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.

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

Directory of Open Access Journals (Sweden)

Shin YC

2014-08-01

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

Random fiber laser based on artificially controlled backscattering fibers.

Science.gov (United States)

Wang, Xiaoliang; Chen, Daru; Li, Haitao; She, Lijuan; Wu, Qiong

2018-01-10

The random fiber laser (RFL), which is a milestone in laser physics and nonlinear optics, has attracted considerable attention recently. Most previously reported RFLs are based on distributed feedback of Rayleigh scattering amplified through the stimulated Raman-Brillouin scattering effect in single-mode fibers, which require long-distance (tens of kilometers) single-mode fibers and high threshold, up to watt level, due to the extremely small Rayleigh scattering coefficient of the fiber. We proposed and demonstrated a half-open-cavity RFL based on a segment of an artificially controlled backscattering single-mode fiber with a length of 210 m, 310 m, or 390 m. A fiber Bragg grating with a central wavelength of 1530 nm and a segment of artificially controlled backscattering single-mode fiber fabricated by using a femtosecond laser form the half-open cavity. The proposed RFL achieves thresholds of 25 mW, 30 mW, and 30 mW, respectively. Random lasing at a wavelength of 1530 nm and extinction ratio of 50 dB is achieved when a segment of 5 m erbium-doped fiber is pumped by a 980 nm laser diode in the RFL. A novel RFL with many short cavities has been achieved with low threshold.

Multiwavelength ytterbium-Brillouin random Rayleigh feedback fiber laser

Science.gov (United States)

Wu, Han; Wang, Zinan; Fan, Mengqiu; Li, Jiaqi; Meng, Qingyang; Xu, Dangpeng; Rao, Yunjiang

2018-03-01

In this letter, we experimentally demonstrate the multiwavelength ytterbium-Brillouin random fiber laser for the first time, in the half-open cavity formed by a fiber loop mirror and randomly distributed Rayleigh mirrors. With a cladding-pumped ytterbium-doped fiber and a long TrueWave fiber, the narrow linewidth Brillouin pump can generate multiple Brillouin Stokes lines with hybrid ytterbium-Brillouin gain. Up to six stable channels with a spacing of about 0.06 nm are obtained. This work extends the operation wavelength of the multiwavelength Brillouin random fiber laser to the 1 µm band, and has potential in various applications.

Laser absorption of carbon fiber reinforced polymer with randomly distributed carbon fibers

Science.gov (United States)

Hu, Jun; Xu, Hebing; Li, Chao

2018-03-01

Laser processing of carbon fiber reinforced polymer (CFRP) is a non-traditional machining method which has many prospective applications. The laser absorption characteristics of CFRP are analyzed in this paper. A ray tracing model describing the interaction of the laser spot with CFRP is established. The material model contains randomly distributed carbon fibers which are generated using an improved carbon fiber placement method. It was found that CFRP has good laser absorption due to multiple reflections of the light rays in the material’s microstructure. The randomly distributed carbon fibers make the absorptivity of the light rays change randomly in the laser spot. Meanwhile, the average absorptivity fluctuation is obvious during movement of the laser. The experimental measurements agree well with the values predicted by the ray tracing model.

Chitosan/siRNA nanoparticles encapsulated in PLGA nanofibers for siRNA delivery

DEFF Research Database (Denmark)

Chen, Menglin; Gao, Shan; Dong, Mingdong

2012-01-01

Composite nanofibers of biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) encapsulating chitosan/siRNA nanoparticles (NPs) were prepared by electrospinning. Acidic/alkaline hydrolysis and a bulk/surface degradation mechanism were investigated in order to achieve an optimized release profile...... for prolonged and efficient gene silencing. Thermo-controlled AFM in situ imaging not only revealed the integrity of the encapsulated chitosan/siRNA polyplex but also shed light on the decreasing Tg of PLGA on the fiber surfaces during release. A triphasic release profile based on bulk erosion was obtained at p......RNA transfection, where the encapsulated chitosan/siRNA NPs exhibited up to 50% EGFP gene silencing activity after 48 h post-transfection on H1299 cells....

Multi-parameter sensor based on random fiber lasers

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Yanping Xu

2016-09-01

Full Text Available We demonstrate a concept of utilizing random fiber lasers to achieve multi-parameter sensing. The proposed random fiber ring laser consists of an erbium-doped fiber as the gain medium and a random fiber grating as the feedback. The random feedback is effectively realized by a large number of reflections from around 50000 femtosecond laser induced refractive index modulation regions over a 10cm standard single mode fiber. Numerous polarization-dependent spectral filters are formed and superimposed to provide multiple lasing lines with high signal-to-noise ratio up to 40dB, which gives an access for a high-fidelity multi-parameter sensing scheme. The number of sensing parameters can be controlled by the number of the lasing lines via input polarizations and wavelength shifts of each peak can be explored for the simultaneous multi-parameter sensing with one sensing probe. In addition, the random grating induced coupling between core and cladding modes can be potentially used for liquid medical sample sensing in medical diagnostics, biology and remote sensing in hostile environments.

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

Science.gov (United States)

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

2016-07-01

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

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

Science.gov (United States)

Rafiei, Pedram; Haddadi, Azita

2017-01-01

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

Random fiber lasers based on artificially controlled backscattering fibers

Science.gov (United States)

Chen, Daru; Wang, Xiaoliang; She, Lijuan; Qiang, Zexuan; Yu, Zhangwei

2017-10-01

The random fiber laser (RFL) which is a milestone in laser physics and nonlinear optics, has attracted considerable attention recently. Most previous RFLs are based on distributed feedback of Rayleigh scattering amplified through stimulated Raman/Brillouin scattering effect in single mode fibers, which required long-distance (tens of kilometers) single mode fibers and high threshold up to watt-level due to the extremely small Rayleigh scattering coefficient of the fiber. We proposed and demonstrated a half-open cavity RFL based on a segment of a artificially controlled backscattering SMF(ACB-SMF) with a length of 210m, 310m or 390m. A fiber Bragg grating with the central wavelength of 1530nm and a segment of ACB-SMF forms the half-open cavity. The proposed RFL achieves the threshold of 25mW, 30mW and 30mW, respectively. Random lasing at the wavelength of 1530nm and the extinction ratio of 50dB is achieved when a segment of 5m EDF is pumped by a 980nm LD in the RFL. Another half-open cavity RFL based on a segment of a artificially controlled backscattering EDF(ACBS-EDF) is also demonstrated without an ACB-SMF. The 3m ACB-EDF is fabricated by using the femtosecond laser with pulse energy of 0.34mJ which introduces about 50 reflectors in the EDF. Random lasing at the wavelength of 1530nm is achieved with the output power of 7.5mW and the efficiency of 1.88%. Two novel RFLs with much short cavities have been achieved with low threshold and high efficiency.

PLGA/alginate composite microspheres for hydrophilic protein delivery

International Nuclear Information System (INIS)

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

2015-01-01

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

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.

Effects of annulus defects and implantation of poly(lactic-co-glycolic acid) (PLGA)/fibrin gel scaffolds on nerves ingrowth in a rabbit model of annular injury disc degeneration.

Science.gov (United States)

Xin, Long; Xu, Weixing; Yu, Leijun; Fan, Shunwu; Wang, Wei; Yu, Fang; Wang, Zhenbin

2017-05-12

Growth of nerve fibers has been shown to occur in a rabbit model of intravertebral disc degeneration (IVD) induced by needle puncture. As nerve growth may underlie the process of chronic pain in humans affected by disc degeneration, we sought to investigate the factors underlying nerve ingrowth in a minimally invasive annulotomy rabbit model of IVD by comparing the effects of empty disc defects with those of defects filled with poly(lactic-co-glycolic acid)/fibrin gel (PLGA) plugs. New Zealand white rabbits (n = 24) received annular injuries at three lumbar levels (L3/4, L4/5, and L5/6). The discs were randomly assigned to four groups: (a) annular defect (1.8-mm diameter; 4-mm depth) by mini-trephine, (b) annular defect implanted with a PLGA scaffold containing a fibrin gel, (c) annular puncture by a 16G needle (5-mm depth), and (d) uninjured L2/3 disc (control). Disc degeneration was evaluated by radiography, MRI, histology, real-time PCR, and analysis of proteoglycan (PG) content. Nerve ingrowth into the discs was assessed by immunostaining with the nerve marker protein gene product 9.5. Injured discs showed a progressive disc space narrowing with significant disc degeneration and proteoglycan loss, as confirmed by imaging results, molecular and compositional analysis, and histological examinations. In 16G punctured discs, nerve ingrowth was observed on the surface of scar tissue. In annular defects, nerve fibers were found to be distributed along small fissures within the fibrocartilaginous-like tissue that filled the AF. In discs filled with PLGA/ fibrin gel, more nerve fibers were observed growing deeper into the inner AF along the open annular track.  In addition, innervations scores showed significantly higher than those of punctured discs and empty defects. A limited vascular proliferation was found in the injured sites and regenerated tissues. Nerve ingrowth was significantly higher in PLGA/fibrin-filled discs than in empty defects. Possible

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

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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.

Synthesis and Characterization of Quantum Dot-Loaded Poly(lactic-co-glycolic) Acid Nanocomposite Fibers by an Electrospinning Process.

Science.gov (United States)

Ankireddy, Seshadri Reddy; Kim, Jongsung

2017-04-01

Poly(lactic-co-glycolic) acid (PLGA) is one of the most successfully developed biodegradable polymers. PLGA is a copolymer of polylactic and glycolic acid. In this work, quantum dot (QD)-loaded PLGA nanofibers were fabricated via a simple one-step electrospinning process. The surface morphology of the fibers was characterized by scanning electron microscopy (SEM). It was shown that the PLGA nanofibers had both smooth and rough surfaces with an average fiber diameter of 150 ± 25 nm and 350 ± 60 nm for the PLGA and QD-loaded PLGA nanofibers, respectively. The needle size, applied voltage, and solvent flow rate in the syringe were maintained at 23 G, 20 kV, and 1.5 mL/h, respectively. The SEM analysis showed that nanofibers with a very thin and uniform size were formed and the InP/ZnS QDs were homogeneously loaded into the PLGA nanofiber matrix. The thermal properties of the PLGA-QD nanofibers were explored by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The surface chemical structure and functionalities were characterized by Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffraction (XRPD).

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)

Wetting morphologies on randomly oriented fibers.

Science.gov (United States)

Sauret, Alban; Boulogne, François; Soh, Beatrice; Dressaire, Emilie; Stone, Howard A

2015-06-01

We characterize the different morphologies adopted by a drop of liquid placed on two randomly oriented fibers, which is a first step toward understanding the wetting of fibrous networks. The present work reviews previous modeling for parallel and touching crossed fibers and extends it to an arbitrary orientation of the fibers characterized by the tilting angle and the minimum spacing distance. Depending on the volume of liquid, the spacing distance between fibers and the angle between the fibers, we highlight that the liquid can adopt three different equilibrium morphologies: 1) a column morphology in which the liquid spreads between the fibers, 2) a mixed morphology where a drop grows at one end of the column or 3) a single drop located at the node. We capture the different morphologies observed using an analytical model that predicts the equilibrium configuration of the liquid based on the geometry of the fibers and the volume of liquid.

Hydroxyapatite fiber reinforced poly(alpha-hydroxy ester) foams for bone regeneration

Science.gov (United States)

Thomson, R. C.; Yaszemski, M. J.; Powers, J. M.; Mikos, A. G.; McIntire, L. V. (Principal Investigator)

1998-01-01

A process has been developed to manufacture biodegradable composite foams of poly(DL-lactic-co-glycolic acid) (PLGA) and hydroxyapatite short fibers for use in bone regeneration. The processing technique allows the manufacture of three-dimensional foam scaffolds and involves the formation of a composite material consisting of a porogen material (either gelatin microspheres or salt particles) and hydroxyapatite short fibers embedded in a PLGA matrix. After the porogen is leached out, an open-cell composite foam remains which has a pore size and morphology defined by the porogen. By changing the weight fraction of the leachable component it was possible to produce composite foams with controlled porosities ranging from 0.47 +/- 0.02 to 0.85 +/- 0.01 (n = 3). Up to a polymer:fiber ratio of 7:6, short hydroxyapatite fibers served to reinforce low-porosity PLGA foams manufactured using gelatin microspheres as a porogen. Foams with a compressive yield strength up to 2.82 +/- 0.63 MPa (n = 3) and a porosity of 0.47 +/- 0.02 (n = 3) were manufactured using a polymer:fiber weight ratio of 7:6. In contrast, high-porosity composite foams (up to 0.81 +/- 0.02, n = 3) suitable for cell seeding were not reinforced by the introduction of increasing quantities of hydroxyapatite short fibers. We were therefore able to manufacture high-porosity foams which may be seeded with cells but which have minimal compressive yield strength, or low porosity foams with enhanced osteoconductivity and compressive yield strength.

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.

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.

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.

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

Science.gov (United States)

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

2017-01-01

Postoperative pain is a complex physiological response to disease and tissue injury. Moderate-to-severe pain typically occurs within 48 h after surgery. Amino amide local anesthetics are widely applied to manage postoperative pain, and they have high efficacy, a low risk for addiction and limited side effects. However, these anesthetics also have short half-lives, often necessitating continuous injection to obtain satisfactory pain relief. 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 (RP), to prolong its analgesic effect. We investigated the influence of polymer and drug concentration on gelation temperature and the in vitro drug release rate from the temperature-sensitive gel. RP-loaded PLGA-PEG-PLGA solution is a liquid at room temperature and forms a gel at temperatures slightly lower than body temperature. With regard to the gel's drug release rate, 37.5, 51.3 and 72.6% of RP was released at 12, 24 and 48 h, respectively. This in vitro drug release profile conformed to the Higuchi equation. To assess pain control efficacy when using the gel, we evaluated the mechanical paw withdrawal reflex threshold, thermal pain threshold and incision cumulative pain scores in a rat incisional model. The results showed that the anti-pain effect of a single injection of RP-loaded gel at the incision site lasted for 48 h, which is significantly longer than the effect produced by injection of RP solution alone. The use of RP-loaded thermosensitive gels could provide a promising method for managing postoperative pain.

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.

Synthesis and characterization of magnetite/PLGA/chitosan nanoparticles

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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.

Synthesis and characterization of magnetite/PLGA/chitosan nanoparticles

International Nuclear Information System (INIS)

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

2015-01-01

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. (paper)

Preclinical Development and In Vivo Efficacy of Ceftiofur-PLGA Microparticles

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

2015-01-01

Drug delivery systems based on polymeric microparticles represent an interesting field of development for the treatment of several infectious diseases for humans and animals. In this work, we developed PLGA microparticles loaded with ceftiofur (PLGA-cef), a third- generation cephalosporin that is used exclusively used in animals. PLGA-cef was prepared by the double emulsion w/o/w method, and exhibited a diameter in the range of 1.5–2.2 μm, and a negative ζ potential in the range of -35 to -55 mV. The loading yield of PLGA-cef was ~7% and encapsulation efficiency was approximately 40%. The pharmacokinetic study demonstrated a sustained release profile of ceftiofur for 20 days. PLGA-cef administrated in a single dose was more effective than ceftiofur non-encapsulated in rats challenged with S. Typhimurium. The in vivo toxicological evaluation showed that PLGA-cef did not affect the blood biochemical, hematological and hemostasis parameters. Overall, the PLGA-cef showed slow in vivo release profile, high antibacterial efficacy, and low toxicity. The results obtained supports the safe application of PLGA-cef as sustained release platform in the veterinary industry. PMID:25915043

Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates

Science.gov (United States)

Dorati, Rossella; DeTrizio, Antonella; Spalla, Melissa; Migliavacca, Roberta; Pagani, Laura; Pisani, Silvia; Chiesa, Enrica; Modena, Tiziana; Genta, Ida

2018-01-01

Nanotechnology is a promising approach both for restoring or enhancing activity of old and conventional antimicrobial agents and for treating intracellular infections by providing intracellular targeting and sustained release of drug inside infected cells. The present paper introduces a formulation study of gentamicin loaded biodegradable nanoparticles (Nps). Solid-oil-in water technique was studied for gentamicin sulfate nanoencapsulation using uncapped Polylactide-co-glycolide (PLGA-H) and Polylactide-co-glycolide-co-Polyethylenglycol (PLGA-PEG) blends. Screening design was applied to optimize: drug payload, Nps size and size distribution, stability and resuspendability after freeze-drying. PLGA-PEG concentration resulted most significant factor influencing particles size and drug content (DC): 8 w/w% DC and 200 nm Nps were obtained. Stirring rate resulted most influencing factor for size distribution (PDI): 700 rpm permitted to obtain homogeneous Nps dispersion (PDI = 1). Further experimental parameters investigated, by 23 screening design, were: polymer blend composition (PLGA-PEG and PLGA-H), Polyvinylalcohol (PVA) and methanol concentrations into aqueous phase. Drug content was increased to 10.5 w/w%. Nanoparticle lyophilization was studied adding cryoprotectants, polyvinypirrolidone K17 and K32, and sodiumcarboxymetylcellulose. Freeze-drying protocol was optimized by a mixture design. A freeze-dried Nps powder free resuspendable with stable Nps size and payload, was developed. The powder was tested on clinic bacterial isolates demonstrating that after encapsulation, gentamicin sulfate kept its activity. PMID:29329209

PEGylated apoptotic protein-loaded PLGA microspheres for cancer therapy

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Byeon HJ

2015-01-01

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

Preparation of Cotton-Wool-Like Poly(lactic acid-Based Composites Consisting of Core-Shell-Type Fibers

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Jian Wang

2015-11-01

Full Text Available In previous works, we reported the fabrication of cotton-wool-like composites consisting of siloxane-doped vaterite and poly(l-lactic acid (SiVPCs. Various irregularly shaped bone voids can be filled with the composite, which effectively supplies calcium and silicate ions, enhancing the bone formation by stimulating the cells. The composites, however, were brittle and showed an initial burst release of ions. In the present work, to improve the mechanical flexibility and ion release, the composite fiber was coated with a soft, thin layer consisting of poly(d,l-lactic-co-glycolic acid (PLGA. A coaxial electrospinning technique was used to prepare a cotton-wool-like material comprising “core-shell”-type fibers with a diameter of ~12 µm. The fibers, which consisted of SiVPC coated with a ~2-µm-thick PLGA layer, were mechanically flexible; even under a uniaxial compressive load of 1.5 kPa, the cotton-wool-like material did not exhibit fracture of the fibers and, after removing the load, showed a ~60% recovery. In Tris buffer solution, the initial burst release of calcium and silicate ions from the “core-shell”-type fibers was effectively controlled, and the ions were slowly released after one day. Thus, the mechanical flexibility and ion-release behavior of the composites were drastically improved by the thin PLGA coating.

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

Energy Technology Data Exchange (ETDEWEB)

Cui, Ning [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Qian, Junmin, E-mail: jmqian@mail.xjtu.edu.cn [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Wang, Jinlei [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China); Ji, Chuanlei [The Orthopaedic Department, XiJing Hospital Affiliated to the Fourth Military Medical University, Xi' an 710032 (China); Xu, Weijun; Wang, Hongjie [State Key Laboratory for Mechanical Behavior of Materials, Xi' an Jiaotong University, Xi' an 710049 (China)

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 50–500 μm, high compressive modulus (566.6 ± 8.8 kPa), suitable glass transition temperature (46.8 ± 0.2 °C) and low degradation rate (> 8 weeks). 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. - Highlights: • Foamy PBLG/PLGA/bioglass composite scaffolds were fabricated by negative templating. • PBLG/PLGA/bioglass composite scaffolds displayed tunable physicochemical properties. • PBLG/PLGA/bioglass composite scaffolds had good biocompatibility in vitro and in vivo. • PBLG/PLGA/bioglass composite scaffolds could promote the healing of bone defects.

Preparation and characterization of a novel degradable nano-hydroxyapatite/poly(lactic-co-glycolic) composite reinforced with bamboo fiber.

Science.gov (United States)

Jiang, Liuyun; Li, Ye; Xiong, Chengdong; Su, Shengpei

2017-06-01

It is a promising and challenging to achieve an ideal poly (lactic-co-glycolic) (PLGA)-based composite. In this paper, bamboo fiber (BF) was firstly designed to incorporate into nano-hydroxyapatite/PLGA (n-HA/PLGA) composite, and a series of novel biodegradable BF/n-HA/PLGA ternary composites with different BF amounts (0wt%, 5wt%, 10wt% and 20wt%) were prepared by solution mixing method. The effect of BF content on the crystallization behavior, interface structure and mechanical property of BF/n-HA/PLGA ternary composite was investigated by X-ray diffraction pattern (XRD), differential scanning calorimeter (DSC) and scanning electron microscope (SEM), comparing with pure PLGA and n-HA/PLGA composite. The results showed that BF further promoted the crystallization of PLGA acting as a heterogeneous nucleation agent, and the addition of 10wt% BF was the best benefit to promote the crystallization. However, the higher addition content of BF caused more agglomeration in n-HA/PLGA matrix, which decreased gradually the mechanical properties of the BF/n-HA/PLGA composite. In conclusion, the addition content of 5wt% BF to n-HA/PLGA matrix was an appropriate proportion, which can achieved the best mechanical reinforce effectiveness, suggesting that BF/n-HA/PLGA composite had more potential in biomedical application than n-HA/PLGA composite. Copyright © 2017 Elsevier B.V. All rights reserved.

Transplantation of autologous endothelial progenitor cells in porous PLGA scaffolds create a microenvironment for the regeneration of hyaline cartilage in rabbits.

Science.gov (United States)

Chang, N-J; Lam, C-F; Lin, C-C; Chen, W-L; Li, C-F; Lin, Y-T; Yeh, M-L

2013-10-01

Repairing articular cartilage is clinically challenging. We investigated a simple, effective and clinically feasible cell-based therapeutic approach using a poly(lactide-co-glycolide) (PLGA) scaffold seeded with autologous endothelial progenitor cells (EPC) to repair a full-thickness osteochondral defect in rabbits using a one-step surgery. EPC obtained by purifying a small amount of peripheral blood from rabbits were seeded into a highly porous, biocompatible PLGA scaffold, namely, EPC-PLGA, and implanted into the osteochondral defect in the medial femoral condyle. Twenty two rabbits were randomized into one of three groups: the empty defect group (ED), the PLGA-only group or the EPC-PLGA group. The defect sites were evaluated 4 and 12 weeks after implantation. At the end of testing, only the EPC-PLGA group showed the development of new cartilage tissue with a smooth, transparent and integrated articular surface. Moreover, histological analysis showed obvious differences in cartilage regeneration. At week 4, the EPC-PLGA group showed considerably higher TGF-β2 and TGF-β3 expression, a greater amount of synthesized glycosaminoglycan (GAG) content, and a higher degree of osteochondral angiogenesis in repaired tissues. At week 12, the EPC-PLGA group showed enhanced hyaline cartilage regeneration with a normal columnar chondrocyte arrangement, higher SOX9 expression, and greater GAG and collagen type II (COLII) content. Moreover, the EPC-PLGA group showed organized osteochondral integration, the formation of vessel-rich tubercular bone and significantly higher bone volume per tissue volume and trabecular thickness (Tb.Th). The present EPC-PLGA cell delivery system generates a suitable in situ microenvironment for osteochondral regeneration without the supplement of exogenous growth factors. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Antimicrobial Properties and Cytocompatibility of PLGA/Ag Nanocomposites

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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.

PLGA Nanoparticles for Ultrasound-Mediated Gene Delivery to Solid Tumors

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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.

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

International Nuclear Information System (INIS)

Meng, Z.X.; Li, H.F.; Sun, Z.Z.; Zheng, W.; Zheng, Y.F.

2013-01-01

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: ► Ca–P phases were coated on PLGA/gelatin electrospun nanofiber membranes within 3 h. ► Ca–P coatings prepared by 3 methods exhibited different structures and components. ► The Ca–P coating weight increase depends on the apatite nucleation velocity. ► Surface hydrophilicity enhanced the velocity and quantity of apatite nucleation. ► The resulting Ca–P apatite coatings exhibit good biocompatibility to MG63 cells.

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

Science.gov (United States)

Meng, Z X; Li, H F; Sun, Z Z; Zheng, W; Zheng, Y F

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. Copyright © 2012 Elsevier B.V. All rights reserved.

Fabrication of orderly nanostructured PLGA scaffolds using anodic aluminum oxide templates.

Science.gov (United States)

Wang, Gou-Jen; Lin, Yan-Cheng; Li, Ching-Wen; Hsueh, Cheng-Chih; Hsu, Shan-Hui; Hung, Huey-Shan

2009-08-01

In this research, two simple fabrication methods to fabricate orderly nanostructured PLGA scaffolds using anodic aluminum oxide (AAO) template were conducted. In the vacuum air-extraction approach, the PLGA solution was cast on an AAO template first. The vacuum air-extraction process was then applied to suck the semi-congealed PLGA into the nanopores of the AAO template to form a bamboo sprouts array of PLGA. The surface roughness of the nanostructured scaffolds, ranging from 20 nm to 76 nm, can be controlled by the sucking time of the vacuum air-extraction process. In the replica molding approach, the PLGA solution was cast on the orderly scraggy barrier-layer surface of an AAO membrane to fabricate a PLGA scaffold of concave nanostructure. Cell culture experiments using the bovine endothelial cells (BEC) demonstrated that the nanostructured PLGA membrane can increase the cell growing rate, especially for the bamboo sprouts array scaffolds with smaller surface roughness.

Preparation and characterization of bee venom-loaded PLGA particles for sustained release.

Science.gov (United States)

Park, Min-Ho; Jun, Hye-Suk; Jeon, Jong-Woon; Park, Jin-Kyu; Lee, Bong-Joo; Suh, Guk-Hyun; Park, Jeong-Sook; Cho, Cheong-Weon

2016-12-14

Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.

Comparison of morphology and mechanical properties of PLGA bioscaffolds

Energy Technology Data Exchange (ETDEWEB)

Leung, L; Chan, C; Baek, S; Naguib, Hani [Department of Mechanical and Industrial Engineering, University of Toronto, 5 King' s College Road, Toronto, Ontario, M5S 3G8 (Canada)], E-mail: naguib@mie.utoronto.ca

2008-06-01

In this study, bioscaffolds using poly(DL-lactide-co-glycolide) acid (PLGA) were fabricated and studied. The gas foaming/salt leaching technique in a batch foaming setup was employed, and the effects of material composition of PLGA on the morphology and mechanical properties using this process were investigated. Two material compositions of PLGA 50/50 and 85/15 were used, and characterization of scaffolds fabricated with these materials showed that a lower relative density can be achieved with an increasing poly(DL-lactide) acid (PDLLA) content; however, higher open-cell porosity was obtained with lower PDLLA content. Furthermore, the effect of PLGA composition on modulus of the scaffolds was minor.

Methods and optical fibers that decrease pulse degradation resulting from random chromatic dispersion

Science.gov (United States)

Chertkov, Michael; Gabitov, Ildar

2004-03-02

The present invention provides methods and optical fibers for periodically pinning an actual (random) accumulated chromatic dispersion of an optical fiber to a predicted accumulated dispersion of the fiber through relatively simple modifications of fiber-optic manufacturing methods or retrofitting of existing fibers. If the pinning occurs with sufficient frequency (at a distance less than or are equal to a correlation scale), pulse degradation resulting from random chromatic dispersion is minimized. Alternatively, pinning may occur quasi-periodically, i.e., the pinning distance is distributed between approximately zero and approximately two to three times the correlation scale.

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.

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.

Active self-healing encapsulation of vaccine antigens in PLGA microspheres

Science.gov (United States)

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

2013-01-01

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

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

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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.

Neurotensin-loaded PLGA/CNC composite nanofiber membranes accelerate diabetic wound healing.

Science.gov (United States)

Zheng, Zhifang; Liu, Yishu; Huang, Wenhua; Mo, Yunfei; Lan, Yong; Guo, Rui; Cheng, Biao

2018-04-13

Diabetic foot ulcers (DFUs) are a threat to human health and can lead to amputation and even death. Recently neurotensin (NT), an inflammatory modulator in wound healing, was found to be beneficial for diabetic wound healing. As we demonstrated previously, polylactide-polyglycolide (PLGA) and cellulose nanocrystals (CNCs) (PLGA/CNC) nanofiber membranes show good cytocompatibility and facilitate fibroblast adhesion, spreading and proliferation. PLGA/CNC nanofiber membranes are novel materials that have not been used previously as NT carriers in diabetic wounds. This study aims to explore the therapeutic efficacy and possible mechanisms of NT-loaded PLGA/CNC nanofiber membranes in full-thickness skin wounds in spontaneously diabetic mice. The results showed that NT could be sustained released from NT-loaded PLGA/CNC composite nanofiber membranes for 2 weeks. NT-loaded PLGA/CNC composite nanofiber membranes induced more rapid healing than other control groups. After NT exposure, the histological scores of the epidermal and dermal regeneration and the ratios of the fibrotic area to the whole area were increased. NT-loaded PLGA/CNC composite nanofiber membranes also decreased the expressions of the inflammatory cytokines IL-1β and IL-6. These results suggest that NT-loaded PLGA/CNC composite nanofiber membranes for sustained delivery of NT should effectively promote tissue regeneration for the treatment of DFUs.

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.

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

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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.

Electrospinnability of poly lactic-co-glycolic acid (PLGA)

DEFF Research Database (Denmark)

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

2017-01-01

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

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.

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

International Nuclear Information System (INIS)

Sadeghi, A.R.; Nokhasteh, S.; Molavi, A.M.; Khorsand-Ghayeni, M.; Naderi-Meshkin, H.; Mahdizadeh, A.

2016-01-01

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.

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

Science.gov (United States)

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

2014-11-28

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

Fabrication of Nanostructured PLGA Scaffolds Using Anodic Aluminum Oxide Templates

OpenAIRE

Hsueh , Cheng-Chih; Wang , Gou-Jen; Hsu , Shan-Hui; Hung , Huey-Shan

2008-01-01

Submitted on behalf of EDA Publishing Association (http://irevues.inist.fr/handle/2042/16838); International audience; PLGA (poly(lactic-co-glycolic acid)) is one of the most used biodegradable and biocompatible materials. Nanostructured PLGA even has great application potentials in tissue engineering. In this research, a fabrication technique for nanostructured PLGA membrane was investigated and developed. In this novel fabrication approach, an anodic aluminum oxide (AAO) film was use as the...

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.

NECL1 coated PLGA as favorable conduits for repair of injured peripheral nerve

International Nuclear Information System (INIS)

Xu, Fuben; Zhang, Kun; Lv, Peizhen; Lu, Rongbin; Zheng, Li; Zhao, Jinmin

2017-01-01

Restoration of normal neurological function of transected peripheral nerve challenged regenerative medicine and surgery. Previous studies showed that Nectin-like molecule 1 (NECL1) is one of the important adhesion molecules on the axons and Schwann cells is located along the internodes in direct apposition to NECL1. In this study, we fabricated PLGA membrane pre-coated with NECL1, mimicking the natural axons to enhance the adhesion of Schwann cells. Investigation of the cellular response in vitro was performed by detecting cytotoxicity, proliferation, morphology, viability, specific markers and Scanning Electron Microscopy (SEM) of Schwann cells cultured in PLGA. Further, the NECL1-coated PLGA conduits were used for peripheral nerve repair after sciatic nerve defect was constructed. Results showed that PLGA-coated NECL1 enhanced cell proliferation compared with PLGA, as evidenced by MTT analysis, cell viability assay and histological evaluation. RT-PCR results showed that GDNF (glial cell line-derived neurotrophic factor), BDNF (brain-derived neurotrophic factor), CNTF (ciliary neurotrophic factor) and neurotrophic factors of axonal regeneration were highly expressed in PLGA/NECL1 group. S100, which is Schwann cell marker, was also elevated in PLGA-NCEL1 in both mRNA and protein expression as demonstrated by PCR and immunohistochemical examination. Moreover, in vivo study showed that implantation of PLGA/NCEL1 tubes in bridging the nerve defect can significantly improve Schwann cell aggregation and attachment and greatly enhance the functional recovery of nerve regeneration as compared with control and PLGA groups. Therefore, the novel blend of PLGA/NECL1 conduits proved to be promising candidate for tissue engineering scaffold. - Highlights: • A fabricated PLGA tubes pre-coated with Nectin-like molecule 1 (NECL1) strategy for sciatic nerve regeneration is proposed. • The NECL1 coated PLGA can promote Schwann cells adhesion and growth meanwhile maintain the

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

Science.gov (United States)

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

2016-02-01

Electrospun PLGA-based scaffolds have been applied extensively in biomedical engineering, such as tissue engineering and drug delivery system. Due to lack of the recognition sites on cells, hydropholicity and single-function, the applications of PLGA fibrous scaffolds are limited. In order to tackle these issues, many works have been done to obtain functional PLGA-based scaffolds, including surface modifications, the fabrication of PLGA-based composite scaffolds and drug-loaded scaffolds. The functional PLGA-based scaffolds have significantly improved cell adhesion, attachment and proliferation. Moreover, the current study has summarized the applications of functional PLGA-based scaffolds in wound dressing, vascular and bone tissue engineering area as well as drug delivery system. Copyright © 2015 Elsevier B.V. All rights reserved.

New PLGA-P188-PLGA matrix enhances TGF-β3 release from pharmacologically active microcarriers and promotes chondrogenesis of mesenchymal stem cells.

Science.gov (United States)

Morille, Marie; Van-Thanh, Tran; Garric, Xavier; Cayon, Jérôme; Coudane, Jean; Noël, Danièle; Venier-Julienne, Marie-Claire; Montero-Menei, Claudia N

2013-08-28

The use of injectable scaffolding materials for in vivo tissue regeneration has raised great interest in various clinical applications because it allows cell implantation through minimally invasive surgical procedures. In case of cartilage repair, a tissue engineered construct should provide a support for the cell and allow sustained in situ delivery of bioactive factors capable of inducing cell differentiation into chondrocytes. Pharmacologically active microcarriers (PAMs), made of biodegradable poly(d,l-lactide-co-glycolide acid) (PLGA), are a unique system, which combines these properties in an adaptable and simple microdevice. However, a limitation of such scaffold is low and incomplete protein release that occurs using the hydrophobic PLGA based microspheres. To circumvent this problem, we developed a novel formulation of polymeric PAMs containing a P188 poloxamer, which protects the protein from denaturation and may positively affect chondrogenesis. This poloxamer was added as a free additive for protein complexation and as a component of the scaffold covalently linked to PLGA. This procedure allows getting a more hydrophilic scaffold but also retaining the protective polymer inside the microcarriers during their degradation. The novel PLGA-P188-PLGA PAMs presenting a fibronectin-covered surface allowed enhanced MSC survival and proliferation. When engineered with TGFβ3, they allowed the sustained release of 70% of the incorporated TGF-β3 over time. Importantly, they exerted superior chondrogenic differentiation potential compared to previous FN-PAM-PLGA-TGF-β3, as shown by an increased expression of specific cartilage markers such as cartilage type II, aggrecan and COMP. Therefore, this microdevice represents an efficient easy-to-handle and injectable tool for cartilage repair. Copyright © 2013 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

Qian, Junmin; Xu, Weijun; Yong, Xueqing; Jin, Xinxia; Zhang, Wei

2014-01-01

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

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.

Bone Regeneration from PLGA Micro-Nanoparticles.

Science.gov (United States)

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

2015-01-01

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

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

Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles

Science.gov (United States)

Busari, Zulaikha A.; Dauda, Kabiru A.; Morenikeji, Olajumoke A.; Afolayan, Funmilayo; Oyeyemi, Oyetunde T.; Meena, Jairam; Sahu, Debasis; Panda, Amulya K.

2017-01-01

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) except in lymphocytes which were significantly higher in Cur-PLGA compared to the free drug (p 0.05). At higher concentrations (1000 and 500 μg/mL), Cur-PLGA entrapped nanoparticle showed higher toxicity compared with the free drug (p 0.05). The antiplasmodial activity and safety of Cur-PLGA was better at lower concentration. PMID:28932197

Machine Learning and Infrared Thermography for Fiber Orientation Assessment on Randomly-Oriented Strands Parts.

Science.gov (United States)

Fernandes, Henrique; Zhang, Hai; Figueiredo, Alisson; Malheiros, Fernando; Ignacio, Luis Henrique; Sfarra, Stefano; Ibarra-Castanedo, Clemente; Guimaraes, Gilmar; Maldague, Xavier

2018-01-19

The use of fiber reinforced materials such as randomly-oriented strands has grown in recent years, especially for manufacturing of aerospace composite structures. This growth is mainly due to their advantageous properties: they are lighter and more resistant to corrosion when compared to metals and are more easily shaped than continuous fiber composites. The resistance and stiffness of these materials are directly related to their fiber orientation. Thus, efficient approaches to assess their fiber orientation are in demand. In this paper, a non-destructive evaluation method is applied to assess the fiber orientation on laminates reinforced with randomly-oriented strands. More specifically, a method called pulsed thermal ellipsometry combined with an artificial neural network, a machine learning technique, is used in order to estimate the fiber orientation on the surface of inspected parts. Results showed that the method can be potentially used to inspect large areas with good accuracy and speed.

Poly(d,l)-lactide-co-glycolide (PLGA) microspheres as immunoadjuvant for Brugia malayi antigens.

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Saini, Vinay; Verma, Shiv Kumar; Murthy, P Kalpana; Kohli, Dharmveer

2013-08-28

Recently we identified in Brugia malayi adult worm extract (BmA) a pro-inflammatory 54-68kDa SDS-PAGE resolved fraction F6 that protects the host from the parasite via Th1/Th2 type responses. We are currently investigating F6 as a potential source of vaccine candidate(s) and the present study is aimed at investigating the suitability of poly(d,l)-lactide-co-glycolide microspheres (PLGA-Ms) as immunoadjuvant for the antigen administration in a single dose. PLGA-Ms were prepared aseptically by a modified double emulsion (w/o/w) solvent evaporation technique and their size, shape, antigen adsorption efficiency, in-process stability, and antigen release were characterized. Swiss mice were immunized by a single subcutaneous administration of BmA and F6 adsorbed on PLGA-Ms (lactide:glycolide ratios 50:50 and 75:25) and the immune responses were compared with administration of 1 or 2 doses of plain BmA and F6. Specific IgG, IgG1, IgG2a, IgG2b, IgE levels in serum, cellular-proliferative response and release of IFN-γ, TNF-α and nitric oxide from the cells of immunized host in response to the antigens/LPS/Con A challenge and antibody-dependant cellular cytotoxicity (ADCC) to parasite life stages were determined. The average size of PLGA-Ms 50:50 was smaller than the size of PLGA-Ms 75:25 and the % antigen adsorption efficiency of PLGA-Ms 50:50 was greater than PLGA-Ms 75:25. Single shot injection of PLGA-Ms 50:50/75:25-BmA/F6 produced better and stronger IgG, IgG1/IgG2a and cell-mediated immune responses than even two injections of plain BmA or F6. Further, PLGA-Ms 50:50-F6 produced stronger responses than PLGA-Ms 50:50-BmA. Anti-PLGA-Ms 50:50-F6 antibodies elicited higher ADCC response to infective larval and microfilarial stages of the parasite than anti-PLGA-Ms 75:25-F6 antibodies. The findings demonstrate that PLGA-Ms 50:50 is an excellent adjuvant for use with F6 in a single administration. This is the first ever report on PLGA as immunoadjuvant for filarial antigens

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

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

2016-03-01

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

Amikacin loaded PLGA nanoparticles against Pseudomonas aeruginosa.

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Sabaeifard, Parastoo; Abdi-Ali, Ahya; Soudi, Mohammad Reza; Gamazo, Carlos; Irache, Juan Manuel

2016-10-10

Amikacin is a very effective aminoglycoside antibiotic but according to its high toxicity, the use of this antibiotic has been limited. The aim of this study was to formulate and characterize amikacin loaded PLGA nanoparticles. Nanoparticles were synthetized using a solid-in-oil-in-water emulsion technique with different ratio of PLGA 50:50 (Resomer 502H) to drug (100:3.5, 80:3.5 and 60:3.5), two different concentrations of stabilizer (pluronic F68) (0.5% or 1%) and varied g forces to recover the final products. The most efficient formulation based on drug loading (26.0±1.3μg/mg nanoparticle) and encapsulation efficiency (76.8±3.8%) was the one obtained with 100:3.5 PLGA:drug and 0.5% luronic F68, recovered by 20,000×g for 20min. Drug release kinetic study indicated that about 50% of the encapsulated drug was released during the first hour of incubation in phospahte buffer, pH7.4, 37°C, 120rpm. Using different cell viability/cytotoxicity assays, the optimized formulation showed no toxicity against RAW macrophages after 2 and 24h of exposure. Furthermore, released drug was active and maintained its bactericidal activity against Pseudomonas aeruginosa in vitro. These results support the effective utilization of the PLGA nanoparticle formulation for amikacin in further in vivo studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Machine Learning and Infrared Thermography for Fiber Orientation Assessment on Randomly-Oriented Strands Parts

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Maldague, Xavier

2018-01-01

The use of fiber reinforced materials such as randomly-oriented strands has grown in recent years, especially for manufacturing of aerospace composite structures. This growth is mainly due to their advantageous properties: they are lighter and more resistant to corrosion when compared to metals and are more easily shaped than continuous fiber composites. The resistance and stiffness of these materials are directly related to their fiber orientation. Thus, efficient approaches to assess their fiber orientation are in demand. In this paper, a non-destructive evaluation method is applied to assess the fiber orientation on laminates reinforced with randomly-oriented strands. More specifically, a method called pulsed thermal ellipsometry combined with an artificial neural network, a machine learning technique, is used in order to estimate the fiber orientation on the surface of inspected parts. Results showed that the method can be potentially used to inspect large areas with good accuracy and speed. PMID:29351240

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

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

2010-01-01

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

Improvement of Characteristics of Clayey Soil Mixed with Randomly Distributed Natural Fibers

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Maity, J.; Chattopadhyay, B. C.; Mukherjee, S. P.

2017-11-01

In subgrade construction for flexible road pavement, properties of clayey soils available locally can be improved by providing randomly distributed fibers in the soil. The fibers added in subgrade constructions are expected to provide better compact interlocking system between the fiber and the soil grain, greater resistance to deformation and quicker dissipation of pore water pressure, thus helping consolidation and strengthening. Many natural fibers like jute, coir, sabai grass etc. which are economical and eco-friendly, are grown in abundance in India. If suitable they can be used as additive material in the subgrade soil to result in increase in strength and decrease in deformability. Such application will also reduce the cost of construction of roads, by providing lesser thickness of pavement layer. In this paper, the efficacy of using natural jute, coir or sabai grass fibers with locally available clayey soil has been studied. A series of Standard Proctor test, Soaked and Unsoaked California Bearing Ratio (CBR) test, and Unconfined Compressive Strength test were done on locally available clayey soil mixed with different types of natural fiber for various length and proportion to study the improvement of strength properties of fiber-soil composites placed at optimum moisture content. From the test results, it was observed that there was a substantial increase in CBR value for the clayey soil when mixed with increasing percentage of all three types of randomly distributed natural fibers up to 2% of the dry weight of soil. The CBR attains maximum value when the length for all types of fibers mixed with the clay taken in this study, attains a value of 10 mm.

