• Title/Summary/Keyword: Poly(lactide-co-glycolide)

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Hybrid Biomaterial of PLGA Microspheres and Hyaluronic Acid as a Potential Injectable Bulking Agent for Urologic and Dermatologic Applications

  • Cho, Eui-Ri;Kang, Sun-Woong;Kim, Byung-Soo
    • 한국생물공학회:학술대회논문집
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    • 2003.10a
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    • pp.644-647
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    • 2003
  • Materials currently used as an injectable bulking agent in the dermatologic and urologic fields revealed several drawbacks such as particles migration, inflammatory reaction, allergic reaction, rapid volume shrinkage, and necessity of a donor site. In this study, we have developed injectable biomaterial comprising poly (DL- lactide-co-glycolide)(PLGA) and hyaluronic acid gel to overcome these problems. PLGA is a biocompatible synthetic material and hyaluronic acid is a common substance found in living organisms. We examined the feasibility of injection through needle and tested biocompatibility in animal model. After transplantation, injected sites and distant organs were examined histologically to verify a new tissue formation, inflammation, and particles migrations. Injected volume was maintained approximately 80 percent for 2 months. Results demonstrated that the developed material was injectable through various gauges of needles and induced a new bulking tissue formation without serious inflammatory reaction.

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Stability of Octreotide Acetate in Aqueous Solutions and PLGA Films

  • Ryu, Ki-Won;Na, Dong-Hee
    • Journal of Pharmaceutical Investigation
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    • v.39 no.5
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    • pp.353-357
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    • 2009
  • As a synthetic analog of the naturally occurring hormone somatostatin, octreotide has been commercially formulated in poly(lactide-co-glycolide) (PLGA) microspheres for the treatment of acromegaly. The purpose of this study was to evaluate stability of octreotide acetate in aqueous solutions at various pH values and PLGA films. Stability-indicating reversed-phase high-performance liquid chromatographic method was developed with good precision and accuracy, and it was applied to the stability studies. In aqueous solutions at pH 2.5-9.0, the degradation of octreotide followed approximately first order kinetics and the most favorable stability was found at pH 4. In PLGA films, the formation of acylated octreotides reached approximately 55% of the released octreotides. Various acylated octreotides was structurally identified by liquid chromatography-mass spectrometric analysis.

In vivo Characterization of Sustained-Release Formulation of Recombinant Human Growth Hormone in Immunosuppressed Rats and Dogs

  • Jo, Yeong-Woo;Park, Yong-Man;Lee, Ghun-Il;Yang, Hi-Chang;Kim, Mi-Ryang;Lee, Sung-Hee;Kwon, Jong-Won;Kim, Won-Bae;Choi, Eung-Chil
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.424.2-424.2
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    • 2002
  • The in vivo release characteristics of rhGH-loaded PLGA microsphere prepared using a double emulsion process from hydrophilic 50:50 poly(D.L-lactide-co-glycolide) (PLGA) polymers were analyzed. This formulation showed particle size of ca 53.1$\mu\textrm{m}$ with high drug incorporation efficiency. To investigate in vivo release kinetics without the interference of formation of antibodies to rhGH in the experimental animals, the animals were immunosuppressed by treatment with Cyclosporin. (omitted)

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Preparation and Characterization of PEG-PLA(PLGA) Micelles for Solubilization of Pioglitazone (Pioglitazone 가용화를 위한 PEG-PLA(PLGA) 고분자 미셀의 제조 및 특성분석)

  • Im, Jeong-Hyuk;Lee, Yong-Kyu;Huh, Kang-Moo
    • Polymer(Korea)
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    • v.32 no.2
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    • pp.143-149
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    • 2008
  • We synthesized PEG-PLA (or PLGA) amphiphilic di-block copolymers, which consist of PEG as biocompatible and hydrophilic block and PLA (or PLGA) as biodegradable and hydrophobic block, by ring opening polymerization of LA in the presence of methoxy PEG as a macroinitiator. The compositions and the molecular weights of the copolymers were controlled by changing the feed ratio of LA (and GA) to PEG initiator. The di-block copolymers could self-assemble in aqueous media to form micellar structure. A hydrophobic model drug, pioglitazone, was loaded into the polymer micelle using solid dispersion and dialysis methods, and the drug-loaded micelles were characterized by AFM, DLS and HPLC measurements. The drug loading capacity and in vitro release studies were performed and evaluated under various conditions. These results indicated that the amphiphilic di-block copolymers of PEG-PLA (or PLGA) could solubilize pioglitazone by solid dispersion method and the drug release was modulated according to micellar chemical compositions.

