observed adhesion development. In addition, we synthesized linear triblock copolymers of polyethylene glycol (PEG) and poly(D,L-lactide-co-glycolide) (PLGA), two of the most widely studied biodegradable polymers in use today. Bulk gels and microparticles of the copolymers were then evaluated for gelling behavior, temperature stability, and drug loading and release kinetics in order assess their suitability as potential carriers of antisense therapeutics. A novel approach to affecting the antisense oligonucleotide release kinetics by varying the relative concentrations of co-encapsulated cationic lipid transfection agents was also presented.

  4. Random walks on random Koch curves

    Energy Technology Data Exchange (ETDEWEB)

    Seeger, S; Hoffmann, K H [Institut fuer Physik, Technische Universitaet, D-09107 Chemnitz (Germany); Essex, C [Department of Applied Mathematics, University of Western Ontario, London, ON N6A 5B7 (Canada)

    2009-06-05

    Diffusion processes in porous materials are often modeled as random walks on fractals. In order to capture the randomness of the materials random fractals are employed, which no longer show the deterministic self-similarity of regular fractals. Finding a continuum differential equation describing the diffusion on such fractals has been a long-standing goal, and we address the question of whether the concepts developed for regular fractals are still applicable. We use the random Koch curve as a convenient example as it provides certain technical advantages by its separation of time and space features. While some of the concepts developed for regular fractals can be used unaltered, others have to be modified. Based on the concept of fibers, we introduce ensemble-averaged density functions which produce a differentiable estimate of probability explicitly and compare it to random walk data.

  5. Photonic crystal fibers -

    DEFF Research Database (Denmark)

    Libori, Stig E. Barkou

    2002-01-01

    During this ph.d. work, attention has been focused on understanding and analyzing the modal behavior of micro-structured fibers. Micro-structured fibers are fibers with a complex dielectric toplogy, and offer a number of novel possibilities, compared to standard silica based optical fibers....... The thesis focuses on understanding the basic mechanisms controlling the modal properties of micro-structured fibers. One important sub-class of micro-structured fibers are fibers that guide light by index effects similar to those index effects that ensure guidance of light in standard optical fibers....... Such micro-structured fibers are the ones most often trated in literature concerning micro-structured fibers. These micro-structured fibers offer a whole range of novel wave guiding characteristics, including the possibility of fibers that guide only one mode irrespective of the frequency of light...

  6. PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive interface.

    Science.gov (United States)

    Priyadarshini, Balasankar Meera; Mitali, Kakran; Lu, Thong Beng; Handral, Harish K; Dubey, Nileshkumar; Fawzy, Amr S

    2017-07-01

    To characterize and deliver fabricated CHX-loaded PLGA-nanoparticles inside micron-sized dentinal-tubules of demineralized dentin-substrates and resin-dentin interface. Nanoparticles fabricated by emulsion evaporation were assessed in-vitro by different techniques. Delivery of drug-loaded nanoparticles to demineralized dentin substrates, interaction with collagen matrix, and ex-vivo CHX-release profiles using extracted teeth connected to experimental setup simulating pulpal hydrostatic pressure were investigated. Furthermore, nanoparticles association/interaction with a commercial dentin-adhesive applied to demineralized dentin substrates were examined. The results showed that the formulated nanoparticles demonstrated attractive physicochemical properties, low cytotoxicity, potent antibacterial efficacy, and slow degradation and gradual CHX release profiles. Nanoparticles delivered efficiently inside dentinal-tubules structure to sufficient depth (>10μm) against the simulated upward pulpal hydrostatic-pressure, even after bonding-resins infiltration and were attached/retained on collagen-fibrils. These results verified the potential significance of this newly introduced drug-delivery therapeutic strategy for future clinical applications and promote for a new era of future dental research. This innovative drug-delivery strategy has proven to be a reliable method for delivering treatments that could be elaborated for other clinical applications in adhesive and restorative dentistry. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  7. PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies.

    Science.gov (United States)

    Riffault, Mathieu; Six, Jean-Luc; Netter, Patrick; Gillet, Pierre; Grossin, Laurent

    2015-12-01

    Despite the promising applications of PLGA based particles, studies examining the fate and consequences of these particles after intra-articular administration in the joint are scanty. This study was carried out to evaluate the neutrality of the unloaded delivery system on different articular cell types. To facilitate tracking, we have thus developed a fluorescent core of particles, combined to a hyaluronate shell for cell recognition. Fluorescence pictures were taken at time intervals to assess the internalization and the corresponding inflammatory response was monitored by RT-qPCR and biochemical measurements. After NPs pre-treatment, mesenchymal stem cells (MSCs) were cultured into chondrogenic, adipogenic or osteogenic differentiation media, to investigate if NPs exposure interferes with differentiation ability. Finally, intra-articular injections were performed in healthy rat knees and joint's structure analysed by histological studies. Particles were detected in cytoplasm 8 h after exposure. Internalization led to a slight and reversible increase of inflammatory markers, but lower than in inflammatory conditions. We have confirmed particles exposure minimal neutrality on MSCs pluripotency. Histological exams of joint after intra-articular injections do not demonstrate any side effects of NPs. Our findings suggest that such a delivery platform is well tolerated locally and could be used to deliver active molecules to the joint.

  8. Manufacture and characterization of chitosan/PLGA nanoparticles nanocomposite buccal films.

    Science.gov (United States)

    Santos, Talitha Caldas Dos; Rescignano, Nicoletta; Boff, Laurita; Reginatto, Flávio Henrique; Simões, Cláudia Maria Oliveira; de Campos, Angela Machado; Mijangos, Carmen Ugarte

    2017-10-01

    Oral bioavailability of C-glycosyl flavonoid enriched fraction of Cecropia glaziovii (EFF-Cg) is limited due to its chemical complexity. The purpose of this study is the prospective evaluation of chitosan buccal films impregnated with EFF-Cg-loaded nanospheres as a drug delivery system for labial herpes treatment or for buccal administration. EFF-Cg-loaded PLGA nanospheres were prepared by double emulsion solvent evaporation technique. Nanoparticles were embedded into buccoadhesive chitosan films in different concentrations in order to obtain nanocomposite films. Films were characterized in term of morphology, mechanical properties and water absorption test. Furthermore a cytotoxicity assay was analyzed to evaluate the biocompatibility of systems. The results obtained from these analyses revealed that nanocomposite films present transparent appearance in all composition and Scanning Electron Microscopy (SEM) images show a continuous and compact section structure. Compared to the control film, mechanical responses of nanocomposites presented lower tensile strength values and no significant effect on the elongation at break. Dynamic Mechanical Analysis (DMA) tests indicated that increasing of NP concentration caused decreased stiffness and an increased of glass transition temperature values. Direct cytotoxicity test shows that nanoparticles and chitosan films not induce cytotoxic effect. Given the promising results, the study concludes that the developed buccal film impregnated with EFF-Cg-loaded nanospheres could be a promising approach for effective delivery of EFF-Cg. Copyright © 2017. Published by Elsevier Ltd.

  9. In Vivo Investigation of ALBO-OS Scaffold Based on Hydroxyapatite and PLGA

    Directory of Open Access Journals (Sweden)

    Vukoman Jokanović

    2016-01-01

    Full Text Available A synthetic bone substitute based on calcium hydroxyapatite (CHA and poly(lactic-co-glycolic acid (PLGA, described in this paper, was synthesized to fulfill specific requirements like biodegradability, satisfying mechanical properties, optimal porosity and nanotopology, osteoinductive and osteoconductive properties, and so forth. Structural and morphological properties of the new scaffold were analyzed by micro computed tomography and scanning electron microscopy, while its physicochemical properties were investigated by X-ray diffraction and infrared spectroscopy. In vivo biological investigations of the synthesized scaffold were conducted over the cutaneous irritation and biofunctionality assays on rabbits and the test of acute systemic toxicity on mice. The results showed that the scaffold is not irritant and that it does not exhibit any symptoms of acute toxicity. Biofunctionality assays which include evaluation of the presence of various cells of immune response, the presence of neoangiogenesis, percentage of mineralization of newly formed bone, and fibroplasia in the tissue indicated that the new scaffold is suitable for the application in maxillofacial and dental surgery as a bone substitute. Also, it showed significant advantages over commercial product Geistlich Bio-Oss® from the aspect of some parameters of immunological response.