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 .43 15.8 8. 1% PEG-InH 281.1 0.35 67.65 24.8 8.52 9.1%Pluronic-InH 319.5 0.347 69 27.6 13.7 PLGA-rhd(1% PEG) 313.3 0.303 n/A n/A n/A PLGA-rhd(1% PLu) 442.7 0.293 n/A n/A n/A PLGA-poly-(lactic-co-glycolic) acid; PEG-poly ethylene glycol; d...

Fiber-Type Random Laser Based on a Cylindrical Waveguide with a Disordered Cladding Layer.

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Zhang, Wei Li; Zheng, Meng Ya; Ma, Rui; Gong, Chao Yang; Yang, Zhao Ji; Peng, Gang Ding; Rao, Yun Jiang

2016-05-25

This letter reports a fiber-type random laser (RL) which is made from a capillary coated with a disordered layer at its internal surface and filled with a gain (laser dye) solution in the core region. This fiber-type optical structure, with the disordered layer providing randomly scattered light into the gain region and the cylindrical waveguide providing confinement of light, assists the formation of random lasing modes and enables a flexible and efficient way of making random lasers. We found that the RL is sensitive to laser dye concentration in the core region and there exists a fine exponential relationship between the lasing intensity and particle concentration in the gain solution. The proposed structure could be a fine platform of realizing random lasing and random lasing based sensing.

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

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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.

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

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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.

Interaction between dimethyldioctadecylammonium bromide-modified PLGA microspheres and hyaluronic acid

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Mulia, Kamarza; Devi, Krisanti, Elsa

2017-02-01

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

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 vaccine candidate against 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.

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

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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.

Modification of PLGA nanoparticles for improved properties as a 99mTc-labeled agent in sentinel lymph node detection.

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Subramanian, Suresh; Pandey, Usha; Gugulothu, Dalapathi; Patravale, Vandana; Samuel, Grace

2013-10-01

We have earlier reported on the possible application of poly [lactide (co-glycolide)] (PLGA) nanoparticles of suitable size to serve as a (99m)Tc-labeled diagnostic tracer in sentinel lymph node detection (SLND). Additional efforts have now been made to improve both the radiolabeling yield and the biological efficacy by modifying the PLGA particles. Two approaches were taken, one based on in situ loading of mebrofenin inside PLGA nanoparticles and the second one based on functionalization of existing terminal carboxylic acid groups on the nanoparticle surface with p-aminobenzyl diethylenetriamine pentaacetic acid (p-NH2-Bz-DTPA) for enhanced availability of functional groups suitable for (99m)Tc complexation. The modified PLGA derivatives were purified and characterized. Radiolabeling of the modified PLGA nanoparticles was carried out with (99m)Tc using stannous chloride as the reducing agent. Mebrofenin encapsulated PLGA nanoparticles (mebrofenin-PLGA) did not show any significant improvement in the radiolabeling yield in comparison to the earlier reported "plain" PLGA nanoparticles, probably due to inaccessibility of the mebrofenin moiety to (99m)Tc upon encapsulation. DTPA-conjugated PLGA nanoparticles (DTPA-PLGA) showed appreciable improvement in radiolabeling yield under more moderate reaction conditions and better stability. In the biological evaluation performed in Wistar rat model, (99m)Tc-DTPA-PLGA nanoparticles showed a considerable increase in uptake in the sentinel node and the percentage popliteal extraction of the preparation was also higher. (99m)Tc-mebrofenin-PLGA did not show any improvement in SLN uptake over plain PLGA nanoparticles. The above results suggest that surface modification of PLGA by covalently coupling DTPA to PLGA nanoparticles prior to (99m)Tc labeling appears to be a superior approach to achieve a suitable (99m)Tc-labeled PLGA nanoparticle preparation for SLND.

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

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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.

Prolonged analgesic effect of PLGA-encapsulated bee venom on formalin-induced pain in rats.

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Jeong, Injae; Kim, Beom-Soo; Lee, Hyejung; Lee, Kang-Min; Shim, Insop; Kang, Sung-Keel; Yin, Chang-Shick; Hahm, Dae-Hyun

2009-10-01

To enhance the medicinal activity of bee venom (BV) acupuncture, bee venom was loaded into biodegradable poly(D,L-lactide-co-glycolide) nanoparticles (BV-PLGA-NPs) by a water-in-oil-in-water-emulsion/solvent-evaporation technique. Rat formalin tests were performed after subcutaneous injection of BV-PLGA-NPs to the Zusanli acupuncture point (ST36) at 0.5, 1, 2, 6, 12, 24, and 48 h before plantar injection of 2% formalin. BV-PLGA-NPs treatment showed comparable analgesic activity to typical BV acupuncture during the late phase, compared with saline-treated controls, and the analgesic effect lasted for 12h. PLGA-encapsulation was also effective in alleviating the edema induced by allergens in bee venom. These results indicate that PLGA-encapsulation provided a more prolonged effect of BV acupuncture treatment, while maintaining a comparable therapeutic effect.

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

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

2014-09-01

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

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

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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.

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.

Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering.

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Wenk, Esther; Meinel, Anne J; Wildy, Sarah; Merkle, Hans P; Meinel, Lorenz

2009-05-01

The development of prototype scaffolds for either direct implantation or tissue engineering purposes and featuring spatiotemporal control of growth factor release is highly desirable. Silk fibroin (SF) scaffolds with interconnective pores, carrying embedded microparticles that were loaded with insulin-like growth factor I (IGF-I), were prepared by a porogen leaching protocol. Treatments with methanol or water vapor induced water insolubility of SF based on an increase in beta-sheet content as analyzed by FTIR. Pore interconnectivity was demonstrated by SEM. Porosities were in the range of 70-90%, depending on the treatment applied, and were better preserved when methanol or water vapor treatments were prior to porogen leaching. IGF-I was encapsulated into two different types of poly(lactide-co-glycolide) microparticles (PLGA MP) using uncapped PLGA (50:50) with molecular weights of either 14 or 35 kDa to control IGF-I release kinetics from the SF scaffold. Embedded PLGA MP were located in the walls or intersections of the SF scaffold. Embedment of the PLGA MP into the scaffolds led to more sustained release rates as compared to the free PLGA MP, whereas the hydrolytic degradation of the two PLGA MP types was not affected. The PLGA types used had distinct effects on IGF-I release kinetics. Particularly the supernatants of the lower molecular weight PLGA formulations turned out to release bioactive IGF-I. Our studies justify future investigations of the developed constructs for tissue engineering applications.

Clinical use of the resorbable bioscaffold poly lactic co-glycolic acid (PLGA) in post-extraction socket for maintaining the alveolar height: A prospective study.

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Hoda, Nadeemul; Saifi, Aamir Malick; Giraddi, Girish B

2016-01-01

A common sequel of tooth extraction is alveolar bone resorption. It makes the placement of dental implants difficult and creates an esthetic problem for the fabrication of conventional prostheses. Therefore, alveolar bone following tooth extraction should be preserved. The present prospective study was conducted to evaluate the efficacy of the resorbable bioscaffold poly lactic co-glycolic acid (PLGA) in maintaining the alveolar height in post-extraction socket. 20 patients were selected based on inclusion and exclusion criteria and were randomly divided into two groups: cases and control comprising of 10 patients each. Atraumatic tooth extraction was done in all patients. PLGA bioscaffold was placed in cases and socket was closed with 3-0 vicryl. In control group, socket was directly closed with 3-0 vicryl. The patients were kept on follow-up and complications such as dry socket, pain, and swelling were recorded. IOPA were taken at 1st, 4th, 12th, and 24th week to record changes in the height of alveolar bone. The radiographic measurements were compared and the differences were statistically analyzed. Reduction in alveolar bone height after placement of PLGA bioscaffold was significantly less in cases as compared to controls at 4th, 12th, and 24th week following extraction. No complications were observed throughout the follow-up period. PLGA scaffold significantly reduces bone resorption. Application is very simple and can be easily performed in a dental setup. However, PLGA scaffold adds significantly to the cost of treatment.

Evaluation of poly(lactic-co-glycolic acid) and poly(DL-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection

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Aniagyei, Stella E.; Sims, Lee B. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Malik, Danial A. [Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Tyo, Kevin M. [Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States); Curry, Keegan C. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Kim, Woihwan [Department of Medicine, University of Louisville, Louisville, KY 40202 (United States); Hodge, Daniel A. [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Duan, Jinghua [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States); Steinbach-Rankins, Jill M., E-mail: jill.steinbach@louisville.edu [Department of Bioengineering, University of Louisville, Louisville, KY 40202 (United States); Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202 (United States); Department of Microbiology and Immunology, University of Louisville, Louisville, KY 40202 (United States); Center for Predictive Medicine, University of Louisville, Louisville, KY 40202 (United States)

2017-03-01

More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections. - Highlights: • PLGA and PLCL EFs exhibit sustained-delivery of ACV through one month. • EFs exhibit high ACV encapsulation efficiency and in vitro biocompatibility. • EFs serve as both physical and chemical barriers to HSV-2 infection. • Potent in vitro efficacy is provided against HSV-2 infection for all formulations. • HSV-2 protection is independent of administration times within one month.

Evaluation of poly(lactic-co-glycolic acid) and poly(DL-lactide-co-ε-caprolactone) electrospun fibers for the treatment of HSV-2 infection

International Nuclear Information System (INIS)

Aniagyei, Stella E.; Sims, Lee B.; Malik, Danial A.; Tyo, Kevin M.; Curry, Keegan C.; Kim, Woihwan; Hodge, Daniel A.; Duan, Jinghua; Steinbach-Rankins, Jill M.

2017-01-01

More diverse multipurpose prevention technologies are urgently needed to provide localized, topical pre-exposure prophylaxis against sexually transmitted infections (STIs). In this work, we established the foundation for a multipurpose platform, in the form of polymeric electrospun fibers (EFs), to physicochemically treat herpes simplex virus 2 (HSV-2) infection. To initiate this study, we fabricated different formulations of poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL) EFs that encapsulate Acyclovir (ACV), to treat HSV-2 infection in vitro. Our goals were to assess the release and efficacy differences provided by these two different biodegradable polymers, and to determine how differing concentrations of ACV affected fiber efficacy against HSV-2 infection and the safety of each platform in vitro. Each formulation of PLGA and PLCL EFs exhibited high encapsulation efficiency of ACV, sustained-delivery of ACV through one month, and in vitro biocompatibility at the highest doses of EFs tested. Additionally, all EF formulations provided complete and efficacious protection against HSV-2 infection in vitro, regardless of the timeframe of collected fiber eluates tested. This work demonstrates the potential for PLGA and PLCL EFs as delivery platforms against HSV-2, and indicates that these delivery vehicles may be expanded upon to provide protection against other sexually transmitted infections. - Highlights: • PLGA and PLCL EFs exhibit sustained-delivery of ACV through one month. • EFs exhibit high ACV encapsulation efficiency and in vitro biocompatibility. • EFs serve as both physical and chemical barriers to HSV-2 infection. • Potent in vitro efficacy is provided against HSV-2 infection for all formulations. • HSV-2 protection is independent of administration times within one month.

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

Directory of Open Access Journals (Sweden)

Sho Koda

2017-01-01

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

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....

Radiation resistant fiber Bragg grating in random air-line fibers for sensing applications in nuclear reactor cores.

Science.gov (United States)

Zaghloul, Mohamed A S; Wang, Mohan; Huang, Sheng; Hnatovsky, Cyril; Grobnic, Dan; Mihailov, Stephen; Li, Ming-Jun; Carpenter, David; Hu, Lin-Wen; Daw, Joshua; Laffont, Guillaume; Nehr, Simon; Chen, Kevin P

2018-04-30

This paper reports the testing results of radiation resistant fiber Bragg grating (FBG) in random air-line (RAL) fibers in comparison with FBGs in other radiation-hardened fibers. FBGs in RAL fibers were fabricated by 80 fs ultrafast laser pulse using a phase mask approach. The fiber Bragg gratings tests were carried out in the core region of a 6 MW MIT research reactor (MITR) at a steady temperature above 600°C and an average fast neutron (>1 MeV) flux >1.2 × 10 14 n/cm 2 /s. Fifty five-day tests of FBG sensors showed less than 5 dB reduction in FBG peak strength after over 1 × 10 20 n/cm 2 of accumulated fast neutron dose. The radiation-induced compaction of FBG sensors produced less than 5.5 nm FBG wavelength shift toward shorter wavelength. To test temporal responses of FBG sensors, a number of reactor anomaly events were artificially created to abruptly change reactor power, temperature, and neutron flux over short periods of time. The thermal sensitivity and temporal responses of FBGs were determined at different accumulated doses of neutron flux. Results presented in this paper reveal that temperature-stable Type-II FBGs fabricated in radiation-hardened fibers can survive harsh in-pile conditions. Despite large parameter drift induced by strong nuclear radiation, further engineering and innovation on both optical fibers and fiber devices could lead to useful fiber sensors for various in-pile measurements to improve safety and efficiency of existing and next generation nuclear reactors.

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

Science.gov (United States)

Javiya, Curie; Jonnalagadda, Sriramakamal

2016-09-01

The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

Interlaminar fracture of random short-fiber SMC composite

Science.gov (United States)

Wang, S. S.; Suemasu, H.; Zahlan, N. M.

1984-01-01

In the experimental phase of the present study of the interlaminar fracture behavior of a randomly oriented short fiber sheet molding compound (SMC) composite, the double cantilever beam fracture test is used to evaluate the mode I interlaminar fracture toughness of different composite thicknesses. In the analytical phase of this work, a geometrically nonlinear analysis is introduced in order to account for large deflections and nonlinear load deflection curves in the evaluation of interlaminar fracture toughness. For the SMC-R50 material studied, interlaminar toughness is an order of magnitude higher than that of unreinforced neat resin, due to unusual damage mechanisms ahead of the crack tip, together with significant fiber bridging across crack surfaces. Composite thickness effects on interlaminar fracture are noted to be appreciable, and a detailed discussion is given on the influence of SMC microstructure.

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

Nanoporous Calcium Silicate and PLGA Bio composite for Bone Repair

International Nuclear Information System (INIS)

Su, J.; Wang, Z.; Wu, Y.; Cao, L.; Ma, Y.; Yu, B.; Li, M.; Yan, Y.

2010-01-01

Nanoporous calcium silicate (n-CS) with high surface area was synthesized using the mixed surfactants of EO20PO70EO20 (polyethylene oxide)20(polypropylene oxide)70(polyethylene oxide)20, 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 macroporous ranging in size from 200 to 500 μ m. 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.

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

International Nuclear Information System (INIS)

Pan, Haitao; Hao, Shaofei; Zheng, Qixin; Li, Jingfeng; Zheng, Jin; Hu, Zhilei; Yang, Shuhua; Guo, Xiaodong; Yang, Qin

2013-01-01

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

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.

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

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

Directory of Open Access Journals (Sweden)

Zhang L

2013-05-01

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

Structural and degradation characteristics of an innovative porous PLGA/TCP scaffold incorporated with bioactive molecular icaritin

Energy Technology Data Exchange (ETDEWEB)

Xie Xinhui; Wang Xinluan; Zhang Ge; He Yixin; Liu Zhong; Peng Jiang; Qin Ling [Department of Orthopaedics and Traumatology, Chinese University of Hong Kong (Hong Kong); Wang Xiaohong; He Kai [Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing (China); Leng Yang, E-mail: lingqin@cuhk.edu.h [Department of Mechanical Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon (Hong Kong)

2010-10-01

Phytomolecules may chemically bind to scaffold materials for medical applications. The present study used an osteoconductive porous poly(l-lactide-co-glycolide)/tricalcium phosphate (PLGA/TCP) to incorporate an exogenous phytoestrogenic molecule icaritin to form a PLGA/TCP/icaritin composite scaffold material with potential slow release of icaritin during scaffold degradation. Accordingly, the present study was designed to investigate its in vitro degradation characteristics and the release pattern of icaritin at three different doses (74 mg, 7.4 mg and 0.74 mg per 100 g PLGA/TCP, i.e. in the PLGA/TCP/icaritin-H, -M and -L groups, respectively). A PLGA/TCP/icaritin porous composite scaffold was fabricated using a computer-controlled printing machine. The PLGA/TCP/icaritin scaffolds were incubated in saline at 37 {sup 0}C for 12 weeks and the pure PLGA/TCP scaffold served as a control. During the 12 weeks in vitro degradation, the scaffolds in all four groups showed changes, including a decrease in weight, volume and pore size of the composite scaffold, while there was a decrease in acidity and an increase in Ca and lactic acid concentrations in the degradation medium, especially after 7 weeks. The rate of degradation was explained by the relationship with the content of icaritin incorporated into the scaffolds. The higher the icaritin content in the scaffolds, the slower the degradation could be observed during 12 weeks. After 12 weeks, the SEM showed that the surface of the PLGA/TCP and PLGA/TCP/icaritin-L groups was relatively smooth with a gradual decrease in number and size of the micropores, while the porous morphology on the surface of the PLGA/TCP/icaritin-M and PLGA/TCP/icaritin-H groups was partly maintained, accompanied by a decrease in phosphate (P) and calcium (Ca) contents at the surface. Though the mechanical property of the PLGA/TCP/icaritin scaffold decreased after degradation, its porous structure was maintained, which was essential for cell

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

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.

Copper oxide loaded PLGA nanospheres: towards a multifunctional nanoscale platform for ultrasound-based imaging and therapy

Science.gov (United States)

Perlman, Or; Weitz, Iris S.; Sivan, Sarit S.; Abu-Khalla, Hiba; Benguigui, Madeleine; Shaked, Yuval; Azhari, Haim

2018-05-01

Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of investigation exploring their potential use for diagnostic and therapeutic purposes. Recent work has demonstrated their anticancer potential, as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capability of CuO-NPs has been demonstrated using conventional ultrasound systems, which, unlike the former, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been delayed from further clinical application due to their inherent toxicity. Herein, we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared by a double emulsion (W/O/W) method with subsequent solvent evaporation. They were characterized as sphere-shaped, with size approximately 200 nm. Preliminary results showed that the viability of PANC-1, human pancreatic adenocarcinoma cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo using poultry heart and liver, and also in vivo using mice, all yielding a significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO-NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties. Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by more than 4 °C within 2 min. The heating efficiency (cumulative equivalent minutes at 43 °C) was increased approximately six-fold, demonstrating the potential for improved ultrasound ablation. In conclusion, CuO-PLGA-NS constitute a versatile platform, potentially useful for

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

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

Science.gov (United States)

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

2015-03-01

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

Endostar-loaded PEG-PLGA nanoparticles: in vitro and in vivo evaluation

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Sanyuan Hu

2010-11-01

Full Text Available Sanyuan Hu1, Yangde Zhang21Xiangya School of Medicine and 2National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Central South University, Changsha, Hunan Province, People’s Republic of ChinaAbstract: Endostar, a novel recombinant human endostatin, which was approved by the Chinese State Food and Drug Administration in 2005, has a broad spectrum of activity against solid tumors. In this study, we aimed to determine whether the anticancer effect of Endostar is increased by using a nanocarrier system. It is expected that the prolonged circulation of endostar will improve its anticancer activity. Endostar-loaded nanoparticles were prepared to improve controlled release of the drug in mice and rabbits, as well as its anticancer effects in mice with colon cancer. A protein release system could be exploited to act as a drug carrier. Nanoparticles were formulated from poly (ethylene glycol modified poly (DL-lactide-co-glycolide (PEG-PLGA by a double emulsion technique. Physical and release characteristics of endostar-loaded nanoparticles in vitro were evaluated by transmission electron microscopy (TEM, photon correlation spectroscopy (PCS, and micro bicinchoninic acid protein assay. The pharmacokinetic parameters of endostar nanoparticles in rabbit and mice plasma were measured by enzyme-linked immunosorbent assay. Western blot was used to detect endostatin in different tissues. To study the effects of endostar-loaded nanoparticles in vivo, nude mice in which tumor cells HT-29 were implanted, were subsequently treated with endostar or endostar-loaded PEG-PLGA nanoparticles. Using TEM and PCS, endostar-loaded PEG-PLGA nanoparticles were found to have a spherical core-shell structure with a diameter of 169.56 ± 35.03 nm. Drug-loading capacity was 8.22% ± 2.35% and drug encapsulation was 80.17% ± 7.83%. Compared with endostar, endostar-loaded PEG-PLGA nanoparticles had a longer elimination half-life and lower peak

A Comparative Cytotoxic Evaluation of Disulfiram Encapsulated PLGA Nanoparticles on MCF-7 Cells.

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Fasehee, Hamidreza; Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran; Ghaffari, Seyed-Hamidollah; Faghihi, Shahab

2017-04-01

Background: Disulfiram is oral aldehyde dehydrogenase (ALDH) inhibitor that has been used in the treatment of alcoholism. Recent studies show that this drug has anticancer properties; however, its rapid degradation has limited its clinical application. Encapsulation of disulfiram polymeric nanoparticles (NPs) may improve its anticancer activities and protect rapid degradation of the drug. Materials and Methods: A poly (lactide-co-Glycolide) (PLGA) was developed for encapsulation of disulfiram and its delivery into breast cancer cells. Disulfiram encapsulated PLGA NPs were prepared by nanoprecipitation method and were characterized by Scanning Electron Microscopy (SEM). The loading and encapsulation efficiency of NPs were determined using UV-Visible spectroscopy. Cell cytotoxicity of free and encapsulated form of disulfiram is also determined using MTT assay. Results: Disulfiram encapsulated PLGA NPs had uniform size with 165 nm. Drug loading and entrapment efficiency were 5.35 ±0.03% and 58.85±1.01%. The results of MTT assay showed that disulfiram encapsulated PLGA NPs were more potent in induction of apoptosis compare to free disulfiram. Conclusion: Based on the results obtained in the present study it can be concluded that encapsulation of disulfiram with PLGA can protect its degradation in improve its cytotoxicity on breast cancer cells.

Improvement of survival in C6 rat glioma model by a sustained drug release from localized PLGA microspheres in a thermoreversible hydrogel.

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Ozeki, Tetsuya; Kaneko, Daiki; Hashizawa, Kosuke; Imai, Yoshihiro; Tagami, Tatsuaki; Okada, Hiroaki

2012-05-10

A local drug delivery system based on sustained drug release is an attractive approach to treat brain tumors. We have developed a novel device using drug-incorporated poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in thermoreversible gelation polymer (TGP) formulation (drug/PLGA/TGP formulation). TGP forms a gel at body temperature but sol at room temperature. Therefore, when this formulation is injected into the brain tumor, the PLGA microspheres in TGP gel are localized at the injection site and do not diffuse throughout the brain tissue; eventually, sustained drug release from PLGA microspheres is achieved at the target site. In this study, two chemotherapeutic drugs (camptothecin (CPT) or vincristine (VCR)) were incorporated into PLGA microspheres to prepare drug/PLGA/TGP formulations. VCR/PLGA microspheres exhibited the higher encapsulation efficiency than CPT/PLGA microspheres (70.1% versus 30.1%). In addition, VCR/PLGA microspheres showed a higher sustained release profile than CPT/PLGA microspheres (54.5% versus 72.5% release, at 28 days). Therapeutic effect (mean survival) was evaluated in the C6 rat glioma model (control group, 18 days; CPT/PLGA/TGP treatment group, 24 days; VCR/PLGA/TGP treatment group, 33 days). In particular, the VCR/PLGA/TGP formulation produced long-term survivors (>60 days). Therefore, this formulation can be therapeutically effective formulation for the glioma therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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Adnan Haider

2014-01-01

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

Development of membranes of PLGA functionalized with antimicrobial agents nanostructured; Desenvolvimento de membranas de PLGA funcionalizadas com agentes antimicrobianos nanoestruturados

Energy Technology Data Exchange (ETDEWEB)

Souza, S.G.; Molin, M.L.A.L.; Nogueira, A.L.; Schneider, E. Duek; Pezzin, A.P.T., E-mail: suelengdesouza@gmail.com [Universidade da Regiao de Joinville (UNIVILLE), SC (Brazil)

2016-07-01

Periodontitis is a disease affecting the tooth supporting tissues, causing loss of bone attachment. One of the possible treatments is through guided tissue regeneration (GTR). Currently, a variety of resorbable membranes are available as alternative to conventional non-resorbable membranes for this application, as the membranes of poly (lactic acid-co-glycolic acid) (PLGA). In this context, this study aimed to produce membranes were biocompatible and nanostructured functionalized with antibacterial agents and evaluate its thermal properties for future application in RTG. For the production of membranes were used as the PLGA polymer matrix. The NpAg were used at concentrations of 5, 7, 8 and 10 ppm and NpZnO were: 10, 50, 100 and 150 ppm. The materials were characterized by TGA and DSC. (author)

Preparation and characterization of gadolinium-loaded PLGA particles surface modified with RGDS for the detection of thrombus

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Zhang Y

2013-10-01

Full Text Available Yu Zhang,1 Jun Zhou,1 Dajing Guo,1 Meng Ao,2 Yuanyi Zheng,2 Zhigang Wang21Department of Radiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Institute of Ultrasound Imaging, Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaAbstract: Thrombotic disease is a leading cause of death and disability worldwide. The development of magnetic resonance molecular imaging provides potential promise for early disease diagnosis. In this study, we explore the preparation and characterization of gadolinium (Gd-loaded poly (lactic-co-glycolic acid (PLGA particles surface modified with the Arg-Gly-Asp-Ser (RGDS peptide for the detection of thrombus. PLGA was employed as the carrier-delivery system, and a double emulsion solvent-evaporation method (water in oil in water was used to prepare PLGA particles encapsulating the magnetic resonance contrast agent Gd diethylenetriaminepentaacetic acid (DTPA. To synthesize the Gd-PLGA/chitosan (CS-RGDS particles, carbodiimide-mediated amide bond formation was used to graft the RGDS peptide to CS to form a CS-RGDS film that coated the surface of the PLGA particles. Blank PLGA, Gd-PLGA, and Gd-PLGA/CS particles were fabricated using the same water in oil in water method. Our results indicated that the RGDS peptide successfully coated the surface of the Gd-PLGA/CS-RGDS particles. The particles had a regular shape, smooth surface, relatively uniform size, and did not aggregate. The high electron density of the Gd-loaded particles and a translucent film around the particles coated with the CS and CS-RGDS films could be observed by transmission electron microscopy. In vitro experiments demonstrated that the Gd-PLGA/CS-RGDS particles could target thrombi and could be imaged using a clinical magnetic resonance scanner. Compared with the Gd-DTPA solution, the longitudinal relaxation time of

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

Science.gov (United States)

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

2015-08-18

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

PLGA/PFC particles loaded with gold nanoparticles as dual contrast agents for photoacoustic and ultrasound imaging

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Wang, Yan J.; Strohm, Eric M.; Sun, Yang; Niu, Chengcheng; Zheng, Yuanyi; Wang, Zhigang; Kolios, Michael C.

2014-03-01

Phase-change contrast agents consisting of a perfluorocarbon (PFC) liquid core stabilized by a lipid, protein, or polymer shell have been proposed for a variety of clinical applications. Previous work has demonstrated that vaporization can be induced by laser irradiation through optical absorbers incorporated inside the droplet. In this study, Poly-lactide-coglycolic acid (PLGA) particles loaded with PFC liquid and silica-coated gold nanoparticles (GNPs) were developed and characterized using photoacoustic (PA) methods. Microsized PLGA particles were loaded with PFC liquid and GNPs (14, 35, 55nm each with a 20nm silica shell) using a double emulsion method. The PA signal intensity and optical vaporization threshold were investigated using a 375 MHz transducer and a focused 532-nm laser (up to 450-nJ per pulse). The laser-induced vaporization threshold energy decreased with increasing GNP size. The vaporization threshold was 850, 690 and 420 mJ/cm2 for 5μm-sized PLGA particles loaded with 14, 35 and 55 nm GNPs, respectively. The PA signal intensity increased as the laser fluence increased prior to the vaporization event. This trend was observed for all particles sizes. PLGA particles were then incubated with MDA-MB-231 breast cancer cells for 6 hours to investigate passive targeting, and the vaporization of the PLGA particles that were internalized within cells. The PLGA particles passively internalized by MDA cells were visualized via confocal fluorescence imaging. Upon PLGA particle vaporization, bubbles formed inside the cells resulting in cell destruction. This work demonstrates that GNPs-loaded PLGA/PFC particles have potential as PA theranostic agents in PA imaging and optically-triggered drug delivery systems.

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

Science.gov (United States)

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

2016-03-01

Porous silk scaffolds, which are considered to be natural polymers, cannot be used alone because they have a long degradation rate, which makes it difficult for them to be replaced by the surrounding tissue. Scaffolds composed of synthetic polymers, such as PLGA, have a short degradation rate, lack hydrophilicity and their release of toxic by-products makes them difficult to use. The present investigations aimed to study hybrid scaffolds fabricated from PLGA, silk and hydroxyapatite nanoparticles (Hap NPs) for optimized bone tissue engineering. The results from variable-pressure field emission scanning electron microscopy (VP-FE-SEM), equipped with EDS, confirmed that the fabricated scaffolds had a porous architecture, and the location of each component present in the scaffolds was examined. Contact angle measurements confirmed that the introduction of silk and HAp NPs helped to change the hydrophobic nature of PLGA to hydrophilic, which is the main constraint for PLGA used as a biomaterial. Thermo-gravimetric analysis (TGA) and FT-IR spectroscopy confirmed thermal decomposition and different vibrations caused in functional groups of compounds used to fabricate the scaffolds, which reflected improvement in their mechanical properties. After culturing osteoblasts for 1, 7 and 14 days in the presence of scaffolds, their viability was checked by MTT assay. The fluorescent microscopy results revealed that the introduction of silk and HAp NPs had a favourable impact on the infiltration of osteoblasts. In vivo experiments were conducted by implanting scaffolds in rat calvariae for 4 weeks. Histological examinations and micro-CT scans from these experiments revealed beneficial attributes offered by silk fibroin and HAp NPs to PLGA-based scaffolds for bone induction. Copyright © 2015 John Wiley & Sons, Ltd.

PTX-loaded three-layer PLGA/CS/ALG nanoparticle based on layer-by-layer method for cancer therapy.

Science.gov (United States)

Wang, Fang; Yuan, Jian; Zhang, Qian; Yang, Siqian; Jiang, Shaohua; Huang, Chaobo

2018-05-17

Poly (lactic-co-glycolic acid) (PLGA) nanoparticles are an ideal paclitaxel (PTX)-carrying system due to its biocompatibility and biodegradability. But it possessed disadvantage of drug burst release. In this research, a layer-by-layer deposition of chitosan (CS) and sodium alginate (ALG) was applied to modify the PLGA nanoparticles. The surface charges and morphology of the PLGA, PLGA/CS and PLGA/CS/ALG particles was measured by capillary electrophoresis and SEM and TEM, respectively. The drug encapsulation and loading efficiency were confirmed by ultraviolet spectrophotometer. The nanoparticles were stable and exhibited controlled drug release performance, with good cytotoxicity to human lung carcinoma cells (HepG 2). Cumulatively, our research suggests that this kind of three-layer nanoparticle with LbL-coated shield has great properties to act as a novel drug-loaded system.

Novel PLGA-based nanoparticles for the oral delivery of insulin

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Malathi S

2015-03-01

Full Text Available Sampath Malathi,1 Perumal Nandhakumar,2 Velayudham Pandiyan,2 Thomas J Webster,3 Sengottuvelan Balasubramanian1 1Department of Inorganic Chemistry, Guindy Campus, University of Madras, Chennai, Tamil Nadu, India; 2Department of Veterinary Biochemistry, Madras Veterinary College, Chennai, Tamil Nadu, India; 3Department of Chemical Engineering, Northeastern University, Boston, USA Background: Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of d-α-tocopherol poly(ethylene glycol 1000 succinate (TPGS-emulsified poly(ethylene glycol (PEG-capped poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs was investigated for sustained delivery of insulin (IS.Objective: To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs as a potential drug carrier for the oral delivery of insulin.Methods: A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6] copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration.Results: The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30 NPs when compared to that of free

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.

Endocytic pathways involved in PLGA nanoparticle uptake by grapevine cells and role of cell wall and membrane in size selection.

Science.gov (United States)

Palocci, Cleofe; Valletta, Alessio; Chronopoulou, Laura; Donati, Livia; Bramosanti, Marco; Brasili, Elisa; Baldan, Barbara; Pasqua, Gabriella

2017-12-01

PLGA NPs' cell uptake involves different endocytic pathways. Clathrin-independent endocytosis is the main internalization route. The cell wall plays a more prominent role than the plasma membrane in NPs' size selection. In the last years, many studies on absorption and cell uptake of nanoparticles by plants have been conducted, but the understanding of the internalization mechanisms is still largely unknown. In this study, polydispersed and monodispersed poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs) were synthesized, and a strategy combining the use of transmission electron microscopy (TEM), confocal analysis, fluorescently labeled PLGA NPs, a probe for endocytic vesicles (FM4-64), and endocytosis inhibitors (i.e., wortmannin, ikarugamycin, and salicylic acid) was employed to shed light on PLGA NP cell uptake in grapevine cultured cells and to assess the role of the cell wall and plasma membrane in size selection of PLGA NPs. The ability of PLGA NPs to cross the cell wall and membrane was confirmed by TEM and fluorescence microscopy. A strong adhesion of PLGA NPs to the outer side of the cell wall was observed, presumably due to electrostatic interactions. Confocal microscopy and treatment with endocytosis inhibitors suggested the involvement of both clathrin-dependent and clathrin-independent endocytosis in cell uptake of PLGA NPs and the latter appeared to be the main internalization pathway. Experiments on grapevine protoplasts revealed that the cell wall plays a more prominent role than the plasma membrane in size selection of PLGA NPs. While the cell wall prevents the uptake of PLGA NPs with diameters over 50 nm, the plasma membrane can be crossed by PLGA NPs with a diameter of 500-600 nm.

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.

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

International Nuclear Information System (INIS)

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

2016-01-01

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

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

Science.gov (United States)

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

2016-01-01

Opioid-induced hyperalgesia (OIH) is one of the major problems associated with prolonged use of opioids for the treatment of chronic pain. Effective treatment for OIH is lacking. In this study, we examined the efficacy and preliminary mechanism of curcumin in attenuating OIH. We employed a newly developed PLGA-curcumin nanoformulation (PLGA-curcumin) in order to improve the solubility of curcumin, which has been a major obstacle in properly characterizing curcumin’s mechanism of action and efficacy. We found that curcumin administered intrathecally or orally significantly attenuated hyperalgesia in mice with morphine-induced OIH. Furthermore, we demonstrated that the effects of curcumin on OIH correlated with the suppression of chronic morphine-induced CaMKIIα activation in the superficial laminae of the spinal dorsal horn. These data suggest that PLGA-curcumin may reverse OIH possibly by inhibiting CaMKIIα and its downstream signaling. PMID:26744842

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

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Xiaoyu Hu

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

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

Directory of Open Access Journals (Sweden)

Min-Ho Park

2015-08-01

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

Narrow linewidth short cavity Brillouin random laser based on Bragg grating array fiber and dynamical population inversion gratings

Science.gov (United States)

Popov, S. M.; Butov, O. V.; Chamorovski, Y. K.; Isaev, V. A.; Mégret, P.; Korobko, D. A.; Zolotovskii, I. O.; Fotiadi, A. A.

2018-06-01

We report on random lasing observed with 100-m-long fiber comprising an array of weak FBGs inscribed in the fiber core and uniformly distributed over the fiber length. Extended fluctuation-free oscilloscope traces highlight power dynamics typical for lasing. An additional piece of Er-doped fiber included into the laser cavity enables a stable laser generation with a linewidth narrower than 10 kHz.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2011-04-22

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

Lingual traction to facilitate fiber-optic intubation of difficult airways: a single-anesthesiologist randomized trial.

Science.gov (United States)

Ching, Yiu-Hei; Karlnoski, Rachel A; Chen, Henian; Camporesi, Enrico M; Shah, Vimal V; Padhya, Tapan A; Mangar, Devanand

2015-04-01

Flexible fiber-optic bronchoscope-guided orotracheal intubation is a valuable technique with demonstrated benefits in the management of difficult airways. Despite its popularity with anesthesia providers, the technique is not fail-safe and airway-related complications secondary to failed intubation attempts remain an important problem. We sought to determine the effect of incorporating lingual traction on the success rate of fiber-optic bronchoscope-guided intubation in patients with anticipated difficult airways. In this prospective, randomized, cohort study, we enrolled 91 adult patients with anticipated difficult airways scheduled for elective surgery to undergo fiber-optic bronchoscope-guided orotracheal intubation alone or with lingual traction by an individual anesthesiologist after induction of general anesthesia and neuromuscular blockade. A total of 78 patients were randomized: 39 patients to the fiber-optic bronchoscope-guided intubation with lingual traction group and 39 patients to the fiber-optic bronchoscope-guided intubation alone group. The primary endpoint was the rate of successful first attempt intubations. The secondary outcome was sore throat grade on post-operative day 1. Fiber-optic intubation with lingual traction compared to fiber-optic intubation alone resulted in a higher success rate (92.3 vs. 74.4 %, χ (2) = 4.523, p = 0.033) and greater odds for successful first attempt intubation (OR 4.138, 95 % CI 1.041-16.444, p = 0.044). Sore throat severity on post-operative day 1 was not significantly different but trended towards worsening grades with lingual traction. In this study, lingual traction was shown to be a valuable maneuver for facilitating fiber-optic bronchoscope-guided intubation in the management of patients with anticipated difficult airways.

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

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Xi J

2017-04-01

Full Text Available Juqun Xi,1–3 Lanyue Da,1 Changshui Yang,1 Rui Chen,4 Lizeng Gao,2 Lei Fan,5 Jie Han5 1Pharmacology Department, Medical School, Yangzhou University, 2Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, 3Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, 4Department of Nephrology, Subei People’s Hospital, Yangzhou University, 5School of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China Abstract: 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. Keywords: PLGA nanoparticles, polydopamine, chemo-photothermal therapy, smart theranostic agent

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

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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.

In Vitro Comparative Study of Oxygen Plasma Treated Poly(Lactic⁻Co⁻Glycolic) (PLGA) Membranes and Supported Nanostructured Oxides for Guided Bone Regeneration Processes.

Science.gov (United States)

Torres-Lagares, Daniel; Castellanos-Cosano, Lizett; Serrera-Figallo, Maria-Angeles; López-Santos, Carmen; Barranco, Angel; Rodríguez-González-Elipe, Agustín; Gutierrez-Perez, Jose-Luis

2018-05-08

(1) Background: The use of physical barriers to prevent the invasion of gingival and connective tissue cells into bone cavities during the healing process is called guided bone regeneration. The objective of this in-vitro study was to compare the growth of human osteoblasts on Poly(Lactic⁻co⁻Glycolic) (PLGA) membranes modified with oxygen plasma and Hydroxyapatite (HA), silicon dioxide (SiO₂), and titanium dioxide (TiO₂) composite nanoparticles, respectively. (2) Methods: All the membranes received a common treatment with oxygen plasma and were subsequently treated with HA nanostructured coatings (n = 10), SiO₂ (n = 10) and TiO₂ (n = 10), respectively and a PLGA control membrane (n = 10). The assays were performed using the human osteoblast line MG-63 acquired from the Center for Scientific Instrumentation (CIC) from the University of Granada. The cell adhesion and the viability of the osteoblasts were analyzed by means of light-field microphotographs of each condition with the inverted microscope Axio Observer A1 (Carl Zeiss). For the determination of the mitochondrial energy balance, the MitoProbe™ JC-1 Assay Kit was employed. For the determination of cell growth and the morphology of adherent osteoblasts, two techniques were employed: staining with phalloidin-TRITC and staining with DAPI. (3) Results: The modified membranes that show osteoblasts with a morphology more similar to the control osteoblasts follow the order: PLGA/PO₂/HA > PLGA/PO₂/SiO₂ > PLGA/PO₂/TiO₂ > PLGA ( p membranes was observed as follows: PLGA/PO₂/SiO₂ > PLGA/PO₂/HA > PLGA/PO₂/TiO₂ > PLGA ( p membranes PLGA/PO₂/HA and PLGA/PO₂/SiO₂. (4) Conclusion: The membrane in which osteoblasts show characteristics more similar to the control osteoblasts is the PLGA/PO₂/HA, followed by the PLGA/PO₂/SiO₂.

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

Science.gov (United States)

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

2016-01-01

Controlled drug release is a process in which a predetermined amount of drug is released for longer period of time, ranging from days to months, in a controlled manner. In this study, novel drug delivery devices were fabricated via blend electrospinning and coaxial electrospinning using poly lactic glycolic acid (PLGA), gum tragacanth (GT) and tetracycline hydrochloride (TCH) as a hydrophilic model drug in different compositions and their performance as a drug carrier scaffold was evaluated. Scanning electron microscopy (SEM) results showed that fabricated PLGA, blend PLGA/GT and core shell PLGA/GT nanofibers had a smooth and bead-less morphology with the diameter ranging from 180 to 460 nm. Drug release studies showed that both the fraction of GT within blend nanofibers and the core-shell structure can effectively control TCH release rate from the nanofibrous membranes. By incorporation of TCH into core-shell nanofibers, drug release was sustained for 75 days with only 19% of burst release within the first 2h. The prolonged drug release, together with proven biocompatibility, antibacterial and mechanical properties of drug loaded core shell nanofibers make them a promising candidate to be used as drug delivery system for periodontal diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Design and Development of Bioceramic Based Functionalized PLGA Nanoparticles of Risedronate for Bone Targeting: In-vitro Characterization and Pharmacodynamic Evaluation.