Nanopharmaceutical Approach for Enhanced Anti-cancer Activity of Betulinic Acid in Lung-cancer Treatment via Activation of PARP: Interaction with DNA as a Target -Anti-cancer Potential of Nano-betulinic Acid in Lung Cancer-

  • Das, Jayeeta;Samadder, Asmita;Das, Sreemanti;Paul, Avijit;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.19 no.1
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    • pp.37-44
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    • 2016
  • Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

Biocompatibility of Poly(MPC-co-EHMA)/Poly(L-1actide-co-glycolide) Blends

  • Gilson Khang;Park, Myoung-Kyu;Jong M. Rhee;Lee, Sang-Jin;Lee, Hai-Bang;Yasuhiko Iwasaki;Nobuo Nakabayashi;Kazuhiko Ishihara
    • Macromolecular Research
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    • v.9 no.2
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    • pp.107-115
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    • 2001
  • Poly(L-lactide-co-glycolide)(PLGA) was blended with poly[$\omega$-methacryloyloxyethyl phospho-rylcholine-co-ethylhexylmethacrylate (PMEH)] (PLGA/PMEH) to endow with new functionality i.e., to improve the cell-, tissue- and blood-compatibility. The characteristics of surface properties were investigated by measurement of contact angle goniometer, Fourier-transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and electron spectroscopy for chemical analysis (ESCA). NIH/3T3 fibroblast and bovine aortic endothelial cell were cultured on control and PLGA/PMEH surfaces for the evaluation of ceil attachment and proliferation in terms of surface functionality such as the concentration of phosphoryl-choline. Also, the behavior of platelet adhesion on PLGA/PMEH was observed in terms of the surface functionality. The contact angles on control and PLGA/PMEH surfaces decreased with increasing PMEH content from 75$^{\circ}$ to about 43$^{\circ}$. It was observed from the FTIR-ATR spectra that phosphorylcholine groups are gradually increased with increasing blended amount of MPC. The experimental P percent values from ESCA analysis were more 3.28∼7.4 times than that of the theoretical P percent for each blend films. These results clearly indicated that the MPC units were concentrated on the surface of PLGA/PMEH blend. The control and PLGA/PMEH films with 0.5 to 10.0 wt% concentration of PMEH were used to evaluate cell adhesion and growth in terms of phosphorylcholine functionality and wettability. Cell adhesion and growth on PLGA/PMEH surfaces were less active than those of control and both cell number decreased with increasing PMEH contents without the effect of surface wettability. It can be explained that the fibronectin adsorption decreased with an increase in the surface density of phosphorylcholine functional group. One can conclude the amount of the protein adsorption and the adhesion number of cells can be controlled and nonspecifically reduced by the introduction with phosphorylcholine group. Morphology of the adhered platelets on the PLGA/PMEH surface showed lower activating than control and the number of adhered platelets on the PLGA/PMEH sample decreased with increasing the phosphorylcholine contents. The amount of fibrinogen adsorbed on the PLGA/PMEH surface demonstrated that the phospholipid polar group played an important role in reducing protein adsorption on the surface. In conclusion, this surface modification technique might be effectively used PLGA film and scaffolds for controlling the adhesion and growth of cell and tissue, furthermore, blood compatibility of the PLGA was improved by blending of the MPC polymer for the application of tissue engineering fields.

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Preparation and Characterization of Ipriflavone-Loaded Poly(L-lactide-co-glycolide) Scaffold for Tissue Engineered Bone (조직공학적 골을 위한 애프리플라본을 함유한 다공성 지지체의 제조 및 그 특성)

  • Jang, Ji-Wook;Lee, Bong;Han, Chang-Whan;Lee, Il-Woo;Lee, Hai-Bang;Khang, Gil-Son
    • Polymer(Korea)
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    • v.27 no.3
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    • pp.226-234
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    • 2003
  • Ipriflavone (IP), a non-hormonal isoflavone derivative, has been shown to interfere with bone remodeling by inhibiting bone resorption and stimulating bone formation. IP consistently increased the amount of Ca incorporated into the cell layer by mesenchymal stem cells (MSCs). In this study, we developed the novel IP loaded poly(L-lactide-co-glycolide) (PLGA) scaffolds for the possibility of the application of the tissue engineered bone. IP/PLGA scaffo1ds were prepared by solvent casting/salt leaching method and were characterized by porosimeter, scanning electron microscopy, determination of residual salt amount, differential scanning calorimetry, and X-ray diffractometer, respectively. IP/PLGA scaffolds were implanted into the back of athymic nude mouse to observe the effect of IP on the osteoinduction compared with control PLGA scaffo1ds. Thin sections were cut from paraffin embedded tissues and histological sections were stained H&E, von Kossa, and immunohistochemical staining for Type I collagen and osteocalcin. It can be observed that the porosity was above 91.7% and the pore size was above 101 $\mu\textrm{m}$. Control scaffo1d and IP/PLGA scaffo1ds of 50% IP were implanted on the back of athymic nude mouse to observe the effect of IP on the induction of cells proliferation for 9 weeks. The evidence of calcification, osteoblast, and osteoid from the undifferentiated stem cells in the subcutaneous sites and other soft connective tissue sites having a preponderance of stem cells has been observed. From these results, it seems that IP plays an important role for bone induction in IP/PLCA scaffolds.