  10. "Click" on PLGA-PEG and hyaluronic acid: Gaining access to anti-leishmanial pentamidine bioconjugates.

    Science.gov (United States)

    Scala, Angela; Piperno, Anna; Micale, Nicola; Mineo, Placido G; Abbadessa, Antonio; Risoluti, Roberta; Castelli, Germano; Bruno, Federica; Vitale, Fabrizio; Cascio, Antonio; Grassi, Giovanni

    2017-12-08

    Pentamidine (Pent), an antiparasitic drug used for the treatment of visceral leishmaniasis, has been modified with terminal azide groups and conjugated to two different polymer backbones (PLGA-PEG [PP] copolymer and hyaluronic acid [HA]) armed with alkyne end-groups. The conjugation has been performed by Copper Catalyzed Azido Alkyne Cycloaddition (CuAAC) using CuSO 4 /sodium ascorbate as metal source. The novel PP-Pent and HA-Pent bioconjugates are proposed, respectively, as non-targeted and targeted drug delivery systems against Leishmania infections. Moreover, Pent has been encapsulated into PP nanoparticles by the oil-in-water emulsion method, with the aim to compare the biological activity of the bioconjugates with that of the classical drug-loaded delivery system that physically entraps the therapeutic agent. Biological assays against Leishmania infantum amastigote-infected macrophages and primary macrophages revealed that Pent, either covalently conjugated with polymers or loaded into polymeric nanoparticles, turned out to be more potent and less toxic than the free Pent. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  11. Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering.

    Science.gov (United States)

    Doğan, Ayşegül; Demirci, Selami; Bayir, Yasin; Halici, Zekai; Karakus, Emre; Aydin, Ali; Cadirci, Elif; Albayrak, Abdulmecit; Demirci, Elif; Karaman, Adem; Ayan, Arif Kursat; Gundogdu, Cemal; Sahin, Fikrettin

    2014-11-01

    Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Evaluation of polymeric PLGA nanoparticles conjugated to curcumin for use in aPDT

    Directory of Open Access Journals (Sweden)

    Renata Celi Carvalho de Souza Pietra

    2017-07-01

    Full Text Available ABSTRACT Antimicrobial photodynamic therapy (aPDT involves the association of a photosensitizing agent with a light source with the goal of causing apoptosis or microbial lysing. The use of compounds with natural active principles is gaining prominence throughout the world. Several studies from groups that are linked to the development of innovations in the pharmaceutical market have used natural dyes, such as curcumin, the efficacy of which has been demonstrated in aPDT trials. Difficulties related to physicochemical stability, solubility and cell penetration are some of the challenges associated with this field. The present work aimed to prepare, investigate the characteristics and improve the photodynamic activity of PLGA-based nanoparticles loaded with curcumin for use in aPDT therapy. Using the simple technique of emulsion during the evaporation of a solvent, the particles were built, characterized and tested against microorganisms with importance for medicine and dentistry. The results revealed that the particles were able to protect the curcumin against degradation and eliminate some microorganism species at nanomolar concentrations.

  13. ICAM-1 targeted catalase encapsulated PLGA-b-PEG nanoparticles against vascular oxidative stress.

    Science.gov (United States)

    Sari, Ece; Tunc-Sarisozen, Yeliz; Mutlu, Hulya; Shahbazi, Reza; Ucar, Gulberk; Ulubayram, Kezban

    2015-01-01

    Targeted delivery of therapeutics is the favourable idea, whereas it is possible to distribute the therapeutically active drug molecule only to the site of action. For this purpose, in this study, catalase encapsulated poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles were developed and an endothelial target molecule (anti-ICAM-1) was conjugated to this carrier system in order to decrease the oxidative stress level in the target site. According to the enzymatic activity results, initial catalase activity of nanoparticles was increased from 27.39 U/mg to up to 45.66 U/mg by adding 5 mg/mL bovine serum albumin (BSA). After 4 h, initial catalase activity was preserved up to 46.98% while free catalase retained less than 4% of its activity in proteolytic environment. Furthermore, FITC labelled anti-ICAM-1 targeted catalase encapsulated nanoparticles (anti-ICAM-1/CatNPs) were rapidly taken up by cultured endothelial cells and concomitantly endothelial cells were resistant to H2O2 induced oxidative impairment.

  14. Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity

    Directory of Open Access Journals (Sweden)

    De Maria Ruggero

    2008-07-01

    Full Text Available Abstract Background PTX is one of the most widely used drug in oncology due to its high efficacy against solid tumors and several hematological cancers. PTX is administered in a formulation containing 1:1 Cremophor® EL (polyethoxylated castor oil and ethanol, often responsible for toxic effects. Its encapsulation in colloidal delivery systems would gain an improved targeting to cancer cells, reducing the dose and frequency of administration. Methods In this paper PTX was loaded in PLGA NS. The activity of PTX-NS was assessed in vitro against thyroid, breast and bladder cancer cell lines in cultures. Cell growth was evaluated by MTS assay, intracellular NS uptake was performed using coumarin-6 labelled NS and the amount of intracellular PTX was measured by HPLC. Results NS loaded with 3% PTX (w/w had a mean size Conclusion These findings suggest that the greater biological effect of PTX-NS could be due to higher uptake of the drug inside the cells as shown by intracellular NS uptake and cell accumulation studies.

  15. Surface modification of PLGA nanoparticles to deliver nitric oxide to inhibit Escherichia coli growth

    Energy Technology Data Exchange (ETDEWEB)

    Reger, Nina A. [Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282 (United States); Meng, Wilson S. [Division of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282 (United States); Gawalt, Ellen S., E-mail: gawalte@duq.edu [Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, PA 15282 (United States); McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219 (United States)

    2017-04-15

    Highlights: • Thin film functionalized PLGA nanoparticles were modified to release nitric oxide from an s-nitrosothiol donor. • The nitric oxide modified nanoparticles were bacteriostatic against Escherichia coli. • The nitric oxide modified nanoparticles increased the effectiveness of tetracycline against Escherichia coli. • The modified nitric oxide nanoparticles did not exhibit cytotoxic effects against fibroblasts. - Abstract: Polymer nanoparticles consisting of poly (DL-lactic-co-glycolic acid) were surface functionalized to deliver nitric oxide. These biodegradable and biocompatible nanoparticles were modified with an S-nitrosothiol molecule, S-nitrosocysteamine, as the nitric oxide delivery molecule. S-nitrosocysteamine was covalently immobilized on the nanoparticle surface using small organic molecule linkers and carbodiimide coupling. Nanoparticle size, zeta potential, and morphology were determined using dynamic light scattering and scanning electron microscopy, respectively. Subsequent attachment of the S-nitrosothiol resulted in a nitric oxide release of 37.1 ± 1.1 nmol per milligram of nanoparticles under physiological conditions. This low concentration of nitric oxide reduced Escherichia coli culture growth by 31.8%, indicating that the nitric oxide donor was effective at releasing nitric oxide even after attachment to the nanoparticle surface. Combining the nitric oxide modified nanoparticles with tetracycline, a commonly prescribed antibiotic for E. coli infections, increased the effectiveness of the antibiotic by 87.8%, which allows for lower doses of antibiotics to be used in order to achieve the same effect. The functionalized nanoparticles were not cytotoxic to mouse fibroblasts.