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Rawat, Purnima; Manglani, Kapil; Gupta, Sarika; Kalam, Abul; Vohora, Divya; Ahmad, Farhan Jalees; Talegaonkar, Sushama

2015-10-01

Bioceramic(Hydroxyapatite) based Poly(D,L-lactide-co-glycolide) (PLGA) and polyethylene glycol (PEG) nanoparticles of Risedronate was prepared by dialysis method for bone-targeting. Risedronate, a targeting moiety that has a strong affinity for bone, was conjugated to PLGA via carbodiimide chemistry. Mono-methoxy PEG(mPEG)-PLGA block polymers were synthesized and used to impart surface hydrophilicity to nanoparticles to avoid its uptake by reticuloendothelial system (RES). The structure of prepared di block copolymers were characterized by FT-IR and NMR spectrometry. Risedronate was adsorbed on the surface of hydroxyapatite (RIS-HA) and it was conjugated with different ratios of mPEG-PLGA. The formation of surface-modified PLGA nanoparticle prepared with various ratios of risedronate as well as hydroxyapatite and mPEG was confirmed by (1)H NMR and FT-IR spectrometry. Size and % entrapment of the prepared nanoparticle was found to be 79.3 ± 2.3 nm and 93 ± 3.1%. Transmission electron microscopy (TEM) revealed that mPEG-PLGA-RIS-HA nanoparticles possess smooth and uniform surface. Pharmacodynamic study was performed on Dexamethasone (DEX) induced osteoporotic model. The effect of various formulations (mPEG-PLGA-RIS, mPEG-PLGA-RIS-HA and RISOFOS tablet) on bone was studied by Volume bone density (VBD) and by histopathological evaluation. Interestingly mPEG-PLGA-RIS-HA, showed a significant enhancement in bone micro-architecture when compared with other formulations. The results strongly implicated that mPEG-PLGA-RIS-HA has a therapeutic benefits over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model.

Mechanical properties of banana/kenaf fiber-reinforced hybrid polyester composites: Effect of woven fabric and random orientation

International Nuclear Information System (INIS)

Alavudeen, A.; Rajini, N.; Karthikeyan, S.; Thiruchitrambalam, M.; Venkateshwaren, N.

2015-01-01

Highlights: • This paper is presents the fabrications of kenaf/banana fiber hybrid composites. • Effect of weaving pattern and random orientation on mechanical properties was studied. • Role of interfacial adhesion due to chemical modifications were analyzed with the aid of SEM. • Hybridization of kenaf and banana fibers in plain woven composites exhibits maximum mechanical strength. - Abstract: The present work deals with the effect of weaving patterns and random orientatation on the mechanical properties of banana, kenaf and banana/kenaf fiber-reinforced hybrid polyester composites. Composites were prepared using the hand lay-up method with two different weaving patterns, namely, plain and twill type. Of the two weaving patterns, the plain type showed improved tensile properties compared to the twill type in all the fabricated composites. Furthermore, the maximum increase in mechanical strength was observed in the plain woven hybrid composites rather than in randomly oriented composites. This indicates minimum stress development at the interface of composites due to the distribution of load transfer along the fiber direction. Moreover, alkali (NaOH) and sodium lauryl sulfate (SLS) treatments appear to provide an additional improvement in mechanical strength through enhanced interfacial bonding. Morphological studies of fractured mechanical testing samples were performed by scanning electron microscopy (SEM) to understand the de-bonding of fiber/matrix adhesion

Efficacy of piroxicam plus cisplatin-loaded PLGA nanoparticles in inducing apoptosis in mesothelioma cells.

Science.gov (United States)

Menale, Ciro; Piccolo, Maria Teresa; Favicchia, Ilaria; Aruta, Maria Grazia; Baldi, Alfonso; Nicolucci, Carla; Barba, Vincenzo; Mita, Damiano Gustavo; Crispi, Stefania; Diano, Nadia

2015-02-01

Combined treatment based on cisplatin-loaded Poly(D,L-lactic-co-glicolic)acid (PLGA) nanoparticles (NP-C) plus the NSAID piroxicam was used as novel treatment for mesothelioma to reduce side effects related to cisplatin toxicity. PLGA nanoparticles were prepared by double emulsion solvent evaporation method. Particle size, drug release profile and in vitro cellular uptake were characterized by TEM, DLS, LC/MS and fluorescence microscopy. MSTO-211H cell line was used to analyse NP-C biological efficacy by FACS and protein analysis. Cisplatin was encapsulated in 197 nm PLGA nanoparticles with 8.2% drug loading efficiency and 47% encapsulation efficiency. Cisplatin delivery from nanoparticles reaches 80% of total encapsulated drug in 14 days following a triphasic trend. PLGA nanoparticles in MSTO-211H cells were localized in the perinuclear space NP-C in combination with piroxicam induced apoptosis using a final cisplatin concentration 1.75 fold less than free drug. Delivered cisplatin cooperated with piroxicam in modulating cell cycle regulators as caspase-3, p53 and p21. Cisplatin loaded PLGA nanoparticles plus piroxicam showed a good efficacy in exerting cytotoxic activity and inducing the same molecular apoptotic effects of the free drugs. Sustained cisplatin release allowed to use less amount of drug, decreasing toxic side effects. This novel approach could represent a new strategy for mesothelioma treatment.

High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

Science.gov (United States)

Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

2011-01-01

Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

CONTROL OF DIMENSIONAL STABILITY AND DEGRADATION RATE IN ELECTROSPUN COMPOSITE SCAFFOLDS COMPOSED OF POLY(D,L-LACTIDE-CO-GLYCOLIDE)AND POLY(Ε-CAPROLACTONE)

Institute of Scientific and Technical Information of China (English)

无

2008-01-01

The purpose of this study is to investigate the effect of composition poly(D,L-lactide-co-glycolide)/poly(ε-caprolactone)(PLGA/PCL)blending on the morphology,shrinkage and degradation behaviors of the electrospun fibers.With the increase of PLGA content in the composite fibers,the average diameter of the electrospun fibers increased from 1.35 μm to 1.95μm.The serious shrinking of the electrospun PLGA meshes could be circumvented by adding 20% PCL in the fibers,resulting from the semi-crystalline nature of PCL.The degradation rate of the electrospun meshes could be modulated by PLGA/PCL composition.In addition,the electrospun meshes containing 20% PCL displayed stable dimensional morphology with degradation.

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.

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

Directory of Open Access Journals (Sweden)

Gui-Feng Tong

2017-09-01

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

In Vitro Comparative Study of Oxygen Plasma Treated Poly(Lactic–Co–Glycolic (PLGA Membranes and Supported Nanostructured Oxides for Guided Bone Regeneration Processes

Directory of Open Access Journals (Sweden)

Daniel Torres-Lagares

2018-05-01

Full Text Available (1 Background: The use of physical barriers to prevent the invasion of gingival and connective tissue cells into bone cavities during the healing process is called guided bone regeneration. The objective of this in-vitro study was to compare the growth of human osteoblasts on Poly(Lactic–co–Glycolic (PLGA membranes modified with oxygen plasma and Hydroxyapatite (HA, silicon dioxide (SiO2, and titanium dioxide (TiO2 composite nanoparticles, respectively. (2 Methods: All the membranes received a common treatment with oxygen plasma and were subsequently treated with HA nanostructured coatings (n = 10, SiO2 (n = 10 and TiO2 (n = 10, respectively and a PLGA control membrane (n = 10. The assays were performed using the human osteoblast line MG-63 acquired from the Center for Scientific Instrumentation (CIC from the University of Granada. The cell adhesion and the viability of the osteoblasts were analyzed by means of light-field microphotographs of each condition with the inverted microscope Axio Observer A1 (Carl Zeiss. For the determination of the mitochondrial energy balance, the MitoProbe™ JC-1 Assay Kit was employed. For the determination of cell growth and the morphology of adherent osteoblasts, two techniques were employed: staining with phalloidin-TRITC and staining with DAPI. (3 Results: The modified membranes that show osteoblasts with a morphology more similar to the control osteoblasts follow the order: PLGA/PO2/HA > PLGA/PO2/SiO2 > PLGA/PO2/TiO2 > PLGA (p < 0.05. When analysing the cell viability, a higher percentage of viable cells bound to the membranes was observed as follows: PLGA/PO2/SiO2 > PLGA/PO2/HA > PLGA/PO2/TiO2 > PLGA (p < 0.05, with a better energy balance of the cells adhered to the membranes PLGA/PO2/HA and PLGA/PO2/SiO2. (4 Conclusion: The membrane in which osteoblasts show characteristics more similar to the control osteoblasts is the PLGA/PO2/HA, followed by the PLGA/PO2/SiO2.

The biological performance of injectable calcium phosphate/PLGA cement in osteoporotic rats

International Nuclear Information System (INIS)

Van de Watering, Floor C J; Cuijpers, Vincent M; Jansen, John A; Van den Beucken, Jeroen J J P; Laverman, Peter; Gotthardt, Martin; Boerman, Otto C; Bronkhorst, Ewald M

2013-01-01

Calcium phosphate cements (CPCs) including poly(D,L-lactic-co-glycolic) acid (PLGA) microparticles are promising candidates for bone regenerative applications. Previous studies with CPC/PLGA demonstrated that the material is non-toxic, biocompatible and osteoconductive. However, the outcome of these studies was based on healthy individuals and consequently does not provide information on bone substitute material performance in a compromised situation, such as osteoporosis. Therefore, this study comparatively evaluated the performance of injectable CPC/PLGA in healthy (SHAM) and osteoporotic rats (OVX) using a rat femoral condyle defect with implantation periods of 4 and 12 weeks. It was hypothesized that in OVX rats the degradation of CPC/PLGA would increase due to a higher osteoclastic activity present in osteoporotic animals and that the obtained space would be rapidly filled with newly formed bone. The results revealed an accelerated degradation of the used CPC/PLGA in osteoporotic animals, but bone formation was less compared to that in healthy animals at 4 and 12 weeks after implantation. In addition, after 4 weeks, the amount of newly formed bone under osteoporotic conditions was less in the femoral condyle defect compared to that present in a non-defect, osteoporotic control femoral condyle, but equal after 12 weeks. On the other hand, in healthy animals, the amount of newly formed bone in the femoral condyle defect was equal to that present in a non-defect control femoral condyle at 4 weeks, while higher after 12 weeks. This indicates that bone regeneration at a defect site under osteoporotic conditions is slower, but can reach native amounts after longer time periods. Consequently, bone regenerative treatments under osteoporotic conditions seem to require additional empowerment of bone substitute materials. (paper)

Comparative evaluation of antibacterial activity of caffeic acid phenethyl ester and PLGA nanoparticle formulation by different methods

Science.gov (United States)

Arasoglu, Tülin; Derman, Serap; Mansuroglu, Banu

2016-01-01

The aim of the present study was to evaluate the antimicrobial activity of nanoparticle and free formulations of the CAPE compound using different methods and comparing the results in the literature for the first time. In parallel with this purpose, encapsulation of CAPE with the PLGA nanoparticle system (CAPE-PLGA-NPs) and characterization of nanoparticles were carried out. Afterwards, antimicrobial activity of free CAPE and CAPE-PLGA-NPs was determined using agar well diffusion, disk diffusion, broth microdilution and reduction percentage methods. P. aeroginosa, E. coli, S. aureus and methicillin-resistant S. aureus (MRSA) were chosen as model bacteria since they have different cell wall structures. CAPE-PLGA-NPs within the range of 214.0 ± 8.80 nm particle size and with an encapsulation efficiency of 91.59 ± 4.97% were prepared using the oil-in-water (o-w) single-emulsion solvent evaporation method. The microbiological results indicated that free CAPE did not have any antimicrobial activity in any of the applied methods whereas CAPE-PLGA-NPs had significant antimicrobial activity in both broth dilution and reduction percentage methods. CAPE-PLGA-NPs showed moderate antimicrobial activity against S. aureus and MRSA strains particularly in hourly measurements at 30.63 and 61.25 μg ml-1 concentrations (both p 0.05). In the reduction percentage method, in which the highest results of antimicrobial activity were obtained, it was observed that the antimicrobial effect on S. aureus was more long-standing (3 days) and higher in reduction percentage (over 90%). The appearance of antibacterial activity of CAPE-PLGA-NPs may be related to higher penetration into cells due to low solubility of free CAPE in the aqueous medium. Additionally, the biocompatible and biodegradable PLGA nanoparticles could be an alternative to solvents such as ethanol, methanol or DMSO. Consequently, obtained results show that the method of selection is extremely important and will influence the

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

International Nuclear Information System (INIS)

Xu Mingen; Li Yanlei; Suo Hairui; Wang Qiujun; Ge Yakun; Xu Ying; Yan Yongnian; Liu Li

2010-01-01

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 μm; macropore: 495 ± 54 μm) 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.

Bone regeneration of critical calvarial defect in goat model by PLGA/TCP/rhBMP-2 scaffolds prepared by low-temperature rapid-prototyping technology.

Science.gov (United States)

Yu, D; Li, Q; Mu, X; Chang, T; Xiong, Z

2008-10-01

Active artificial bone composed of poly lactide-co-glycolide (PLGA)/ tricalcium phosphate (TCP) was prefabricated using low-temperature rapid-prototyping technology so that the process of osteogenesis could be observed in it. PLGA and TCP were the primary materials, they were molded at low temperature, then recombinant human bone morphogenetic protein-2 (rhBMP-2) was added to form an active artificial bone. Goats with standard cranial defects were randomly divided into experimental (implants with rhBMP-2 added) and control (implants without rhBMP-2) groups, and osteogenesis was observed and evaluated by imaging and biomechanical and histological examinations. The PLGA-TCP artificial bone scaffold (90% porosity) had large and small pores of approximately 360microm and 3-5microm diameter. Preliminary and complete repair of the cranial defect in the goats occurred 12 and 24 weeks after surgery, respectively. The three-point bending strength of the repaired defects attained that of the normal cranium. In conclusion, low-temperature rapid-prototyping technology can preserve the biological activity of this scaffold material. The scaffold has a good three-dimensional structure and it becomes an active artificial bone after loading with rhBMP-2 with a modest degradation rate and excellent osteogenesis in the goat.

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.

Synergistic effect of PLGA nanoparticles and submicron triglyceride droplets in enhancing the intestinal solubilisation of a lipophilic weak base.

Science.gov (United States)

Joyce, Paul; Prestidge, Clive A

2018-06-15

A novel hybrid microparticulate system composed of poly(lactic-co-glycolic) acid (PLGA) nanoparticles and submicron medium-chain triglyceride (MCT) droplets was fabricated to overcome the pH-dependent solubility and precipitation challenges associated with a model poorly water-soluble weak base, cinnarizine (CIN). Molecular CIN was confined within both the lipid and polymer phase of PLGA-lipid hybrid (PLH) and PLGA-lipid-mannitol hybrid (PLMH) particles, which offered significant biopharmaceutical advantages in comparison to the unformulated drug, submicron MCT droplets and PLGA nanoparticles. This was highlighted by a substantial reduction in the pH-induced precipitation during in vitro gastrointestinal two-step dissolution studies. A >2.5-fold solubilisation enhancement was observed for the composite particles during simulated intestinal conditions, compared to pure CIN. Furthermore, the drug solubilisation capacity during in vitro intestinal digesting conditions was ~2-2.5 times greater for PLMH particles compared to the precursor emulsion droplets and PLGA nanoparticles. The observations from this study indicate that a synergy exists between the degradation products of PLGA nanoparticles and lipid droplets, whereby the dual-phase release and dissolution mechanism of the hybrid particles aids in prolonging pH-provoked precipitation. Subsequently, the ability for PLGA polymers and oligomers to act as polymeric precipitation inhibitors has been highlighted for the first time. Copyright © 2018 Elsevier B.V. All rights reserved.

Surface functionalisation of PLGA nanoparticles for gene silencing

DEFF Research Database (Denmark)

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

2010-01-01

. In addition, particles containing cetylated-PEI achieved 64% silencing of TNFα in J774.1 cells. This rapid method for surface modification of PLGA nanoparticles promotes its application for alternative cetylated functional derivatives as a strategy to control specific biological properties of nanoparticles....

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

Science.gov (United States)

Rauta, Pradipta Ranjan; Nayak, Bismita

2015-05-01

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

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.

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.

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.

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

International Nuclear Information System (INIS)

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

2015-01-01

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. (paper)

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.

Bone repair by cell-seeded 3D-bioplotted composite scaffolds made of collagen treated tricalciumphosphate or tricalciumphosphate-chitosan-collagen hydrogel or PLGA in ovine critical-sized calvarial defects.

Science.gov (United States)

Haberstroh, Kathrin; Ritter, Kathrin; Kuschnierz, Jens; Bormann, Kai-Hendrik; Kaps, Christian; Carvalho, Carlos; Mülhaupt, Rolf; Sittinger, Michael; Gellrich, Nils-Claudius

2010-05-01

The aim of this study was to investigate the osteogenic effect of three different cell-seeded 3D-bioplotted scaffolds in a ovine calvarial critical-size defect model. The choice of scaffold-materials was based on their applicability for 3D-bioplotting and respective possibility to produce tailor-made scaffolds for the use in cranio-facial surgery for the replacement of complex shaped boneparts. Scaffold raw-materials are known to be osteoinductive when being cell-seeded [poly(L-lactide-co-glycolide) (PLGA)] or having components with osteoinductive properties as tricalciumphosphate (TCP) or collagen (Col) or chitosan. The scaffold-materials PLGA, TCP/Col, and HYDR (TCP/Col/chitosan) were cell-seeded with osteoblast-like cells whether gained from bone (OLB) or from periost (OLP). In a prospective and randomized design nine sheep underwent osteotomy to create four critical-sized calvarial defects. Three animals each were assigned to the HYDR-, the TCP/Col-, or the PLGA-group. In each animal, one defect was treated with a cell-free, an OLB- or OLP-seeded group-specific scaffold, respectively. The fourth defect remained untreated as control (UD). Fourteen weeks later, animals were euthanized for histo-morphometrical analysis of the defect healing. OLB- and OLP-seeded HYDR and OLB-seeded TCP/Col scaffolds significantly increased the amount of newly formed bone (NFB) at the defect bottom and OLP-seeded HYDR also within the scaffold area, whereas PLGA-scaffolds showed lower rates. The relative density of NFB was markedly higher in the HYDR/OLB group compared to the corresponding PLGA group. TCP/Col had good stiffness to prepare complex structures by bioplotting but HYDR and PLGA were very soft. HYDR showed appropriate biodegradation, TCP/Col and PLGA seemed to be nearly undegraded after 14 weeks. 3D-bioplotted, cell-seeded HYDR and TCP/Col scaffolds increased the amount of NFB within ovine critical-size calvarial defects, but stiffness, respectively, biodegradation of

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.

Comparative evaluation of antibacterial activity of caffeic acid phenethyl ester and PLGA nanoparticle formulation by different methods

International Nuclear Information System (INIS)

Arasoglu, Tülin; Mansuroglu, Banu; Derman, Serap

2016-01-01

The aim of the present study was to evaluate the antimicrobial activity of nanoparticle and free formulations of the CAPE compound using different methods and comparing the results in the literature for the first time. In parallel with this purpose, encapsulation of CAPE with the PLGA nanoparticle system (CAPE-PLGA-NPs) and characterization of nanoparticles were carried out. Afterwards, antimicrobial activity of free CAPE and CAPE-PLGA-NPs was determined using agar well diffusion, disk diffusion, broth microdilution and reduction percentage methods. P. aeroginosa, E. coli, S. aureus and methicillin-resistant S. aureus (MRSA) were chosen as model bacteria since they have different cell wall structures. CAPE-PLGA-NPs within the range of 214.0 ± 8.80 nm particle size and with an encapsulation efficiency of 91.59 ± 4.97% were prepared using the oil-in-water (o–w) single-emulsion solvent evaporation method. The microbiological results indicated that free CAPE did not have any antimicrobial activity in any of the applied methods whereas CAPE-PLGA-NPs had significant antimicrobial activity in both broth dilution and reduction percentage methods. CAPE-PLGA-NPs showed moderate antimicrobial activity against S. aureus and MRSA strains particularly in hourly measurements at 30.63 and 61.25 μg ml −1 concentrations (both p < 0.05), whereas they failed to show antimicrobial activity against Gram-negative bacteria (P. aeroginosa and E. coli, p > 0.05). In the reduction percentage method, in which the highest results of antimicrobial activity were obtained, it was observed that the antimicrobial effect on S. aureus was more long-standing (3 days) and higher in reduction percentage (over 90%). The appearance of antibacterial activity of CAPE-PLGA-NPs may be related to higher penetration into cells due to low solubility of free CAPE in the aqueous medium. Additionally, the biocompatible and biodegradable PLGA nanoparticles could be an alternative to solvents such as

Corrosion and drug release properties of EN-plating/PLGA composite coating on MAO film

International Nuclear Information System (INIS)

Lu Ping; Liu Yin; Guo Meiqing; Fang Haidong; Xu Xinhua

2011-01-01

The electroless nickel plating/poly(DL-lactide-co-glycolide) composite coating (EN-plating/PLGA composite coating) was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy AZ81 to double control the corrosion and drug release in the hanks' solution. The EN-plating was fabricated on the MAO coating to improve the corrosion resistance by overlaying most pores and micro-cracks on the surface of the MAO film. Meanwhile, a double layered organic poly(DL-lactide-co-glycolide)/paclitaxel (PLGA/PTX) drug releasing coating with a top layered PLGA drug controlled releasing coating on EN plating was prepared to control the drug release rate by adjusting the different lactide: glycolide (LA:GA) ratio of PLGA. Scanning electron microscopy (SEM) and the X-ray powder diffraction (XRD) were used to analyze the morphology and the composition of the EN-plating. The corrosion behavior of the magnesium alloy substrate and the status of the drug in the PLGA matrix were respectively evaluated by Potentiodynamic polarization and Differential scanning calorimetry (DSC). The drug release was determined by ultraviolet-visible (UV-visible) spectrophotometer. EN-plating coating which was composed of compact cauliflower nodules was uniform in size and defect free with no pores or cracks. EN-plating could seal the microcracks and microholes on the outer layer of the MAO coating effectively. The corrosion resistance was improved by preventing the corrosive ions from diffusing to the magnesium alloy substrate. The drug release rate of PTX exhibited a nearly linear sustained-release profile with no significant burst releases. - Research highlights: → An organic and in organic EN-plating/PLGA composite coating was first fabricated on the surface of the MAO film. → This composite coating the magnesium alloy AZ81could double control the corrosion and drug release in the hanks' solution. → The drug release rate could be controlled by LG:GA ratio and the PTX

Corrosion and drug release properties of EN-plating/PLGA composite coating on MAO film

Energy Technology Data Exchange (ETDEWEB)

Lu Ping [School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072 (China); Liu Yin [Department of Cardiology, Tianjin Chest Hospital, Tianjin 300051 (China); Guo Meiqing; Fang Haidong [School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072 (China); Xu Xinhua, E-mail: xhxu_tju@eyou.com [School of Materials Science and Engineering, and Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin 300072 (China)

2011-10-10

The electroless nickel plating/poly(DL-lactide-co-glycolide) composite coating (EN-plating/PLGA composite coating) was fabricated on the surface of the micro-arc oxidation (MAO) film of the magnesium alloy AZ81 to double control the corrosion and drug release in the hanks' solution. The EN-plating was fabricated on the MAO coating to improve the corrosion resistance by overlaying most pores and micro-cracks on the surface of the MAO film. Meanwhile, a double layered organic poly(DL-lactide-co-glycolide)/paclitaxel (PLGA/PTX) drug releasing coating with a top layered PLGA drug controlled releasing coating on EN plating was prepared to control the drug release rate by adjusting the different lactide: glycolide (LA:GA) ratio of PLGA. Scanning electron microscopy (SEM) and the X-ray powder diffraction (XRD) were used to analyze the morphology and the composition of the EN-plating. The corrosion behavior of the magnesium alloy substrate and the status of the drug in the PLGA matrix were respectively evaluated by Potentiodynamic polarization and Differential scanning calorimetry (DSC). The drug release was determined by ultraviolet-visible (UV-visible) spectrophotometer. EN-plating coating which was composed of compact cauliflower nodules was uniform in size and defect free with no pores or cracks. EN-plating could seal the microcracks and microholes on the outer layer of the MAO coating effectively. The corrosion resistance was improved by preventing the corrosive ions from diffusing to the magnesium alloy substrate. The drug release rate of PTX exhibited a nearly linear sustained-release profile with no significant burst releases. - Research highlights: {yields} An organic and in organic EN-plating/PLGA composite coating was first fabricated on the surface of the MAO film. {yields} This composite coating the magnesium alloy AZ81could double control the corrosion and drug release in the hanks' solution. {yields} The drug release rate could be controlled by LG

Distributed feedback multimode Brillouin–Raman random fiber laser in the S-band

International Nuclear Information System (INIS)

Ahmad, H; Zulkifli, M Z; Jemangin, M H; Harun, S W

2013-01-01

A novel S-band multimode Brillouin–Raman random fiber laser based on distributed feedback of Rayleigh scattered light is demonstrated. It relies on a short length, 7.7 km long angle-cleaved dispersion compensating fiber in a mirror-less open cavity. Two 1425 nm laser diodes at a modest operating power amplify a Brillouin pump (BP) signal, which in turn generates a multi-wavelength laser output through the stimulated Brillouin scattering. Eleven Brillouin Stokes lines, spanning from 1515.15 to 1516.00 nm, were obtained at a Raman pump power of 361.66 mW. Out of these, five odd Brillouin Stokes lines were generated with a flat peak power of about 0 dBm. (letter)

A Biomimetic Approach to Active Self-Microencapsulation of Proteins in PLGA

Science.gov (United States)

Shah, Ronak B.; Schwendeman, Steven P.

2014-01-01

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 pH 7. 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 42 h. 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

Additive non-uniform random sampling in superimposed fiber Bragg grating strain gauge

Science.gov (United States)

Ma, Y. C.; Liu, H. Y.; Yan, S. B.; Yang, Y. H.; Yang, M. W.; Li, J. M.; Tang, J.

2013-05-01

This paper demonstrates an additive non-uniform random sampling and interrogation method for dynamic and/or static strain gauge using a reflection spectrum from two superimposed fiber Bragg gratings (FBGs). The superimposed FBGs are designed to generate non-equidistant space of a sensing pulse train in the time domain during dynamic strain gauge. By combining centroid finding with smooth filtering methods, both the interrogation speed and accuracy are improved. A 1.9 kHz dynamic strain is measured by generating an additive non-uniform randomly distributed 2 kHz optical sensing pulse train from a mean 500 Hz triangular periodically changing scanning frequency.

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

Science.gov (United States)

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

2014-06-05

The increasing realisation of the impact of size and surface properties on the bio-distribution of drug loaded colloidal particles has driven the application of micro fabrication technologies for the precise engineering of drug loaded microparticles. This paper demonstrates an alternative approach for producing size controlled drug loaded PLGA based microparticles using silicon Microfluidic Flow Focusing Devices (MFFDs). Based on the precise geometry and dimensions of the flow focusing channel, microparticle size was successfully optimised by modifying the polymer type, disperse phase (Qd) flow rate, and continuous phase (Qc) flow rate. The microparticles produced ranged in sizes from 5 to 50 μm and were highly monodisperse (coefficient of variation <5%). A comparison of Ciclosporin (CsA) loaded PLGA microparticles produced by MFFDs vs conventional production techniques was also performed. MFFDs produced microparticles with a narrower size distribution profile, relative to the conventional approaches. In-vitro release kinetics of CsA was found to be influenced by the production technique, with the MFFD approach demonstrating the slowest rate of release over 7 days (4.99 ± 0.26%). Finally, MFFDs were utilised to produce pegylated microparticles using the block co-polymer, PEG-PLGA. In contrast to the smooth microparticles produced using PLGA, PEG-PLGA microparticles displayed a highly porous surface morphology and rapid CsA release, with 85 ± 6.68% CsA released after 24h. The findings from this study demonstrate the utility of silicon MFFDs for the precise control of size and surface morphology of PLGA based microparticles with potential drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to facilitate the oral delivery efficiency.

Science.gov (United States)

Yu, Fei; Ao, Mingtao; Zheng, Xiao; Li, Nini; Xia, Junjie; Li, Yang; Li, Donghui; Hou, Zhenqing; Qi, Zhongquan; Chen, Xiao Dong

2017-11-01

The natural product berberine (BBR), present in various plants, arouses great interests because of its numerous pharmacological effects. However, the further development and application of BBR had been hampered by its poor oral bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent evaporation method for enhancing the oral BBR efficiency. The advantage of this new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR-SPC) could be used to enhance the liposolubility of BBR and improve the affinity with the biodegradable polymer to increase the drug-loading capacity and controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4 times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our knowledge, this is the first report on using polymer material for effective encapsulation of BBR to improve its oral bioavailability. The prepared BBR delivery systems demonstrated a uniform spherical shape, a well-dispersed core-shell structure and a small particle size (149.6 ± 5.1 nm). The crystallographic and thermal analysis has indicated that the BBR dispersed in the PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR-SPC was ∼343% compared with that of BBR. These positive results demonstrated that PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug delivery of BBR.

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

International Nuclear Information System (INIS)

Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

2013-01-01

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.

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.

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.

Permeation of PLGA nanoparticles across different in vitro models

CSIR Research Space (South Africa)

Nkabinde, LA

2012-07-01

Full Text Available of drug candidates when formulated as nanoparticles. PLGA nanoparticles were prepared by means of a double emulsion solvent evaporation technique and evaluated in terms of size, encapsulation efficiency, surface charge, isoniazid release and in vitro...

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....

Development of membranes of PLGA functionalized with antimicrobial agents nanostructured

International Nuclear Information System (INIS)

Souza, S.G.; Molin, M.L.A.L.; Nogueira, A.L.; Schneider, E. Duek; Pezzin, A.P.T.

2016-01-01

Periodontitis is a disease affecting the tooth supporting tissues, causing loss of bone attachment. One of the possible treatments is through guided tissue regeneration (GTR). Currently, a variety of resorbable membranes are available as alternative to conventional non-resorbable membranes for this application, as the membranes of poly (lactic acid-co-glycolic acid) (PLGA). In this context, this study aimed to produce membranes were biocompatible and nanostructured functionalized with antibacterial agents and evaluate its thermal properties for future application in RTG. For the production of membranes were used as the PLGA polymer matrix. The NpAg were used at concentrations of 5, 7, 8 and 10 ppm and NpZnO were: 10, 50, 100 and 150 ppm. The materials were characterized by TGA and DSC. (author)

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.

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.

A Mechanistic Model for Drug Release in PLGA Biodegradable Stent Coatings Coupled with Polymer Degradation and Erosion

Science.gov (United States)

Zhu, Xiaoxiang; Braatz, Richard D.

2015-01-01

Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) coating for applications in drug-eluting stents has been receiving increasing interest as a result of its unique properties compared with biodurable polymers in delivering drug for reducing stents-related side effects. In this work, a mathematical model for describing the PLGA degradation and erosion and coupled drug release from PLGA stent coating is developed and validated. An analytical expression is derived for PLGA mass loss that predicts multiple experimental studies in the literature. An analytical model for the change of the number-average degree of polymerization (or molecular weight) is also derived. The drug transport model incorporates simultaneous drug diffusion through both the polymer solid and the liquid-filled pores in the coating, where an effective drug diffusivity model is derived taking into account factors including polymer molecular weight change, stent coating porosity change, and drug partitioning between solid and aqueous phases. The model is used to describe in vitro sirolimus release from PLGA stent coating, and demonstrates the significance of simultaneous sirolimus release via diffusion through both polymer solid and pore space. The proposed model is compared to existing drug transport models, and the impact of model parameters, limitations and possible extensions of the model are also discussed. PMID:25345656

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 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...

pH-dependent antibacterial effects on oral microorganisms through pure PLGA implants and composites with nanosized bioactive glass.

Science.gov (United States)

Hild, Nora; Tawakoli, Pune N; Halter, Jonas G; Sauer, Bärbel; Buchalla, Wolfgang; Stark, Wendelin J; Mohn, Dirk

2013-11-01

Biomaterials made of biodegradable poly(α-hydroxyesters) such as poly(lactide-co-glycolide) (PLGA) are known to decrease the pH in the vicinity of the implants. Bioactive glass (BG) is being investigated as a counteracting agent buffering the acidic degradation products. However, in dentistry the question arises whether an antibacterial effect is rather obtained from pure PLGA or from BG/PLGA composites, as BG has been proved to be antimicrobial. In the present study the antimicrobial properties of electrospun PLGA and BG45S5/PLGA fibres were investigated using human oral bacteria (specified with mass spectrometry) incubated for up to 24 h. BG45S5 nanoparticles were prepared by flame spray synthesis. The change in colony-forming units (CFU) of the bacteria was correlated with the pH of the medium during incubation. The morphology and structure of the scaffolds as well as the appearance of the bacteria were followed bymicroscopy. Additionally, we studied if the presence of BG45S5 had an influence on the degradation speed of the polymer. Finally, it turned out that the pH increase induced by the presence of BG45S5 in the scaffold did not last long enough to show a reduction in CFU. On the contrary, pure PLGA demonstrated antibacterial properties that should be taken into consideration when designing biomaterials for dental applications. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The Study on Biocompatibility of Porous nHA/PLGA Composite Scaffolds for Tissue Engineering with Rabbit Chondrocytes In Vitro

Directory of Open Access Journals (Sweden)

Lei Chen

2013-01-01

Full Text Available Objective. To examine the biocompatibility of a novel nanohydroxyapatite/poly[lactic-co-glycolic acid] (nHA/PLGA composite and evaluate its feasibility as a scaffold for cartilage tissue engineering. Methods. Chondrocytes of fetal rabbit were cultured with nHA/PLGA scaffold in vitro and the cell viability was assessed by MTT assay first. Cells adhering to nHA/PLGA scaffold were then observed by inverted microscope and scanning electron microscope (SEM. The cell cycle profile was analyzed by flow cytometry. Results. The viability of the chondrocytes on the scaffold was not affected by nHA/PLGA comparing with the control group as it was shown by MTT assay. Cells on the surface and in the pores of the scaffold increased in a time-dependent manner. Results obtained from flow cytometry showed that there was no significant difference in cell cycle profiles between the coculture group and control (P>0.05. Conclusion. The porous nHA/PLGA composite scaffold is a biocompatible and good kind of scaffold for cartilage tissue engineering.

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

Additive non-uniform random sampling in superimposed fiber Bragg grating strain gauge

International Nuclear Information System (INIS)

Ma, Y C; Liu, H Y; Yan, S B; Li, J M; Tang, J; Yang, Y H; Yang, M W

2013-01-01

This paper demonstrates an additive non-uniform random sampling and interrogation method for dynamic and/or static strain gauge using a reflection spectrum from two superimposed fiber Bragg gratings (FBGs). The superimposed FBGs are designed to generate non-equidistant space of a sensing pulse train in the time domain during dynamic strain gauge. By combining centroid finding with smooth filtering methods, both the interrogation speed and accuracy are improved. A 1.9 kHz dynamic strain is measured by generating an additive non-uniform randomly distributed 2 kHz optical sensing pulse train from a mean 500 Hz triangular periodically changing scanning frequency. (paper)

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.

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.

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.

A reproducible accelerated in vitro release testing method for PLGA microspheres.

Science.gov (United States)

Shen, Jie; Lee, Kyulim; Choi, Stephanie; Qu, Wen; Wang, Yan; Burgess, Diane J

2016-02-10

The objective of the present study was to develop a discriminatory and reproducible accelerated in vitro release method for long-acting PLGA microspheres with inner structure/porosity differences. Risperidone was chosen as a model drug. Qualitatively and quantitatively equivalent PLGA microspheres with different inner structure/porosity were obtained using different manufacturing processes. Physicochemical properties as well as degradation profiles of the prepared microspheres were investigated. Furthermore, in vitro release testing of the prepared risperidone microspheres was performed using the most common in vitro release methods (i.e., sample-and-separate and flow through) for this type of product. The obtained compositionally equivalent risperidone microspheres had similar drug loading but different inner structure/porosity. When microsphere particle size appeared similar, porous risperidone microspheres showed faster microsphere degradation and drug release compared with less porous microspheres. Both in vitro release methods investigated were able to differentiate risperidone microsphere formulations with differences in porosity under real-time (37 °C) and accelerated (45 °C) testing conditions. Notably, only the accelerated USP apparatus 4 method showed good reproducibility for highly porous risperidone microspheres. These results indicated that the accelerated USP apparatus 4 method is an appropriate fast quality control tool for long-acting PLGA microspheres (even with porous structures). Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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

2018-01-01

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. PMID:28244880

Injectable Shear-Thinning CaSO4/FGF-18-Incorporated Chitin-PLGA Hydrogel Enhances Bone Regeneration in Mice Cranial Bone Defect Model.

Science.gov (United States)

Sivashanmugam, A; Charoenlarp, Pornkawee; Deepthi, S; Rajendran, Arunkumar; Nair, Shantikumar V; Iseki, Sachiko; Jayakumar, R

2017-12-13

For craniofacial bone regeneration, shear-thinning injectable hydrogels are favored over conventional scaffolds because of their improved defect margin adaptability, easier handling, and ability to be injected manually into deeper tissues. The most accepted method, after autografting, is the use of recombinant human bone morphogenetic protein-2 (BMP-2); however, complications such as interindividual variations, edema, and poor cost-efficiency in supraphysiological doses have been reported. The endogenous synthesis of BMP-2 is desirable, and a molecule which induces this is fibroblast growth factor-18 (FGF-18) because it can upregulate the BMP-2 expression  by supressing noggin. We developed a chitin-poly(lactide-co-glycolide) (PLGA) composite hydrogel by regeneration chemistry and then incorporated CaSO 4 and FGF-18 for this purpose. Rheologically, a 7-fold increase in the elastic modulus was observed in the CaSO 4 -incorporated chitin-PLGA hydrogels as compared to the chitin-PLGA hydrogel. Shear-thinning Herschel-Bulkley fluid nature was observed for both hydrogels. Chitin-PLGA/CaSO 4 gel showed sustained release of FGF-18. In vitro osteogenic differentiation showed an enhanced alkaline phosphatase (ALP) expression in the FGF-18-containing chitin-PLGA/CaSO 4 gel when compared to cells alone. Further, it was confirmed by studying the expression of osteogenic genes [RUNX2, ALP, BMP-2, osteocalcin (OCN), and osteopontin (OPN)], immunofluorescence staining of BMP-2, OCN, and OPN, and alizarin red S staining. Incorporation of FGF-18 in the hydrogel increased the endothelial cell migration. Further, the regeneration potential of the prepared hydrogels was tested in vivo, and longitudinal live animal μ-CT was performed. FGF-18-loaded chitin-PLGA/CaSO 4 showed early and almost complete bone healing in comparison with chitin-PLGA/CaSO 4 , chitin-PLGA/FGF-18, chitin-PLGA, and sham control systems, as confirmed by hematoxylin and eosin and osteoid tetrachrome stainings

Chlamydia trachomatis recombinant MOMP encapsulated in PLGA nanoparticles triggers primarily T helper 1 cellular and antibody immune responses in mice: a desirable candidate nanovaccine

Directory of Open Access Journals (Sweden)

Fairley SJ

2013-05-01

Full Text Available Stacie J Fairley, Shree R Singh, Abebayehu N Yilma, Alain B Waffo, Praseetha Subbarayan, Saurabh Dixit, Murtada A Taha, Chino D Cambridge, Vida A Dennis Center for NanoBiotechnology Research, Alabama State University, Montgomery, AL, USA Abstract: We recently demonstrated by in vitro experiments that PLGA (poly D, L-lactide-co-glycolide potentiates T helper 1 (Th1 immune responses induced by a peptide derived from the recombinant major outer membrane protein (rMOMP of Chlamydia trachomatis, and may be a promising vaccine delivery system. Herein we evaluated the immune-potentiating potential of PLGA by encapsulating the full-length rMOMP (PLGA-rMOMP, characterizing it in vitro, and investigating its immunogenicity in vivo. Our hypothesis was that PLGA-rMOMP triggers Th1 immune responses in mice, which are desirable prerequisites for a C. trachomatis candidate nanovaccine. Physical-structural characterizations of PLGA-rMOMP revealed its size (approximately 272 nm, zeta potential (−14.30 mV, apparent spherical smooth morphology, and continuous slow release pattern. PLGA potentiated the ability of encapsulated rMOMP to trigger production of cytokines and chemokines by mouse J774 macrophages. Flow cytometric analyses revealed that spleen cells from BALB/c mice immunized with PLGA-rMOMP had elevated numbers of CD4+ and CD8+ T cell subsets, and secreted more rMOMP-specific interferon-gamma (Th1 and interleukin (IL-12p40 (Th1/Th17 than IL-4 and IL-10 (Th2 cytokines. PLGA-rMOMP-immunized mice produced higher serum immunoglobulin (IgG and IgG2a (Th1 than IgG1 (Th2 rMOMP-specific antibodies. Notably, sera from PLGA-rMOMP-immunized mice had a 64-fold higher Th1 than Th2 antibody titer, whereas mice immunized with rMOMP in Freund's adjuvant had only a four-fold higher Th1 than Th2 antibody titer, suggesting primarily induction of a Th1 antibody response in PLGA-rMOMP-immunized mice. Our data underscore PLGA as an effective delivery system for a C

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

is constant, and equal to the constant current value. A computation of resistivity from fiber density and diameter will be presented for a model of glass wool that consists of parallel randomly placed fibers with equal diameters. The computation is based on Voronoi polygons, and the results will be compared...

PLGA nanoparticles introduction into mitoxantrone-loaded ultrasound-responsive liposomes: In vitro and in vivo investigations.

Science.gov (United States)

Xin, Yuxuan; Qi, Qi; Mao, Zhenmin; Zhan, Xiaoping

2017-08-07

A novel ultrasound-responsive liposomal system for tumor targeting was prepared in order to increase the antitumor efficacy and decrease serious side effects. In this paper, PLGA nanoparticles were used ultrasound-responsive agents instead of conventional microbubbles. The PLGA-nanoparticles were prepared by an emulsion solvent evaporation method. The liposomes were prepared by a lipid film hydration method. Particle size, zeta potential, encapsulation efficiency and drug loading capacity of the liposomes were studied by light scattering analysis and dialysis. Transmission electron microscopy (TEM) and atomic force microscope (AFM) were used to investigate the morphology of liposomes. The release in vitro was carried out in the pH 7.4 phosphate buffer solutions, as a result, liposome L3 encapsulating PLGA-nanoparticles displayed good stability under simulative physiological conditions and quickly responsive release under the ultrasound. The release in vivo was carried out on the rats, as a result, liposome L3 showed higher bioavailability than traditional intravenous injectable administration, and liposome L3 showed higher elimination ratio after stimulation by ultrasound than L3 without stimulation. Thus, the novel ultrasound-responsive liposome encapsulating PLGA-nanoparticles has a potential to be developed as a new drug delivery system for anti-tumor drug. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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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.

Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method

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Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

2012-01-01

Background Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Methods Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. Results The nanoparticles prepared in this study were spherical, with an average particle size of 85–424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Conclusion Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug. PMID:22275837

Humidity-dependent compression-induced glass transition of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA).