CELLULAR RESPONSES ON ANODIZED TITANIUM DISCS COATED WITH $1{\alpha}$,25-DIHYDROXYVITAMIN D3 INCORPORATED POLY (D,L-LACTIDE-CO-GLYCOLIDE) (PLGA) NANOPARTICLES

  • Cho, Young-Jin;Heo, Seong-Joo;Koak, Jai-Young;Kim, Seong-Kyun;Lee, Joo-Hee
    • The Journal of Korean Academy of Prosthodontics
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    • v.46 no.6
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    • pp.620-627
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    • 2008
  • STATEMENT OF PROBLEM: A biochemical approach for surface modification has offered an alternative for physicochemical and morphological methods to obtain desirable bone-implant interfaces. PURPOSE: The purpose of the present study was to investigate cell responses to poly (D,L-lactide-co-glycolide) (PLGA)/$1{\alpha}$,25-(OH)$_2D_3$ coating with reference to cellular proliferation and differentiation in vitro. MATERIAL AND METHODS: 96 titanium discs were fabricated and divided into four groups. Group 1 was anodized under 300 V as control. Group 2, 3 and 4 were anodized then coated with 3 ml PLGA/$1{\alpha}$,25-(OH)$_2D_3$ solutions. Amount of the solutions were 2 ul, 20 ul and 200ul respectively. The osteoblast-like Human Osteogenic Sarcoma (HOS) cells were seeded and cultured for 1, 3 and 7 days. MTSbased cell proliferation assay and ALPase activity test were carried out. RESULTS: PLGA nanoparticles were observed as fine, smooth and round and HOS cells attached to the anodized surfaces through strand-like and sheet-like filopodia. After 3 days of culture, the dendritic filopodia were exaggerated and sheet-like cytoplasmic projections covered the coated titanium surfaces. After 3 days of culture, all of the groups showed increased cellular proliferation and the lowest proliferation rate was measured on group 2. Higher amount of incorporated $1{\alpha}$,25-(OH)$_2D_3$ (Group 3 and 4) improved cellular proliferation but the differences were not significant statistically (P > .05). But they increased the rate of ALP activities than the control group at day 3 (P < .05). CONCLUSION: Biodegradable PLGA nanoparticles incorporated with vitamin D metabolite positively affected proliferation and differentiation of cells on the anodized titanium surface.

Preparation and BDNF Release Profile of BDNF-loaded PLGA Scaffolds for Tissue Engineered Nerve Regeneration (신경재생을 위한 BDNF를 함유한 PLGA 지지체의 제조 및 방출)

  • Kim, Cho-Min;Kim, Soon-Hee;Oh, A-Young;Kim, Geun-Ah;Lee, Il-Woo;Rhee, John-M.;Khang, Gil-Son
    • Polymer(Korea)
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    • v.32 no.6
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    • pp.529-536
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    • 2008
  • We manufactured poly (L-lactide-co-glycolide) (PLGA) scaffolds impregnated demineralized bone particle (DBP) and hyaluronic acid (HA) by ice-particle leaching method and tested their ability of sustained release of brain derived neurotrophic factor (BDNF). BDNF (50 and 200 ng) mixed with PLGA, DBP/PLGA, HA/PLGA and DBP/HA/PLGA scaffold. The release profiles of BDNF from BDNF loaded scaffolds were assayed using ELISA. Morphological changes of scaffolds by BDNF release were also observed by SEM. BDNF stably and sustainedly released from DBP/HNPLGA than from PLGA and DBP/PLGA scaffolds. DBP/HA/PLGA scaffolds showed the great structural changes, which demonstrated BDNF release amount from DBP/HA/PLGA scaffolds were highest in all groups. We suggest that BDNF loaded DBP/HNPLGA scaffold would be very useful for nerve regeneration.

Effect of PLGA Scaffold Containing Demineralized Bone Solution for Articular Cartilage Tissue Engineering: In Vitro Test (조직공학적 연골재생을 위한 In Vitro 환경에서의 탈미네랄화 골분용액을 함유한 PLGA 지지체의 효과)

  • Ahn, Woo-Young;Kim, Hye-Lin;Song, Jeong-Eun;Lee, Dong-Won;Khang, Gil-Son
    • Polymer(Korea)
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    • v.35 no.6
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    • pp.499-504
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    • 2011
  • Articular cartilage has an intrinsic difficulty in recovering damages, which requires its tissue engineering treatment. Demineralized bone particle (DBP) contains various bioactive molecules. It is widely used biomaterials in the field of tissue engineering. We developed the synthetic/natural hybrid scaffolds with poly(lactide-co-glycolide) (PLGA) and solution of DBP. The chondrocytes were seeded on the PLGA-DBP scaffolds and MTT assay, morphological observation, biological assay for collagen, sGAG, and RT-PCR were performed to analyze the effect of the DBP on cell viability and extracellular matrix secretion. In SEM observation, we observed that PLGA-DBP scaffolds had uniform porosity. As MTT assay showed scaffolds containing DB solution had higher cell viability then only PLGA scaffolds. The PLGA-DBP scaffolds had better ECM production than PLGA scaffold. It was proven by the higher specific mRNA expression in the PLGA-DBP scaffold than that in PLGA scaffold. These results indicated that PLGA-DBP scaffolds might serve as potential cell delivery vehicles and structural bases for in vitro tissue engineered articular cartilage.