  16. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Science.gov (United States)

    Hua, Xin; Tan, Shengnan; Bandara, H M H N; Fu, Yujie; Liu, Siguo; Smyth, Hugh D C

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  17. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xin Hua

    Full Text Available Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF. An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  18. Room-temperature attachment of PLGA microspheres to titanium surfaces for implant-based drug release

    Science.gov (United States)

    Xiao, Dongqin; Liu, Qing; Wang, Dongwei; Xie, Tao; Guo, Tailin; Duan, Ke; Weng, Jie

    2014-08-01

    Drug release from implant surfaces is an effective approach to impart biological activities, (e.g., antimicrobial and osteogenic properties) to bone implants. Coatings of polylactide-based polymer are a candidate for this purpose, but a continuous (fully covering) coating may be non-optimal for implant-bone fixation. This study reports a simple room-temperature method for attaching poly (lactide-co-glycolide) (PLGA) microspheres to titanium (Ti) surfaces. Microspheres were prepared with polyvinyl alcohol (PVA) or polyvinylpyrrolidone (PVP) as the emulsifier. Microspheres were attached to Ti discs by pipetting as a suspension onto the surfaces followed by vacuum drying. After immersion in shaking water bath for 14 d, a substantial proportion of the microspheres remained attached to the discs. In contrast, if the vacuum-drying procedure was omitted, only a small fraction of the microspheres remained attached to the discs after immersion for only 5 min. Microspheres containing triclosan (a broad-spectrum antibiotic) were attached by porous-surfaced Ti discs. In vitro experiments showed that the microsphere-carrying discs were able to kill Staphylococcus aureus and Escherichia Coli, and support the adhesion and growth of primary rat osteoblasts. This simple method may offer a flexible technique for bone implant-based drug release.

  19. Aptamer-functionalized PEG-PLGA nanoparticles for enhanced anti-glioma drug delivery.

    Science.gov (United States)

    Guo, Jianwei; Gao, Xiaoling; Su, Lina; Xia, Huimin; Gu, Guangzhi; Pang, Zhiqing; Jiang, Xinguo; Yao, Lei; Chen, Jun; Chen, Hongzhuan

    2011-11-01

    Targeted delivery of therapeutic nanoparticles in a disease-specific manner represents a potentially powerful technology especially when treating infiltrative brain tumors such as gliomas. We developed a nanoparticulate drug delivery system decorated with AS1411 (Ap), a DNA aptamer specifically binding to nucleolin which was highly expressed in the plasma membrane of both cancer cells and endothelial cells in angiogenic blood vessels, as the targeting ligand to facilitate anti-glioma delivery of paclitaxel (PTX). Ap was conjugated to the surface of PEG-PLGA nanoparticles (NP) via an EDC/NHS technique. With the conjugation confirmed by Urea PAGE and XPS, the resulting Ap-PTX-NP was uniformly round with particle size at 156.0 ± 54.8 nm and zeta potential at -32.93 ± 3.1 mV. Ap-nucleolin interaction significantly enhanced cellular association of nanoparticles in C6 glioma cells, and increased the cytotoxicity of its payload. Prolonged circulation and enhanced PTX accumulation at the tumor site was achieved for Ap-PTX-NP, which eventually obtained significantly higher tumor inhibition on mice bearing C6 glioma xenografts and prolonged animal survival on rats bearing intracranial C6 gliomas when compared with PTX-NP and Taxol(®). The results of this contribution demonstrated the potential utility of AS1411-functionalized nanoparticles for a therapeutic application in the treatment of gliomas. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Osteoblasts Interaction with PLGA Membranes Functionalized with Titanium Film Nanolayer by PECVD. In vitro Assessment of Surface Influence on Cell Adhesion during Initial Cell to Material Interaction

    Directory of Open Access Journals (Sweden)

    Antonia Terriza

    2014-03-01

    Full Text Available New biomaterials for Guided Bone Regeneration (GBR, both resorbable and non-resorbable, are being developed to stimulate bone tissue formation. Thus, the in vitro study of cell behavior towards material surface properties turns a prerequisite to assess both biocompatibility and bioactivity of any material intended to be used for clinical purposes. For this purpose, we have developed in vitro studies on normal human osteoblasts (HOB® HOB® osteoblasts grown on a resorbable Poly (lactide-co-glycolide (PLGA membrane foil functionalized by a very thin film (around 15 nm of TiO2 (i.e., TiO2/PLGA membranes, designed to be used as barrier membrane. To avoid any alteration of the membranes, the titanium films were deposited at room temperature in one step by plasma enhanced chemical vapour deposition. Characterization of the functionalized membranes proved that the thin titanium layer completely covers the PLGA foils that remains practically unmodified in their interior after the deposition process and stands the standard sterilization protocols. Both morphological changes and cytoskeletal reorganization, together with the focal adhesion development observed in HOB osteoblasts, significantly related to TiO2 treated PLGA in which the Ti deposition method described has revealed to be a valuable tool to increase bioactivity of PLGA membranes, by combining cell nanotopography cues with the incorporation of bioactive factors.

  1. Osteoblasts Interaction with PLGA Membranes Functionalized with Titanium Film Nanolayer by PECVD. In vitro Assessment of Surface Influence on Cell Adhesion during Initial Cell to Material Interaction

    Science.gov (United States)

    Terriza, Antonia; Vilches-Pérez, José I.; González-Caballero, Juan L.; de la Orden, Emilio; Yubero, Francisco; Barranco, Angel; Gonzalez-Elipe, Agustín R.; Vilches, José; Salido, Mercedes

    2014-01-01

    New biomaterials for Guided Bone Regeneration (GBR), both resorbable and non-resorbable, are being developed to stimulate bone tissue formation. Thus, the in vitro study of cell behavior towards material surface properties turns a prerequisite to assess both biocompatibility and bioactivity of any material intended to be used for clinical purposes. For this purpose, we have developed in vitro studies on normal human osteoblasts (HOB®) HOB® osteoblasts grown on a resorbable Poly (lactide-co-glycolide) (PLGA) membrane foil functionalized by a very thin film (around 15 nm) of TiO2 (i.e., TiO2/PLGA membranes), designed to be used as barrier membrane. To avoid any alteration of the membranes, the titanium films were deposited at room temperature in one step by plasma enhanced chemical vapour deposition. Characterization of the functionalized membranes proved that the thin titanium layer completely covers the PLGA foils that remains practically unmodified in their interior after the deposition process and stands the standard sterilization protocols. Both morphological changes and cytoskeletal reorganization, together with the focal adhesion development observed in HOB osteoblasts, significantly related to TiO2 treated PLGA in which the Ti deposition method described has revealed to be a valuable tool to increase bioactivity of PLGA membranes, by combining cell nanotopography cues with the incorporation of bioactive factors. PMID:28788538

  2. Photonic Bandgap Fibers

    DEFF Research Database (Denmark)

    Barkou, Stig Eigil; Broeng, Jes; Bjarklev, Anders Overgaard

    1999-01-01

    Photonic bandgap fibers are describes using a new Kagomé cladding structure. These fibers may potentially guide light in low-index regions. Such fibers offer new dispersion properties, and large design flexibility.......Photonic bandgap fibers are describes using a new Kagomé cladding structure. These fibers may potentially guide light in low-index regions. Such fibers offer new dispersion properties, and large design flexibility....