Science.gov (United States)

Kim, Hyun Chang; Lee, Hoyoung; Jung, Hyunjung; Choi, Yun Hwa; Meron, Mati; Lin, Binhua; Bang, Joona; Won, You-Yeon

2015-07-28

Constant rate compression isotherms of the air-water interfacial Langmuir films of poly(D,L-lactic acid-ran-glycolic acid) (PLGA) show a distinct feature of an exponential increase in surface pressure in the high surface polymer concentration regime. We have previously demonstrated that this abrupt increase in surface pressure is linked to the glass transition of the polymer film, but the detailed mechanism of this process is not fully understood. In order to obtain a molecular-level understanding of this behavior, we performed extensive characterizations of the surface mechanical, structural and rheological properties of Langmuir PLGA films at the air-water interface, using combined experimental techniques including the Langmuir film balance, X-ray reflectivity and double-wall-ring interfacial rheometry methods. We observed that the mechanical and structural responses of the Langmuir PLGA films are significantly dependent on the rate of film compression; the glass transition was induced in the PLGA film only at fast compression rates. Surprisingly, we found that this deformation rate dependence is also dependent on the humidity of the environment. With water acting as a plasticizer for the PLGA material, the diffusion of water molecules through the PLGA film seems to be the key factor in the determination of the glass transformation properties and thus the mechanical response of the PLGA film against lateral compression. Based on our combined results, we hypothesize the following mechanism for the compression-induced glass transformation of the Langmuir PLGA film; (1) initially, a humidified/non-glassy PLGA film is formed in the full surface-coverage region (where the surface pressure shows a plateau) during compression; (2) further compression leads to the collapse of the PLGA chains and the formation of new surfaces on the air side of the film, and this newly formed top layer of the PLGA film is transiently glassy in character because the water evaporation rate

The studies of PLGA nanoparticles loading atorvastatin calcium for oral administration in vitro and in vivo

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Zhenbao Li

2017-05-01

Full Text Available A biodegradable poly(lactic-co-glycolic acid loading atorvastatin calcium (AC nanoparticles (AC-PLGA-NPs were prepared by probe ultrasonication and evaporation method aiming at improving the oral bioavailability of AC. The effects of experimental parameters, including stabilizer species, stabilizer concentration and pH of aqueous phase, on particle size were also evaluated. The resultant nanoparticles were in spherical shape with an average diameter of 174.7 nm and a narrow particle size distribution. And the drug loading and encapsulation efficiency were about 8% and 71%, respectively. The particle size and polydispersion were almost unchanged in 10 days. The release curves of AC-PLGA-NPs in vitro displaying sustained release characteristics indicated that its release mechanisms were matrix erosion and diffusion. The pharmacokinetic study in vivo revealed that the Cmax and AUC0-∞ of AC-PLGA-NPs in rats were nearly 3.7-fold and 4.7-fold higher than that of pure atorvastatin calcium suspension. Our results demonstrated that the delivery of AC-PLGA-NPs could be a promising approach for the oral delivery of AC for enhanced bioavailability.

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

PLGA 50:50 nanoparticles of paclitaxel: Development, in vitro anti ...

Indian Academy of Sciences (India)

lation of novel drug delivery systems to deliver such extreme hydrophobic drug. ... drug delivery system for PTX using biodegradable PLGA. 50:50 .... To this, 200 μl of protein precipitat- ..... Murthy R R 2004 The AAPS Journal 6 Article 23.

Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells.

Science.gov (United States)

Maran, Avudaiappan; Dadsetan, Mahrokh; Buenz, Colleen M; Shogren, Kristen L; Lu, Lichun; Yaszemski, Michael J

2013-09-01

Osteosarcoma is a bone tumor that affects children and young adults. 2-Methoxyestradiol (2-ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2-ME, we have encapsulated 2-ME in a composite of oligo-(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic-co-glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2-ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2-ME can be released in a controlled manner over 21-days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2-ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2-ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2-ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer-mediated delivery produces anti-tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2-ME and could be further explored in the treatment of osteosarcoma. Copyright © 2012 Wiley Periodicals, Inc.

PLGA nanoparticles for peptide receptor radionuclide therapy of neuroendocrine tumors: a novel approach towards reduction of renal radiation dose.

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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

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.

Ketamine nano-delivery based on poly-lactic-co-glycolic acid (PLGA) nanoparticles

Science.gov (United States)

Hirano, Sota; Bovi, Michele; Romeo, Alessandro; Guzzo, Flavia; Chiamulera, Cristiano; Perduca, Massimiliano

2018-04-01

This work describes a novel method for the generation of a ketamine nano-delivery, to improve brain blood barrier permeability and increase drug therapeutic window as anaesthetic, analgesic and potential antidepressant. The approach herein described is based on ketamine-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles coupled to an apolipoprotein E (ApoE) peptide for delivery to the central nervous system. PLGA particles were synthesized with amount of drug, coupled with the ApoE peptide on the surface, and validated by physical characterization. The produced nanodevice showed a good colloidal stability in water, confirmed by zeta potential measurements, with a diameter in the range of 185-205 nm. The ketamine encapsulation was verified by liquid chromatography-mass spectrometry analyses obtaining an encapsulation efficiency up to 21.2 ± 3.54%. Once the occurrence of ApoE peptide functionalization was confirmed with fluorescence spectroscopy, the thermal stability and morphological information were obtained by differential scanning calorimetry and further dynamic light scattering measurements. The spherical shape and a rough nanoparticles surface were observed by atomic force microscopy. The reliability of this approach may be further developed as a protocol to be used to generate PLGA nanoparticles greater than 100 nm able to better penetrate blood brain barrier and release a neuroactive molecule at lower doses.

Culture of bovine articular chondrocytes in funnel-like collagen-PLGA hybrid sponges

International Nuclear Information System (INIS)

Lu Hongxu; Ko, Young-Gwang; Kawazoe, Naoki; Chen Guoping

2011-01-01

Three-dimensional porous scaffolds play an important role in tissue engineering and regenerative medicine. Structurally, these porous scaffolds should have an open and interconnected porous architecture to facilitate a homogeneous cell distribution. Moreover, the scaffolds should be mechanically strong to support new tissue formation. We developed a novel type of funnel-like collagen sponge using embossing ice particulates as a template. The funnel-like collagen sponges could promote the homogeneous cell distribution, ECM production and chondrogenesis. However, the funnel-like collagen sponges deformed during cell culture due to their weak mechanical strength. To solve this problem, we reinforced the funnel-like collagen sponges with a knitted poly(D,L-lactic-co-glycolic acid) (PLGA) mesh by hybridizing these two types of materials. The hybrid scaffolds were used to culture bovine articular chondrocytes. The cell adhesion, distribution, proliferation and chondrogenesis were investigated. The funnel-like structure promoted the even cell distribution and homogeneous ECM production. The PLGA knitted mesh protected the scaffold from deformation during cell culture. Histological and immunohistochemical staining and cartilaginous gene expression analyses revealed the cartilage-like properties of the cell/scaffold constructs after in vivo implantation. The hybrid scaffold, composed of a funnel-like collagen sponge and PLGA mesh, would be a useful tool for cartilage tissue engineering.

Culture of bovine articular chondrocytes in funnel-like collagen-PLGA hybrid sponges

Energy Technology Data Exchange (ETDEWEB)

Lu Hongxu; Ko, Young-Gwang; Kawazoe, Naoki; Chen Guoping, E-mail: Guoping.Chen@nims.go.jp [Tissue Regeneration Materials Unit, International Center for Materials Nanoarchitectonics (MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044 (Japan)

2011-08-15

Three-dimensional porous scaffolds play an important role in tissue engineering and regenerative medicine. Structurally, these porous scaffolds should have an open and interconnected porous architecture to facilitate a homogeneous cell distribution. Moreover, the scaffolds should be mechanically strong to support new tissue formation. We developed a novel type of funnel-like collagen sponge using embossing ice particulates as a template. The funnel-like collagen sponges could promote the homogeneous cell distribution, ECM production and chondrogenesis. However, the funnel-like collagen sponges deformed during cell culture due to their weak mechanical strength. To solve this problem, we reinforced the funnel-like collagen sponges with a knitted poly(D,L-lactic-co-glycolic acid) (PLGA) mesh by hybridizing these two types of materials. The hybrid scaffolds were used to culture bovine articular chondrocytes. The cell adhesion, distribution, proliferation and chondrogenesis were investigated. The funnel-like structure promoted the even cell distribution and homogeneous ECM production. The PLGA knitted mesh protected the scaffold from deformation during cell culture. Histological and immunohistochemical staining and cartilaginous gene expression analyses revealed the cartilage-like properties of the cell/scaffold constructs after in vivo implantation. The hybrid scaffold, composed of a funnel-like collagen sponge and PLGA mesh, would be a useful tool for cartilage tissue engineering.

Development of biodegradable PLGA nanoparticles surface engineered with hyaluronic acid for targeted delivery of paclitaxel to triple negative breast cancer cells.

Science.gov (United States)

Cerqueira, Brenda Brenner S; Lasham, Annette; Shelling, Andrew N; Al-Kassas, Raida

2017-07-01

This study aimed at development of poly (lactic-co-glycolic acid) (PLGA) nanoparticles embedded with paclitaxel and coated with hyaluronic acid (HA-PTX-PLGA) to actively target the drug to a triple negative breast cancer cells. Nanoparticles were successfully fabricated using a modified oil-in-water emulsion method. The effect of various formulations parameters on the physicochemical properties of the nanoparticles was investigated. SEM imaging confirmed the spherical shape and nano-scale size of the nanoparticles. A sustained drug release profile was obtained and enhanced PTX cytotoxicity was observed when MDA-MB-231 cells were incubated with the HA-PTX-PLGA formulation compared to cells incubated with the non-HA coated nanoparticles. Moreover, HA-PLGA nanoparticles exhibited improved cellular uptake, based on a possible receptor mediated endocytosis due to interaction of HA with CD44 receptors when compared to non-coated PLGA nanoparticles. The non-haemolytic potential of the nanoparticles indicated the suitability of the developed formulation for intravenous administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved design and characterization of PLGA/PLA-coated Chitosan based micro-implants for controlled release of hydrophilic drugs.

Science.gov (United States)

Manna, Soumyarwit; Donnell, Anna M; Kaval, Necati; Al-Rjoub, Marwan F; Augsburger, James J; Banerjee, Rupak K

2018-05-29

Repetitive intravitreal injections of Methotrexate (MTX), a hydrophilic chemotherapeutic drug, are currently used to treat selected vitreoretinal (VR) diseases, such as intraocular lymphoma. To avoid complications associated with the rapid release of MTX from the injections, a Polylactic acid (PLA) and Chitosan (CS)-based MTX micro-implant prototype was fabricated in an earlier study, which showed a sustained therapeutic release rate of 0.2-2.0 µg/day of MTX for a period ∼1 month in vitro and in vivo. In the current study, different combinations of Poly(lactic-co-glycolic) acid (PLGA)/PLA coatings were used for lipophilic surface modification of the CS-MTX micro-implant, such as PLGA 5050, PLGA 6535 and PLGA 7525 (PLA: PGA - 50:50, 65:35, 75:25, respectively; M.W: 54,400 - 103,000) and different PLA, such as PLA 100 and PLA 250 (MW: 102,000 and 257,000, respectively). This improved the duration of total MTX release from the coated CS-MTX micro-implants to ∼3-5 months. With an increase in PLA content in PLGA and molecular weight of PLA, a) the initial burst of MTX and the mean release rate of MTX can be reduced; and b) the swelling and biodegradation of the micro-implants can be delayed. The controlled drug release mechanism is caused by a combination of diffusion process and hydrolysis of the polymer coating, which can be modulated by a) PLA content in PLGA and b) molecular weight of PLA, as inferred from Korsmeyer Peppas model, Zero order, First order and Higuchi model fits. This improved micro-implant formulation has the potential to serve as a platform for controlled release of hydrophilic drugs to treat selected VR diseases. Copyright © 2018. Published by Elsevier B.V.

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.

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

International Nuclear Information System (INIS)

Sousa, F F O; Luzardo-Alvarez, A; Blanco-Mendez, J; Perez-Estevez, A; Seoane-Prado, R

2010-01-01

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 μm. 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.

Development of PLGA-coated β-TCP scaffolds containing VEGF for bone tissue engineering.

Science.gov (United States)

Khojasteh, Arash; Fahimipour, Farahnaz; Eslaminejad, Mohamadreza Baghaban; Jafarian, Mohammad; Jahangir, Shahrbanoo; Bastami, Farshid; Tahriri, Mohammadreza; Karkhaneh, Akbar; Tayebi, Lobat

2016-12-01

Bone tissue engineering is sought to apply strategies for bone defects healing without limitations and short-comings of using either bone autografts or allografts and xenografts. The aim of this study was to fabricate a thin layer poly(lactic-co-glycolic) acid (PLGA) coated beta-tricalcium phosphate (β-TCP) scaffold with sustained release of vascular endothelial growth factor (VEGF). PLGA coating increased compressive strength of the β-TCP scaffolds significantly. For in vitro evaluations, canine mesenchymal stem cells (cMSCs) and canine endothelial progenitor cells (cEPCs) were isolated and characterized. Cell proliferation and attachment were demonstrated and the rate of cells proliferation on the VEGF released scaffold was significantly more than compared to the scaffolds with no VEGF loading. A significant increase in expression of COL1 and RUNX2 was indicated in the scaffolds loaded with VEGF and MSCs compared to the other groups. Consequently, PLGA coated β-TCP scaffold with sustained and localized release of VEGF showed favourable results for bone regeneration in vitro, and this scaffold has the potential to use as a drug delivery device in the future. Copyright © 2016. Published by Elsevier B.V.

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

Directory of Open Access Journals (Sweden)

Piergiorgio Gentile

2014-02-01

Full Text Available 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.

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.)

Fabrication of nanocrystalline hydroxyapatite doped degradable composite hollow fiber for guided and biomimetic bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Zhang Ning [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Nichols, Heather L. [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Tylor, Shila [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States); Wen Xuejun [Department of Bioengineering, Clemson University, Clemson, SC, 29634 (United States)]. E-mail: xjwen@clemson.edu

2007-04-15

Natural bone tissue possesses a nanocomposite structure interwoven in a three-dimensional (3-D) matrix, which plays critical roles in conferring appropriate physical and biological properties to the bone tissue. Single type of material may not be sufficient to mimic the composition, structure and properties of native bone, therefore, composite materials consisting of both polymers, bioceramics, and other inorganic materials have to be designed. Among a variety of candidate materials, polymer-nanoparticle composites appear most promising for bone tissue engineering applications because of superior mechanical properties, improved durability, and surface bioactivity when compared with conventional polymers or composites. The long term objective of this project is to use highly aligned, bioactive, biodegradable scaffold mimicking natural histological structure of human long bone, and to engineer and regenerate human long bone both in vitro and in vivo. In this study, bioactive, degradable, and highly permeable composite hollow fiber membranes (HFMs) were fabricated using a wet phase phase-inversion approach. The structure of the hollow fiber membranes was examined using scanning electron microscopy (SEM); degradation behavior was examined using weigh loss assay, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC); and bioactivity was evaluated with the amount of calcium deposition from the culture media onto HFM surface. Doping PLGA HFMs with nanoHA results in a more bioactive and slower degrading HFM than pure PLGA HFMs.

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).

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

International Nuclear Information System (INIS)

Zhang, Hao-Xuan; Zhang, Xiu-Ping; Xiao, Gui-Yong; Hou, Yong; Cheng, Lei; Si, Meng; Wang, Shuai-Shuai; Li, Yu-Hua; Nie, Lin

2016-01-01

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).

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.

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

International Nuclear Information System (INIS)

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

2014-01-01

In this study, 3D porous bioactive composite scaffolds were produced and evaluated for their physico-chemical and biological properties. Polymer poly-L-lactide-co-glycolide (PLGA) matrix scaffolds were modified with sol–gel-derived bioactive glasses (SBGs) of CaO–SiO 2 –P 2 O 5 systems. We hypothesized that SBG incorporation into PLGA matrix would improve the chemical and biological activity of composite materials as well as their mechanical properties. We applied two bioactive glasses, designated as S2 or A2, differing in the content of SiO 2 and CaO (i.e. 80 mol% SiO 2 , 16 mol% CaO for S2 and 40 mol% SiO 2 , 52 mol% CaO for A2). The composites were characterized for their porosity, bioactivity, microstructure and mechanical properties. The osteoinductive properties of these composites were evaluated in human bone marrow stromal cell (hBMSC) cultures grown in either standard growth medium or treated with recombinant human bone morphogenetic protein-2 (rhBMP-2) or dexamethasone (Dex). After incubation in simulated body fluid, calcium phosphate precipitates formed inside the pores of both A2-PLGA and S2-PLGA scaffolds. The compressive strength of the latter was increased slightly compared to PLGA. Both composites promoted superior hBMSC attachment to the material surface and stimulated the expression of several osteogenic markers in hBMSC compared to cells grown on unmodified PLGA. There were also marked differences in the response of hBMSC to composite scaffolds, depending on chemical compositions of the scaffolds and culture treatments. Compared to silica-rich S2-PLGA, hBMSC grown on calcium-rich A2-PLGA were overall less responsive to rhBMP-2 or Dex and the osteoinductive properties of these A2-PLGA scaffolds seemed partially dependent on their ability to induce BMP signaling in untreated hBMSC. Thus, beyond the ability of currently studied composites to enhance hBMSC osteogenesis, it may become possible to modulate the osteogenic response of h

Activation of Antigen-Specific CD8(+) T Cells by Poly-DL-Lactide/Glycolide (PLGA) Nanoparticle-Primed Gr-1(high) Cells.

Science.gov (United States)

Luo, Wen-Hui; Yang, Ya-Wun

2016-04-01

The aim of this study was to investigate the induction of antigen-specific T cell activation and cell cycle modulation by a poly-DL-lactide/glycolide (PLGA) nanoparticle (NP)-primed CD11b(+)Gr-1(high) subset isolated from mouse bone marrow. PLGA NPs containing the ovalbumin (OVA) antigen were prepared using the double emulsion and solvent evaporation method, and protein release rate and cell viability were determined. The Lin2(¯)CD11b(+)Gr-1(high)Ly6c(low) (Gr-1(high)) subset was sorted from the bone marrow of C57BL/6 J mice by fluorescence-activated cell sorting (FACS) and co-cultured with OT-I CD8(+) splenic T cells. Proliferation of OT-I CD8(+) T cells was monitored, and cell cycles were determined by 5-bromo-2'-deoxyuridine (BrdU) labeling. Treatment of Gr-1(high) cells with PLGA/OVA NPs upregulated expression of the SIINFEKL-H2K(b) complex in the context of MHC I. Co-cultures of OT-I CD8(+) T cells with the PLGA/OVA NP-primed Gr-1(high) cells induced the proliferation of T cells in vitro and modulated cell division and morphology. Treatment of Gr-1(high) cells with PLGA/OVA NPs also induced cell apoptosis and necrosis. This study demonstrated the function of PLGA/OVA NPs in the activation of OT-I CD8(+) T cells and the capability of cross-presentation via the Gr-1(high) polymorphonuclear subset from mouse bone marrow.

PLGA and PHBV Microsphere Formulations and Solid-State Characterization

DEFF Research Database (Denmark)

Yang, Chiming; Plackett, David; Needham, David

2009-01-01

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

Multifunctional PLGA Nanobubbles as Theranostic Agents: Combining Doxorubicin and P-gp siRNA Co-Delivery Into Human Breast Cancer Cells and Ultrasound Cellular Imaging.

Science.gov (United States)

Yang, Hong; Deng, Liwei; Li, Tingting; Shen, Xue; Yan, Jie; Zuo, Liangming; Wu, Chunhui; Liu, Yiyao

2015-12-01

Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. One of the effective approaches to overcome MDR is to use nanoparticle-mediated the gene silence of chemotherapeutic export proteins by RNA interference to increase drug accumulation in drug resistant cancer cells. In this work, a new co-delivery system, DOX-PLGA/PEI/P-gp shRNA nanobubbles (NBs) around 327 nm, to overcome doxorubicin (DOX) resistance in MCF-7 human breast cancer was designed and developed. Positively charged polyethylenimine (PEI) were modified onto the surface of DOX-PLGA NBs through DCC/NHS crosslinking, and could efficiently condense P-gp shRNA into DOX-PLGA/PEI NBs at vector/shRNA weight ratios of 70:1 and above. An in vitro release profile demonstrated an efficient DOX release (more than 80%) from DOX-PLGA/PEI NBs at pH 4.4, suggesting a pH-responsive drug release for the multifunctionalized NBs. Cellular experimental results further showed that DOX-PLGA/PEI/P-gp shRNA NBs could facilitate cellular uptake of DOX into cells and increase the cell proliferation suppression effect of DOX against MCF-7/ADR cells (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The IC50 of DOX-PLGA NBs against MCF-7/ADR cells was 2-fold lower than that of free DOX. The increased cellular uptake and nuclear accumulation of DOX delivered by DOX-PLGA/PEI/P-gp shRNA NBs in MCF-7/ADR cells was confirmed by fluorescence microscopy and fluorescence spectrophotometry, and might be owning to the down-regulation of P-gp and reduced the efflux of DOX. The cellular uptake mechanism of DOX-PLGA/PEI/P-gp shRNA NBs indicated that the macropinocytosis was one of the pathways for the uptake of NBs by MCF-7/ADR cells, which was also an energy-dependent process. Furthermore, the in vitro cellular ultrasound imaging suggested that the employment of the DOX-PLGA/PEI/P-gp shRNA NBs could efficiently enhance ultrasound imaging of cancer cells. These results demonstrated

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.

PLGA/Nano-Zn O Composite Particles for Use in Biomedical Applications: Preparation, Characterization, and Antimicrobial Activity

International Nuclear Information System (INIS)

Stankovic, A.; Stevanovic, M.; Sezen, M.; Milenkovic, M.; Kaisarevic, S.; Andric, N.

2016-01-01

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 (Zn O) 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 Zn O nanoparticles (nano-Zn O) have been synthesized via microwave synthesis method. In addition to obtaining nano-Zn O, a further aim was to examine their immobilization in the PLGA polymer matrix (PLGA/nano-Zn O) and this was done by a simple physicochemical solvent/non solvent 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-Zn O particles are spherical, uniform, and with diameters below 1μ. 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 HepG_2 cells by application of MTT assay and the antimicrobial activity was evaluated by broth micro dilution method against different groups of microorganisms (Gram-positive bacteria, Gram-negative bacteria, and yeast Candida albicans)

Aspartic acid-based modified PLGA-PEG nanoparticles for bone targeting: in vitro and in vivo evaluation.

Science.gov (United States)

Fu, Yin-Chih; Fu, Tzu-Fun; Wang, Hung-Jen; Lin, Che-Wei; Lee, Gang-Hui; Wu, Shun-Cheng; Wang, Chih-Kuang

2014-11-01

Nanoparticles (NP) that target bone tissue were developed using PLGA-PEG (poly(lactic-co-glycolic acid)-polyethylene glycol) diblock copolymers and bone-targeting moieties based on aspartic acid, (Asp)(n(1,3)). These NP are expected to enable the transport of hydrophobic drugs. The molecular structures were examined by (1)H NMR or identified using mass spectrometry and Fourier transform infrared (FT-IR) spectra. The NP were prepared using the water miscible solvent displacement method, and their size characteristics were evaluated using transmission electron microscopy (TEM) and dynamic light scattering. The bone targeting potential of the NP was evaluated in vitro using hydroxyapatite affinity assays and in vivo using fluorescent imaging in zebrafish and rats. It was confirmed that the average particle size of the NP was <200 nm and that the dendritic Asp3 moiety of the PLGA-PEG-Asp3 NP exhibited the best apatite mineral binding ability. Preliminary findings in vivo bone affinity assays in zebrafish and rats indicated that the PLGA-PEG-ASP3 NP may display increased bone-targeting efficiency compared with other PLGA-PEG-based NP that lack a dendritic Asp3 moiety. These NP may act as a delivery system for hydrophobic drugs, warranting further evaluation of the treatment of bone disease. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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.

PLGA biodegradable nanoparticles containing perphenazine or chlorpromazine hydrochloride: effect of formulation and release.

Science.gov (United States)

Halayqa, Mohammed; Domańska, Urszula

2014-12-22

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

Directory of Open Access Journals (Sweden)

Mohammed Halayqa

2014-12-01

Full Text Available In our study, poly(dl-lactide-co-glycolide (PLGA nanoparticles loaded with perphenazine (PPH and chlorpromazine hydrochloride (CPZ-HCl were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol (PVA concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4 by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.

The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth: Different administration routes.

Science.gov (United States)

Fasehee, Hamidreza; Zarrinrad, Ghazaleh; Tavangar, Seyed Mohammad; Ghaffari, Seyed Hamidollah; Faghihi, Shahab

2016-06-01

The strong anticancer activity of disulfiram is hindered by its rapid degradation in blood system. A novel folate-receptor-targeted poly (lactide-co-glycolide) (PLGA)-polyethylene glycol (PEG) nanoparticle (NP) is developed for encapsulation and delivery of disulfiram into breast cancer tumor using passive (EPR effect) and active (folate receptor) targeting. The anticancer activity of disulfiram and its effect on caspase-3 activity and cell cycle are studied. The administration of encapsulated PLGA NPs using intra-peritoneal, intravenous and intra-tumor routes is investigated using animal model. Disulfiram shows strong cytotoxicity against MCF7 cell line. The activity of caspase-3 inhibited with disulfiram via dose dependent manner while the drug causes cell cycle arrest in G0/G1 and S phase time-dependently. The encapsulated disulfiram shows higher activity in apoptosis induction as compared to free drug. In nontoxic dose of encapsulated disulfiram, the highest and lowest efficacy of NPs in tumor growth inhibition is observed for intravenous injection and intraperitoneal injection. It is suggested that administration of disulfiram by targeted PLGA nanoparticles using intravenous injection would present an alternative therapeutic approach for solid tumor treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of polymer viscosity on physicochemical properties and ocular tolerance of FB-loaded PLGA nanospheres.

Science.gov (United States)

Araújo, J; Vega, E; Lopes, C; Egea, M A; Garcia, M L; Souto, E B

2009-08-01

Poly(lactide-co-glycolide) acid (PLGA) nanospheres incorporating flurbiprofen (FB) were produced by the solvent displacement technique, for ocular applications aiming to avoid/minimize inflammation induced by surgical trauma. In this work, a PLGA of low viscosity has been tested and the results obtained were compared with those previously reported by Vega et al. The physicochemical properties of the developed formulations were evaluated by measuring particle size, zeta potential and FB entrapment efficiency, showing no significant differences. Release studies demonstrated that the formulation produced with PLGA of higher viscosity revealed a slower drug release rate. Stability analysis, for a period of 75 days, was performed using three complementary methods: (i) turbidity experiments using a Turbiscan optical analyzer, (ii) particle size measurements, and (iii) zeta potential analysis. The results revealed long-term physicochemical stability suitability for ophthalmic use, being independent from the polymer viscosity. The ocular tolerance was assessed by an alternative in vitro method to animal experimentation, the HET-CAM. For all developed formulations no ocular irritancy has been detected.

Ibuprofen delivered by poly(lactic-co-glycolic acid) (PLGA) nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

Science.gov (United States)

Bonelli, Patrizia; Tuccillo, Franca M; Federico, Antonella; Napolitano, Maria; Borrelli, Antonella; Melisi, Daniela; Rimoli, Maria G; Palaia, Raffaele; Arra, Claudio; Carinci, Francesco

2012-01-01

Purpose Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in MKN-45 cells. Methods MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry. Results Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum concentration at 24 hours. The inhibition of proliferation was confirmed to be due to the intracellular release of ibuprofen from the NPs. Using PLGA NPs as carriers, ibuprofen exerted an antiproliferative activity at concentrations > 100 times less than free ibuprofen, suggesting greater efficiency and less cellular toxicity. In addition, when carried by PLGA NPs, ibuprofen more quickly induced the expression of transcripts involved in proliferation and invasiveness processes. Conclusion Ibuprofen exerted an antiproliferative effect on MKN-45 cells at low concentrations. This effect was achieved using PLGA NPs as carriers of low doses of ibuprofen. PMID:23180963

Scolicidal and apoptotic activities of albendazole sulfoxide and albendazole sulfoxide-loaded PLGA-PEG as a novel nanopolymeric particle against Echinococcus granulosus protoscoleces.

Science.gov (United States)

Naseri, Marziyeh; Akbarzadeh, Abolfazl; Spotin, Adel; Akbari, Nagibeh Asl Rahnemaii; Mahami-Oskouei, Mahmoud; Ahmadpour, Ehsan

2016-12-01

Treatment failures of human cystic echinococcosis (CE) with albendazole (ABZ) have attributed to its low solubility and poor drug absorption rate, resulting in low drug level in plasma. The scolicidal effects of ABZ-loaded liposome nanoparticles have recently evaluated; however, these particles have several challenges due to their low encapsulated load. This investigation was designed to evaluate and compare in vitro apoptotic activities of ABZ sulfoxide (ABZs) and ABZs-loaded poly(lactic-co-glycolic acid) (PLGA)-PEG against protoscoleces (PSCs). ABZs-loaded PLGA-PEG was prepared by a double-emulsion method (W1/O/W2). Various concentrations of ABZs and ABZs-loaded PLGA-PEG (50, 100, 150, and 200 μg/ml) were experimentally tested against PSC of CE at different exposure times (5, 10, 20, 30, and 60 min). ABZs-loaded PLGA-PEG at concentrations of 150 and 200 μg/ml was able to act at a 100 % scolicidal rate in all exposure times (5 to 60 min), while ABZs at a concentration of 200 μg/ml demonstrated 94, 100, and 100 % mortality rates following 20, 30, and 60 min of exposure times, respectively. The messenger RNA (mRNA) expression of caspase-3 was assessed by semi-quantitative RT-PCR after 15 h of exposure. Caspase-3 mRNA expression was higher in both PSC treated with ABZs and PSC treated with ABZs-loaded PLGA-PEG than that in control groups (P  0.05). DNA fragmentation assay and ultrastructural changes revealed that ABZs and ABZs-loaded PLGA-PEG induced the apoptosis of PSC by activation of caspase-3. The higher permeability and scolicidal rate of ABZs-loaded PLGA-PEG can be addressed as an effectual alternative strategy to improve the treatment of human CE.

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

CSIR Research Space (South Africa)

Tukulula, M

2015-02-01

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

Distributed fiber sparse-wideband vibration sensing by sub-Nyquist additive random sampling

Science.gov (United States)

Zhang, Jingdong; Zheng, Hua; Zhu, Tao; Yin, Guolu; Liu, Min; Bai, Yongzhong; Qu, Dingrong; Qiu, Feng; Huang, Xianbing

2018-05-01

The round trip time of the light pulse limits the maximum detectable vibration frequency response range of phase-sensitive optical time domain reflectometry ({\\phi}-OTDR). Unlike the uniform laser pulse interval in conventional {\\phi}-OTDR, we randomly modulate the pulse interval, so that an equivalent sub-Nyquist additive random sampling (sNARS) is realized for every sensing point of the long interrogation fiber. For an {\\phi}-OTDR system with 10 km sensing length, the sNARS method is optimized by theoretical analysis and Monte Carlo simulation, and the experimental results verify that a wide-band spars signal can be identified and reconstructed. Such a method can broaden the vibration frequency response range of {\\phi}-OTDR, which is of great significance in sparse-wideband-frequency vibration signal detection, such as rail track monitoring and metal defect detection.

Evaluation of PLGA containing anti-CTLA4 inhibited endometriosis progression by regulating CD4+CD25+Treg cells in peritoneal fluid of mouse endometriosis model.

Science.gov (United States)

Liu, Qi; Ma, Pingchuan; Liu, Lanxia; Ma, Guilei; Ma, Jingjing; Liu, Xiaoxuan; Liu, Yijin; Lin, Wanjun; Zhu, Yingjun

2017-01-01

Our study investigated poly(lactic-co-glycolic acid) (PLGA) as protein delivery vehicles encapsulate CTLA-4-antibody (anti-CTLA-4) which is essential for CD4+CD25+Treg cells suppressive function exposing superior potential for inhibiting endometriosis progress in mouse model than single anti-CTLA-4. Anti-CTLA-4 loaded PLGA combined to ligands CTLA-4 in surface of CD4+CD25+Treg cells which distributed in peritoneal fluid of mouse endometriosis model. The particle size, zeta potential of the anti-CTLA-4 loaded nanoparticles was detected by dynamic light scattering. Morphology of nanoparticles was evaluated by transmission electron microscopy (TEM). Confocal laser scanning microscopy (CLSM) indicated distribution of anti-CTLA-4 with PLGA or without in peritoneal fluid. Cumulative anti-CTLA-4 release from nanoparticles was evaluated by Micro BCA assay. The percentage of CD4+CD25+Treg cells in peritoneal fluid was demonstrated by flow cytometer. In vitro experiment we co-culture ectopic endometrial cells (EEC) with isolated CD4+CD25+Treg cells in peritoneal fluid (PF), proliferation and invasion of ectopic endometrial cells (EEC) was measured by BrdU ELISA assay and Matrigel invasion assay. In comparison with anti-CTLA-4 without nanoparticles, the bioconjugates PLGA/anti-CTLA-4 were tolerated in peritoneal fluid with a controlled release of anti-CTLA-4 in 3, 7, 14days. Moreover, PLGA/anti-CTLA-4 had superior protective regulation ability to reduce level of CD4+CD25+Treg cells in peritoneal fluid. Most strikingly, in vitro experiment, PLGA/anti-CTLA-4 exhibited better ability in inhibiting proliferation and invasion of ectopic endometrial cells in co-culture system compared with anti-CTLA-4. Progressively, PLGA/anti-CTLA-4 had better suppressive activity to inhibited IL-10 and TGF-beta secreted by CD4+CD25+Treg cells which indicating that PLGA/anti-CTLA-4 suppressed cells proliferation and invasion through reduced IL-10 and TGF-beta production. Thus, PLGA/anti-CTLA-4 may

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.

Impact of surfactants on the target recognition of Fab-conjugated PLGA nanoparticles.

Science.gov (United States)

Kennedy, Patrick J; Perreira, Ines; Ferreira, Daniel; Nestor, Marika; Oliveira, Carla; Granja, Pedro L; Sarmento, Bruno

2018-06-01

Targeted drug delivery with nanoparticles (NPs) requires proper surface ligand presentation and availability. Surfactants are often used as stabilizers in the production of targeted NPs. Here, we evaluated the impact of surfactants on ligand functionalization and downstream molecular recognition. Our model system consisted of fluorescent poly(lactic-co-glycolic acid) (PLGA) NPs that were nanoprecipitated in one of a small panel of commonly-used surfactants followed by equivalent washes and conjugation of an engineered Fab antibody fragment. Size, polydispersity index and zeta potential were determined by dynamic light scattering and laser Doppler anemometry, and Fab presence on the NPs was assessed by enzyme-linked immunosorbent assay. Most importantly, Fab-decorated NP binding to the cell surface receptor was monitored by fluorescence-activated cell sorting. 2% polyvinyl alcohol, 1% sodium cholate, 0.5% Pluronic F127 (F127) and 2% Tween-80 were initially tested. Of the four surfactants tested, PLGA NPs in 0.5% F127 and 2% Tween-80 had the highest cell binding. These two surfactants were then retested in two different concentrations, 0.5% and 2%. The Fab-decorated PLGA NPs in 2% F127 had the highest cell binding. This study highlights the impact of common surfactants and their concentrations on the downstream targeting of ligand-decorated NPs. Similar principles should be applied in the development of future targeted nanosystems where surfactants are employed. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of cryoprotection on the use of PLGA encapsulated iron oxide nanoparticles for magnetic cell labeling

International Nuclear Information System (INIS)

Tang, Kevin S; Shapiro, Erik M; Hashmi, Sarah M

2013-01-01

Magnetic PLGA nanoparticles are a significant advancement in the quest to translate MRI-based cell tracking to the clinic. The benefits of these types of particles are that they encapsulate large amounts of iron oxide nanocrystals within an FDA-approved polymer matrix, combining the best aspects of inert micron-sized iron oxide particles, or MPIOs, and biodegradable small particles of iron oxide, or SPIOs. Practically, PLGA nanoparticle fabrication and storage requires some form of cryoprotectant to both protect the particle during freeze drying and to promote resuspension. While this is a commonly employed procedure in the fabrication of drug loaded PLGA nanoparticles, it has yet to be investigated for magnetic particles and what effect this might have on internalization of magnetic particles. As such, in this study, magnetic PLGA nanoparticles were fabricated with various concentrations of two common cryoprotectants, dextrose and sucrose, and analyzed for their ability to magnetically label cells. It was found that cryoprotection with either sugar significantly enhanced the ability to resuspend nanoparticles without aggregation. Magnetic cell labeling was impacted by sugar concentration, with higher sugar concentrations used during freeze drying more significantly reducing magnetic cell labeling than lower concentrations. These studies suggest that cryoprotection with 1% dextrose is an optimal compromise that preserves monodispersity following resuspension and high magnetic cell labeling. (paper)

Development of facile drug delivery platform of ranibizumab fabricated PLGA-PEGylated magnetic nanoparticles for age-related macular degeneration therapy.

Science.gov (United States)

Yan, Jian; Peng, Xifeng; Cai, Yulian; Cong, Wendong

2018-06-01

The present anti-angiogenic therapies for neovascular age-related macular degeneration require effective drug delivery systems for transfer drug molecules. Ranibizumab is an active humanized monoclonal antibody that counteracts active forms of vascular endothelial growth factor A in the neovascular age-related macular degeneration therapy. The development of ranibizumab-related therapies, we have designed the effective drug career with engineered magnetic nanoparticles (Fe 3 O 4 ) as a facile platform of ranibizumab delivery for the treatment of neovascular age-related macular degeneration. Ranibizumab conjugated iron oxide (Fe 3 O 4 )/PEGylated poly lactide-co-glycolide (PEG-PLGA) was successfully designed and the synthesized materials are analyzed different analytical techniques. The microscopic techniques (Scanning Electron Microscopy (SEM) & Transmission Electron Microscopy (TEM)) are clearly displayed that spherical nanoparticles into the PEG-PLGA matrix and presence of elements and chemical interactions confirmed by the results of energy dispersive X-ray analysis (EDX) and Fourier trans-form infrared (FTIR) spectroscopic methods. The in vitro anti-angiogenic evaluation of Fe 3 O 4 /PEG-PLGA polymer nanomaterial efficiently inhibits the tube formation in the Matrigel-based assay method by using human umbilical vein endothelial cells. Ranibizumab treated Fe 3 O 4 /PEG-PLGA polymer nanomaterials not disturbed cell proliferation and the results could not display the any significant differences in human endothelial cells. The present investigated results describe that Fe 3 O 4 /PEG-PLGA polymer nanomaterials can be highly favorable and novel formulation for the treatment of neovascular age-related macular degeneration. Copyright © 2018 Elsevier B.V. All rights reserved.

PLGA nanoparticles modified with a BBB-penetrating peptide co-delivering Aβ generation inhibitor and curcumin attenuate memory deficits and neuropathology in Alzheimer's disease mice.

Science.gov (United States)

Huang, Na; Lu, Shuai; Liu, Xiao-Ge; Zhu, Jie; Wang, Yu-Jiong; Liu, Rui-Tian

2017-10-06

Alzheimer's disease (AD) is the most common form of dementia, characterized by the formation of extracellular senile plaques and neuronal loss caused by amyloid β (Aβ) aggregates in the brains of AD patients. Conventional strategies failed to treat AD in clinical trials, partly due to the poor solubility, low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier (BBB). Moreover, AD is a complex, multifactorial neurodegenerative disease; one-target strategies may be insufficient to prevent the processes of AD. Here, we designed novel kind of poly(lactide-co-glycolic acid) (PLGA) nanoparticles by loading with Aβ generation inhibitor S1 (PQVGHL peptide) and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT (cyclic CRTIGPSVC peptide), an iron-mimic peptide that targets transferrin receptor (TfR), to improve BBB penetration. The average particle size of drug-loaded PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm, respectively. The results of Y-maze and new object recognition test demonstrated that our PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice. Moreover, PLGA nanoparticles remarkably decreased the level of Aβ, reactive oxygen species (ROS), TNF-α and IL-6, and enhanced the activities of super oxide dismutase (SOD) and synapse numbers in the AD mouse brains. Compared with other PLGA nanoparticles, CRT peptide modified-PLGA nanoparticles co-delivering S1 and curcumin exhibited most beneficial effect on the treatment of AD mice, suggesting that conjugated CRT peptide, and encapsulated S1 and curcumin exerted their corresponding functions for the treatment.

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.

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.

Science.gov (United States)

Zhang, Hao-Xuan; Zhang, Xiu-Ping; Xiao, Gui-Yong; Hou, Yong; Cheng, Lei; Si, Meng; Wang, Shuai-Shuai; Li, Yu-Hua; Nie, Lin

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

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

DEFF Research Database (Denmark)

Wan, Feng; Yang, Mingshi

2016-01-01

Currently, most of the approved protein and peptide-based medicines are delivered via conventional parenteral injection (intramuscular, subcutaneous or intravenous). A frequent dosing regimen is often necessary because of their short plasma half-lives, causing poor patient compliance (e.g. pain......, abscess, etc.), side effects owing to typical peak-valley plasma concentration time profiles, and increased costs. Among many sustained-release formulations poly lactic-co-glycolic acid (PLGA)-based depot microparticle systems may represent one of the most promising approaches to provide protein...... 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...

PLGA encapsulation and radioiodination of indole-3-carbinol: investigation of anticancerogenic effects against MCF7, Caco2 and PC3 cells by in vitro assays

International Nuclear Information System (INIS)

Gorkem Yildiz; Ayfer Yurt Kilcar; Medine, E.I.; Volkan Tekin; Ozge Kozgus Guldu; Zumrut Biber Muftuler, F.

2017-01-01

Encapsulation with PLGA of I3C and radioiodination have been performed. Anticancerogenic effects of I3C and I3C-PLGA have been investigated utilizing in vitro methods on breast adenocarcinoma epithelial (MCF7), colon adenocarcinoma epithelial (Caco2), prostate carcinoma epithelial (PC3) cells. Characterization of I3C-PLGA have been performed with DLS method and SEM analysis. I3C and I3C-PLGA compounds have been radiolabeled in high yields with "1"3"1I which is widely used for diagnosis and treatment in Nuclear Medicine. All experimental results demonstrated that radioiodinated compounds are promising in order to be used in Nuclear Medicine as well as present study contributed previously reported studies. (author)

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.

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.

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.

Quercetin-loaded PLGA nanoparticles: a highly effective antibacterial agent in vitro and anti-infection application in vivo

International Nuclear Information System (INIS)

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

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.

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.

Brillouin lasing in single-mode tapered optical fiber with inscribed fiber Bragg grating array

Directory of Open Access Journals (Sweden)

S.M. Popov

2018-06-01

Full Text Available A tapered optical fiber has been manufactured with an array of fiber Bragg gratings (FBG inscribed during the drawing process. The total fiber peak reflectivity is 5% and the reflection bandwidth is ∼3.5 nm. A coherent frequency domain reflectometry has been applied for precise profiling of the fiber core diameter and grating reflectivity both distributed along the whole fiber length. These measurements are in a good agreement with the specific features of Brillouin lasing achieved in the semi-open fiber cavity configuration. Keywords: Tapered optical fibers, Fiber Bragg gratings, Random lasers

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...

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

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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.

New Polylactic Acid Composites Reinforced with Artichoke Fibers

OpenAIRE

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

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...

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.

Melatonin releasing PLGA micro/nanoparticles and their effect on osteosarcoma cells.

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Altındal, Damla Çetin; Gümüşderelioğlu, Menemşe

2016-02-01

Melatonin loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles and microparticles in the diameter of ∼200 nm and 3.5 μm, respectively, were prepared by emulsion-diffusion-evaporation method. Melatonin entrapment into the particles was significantly improved with the addition of 0.2% (w/v) melatonin into the aqueous phase and encapsulation efficiencies were found as 14 and 27% for nanoparticles and microparticles, respectively. At the end of 40 days, ∼70% of melatonin was released from both of particles, with high burst release. Both blank and melatonin loaded PLGA nanoparticles caused toxic effect on the MG-63 cells due to their uptake by the cells. However, when 0.05 mg microparticle that is carrying ∼1.7 μg melatonin was added to the cm(2) of culture, inhibitory effect of melatonin on the cells were obviously observed. The results would provide an expectation about the usage of melatonin as an adjunct to the routine chemotherapy of osteosarcoma by encapsulating it into a polymeric carrier system.

Brain-targeted delivery of trans-activating transcriptor-conjugated magnetic PLGA/lipid nanoparticles.

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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.

Mannan-Modified PLGA Nanoparticles for Targeted Gene Delivery

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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.

Development of andrographolide loaded PLGA microspheres: optimization, characterization and in vitro-in vivo correlation.

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Jiang, Yunxia; Wang, Fang; Xu, Hui; Liu, Hui; Meng, Qingguo; Liu, Wanhui

2014-11-20

The purpose of this study was to develop a sustained-release drug delivery system based on the injectable PLGA microspheres loaded with andrographolide. The andrographolide loaded PLGA microspheres were prepared by emulsion solvent evaporation method with optimization of formulation using response surface methodology (RSM). Physicochemical characterization, in vitro release behavior and in vivo pharmacokinetics of the optimized formulation were then evaluated. The percent absorbed in vivo was determined by deconvolution using the Loo-Riegelman method, and then the in vitro-in vivo correlation (IVIVC) was established. Results showed that the microspheres were spherical with a smooth surface. Average particle size, entrapment efficiency and drug loading were found to be 53.18±2.11 μm, 75.79±3.02% and 47.06±2.18%, respectively. In vitro release study showed a low initial burst release followed by a prolonged release up to 9 days and the release kinetics followed the Korsmeyer-Peppas model. After a single intramuscular injection, the microspheres maintained relatively high plasma concentration of andrographolide over one week. A good linear relationship was observed between the in vitro and in vivo release behavior (R(2)=0.9951). These results suggest the PLGA microspheres could be developed as a potential delivery system for andrographolide with high drug loading capacity and sustained drug release. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of Motor Neuron-Like Cell Differentiation of hEnSCs on Biodegradable PLGA Nanofiber Scaffolds.

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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.

Synthesis of PLGA nanoparticles of tea polyphenols and their strong in vivo protective effect against chemically induced DNA damage

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Srivastava AK

2013-04-01

Full Text Available Amit Kumar Srivastava,1 Priyanka Bhatnagar,2 Madhulika Singh,1 Sanjay Mishra,1 Pradeep Kumar,2 Yogeshwer Shukla,1 Kailash Chand Gupta1,2 1Proteomics Laboratory, Indian Institute of Toxicology Research (CSIR, Lucknow, India; 2Nucleic Acid Research Laboratory, Institute of Genomics and Integrative Biology (CSIR, Delhi University Campus, India Abstract: In spite of proficient results of several phytochemicals in preclinical settings, the conversion rate from bench to bedside is not very encouraging. Many reasons are attributed to this limited success, including inefficient systemic delivery and bioavailability under in vivo conditions. To achieve improved efficacy, polyphenolic constituents of black (theaflavin [TF] and green (epigallocatechin-3-gallate [EGCG] tea in poly(lactide-co-glycolide nanoparticles (PLGA-NPs were entrapped with entrapment efficacy of ~18% and 26%, respectively. Further, their preventive potential against 7,12-dimethylbenzanthracene (DMBA-induced DNA damage in mouse skin using DNA alkaline unwinding assay was evaluated. Pretreatment (topically of mouse skin with either TF or EGCG (100 µg/mouse doses exhibits protection of 45.34% and 28.32%, respectively, against DMBA-induced DNA damage. However, pretreatment with TF-loaded PLGA-NPs protects against DNA damage 64.41% by 1/20th dose of bulk, 71.79% by 1/10th dose of bulk, and 72.46% by 1/5th dose of bulk. Similarly, 51.28% (1/20th of bulk, 57.63% (1/10th of bulk, and 63.14% (1/5th of bulk prevention was noted using EGCG-loaded PLGA-NP doses. These results showed that tea polyphenol-loaded PLGA-NPs have ~30-fold dose-advantage than bulk TF or EGCG doses. Additionally, TF- or EGCG-loaded PLGA-NPs showed significant potential for induction of DNA repair genes (XRCC1, XRCC3, and ERCC3 and suppression of DNA damage responsive genes (p53, p21, MDM2, GADD45α, and COX-2 as compared with respective bulk TF or EGCG doses. Taken together, TF- or EGCG-loaded PLGA-NPs showed a superior

Development of a novel CsA-PLGA drug delivery system based on a glaucoma drainage device for the prevention of postoperative fibrosis

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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.

Development of a novel CsA-PLGA drug delivery system based on a glaucoma drainage device for the prevention of postoperative fibrosis

International Nuclear Information System (INIS)

Dai, Zhaoxing; Yu, Xiaobo; Hong, Jiaxu; Liu, Xi; Sun, Jianguo; Sun, Xinghuai

2016-01-01

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.

Preparation of a reproducible long-acting formulation of risperidone-loaded PLGA microspheres using microfluidic method.

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Jafarifar, Elham; Hajialyani, Marziyeh; Akbari, Mona; Rahimi, Masoud; Shokoohinia, Yalda; Fattahi, Ali

2017-09-01

The aim of the present study is to prepare risperidone-loaded poly lactic-co-glycolic acid (PLGA) microspheres within microfluidic system and to achieve a formulation with uniform size and monotonic and reproducible release profile. In comparison to batch method, T-junction and serpentine chips were utilized and optimizing study was carried out at different processing parameters (e.g. PLGA and surfactant concentration and flow rates ratio of outer to inner phase). The computational fluid dynamic (CFD) modeling was performed, and loading and release study were carried out. CFD simulation indicates that increasing the flow rate of aqueous phase cause to decrease the droplet size, while the change in size of microspheres did not follow a specific pattern in the experimental results. The most uniform microspheres and narrowest standard deviation (66.79 μm ± 3.32) were achieved using T-junction chip, 1% polyvinylalcohol, 1% PLGA and flow rates ratio of 20. The microfluidic-assisted microspheres were more uniform with narrower size distribution. The release of risperidone from microspheres produced by the microfluidic method was more reproducible and closer to zero-order kinetic model. The release profile of formulation with 2:1 drug-to-polymer ratio was the most favorable release, in which 41.85% release could be achieved during 24 days.

Preparation and characterization of PLGA-β-CD polymeric nanoparticles containing methotrexate and evaluation of their effects on T47D cell line.

Science.gov (United States)

Gorjikhah, Fatemeh; Azizi Jalalian, Farid; Salehi, Roya; Panahi, Yunes; Hasanzadeh, Arash; Alizadeh, Effat; Akbarzadeh, Abolfazl; Davaran, Soodabeh

2017-05-01

Among all cancers that affect women, breast cancer has most mortality rate. It is essential to attain more safe and efficient anticancer drugs. Recent advances in medical nanotechnology and biotechnology have caused in novel improvements in breast and other cancer drug delivery. Methotrexate is an anticancer drug that prevents the dihydrofolate reductase enzyme, which inhibits in the formation of DNA, RNA and proteins which have poor water-solubility. For enhancing the solubility and stability of drugs in delivery systems, we used methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles. The PLGA- beta-cyclodextrin nanoparticles were synthesized by a double emulsion method and characterized with FT-IR and SEM. T47D breast cancer cell lines were treated with equal concentrations of methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles and free methotrexate. MTT assay confirmed that methotrexate-loaded PLGA- beta-cyclodextrin nanoparticles enhanced cytotoxicity and drug delivery in T47D breast cancer cells. These results indicate that encapsulated drugs could be effective in controlled drug release for a sustained period would serve the purpose for long-term treatment of many diseases such as breast cancer.

New Perspective in the Formulation and Characterization of Didodecyldimethylammonium Bromide (DMAB Stabilized Poly(Lactic-co-Glycolic Acid (PLGA Nanoparticles.

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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

Enteric-coated capsules filled with mono-disperse micro-particles containing PLGA-lipid-PEG nanoparticles for oral delivery of insulin.

Science.gov (United States)

Yu, Fei; Li, Yang; Liu, Chang Sheng; Chen, Qin; Wang, Gui Huan; Guo, Wei; Wu, Xue E; Li, Dong Hui; Wu, Winston Duo; Chen, Xiao Dong

2015-04-30

The success of the oral delivery of insulin (INS) as a therapeutic protein drug would significantly improve the quality of life of diabetic patients who would otherwise receive multiple daily INS injections. The oral delivery of INS, however, is still limited in its delivery efficiency, which could be due to the chemical, enzymatic, and adsorption barriers. In this work, in an attempt to improve the delivery efficiency, the INS-loaded polymer-lipid hybrid nanoparticles (INS-PLGA-lipid-PEG NPs) were designed and constructed through a double-emulsion solvent evaporation technique, followed by formulation of the spherical micro-particles using a spray freeze dryer (SFD). This kind of dryers has a uniquely designed microfluidic aerosol nozzle (MFAN), ensuring the formation of uniform particles. The resulted particles of ∼212 μm could easily be reverted to discrete INS-PLGA-lipid-PEG NPs in an aqueous solution. The INS-PLGA-lipid-PEG NPs created in this work showed a highly negative surface charge, excellent entrapment efficiency (92.3%) and a sustained drug release (∼24 h). Confocal laser scanning microscopy and flow cytometer were used to show that the cellular uptake efficiency for the INS-PLGA-lipid-PEG NPs was more effective than the INS in Caco-2 cells. More importantly, the in vivo pharmacodynamics demonstrated that the orally delivered system induced a prolonged decrease in blood glucose levels among diabetic rats. The relative bioavailability of INS compared with subcutaneous injection in diabetic rats was found to be approximately 12%. These results suggested that the encapsulated INS-PLGA-lipid-PEG NPs are promising and should be investigated further in the near future as an effective INS oral delivery system. Copyright © 2015. Published by Elsevier B.V.

Modification of TiO(2) nanotube surfaces by electro-spray deposition of amoxicillin combined with PLGA for bactericidal effects at surgical implantation sites.

Science.gov (United States)

Lee, Jung-Hwan; Moon, Seung-Kyun; Kim, Kwang-Mahn; Kim, Kyoung-Nam

2013-01-01

To fabricate the antibiotic-releasing coatings on TiO(2) nanotube surfaces for wide applications of implant and bone plate in medical and dental surgery, the optimal deposition time of amoxicillin/PLGA solution simultaneously performing non-toxicity and a high bactericidal effect for preventing early implant failures was found. FE-SEM, ESD and FT-IR were used for confirming deposition of amoxicillin/PLGA on the TiO(2) surface. Also, the elution of amoxicillin/PLGA in a TiO(2) nanotube surface was measured by a UV-VIS spectrophotometer. The bactericidal effect of amoxicillin on the TiO(2) nanotube surface was evaluated by using Staphylococcus aureus (S. aureus). The cytotoxicity and cell proliferation were observed by WST assay using MC3T3-E1 osteoblast cells. The results indicated that the TiO(2) nanotube surface controlled by electro-spray deposition time with amoxicillin/PLGA solution could provide a high bactericidal effect against S. aureus by the bactericidal effect of amoxicillin, as well as good osteoblast cell proliferation at the TiO(2) nanotube surface without toxicity. This study used electro-spray deposition (ESD) methodology to obtain amoxicillin deposition in nanotube structures of TiO(2) and found the optimal deposition time of amoxicillin/PLGA solution simultaneously performing non-toxicity and a high bactericidal effect for preventing early implant failures.

Poly(D,L-Lactide-Co-Glycolide) Tubes With Multifilament Chitosan Yarn or Chitosan Sponge Core in Nerve Regeneration.

Science.gov (United States)

Wlaszczuk, Adam; Marcol, Wiesław; Kucharska, Magdalena; Wawro, Dariusz; Palen, Piotr; Lewin-Kowalik, Joanna

2016-11-01

The influence of different kinds of nerve guidance conduits on regeneration of totally transected rat sciatic nerves through a 7-mm gap was examined. Five different types of conduits made of chitosan and poly(D,L-lactide-co-glycolide) (PLGA) were constructed and tested in vivo. We divided 50 animals into equal groups of 10, with a different type of conduit implanted in each group: chitosan sponge core with an average molecular mass of polymer (Mv) of 287 kDa with 7 channels in a PLGA sleeve, chitosan sponge core with an Mv of 423 kDa with 7 channels in a PLGA sleeve, chitosan sponge core (Mv, 423 kDa) with 13 channels in a PLGA sleeve, chitosan multifilament yarn in a PLGA sleeve, and a PLGA sleeve only. Seven weeks after the operation, we examined the distance covered by regenerating nerve fibers, growing of nerves into the conduit's core, and intensity and type of inflammatory reaction in the conduit, as well as autotomy behavior (reflecting neuropathic pain intensity) in the animals. Two types of conduits were allowing nerve outgrowth through the gap with minor autotomy and minor inflammatory reactions. These were the conduits with chitosan multifilament yarn in a PLGA sleeve and the conduits with 13-channel microcrystalline chitosan sponge in a PLGA sleeve. The type of chitosan used to build the nerve guidance conduit influences the intensity and character of inflammatory reaction present during nerve regeneration, which in turn affects the distance crossed by regenerating nerve fibers, growing of the nerve fibers into the conduit's core, and the intensity of autotomy in the animals. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

High-Fiber Orange Juice as a Nutrition Supplement in Women: A Randomized, Double-Blind, Placebo-Controlled Study of Tolerance and Effectiveness.

Science.gov (United States)

Bergamasco, Christiane; Horie, Lilian Mika; Torrinhas, Raquel Susana; Waitzberg, Dan L

2015-11-01

The daily consumption of dietary fiber is frequently below suggested recommendations. Using a double-blind, controlled, randomized study, we assessed the efficiency and tolerance of a fiber-enriched orange juice to supplement fiber intake in women. After 1 week of noninterventional observation, 192 healthy adult women ingested 400 mL of orange juice for 21 days, which either was not (placebo group) or was enriched with fiber (fiber group). Orange juice ingestion was registered daily and controlled for each week during the study period. Macronutrient, fiber, and energy intake were determined using a 3-day food record, validated food chemical composition databases, and the "Pro Diet" software. Gastrointestinal symptoms were self-evaluated daily by scoring 4 grades of symptom intensity and using a visual analog scale to grade pain severity. No changes were observed for macronutrient and energy ingestion. For the placebo group (n = 97), the total fiber intake record was under the daily recommended value. In contrast, the fiber group (n = 95) displayed higher comparative values of total and soluble fiber consumption (P ≤ .001), achieving the daily recommended values of fiber intake. Both groups reported an increased frequency of slight bloating and rumbles over time (P ≤ .05). The fiber group also experienced a higher frequency of slight flatulence over time (P = .002). Consumption of fiber-enriched orange juice was efficient to achieve the daily fiber intake recommendation for women, was not accompanied by intense adverse events, and may represent a suitable method to supplement fiber intake in woman. © 2014 American Society for Parenteral and Enteral Nutrition.

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.

Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

Science.gov (United States)

Hiremath, Jagadish; Kang, Kyung-il; Xia, Ming; Elaish, Mohamed; Binjawadagi, Basavaraj; Ouyang, Kang; Dhakal, Santosh; Arcos, Jesus; Torrelles, Jordi B; Jiang, X; Lee, Chang Won; Renukaradhya, Gourapura J

2016-01-01

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.

Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

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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.

Photoprotective efficiency of PLGA-curcumin nanoparticles versus curcumin through the involvement of ERK/AKT pathway under ambient UV-R exposure in HaCaT cell line.

Science.gov (United States)

Chopra, Deepti; Ray, Lipika; Dwivedi, Ashish; Tiwari, Shashi Kant; Singh, Jyoti; Singh, Krishna P; Kushwaha, Hari Narayan; Jahan, Sadaf; Pandey, Ankita; Gupta, Shailendra K; Chaturvedi, Rajnish Kumar; Pant, Aditya Bhushan; Ray, Ratan Singh; Gupta, Kailash Chand

2016-04-01

Curcumin (Cur) has been demonstrated to have wide pharmacological window including anti-oxidant and anti-inflammatory properties. However, phototoxicity under sunlight exposure and poor biological availability limits its applicability. We have synthesized biodegradable and non-toxic polymer-poly (lactic-co-glycolic) acid (PLGA) encapsulated formulation of curcumin (PLGA-Cur-NPs) of 150 nm size range. Photochemically free curcumin generates ROS, lipid peroxidation and induces significant UVA and UVB mediated impaired mitochondrial functions leading to apoptosis/necrosis and cell injury in two different origin cell lines viz., mouse fibroblasts-NIH-3T3 and human keratinocytes-HaCaT as compared to PLGA-Cur-NPs. Molecular docking studies suggested that intact curcumin from nanoparticles, bind with BAX in BIM SAHB site and attenuate it to undergo apoptosis while upregulating anti-apoptotic genes like BCL2. Real time studies and western blot analysis with specific phosphorylation inhibitor of ERK1 and AKT1/2/3 confirm the involvement of ERK/AKT signaling molecules to trigger the survival cascade in case of PLGA-Cur-NPs. Our finding demonstrates that low level sustained release of curcumin from PLGA-Cur-NPs could be a promising way to protect the adverse biological interactions of photo-degradation products of curcumin upon the exposure of UVA and UVB. Hence, the applicability of PLGA-Cur-NPs could be suggested as prolonged radical scavenging ingredient in curcumin containing products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antioxidant Effects of Quercetin and Catechin Encapsulated into PLGA Nanoparticles

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Hector Pool

2012-01-01

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

Curcumin Conjugated with PLGA Potentiates Sustainability, Anti-Proliferative Activity and Apoptosis in Human Colon Carcinoma Cells

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Waghela, Bhargav N.; Sharma, Anupama; Dhumale, Suhashini; Pandey, Shashibahl M.; Pathak, Chandramani

2015-01-01

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. PMID:25692854

Characterization of Plasmid DNA Location within Chitosan/PLGA/pDNA Nanoparticle Complexes Designed for Gene Delivery

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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.

Micromechanisms of damage in unidirectional fiber reinforced composites

DEFF Research Database (Denmark)

Mishnaevsky, Leon; Brøndsted, Povl

2009-01-01

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...... 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......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...

Interactions of PLGA nanoparticles with blood components: protein adsorption, coagulation, activation of the complement system and hemolysis studies.

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Fornaguera, Cristina; Calderó, Gabriela; Mitjans, Montserrat; Vinardell, Maria Pilar; Solans, Conxita; Vauthier, Christine

2015-04-14

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.

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

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Zhou L

2015-08-01

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

Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells

International Nuclear Information System (INIS)

Loew, Karin; Wagner, Sylvia; Briesen, Hagen von; Knobloch, Thomas; Wiehe, Arno; Engel, Andrea; Langer, Klaus

2011-01-01

The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.

Sustained Release of Lidocaine from Solvent-Free Biodegradable Poly[(d,l)-Lactide-co-Glycolide] (PLGA): In Vitro and In Vivo Study.

Science.gov (United States)

Kau, Yi-Chuan; Liao, Chia-Chih; Chen, Ying-Chi; Liu, Shih-Jung

2014-09-16

Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l)-lactide-co-glycolide] (PLGA) was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm) and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release) and reached completion around day 28. Scanning electron microscope (SEM) photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered). In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

Sustained Release of Lidocaine from Solvent-Free Biodegradable Poly[(d,l-Lactide-co-Glycolide] (PLGA: In Vitro and In Vivo Study

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Yi-Chuan Kau

2014-09-01

Full Text Available Local anesthetics are commonly used for pain relief by regional nerve blocking. In this study, we fabricated solvent-free biodegradable pellets to extend the duration of lidocaine release without any significant local or systemic toxicity levels. To manufacture the pellets, poly[(d,l-lactide-co-glycolide] (PLGA was first pre-mixed with lidocaine powder into different ratios. The powder mixture was then compressed with a mold (diameter of 1, 5, 8 or 10 mm and sintered at 65 °C to form pellets. The in vitro release study showed that the lidocaine/PLGA pellets exhibited a tri-phase release behavior (a burst, a diffusion-controlled release and a degradation-dominated release and reached completion around day 28. Scanning electron microscope (SEM photos show that small channels could be found on the surfaces of the pellets on day 2. Furthermore, the polymer matrix swelled and fell apart on day 7, while the pellets became viscous after 10 days of in vitro elution. Perineural administration of the lidocaine/PLGA pellets produced anti-hypersensitivity effects lasting for at least 24 h in rats, significant when compared to the control group (a pure PLGA was pellet administered. In addition, no inflammation was detected within the nerve and in the neighboring muscle by histopathology.

Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Loew, Karin; Wagner, Sylvia; Briesen, Hagen von [Fraunhofer-Institute for Biomedical Engineering, D-66386 Strasse Ingbert (Germany); Knobloch, Thomas [Institute of Pharmaceutical Technology, Biocenter of Goethe-University, D-60438 Frankfurt (Germany); Wiehe, Arno [Biolitec AG, D-07745 Jena (Germany); Engel, Andrea; Langer, Klaus, E-mail: hagen.briesen@ibmt.fraunhofer.de [Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, D-48149 Muenster (Germany)

2011-06-17

The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.

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.

Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration.

Science.gov (United States)

Cai, Hui; Wen, Xingxing; Wen, Lu; Tirelli, Nicola; Zhang, Xiao; Zhang, Yue; Su, Huanpeng; Yang, Fan; Chen, Gang

2014-01-01

In this paper, the potential of poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) for carrying single or compound drugs traversing the round window membrane (RWM) was examined after the round window (RW) administration of different NPs to guinea pigs. First, coumarin-6 was incorporated into PLGA NPs as a fluorescent probe to investigate its ability to cross the RWM. Then, PLGA NPs with salvianolic acid B (Sal B), tanshinone IIA (TS IIA), and total panax notoginsenoside (PNS) including notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Rb1 (Rb1) were developed to evaluate whether NPs loaded with compound drugs would pass through the RWM and improve the local bioavailability of these agents. PLGA NPs loaded with single or compound drugs were prepared by the emulsification solvent evaporation method, and their particle size distribution, particle morphology, and encapsulation efficiency were characterized. In vitro release study showed sustained-release profiles of Sal B, TS IIA, and PNS from the NPs. The pharmacokinetic results showed that NPs applied to the RWM significantly improved drug distribution within the inner ear. The AUC0-t of coumarin-6 in the perilymph (PL) following RW administration of NPs was 4.7-fold higher than that of coumarin-6 solution, and the Cmax was 10.9-fold higher. Furthermore, the AUC(0-t) of R1, Rg1, and Rb1 were 4.0-, 3.1-, and 7.1-fold greater, respectively, after the application of NPs compared to the compound solution, and the Cmax were, respectively, 14.4-, 10.0-, and 16.7-fold higher. These findings suggest that PLGA NPs with unique properties at the nanoscale dimensions have a powerful ability to transport single or compound drugs into the PL through the RWM and remarkably enhance the local bioavailability of the encapsulated drugs in the inner ear. The use of PLGA NPs as nanoscale delivery vehicles to carry drugs across the RWM may be a promising strategy for the treatment of inner ear diseases.

Ibuprofen delivered by poly(lactic-co-glycolic acid (PLGA nanoparticles to human gastric cancer cells exerts antiproliferative activity at very low concentrations

Directory of Open Access Journals (Sweden)

Bonelli P

2012-11-01

Full Text Available Patrizia Bonelli,1 Franca M Tuccillo,1 Antonella Federico,5 Maria Napolitano,2 Antonella Borrelli,1 Daniela Melisi,6 Maria G Rimoli,6 Raffaele Palaia,3 Claudio Arra,4 Francesco Carinci71Laboratory of Molecular Biology and Viral Oncogenesis; 2Department of Clinical Immunology; 3Department of Gastrointestinal-Hepatobiliary-Pancreatic Cancer Oncology Surgery; 4Animal Facility, National Cancer Institute G Pascale, Naples, Italy; 5Microtech Laboratory, Naples, Italy; 6Pharmaceutical and Toxicological Chemistry Department, School of Pharmacy, University "Federico II", Naples, Italy; 7Department of Maxillofacial Surgery, University of Ferrara, Ferrara, ItalyPurpose: Epidemiological, clinical, and laboratory studies have suggested that ibuprofen, a commonly used nonsteroidal anti-inflammatory drug, inhibits the promotion and proliferation of certain tumors. Recently, we demonstrated the antiproliferative effects of ibuprofen on the human gastric cancer cell line MKN-45. However, high doses of ibuprofen were required to elicit these antiproliferative effects in vitro. The present research compared the antiproliferative effects of ibuprofen delivered freely and released by poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs in MKN-45 cells.Methods: MKN-45 human gastric adenocarcinoma cells were treated with ibuprofen-loaded PLGA NPs. The proliferation of MKN-45 cells was then assessed by cell counting. The uptake of NPs was imaged by fluorescence microscopy and flow cytometry. The release of ibuprofen from ibuprofen-loaded PLGA NPs in the cells was evaluated by gas chromatography–mass spectrometry.Results: Dramatic inhibition of cellular proliferation was observed in cells treated with ibuprofen-loaded PLGA NPs versus those treated with free ibuprofen at the same concentration. The localization of NPs was cytoplasmic. The initiation of ibuprofen release was rapid, commencing within 2 hours, and then increased slowly over time, reaching a maximum

A study of a three-dimensional PLGA sponge containing natural polymers co-cultured with endothelial and mesenchymal stem cells as a tissue engineering scaffold

International Nuclear Information System (INIS)

Shim, Jung Bo; Kim, Hyeongseok; Khang, Gilson; Ankeny, Randall F; Nerem, Robert M

2014-01-01

The interaction between vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in a complex hemodynamic and mechanical environment plays an important role in the control of blood vessel growth and function. Despite the importance of VSMCs, substitutes are needed for vascular therapies. A potential VSMC substitute is human adult bone marrow derived mesenchymal stem cells (hMSCs). In this study, the effect of poly(lactic-co-glycolic acid) (PLGA) scaffolds containing three natural polymers (demineralized bone particles, silk, and small intestine submucosa) on the phenotype of MSCs and SMCs cultured with or without ECs was investigated. The study objective was to create a media equivalent for a tissue engineered blood vessel using PLGA, natural polymers, and MSCs co-cultured with ECs. The PLGA containing the natural polymers silk and SIS showed increased proliferation and cell adhesion. The presence of silk and DBP promoted a MSC phenotype change into a SMC-like phenotype at the mRNA level; however these differences at the protein level were not seen. Additionally, PLGA containing SIS did not induce SMC gene or protein upregulation. Finally, the effect of ECs in combination with the natural polymers was tested. When co-cultured with ECs, the mRNA of SMC specific markers in MSCs and SMCs were increased when compared to SMCs or MSCs alone. However, MSCs, when co-cultured with ECs on PLGA containing silk, exhibited significantly increased α-SMA and calponin expression when compared to PLGA only scaffolds. These results indicate that the natural polymer silk in combination with the co-culture of endothelial cells was most effective at increasing cell viability and inducing a SMC-like phenotype at the mRNA and protein level in MSCs. (paper)

Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications.

Science.gov (United States)

Gomes, Carmen; Moreira, Rosana G; Castell-Perez, Elena

2011-03-01

Eugenol and trans-cinnamaldehyde are natural compounds known to be highly effective antimicrobials; however, both are hydrophobic molecules, a limitation to their use within the food industry. The goal of this study was to synthesize spherical poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped eugenol and trans-cinnamaldehyde for future antimicrobial delivery applications. The emulsion evaporation method was used to form the nanoparticles in the presence of poly (vinyl alcohol) (PVA) as a surfactant. The inclusion of antimicrobial compounds into the PLGA nanoparticles was accomplished in the organic phase. Synthesis was followed by ultrafiltration (performed to eliminate the excess of PVA and antimicrobial compound) and freeze-drying. The nanoparticles were characterized by their shape, size, entrapment efficiency, and antimicrobial efficiency. The entrapment efficiency for eugenol and trans-cinnamaldehyde was approximately 98% and 92%, respectively. Controlled release experiments conducted in vitro at 37 °C and 100 rpm for 72 h showed an initial burst followed by a slower rate of release of the antimicrobial entrapped inside the PLGA matrix. All loaded nanoparticles formulations proved to be efficient in inhibiting growth of Salmonella spp. (Gram-negative bacterium) and Listeria spp. (Gram-positive bacterium) with concentrations ranging from 20 to 10 mg/mL. Results suggest that the application of these antimicrobial nanoparticles in food systems may be effective at inhibiting specific pathogens. Nanoencapsulation of lipophilic antimicrobial compounds has great potential for improving the effectiveness and efficiency of delivery in food systems. This study consisted of synthesizing PLGA nanoparticles with entrapped eugenol and trans-cinnamaldehyde. By characterizing these new delivery systems, one can understand the controlled-release mechanism and antimicrobial efficiency that provides a foundation that will enable food manufacturers to design

Multi-kW coherent combining of fiber lasers seeded with pseudo random phase modulated light

Science.gov (United States)

Flores, Angel; Ehrehreich, Thomas; Holten, Roger; Anderson, Brian; Dajani, Iyad

2016-03-01

We report efficient coherent beam combining of five kilowatt-class fiber amplifiers with a diffractive optical element (DOE). Based on a master oscillator power amplifier (MOPA) configuration, the amplifiers were seeded with pseudo random phase modulated light. Each non-polarization maintaining fiber amplifier was optically path length matched and provides approximately 1.2 kW of near diffraction-limited output power (measured M2polarization control. A low power sample of the combined beam after the DOE provided an error signal for active phase locking which was performed via Locking of Optical Coherence by Single-Detector Electronic-Frequency Tagging (LOCSET). After phase stabilization, the beams were coherently combined via the 1x5 DOE. A total combined output power of 4.9 kW was achieved with 82% combining efficiency and excellent beam quality (M2splitter loss was 5%. Similarly, losses due in part to non-ideal polarization, ASE content, uncorrelated wavefront errors, and misalignment errors contributed to the efficiency reduction.

Preparation and characterization of PLGA nanospheres encapsulated with Autoclaved Leishmania Major (ALM) and Quillaja Saponin

International Nuclear Information System (INIS)

Tafaghodi, M.; Tabasi, S. Abolghasem Sajadi; Kharazizdeh, M.

2008-01-01

Several antigens, adjuvants and delivery systems have been evaluated for induction of protective immune responses against leishmaniasis, but have mostly been inefficient. In this study, poly (d,1-lactide-co-glycolide) (PLGA) nanospheres as antigen delivery system and Quillaja saponins (QS) as an immunoadjuvant have been used to increase the immune responses against Autoclaved Lieshmania major (ALM). PLGA nanospheres were prepared using a double emulsion (W/O/W) technique. The internal aqueous phase contained ALM and saponin, while the oily phase contained the solution of PLGA in dichloromethane and the external aqueous phase was polyvinylacohol (PVA) 7.5% (W/V) solution. Particulate characteristics were studied by scanning electron microscope and particle size analyzer. The encapsulation efficiency was determined by Lowry method and the release profile of antigen and saponin from nanospheres was evaluated for one week. Nanospheres were spherical in shape having smooth surfaces. Mean diameters for nanospheres loaded with ALM and ALM+QS were 300+-123 nm and 294+-106 nm respectively. Encapsulation efficiencies for ALM and QS were found 71+-14.8% and 55.8+- 23.1% respectively. Evaluation of the release profiles of ALM and QS from nanospheres in one week showed that 44.8 +-0.8% of ALM and 29.5+- 0.21% of QS had been released from naospheres. In conclusion, the prepared nanospheres with desirable size, encapsulation efficiency, and slow rate of release, had acceptable features for future in vivo studies. (author)

Weft-knitted silk-poly(lactide-co-glycolide) mesh scaffold combined with collagen matrix and seeded with mesenchymal stem cells for rabbit Achilles tendon repair.

Science.gov (United States)

Zhang, Wenyuan; Yang, Yadong; Zhang, Keji; Li, Ying; Fang, Guojian

2015-02-01

Natural silk fibroin fiber scaffolds have excellent mechanical properties, but degrade slowly. In this study, we used poly(lactide-co-glycolide) (PLGA, 10:90) fibers to adjust the overall degradation rate of the scaffolds and filled them with collagen to reserve space for cell growth. Silk fibroin-PLGA (36:64) mesh scaffolds were prepared using weft-knitting, filled with type I collagen, and incubated with rabbit autologous bone marrow-derived mesenchymal stem cells (MSCs). These scaffold-cells composites were implanted into rabbit Achilles tendon defects. At 16 weeks after implantation, morphological and histological observations showed formation of tendon-like tissues that expressed type I collagen mRNA and a uniformly dense distribution of collagen fibers. The maximum load of the regenerated Achilles tendon was 58.32% of normal Achilles tendon, which was significantly higher than control group without MSCs. These findings suggest that it is feasible to construct tissue engineered tendon using weft-knitted silk fibroin-PLGA fiber mesh/collagen matrix seeded with MSCs for rabbit Achilles tendon defect repair.

Multivariate analysis for the optimization of microfluidics-assisted nanoprecipitation method intended for the loading of small hydrophilic drugs into PLGA nanoparticles.

Science.gov (United States)

Chiesa, E; Dorati, R; Modena, T; Conti, B; Genta, I

2018-01-30

Design of Experiment-assisted evaluation of critical process (total flow rate, TFR, flow rate ratio, FRR) and formulation (polymer concentration and structure, drug:polymer ratio) variables in a novel microfluidics-based device, a staggered herringbone micromixer (SHM), for poly(lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (NPs) manufacturing was performed in order to systematically evaluate and mathematically describe their effects on NPs sizes and drug encapsulation; a small hydrophilic moiety, N-acetylcysteine, was chosen as challenging model drug. SHM-assisted nanoprecipitation method consistently yielded NPs with tailor made sizes (in the range of 100-900 nm) and polydispersity index range from 0.061 to 0.286. Significant effects on NPs sizes were highlighted for TFR and FRR: increasing TFR (from 5 to 15 mL/min) and decreasing FRR (from 1:1 to 1:5 v/v, acetonitrile: buffer) NPs with mean diameter <200 nm were obtained. SHM technique allowed for flexible, application-specific tuning of PLGA NPs size using organic solvents with relatively low toxicity (acetone, acetonitrile), varying aqueous phase composition (Tris buffer vs PVA aqueous solution) and PLGA characteristics (Mw ranging from 25-90 kDa, capped or un-capped PLGA, different lactide:glycolide molar ratio). A very satisfactory N-Ac encapsulation efficiency (more than 67%) and a prolonged release (by 168 h) were achieved. Copyright © 2017 Elsevier B.V. All rights reserved.

Kanamycin Sulphate Loaded PLGA-Vitamin-E-TPGS Long Circulating Nanoparticles Using Combined Coating of PEG and Water-Soluble Chitosan

Directory of Open Access Journals (Sweden)

Sanaul Mustafa

2017-01-01

Full Text Available Kanamycin sulphate (KS is a Mycobacterium tuberculosis protein synthesis inhibitor. Due to its intense hydrophilicity, KS is cleared from the body within 8 h. KS has a very short plasma half-life (2.5 h. KS is used in high concentrations to reach the therapeutic levels in plasma, which results in serious nephrotoxicity/ototoxicity. To overcome aforementioned limitations, the current study aimed to develop KS loaded PLGA-Vitamin-E-TPGS nanoparticles (KS-PLGA-TPGS NPs, to act as an efficient carrier for controlled delivery of KS. To achieve a substantial extension in blood circulation, a combined design, affixation of polyethylene glycol (PEG to KS-PLGA-TPGS NPs and adsorption of water-soluble chitosan (WSC (cationic deacetylated chitin to particle surface, was raised for surface modification of NPs. Surface modified NPs (KS-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 pharmacokinetics and in vivo biodistribution following intramuscular administration were investigated. NPs surface charge was close to neutral +3.61 mV and significantly affected by the WSC coating. KS-PEG-WSC NPs presented striking prolongation in blood circulation, reduced protein binding, and long drew-out the blood circulation half-life with resultant reduced kidney sequestration vis-à-vis KS-PLGA-TPGS NPs. The studies, therefore, indicate the successful formulation development of KS-PEG-WSC NPs with reduced frequency of dosing of KS indicating low incidence of nephrotoxicity/ototoxicity.

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.

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

Science.gov (United States)

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

2015-03-30

Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique. The nanoparticles were characterized in terms of size, zeta potential, insulin encapsulation efficiency and loading capacity. Upon pre-assembly with lipids, there was an increased distribution of insulin into the organic phase of the emulsion, eventually resulting in significantly enhanced encapsulation efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid-insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer during release studies in buffers, whereas insulin was released in a non-complexed form as a burst of approximately 80% of the loaded insulin. In conclusion, the protein load in PLGA nanoparticles can be significantly increased by employing self-assembled protein-lipid complexes. Copyright © 2014 Elsevier B.V. All rights reserved.

Steel fiber reinforced concrete

International Nuclear Information System (INIS)

Baloch, S.U.

2005-01-01

Steel-Fiber Reinforced Concrete is constructed by adding short fibers of small cross-sectional size .to the fresh concrete. These fibers reinforce the concrete in all directions, as they are randomly oriented. The improved mechanical properties of concrete include ductility, impact-resistance, compressive, tensile and flexural strength and abrasion-resistance. These uniqlte properties of the fiber- reinforcement can be exploited to great advantage in concrete structural members containing both conventional bar-reinforcement and steel fibers. The improvements in mechanical properties of cementitious materials resulting from steel-fiber reinforcement depend on the type, geometry, volume fraction and material-properties of fibers, the matrix mix proportions and the fiber-matrix interfacial bond characteristics. Effects of steel fibers on the mechanical properties of concrete have been investigated in this paper through a comprehensive testing-programme, by varying the fiber volume fraction and the aspect-ratio (Lid) of fibers. Significant improvements are observed in compressive, tensile, flexural strength and impact-resistance of concrete, accompanied by marked improvement in ductility. optimum fiber-volume fraction and aspect-ratio of steel fibers is identified. Test results are analyzed in details and relevant conclusions drawn. The research is finally concluded with future research needs. (author)

Biodegradable PLGA85/15 nanoparticles as a delivery vehicle for Chlamydia trachomatis recombinant MOMP-187 peptide

International Nuclear Information System (INIS)

Taha, Murtada A; Singh, Shree R; Dennis, Vida A

2012-01-01

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 −1 to eukaryotic cells (>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. (paper)

Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA.

Science.gov (United States)

Jensen, Ditte Krohn; Jensen, Linda Boye; Koocheki, Saeid; Bengtson, Lasse; Cun, Dongmei; Nielsen, Hanne Mørck; Foged, Camilla

2012-01-10

Matrix systems based on biocompatible and biodegradable polymers like the United States Food and Drug Administration (FDA)-approved polymer poly(DL-lactide-co-glycolide acid) (PLGA) are promising for the delivery of small interfering RNA (siRNA) due to favorable safety profiles, sustained release properties and improved colloidal stability, as compared to polyplexes. The purpose of this study was to design a dry powder formulation based on cationic lipid-modified PLGA nanoparticles intended for treatment of severe lung diseases by pulmonary delivery of siRNA. The cationic lipid dioleoyltrimethylammoniumpropane (DOTAP) was incorporated into the PLGA matrix to potentiate the gene silencing efficiency. The gene knock-down level in vitro was positively correlated to the weight ratio of DOTAP in the particles, and 73% silencing was achieved in the presence of 10% (v/v) serum at 25% (w/w) DOTAP. Optimal properties were found for nanoparticles modified with 15% (w/w) DOTAP, which reduced the gene expression with 54%. This formulation was spray-dried with mannitol into nanocomposite microparticles of an aerodynamic size appropriate for lung deposition. The spray-drying process did not affect the physicochemical properties of the readily re-dispersible nanoparticles, and most importantly, the in vitro gene silencing activity was preserved during spray-drying. The siRNA content in the powder was similar to the theoretical loading and the siRNA was intact, suggesting that the siRNA is preserved during the spray-drying process. Finally, X-ray powder diffraction analysis demonstrated that mannitol remained in a crystalline state upon spray-drying with PLGA nanoparticles suggesting that the sugar excipient might exert its stabilizing effect by sterical inhibition of the interactions between adjacent nanoparticles. This study demonstrates that spray-drying is an excellent technique for engineering dry powder formulations of siRNA nanoparticles, which might enable the local

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...

Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus

Directory of Open Access Journals (Sweden)

Liu X

2017-09-01

Full Text Available Xiangwei Liu,1,* Naiwen Tan,1,* Yuchao Zhou,1 Hongbo Wei,1,* Shuai Ren,1 Fan Yu,2 Hui Chen,3 Chengming Jia,4 Guodong Yang,5 Yingliang Song1 1State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Implant Dentistry, 2Department of Prosthodontics, School of Stomatology, 3Department of Plastic Surgery, Tangdu Hospital, 4Department of Traditional Chinese Medicine, Xijing Hospital, 5Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, China *These authors contributed equally to this work Abstract: Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204 and dispersed them in the poly(lactic-co-glycolic acid (PLGA solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient

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

Polymeric nanoparticles are widely investigated as drug delivery systems for oral administration. However, the hydrophobic nature of many polymers hampers effective loading of the particles with hydrophilic macromolecules such as insulin. Thus, the aim of this work was to improve the loading...... of insulin into poly(lactic-co-glycolic) acid (PLGA) nanoparticles by pre-assembly with amphiphilic lipids. Insulin was complexed with soybean phosphatidylcholine or sodium caprate by self-assembly and subsequently loaded into PLGA nanoparticles by using the double emulsion-solvent evaporation technique...... efficiencies (90% as compared to 24% in the absence of lipids). Importantly, the insulin loading capacity was increased up to 20% by using the lipid–insulin complexes. The results further showed that a main fraction of the lipid was incorporated into the nanoparticles and remained associated to the polymer...