  3. Analysis of Document Authentication Technique using Soft Magnetic Fibers

    Science.gov (United States)

    Aoki, Ayumi; Ikeda, Takashi; Yamada, Tsutomu; Takemura, Yasushi; Matsumoto, Tsutomu

    An artifact-metric system using magnetic fibers can be applied for authentications of stock certificate, bill, passport, plastic cards and other documents. Security of the system is guaranteed by its feature of difficulty in copy. This authentication system is based on randomly dispersed magnetic fibers embedded in documents. In this paper, a theoretical analysis was performed in order to evaluate this system. The position of the magnetic fibers was determined by a conventional function of random number generator. By measuring output waveforms by a magnetoresistance (MR) sensor, a false match rate (FMR) could be calculated. Optimizations of the density of the magnetic fibers and the dimension of the MR sensor were achieved.

  4. Orbital angular momentum in optical fibers

    Science.gov (United States)

    Bozinovic, Nenad

    Internet data traffic capacity is rapidly reaching limits imposed by nonlinear effects of single mode fibers currently used in optical communications. Having almost exhausted available degrees of freedom to orthogonally multiplex data in optical fibers, researchers are now exploring the possibility of using the spatial dimension of fibers, via multicore and multimode fibers, to address the forthcoming capacity crunch. While multicore fibers require complex manufacturing, conventional multi-mode fibers suffer from mode coupling, caused by random perturbations in fibers and modal (de)multiplexers. Methods that have been developed to address the problem of mode coupling so far, have been dependent on computationally intensive digital signal processing algorithms using adaptive optics feedback or complex multiple-input multiple-output algorithms. Here we study the possibility of using the orbital angular momentum (OAM), or helicity, of light, as a means of increasing capacity of future optical fiber communication links. We first introduce a class of specialty fibers designed to minimize mode coupling and show their potential for OAM mode generation in fibers using numerical analysis. We then experimentally confirm the existence of OAM states in these fibers using methods based on fiber gratings and spatial light modulators. In order to quantify the purity of created OAM states, we developed two methods based on mode-image analysis, showing purity of OAM states to be 90% after 1km in these fibers. Finally, in order to demonstrate data transmission using OAM states, we developed a 4-mode multiplexing and demultiplexing systems based on free-space optics and spatial light modulators. Using simple coherent detection methods, we successfully transmit data at 400Gbit/s using four OAM modes at a single wavelength, over 1.1 km of fiber. Furthermore, we achieve data transmission at 1.6Tbit/s using 10 wavelengths and two OAM modes. Our study indicates that OAM light can exist

  5. Nearly-octave wavelength tuning of a continuous wave fiber laser

    Science.gov (United States)

    Zhang, Lei; Jiang, Huawei; Yang, Xuezong; Pan, Weiwei; Cui, Shuzhen; Feng, Yan

    2017-02-01

    The wavelength tunability of conventional fiber lasers are limited by the bandwidth of gain spectrum and the tunability of feedback mechanism. Here a fiber laser which is continuously tunable from 1 to 1.9 μm is reported. It is a random distributed feedback Raman fiber laser, pumped by a tunable Yb doped fiber laser. The ultra-wide wavelength tunability is enabled by the unique property of random distributed feedback Raman fiber laser that both stimulated Raman scattering gain and Rayleigh scattering feedback are available at any wavelength. The dispersion property of the gain fiber is used to control the spectral purity of the laser output.

  6. Protein from Meat or Vegetable Sources in Meals Matched for Fiber Content has Similar Effects on Subjective Appetite Sensations and Energy Intake—A Randomized Acute Cross-Over Meal Test Study

    Directory of Open Access Journals (Sweden)

    Lone V. Nielsen

    2018-01-01

    Full Text Available Higher-protein meals decrease hunger and increase satiety compared to lower-protein meals. However, no consensus exists about the different effects of animal and vegetable proteins on appetite. We investigated how a meal based on vegetable protein (fava beans/split peas affected ad libitum energy intake and appetite sensations, compared to macronutrient-balanced, iso-caloric meals based on animal protein (veal/pork or eggs. Thirty-five healthy men were enrolled in this acute cross-over study. On each test day, participants were presented with one of four test meals (~3550 kilojoules (kJ 19% of energy from protein, based on fava beans/split peas (28.5 g fiber, pork/veal or eggs supplemented with pea fiber to control for fiber content (28.5 g fiber, or eggs without supplementation of fiber (6.0 g fiber. Subjective appetite sensations were recorded at baseline and every half hour until the ad libitum meal three hours later. There were no differences in ad libitum energy intake across test meals (p > 0.05. Further, no differences were found across meals for hunger, satiety, fullness, prospective food consumption, or composite appetite score (all p > 0.05. Iso-caloric, macronutrient-balanced, fiber-matched meals based on vegetable protein (fava beans/split peas or animal protein (veal/pork or eggs had similar effects on ad libitum energy intake and appetite sensations.

  7. Protein from Meat or Vegetable Sources in Meals Matched for Fiber Content has Similar Effects on Subjective Appetite Sensations and Energy Intake-A Randomized Acute Cross-Over Meal Test Study.

    Science.gov (United States)

    Nielsen, Lone V; Kristensen, Marlene D; Klingenberg, Lars; Ritz, Christian; Belza, Anita; Astrup, Arne; Raben, Anne

    2018-01-16

    Higher-protein meals decrease hunger and increase satiety compared to lower-protein meals. However, no consensus exists about the different effects of animal and vegetable proteins on appetite. We investigated how a meal based on vegetable protein (fava beans/split peas) affected ad libitum energy intake and appetite sensations, compared to macronutrient-balanced, iso-caloric meals based on animal protein (veal/pork or eggs). Thirty-five healthy men were enrolled in this acute cross-over study. On each test day, participants were presented with one of four test meals (~3550 kilojoules (kJ) 19% of energy from protein), based on fava beans/split peas (28.5 g fiber), pork/veal or eggs supplemented with pea fiber to control for fiber content (28.5 g fiber), or eggs without supplementation of fiber (6.0 g fiber). Subjective appetite sensations were recorded at baseline and every half hour until the ad libitum meal three hours later. There were no differences in ad libitum energy intake across test meals (p > 0.05). Further, no differences were found across meals for hunger, satiety, fullness, prospective food consumption, or composite appetite score (all p > 0.05). Iso-caloric, macronutrient-balanced, fiber-matched meals based on vegetable protein (fava beans/split peas) or animal protein (veal/pork or eggs) had similar effects on ad libitum energy intake and appetite sensations.

  8. Evaluation of 3D printed PCL/PLGA/β-TCP versus collagen membranes for guided bone regeneration in a beagle implant model.

    Science.gov (United States)

    Won, J-Y; Park, C-Y; Bae, J-H; Ahn, G; Kim, C; Lim, D-H; Cho, D-W; Yun, W-S; Shim, J-H; Huh, J-B

    2016-10-07

    Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/β-tricalcium phosphate (PCL/PLGA/β-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/β-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/β-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/β-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/β-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/β-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

  9. Engineering PLGA nano-based systems through understanding the influence of nanoparticle properties and cell-penetrating peptides for cochlear drug delivery.