3D Representative Volume Element Reconstruction of Fiber Composites via Orientation Tensor and Substructure Features

Energy Technology Data Exchange (ETDEWEB)

Li, Yi; Chen, Wei; Xu, Hongyi; Jin, Xuejun

2016-01-01

To provide a seamless integration of manufacturing processing simulation and fiber microstructure modeling, two new stochastic 3D microstructure reconstruction methods are proposed for two types of random fiber composites: random short fiber composites, and Sheet Molding Compounds (SMC) chopped fiber composites. A Random Sequential Adsorption (RSA) algorithm is first developed to embed statistical orientation information into 3D RVE reconstruction of random short fiber composites. For the SMC composites, an optimized Voronoi diagram based approach is developed for capturing the substructure features of SMC chopped fiber composites. The proposed methods are distinguished from other reconstruction works by providing a way of integrating statistical information (fiber orientation tensor) obtained from material processing simulation, as well as capturing the multiscale substructures of the SMC composites.

Radiative characterization of random fibrous media with long cylindrical fibers: Comparison of single- and multi-RTE approaches

Science.gov (United States)

Randrianalisoa, Jaona; Haussener, Sophia; Baillis, Dominique; Lipiński, Wojciech

2017-11-01

Radiative heat transfer is analyzed in participating media consisting of long cylindrical fibers with a diameter in the limit of geometrical optics. The absorption and scattering coefficients and the scattering phase function of the medium are determined based on the discrete-level medium geometry and optical properties of individual fibers. The fibers are assumed to be randomly oriented and positioned inside the medium. Two approaches are employed: a volume-averaged two-intensity approach referred to as multi-RTE approach and a homogenized single-intensity approach referred to as the single-RTE approach. Both approaches require effective properties, determined using direct Monte Carlo ray tracing techniques. The macroscopic radiative transfer equations (for single intensity or two volume-averaged intensities) with the corresponding effective properties are solved using Monte Carlo techniques and allow for the determination of the radiative flux distribution as well as overall transmittance and reflectance of the medium. The results are compared against predictions by the direct Monte Carlo simulation on the exact morphology. The effects of fiber volume fraction and optical properties on the effective radiative properties and the overall slab radiative characteristics are investigated. The single-RTE approach gives accurate predictions for high porosity fibrous media (porosity about 95%). The multi-RTE approach is recommended for isotropic fibrous media with porosity in the range of 79-95%.

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

CSIR Research Space (South Africa)

Mandiwana, V

2015-09-01

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

The biological activities of (1,3)-(1,6)-{beta}-d-glucan and porous electrospun PLGA membranes containing {beta}-glucan in human dermal fibroblasts and adipose tissue-derived stem cells

Energy Technology Data Exchange (ETDEWEB)

Woo, Yeon I; Park, Bong Joo; Kim, Hye-Lee; Lee, Mi Hee; Kim, Jungsung; Park, Jong-Chul [Department of Medical Engineering, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Yang, Young-Il [Department of Pathology, School of Medicine, Paik Institute for Clinical Research, Inje University, 633-165 Gae-dong, Busan-jin-gu, Busan 614-735 (Korea, Republic of); Kim, Jung Koo [Department of Biomedical Engineering, College of Biomedical Science and Engineering, Inje University, Kimhae 621-749 (Korea, Republic of); Tsubaki, Kazufumi [R and D division, Asahi Denka Co. Ltd, 7-2-35 Higashi-ogu, Arakawa-ku, Tokyo 116-8554 (Japan); Han, Dong-Wook, E-mail: parkjc@yuhs.a [Department of Nanomedical Engineering, College of Nanoscience and Nanotechnology, Pusan National University, geumjeong-gu, Busan 609-735 (Korea, Republic of)

2010-08-01

In this study, we investigated the possible roles of (1,3)-(1,6)-{beta}-d-glucan ({beta}-glucan) and porous electrospun poly-lactide-co-glycolide (PLGA) membranes containing {beta}-glucan for skin wound healing, especially their effect on adult human dermal fibroblast (aHDF) and adipose tissue-derived stem cell (ADSC) activation, proliferation, migration, collagen gel contraction and biological safety tests of the prepared membrane. This study demonstrated that {beta}-glucan and porous PLGA membranes containing {beta}-glucan have enhanced the cellular responses, proliferation and migration, of aHDFs and ADSCs and the result of a collagen gel contraction assay also revealed that collagen gels contract strongly after 4 h post-gelation incubation with {beta}-glucan. Furthermore, we confirmed that porous PLGA membranes containing {beta}-glucan are biologically safe for wound healing study. These results indicate that the porous PLGA membranes containing {beta}-glucan interacted favorably with the membrane and the topical administration of {beta}-glucan was useful in promoting wound healing. Therefore, our study suggests that {beta}-glucan and porous PLGA membranes containing {beta}-glucan may be useful as a material for enhancing wound healing.

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 random...

Softening in Random Networks of Non-Identical Beams.

Science.gov (United States)

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

2016-02-01

Random fiber networks are assemblies of elastic elements connected in random configurations. They are used as models for a broad range of fibrous materials including biopolymer gels and synthetic nonwovens. Although the mechanics of networks made from the same type of fibers has been studied extensively, the behavior of composite systems of fibers with different properties has received less attention. In this work we numerically and theoretically study random networks of beams and springs of different mechanical properties. We observe that the overall network stiffness decreases on average as the variability of fiber stiffness increases, at constant mean fiber stiffness. Numerical results and analytical arguments show that for small variabilities in fiber stiffness the amount of network softening scales linearly with the variance of the fiber stiffness distribution. This result holds for any beam structure and is expected to apply to a broad range of materials including cellular solids.

Cationic PLGA/Eudragit RL nanoparticles for increasing retention time in synovial cavity after intra-articular injection in knee joint

Directory of Open Access Journals (Sweden)

Kim SR

2015-08-01

Full Text Available Sung Rae Kim,1 Myoung Jin Ho,2 Eugene Lee,3 Joon Woo Lee,3 Young Wook Choi,1 Myung Joo Kang21College of Pharmacy, Chung-Ang University, Dongjak-gu, Seoul, 2College of Pharmacy, Dankook University, Dongnam-gu, Cheonan, Chungnam, 3Department of Radiology, Seoul National University Bundang Hospital, Bundang-gu, Seongnam, Gyeonggi-do, South KoreaAbstract: Positively surface-charged poly(lactide-co-glycolide (PLGA/Eudragit RL nanoparticles (NPs were designed to increase retention time and sustain release profile in joints after intra-articular injection, by forming micrometer-sized electrostatic aggregates with hyaluronic acid, an endogenous anionic polysaccharide found in high amounts in synovial fluid. The cationic NPs consisting of PLGA, Eudragit RL, and polyvinyl alcohol were fabricated by solvent evaporation technique. The NPs were 170.1 nm in size, with a zeta potential of 21.3 mV in phosphate-buffered saline. Hyperspectral imaging (CytoViva® revealed the formation of the micrometer-sized filamentous aggregates upon admixing, due to electrostatic interaction between NPs and the polysaccharides. NPs loaded with a fluorescent probe (1,1'-dioctadecyl-3,3,3',3' tetramethylindotricarbocyanine iodide, DiR displayed a significantly improved retention time in the knee joint, with over 50% preservation of the fluorescent signal 28 days after injection. When DiR solution was injected intra-articularly, the fluorescence levels rapidly decreased to 30% of the initial concentration within 3 days in mice. From these findings, we suggest that PLGA-based cationic NPs could be a promising tool for prolonged delivery of therapeutic agents in joints selectively.Keywords: PLGA, Eudragit RL, hyaluronic acid, cationic nanoparticles, intra-articular injection, electrostatic interaction

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

International Nuclear Information System (INIS)

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

2013-01-01

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

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

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...

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

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.

Synthesis of PLGA-Lipid Hybrid Nanoparticles for siRNA Delivery Using the Emulsion Method PLGA-PEG-Lipid Nanoparticles for siRNA Delivery.

Science.gov (United States)

Wang, Lei; Griffel, Benjamin; Xu, Xiaoyang

2017-01-01

The effective delivery of small interfering RNA (siRNA) to tumor cells remains a challenge for applications in cancer therapy. The development of polymeric nanoparticles with high siRNA loading efficacy has shown great potential for cancer targets. Double emulsion solvent evaporation technique is a useful tool for encapsulation of hydrophilic molecules (e.g., siRNA). Here we describe a versatile platform for siRNA delivery based on PLGA-PEG-cationic lipid nanoparticles by using the double emulsion method. The resulting nanoparticles show high encapsulation efficiency for siRNA (up to 90%) and demonstrate effective downregulation of the target genes in vitro and vivo.

In vitro study of 3D PLGA/n-HAp/β-TCP composite scaffolds with etched oxygen plasma surface modification in bone tissue engineering

Energy Technology Data Exchange (ETDEWEB)

Roh, Hee-Sang [Department of Dental Materials, School of Dentistry, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452 (Korea, Republic of); Jung, Sang-Chul [Department of Environmental Engineering, Sunchon National University, 255 Jungang-ro, Sunchon 57922 (Korea, Republic of); Kook, Min-Suk [Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186 (Korea, Republic of); Kim, Byung-Hoon, E-mail: kim5055@chosun.ac.kr [Department of Dental Materials, School of Dentistry, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452 (Korea, Republic of)

2016-12-01

Highlights: • PLGA and PLGA/n-HAp/β-TCP scaffolds were successfully fabricated by 3D printing. • Oxygen plasma etching increases the wettability and surface roughness. • Bioceramics and oxygen plasma etching and could be used to improve the cell affinity. - Abstract: Three-dimensional (3D) scaffolds have many advantageous properties for bone tissue engineering application, due to its controllable properties such as pore size, structural shape and interconnectivity. In this study, effects on oxygen plasma surface modification and adding of nano-hydroxyapatite (n-HAp) and β-tricalcium phosphate (β-TCP) on the 3D PLGA/n-HAp/β-TCP scaffolds for improving preosteoblast cell (MC3T3-E1) adhesion, proliferation and differentiation were investigated. The 3D PLGA/n-HAp/β-TCP scaffolds were fabricated by 3D Bio-Extruder equipment. The 3D scaffolds were prepared with 0°/90° architecture and pore size of approximately 300 μm. In addition 3D scaffolds surface were etched by oxygen plasma to enhance the hydrophilic property and surface roughness. After oxygen plasma treatment, the surface chemistry and morphology were investigated by Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy. And also hydrophilic property was measured by contact angle. The MC3T3-E1 cell proliferation and differentiation were investigated by MTT assay and ALP activity. In present work, the 3D PLGA/HAp/beta-TCP composite scaffold with suitable structure for the growth of osteoblast cells was successfully fabricated by 3D rapid prototyping technique. The surface hydrophilicity and roughness of 3D scaffold increased by oxygen plasma treatment had a positive effect on cell adhesion, proliferation, and differentiation. Furthermore, the differentiation of MC3T3-E1 cell was significantly enhanced by adding of n-HAp and β-TCP on 3D PLGA scaffold. As a result, combination of bioceramics and oxygen plasma treatment showed a synergistic effect on

Estradiol-loaded PLGA nanoparticles for improving low bone mineral density of cancellous bone caused by osteoporosis: Application of enhanced charged nanoparticles with iontophoresis.

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Takeuchi, Issei; Kobayashi, Shiori; Hida, Yukari; Makino, Kimiko

2017-07-01

Postmenopausal osteoporosis among older women, which occurs by an ovarian hormone deficiency, is one of the major public health problems. 17 β-estradiol (E2) is used to prevent and treat this disease as a drug of hormone replacement therapy. In oral administration, E2 is significantly affected by first-pass hepatic metabolism, and high dose administration must be needed to obtain drug efficacy. Therefore, alternative administration route is needed, and we have focused on the transdermal drug delivery system. In this study, we have prepared E2-loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles for osteoporosis by using a combination of an antisolvent diffusion method with preferential solvation. The average particle diameter of the nanoparticles was 110.0±41.0nm and the surface charge number density was 82 times higher than that of conventional E2-loaded PLGA nanoparticles. Therapeutic evaluation of E2-loaded PLGA nanoparticles was carried out using ovariectomized female rats. Therapeutic efficacy was evaluated to measure bone mineral density of cancellous bone using an X-ray CT system. When the E2-loaded PLGA nanoparticles were administrated once a week, bone mineral density was significantly higher than that of the non-treated group at 60days after the start of treatment. Also, in the group administered this nanoparticle twice a week, the bone mineral density increased significantly at 45days after the start of treatment. From these results, it was revealed that E2-loaded PLGA nanoparticles with iontophoresis were useful to recover bone mineral density of cancellous bone, and it was also suggested that they extend the dosing interval of E2. Copyright © 2017 Elsevier B.V. All rights reserved.

Oral DNA vaccination of rainbow trout, Oncorhynchus mykiss (Walbaum), against infectious haematopoietic necrosis virus using PLGA [Poly(D,L-Lactic-Co-Glycolic Acid)] nanoparticles.

Science.gov (United States)

Adomako, M; St-Hilaire, S; Zheng, Y; Eley, J; Marcum, R D; Sealey, W; Donahower, B C; Lapatra, S; Sheridan, P P

2012-03-01

A DNA vaccine against infectious haematopoietic necrosis virus (IHNV) is effective at protecting rainbow trout, Oncorhynchus mykiss, against disease, but intramuscular injection is required and makes the vaccine impractical for use in the freshwater rainbow trout farming industry. Poly (D,L-lactic-co-glycolic acid) (PLGA) is a U.S. Food and Drug Administration (FDA) approved polymer that can be used to deliver DNA vaccines. We evaluated the in vivo absorption of PLGA nanoparticles containing coumarin-6 when added to a fish food pellet. We demonstrated that rainbow trout will eat PLGA nanoparticle coated feed and that these nanoparticles can be detected in the epithelial cells of the lower intestine within 96 h after feeding. We also detected low levels of gene expression and anti-IHNV neutralizing antibodies when fish were fed or intubated with PLGA nanoparticles containing IHNV G gene plasmid. A virus challenge evaluation suggested a slight increase in survival at 6 weeks post-vaccination in fish that received a high dose of the oral vaccine, but there was no difference when additional fish were challenged at 10 weeks post-vaccination. The results of this study suggest that it is possible to induce an immune response using an orally delivered DNA vaccine, but the current system needs improvement. © 2012 Blackwell Publishing Ltd.

Towards development of novel immunization strategies against leishmaniasis using PLGA nanoparticles loaded with kinetoplastid membrane protein-11

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Santos DM

2012-04-01

Full Text Available Diego M Santos1, Marcia W Carneiro1, Tatiana R de Moura1, Kiyoshi Fukutani1, Jorge Clarencio1, Manuel Soto2, Socorro Espuelas3,4, Claudia Brodskyn1,5, Aldina Barral1,5, Manoel Barral-Netto1,5, Camila I de Oliveira1,51Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brazil; 2Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Departamento de Biologia Molecular, Universidad Autonoma de Madrid, Madrid; 3Departamento de Farmacia y Tecnología Farmacéutica, 4Instituto de Salud Tropical, Facultad de Farmacia, Universidad de Navarra, Pamplona, Spain; 5Instituto de Investigação em Imunologia, Salvador, BA, BrazilBackground: 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.Methods: 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.Results: Both immunization strategies elicited detectable cellular immune responses with the presence of both proinflammatory and anti

Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections.

Science.gov (United States)

Günday Türeli, Nazende; Torge, Afra; Juntke, Jenny; Schwarz, Bianca C; Schneider-Daum, Nicole; Türeli, Akif Emre; Lehr, Claus-Michael; Schneider, Marc

2017-08-01

Current pulmonary treatments against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies. NPs were prepared under controlled conditions by utilizing MicroJet Reactor (MJR) to yield a particle size of 190.4±28.6nm with 0.089 PDI. Encapsulation efficiency of the drug was 79% resulting in a loading of 14%. Release was determined to be controlled and medium-independent in PBS, PBS+0.2% Tween 80 and simulated lung fluid. Cytotoxicity assays with Calu-3 cells and CF bronchial epithelial cells (CFBE41o - ) indicated that complex-loaded PLGA NPs were non-toxic at concentrations ≫ MIC cipro against lab strains of the bacteria. Antibacterial activity tests revealed enhanced activity when applied as nanoparticles. NPs' colloidal stability in mucus was proven. Notably, a decrease in mucus turbidity was observed upon incubation with NPs. Herewith, ciprofloxacin complex-loaded PLGA NPs are introduced as promising pulmonary nano drug delivery systems against P.aeruginosa infections in CF lung. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2015-01-01

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

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

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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.

Comparative Efficacies of Collagen-Based 3D Printed PCL/PLGA/?-TCP Composite Block Bone Grafts and Biphasic Calcium Phosphate Bone Substitute for Bone Regeneration

OpenAIRE

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

2017-01-01

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 ?-tricalcium phosphate (?-TCP) in a 4:4:2 ratio, PCL/PLGA/?-TCP particulate bone grafts were fabricated using 3D printing technology. Fabricated particulate bone grafts were mixed with atelocollagen to produce collagen-based PCL/P...

Improving release completeness from PLGA-based implants for the acid-labile model protein ovalbumin.

Science.gov (United States)

Duque, Luisa; Körber, Martin; Bodmeier, Roland

2018-03-01

The objectives of this study were to assess the feasibility of hot melt extrusion (HME) for the preparation of PLGA-based ovalbumin-loaded implants as well as to characterize and improve protein release from the implants. Ovalbumin (OVA) was stable during extrusion, which was attributed to a protective effect of the biodegradable matrix. OVA release was characterized by a low burst, a slow release up to day 21, which plateaued thereafter resulting in incomplete release for all evaluated protein loadings. Release incompleteness was accompanied by the formation of an insoluble residual mass. Further characterization of this mass indicated that it consisted of non-covalent protein aggregates and polymer, where ovalbumin was ionically bound as the pH inside the degrading matrix decreased below the pI of the protein. Although higher protein release was obtained with the inclusion of weak bases because of their neutralizing effect, OVA aggregation and release incompleteness were not fully avoided. With the use of shellac, a well-known enteric and biocompatible polymer, as protective excipient, a distinct late release phase occurred and release completeness was increased to more than 75% cumulative release. Shellac apparently protected the protein against the acidic microclimate due to its low solubility at low pH. Protected OVA was thus released once the pH increased due to a declining PLGA-oligomer formation. The result was a triphasic release profile consisting of an initial burst, a slow diffusion phase over about 7 weeks, and an erosion-controlled dissolution phase over the next 3 weeks. An acid-labile protein like OVA was thus feasibly protected from interactions with PLGA and its degradation products, resulting in a controlled delivery of more than 85% of the original payload. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantum-noise randomized data encryption for wavelength-division-multiplexed fiber-optic networks

International Nuclear Information System (INIS)

Corndorf, Eric; Liang Chuang; Kanter, Gregory S.; Kumar, Prem; Yuen, Horace P.

2005-01-01

We demonstrate high-rate randomized data-encryption through optical fibers using the inherent quantum-measurement noise of coherent states of light. Specifically, we demonstrate 650 Mbit/s data encryption through a 10 Gbit/s data-bearing, in-line amplified 200-km-long line. In our protocol, legitimate users (who share a short secret key) communicate using an M-ry signal set while an attacker (who does not share the secret key) is forced to contend with the fundamental and irreducible quantum-measurement noise of coherent states. Implementations of our protocol using both polarization-encoded signal sets as well as polarization-insensitive phase-keyed signal sets are experimentally and theoretically evaluated. Different from the performance criteria for the cryptographic objective of key generation (quantum key-generation), one possible set of performance criteria for the cryptographic objective of data encryption is established and carefully considered

Excitation of random intense single-cycle light-pulse chains in optical fiber

International Nuclear Information System (INIS)

Ding, Y C; Zhang, F L; Gao, J B; Chen, Z Y; Lin, C Y; Yu, M Y

2014-01-01

Excitation of intense periodic single-cycle light pulses in a stochastic background arising from continuous wave stimulated Brillouin scattering (SBS) in a long optical fiber with weak optical feedback is found experimentally and modeled theoretically. Such intense light-pulse chains occur randomly and the optical feedback is a requirement for their excitation. The probability of these forms, among the large number of experimental output signals with identifiable waveforms, appearing is only about 3%, with the remainder exhibiting regular SBS characteristics. It is also found that pulses with low period numbers appear more frequently and the probability distribution for their occurrence in terms of the pulse power is roughly L-shaped, like that for rogue waves. The results from a three-wave-coupling model for SBS including feedback phase control agree well qualitatively with the observed phenomena. (paper)

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

International Nuclear Information System (INIS)

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

2014-01-01

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 1 H-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

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

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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.

Protective efficacy of cationic-PLGA microspheres loaded with DNA vaccine encoding the sip gene of Streptococcus agalactiae in tilapia.

Science.gov (United States)

Ma, Yan-Ping; Ke, Hao; Liang, Zhi-Ling; Ma, Jiang-Yao; Hao, Le; Liu, Zhen-Xing

2017-07-01

Streptococcus agalactiae (S. agalactiae) is an important fish pathogen, which has received more attention in the past decade due to the increasing economic losses in the tilapia industry worldwide. As existing effective vaccines of S. agalactiae in fish have obvious disadvantage, to select immunoprotective antigens and package materials would undoubtedly contribute to the development of novel oral vaccines. In the present study, surface immunogenic protein (sip) was selected from the S. agalactiae serovar I a genomes as immunogenic protein in DNA vaccine form with cationic chitosan and biodegradable and biocompatible PLGA. The pcSip plasmid in cationic-PLGA was successfully expressed in tissues of immunized tilapia and the immunogenicity was assessed in tilapia challenge model. A significant increase was observed in the cytokine levels of IL-1β, TNF-α, CC1, CC2 in spleen and kidney tissues. Furthermore, immunized tilapia conferred different levels of protection against challenge with a lethal dose of highly virulent serovar I a S. agalactiae. Our results indicated that the pcSip plasmid in cationic-PLGA induced high level of antibodies and protection against S. agalactiae infection, could be effective oral DNA vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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Qian YZ

2016-08-01

Full Text Available Yunzhu Qian,1,2 Hanbang Chen,1 Yang Xu,1 Jianxin Yang,2 Xuefeng Zhou,3 Feimin Zhang,1 Ning Gu3 1Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 2Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou, 3School of Biological Science and Medical Engineering, Southeast University, Nanjing, People’s Republic of China Abstract: Constructing biomimetic structure and incorporating bioactive molecules is an effective strategy to achieve a more favorable cell response. To explore the effect of electrospinning (ES nanofibrous architecture and collagen I (COL I-incorporated modification on tuning osteoblast response, a resorbable membrane composed of poly(lactic-co-glycolic acid/poly(caprolactone (PLGA/PCL; 7:3 w/w was developed via ES. COL I was blended into PLGA/PCL solution to prepare composite ES membrane. Notably, relatively better cell response was delivered by the bioactive ES-based membrane which was fabricated by modification of 3,4-dihydroxyphenylalanine and COL I. After investigation by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle measurement, and mechanical test, polyporous three-dimensional nanofibrous structure with low tensile force and the successful integration of COL I was obtained by the ES method. Compared with traditional PLGA/PCL membrane, the surface hydrophilicity of collagen-incorporated membranes was largely enhanced. The behavior of mouse preosteoblast MC3T3-E1 cell infiltration and proliferation on membranes was studied at 24 and 48 hours. The negative control was fabricated by solvent casting. Evaluation of cell adhesion and morphology demonstrated that all the ES membranes were more favorable for promoting the cell adhesion and spreading than the casting membrane. Cell Counting Kit-8 assays revealed that biomimetic architecture, surface topography, and bioactive properties of membranes were favorable for cell

Periodontal wound healing/regeneration following the application of rhGDF-5 in a beta-TCP/PLGA carrier in critical-size supra-alveolar periodontal defects in dogs.

Science.gov (United States)

Kwon, David H; Bisch, Frederick C; Herold, Robert W; Pompe, Cornelius; Bastone, Patrizia; Rodriguez, Nancy A; Susin, Cristiano; Wikesjö, Ulf M E

2010-07-01

The objective of this study was to evaluate the effect of a novel recombinant human GDF-5 (rhGDF-5) construct intended for onlay and inlay indications on periodontal wound healing/regeneration. Contralateral, surgically created, critical-size, 6-mm, supra-alveolar periodontal defects in five adult Hound Labrador mongrel dogs received rhGDF-5 coated onto beta-tricalcium phosphate (beta-TCP) particles and immersed in a bioresorbable poly(lactic-co-glycolic acid) (PLGA) composite or the beta-TCP/PLGA carrier alone (control). The rhGDF-5 and control constructs were moulded around the teeth and allowed to set. The gingival flaps were then advanced; flap margins were adapted 3-4 mm coronal to the teeth and sutured. The animals were euthanized at 8 weeks post-surgery when block biopsies were collected for histometric analysis. Healing was generally uneventful. A few sites exhibited minor exposures. Three control sites and one rhGDF-5 site (in separate animals) experienced more extensive wound dehiscencies. The rhGDF-5 and control constructs were easy to apply and exhibited adequate structural integrity to support the mucoperiosteal flaps in this challenging onlay model. Limited residual beta-TCP particles were observed at 8 weeks for both rhGDF-5/beta-TCP/PLGA and beta-TCP/PLGA control sites. The rhGDF-5/beta-TCP/PLGA sites showed significantly greater cementum (2.34 +/- 0.44 versus 1.13 +/- 0.25 mm, p=0.02) and bone (2.92 +/- 0.66 versus 1.21 +/- 0.30 mm, p=0.02) formation compared with the carrier control. Limited ankylosis was observed in four of five rhGDF-5/beta-TCP/PLGA sites but not in control sites. Within the limitations of this study, the results suggest that rhGDF-5 is a promising candidate technology in support of periodontal wound healing/regeneration. Carrier and rhGDF-5 dose optimization are necessary before further advancement of the technology towards clinical evaluation.

Surface modification of PLGA nanospheres with Gd-DTPA and Gd-DOTA for high-relaxivity MRI contrast agents

NARCIS (Netherlands)

Ratzinger, Gerda; Agrawal, Prashant; Körner, Wilfried; Lonkai, Julia; Sanders, Honorius M. H. F.; Terreno, Enzo; Wirth, Michael; Strijkers, Gustav J.; Nicolay, Klaas; Gabor, Franz

2010-01-01

The preparation of particulate contrast agents for magnetic resonance imaging (MRI) based on biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanocarriers is reported. By spacer-aided covalent surface-grafting of the prominent chelating ligands diethylenetriaminepentaacetic acid (DTPA) and

Surface modification of PLGA nanospheres with Gd-DTPA and Gd-DOTA for high-relaxivity MRI contrast agents

NARCIS (Netherlands)

Ratzinger, G.; Agrawal, P.; Koerner, W.; Lonkai, J.; Sanders, H.M.H.F.; Terreno, E.; Wirth, M.; Strijkers, G. J.; Nicolay, K.; Gabor, F.

2010-01-01

The preparation of particulate contrast agents for magnetic resonance imaging (MRI) based on biodegradable poly(d,l-lactide-co-glycolide) (PLGA) nanocarriers is reported. By spacer-aided covalent surface-grafting of the prominent chelating ligands diethylenetriaminepentaacetic acid (DTPA) and

New Polylactic Acid Composites Reinforced with Artichoke Fibers

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Luigi Botta

2015-11-01

Full Text Available 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 mechanical tests. The morphology of the fracture surfaces was analyzed through scanning electron microscopy (SEM. Moreover, a theoretical model, i.e., Hill’s method, was used to fit the experimental Young’s modulus of the biocomposites. The quasi-static tensile tests revealed that the modulus of UNID composites is significantly higher than that of the neat PLA (i.e., ~40%. Moreover, the tensile strength is slightly higher than that of the neat matrix. The other way around, the stiffness of RANDOM composites is not significantly improved, and the tensile strength decreases in comparison to the neat PLA.

Poly(lactide-co-glycolide) nanofibrous scaffolds chemically coated with gold-nanoparticles as osteoinductive agents for osteogenesis

Science.gov (United States)

Lee, Donghyun; Heo, Dong Nyoung; Lee, Sang Jin; Heo, Min; Kim, Jeongho; Choi, Samjin; Park, Hun-Kuk; Park, Young Guk; Lim, Ho-Nam; Kwon, Il Keun

2018-02-01

Poly(lactide-co-glycolide) (PLGA) is a biocompatible and biodegradable polymer that has been widely used in devices for tissue engineering and drug delivery applications. Gold nanoparticles (GNPs) have also been used as biomaterials and have been found to have a positive effect on bone formation. In this study, we synthesized thiol end-capped PLGA (PLGA-SH) and used it for binding GNPs. This PLGA was processed into a sheet form via electrospinning. GNPs with an approximate size of 30 nm were attached onto the PLGA-SH sheet surfaces (PLGA-GNPs). This membrane was characterized by thermogravimetric analysis, ultraviolet/visible spectrophotometry, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and confocal laser scanning microscopy. Characterization results show that the GNPs are well attached on the PLGA-SH sheet and it is possible to control the GNPs load. Additionally, in-vitro results showed that PLGA-GNPs have good biocompatibility. They were also found to enhance osteogenic differentiation of human adipose derived stem cells. From these results, we have determined that the PLGA-GNP fibers can be useful as materials for bone regeneration and can also potentially serve as drug carriers.

Stochastic phenomena in a fiber Raman amplifier

Energy Technology Data Exchange (ETDEWEB)

Kalashnikov, Vladimir [Aston Institute of Photonic Technologies, Aston University, Birmingham (United Kingdom); Institute of Photonics, Vienna University of Technology (Austria); Sergeyev, Sergey V. [Aston Institute of Photonic Technologies, Aston University, Birmingham (United Kingdom); Ania-Castanon, Juan Diego [Instituto de Optica CSIC, Madrid (Spain); Jacobsen, Gunnar [Acreo, Kista (Sweden); Popov, Sergei [Royal Institute of Technology (KTH), Stockholm (Sweden)

2017-01-15

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 output signals having probability heavily deviated from the Gaussian distribution. (copyright 2016 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Design and Optimization of PLGA-Based Diclofenac Loaded Nanoparticles

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Cooper, Dustin L.; Harirforoosh, Sam

2014-01-01

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

Design and optimization of PLGA-based diclofenac loaded nanoparticles.

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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.

MECHANICAL CHARACTERIZATION AND ANALYSIS OF RANDOMLY DISTRIBUTED SHORT BANANA FIBER REINFORCED EPOXY COMPOSITES

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R. K. Misra

2014-03-01

Full Text Available Short banana fiber reinforced composites have been prepared in laboratory to determine mechanical properties. It has been observed that as soon as the percentage of the banana fiber increases slightly there is a tremendous increase in ultimate tensile strength, % of strain and young modulus of elasticity. Reinforcement of banana fibers in epoxy resin increases stiffness and decreases damping properties of the composites. Therefore, 2.468% banana fiber reinforced composite plate stabilizes early as compared to 7.7135 % banana fiber reinforced composite plate but less stiff as compared to 7.7135 % banana fiber reinforced composite plate

Preparation, Optimization and Activity Evaluation of PLGA/Streptokinase Nanoparticles Using Electrospray

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Nasrin Yaghoobi

2017-04-01

Full Text Available Purpose: PLGA nanoparticles (NPs have been extensively investigated as carriers of different drug molecules to enhance their therapeutic effects or preserve them from the aqueous environment. Streptokinase (SK is an important medicine for thrombotic diseases. Methods: In this study, we used electrospray to encapsulate SK in PLGA NPs and evaluate its activity. This is the first paper which investigates activity of an electrosprayed enzyme. Effect of three input parameters, namely, voltage, internal diameter of needle (nozzle and concentration ratio of polymer to protein on size and size distribution (SD of NPs was evaluated using artificial neural networks (ANNs. Optimizing the SD has been rarely reported so far in electrospray. Results: From the results, to obtain lowest size of nanoparticles, ratio of polymer/enzyme and needle internal diameter (ID should be low. Also, minimum SD was obtainable at high values of voltage. The optimum preparation had mean (SD size, encapsulation efficiency and loading capacity of 37 (12 nm, 90% and 8.2%, respectively. Nearly, 20% of SK was released in the first 30 minutes, followed by cumulative release of 41% during 72 h. Activity of the enzyme was also checked 30 min after preparation and 19.2% activity was shown. Conclusion: Our study showed that electrospraying could be an interesting approach to encapsulate proteins/enzymes in polymeric nanoparticles. However, further works are required to assure maintaining the activity of the enzyme/protein after electrospray.

PLGA nanoparticles prepared by nano-emulsion templating using low-energy methods as efficient nanocarriers for drug delivery across the blood-brain barrier.

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Fornaguera, C; Dols-Perez, A; Calderó, G; García-Celma, M J; Camarasa, J; Solans, C

2015-08-10

Neurodegenerative diseases have an increased prevalence and incidence nowadays, mainly due to aging of the population. In addition, current treatments lack efficacy, mostly due to the presence of the blood-brain barrier (BBB) that limits the penetration of the drugs to the central nervous system. Therefore, novel drug delivery systems are required. Polymeric nanoparticles have been reported to be appropriate for this purpose. Specifically, the use of poly-(lactic-co-glycolic acid) (PLGA) seems to be advantageous due to its biocompatibility and biodegradability that ensure safe therapies. In this work, a novel approximation to develop loperamide-loaded nanoparticles is presented: their preparation by nano-emulsion templating using a low-energy method (the phase inversion composition, PIC, method). This nano-emulsification approach is a simple and very versatile technology, which allows a precise size control and it can be performed at mild process conditions. Drug-loaded PLGA nanoparticles were obtained using safe components by solvent evaporation of template nano-emulsions. Characterization of PLGA nanoparticles was performed, together with the study of the BBB crossing. The in vivo results of measuring the analgesic effect using the hot-plate test evidenced that the designed PLGA loperamide-loaded nanoparticles are able to efficiently cross the BBB, with high crossing efficiencies when their surface is functionalized with an active targeting moiety (a monoclonal antibody against the transferrin receptor). These results, together with the nanoparticle characterization performed here are expected to provide sufficient evidences to end up to clinical trials in the near future. Copyright © 2015 Elsevier B.V. All rights reserved.

PLGA-soya lecithin based micelles for enhanced delivery of methotrexate: Cellular uptake, cytotoxic and pharmacokinetic evidences.

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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.

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

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Gerald Artner

2017-01-01

Full Text Available 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 frequency range of 4 to 6 GHz. The decrease in material anisotropy results in negligible influence on antennas. This is shown by measuring the proposed CFRP as ground plane material for both a narrowband wire monopole antenna for 5.9 GHz and an ultrawideband conical monopole antenna for 1–10 GHz. For comparison, all measurements are repeated with a twill-weave CFRP.

Advances in high power linearly polarized fiber laser and its application

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Zhou, Pu; Huang, Long; Ma, Pengfei; Xu, Jiangming; Su, Rongtao; Wang, Xiaolin

2017-10-01

Fiber lasers are now attracting more and more research interest due to their advantages in efficiency, beam quality and flexible operation. Up to now, most of the high power fiber lasers have random distributed polarization state. Linearlypolarized (LP) fiber lasers, which could find wide application potential in coherent detection, coherent/spectral beam combining, nonlinear frequency conversion, have been a research focus in recent years. In this paper, we will present a general review on the achievements of various kinds of high power linear-polarized fiber laser and its application. The recent progress in our group, including power scaling by using power amplifier with different mechanism, high power linearly polarized fiber laser with diversified properties, and various applications of high power linear-polarized fiber laser, are summarized. We have achieved 100 Watt level random distributed feedback fiber laser, kilowatt level continuous-wave (CW) all-fiber polarization-maintained fiber amplifier, 600 watt level average power picosecond polarization-maintained fiber amplifier and 300 watt level average power femtosecond polarization-maintained fiber amplifier. In addition, high power linearly polarized fiber lasers have been successfully applied in 5 kilowatt level coherent beam combining, structured light field and ultrasonic generation.

Multiscale probabilistic modeling of a crack bridge in glass fiber reinforced concrete

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Rypla R.

2017-06-01

Full Text Available The present paper introduces a probabilistic approach to simulating the crack bridging effects of chopped glass strands in cement-based matrices and compares it to a discrete rigid body spring network model with semi-discrete representation of the chopped strands. The glass strands exhibit random features at various scales, which are taken into account by both models. Fiber strength and interface stress are considered as random variables at the scale of a single fiber bundle while the orientation and position of individual bundles with respect to a crack plane are considered as random variables at the crack bridge scale. At the scale of the whole composite domain, the distribution of fibers and the resulting number of crack-bridging fibers is considered. All the above random effects contribute to the variability of the crack bridge performance and result in size-dependent behavior of a multiply cracked composite.

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.

Nanofibrous poly(lactide-co-glycolide membranes loaded with diamond nanoparticles as promising substrates for bone tissue engineering

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Parizek M

2012-04-01

Full Text Available Martin Parizek1, Timothy EL Douglas2, Katarina Novotna1, Alexander Kromka3, Mariea A Brady4, Andrea Renzing4, Eske Voss4, Marketa Jarosova3, Lukas Palatinus3, Pavel Tesarek5, Pavla Ryparova5, Vera Lisa1, Ana M dos Santos2, Lucie Bacakova11Department of Biomaterials and Tissue Engineering, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 2Polymer Chemistry and Biomaterials Group, Ghent University, Ghent, Belgium; 3Institute of Physics, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 4Department of Oral and Maxillofacial Surgery, University of Kiel, Kiel, Germany; 5Czech Technical University in Prague, Faculty of Civil Engineering, Prague, Czech RepublicBackground: Nanofibrous scaffolds loaded with bioactive nanoparticles are promising materials for bone tissue engineering.Methods: In this study, composite nanofibrous membranes containing a copolymer of L-lactide and glycolide (PLGA and diamond nanoparticles were fabricated by an electrospinning technique. PLGA was dissolved in a mixture of methylene chloride and dimethyl formamide (2:3 at a concentration of 2.3 wt%, and nanodiamond (ND powder was added at a concentration of 0.7 wt% (about 23 wt% in dry PLGA.Results: In the composite scaffolds, the ND particles were either arranged like beads in the central part of the fibers or formed clusters protruding from the fibers. In the PLGA-ND membranes, the fibers were thicker (diameter 270 ± 9 nm than in pure PLGA meshes (diameter 218 ± 4 nm, but the areas of pores among these fibers were smaller than in pure PLGA samples (0.46 ± 0.02 µm2 versus 1.28 ± 0.09 µm2 in pure PLGA samples. The PLGA-ND membranes showed higher mechanical resistance, as demonstrated by rupture tests of load and deflection of rupture probe at failure. Both types of membranes enabled the attachment, spreading, and subsequent proliferation of human osteoblast-like MG-63 cells to a similar extent, although these

Numerical approach of the injection molding process of fiber-reinforced composite with considering fiber orientation

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Nguyen Thi, T. B.; Yokoyama, A.; Ota, K.; Kodama, K.; Yamashita, K.; Isogai, Y.; Furuichi, K.; Nonomura, C.

2014-05-01

One of the most important challenges in the injection molding process of the short-glass fiber/thermoplastic composite parts is being able to predict the fiber orientation, since it controls the mechanical and the physical properties of the final parts. Folgar and Tucker included into the Jeffery equation a diffusive type of term, which introduces a phenomenological coefficient for modeling the randomizing effect of the mechanical interactions between the fibers, to predict the fiber orientation in concentrated suspensions. Their experiments indicated that this coefficient depends on the fiber volume fraction and aspect ratio. However, a definition of the fiber interaction coefficient, which is very necessary in the fiber orientation simulations, hasn't still been proven yet. Consequently, this study proposed a developed fiber interaction model that has been introduced a fiber dynamics simulation in order to obtain a global fiber interaction coefficient. This supposed that the coefficient is a sum function of the fiber concentration, aspect ratio, and angular velocity. The proposed model was incorporated into a computer aided engineering simulation package C-Mold. Short-glass fiber/polyamide-6 composites were produced in the injection molding with the fiber weight concentration of 30 wt.%, 50 wt.%, and 70 wt.%. The physical properties of these composites were examined, and their fiber orientation distributions were measured by micro-computed-tomography equipment μ-CT. The simulation results showed a good agreement with experiment results.

Influence of different stabilizers on the encapsulation of desmopressin acetate into PLGA nanoparticles.

Science.gov (United States)

Primavessy, Daniel; Günday Türeli, Nazende; Schneider, Marc

2017-09-01

To address targeting and bioavailability issues of peptidic drugs like desmopressin, the encapsulation into nanoparticles (NP) has become standard in pharmaceutics. This study investigated the encapsulation of desmopressin into PLGA NP by the use of pharmaceutically common stabilizers as a precursor to future, optional targeting and bioavailability experiments. Polymer dry weights were measured by freeze drying and thermo gravimetric analysis (TGA). Particle sizes (ranging between 105 and 130nm, PDIDoppler-Anemometry (LDA) respectively. Highest loading efficiencies, quantified by RP-HPLC, were achieved with Pluronic F-68 as stabilizer of the inner aqueous phase (1.16±0.07μg desmopressin/mg PLGA) and were significantly higher than coating approaches and approaches without stabilizer (0.74±0.01μg/mg). Optimized nanoformulations are thus in competition with the concentration of commercial non-nanoparticulate desmopressin products. Stability of desmopressin after the process was evaluated by HPLC peak purity analysis (diode array detector) and by mass spectrometry. Desmopressin was shown to remain intact during the whole process; however, despite these very good results the encapsulation efficiency turned out to be a bottle neck and makes the system a challenge for potential applications. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

Ge Zigang; Tian Xianfeng; Heng, Boon Chin; Fan, Victor; Yeo Jinfei; Cao Tong, E-mail: omscaot@nus.edu.s [Stem Cell Laboratory, Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119074 (Singapore)

2009-04-15

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Nanobody conjugated PLGA nanoparticles for active targeting of African Trypanosomiasis.