    Science.gov (United States)

    Cai, Hui; Liang, Zhongping; Huang, Wenli; Wen, Lu; Chen, Gang

    2017-10-30

    The properties of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and penetration enhancers play a deciding role in the inner ear drug delivery of NPs across the round window membrane (RWM). Thus, PLGA nano-based systems with a variety of particle sizes and surface chemistries and those combined with cell-penetrating peptides (CPPs) as penetration enhancers were devised to explore their impact on the cochlear drug delivery in vivo. First, we demonstrated that the properties of NPs dictated the extent of NP cochlear entry by near-infrared fluorescence imaging. NPs with the sizes of 150 and 300nm had faster entry than that of 80nm NPs. At 0.5h, among the NPs unmodified and modified with chitosan (CS), poloxamer 407 (P407) and methoxy polyethylene glycol, CS-PLGA-NPs (positive surface charge) carried payload to the cochlea fastest, whereas P407-PLGA-NPs (surface hydrophilicity) showed the greatest distribution in the cochlea at 24h. Compared to other CPPs (TAT, penetratin and poly(arginine)8), low molecular weight protamine (LMWP) performed an outstanding enhanced NP cellular uptake in HEI-OC1 cells and cochlear entry. More importantly, NPs with optimized properties and CPPs may be combined to improve RWM penetration. For the first time, we confirmed that the combination of P407-PLGA-NPs (mean diameter: 100-200nm) and LMWP provided a synergistic enhancement in NP entry to the organ of Corti and stria vascularis without inducing pathological alteration of cochlear tissues and RWM. Taken together, we propose an effective PLGA nano-based strategy for enhanced drug delivery to the inner ear tissues that combines hydrophilic molecule-modified NPs and CPPs, ultimately opening an avenue for superior inner ear therapy. Copyright © 2017. Published by Elsevier B.V.

  10. Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics.

    Science.gov (United States)

    Shen, Xue; Li, Tingting; Chen, Zhongyuan; Geng, Yue; Xie, Xiaoxue; Li, Shun; Yang, Hong; Wu, Chunhui; Liu, Yiyao

    2017-01-01

    Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe3O4 nanocrystals, and doxorubicin (DOX) into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability waŝ14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 μg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T2-weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual

  11. Definition of formulation design space, in vitro bioactivity and in vivo biodistribution for hydrophilic drug loaded PLGA/PEO-PPO-PEO nanoparticles using OFAT experiments.

    Science.gov (United States)

    Simonoska Crcarevska, M; Geskovski, N; Calis, S; Dimchevska, S; Kuzmanovska, S; Petruševski, G; Kajdžanoska, M; Ugarkovic, S; Goracinova, K

    2013-04-11

    Modified nanoprecipitation method was used for improved incorporation of hydrophilic drug (irinotecan hydrochloride) into the PLGA/PEO-PPO-PEO blended and blended/adsorbed nanoparticles. One factor at a time (OFAT) variation experiments were conducted in order to determine key formulation factors (concentration and volume of drug solution, evaporation rate and PLGA/PEO-PPO-PEO ratio) influencing nanoparticle properties (particle size and size distribution, encapsulation efficiency, drug content, zeta potential, drug dissolution rate, as well as protein binding capacity). The insight into in vivo behavior of prepared nanoparticles and their potential for effective anticancer treatment was gained by performing biodistribution and cell culture studies as part of OFAT experiments. The mean particle size, mainly dependent upon PLGA/PEO-PPO-PEO ratio, was in the range of 112-125 nm, with narrow unimodal distribution (PDI∼0.1). Encapsulation efficiency (32-63%) was impacted by evaporation rate and PLGA/PEO-PPO-PEO ratio. Drug content (0.2-1.51%) and controlled release properties were related to the influence of all tested formulation factors. Structural information for the studied nanoparticles was obtained using DSC and FT-IR spectroscopy. Zeta potential values indicated that presence of PEO-PPO-PEO in the formulations shielded the high surface negative charge of PLGA. PEO-PPO-PEO surface coverage of PLGA/PEO-PPO-PEO blended as well as blended/adsorbed nanoparticles depended upon amount of used PEO-PPO-PEO during preparation procedure and was related to the protein resistant characteristics of nanoparticles. Results from in vivo studies evidenced prolonged blood circulation time of the prepared nanoparticles, while cell culture studies indicated higher in vitro bioefficacy compared to free drug. Performed experiments defined possible design space and justified further optimization of formulation using experimental design studies. Copyright © 2013 Elsevier B.V. All

  12. Chondrogenesis of adipose stem cells in a porous PLGA scaffold impregnated with plasmid DNA containing SOX trio (SOX-5,-6 and -9) genes.

    Science.gov (United States)

    Im, Gun-Il; Kim, Hye-Joung; Lee, Jin H

    2011-07-01

    We developed a chondrogenic scaffold system in which plasmid DNA (pDNA) containing SOX trio (SOX-5, -6, and -9) genes was incorporated into a PLGA scaffold and slowly released to transfect adipose stem cells (ASCs) seeded in the scaffold. The purpose of this study was to test the in vitro and in vivo efficacy of the system to induce chondrogenic differentiation of ASCs. The pDNA/PEI-PEG complex-incorporated PLGA/Pluronic F127 porous scaffolds were fabricated by a precipitation/particulate leaching method. The following five kinds of pDNA were incorporated into the scaffolds: 1) pECFP-C1 vector without an interposed gene (control group); 2) SOX-5 plasmids; 3) SOX-6 plasmids; 4) SOX-9 plasmids; and 5) one-third doses of each plasmid (SOX-5, -6, and -9). ASCs were seeded on pDNA-incorporated PLGA scaffolds and cultured in chondrogenic media for 21 days. ASCs were also isolated from rabbits, seeded in pDNA-incorporated PLGA scaffolds, and then implanted in the osteochondral defect created on the patellar groove. The rabbits were sacrificed and analyzed grossly and microscopically 8 weeks after implantation. The percentage of transfected cells was highest on day 14, around 70%. After 21 days, PLGA scaffolds incorporated with each gene showed markedly increased expression of the corresponding gene and protein. Glycosaminoglycan (GAG) assay and Safranin-O staining showed an increased proteoglycan production in SOX trio pDNA-incorporated scaffolds. The COL2A1 gene and protein were notably increased in SOX trio pDNA-incorporated scaffolds than in the control, while COL10A1 protein expression decreased. Gross and histological findings from the in vivo study showed enhanced cartilage regeneration in ASCs/SOX trio pDNA-incorporated PLGA scaffolds. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Response of human dental pulp cells to a silver-containing PLGA/TCP-nanofabric as a potential antibacterial regenerative pulp-capping material.

    Science.gov (United States)

    Cvikl, Barbara; Hess, Samuel C; Miron, Richard J; Agis, Hermann; Bosshardt, Dieter; Attin, Thomas; Schmidlin, Patrick R; Lussi, Adrian

    2017-02-27

    Damage or exposure of the dental pulp requires immediate therapeutic intervention. This study assessed the biocompatibility of a silver-containing PLGA/TCP-nanofabric scaffold (PLGA/Ag-TCP) in two in vitro models, i.e. the material adapted on pre-cultured cells and cells directly cultured on the material, respectively. Collagen saffolds with and without hyaluronan acid (Coll-HA; Coll) using both cell culturing methods and cells growing on culture plates served as reference. Cell viability and proliferation were assessed after 24, 48, and 72 h based on formazan formation and BrdU incorporation. Scaffolds were harvested. Gene expression of interleukin(IL)-6, tumor necrosis factor (TNF)-alpha, and alkaline phosphatase (AP) was assessed 24 h after stimulation. In both models formazan formation and BrdU incorporation was reduced by PLGA/Ag-TCP on dental pulp cells, while no significant reduction was found in cells with Coll and Coll-HA. Cells with PLGA/Ag-TCP for 72 h showed similar relative BrdU incorporation than cells stimulated with Coll and Coll-HA. A prominent increase in the pro-inflammatory genes IL-6 and TNF-α was observed when cells were cultured with PLGA/Ag-TCP compared to the other groups. This increase was parallel with a slight increase in AP expression. Overall, no differences between the two culture methods were observed. PLGA/Ag-TCP decreased viability and proliferation rate of human dental pulp cells and increased the pro-inflammatory capacity and alkaline phosphatase expression. Whether these cellular responses observed in vitro translate into pulp regeneration in vivo will be assessed in further studies.