Science.gov (United States)

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

2015-01-10

Targeted delivery of therapeutics is an alternative approach for the selective treatment of infectious diseases. The surface of African trypanosomes, the causative agents of African trypanosomiasis, is covered by a surface coat consisting of a single variant surface glycoprotein, termed VSG. This coat is recycled by endocytosis at a very high speed, making the trypanosome surface an excellent target for the delivery of trypanocidal drugs. Here, we report the design of a drug nanocarrier based on poly ethylen glycol (PEG) covalently attached (PEGylated) to poly(D,L-lactide-co-glycolide acid) (PLGA) to generate PEGylated PLGA nanoparticles. This nanocarrier was coupled to a single domain heavy chain antibody fragment (nanobody) that specifically recognizes the surface of the protozoan pathogen Trypanosoma brucei. Nanoparticles were loaded with pentamidine, the first-line drug for T. b. gambiense acute infection. An in vitro effectiveness assay showed a 7-fold decrease in the half-inhibitory concentration (IC50) of the formulation relative to free drug. Furthermore, in vivo therapy using a murine model of African trypanosomiasis demonstrated that the formulation cured all infected mice at a 10-fold lower dose than the minimal full curative dose of free pentamidine and 60% of mice at a 100-fold lower dose. This nanocarrier has been designed with components approved for use in humans and loaded with a drug that is currently in use to treat the disease. Moreover, this flexible nanobody-based system can be adapted to load any compound, opening a range of new potential therapies with application to other diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Two-layer membranes of calcium phosphate/collagen/PLGA nanofibres: in vitro biomineralisation and osteogenic differentiation of human mesenchymal stem cells

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Hild, Nora; Schneider, Oliver D.; Mohn, Dirk; Luechinger, Norman A.; Koehler, Fabian M.; Hofmann, Sandra; Vetsch, Jolanda R.; Thimm, Benjamin W.; Müller, Ralph; Stark, Wendelin J.

2011-02-01

The present study evaluates the in vitro biomedical performance of an electrospun, flexible, anisotropic bilayer with one layer containing a collagen to mineral ratio similar to that in bone. The double membrane consists of a poly(lactide-co-glycolide) (PLGA) layer and an amorphous calcium phosphate (a-CaP)/collagen (Col)/PLGA layer. In vitro biomineralisation and a cell culture study with human mesenchymal stem cells (hMSC) were conducted to characterise such membranes for possible application as biomaterials. Nanofibres with different a-CaP/Col/PLGA compositions were synthesised by electrospinning to mimic the actual composition of bone tissue. Immersion in simulated body fluid and in cell culture medium resulted in the deposition of a hydroxyapatite layer. Incubation of hMSC for 4 weeks allowed for assessment of the proliferation and osteogenic differentiation of the cells on both sides of the double membrane. Confocal laser scanning microscopy was used to observe the proper adhesion of the cells. Calcium and collagen content was proven by Alizarin red S and Sirius red assays. Acute cytotoxic effects of the nanoparticles or the chemicals used in the scaffold preparation could be excluded based on viability assays (alamarBlue and alkaline phosphatase activity). The findings suggest possible application of such double membranes is in treatment of bone defects with complex geometries as wound dressing material.The present study evaluates the in vitro biomedical performance of an electrospun, flexible, anisotropic bilayer with one layer containing a collagen to mineral ratio similar to that in bone. The double membrane consists of a poly(lactide-co-glycolide) (PLGA) layer and an amorphous calcium phosphate (a-CaP)/collagen (Col)/PLGA layer. In vitro biomineralisation and a cell culture study with human mesenchymal stem cells (hMSC) were conducted to characterise such membranes for possible application as biomaterials. Nanofibres with different a-CaP/Col/PLGA

[Design and biological evaluation of poly-lactic-co-glycolic acid (PLGA) mesh/collagen-chitosan hybrid scaffold (CCS) as a dermal substitute].

Science.gov (United States)

Wang, Xin-Gang; You, Chuan-Gang; Sun, Hua-Feng; Hu, Xin-Lei; Han, Chun-Mao; Zhang, Li-Ping; Zheng, Yu-Rong; Li, Qi-Yin

2011-02-01

To design and construct a kind of dermal regeneration template with mesh, and to preliminarily evaluate its biological characteristics. PLGA mesh was integrated into CCS with freeze-drying method for constructing PLGA mesh/CCS composite (PCCS). The micromorphologies and mechanical properties among PLGA mesh, CCS, and PCCS were compared. PCCS and CCS was respectively implanted into subcutaneous tissue of SD rats (PCCS and CCS groups, 9 rats in each group). The tissue samples were collected at post operation week (POW) 1, 2, and 4 for histopathological and immunohistochemical observation. Protein levels of CD68, MPO, IL-1beta, IL-10 were examined by Western blot, with expression of gray value. Data were processed with one-way analysis of variance and t test. Three-dimensional porous structure of PCCS was similar to that of CCS. Mechanical property of PLGA mesh and PCCS was respectively (3.07 +/- 0.10), (3.26 +/- 0.15) MPa, and they were higher than that of CCS [(0.42 +/- 0.21) MPa, F = 592.3, P CCS group were observed at POW 4. A large accumulation of macrophages was observed in both groups, especially at POW 2, and more macrophage infiltration was observed in CCS group. The protein level of IL-10 in PCCS group at POW 2 was obviously higher than that in CCS group, while the protein levels of CD68, MPO, IL-1beta were significantly decreased as compared with those in CCS group (with t value from -4.06 to 2.89, P < 0.05 or P < 0.01). PCCS has excellent mechanical property with appropriate three-dimensional porous structure. Meanwhile, it can rapidly induce formation of new tissue and vascularization, and it has a prospect of serving as a dermal substitute.

Strategies for encapsulation of small hydrophilic and amphiphilic drugs in PLGA microspheres: State-of-the-art and challenges

NARCIS (Netherlands)

Ramazani, F.; Chen, Weiluan; van Nostrum, C.F.; Storm, Gerrit; Kiessling, F.; Lammers, Twan Gerardus Gertudis Maria; Hennink, W.E.; Kok, R.J.

2016-01-01

Poly(lactide-co-glycolide) (PLGA) microspheres are efficient delivery systems for controlled release of low molecular weight drugs as well as therapeutic macromolecules. The most common microencapsulation methods are based on emulsification procedures, in which emulsified droplets of polymer and

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

, sucrose and sorbitol as cryoprotectants was evaluated. METHODS: Cryoprotectants were co-encapsulated with insulin into PLGA nanoparticles and lyophilized using an optimized cycle with freezing at -80°C, in liquid nitrogen, or ramped cooling at -40°C. Upon lyophilization, the stability of protein structure...

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.

Alterations of fecal steroid composition induced by changes in dietary fiber consumption.

Science.gov (United States)

Ullrich, I H; Lai, H Y; Vona, L; Reid, R L; Albrink, M J

1981-10-01

The short-term effects of high carbohydrate diets of normal foods either high or low in dietary fiber on fecal steroids and fiber was assessed in eight healthy young men. Each subject consumed in random order for 4 days a diet containing 59 g (high fiber) or 21 g (low fiber) neutral detergent fiber. After a 9-day rest period he consumed the other diet. Analysis of random fecal samples during their usual diet and after 4 days of each experimental diet showed an increased in primary bile acids from less than 4 to 32% of total bile acids, and a decreases of coprostanol from 76% (control diet) or 64% (low fiber diet) to 45% of total neutral sterol after the high fiber diet. Fecal fiber concentration doubled after the high fiber diet. We conclude that 4 days of high fiber diet is sufficient to cause a large increase in primary and decrease in secondary fecal steroids. Such changes have implications for prevention of arteriosclerosis and cancer of the colon.

Computational model of spalling and effective fibers on toughening in fiber reinforced composites at an early stage of crack formation

Directory of Open Access Journals (Sweden)

Chong Wang

Full Text Available This work suggests a computational model that takes account of effective fibers on toughening in FRC at an early stage of crack formation. We derived the distribution of pressure provoked by a random inclined fiber in the matrix and calculated stresses through integrating the pressure and tangent stress along the fiber/matrix interface with the Kelvin's fundamental solution and the Mindlin's complementary solution. The evolution of spalling in the matrix was traced. The percentages of effective fibers were evaluated with variations in strength, interface resistance, diameter and elasticity modulus. The main conclusion is that low elasticity modulus combined high strength of fibers raises dramatically the effective fibers, which would benefit toughening.

Design of a flat-top fiber Bragg filter via quasi-random modulation of the refractive index.

Science.gov (United States)

Derevyanko, Stanislav

2008-10-15

The statistics of the reflection spectrum of a short-correlated disordered fiber Bragg grating are studied. The averaged spectrum appears to be flat inside the bandgap and has significantly suppressed sidelobes compared to the uniform grating of the same bandwidth. This is due to the Anderson localization of the modes of a disordered grating. This observation prompts a new algorithm for designing passband reflection gratings. Using the stochastic invariant imbedding approach it is possible to obtain the probability distribution function for the random reflection coefficient inside the bandgap and obtain both the variance of the averaged reflectivity as well as the distribution of the time delay of the grating.

Positive effects of cell-free porous PLGA implants and early loading exercise on hyaline cartilage regeneration in rabbits.

Science.gov (United States)

Chang, Nai-Jen; Lin, Chih-Chan; Shie, Ming-You; Yeh, Ming-Long; Li, Chien-Feng; Liang, Peir-In; Lee, Kuan-Wei; Shen, Pei-Hsun; Chu, Chih-Jou

2015-12-01

The regeneration of hyaline cartilage remains clinically challenging. Here, we evaluated the therapeutic effects of using cell-free porous poly(lactic-co-glycolic acid) (PLGA) graft implants (PGIs) along with early loading exercise to repair a full-thickness osteochondral defect. Rabbits were randomly allocated to a treadmill exercise (TRE) group or a sedentary (SED) group and were prepared as either a PGI model or an empty defect (ED) model. TRE was performed as a short-term loading exercise; SED was physical inactivity in a free cage. The knees were evaluated at 6 and 12 weeks after surgery. At the end of testing, none of the knees developed synovitis, formed osteophytes, or became infected. Macroscopically, the PGI-TRE group regenerated a smooth articular surface, with transparent new hyaline-like tissue soundly integrated with the neighboring cartilage, but the other groups remained distinct at the margins with fibrous or opaque tissues. In a micro-CT analysis, the synthesized bone volume/tissue volume (BV/TV) was significantly higher in the PGI-TRE group, which also had integrating architecture in the regeneration site. The thickness of the trabecular (subchondral) bone was improved in all groups from 6 to 12 weeks. Histologically, remarkable differences in the cartilage regeneration were visible. At week 6, compared with SED groups, the TRE groups manifested modest inflammatory cells with pro-inflammatory cytokines (i.e., TNF-α and IL-6), improved collagen alignment and higher glycosaminoglycan (GAG) content, particularly in the PGI-TRE group. At week 12, the PGI-TRE group had the best regeneration outcomes, showing the formation of hyaline-like cartilage, the development of columnar rounded chondrocytes that expressed enriched levels of collagen type II and GAG, and functionalized trabecular bone with osteocytes. In summary, the combination of implanting cell-free PLGA and performing an early loading exercise can significantly promote the full

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.

Study of Optical Fiber Sensors for Cryogenic Temperature Measurements.

Science.gov (United States)

De Miguel-Soto, Veronica; Leandro, Daniel; Lopez-Aldaba, Aitor; Beato-López, Juan Jesus; Pérez-Landazábal, José Ignacio; Auguste, Jean-Louis; Jamier, Raphael; Roy, Philippe; Lopez-Amo, Manuel

2017-11-30

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.

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.

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/m 2 ), 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 < 0.001), fasting glucose by 0.17 mmol/L (95% CI: -0.28, -0.06 mmol/L; P = 0.002), and fasting insulin by 15.88 pmol/L (95% CI: -29.05, -2.71 pmol/L; P = 0.02) compared with the effects of placebo treatments. No publication bias was identified. Considerable between-study heterogeneity was observed for most outcomes. Conclusions: Isolated soluble fiber

Accelerated in vitro release testing of implantable PLGA microsphere/PVA hydrogel composite coatings.

Science.gov (United States)

Shen, Jie; Burgess, Diane J

2012-01-17

Dexamethasone loaded poly(lactic-co-glycolic acid) (PLGA) microsphere/PVA hydrogel composites have been investigated as an outer drug-eluting coating for implantable devices such as glucose sensors to counter negative tissue responses to implants. The objective of this study was to develop a discriminatory, accelerated in vitro release testing method for this drug-eluting coating using United States Pharmacopeia (USP) apparatus 4. Polymer degradation and drug release kinetics were investigated under "real-time" and accelerated conditions (i.e. extreme pH, hydro-alcoholic solutions and elevated temperatures). Compared to "real-time" conditions, the initial burst and lag phases were similar using hydro-alcoholic solutions and extreme pH conditions, while the secondary apparent zero-order release phase was slightly accelerated. Elevated temperatures resulted in a significant acceleration of dexamethasone release. The accelerated release data were able to predict "real-time" release when applying the Arrhenius equation. Microsphere batches with faster and slower release profiles were investigated under "real-time" and elevated temperature (60°C) conditions to determine the discriminatory ability of the method. The results demonstrated both the feasibility and the discriminatory ability of this USP apparatus 4 method for in vitro release testing of drug loaded PLGA microsphere/PVA hydrogel composites. This method may be appropriate for similar drug/device combination products and drug delivery systems. Copyright © 2011 Elsevier B.V. All rights reserved.

Fabrication of surfactant-free quercetin-loaded PLGA nanoparticles: evaluation of hepatoprotective efficacy by nuclear scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Ganguly, Soumya; Gaonkar, Raghuvir H. [CSIR-Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division (India); Sinha, Samarendu; Gupta, Amit [Thakurpukur Cancer Centre and Welfare Home Campus, Regional Radiation Medicine Centre (India); Chattopadhyay, Dipankar [University of Calcutta, Department of Polymer Science & Technology, University College of Science & Technology (India); Chattopadhyay, Sankha [Variable Energy Cyclotron Centre, Radiopharmaceuticals Laboratory, Board of Radiation and Isotope Technology (India); Sachdeva, Satbir S. [Radiopharmaceuticals Production (India); Ganguly, Shantanu [Thakurpukur Cancer Centre and Welfare Home Campus, Regional Radiation Medicine Centre (India); Debnath, Mita C., E-mail: mitacd@iicb.res.in, E-mail: mita-chdebnath@yahoo.com [CSIR-Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division (India)

2016-07-15

The purpose of this study was to develop surfactant-free quercetin-loaded PLGA nanoparticles (Qr-NPs) and investigate the hepatoprotective efficacy of the product non-invasively by nuclear scintigraphy. The nanoparticles were prepared using PLGA by dialysis method and ranged in size between 50 and 250 nm with a narrow range of distribution. They were found to arrive at the fenestra of liver sinusoidal epithelium for accumulation. The sizes of nanoparticles (batch S1) were optimal to reach the target and offer enough protection of the hepatocytes degenerated by CCl{sub 4} intoxication as determined by various biochemical and histopathological tests. In vitro studies exhibited the cytotoxic effect of the formulation against HepG2 cell line. The hepatoprotective efficacy of Qr-NPs evaluated non-invasively by nuclear scintigraphic technique using {sup 99m}Tc-labelled sulphur colloid revealed abnormality in liver at the area of decreased uptake in rats of CCl{sub 4}-treated group, which disappeared in Qr-NP-treated group. In dynamic studies with {sup 99m}Tc-mebrofenin, excretion was severely impaired in CCl{sub 4}-treated group but was moderate in drug-treated group, proving the recovery of animals from damage.Graphical Abstract.

Characterization of a PLGA sandwiched cell/fibrin tubular construct and induction of the adipose derived stem cells into smooth muscle cells

International Nuclear Information System (INIS)

Wang Xiaohong; Maekitie, Antti A.; Paloheimo, Kaija-Stiina; Tuomi, Jukka; Paloheimo, Markku; Sui Shaochun; Zhang Qiqing

2011-01-01

A poly(DL-lactic-co-glycolic acid) (PLGA) sandwiched adipose derived stem cell (ADSC)/fibrin tubular construct, fabricated using a step-by-step mold/extraction method, was characterized in this work. The ADSCs were also induced into smooth-muscle-like cells using growth factors such as hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB), transforming growth factor β1 (TGFβ1), and basic fibroblast growth factor (b-FGF). Compared with the non-induced cells, the proliferation ability of induced cells was much smaller. The PLGA sandwiched cell/hydrogel construct was shown to be useful for controlling the cellular microenvironment and cellular behaviors such as growth, migration, proliferation and differentiation. This strategy seems promising in tissue engineering and organ manufacturing.

Characterization of a PLGA sandwiched cell/fibrin tubular construct and induction of the adipose derived stem cells into smooth muscle cells

Energy Technology Data Exchange (ETDEWEB)

Wang Xiaohong, E-mail: wangxiaohong@tsinghua.edu.cn [BIT Research Centre, School of Science and Technology, Aalto University, P.O. Box 15500, 00076 Aalto (Finland); Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Maekitie, Antti A.; Paloheimo, Kaija-Stiina; Tuomi, Jukka; Paloheimo, Markku [BIT Research Centre, School of Science and Technology, Aalto University, P.O. Box 15500, 00076 Aalto (Finland); Sui Shaochun [Key Laboratory for Advanced Materials Processing Technology, Ministry of Education and Center of Organ Manufacturing, Department of Mechanical Engineering, Tsinghua University, Beijing 100084 (China); Zhang Qiqing [Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Key Laboratory of Biomedical Material of Tianjin, Tianjin 300192 (China)

2011-05-10

A poly(DL-lactic-co-glycolic acid) (PLGA) sandwiched adipose derived stem cell (ADSC)/fibrin tubular construct, fabricated using a step-by-step mold/extraction method, was characterized in this work. The ADSCs were also induced into smooth-muscle-like cells using growth factors such as hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB), transforming growth factor {beta}1 (TGF{beta}1), and basic fibroblast growth factor (b-FGF). Compared with the non-induced cells, the proliferation ability of induced cells was much smaller. The PLGA sandwiched cell/hydrogel construct was shown to be useful for controlling the cellular microenvironment and cellular behaviors such as growth, migration, proliferation and differentiation. This strategy seems promising in tissue engineering and organ manufacturing.

Silkworm cocoons inspire models for random fiber and particulate composites

Energy Technology Data Exchange (ETDEWEB)

Fujia, Chen; Porter, David; Vollrath, Fritz [Department of Zoology, University of Oxford, Oxford OX1 3PS (United Kingdom)

2010-10-15

The bioengineering design principles evolved in silkworm cocoons make them ideal natural prototypes and models for structural composites. Cocoons depend for their stiffness and strength on the connectivity of bonding between their constituent materials of silk fibers and sericin binder. Strain-activated mechanisms for loss of bonding connectivity in cocoons can be translated directly into a surprisingly simple yet universal set of physically realistic as well as predictive quantitative structure-property relations for a wide range of technologically important fiber and particulate composite materials.

A Study of Array Direction HDPE Fiber Reinforced Mortar

Science.gov (United States)

Kamsuwan, Trithos

2018-02-01

This paper presents the effect of array direction HDPE fiber using as the reinforced material in cement mortar. The experimental data were created reference to the efficiency of using HDPE fiber reinforced on the tensile properties of cement mortar with different high drawn ratio of HDPE fibers. The fiber with the different drawn ratio 25x (d25 with E xx), and 35x (d35 with E xx) fiber volume fraction (0%, 1.0%, 1.5%) and fiber length 20 mm. were used to compare between random direction and array direction of HDPE fibers and the stress - strain displacement relationship behavior of HDPE short fiber reinforced cement mortar were investigated. It was found that the array direction with HDPE fibers show more improved in tensile strength and toughness when reinforced in cement mortar.

Random photonic crystal optical memory

International Nuclear Information System (INIS)

Wirth Lima Jr, A; Sombra, A S B

2012-01-01

Currently, optical cross-connects working on wavelength division multiplexing systems are based on optical fiber delay lines buffering. We designed and analyzed a novel photonic crystal optical memory, which replaces the fiber delay lines of the current optical cross-connect buffer. Optical buffering systems based on random photonic crystal optical memory have similar behavior to the electronic buffering systems based on electronic RAM memory. In this paper, we show that OXCs working with optical buffering based on random photonic crystal optical memories provides better performance than the current optical cross-connects. (paper)

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

Science.gov (United States)

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

2013-04-01

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

Antibacterial activity on electrospun poly(lactide-co-glycolide) based membranes via Magainin II grafting

Energy Technology Data Exchange (ETDEWEB)

Yüksel, Emre; Karakeçili, Ayşe, E-mail: akarakecili@eng.ankara.edu.tr

2014-12-01

An antimicrobial peptide (AMP), Magainin II (Mag II) was covalently immobilized on poly(lactide-co-glycolide) (PLGA) and PLGA/gelatin electrospun fibrous membranes. The surface immobilization was characterized by X-ray Photoelectron Spectroscopy (XPS). Scanning Electron Microscopy (SEM) and Atomic Force Microscopy studies showed that the surface morphology of the fibers at micron scale was not affected by the immobilization process. The antibacterial activity of the bound Mag II was tested against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Bacterial adhesion tests, SEM and confocal analyses revealed that the attachment and survival of bacteria were inhibited on Mag II functionalized membranes. AMP immobilization strategy was introduced as a new perspective for the modulation of antibacterial properties on PLGA based materials prepared by electrospinning. - Highlights: • PLGA and PLGA/gelatin fibrous membranes were prepared by electrospinning. • Antimicrobial peptide Mag II was successfully immobilized on PLGA based membranes. • The antibacterial activity was tested against E. coli and S. aureus. • Bacterial adhesion was inhibited on Mag II functionalized membranes.

Neuronal uptake and neuroprotective effect of curcumin-loaded PLGA nanoparticles on the human SK-N-SH cell line.

Science.gov (United States)

Doggui, Sihem; Sahni, Jasjeet Kaur; Arseneault, Madeleine; Dao, Lé; Ramassamy, Charles

2012-01-01

Curcumin, a natural polyphenolic pigment present in the spice turmeric (Curcuma longa), is known to possess a pleiotropic activity such as antioxidant, anti-inflammatory, and anti-amyloid-β activities. However, these benefits of curcumin are limited by its poor aqueous solubility and oral bioavailability. In the present study, a polymer-based nanoparticle approach has been utilized to deliver drugs to neuronal cells. Curcumin was encapsulated in biodegradable poly (lactide-co-glycolide) (PLGA) based-nanoparticulate formulation (Nps-Cur). Dynamic laser light scattering and transmission electronic microscopy analysis indicated a particle diameter ranging from 80 to 120 nm. The entrapment efficiency was 31% with 15% drug-loading. In vitro release kinetics of curcumin from Nps-Cur revealed a biphasic pattern with an initial exponential phase followed by a slow release phase. Cellular internalization of Nps-Cur was confirmed by fluorescence and confocal microscopy with a wide distribution of the fluorescence in the cytoplasm and within the nucleus. The prepared nanoformulation was characterized for cellular toxicity and biological activity. Cytotoxicity assays showed that void PLGA-nanoparticles (Nps) and curcumin-loaded PLGA nanoparticles (Nps-Cur) were nontoxic to human neuroblastoma SK-N-SH cells. Moreover, Nps-Cur was able to protect SK-N-SH cells against H2O2 and prevent the elevation of reactive oxygen species and the consumption of glutathione induced by H2O2. Interestingly, Nps-Cur was also able to prevent the induction of the redox-sensitive transcription factor Nrf2 in the presence of H2O2. Taken together, these results suggest that Nps-Cur could be a promising drug delivery strategy to protect neurons against oxidative damage as observed in Alzheimer's disease.

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.

Boron containing poly-(lactide-co-glycolide) (PLGA) scaffolds for bone tissue engineering

International Nuclear Information System (INIS)

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; Şahin, Fikrettin

2014-01-01

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

Strength behaviour of kerosene coated coir fiber-reinforced expansive soil

OpenAIRE

Ramasubbarao Godavarthi Venkata

2014-01-01

Coir fibers are extracted from the husks surrounding the coconut. Coir fibers can be effectively used as reinforcing material but it has less durability and hence coir fiber coated with kerosene is used as reinforcement in the present study. The objective of the present investigation is to study the strength behavior of expansive soil reinforced with 5mm long randomly distributed kerosene coated coir fibers in 0% (unreinforced), 0.5%, 1% and 1.5% by dry wei...

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.

Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis

International Nuclear Information System (INIS)

Pillai, Rajeev Raghavan; Rabinovich, Monica; Gonsalves, Kenneth E; Somayaji, Shankari N; Hudson, Michael C

2008-01-01

The goal of this investigation is to develop poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of antibiotics such as nafcillin to osteoblasts. This is important in order to treat Staphylococcus aureus-mediated osteomyelitis. The latter is often chronic and highly resistant to antibiotics. Nafcillin (a penicillinase-resistant penicillin)-loaded nanoparticles were prepared by a single emulsion/solvent evaporation method. In vitro drug release studies were conducted in an incubator shaker at 37 deg. C in phosphate buffer saline. Drug loading and release were determined by UV-Vis spectroscopy. A viability study was conducted in S. aureus-infected mouse osteoblasts. In vitro release study showed an initial burst release and a second phase of slow release. Following 24 and 48 h of incubation, all formulations of nanoparticles loaded with nafcillin either killed or significantly reduced all of the intracellular bacteria. Our data demonstrate that effective killing of intracellular S. aureus is possible by treating the infected osteoblasts with nanoparticles loaded with nafcillin

Nafcillin-loaded PLGA nanoparticles for treatment of osteomyelitis

Energy Technology Data Exchange (ETDEWEB)

Pillai, Rajeev Raghavan; Rabinovich, Monica; Gonsalves, Kenneth E [Polymer Nanotechnology Laboratory at Center for Optoelectronics and Department of Chemistry, University of North Carolina, Charlotte, NC 28223 (United States); Somayaji, Shankari N; Hudson, Michael C [Department of Biology, University of North Carolina, Charlotte, NC 28223 (United States)], E-mail: kegonsal@uncc.edu

2008-09-01

The goal of this investigation is to develop poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of antibiotics such as nafcillin to osteoblasts. This is important in order to treat Staphylococcus aureus-mediated osteomyelitis. The latter is often chronic and highly resistant to antibiotics. Nafcillin (a penicillinase-resistant penicillin)-loaded nanoparticles were prepared by a single emulsion/solvent evaporation method. In vitro drug release studies were conducted in an incubator shaker at 37 deg. C in phosphate buffer saline. Drug loading and release were determined by UV-Vis spectroscopy. A viability study was conducted in S. aureus-infected mouse osteoblasts. In vitro release study showed an initial burst release and a second phase of slow release. Following 24 and 48 h of incubation, all formulations of nanoparticles loaded with nafcillin either killed or significantly reduced all of the intracellular bacteria. Our data demonstrate that effective killing of intracellular S. aureus is possible by treating the infected osteoblasts with nanoparticles loaded with nafcillin.

Phytoestrogens/insoluble fibers and colonic estrogen receptor β: Randomized, double-blind, placebo-controlled study

Science.gov (United States)

Principi, Mariabeatrice; Di Leo, Alfredo; Pricci, Maria; Scavo, Maria Principia; Guido, Raffaella; Tanzi, Sabina; Piscitelli, Domenico; Pisani, Antonio; Ierardi, Enzo; Comelli, Maria Cristina; Barone, Michele

2013-01-01

AIM: To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS: A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS: No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69 vs 37.708 ± 5.31, P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13, P = 0.04), mRNA (2.278 ± 1.19 vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67, P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06 vs 0.532 ± 0.11, P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION: The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study. PMID:23885143

Preparation and In Vitro/Ex Vivo Evaluation of Moxifloxacin-Loaded PLGA Nanosuspensions for Ophthalmic Application.

Science.gov (United States)

Mudgil, Meetali; Pawar, Pravin K

2013-01-01

The aim of the present investigation was to prepare a colloidal ophthalmic formulation to improve the residence time of moxifloxacin. Moxifloxacin-loaded poly(dl-lactide-co-glycolide) (PLGA) nanosuspensions were prepared by using the solvent evaporation technique. The nanosuspensions were characterised physically by using different techniques like particle size, zeta potential, FTIR, DSC, and XRD analysis. In vitro and ex vivo studies of nanosuspensions were carried out using a modified USP dissolution apparatus and all-glass Franz diffusion cells, respectively. The antibacterial activities of the nanosuspension and marketed formulations were performed against S. aureus and P. aeroginosa. The moxifloxacin-loaded PLGA nanosuspensions showed uniform particle size, ranging between 164-490 nm with negative zeta potential for all batches. The percentage entrapment efficiency of the drug-loaded nano-suspension was found to be between 84.09 to 92.05%. In vitro drug release studies suggest that all of the formulations showed extended drug release profiles and follow Korsemeyer-Peppas release kinetics. In vitro corneal permeability was found to be comparable with that of the marketed formulation across isolated goat cornea, indicating the suitability of the nanosuspension formulation in the ophthalmic delivery of moxifloxacin. The optimised nano-suspension was found to be more active against S. aureus and P. aeruginosa compared to the marketed eye drops.

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

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.

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.

Fiber optic coherent laser radar 3d vision system

International Nuclear Information System (INIS)

Sebastian, R.L.; Clark, R.B.; Simonson, D.L.

1994-01-01

Recent advances in fiber optic component technology and digital processing components have enabled the development of a new 3D vision system based upon a fiber optic FMCW coherent laser radar. The approach includes a compact scanner with no moving parts capable of randomly addressing all pixels. The system maintains the immunity to lighting and surface shading conditions which is characteristic of coherent laser radar. The random pixel addressability allows concentration of scanning and processing on the active areas of a scene, as is done by the human eye-brain system

In vitro and in vivo evaluation of poly(L-lactide-co glycolide)( PLGA) micro bubbles as a contrast agent

International Nuclear Information System (INIS)

Cui, W.; Bei, J.; Wang, S.; Zhao, Y.; Zhi, G.

2005-01-01

To achieve reliable and reproducible myocardial opacification after intravenous administration of echocardiographic contrast agents, this study was performed to fabricate a kind of poly(L-lactide-co-glycolide) (PLGA) micro bubbles-based contrast agent with a modified double emulsion method which incorporates and later sublimes po rogen, leaving voids capable of being filled with gas in their places. The morphology and size distribution of the micro bubbles were investigated. The porous inner structure formed in the micro bubble contrast agents were further proved by con focal laser scanning microscope (CLSM). All the results satisfied the requirements of ideal contrast agents. Acoustic measurement set-up detected the excellent scatter ability of the PLGA (70/30) micro bubbles. It demonstrated this kind of polymer-shell contrast agents could achieve efficient left ventricular opacification and the improved delineation of left ventricular endocardial borders. Especially the safe and successful myocardial opacification in close-chest dogs were observed

High-resolution direct 3D printed PLGA scaffolds: print and shrink

International Nuclear Information System (INIS)

Chia, Helena N; Wu, Benjamin M

2015-01-01

Direct three-dimensional printing (3DP) produces the final part composed of the powder and binder used in fabrication. An advantage of direct 3DP is control over both the microarchitecture and macroarchitecture. Prints which use porogen incorporated in the powder result in high pore interconnectivity, uniform porosity, and defined pore size after leaching. The main limitations of direct 3DP for synthetic polymers are the use of organic solvents which can dissolve polymers used in most printheads and limited resolution due to unavoidable spreading of the binder droplet after contact with the powder. This study describes a materials processing strategy to eliminate the use of organic solvent during the printing process and to improve 3DP resolution by shrinking with a non-solvent plasticizer. Briefly, poly(lactic-co-glycolic acid) (PLGA) powder was prepared by emulsion solvent evaporation to form polymer microparticles. The printing powder was composed of polymer microparticles dry mixed with sucrose particles. After printing with a water-based liquid binder, the polymer microparticles were fused together to form a network by solvent vapor in an enclosed vessel. The sucrose is removed by leaching and the resulting scaffold is placed in a solution of methanol. The methanol acts as a non-solvent plasticizer and allows for polymer chain rearrangement and efficient packing of polymer chains. The resulting volumetric shrinkage is ∼80% at 90% methanol. A complex shape (honey-comb) was designed, printed, and shrunken to demonstrate isotropic shrinking with the ability to reach a final resolution of ∼400 μm. The effect of type of alcohol (i.e. methanol or ethanol), concentration of alcohol, and temperature on volumetric shrinking was studied. This study presents a novel materials processing strategy to overcome the main limitations of direct 3DP to produce high resolution PLGA scaffolds. (paper)

High-resolution direct 3D printed PLGA scaffolds: print and shrink.

Science.gov (United States)

Chia, Helena N; Wu, Benjamin M

2014-12-17

Direct three-dimensional printing (3DP) produces the final part composed of the powder and binder used in fabrication. An advantage of direct 3DP is control over both the microarchitecture and macroarchitecture. Prints which use porogen incorporated in the powder result in high pore interconnectivity, uniform porosity, and defined pore size after leaching. The main limitations of direct 3DP for synthetic polymers are the use of organic solvents which can dissolve polymers used in most printheads and limited resolution due to unavoidable spreading of the binder droplet after contact with the powder. This study describes a materials processing strategy to eliminate the use of organic solvent during the printing process and to improve 3DP resolution by shrinking with a non-solvent plasticizer. Briefly, poly(lactic-co-glycolic acid) (PLGA) powder was prepared by emulsion solvent evaporation to form polymer microparticles. The printing powder was composed of polymer microparticles dry mixed with sucrose particles. After printing with a water-based liquid binder, the polymer microparticles were fused together to form a network by solvent vapor in an enclosed vessel. The sucrose is removed by leaching and the resulting scaffold is placed in a solution of methanol. The methanol acts as a non-solvent plasticizer and allows for polymer chain rearrangement and efficient packing of polymer chains. The resulting volumetric shrinkage is ∼80% at 90% methanol. A complex shape (honey-comb) was designed, printed, and shrunken to demonstrate isotropic shrinking with the ability to reach a final resolution of ∼400 μm. The effect of type of alcohol (i.e. methanol or ethanol), concentration of alcohol, and temperature on volumetric shrinking was studied. This study presents a novel materials processing strategy to overcome the main limitations of direct 3DP to produce high resolution PLGA scaffolds.

Preparation and In Vitro/Ex Vivo Evaluation of Moxifloxacin-Loaded PLGA Nanosuspensions for Ophthalmic Application

OpenAIRE

MUDGIL, Meetali; PAWAR, Pravin

2013-01-01

The aim of the present investigation was to prepare a colloidal ophthalmic formulation to improve the residence time of moxifloxacin. Moxifloxacin-loaded poly(dl-lactide-co-glycolide) (PLGA) nanosuspensions were prepared by using the solvent evaporation technique. The nanosuspensions were characterised physically by using different techniques like particle size, zeta potential, FTIR, DSC, and XRD analysis. In vitro and ex vivo studies of nanosuspensions were carried out using a modified USP d...

Effect of fiber extensibility on the fracture toughness of short fiber or brittle matrix composites

International Nuclear Information System (INIS)

Jain, L.K.; Wetherhold, R.C.

1992-01-01

A micromechanical model based on probabilistic principles is proposed to determine the effective fracture toughness increment and the bridging stress-crack opening displacement relationship for brittle matrix composites reinforced with short, poorly bonded fibers. Emphasis is placed on studying the effect of fiber extensibility on the bridging stress and the bridging fracture energy, and to determine its importance in cementitious matrix composites. Since the fibers may not be in an ideal aligned or random state, the analysis is placed in sufficiently general terms to consider any prescribable fiber orientation distribution. The model incorporates the snubbing effect observed during pull-out of fibers inclined at an angle to the crack face normal. In addition, the model allows the fibers to break; any fiber whose load meets or exceeds a single-valued failure stress will fracture rather than pull out. The crack bridging results may be expressed as the sum of results for inextensible fibers and an additional term due to fiber extensibility. An exact analysis is given which gives the steady-state bridging toughness G directly, but presents a non-linear problem for the bridging stress-crack opening (σ b -γ) relationship. An approximate analysis is then presented which gives both G and σ b -γ directly. To illustrate the effect extensibility on bridging stress and fracture energy increment due to bridging fibers, a comparison with the inextensible fiber case is provided. It is found that effect of extensibility on fracture energy is negligible for common materials systems. However extensibility may have a significant effect on the bridging stress-crack opening relationship. The effect of other physical and material parameters such as fiber length, fiber orientation and snubbing friction coefficient is also studied. 28 refs., 9 figs., 1 tab

Ebola Vaccination Using a DNA Vaccine Coated on PLGA-PLL/γPGA Nanoparticles Administered Using a Microneedle Patch.

Science.gov (United States)

Yang, Hung-Wei; Ye, Ling; Guo, Xin Dong; Yang, Chinglai; Compans, Richard W; Prausnitz, Mark R

2017-01-01

Ebola DNA vaccine is incorporated into PLGA-PLL/γPGA nanoparticles and administered to skin using a microneedle (MN) patch. The nanoparticle delivery system increases vaccine thermostability and immunogenicity compared to free vaccine. Vaccination by MN patch produces stronger immune responses than intramuscular administration. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polarization chaos and random bit generation in nonlinear fiber optics induced by a time-delayed counter-propagating feedback loop.

Science.gov (United States)

Morosi, J; Berti, N; Akrout, A; Picozzi, A; Guasoni, M; Fatome, J

2018-01-22

In this manuscript, we experimentally and numerically investigate the chaotic dynamics of the state-of-polarization in a nonlinear optical fiber due to the cross-interaction between an incident signal and its intense backward replica generated at the fiber-end through an amplified reflective delayed loop. Thanks to the cross-polarization interaction between the two-delayed counter-propagating waves, the output polarization exhibits fast temporal chaotic dynamics, which enable a powerful scrambling process with moving speeds up to 600-krad/s. The performance of this all-optical scrambler was then evaluated on a 10-Gbit/s On/Off Keying telecom signal achieving an error-free transmission. We also describe how these temporal and chaotic polarization fluctuations can be exploited as an all-optical random number generator. To this aim, a billion-bit sequence was experimentally generated and successfully confronted to the dieharder benchmarking statistic tools. Our experimental analysis are supported by numerical simulations based on the resolution of counter-propagating coupled nonlinear propagation equations that confirm the observed behaviors.

Assessment of the mechanical properties of sisal fiber-reinforced silty clay using triaxial shear tests.

Science.gov (United States)

Wu, Yankai; Li, Yanbin; Niu, Bin

2014-01-01

Fiber reinforcement is widely used in construction engineering to improve the mechanical properties of soil because it increases the soil's strength and improves the soil's mechanical properties. However, the mechanical properties of fiber-reinforced soils remain controversial. The present study investigated the mechanical properties of silty clay reinforced with discrete, randomly distributed sisal fibers using triaxial shear tests. The sisal fibers were cut to different lengths, randomly mixed with silty clay in varying percentages, and compacted to the maximum dry density at the optimum moisture content. The results indicate that with a fiber length of 10 mm and content of 1.0%, sisal fiber-reinforced silty clay is 20% stronger than nonreinforced silty clay. The fiber-reinforced silty clay exhibited crack fracture and surface shear fracture failure modes, implying that sisal fiber is a good earth reinforcement material with potential applications in civil engineering, dam foundation, roadbed engineering, and ground treatment.

Assessment of the Mechanical Properties of Sisal Fiber-Reinforced Silty Clay Using Triaxial Shear Tests

Directory of Open Access Journals (Sweden)

Yankai Wu

2014-01-01

Full Text Available Fiber reinforcement is widely used in construction engineering to improve the mechanical properties of soil because it increases the soil’s strength and improves the soil’s mechanical properties. However, the mechanical properties of fiber-reinforced soils remain controversial. The present study investigated the mechanical properties of silty clay reinforced with discrete, randomly distributed sisal fibers using triaxial shear tests. The sisal fibers were cut to different lengths, randomly mixed with silty clay in varying percentages, and compacted to the maximum dry density at the optimum moisture content. The results indicate that with a fiber length of 10 mm and content of 1.0%, sisal fiber-reinforced silty clay is 20% stronger than nonreinforced silty clay. The fiber-reinforced silty clay exhibited crack fracture and surface shear fracture failure modes, implying that sisal fiber is a good earth reinforcement material with potential applications in civil engineering, dam foundation, roadbed engineering, and ground treatment.

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.

Modeling of Thermal Phase Noise in a Solid Core Photonic Crystal Fiber-Optic Gyroscope.

Science.gov (United States)

Song, Ningfang; Ma, Kun; Jin, Jing; Teng, Fei; Cai, Wei

2017-10-26

A theoretical model of the thermal phase noise in a square-wave modulated solid core photonic crystal fiber-optic gyroscope has been established, and then verified by measurements. The results demonstrate a good agreement between theory and experiment. The contribution of the thermal phase noise to the random walk coefficient of the gyroscope is derived. A fiber coil with 2.8 km length is used in the experimental solid core photonic crystal fiber-optic gyroscope, showing a random walk coefficient of 9.25 × 10 -5 deg/√h.

Localised controlled release of simvastatin from porous chitosan–gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application

Energy Technology Data Exchange (ETDEWEB)

Gentile, Piergiorgio [Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin (Italy); School of Clinical Dentistry, University of Sheffield, 19 Claremont Crescent, Sheffield (United Kingdom); Nandagiri, Vijay Kumar [Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin (Italy); School of Pharmacy, Royal College of Surgeons in Ireland, 123, St. Stephen Green, Dublin 2 (Ireland); Daly, Jacqueline [Division of Biology, Department of Anatomy, Royal College of Surgeons in Ireland, 123, St. Stephen Green, Dublin 2 (Ireland); Chiono, Valeria; Mattu, Clara; Tonda-Turo, Chiara; Ciardelli, Gianluca [Department of Mechanical and Aerospace Engineering, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Turin (Italy); Ramtoola, Zebunnissa, E-mail: zramtoola@rcsi.ie [School of Pharmacy, Royal College of Surgeons in Ireland, 123, St. Stephen Green, Dublin 2 (Ireland)

2016-02-01

Localised controlled release of simvastatin from porous freeze-dried chitosan–gelatin (CH–G) scaffolds was investigated by incorporating simvastatin loaded poly-(DL-lactide-co-glycolide) acid (PLGA) microparticles (MSIMs) into the scaffolds. MSIMs at 10% w/w simvastatin loading were prepared using a single emulsion-solvent evaporation method. The MSIM optimal amount to be incorporated into the scaffolds was selected by analysing the effect of embedding increasing amounts of blank PLGA microparticles (BL-MPs) on the scaffold physical properties and on the in vitro cell viability using a clonal human osteoblastic cell line (hFOB). Increasing the BL-MP content from 0% to 33.3% w/w showed a significant decrease in swelling degree (from 1245 ± 56% to 570 ± 35%). Scaffold pore size and distribution changed significantly as a function of BL-MP loading. Compressive modulus of scaffolds increased with increasing BL-MP amount up to 16.6% w/w (23.0 ± 1.0 kPa). No significant difference in cell viability was observed with increasing BL-MP loading. Based on these results, a content of 16.6% w/w MSIM particles was incorporated successfully in CH–G scaffolds, showing a controlled localised release of simvastatin able to influence the hFOB cell proliferation and the osteoblastic differentiation after 11 days. - Highlights: • Simvastatin loaded PLGA microparticle engrafted porous CH–G scaffolds were produced. • The microparticle optimal amount to be incorporated into the scaffolds was studied. • Physical properties of scaffolds changed as a function of microparticle loading. • The level of simvastatin released enhanced cell proliferation and mineralisation.