  14. Development of a novel CsA-PLGA drug delivery system based on a glaucoma drainage device for the prevention of postoperative fibrosis

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Zhaoxing; Yu, Xiaobo; Hong, Jiaxu; Liu, Xi [Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031 (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031 (China); Sun, Jianguo, E-mail: sjgsun@126.com [Research Center, Eye & ENT Hospital, Fudan University, Shanghai 200031 (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031 (China); State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200031 (China); Sun, Xinghuai, E-mail: xhsun@shmu.edu.cn [Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031 (China); Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031 (China)

    2016-09-01

    The formation of a scar after glaucoma surgery often leads to unsuccessful control of intraocular pressure, and should be prevented by using a variety of methods. We designed and developed a novel drug delivery system (DDS) comprising cyclosporine A (CsA) and poly(lactic-co-glycolic acid) (PLGA) based on a glaucoma drainage device (GDD) that can continuously release CsA to prevent postoperative fibrosis following glaucoma surgery. The CsA@PLGA@GDD DDS was observed by field emission scanning electron microscopy and revealed an asymmetric pore structure. Thermogravimetric analysis was performed to measure the weight loss and evaluate the thermal stability of the CsA@PLGA@GDD DDS. The in vitro drug release profile of the DDS was studied using high performance liquid chromatography, which confirmed that the DDS released CsA at a stable rate and maintained adequate CsA concentrations for a relatively long time. The biocompatibility of the DDS and the inhibitory effects on the postoperative fibrosis were investigated in vitro using rabbit Tenon's fibroblasts. The in vivo safety and efficacy of the DDS were examined by implanting the DDS into Tenon's capsules in New Zealand rabbits. Bleb morphology, intraocular pressure, anterior chamber reactions, and anterior chamber angiography were studied at a series of set times. The DDS kept the filtration pathway unblocked for a longer time compared with the control GDD. The results indicate that the CsA@PLGA@GDD DDS represents a safe and effective strategy for preventing scar formation after glaucoma surgery. - Highlights: • CsA@PLGA@GDD drug delivery system (DDS) was designed and prepared successfully. • The DDS released CsA at a stable rate for > 3 months. • The DDS kept filtration pathway unblocked for a longer time than control. • CsA@PLGA@GDD DDS prevented glaucoma scar formation as a safe and effective strategy.

  15. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

    Directory of Open Access Journals (Sweden)

    Jagadish Hiremath

    Full Text Available Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV. Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA nanoparticle (PLGA-NP based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2 chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

  16. Chemical approach to solvent removal during nanoencapsulation: its application to preparation of PLGA nanoparticles with non-halogenated solvent

    Science.gov (United States)

    Lee, Youngme; Sah, Eric; Sah, Hongkee

    2015-11-01

    The objective of this study was to develop a new oil-in-water emulsion-based nanoencapsulation method for the preparation of PLGA nanoparticles using a non-halogenated solvent. PLGA (60-150 mg) was dissolved in 3 ml of methyl propionate, which was vortexed with 4 ml of a 0.5-4 % polyvinyl alcohol solution. This premix was sonicated for 2 min, added into 30 ml of the aqueous polyvinyl alcohol solution, and reacted with 3 ml of 10 N NaOH. Solvent removal was achieved by the alkaline hydrolysis of methyl propionate dissolved in an aqueous phase into water-soluble methanol and sodium propionate. It was a simple but effective technique to quickly harden nanoemulsion droplets into nanoparticles. The appearing PLGA nanoparticles were recovered by ultracentrifugation and/or dialysis, lyophilized with trehalose, and redispersed by water. This nanoencapsulation technique permitted a control of their mean diameters over 151.7 ± 3.8 to 440.2 ± 22.2 nm at mild processing conditions. When the aqueous polyvinyl alcohol concentration was set at ≥1 %, nanoparticles showed uniform distributions with polydispersity indices below 0.1. There were no significant changes in their mean diameters and size distribution patterns before and after lyophilization. When mestranol was encapsulated into nanoparticles, the drug was completely nanoencapsulated: depending on experimental conditions, their encapsulation efficiencies were determined to be 99.4 ± 7.2 to 105.8 ± 6.3 %. This simple, facile nanoencapsulation technique might have versatile applications for the preparation of polymeric nanoparticulate dosage forms.

  17. Antiproliferative effect of ASC-J9 delivered by PLGA nanoparticles against estrogen-dependent breast cancer cells.

    Science.gov (United States)

    Verderio, Paolo; Pandolfi, Laura; Mazzucchelli, Serena; Marinozzi, Maria Rosaria; Vanna, Renzo; Gramatica, Furio; Corsi, Fabio; Colombo, Miriam; Morasso, Carlo; Prosperi, Davide

    2014-08-04

    Among polymeric nanoparticles designed for cancer therapy, PLGA nanoparticles have become one of the most popular polymeric devices for chemotherapeutic-based nanoformulations against several kinds of malignant diseases. Promising properties, including long-circulation time, enhanced tumor localization, interference with "multidrug" resistance effects, and environmental biodegradability, often result in an improvement of the drug bioavailability and effectiveness. In the present work, we have synthesized 1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyhepta-1,4,6-trien-3-one (ASC-J9) and developed uniform ASC-J9-loaded PLGA nanoparticles of about 120 nm, which have been prepared by a single-emulsion process. Structural and morphological features of the nanoformulation were analyzed, followed by an accurate evaluation of the in vitro drug release kinetics, which exhibited Fickian law diffusion over 10 days. The intracellular degradation of ASC-J9-bearing nanoparticles within estrogen-dependent MCF-7 breast cancer cells was correlated to a time- and dose-dependent activity of the released drug. A cellular growth inhibition associated with a specific cell cycle G2/M blocking effect caused by ASC-J9 release inside the cytosol allowed us to put forward a hypothesis on the action mechanism of this nanosystem, which led to the final cell apoptosis. Our study was accomplished using Annexin V-based cell death analysis, MTT assessment of proliferation, radical scavenging activity, and intracellular ROS evaluation. Moreover, the intracellular localization of nanoformulated ASC-J9 was confirmed by a Raman optical imaging experiment designed ad hoc. PLGA nanoparticles and ASC-J9 proved also to be safe for a healthy embryo fibroblast cell line (3T3-L1), suggesting a possible clinical translation of this potential nanochemotherapeutic to expand the inherently poor bioavailability of hydrophobic ASC-J9 that could be proposed for the treatment of malignant breast cancer.

  18. Meniscal repair in vivo using human chondrocyte-seeded PLGA mesh scaffold pretreated with platelet-rich plasma.

    Science.gov (United States)

    Kwak, Hong Suk; Nam, Jinwoo; Lee, Ji-Hye; Kim, Hee Joong; Yoo, Jeong Joon

    2017-02-01

    The objective of this study was to test the hypothesis that platelet-rich plasma (PRP) pretreatment on a poly-lactic-co-glycolic acid (PLGA) mesh scaffold enhances the healing capacity of the meniscus with human chondrocyte-seeded scaffolds in vivo, even when the seeded number of cells was reduced from 10 million to one million. A flexible PLGA mesh scaffold was pretreated with PRP using a centrifugal technique. One million human articular chondrocytes were seeded onto the scaffold by dynamic oscillation. After 7 days, scaffolds were placed between human meniscal discs and were implanted subcutaneously in nude mice for 6 weeks (n = 16/group). Fluorescence microscopy demonstrated uniform attachment of the chondrocytes throughout the scaffolds 24 h following seeding. Cell attachment analysis revealed a significantly increased number of chondrocytes on PRP-pretreated than non-treated scaffolds (p < 0.05). Field emission scanning electron microscopy revealed chondrocytes attached to the PRP-pretreated scaffolds interconnecting their cellular processes with the fibrin network at 24 h and day 7 of culture. Of the 16 constructs containing PRP-pretreated scaffolds implanted in mice, six menisci healed completely, nine healed incompletely and one did not heal. Histological results from the 16 control constructs containing non-treated scaffolds revealed that none had healed completely, four healed incompletely and 12 did not heal. The histological outcome between the groups was significantly different (p < 0.05). These findings suggest that human articular chondrocytes on PRP-pretreated PLGA mesh scaffolds demonstrate increased cell attachment and enhance the healing capacity of meniscus with a reduced number of seeding cells in a meniscal repair mouse model. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Chemopreventive efficacy of curcumin-loaded PLGA microparticles in a transgenic mouse model of HER-2-positive breast cancer.