Localised controlled release of simvastatin from porous chitosan–gelatin scaffolds engrafted with simvastatin loaded PLGA-microparticles for bone tissue engineering application

International Nuclear Information System (INIS)

Gentile, Piergiorgio; Nandagiri, Vijay Kumar; Daly, Jacqueline; Chiono, Valeria; Mattu, Clara; Tonda-Turo, Chiara; Ciardelli, Gianluca; Ramtoola, Zebunnissa

2016-01-01

Localised controlled release of simvastatin from porous freeze-dried chitosan–gelatin (CH–G) scaffolds was investigated by incorporating simvastatin loaded poly-(DL-lactide-co-glycolide) acid (PLGA) microparticles (MSIMs) into the scaffolds. MSIMs at 10% w/w simvastatin loading were prepared using a single emulsion-solvent evaporation method. The MSIM optimal amount to be incorporated into the scaffolds was selected by analysing the effect of embedding increasing amounts of blank PLGA microparticles (BL-MPs) on the scaffold physical properties and on the in vitro cell viability using a clonal human osteoblastic cell line (hFOB). Increasing the BL-MP content from 0% to 33.3% w/w showed a significant decrease in swelling degree (from 1245 ± 56% to 570 ± 35%). Scaffold pore size and distribution changed significantly as a function of BL-MP loading. Compressive modulus of scaffolds increased with increasing BL-MP amount up to 16.6% w/w (23.0 ± 1.0 kPa). No significant difference in cell viability was observed with increasing BL-MP loading. Based on these results, a content of 16.6% w/w MSIM particles was incorporated successfully in CH–G scaffolds, showing a controlled localised release of simvastatin able to influence the hFOB cell proliferation and the osteoblastic differentiation after 11 days. - Highlights: • Simvastatin loaded PLGA microparticle engrafted porous CH–G scaffolds were produced. • The microparticle optimal amount to be incorporated into the scaffolds was studied. • Physical properties of scaffolds changed as a function of microparticle loading. • The level of simvastatin released enhanced cell proliferation and mineralisation.

Efficacy of rhBMP-2 loaded PCL/PLGA/β-TCP guided bone regeneration membrane fabricated by 3D printing technology for reconstruction of calvaria defects in rabbit

International Nuclear Information System (INIS)

Shim, Jin-Hyung; Jeong, Chang-Mo; Huh, Jung-Bo; Jang, Jinah; Jeong, Sung-In; Cho, Dong-Woo; Yoon, Min-Chul

2014-01-01

We successfully fabricated a three-dimensional (3D) printing-based PCL/PLGA/β-TCP guided bone regeneration (GBR) membrane that slowly released rhBMP-2. To impregnate the GBR membrane with intact rhBMP-2, collagen solution encapsulating rhBMP-2 (5 µg ml −1 ) was infused into pores of a PCL/PLGA/β-TCP membrane constructed using a 3D printing system with four dispensing heads. In a release profile test, sustained release of rhBMP-2 was observed for up to 28 d. To investigate the efficacy of the GBR membrane on bone regeneration, PCL/PLGA/β-TCP membranes with or without rhBMP-2 were implanted in an 8 mm calvaria defect of rabbits. Bone formation was evaluated at weeks 4 and 8 histologically and histomorphometrically. A space making ability of the GBR membrane was successfully maintained in both groups, and significantly more new bone was formed at post-implantation weeks 4 and 8 by rhBMP-2 loaded GBR membranes. Interestingly, implantation with rhBMP-2 loaded GBR membranes led to almost entire healing of calvaria defects within 8 weeks. (paper)

Study of the Effect of Reinforced Glass Fibers on Fatigue Properties for Composite Materials

Directory of Open Access Journals (Sweden)

Mohamed G. Hamad

2013-05-01

Full Text Available This  research  included  the  study of  the effect  of  reinforced  glass fibers  on  fatigue  properties  for composite materials. Polyester  resin  is used  as  connective  material(matrix in two types  of  glass  fibers  for reinforced. The  first  type  is regular  glass fibers  (woven  roving with the  directional(0-90, the second  is  glass  fibers  with  the  random  direction. The first type is the panels with regular reinforced (0-90, and with number of layer (1,2.The  second  type  is  the  panels with random  reinforced  and  with  number  of  layers (1,2. The  results  and  the  laboratory  examinations  for  the samples  reinforce  with  fibers  have  manifested (0-90  that there  is  a decrease  in the number  of  cycles  to the  fatigue  limit  when  the  number  of  reinforce  layers  have  increased . And  an elasticity of this  type  of  samples  are decreased  by  increasing  the number  of  reinforced  layers  with  fiber  .We  find  the  random  reinforced  number  of  fatigue  cycles  for the samples  with  two  layers  of  random  reinforced  are  decreased  more  than the samples  with  one  layer of random  reinforced .

Theoretical and experimental study of the effect of fiber heads on the mechanical properties of non-continuous basalt fiber reinforced composites

Directory of Open Access Journals (Sweden)

2007-02-01

Full Text Available The effect of basalt fibers, produced by the Junkers technology and used as reinforcement in polymer composites, was modeled on the properties of composites, adapting the statistical fiber mat model of Poisson type. The random distribution was approximated by so-called effective spheres that act as defect sites in composites, reducing their strength. The role of fiber heads in strength reduction and the corresponding failure modes were analyzed theoretically using a model and by experiments performed on specimens containing a single fiber head located at different distances from the crack initiation. The applicability of the model was proven both experimentally and by finite element analysis. Based on all these investigations, the effective cross section reduction, and hence the strength reduction (predicted by the model caused by the presence of fiber heads was proven.

Optimization of ciprofloxacin complex loaded PLGA nanoparticles for pulmonary treatment of cystic fibrosis infections: Design of experiments approach.

Science.gov (United States)

Günday Türeli, Nazende; Türeli, Akif Emre; Schneider, Marc

2016-12-30

Design of Experiments (DoE) is a powerful tool for systematic evaluation of process parameters' effect on nanoparticle (NP) quality with minimum number of experiments. DoE was employed for optimization of ciprofloxacin loaded PLGA NPs for pulmonary delivery against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lungs. Since the biofilm produced by bacteria was shown to be a complicated 3D barrier with heterogeneous meshes ranging from 100nm to 500nm, nanoformulations small enough to travel through those channels were assigned as target quality. Nanoprecipitation was realized utilizing MicroJet Reactor (MJR) technology based on impinging jets principle. Effect of MJR parameters flow rate, temperature and gas pressure on particle size and PDI was investigated using Box-Behnken design. The relationship between process parameters and particle quality was demonstrated by constructed fit functions (R 2 =0.9934 p65%. Response surface plots provided experimental data-based understanding of MJR parameters' effect, thus NP quality. Presented work enables ciprofloxacin loaded PLGA nanoparticle preparations with pre-defined quality to fulfill the requirements of local drug delivery under CF disease conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

A bFGF-releasing silk/PLGA-based biohybrid scaffold for ligament/tendon tissue engineering using mesenchymal progenitor cells.

Science.gov (United States)

Sahoo, Sambit; Toh, Siew Lok; Goh, James C H

2010-04-01

An ideal scaffold that provides a combination of suitable mechanical properties along with biological signals is required for successful ligament/tendon regeneration in mesenchymal stem cell-based tissue engineering strategies. Among the various fibre-based scaffolds that have been used, hybrid fibrous scaffolds comprising both microfibres and nanofibres have been recently shown to be particularly promising. This study developed a biohybrid fibrous scaffold system by coating bioactive bFGF-releasing ultrafine PLGA fibres over mechanically robust slowly-degrading degummed knitted microfibrous silk scaffolds. On the ECM-like biomimetic architecture of ultrafine fibres, sustained release of bFGF mimicked the ECM in function, initially stimulating mesenchymal progenitor cell (MPC) proliferation, and subsequently, their tenogeneic differentiation. The biohybrid scaffold system not only facilitated MPC attachment and promoted cell proliferation, with cells growing both on ultrafine PLGA fibres and silk microfibres, but also stimulated tenogeneic differentiation of seeded MPCs. Upregulated gene expression of ligament/tendon-specific ECM proteins and increased collagen production likely contributed to enhancing mechanical properties of the constructs, generating a ligament/tendon analogue that has the potential to be used to repair injured ligaments/tendons. Copyright 2010 Elsevier Ltd. All rights reserved.

Efficacy of high-fiber diets in the management of type 2 diabetes mellitus.

Science.gov (United States)

Wolfram, Taylor; Ismail-Beigi, Faramarz

2011-01-01

To review outcomes of randomized controlled clinical trials exploring the efficacy of different types of diets containing various amounts of fiber in the management of type 2 diabetes mellitus. We searched PubMed, Medline, and Google Scholar for published data from the past decade (through December 2009) on dietary patterns and risk of type 2 diabetes mellitus. Only randomized controlled trials investigating the effect of whole grains, fiber, or vegetarian diets on type 2 diabetes were included. Search criteria included whole grain, fruit, vegetable, fiber, and meat intake regarding insulin sensitivity and glycemic responses in healthy, prediabetic, and diabetic persons. A total of 14 randomized clinical trials were included. Addition of insoluble or soluble fiber to meals, increased consumption of diets rich in whole grains and vegetables, and vegan diets improve glucose metabolism and increase insulin sensitivity. The greatest improvement in blood lipids, body weight, and hemoglobin A(1c) level occurred in participants following low-fat, plant-based diets. Increased consumption of vegetables, whole grains, and soluble and insoluble fiber is associated with improved glucose metabolism in both diabetic and nondiabetic individuals. Improvements in insulin sensitivity and glucose homeostasis were more evident in participants following a plant-based diet compared with other commonly used diets.

PLGA nano/microparticles loaded with cresyl violet as a tracer for drug delivery: Characterization and in-situ hyperspectral fluorescence and 2-photon localization

Energy Technology Data Exchange (ETDEWEB)

Lunardi, Claure N., E-mail: clunardi@unb.br [Laboratory of Photochemistry and Nanobiotechnology, University of Brasília, Brasília (Brazil); Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY (United States); Gomes, Anderson J. [Laboratory of Photochemistry and Nanobiotechnology, University of Brasília, Brasília (Brazil); Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY (United States); Palepu, Sandeep; Galwaduge, P. Thilanka; Hillman, Elizabeth M.C. [Department of Biomedical Engineering and Radiology, Laboratory for Functional Optical Imaging, Columbia University, New York, NY (United States)

2017-01-01

Here we present the production, characterization and in-vivo assessment of cresyl violet-loaded biodegradable PLGA nano/microparticles (CV-NP and CV-MP). We demonstrate that the beneficial spectral characteristics of cresyl violet make it suitable as a tracer for particle-based drug delivery using both hyperspectral wide field and two-photon excited fluorescence microscopy. Particles were prepared using a cosolvent method, after which the physicochemical properties such as morphology, particle size, drug entrapment efficiency, drug loading and in vitro drug release behavior were measured in addition to spectroscopic properties, such as absorption, fluorescence and infrared spectra. The particles were then tested in an in vivo mouse model to assess their biodistribution characteristics. The location and integrity of particles after injection was determined using both hyperspectral fluorescence and two-photon microscopy within intact organs in situ. Our results show that cresyl violet is efficiently entrapped into PLGA particles, and that the particles are spherical in shape, ranging from 300 to 5070 nm in diameter. Particle biodistribution in the mouse was found to depend on particle size, as expected. Cresyl violet is shown to be an ideal tracer to assess the properties PLGA particle-based drug delivery in combination with our novel multi-scale optical imaging techniques for in-situ particle localization. - Highlights: • Cresyl violet entrapment into polymeric particles • Cresyl violet suitable as a tracer for particle-based drug delivery • Hyperspectral analysis of polymer nano/microparticles • Two-photon microscopy of polymeric nano/microparticles.

Polylactic-co-glycolic acid mesh coated with fibrin or collagen and biological adhesive substance as a prefabricated, degradable, biocompatible, and functional scaffold for regeneration of the urinary bladder wall.

Science.gov (United States)

Salem, Salah Abood; Hwei, Ng Min; Bin Saim, Aminuddin; Ho, Christopher C K; Sagap, Ismail; Singh, Rajesh; Yusof, Mohd Reusmaazran; Md Zainuddin, Zulkifili; Idrus, Ruszymah Bt Hj

2013-08-01

The chief obstacle for reconstructing the bladder is the absence of a biomaterial, either permanent or biodegradable, that will function as a suitable scaffold for the natural process of regeneration. In this study, polylactic-co-glycolic acid (PLGA) plus collagen or fibrin was evaluated for its suitability as a scaffold for urinary bladder construct. Human adipose-derived stem cells (HADSCs) were cultured, followed by incubation in smooth muscle cells differentiation media. Differentiated HADSCs were then seeded onto PLGA mesh supported with collagen or fibrin. Evaluation of cell-seeded PLGA composite immersed in culture medium was performed under a light and scanning microscope. To determine if the composite is compatible with the urodynamic properties of urinary bladder, porosity and leaking test was performed. The PLGA samples were subjected to tensile testing was pulled until PLGA fibers break. The results showed that the PLGA composite is biocompatible to differentiated HADSCs. PLGA-collagen mesh appeared to be optimal as a cell carrier while the three-layered PLGA-fibrin composite is better in relation to its leaking/ porosity property. A biomechanical test was also performed for three-layered PLGA with biological adhesive and three-layered PLGA alone. The tensile stress at failure was 30.82 ± 3.80 (MPa) and 34.36 ± 2.57 (MPa), respectively. Maximum tensile strain at failure was 19.42 ± 2.24 (mm) and 23.06 ± 2.47 (mm), respectively. Young's modulus was 0.035 ± 0.0083 and 0.043 ± 0.012, respectively. The maximum load at break was 58.55 ± 7.90 (N) and 65.29 ± 4.89 (N), respectively. In conclusion, PLGA-Fibrin fulfils the criteria as a scaffold for urinary bladder reconstruction. Copyright © 2013 Wiley Periodicals, Inc.

Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation.

Science.gov (United States)

Wright, Leah; Rao, Shasha; Thomas, Nicky; Boulos, Ramiz A; Prestidge, Clive A

2018-04-11

Novel antibiotic Ramizol ® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing. The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance. Ramizol ® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague-Dawley rats. Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague-Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in T max and T 1/2 when compared to the oral and IV routes. Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol ® . This formulation will allow further development of Ramizol ® for systemic infection eradication.

Three-dimensional simulated microgravity culture improves the proliferation and odontogenic differentiation of dental pulp stem cell in PLGA scaffolds implanted in mice.

Science.gov (United States)

Li, Yanping; He, Lina; Pan, Shuang; Zhang, Lin; Zhang, Weiwei; Yi, Hong; Niu, Yumei

2017-02-01

Tooth regeneration through stem cell-based therapy is a promising treatment for tooth decay and loss. Human dental pulp stem cells (hDPSCs) have been widely identified as the stem cells with the most potential for tooth tissue regeneration. However, the culture of hDPSCs in vitro for tissue engineering is challenging, as cells may proliferate slowly or/and differentiate poorly in vivo. Dynamic three‑dimensional (3D) simulated microgravity (SMG) created using the rotary cell culture system is considered to an effective tool, which contributes to several cell functions. Thus, the present study aimed to investigate the effect of dynamic 3D SMG culture on the proliferation and odontogenic differentiation abilities of hDPSCs in poly (lactic‑co‑glycolic acid) (PLGA) scaffolds in nude mice. The hDPSCs on PLGA scaffolds were maintained separately in the 3D SMG culture system and static 3D cultures with osteogenic medium for 7 days in vitro. Subsequently, the cell‑PLGA complexes were implanted subcutaneously on the backs of nude mice for 4 weeks. The results of histological and immunohistochemical examinations of Ki‑67, type I collagen, dentin sialoprotein and DMP‑1 indicated that the proliferation and odontogenic differentiation abilities of the hDPSCs prepared in the 3D SMG culture system were higher, compared with those prepared in the static culture system. These findings suggested that dynamic 3D SMG culture likely contributes to tissue engineering by improving the proliferation and odontogenic differentiation abilities of hDPSCs in vivo.

Chemical approach to solvent removal during nanoencapsulation: its application to preparation of PLGA nanoparticles with non-halogenated solvent

Energy Technology Data Exchange (ETDEWEB)

Lee, Youngme [Ewha Womans University, College of Pharmacy (Korea, Republic of); Sah, Eric [University of Notre Dame, College of Science (United States); Sah, Hongkee, E-mail: hsah@ewha.ac.kr [Ewha Womans University, College of Pharmacy (Korea, Republic of)

2015-11-15

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.Graphical AbstractSchematic illustration of an innovative chemical approach to solvent removal during nanoencapsulation. Methyl propionate present in the aqueous continuous phase reacts with sodium hydroxide, thereby producing methanol and sodium propionate. Its alkaline hydrolysis allows the continuous extraction of the solvent out of nanoemulsion

Chemical approach to solvent removal during nanoencapsulation: its application to preparation of PLGA nanoparticles with non-halogenated solvent

International Nuclear Information System (INIS)

Lee, Youngme; Sah, Eric; Sah, Hongkee

2015-01-01

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.Graphical AbstractSchematic illustration of an innovative chemical approach to solvent removal during nanoencapsulation. Methyl propionate present in the aqueous continuous phase reacts with sodium hydroxide, thereby producing methanol and sodium propionate. Its alkaline hydrolysis allows the continuous extraction of the solvent out of nanoemulsion

SYNTHESIS AND CHARACTERIZATION OF CANNABIS INDICA FIBER REINFORCED COMPOSITES

Directory of Open Access Journals (Sweden)

Amar Singh Singha

2011-04-01

Full Text Available This paper reports on the synthesis of Cannabis indica fiber-reinforced composites using Urea-Resorcinol-Formaldehyde (URF as a novel matrix through compression molding technique. The polycondensation between urea, resorcinol, and formaldehyde in different molar ratios was applied to the synthesis of the URF polymer matrix. A thermosetting matrix based composite, reinforced with lignocellulose from Cannabis indica with different fiber loadings 10, 20, 30, 40, and 50% by weight, was obtained. The mechanical properties of randomly oriented intimately mixed fiber particle reinforced composites were determined. Effects of fiber loadings on mechanical properties such as tensile, compressive, flexural strength, and wear resistance were evaluated. Results showed that mechanical properties of URF resin matrix increased considerably when reinforced with particles of Cannabis indica fiber. Thermal (TGA/DTA/DTG and morphological studies (SEM of the resin, fiber and polymer composite thus synthesized were carried out.

Molybdenum cluster loaded PLGA nanoparticles: An innovative theranostic approach for the treatment of ovarian cancer.

Science.gov (United States)

Brandhonneur, N; Hatahet, T; Amela-Cortes, M; Molard, Y; Cordier, S; Dollo, G

2018-04-01

We evaluate poly (d,l-lactide-co-glycolide) (PLGA) nanoparticles embedding inorganic molybdenum octahedral cluster for photodynamic therapy of cancer (PDT). Tetrabutyl ammonium salt of Mo 6 Br 14 cluster unit, (TBA) 2 Mo 6 Br 14 , presents promising photosensitization activity in the destruction of targeted cancer cells. Stable cluster loaded nanoparticles (CNPs) were prepared by solvent displacement method showing spherical shapes, zeta potential values around -30 mV, polydispersity index lower than 0.2 and sizes around 100 nm. FT-IR and DSC analysis revealed the lack of strong chemical interaction between the cluster and the polymer within the nanoparticles. In vitro release study showed that (TBA) 2 Mo 6 Br 14 was totally dissolved in 20 min, while CNPs were able to control the release of encapsulated cluster. In vitro cellular viability studies conducted on A2780 ovarian cancer cell line treated up to 72 h with cluster or CNPs did not show any sign of toxicity in concentrations up to 20 µg/ml. This concentration was selected for photo-activation test on A2780 cells and CNPs were able to generate oxygen singlet resulting in a decrease of the cellular viability up to 50%, respectively compared to non-activated conditions. This work presents (TBA) 2 Mo 6 Br 14 as a novel photosensitizer for PDT and suggests PLGA nanoparticles as an efficient delivery system intended for tumor targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

Research status of large mode area single polarization active fiber

Science.gov (United States)

Xiao, Chun; Zhang, Ge; Yang, Bin-hua; Cheng, Wei-feng; Gu, Shao-yi

2018-03-01

As high power fiber laser used more and more widely, to increase the output power of fiber laser and beam quality improvement have become an important goal for the development of high power fiber lasers. The use of large mode fiber is the most direct and effective way to solve the nonlinear effect and fiber damage in the fiber laser power lifting process. In order to reduce the effect of polarization of the fiber laser system, the study found that when introduces a birefringence in the single-mode fiber, the polarization state changes caused by the birefringence is far greater than the random polarization state changes, then the external disturbance is completely submerged, finally the polarization can be controlled and stabilized. Through the fine design of the fiber structure, if the birefringence is high enough to achieve the separation of the two polarization states, the fiber will have a different cut-off mechanism to eliminate polarization which is not need, which will realize single mode single polarization transmission in a band. In this paper, different types of single polarization fiber design are presented and the application of these fibers are also discussed.

Wave propagation through a dielectric layer containing densely packed fibers

International Nuclear Information System (INIS)

Lee, Siu-Chun

2011-01-01

This paper presents the theoretical formulation for the propagation of electromagnetic wave through a dielectric layer containing a random dense distribution of fibers. The diameter of the fibers is comparable to the inter-fiber spacing and wavelength of the incident radiation, but is much smaller than the thickness of the layer. Discontinuity of refractive index across the boundaries of the dielectric layer resulted in multiple internal reflection of both the primary source wave and the scattered waves. As a result the incident waves on the fibers consist of the multiply-reflected primary waves, scattered waves from other fibers, and scattered-reflected waves from the boundaries. The effective propagation constant of the dielectric fiber layer was developed by utilizing the Effective field-Quasicrystalline approximation. The influence of the refractive index of the dielectric medium on the radiative properties of a dense fiber layer was examined by means of numerical analyses.

Poisson's ratio of fiber-reinforced composites

Science.gov (United States)

Christiansson, Henrik; Helsing, Johan

1996-05-01

Poisson's ratio flow diagrams, that is, the Poisson's ratio versus the fiber fraction, are obtained numerically for hexagonal arrays of elastic circular fibers in an elastic matrix. High numerical accuracy is achieved through the use of an interface integral equation method. Questions concerning fixed point theorems and the validity of existing asymptotic relations are investigated and partially resolved. Our findings for the transverse effective Poisson's ratio, together with earlier results for random systems by other authors, make it possible to formulate a general statement for Poisson's ratio flow diagrams: For composites with circular fibers and where the phase Poisson's ratios are equal to 1/3, the system with the lowest stiffness ratio has the highest Poisson's ratio. For other choices of the elastic moduli for the phases, no simple statement can be made.

Durability-Based Design Criteria for a Chopped-Glass-Fiber Automotive Structural Composite; TOPICAL

International Nuclear Information System (INIS)

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

1999-01-01

This report provides recommended durability-based design criteria for a chopped-glass-fiber reinforced polymeric composite for automotive structural applications. The criteria closely follow the framework of an earlier criteria document for a continuous-strand-mat (CSM) glass-fiber reference composite. Together these design criteria demonstrate a framework that can be adapted for future random-glass-fiber composites for automotive structural applications

Elimination of drift in a fiber-Bragg-grating-based multiplexed Michelson interferometer measurement system.

Science.gov (United States)

Ren, Junyu; Xie, Fang; Chen, Zhimin

2010-02-01

Random phase drift in single-mode optical fiber interferometers used with measurement systems, which is resulted from various types of environmental disturbances, should be eliminated in order to obtain high measurement precision. We propose an optical fiber interferometric measurement system which has the function of self-eliminating the random phase drift and is stable and robust enough for real-time precision measurement. By employing the characteristics of fiber Bragg gratings, the system interleaves two fiber Michelson interferometers together that share the common-interferometric-optical path. The signal of one of the interferometers is used to stabilize the system while the signal of the other interferometer is used for measurement. An electronic feedback loop for the stabilizing action is designed. The bandwidth of the feedback loop is 5 kHz, sufficiently wide to eliminate random phase drift resulted from various environmental disturbances. The system is endowed with high stability and therefore suitable for real-time precision measurement. By means of an active phase tracking technique to measure displacement, the linear regression coefficient of the displacement measurement results is 0.9998.

Evolution of regular geometrical shapes in fiber lumens

KAUST Repository

Le, Ngoc Lieu

2017-08-17

The geometry of polymeric hollow fibers for hemodialysis or desalination is a key factor determining their performance. Deformations are frequently observed, but they are rather random. Here we were able to exactly control the shape evolution of the internal channels or lumens of polymeric hollow fibers, leading to polygonal geometries with increasing number of sides. The elasticity of the incipient channel skin and instabilities during fiber formation are affected by the internal coagulant fluid composition and flow rate; and highly influence the polygonal shape. We propose a holistic explanation by analyzing the thermodynamic, kinetic and rheological aspects involved in the skin formation and their synergy.

A probabilistic analysis of electrical equipment vulnerability to carbon fibers

Science.gov (United States)

Elber, W.

1980-01-01

The statistical problems of airborne carbon fibers falling onto electrical circuits were idealized and analyzed. The probability of making contact between randomly oriented finite length fibers and sets of parallel conductors with various spacings and lengths was developed theoretically. The probability of multiple fibers joining to bridge a single gap between conductors, or forming continuous networks is included. From these theoretical considerations, practical statistical analyses to assess the likelihood of causing electrical malfunctions was produced. The statistics obtained were confirmed by comparison with results of controlled experiments.

Compressive failure model for fiber composites by kink band initiation from obliquely aligned, shear-dislocated fiber breaks

Energy Technology Data Exchange (ETDEWEB)

Bai, J.; Phoenix, S.L. [Cornell University, Ithaca, NY (United States). Dept. of Theoretical and Applied Mechanics

2005-04-01

Predicting compressive failure of a unidirectional fibrous composite is a longstanding and challenging problem that we study from a new perspective. Motivated by previous modelling of tensile failure as well as experimental observations on compressive failures in single carbon fibers, we develop a new micromechanical model for the compressive failure process in unidirectional, planar composites. As the compressive load is increased, random fiber failures are assumed to occur due to statistically distributed flaws, analogous to what occurs in tension. These breaks are often shear-mode failures with slanted surfaces that induce shear dislocations, especially when they occur in small groups aligned obliquely. Our model includes interactions of dislocated and neighboring intact fibers through a system of fourth-order, differential equations governing transverse deformation, and also allows for local matrix plastic yielding and debonding from the fiber near and within the dislocation arrays. Using the Discrete Fourier Transform method, we find a 'building-block' analytical solution form, which naturally embodies local length scales of fiber microbuckling and instability. Based on the influence function, superposition approach, a computationally efficient scheme is developed to model the evolution of fiber and matrix stresses. Under increasing compressive strain the simulations show that matrix yielding and debonding crucially lead to large increases in bending strains in fibers next to small groups of obliquely aligned, dislocated breaks. From the paired locations of maximum fiber bending in flanking fibers, the triggering of an unstable kink band becomes realistic. The geometric features of the kink band, such as the fragment lengths and orientation angles, will depend on the fiber and matrix mechanical and geometric properties. In carbon fiber-polymer matrix systems our model predicts a much lower compressive failure stress than obtained from Rosen

Growth, structure, and optical properties of carbon-reinforced silica fibers

International Nuclear Information System (INIS)

Zhang, Z. J.; Ajayan, P. M.; Ramanath, G.; Vacik, J.; Xu, Y. H.

2001-01-01

We report the synthesis of carbon-reinforced silica fibers by methane exposure of metallocene-treated oxidized-Si(001) substrates at 1100 degree C. The SiO 2 cap layer transforms into silica fibers reinforced by glassy carbon in the core during methane exposure. High-resolution electron microscopy and spatially resolved spectroscopy measurements of the fibers reveal an amorphous structure without a hollow, and domains of glassy carbon embedded at the fiber core. The carbon-reinforced fibers are optically transparent and have an optical band gap of ≅3.1 eV. These fibers are organized in radial patterns that vary for different metallocene species. On nickelocene-treated substrates, the fibers originate from the circumference of the circular templates and grow outwards, forming radial patterns. On ferrocene-treated substrates, randomly oriented fibers grow within as well as slightly outside the perimeter of the templates, forming wreath-like patterns. Aligned growth of such fibers could be useful for fabricating optoelectronics devices and reinforced composites. [copyright] 2001 American Institute of Physics

Effects of curcumin-loaded PLGA nanoparticles on the RG2 rat glioma model.

Science.gov (United States)

Orunoğlu, Merdan; Kaffashi, Abbas; Pehlivan, Sibel Bozdağ; Şahin, Selma; Söylemezoğlu, Figen; Oğuz, Kader Karli; Mut, Melike

2017-09-01

Curcumin, the active ingredient of turmeric, has a remarkable antitumor activity against various cancers, including glioblastoma. However, it has poor absorption and low bioavailability; thus, to cross the blood-brain barrier and reach tumor tissue, it needs to be transferred to tumor site by special drug delivery systems, such as nanoparticles. We aimed to evaluate the antitumor activity of curcumin on glioblastoma tissue in the rat glioma-2 (RG2) tumor model when it is loaded on poly(lactic-co-glycolic acid)-1,2-distearoyl-glycerol-3-phospho-ethanolamine-N-[methoxy (polyethylene glycol)-2000] ammonium salt (PLGA-DSPE-PEG) hybrid nanoparticles. Glioblastoma was induced in 42 adult female Wistar rats (250-300g) by RG2 tumor model. The curcumin-loaded nanoparticles were injected by intravenous (n=6) or intratumoral route (n=6). There were five control groups, each containing six rats. First control group was not applied any treatment. The remaining four control groups were given empty nanoparticles or curcumin alone by intravenous or intratumoral route, respectively. The change in tumor volume was assessed by magnetic resonance imaging and histopathology before and 5days after drug injections. Tumor size decreased significantly after 5days of intratumoral injection of curcumin-loaded nanoparticle (from 66.6±44.6 to 34.9±21.7mm 3 , p=0.028), whereas it significantly increased in nontreated control group (from 33.9±21.3 to 123.7±41.1mm 3 , p=0.036) and did not significantly change in other groups (p>0.05 for all). In this in vivo experimental model, intratumoral administration of curcumin-loaded PLGA-DSPE-PEG hybrid nanoparticles was effective against glioblastoma. Curcumine-loaded nanoparticles may have potential application in chemotherapy of glioblastoma. Copyright © 2017 Elsevier B.V. All rights reserved.

FM-AM Conversion Induced by Polarization Mode Dispersion in Fiber Systems

International Nuclear Information System (INIS)

Xiao-Dong, Huang; Sheng-Zhi, Zhao; Jian-Jun, Wang; Ming-Zhong, Li; Dang-Peng, Xu; Hong-Huan, Lin; Rui, Zhang; Ying, Deng; Xiao-Min, Zhang

2010-01-01

The conversion of the frequency modulated pulse induced from frequency modulation (FM) to amplitude modulation (AM) by the polarization mode dispersion (PMD) is theoretically and experimentally investigated. When there is no polarizer at the output end of a fiber system, the amplitude modulation depth is stable by 8%. Random amplitude modulation is observed when a polarizer is placed at the output end of the fiber system. The observed minimum and maximum modulation depths in our experiment are 5% and 80%, respectively. Simulation results show that the amplitude modulation is stable by 4% induced mainly by group velocity dispersion (GVD) when there is no polarizer, and the amplitude modulation depth displays the random variation character induced by the GVD and PMD. Lastly, a new fiber system scheme is proposed and little amplitude modulation is observed at the top of the output pulse

Co-delivery of Cbfa-1-targeting siRNA and SOX9 protein using PLGA nanoparticles to induce chondrogenesis of human mesenchymal stem cells.

Science.gov (United States)

Jeon, Su Yeon; Park, Ji Sun; Yang, Han Na; Lim, Hye Jin; Yi, Se Won; Park, Hansoo; Park, Keun-Hong

2014-09-01

During stem cell differentiation, various cellular responses occur that are mediated by transcription factors and proteins. This study evaluated the abilities of SOX9, a crucial protein during the early stage of chondrogenesis, and siRNA targeting Cbfa-1, a transcription factor that promotes osteogenesis, to stimulate chondrogenesis. Non-toxic poly-(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were coated with Cbfa-1-targeting siRNA and loaded with SOX9 protein. Coomassie blue staining and circular dichroism revealed that the loaded SOX9 protein maintained its stability and bioactivity. These NPs easily entered human mesenchymal stem cells (hMSCs) in vitro and caused them to differentiate into chondrocytes. Markers that are typically expressed in mature chondrocytes were examined. These markers were highly expressed at the mRNA and protein levels in hMSCs treated with PLGA NPs coated with Cbfa-1-targeting siRNA and loaded with SOX9 protein. By contrast, these cells did not express osteogenesis-related markers. hMSCs were injected into mice following internalization of PLGA NPs coated with Cbfa-1-targeting siRNA and loaded with SOX9 protein. When the injection site was excised, markers of chondrogenesis were found to be highly expressed at the mRNA and protein levels, similar to the in vitro results. When hMSCs internalized these NPs and were then cultured in vitro or injected into mice, chondrogenesis-related extracellular matrix components were highly expressed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hybrid carbon/glass fiber composites: Micromechanical analysis of structure–damage resistance relationships

DEFF Research Database (Denmark)

Mishnaevsky, Leon; Dai, Gaoming

2014-01-01

A computational study of the effect of microstructure of hybrid carbon/glass fiber composites on their strength is presented. Unit cells with hundreds of randomly located and misaligned fibers of various properties and arrangements are subject to tensile and compression loading, and the evolution...... strength than pure composites, while the strength of hybrid composites under inform force loading increases steadily with increasing the volume content of carbon fibers....... of fiber damages is analyzed in numerical experiments. The effects of fiber clustering, matrix properties, nanoreinforcement, load sharing rules on the strength and damage resistance of composites are studied. It was observed that hybrid composites under uniform displacement loading might have lower...

Electrospun Poly(lactic acid)-Based Fibrous Nanocomposite Reinforced by Cellulose Nanocrystals: Impact of Fiber Uniaxial Alignment on Microstructure and Mechanical Properties.

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Huan, Siqi; Liu, Guoxiang; Cheng, Wanli; Han, Guangping; Bai, Long

2018-03-12

Uniform poly(lactic acid)/cellulose nanocrystal (PLA/CNC) fibrous mats composed of either random or aligned fibers reinforced with up to 20 wt % CNCs were successfully produced by two different electrospinning processes. Various concentrations of CNCs could be stably dispersed in PLA solution prior to fiber manufacture. The microstructure of produced fibrous mats, regardless of random or aligned orientation, was transformed from smooth to nanoporous surface by changing CNC loading levels. Aligning process through secondary stretching during high-speed collection can also affect the porous structure of fibers. With the same CNC loading, fibrous mats produced with aligned fibers had higher degree of crystallinity than that of fibers with random structure. The thermal properties and mechanical performances of PLA/CNC fibrous mats can be enhanced, showing better enhancement effect of aligned fibrous structure. This results from a synergistic effect of the increased crystallinity of fibers, the efficient stress transfer from PLA to CNCs, and the ordered arrangement of electrospun fibers in the mats. This research paves a way for developing an electrospinning system that can manufacture high-performance CNC-enhanced PLA fibrous nanocomposites.

Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells.

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Chang, Jiang; Paillard, Archibald; Passirani, Catherine; Morille, Marie; Benoit, Jean-Pierre; Betbeder, Didier; Garcion, Emmanuel

2012-06-01

Nanomedicines represent an alternative for the treatment of aggressive glioblastoma tumors. Behaviour of PLGA-nanoparticles (NPs) was here investigated as a function of their protein adsorption characteristics at the different biological interfaces they are expected to face in order to reach brain cancer cells. NPs were studied for size, zeta potential, blood half-life, in vitro endocytic behavior and in vivo accumulation within healthy rat brain and brain tumors. While slightly modifying size (80 to 90 nm) and zeta potential (-44 to -32 mV) protein coating of PLGA-NPs by bovine serum albumin (BSA) or transferrin (Tf) greatly prolonged their blood half-life when intravenously injected in rats and mice. In contrast with THP-1 monocytes, differentiated THP-1 macrophages, F98 glioma cells and astrocytes internalized BSA- and Tf-NPs in vitro. Increase of Tf-NP uptake by F98 cells through caveolae- and clathrin-mediated pathways supports specific interaction between Tf and overexpressed Tf-receptor. Finally, in vivo targeting of healthy brain was found higher with Tf-NPs than with BSA-NPs while both NPs entered massively within brain-developed tumors. Taken together, those data evidence that Tf-NPs represent an interesting nanomedicine to deliver anticancer drugs to glioma cells through systemic or locoregional strategies at early and late tumor stages.

Electro-magnetic properties of composites with aligned Fe-Co hollow fibers

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Seungchan Cho

2016-05-01

Full Text Available A novel Fe-Co binary hollow fiber was synthesized by electroless plating using hydrolyzed polyester fiber and its anisotropy characteristic was investigated for electromagnetic wave absorbing materials. The hollow fibers in parallel with magnetic field show higher saturated magnetization of 202 emu/g at the applied magnetic field of 10 kOe and lower coercivity (27.658 Oe, compared with the random and vertical oriented hollow fibers. From complex permittivity measurement, the Fe-Co hollow fiber composites clearly display a single dielectric resonance, located at ∼14 GHz. The Fe-Co hollow fibers not only provide excellent EM properties in GHz frequency ranges, resulting mainly from the strong resonance, but also adjust the soft magnetic properties through fiber alignments. The cavitary structure of the Fe-Co hollow fibers, not only giving rise to a dielectric loss resonance and also adjusting its peak frequency, may be a pathway to useful EM wave absorptive devices in GHz frequency ranges.

Balanced PIN-TIA photoreceiver with integrated 3 dB fiber coupler for distributed fiber optic sensors

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Datta, Shubhashish; Rajagopalan, Sruti; Lemke, Shaun; Joshi, Abhay

2014-06-01

We report a balanced PIN-TIA photoreceiver integrated with a 3 dB fiber coupler for distributed fiber optic sensors. This detector demonstrates -3 dB bandwidth >15 GHz and coupled conversion gain >65 V/W per photodiode through either input port of the 3 dB coupler, and can be operated at local oscillator power of +17 dBm. The combined common mode rejection of the balanced photoreceiver and the integrated 3 dB coupler is >20 dB. We also present measurement results with various optical stimuli, namely impulses, sinusoids, and pseudo-random sequences, which are relevant for time domain reflectometry, frequency domain reflectometry, and code correlation sensors, respectively.

PEGylated composite nanoparticles of PLGA and polyethylenimine for safe and efficient delivery of pDNA to lungs.

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Kolte, Atul; Patil, Sushilkumar; Lesimple, Pierre; Hanrahan, John W; Misra, Ambikanandan

2017-05-30

Achieving stable, efficient and non-toxic pulmonary gene delivery is most challenging requirement for successful gene therapy to lung. Composite nanoparticles (NPs) of the poly(lactic-co-glycolic acid) (PLGA) and cationic polymer polyethyleneimine (PEI) is an efficient alternative to viral and liposomal vectors for the pulmonary delivery of pDNA. NPs with different weight ratios (0-12.5%w/w) of PLGA/PEI were prepared and characterized for size, morphology, surface charge, pDNA loading and in vitro release. The in vitro cell uptake and transfection studies in the CFBE41o-cell line revealed that NPs with 10% w/w PEI were more efficient but they exhibited significant cytotoxicity in MTT assays, challenging the safety of this formulation. Surface modifications of these composite NPs through PEGylation reduced toxicity and enhanced cellular uptake and pDNA expression. PEGylation improved diffusion of NPs through the mucus barrier and prevented uptake by pulmonary macrophages. Finally, PEGylated composite NPs were converted to DPI by lyophilization and combined with lactose carrier particles, which resulted in improved aerosolization properties and lung deposition, without affecting pDNA bioactivity. This study demonstrates that a multidisciplinary approach may enable the local delivery of pDNA to lung tissue for effective treatment of deadly lung diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of accelerated artificial daylight aging on bending strength and bonding of glass fibers in fiber-embedded maxillofacial silicone prostheses.

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Hatamleh, Muhanad M; Watts, David C

2010-07-01

The purpose of this study was to test the effect of different periods of accelerated artificial daylight aging on bond strength of glass fiber bundles embedded into maxillofacial silicone elastomer and on bending strength of the glass fiber bundles. Forty specimens were fabricated by embedding resin-impregnated fiber bundles (1.5-mm diameter, 20-mm long) into maxillofacial silicone elastomer. Specimens were randomly allocated into four groups, and each group was subjected to different periods of accelerated daylight aging as follows (in hours); 0, 200, 400, and 600. The aging cycle included continuous exposure to quartz-filtered visible daylight (irradiance 760 W/m(2)) under an alternating weathering cycle (wet for 18 minutes, dry for 102 minutes). Pull-out tests were performed to evaluate bond strength between fiber bundles and silicone using a universal testing machine at 1 mm/min crosshead speed. Also a three-point bending test was performed to evaluate bending strength of the fiber bundles. One-way ANOVA and Bonferroni post hoc tests were carried out to detect statistical significance (p aging only. After 200 hours of exposure to artificial daylight and moisture conditions, bond strength between glass fibers and heat-cured silicones is optimal, and the bending strength of the glass fiber bundles is enhanced.

Electrospun Nanofiber Scaffolds with Gradations in Fiber Organization

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Khandalavala, Karl; Jiang, Jiang; Shuler, Franklin D.; Xie, Jingwei

2015-01-01

The goal of this protocol is to report a simple method for generating nanofiber scaffolds with gradations in fiber organization and test their possible applications in controlling cell morphology/orientation. Nanofiber organization is controlled with a new fabrication apparatus that enables the gradual decrease of fiber organization in a scaffold. Changing the alignment of fibers is achieved through decreasing deposition time of random electrospun fibers on a uniaxially aligned fiber mat. By covering the collector with a moving barrier/mask, along the same axis as fiber deposition, the organizational structure is easily controlled. For tissue engineering purposes, adipose-derived stem cells can be seeded to these scaffolds. Stem cells undergo morphological changes as a result of their position on the varied organizational structure, and can potentially differentiate into different cell types depending on their locations. Additionally, the graded organization of fibers enhances the biomimicry of nanofiber scaffolds so they more closely resemble the natural orientations of collagen nanofibers at tendon-to-bone insertion site compared to traditional scaffolds. Through nanoencapsulation, the gradated fibers also afford the possibility to construct chemical gradients in fiber scaffolds, and thereby further strengthen their potential applications in fast screening of cell-materials interaction and interfacial tissue regeneration. This technique enables the production of continuous gradient scaffolds, but it also can potentially produce fibers in discrete steps by controlling the movement of the moving barrier/mask in a discrete fashion. PMID:25938562

Effect of various fiber types and choice feeding of fiber on performance, gut development, humoral immunity, and fiber preference in broiler chicks.