    Science.gov (United States)

    Grill, Alex E; Shahani, Komal; Koniar, Brenda; Panyam, Jayanth

    2017-04-17

    Curcumin has shown promising inhibitory activity against HER-2-positive tumor cells in vitro but suffers from poor oral bioavailability in vivo. Our lab has previously developed a polymeric microparticle formulation for sustained delivery of curcumin for chemoprevention. The goal of this study was to examine the anticancer efficacy of curcumin-loaded polymeric microparticles in a transgenic mouse model of HER-2 cancer, Balb-neuT. Microparticles were injected monthly, and mice were examined for tumor appearance and growth. Initiating curcumin microparticle treatment at 2 or 4 weeks of age delayed tumor appearance by 2-3 weeks compared to that in control mice that received empty microparticles. At 12 weeks, abnormal (lobular hyperplasia, carcinoma in situ, and invasive carcinoma) mammary tissue area was significantly decreased in curcumin microparticle-treated mice, as was CD-31 staining. Curcumin treatment decreased mammary VEGF levels significantly, which likely contributed to slower tumor formation. When compared to saline controls, however, blank microparticles accelerated tumorigenesis and curcumin treatment abrogated this effect, suggesting that PLGA microparticles enhance tumorigenesis in this model. PLGA microparticle administration was shown to be associated with higher plasma lactic acid levels and increased activation of NF-κΒ. The unexpected side effects of PLGA microparticles may be related to the high dose of the microparticles that was needed to achieve sustained curcumin levels in vivo. Approaches that can decrease the overall dose of curcumin (for example, by increasing its potency or reducing its clearance rate) may allow the development of sustained release curcumin dosage forms as a practical approach to cancer chemoprevention.

  20. Photonic crystal fibers

    DEFF Research Database (Denmark)

    Lægsgaard, Jesper; Hansen, K P; Nielsen, M D

    2003-01-01

    Photonic crystal fibers having a complex microstructure in the transverse plane constitute a new and promising class of optical fibers. Such fibers can either guide light through total internal reflection or the photonic bandgap effect, In this paper, we review the different types and applications...... of photonic crystal fibers with particular emphasis on recent advances in the field....

  1. Genotoxicity testing of PLGA-PEO nanoparticles in TK6 cells by the comet assay and the cytokinesis-block micronucleus assay.

    Science.gov (United States)

    Kazimirova, Alena; Magdolenova, Zuzana; Barancokova, Magdalena; Staruchova, Marta; Volkovova, Katarina; Dusinska, Maria

    2012-10-09

    The in vitro genotoxicity of PLGA-PEO (poly-lactic-co-glycolic acid-polyethylene oxide copolymer) nanoparticles was assessed in TK6 cells using the comet assay as well as cytokinesis-block micronucleus (CBMN) assay. The cells were exposed to 0.12-75μg/cm² of PLGA-PEO nanoparticles during 2 and 24h for analysis in the comet assay, and to 3-75μg/cm² of these nanoparticles during 4, 24, 48 and 72h, respectively, for analysis in the CBMN assay. Two different protocols for treatment with cytochalasin B were used. We found that PLGA-PEO was neither cytotoxic (measured by relative cell growth activity and cytokinesis-block proliferation index (CBPI)), nor did it induce DNA strand-breaks (detected by the comet assay) or oxidative DNA lesions (measured by the comet assay modified with lesion-specific enzyme formamidopyrimidine-DNA-glycosylase). There were no statistically significant differences in the frequencies of micronucleated binucleated cells (MNBNCs) between untreated and treated cells in either of the conditions used. This suggests that PLGA-PEO did not have potential genotoxicity. However, using two experimental protocols of the micronucleus assay, PLGA-PEO nanoparticles showed a weak but significant increase in the level of MN in mononucleated cells, in cells treated for 48h with PLGA-PEO nanoparticles when cytochalasin B was added for the last 24h (1st protocol), and in cells treated for 24h with PLGA-PEO nanoparticles followed by washing of NPs and addition of cytochalasin B for another 24h (2nd protocol). It remains unclear whether the increase of MNMNC after treatment with PLGA-PEO nanoparticles is the effect of a possible, weak aneugenic potential or early effect of these particles, or due to another reason. These results suggest that aneugenicity in addition to clastogenicity may be considered as an important biomarker when assessing the genotoxic potential of polymeric nanoparticles. © 2012 Elsevier B.V. All rights reserved.

  2. Multifunctional PLGA particles containing poly(l-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity.

    Science.gov (United States)

    Stevanović, Magdalena; Bračko, Ines; Milenković, Marina; Filipović, Nenad; Nunić, Jana; Filipič, Metka; Uskoković, Dragan P

    2014-01-01

    A water-soluble antioxidant (ascorbic acid, vitamin C) was encapsulated together with poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) within a poly(lactide-co-glycolide) (PLGA) polymeric matrix and their synergistic effects were studied. The PLGA/AgNpPGA/ascorbic acid particles synthesized by a physicochemical method with solvent/non-solvent systems are spherical, have a mean diameter of 775 nm and a narrow size distribution with a polydispersity index of 0.158. The encapsulation efficiency of AgNpPGA/ascorbic acid within PLGA was determined to be >90%. The entire amount of encapsulated ascorbic acid was released in 68 days, and the entire amount of AgNpPGAs was released in 87 days of degradation. The influence of PLGA/AgNpPGA/ascorbic acid on cell viability, generation of reactive oxygen species (ROS) in HepG2 cells, as well as antimicrobial activity against seven different pathogens was investigated. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated good biocompatibility of these PLGA/AgNpPGA/ascorbic acid particles. We measured the kinetics of ROS formation in HepG2 cells by a DCFH-DA assay, and found that PLGA/AgNpPGA/ascorbic acid caused a significant decrease in DCF fluorescence intensity, which was 2-fold lower than that in control cells after a 5h exposure. This indicates that the PLGA/AgNpPGA/ascorbic acid microspheres either act as scavengers of intracellular ROS and/or reduce their formation. Also, the results of antimicrobial activity of PLGA/AgNpPGA/ascorbic acid obtained by the broth microdilution method showed superior and extended activity of these particles. The samples were characterized using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, zeta potential and particle size analysis. This paper presents a new approach to the treatment of infection that at the same time offers a very pronounced antioxidant effect. Copyright © 2013 Acta

  3. Multifunctional PLGA particles containing poly(l-glutamic acid)-capped silver nanoparticles and ascorbic acid with simultaneous antioxidative and prolonged antimicrobial activity

    OpenAIRE

    Stevanović, Magdalena; Bračko, Ines; Milenković, Marina; Filipović, Nenad; Nunić, Jana; Filipič, Metka; Uskoković, Dragan

    2014-01-01

    A water-soluble antioxidant (ascorbic acid, vitamin C) was encapsulated together with poly(l-glutamic acid)-capped silver nanoparticles (AgNpPGA) within a poly(lactide-co-glycolide) (PLGA) polymeric matrix and their synergistic effects were studied. The PLGA/AgNpPGA/ascorbic acid particles synthesized by a physicochemical method with solvent/non-solvent systems are spherical, have a mean diameter of 775 nm and a narrow size distribution with a polydispersity index of 0.158. The encapsulation ...

  4. Click chemistry on the surface of PLGA-b-PEG polymeric nanoparticles: a novel targetable fluorescent imaging nanocarrier

    Energy Technology Data Exchange (ETDEWEB)

    Pucci, Andrea; Locatelli, Erica [University of Bologna, Dipartimento di Chimica Industriale ' Toso Montanari' (Italy); Ponti, Jessica; Uboldi, Chiara [Institute for Health and Consumer Protection, Joint Research Centre, Nanobiosciences Unit (Italy); Molinari, Valerio; Comes Franchini, Mauro, E-mail: mauro.comesfranchini@unibo.it [University of Bologna, Dipartimento di Chimica Industriale ' Toso Montanari' (Italy)

    2013-08-15

    In the quest for biocompatible nanocarriers for biomedical applications, a great deal of effort is put on engineering the nanocomposites surface in order to render them specific to the particular purpose. We developed biocompatible PLGA-b-PEG-based nanoparticles carrying a double functionality (i.e., carboxylic and acetylenic) able to serve as flexible highly selective grafting centers for cancer diagnosis and treatment. As a proof of concept, the nanocarrier was successfully functionalized with a tailored fluorescent molecule by means of click chemistry and with a targeting agent specific for glioblastoma multiforme via amidic bond formation.

  5. Biodegradable PLGA85/15 nanoparticles as a delivery vehicle for Chlamydia trachomatis recombinant MOMP-187 peptide

    Science.gov (United States)

    Taha, Murtada A.; Singh, Shree R.; Dennis, Vida A.

    2012-08-01

    Development of a Chlamydia trachomatis vaccine has been a formidable task partly because of an ineffective delivery system. Our laboratory has generated a recombinant peptide of C. trachomatis major outer membrane protein (MOMP) (rMOMP-187) and demonstrated that it induced at 20 μg ml-1 maximal interleukin (IL)-6 and IL-12p40 Th1 cytokines in mouse J774 macrophages. In a continuous pursuit of a C. trachomatis effective vaccine-delivery system, we encapsulated rMOMP-187 in poly(d,l-lactic-co-glycolic acid) (PLGA, 85:15 PLA/PGA ratio) to serve as a nanovaccine candidate. Physiochemical characterizations were assessed by Fourier transform-infrared spectroscopy, atomic force microscopy, Zetasizer, Zeta potential, transmission electron microcopy and differential scanning calorimetry. The encapsulated rMOMP-187 was small (˜200 nm) with an apparently smooth uniform oval structure, thermally stable (54 °C), negatively charged ( - 27.00 mV) and exhibited minimal toxicity at concentrations 95% viable cells) over a 24-72 h period. We achieved a high encapsulation efficiency of rMOMP-187 (˜98%) in PLGA, a loading peptide capacity of 2.7% and a slow release of the encapsulated peptide. Stimulation of J774 macrophages with a concentration as low as 1 μg ml -1 of encapsulated rMOMP-187 evoked high production levels of the Th1 cytokines IL-6 (874 pg ml-1) and IL-12p40 (674 pg ml-1) as well as nitric oxide (8 μM) at 24 h post-stimulation, and in a dose-response and time-kinetics manner. Our data indicate the successful encapsulation and characterization of rMOMP-187 in PLGA and, more importantly, that PLGA enhanced the capacity of the peptide to induce Th1 cytokines and NO in vitro. These findings make this nanovaccine an attractive candidate in pursuit of an efficacious vaccine against C. trachomatis.

  6. Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres.

    Science.gov (United States)

    Andhariya, Janki V; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J; Shen, Jie

    2017-03-30

    The objective of the present study was to develop a discriminatory and reproducible accelerated release testing method for naltrexone loaded parenteral polymeric microspheres. The commercially available naltrexone microsphere product (Vivitrol ® ) was used as the testing formulation in the in vitro release method development, and both sample-and-separate and USP apparatus 4 methods were investigated. Following an in vitro drug stability study, frequent media replacement and addition of anti-oxidant in the release medium were used to prevent degradation of naltrexone during release testing at "real-time" (37°C) and "accelerated" (45°C), respectively. The USP apparatus 4 method was more reproducible than the sample-and-separate method. In addition, the accelerated release profile obtained using USP apparatus 4 had a shortened release duration (within seven days), and good correlation with the "real-time" release profile. Lastly, the discriminatory ability of the developed accelerated release method was assessed using compositionally equivalent naltrexone microspheres with different release characteristics. The developed accelerated USP apparatus 4 release method was able to detect differences in the release characteristics of the prepared naltrexone microspheres. Moreover, a linear correlation was observed between the "real-time" and accelerated release profiles of all the formulations investigated, suggesting that the release mechanism(s) may be similar under both conditions. These results indicate that the developed accelerated USP apparatus 4 method has the potential to be an appropriate fast quality control tool for long-acting naltrexone PLGA microspheres. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Development of PLGA nanoparticles simultaneously loaded with vincristine and verapamil for treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Song, Xiang Rong; Zheng, Yu; He, Gu; Yang, Li; Luo, You Fu; He, Zhi Yao; Li, Shuang Zhi; Li, Jun Ming; Yu, Shui; Luo, Xun; Hou, Shi Xiang; Wei, Yu Quan

    2010-12-01

    Hepatocellular carcinoma (HCC) is one of the malignant tumors with poor chemo-sensitivity to vincristine sulfate (VCR) due to multi-drug resistance (MDR). Combinations of encapsulated VCR and verapamil hydrochloride (VRP, a chemo-sensitizer) might be a potential strategy to improve HCC therapeutic efficacy of VCR. PLGA nanoparticles (PLGANPs) simultaneously loaded with VCR and VRP (CVn) were prepared. The entrapment efficiencies of VCR and VRP were 70.92 ± 3.78% and 85.78 ± 3.23%, respectively (n = 3). The HCC therapeutic activity of CVn was assessed using MTT assay. In BEL7402 and BEL7402/5-FU human hepatocarcinoma cell lines, CVn had the same antitumor effect as one free drug/another agent-loaded PLGANPs (C + Vn or Cn + V) combination and coadministration of two single-agent-loaded PLGANPs (Cn + Vn), which was slightly higher than that of the free VCR/VRP combination (C - V). CVn might cause lower normal tissue drug toxicity by the enhanced permeation and retention effect in vivo. Additionally, CVn might cause fewer drug-drug interaction and be the most potential formulation to simultaneously deliver VCR and VRP to the target cell in vivo than the other three nanoparticle formulations (C + Vn, Cn + V, and Cn + Vn). Therefore, we speculate that CVn might be the most effective preparation in the treatment of drug-resistant human HCC in vivo. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

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

    Directory of Open Access Journals (Sweden)

    R Dinarvand

    2008-09-01

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

  9. Fiber optic temperature sensor

    Science.gov (United States)

    Sawatari, Takeo (Inventor); Gaubis, Philip A. (Inventor)

    2000-01-01

    A fiber optic temperature sensor uses a light source which transmits light through an optical fiber to a sensor head at the opposite end of the optical fiber from the light source. The sensor head has a housing coupled to the end of the optical fiber. A metallic reflective surface is coupled to the housing adjacent the end of the optical fiber to form a gap having a predetermined length between the reflective surface and the optical fiber. A detection system is also coupled to the optical fiber which determines the temperature at the sensor head from an interference pattern of light which is reflected from the reflective surface.

  10. Drop morphologies on flexible fibers: influence of elastocapillary effects.