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PLGA Microspheres (plga + microsphere)
Selected AbstractsRepair of rabbit segmental defects with the thrombin peptide, TP508JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2004Michael R. Sheller Abstract The synthetic peptide, TP508 (Chrysalin®), was delivered to rabbit segmental bone defects in biodegradable controlled-release PLGA microspheres to determine its potential efficacy for enhancing healing of non-critically and critically sized segmental defects. Non-critically sized radial defects were created in the forelimbs of New Zealand White rabbits, which were randomized into three treatment groups receiving 10, 50 and 100 ,g doses of TP508 in the right radius and control microspheres (without TP508) in the left radius. Torsional testing of the radii at six weeks showed a significant increase in ultimate torque, failure torque, ultimate energy, failure energy, and stiffness when treated with TP508 compared to controls (p < 0.01 for all measures). Thus, TP508 appeared to enhance or accelerate bone growth in these defects. In a second set of experiments, critically sized ulnar defects were created in the forelimbs of New Zealand White rabbits, which were randomized into two groups with each rabbit receiving microspheres with 100 or 200 ,g of TP508 into the right ulnar defect and control microspheres (without TP508) alone into the left ulnar defect. Bone healing was evaluated with plain radiographs, synchrotron-based microtomography, and mechanical testing. Radiographs of the rabbit limbs scored by three blinded, independent reviewers demonstrated a significantly higher degree of healing when treated with TP508 than their untreated control limbs (p < 0.05). Three-dimensional synchrotron tomography of a limited number of samples showed that the new bone in TP508-treated samples had a less porous surface appearance and open marrow spaces, suggesting progression of bone remodeling. Torsional testing of the ulnae at nine weeks showed a significant increase in maximum torque and failure energy when treated with TP508 compared to controls (p < 0.01 for both measures). These results suggest that TP508 in a controlled release delivery vehicle has the potential to enhance healing of segmental defects in both critically and non-critically sized defects. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Pharmaceutical and immunological evaluation of a single-shot hepatitis B vaccine formulated with PLGA microspheresJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2002Li Shi Abstract A single-shot Hepatitis B vaccine formulation using poly(d,l)-lactide-co-glycolide acid (PLGA) microspheres as a delivery system was examined using a variety of biophysical and biochemical techniques as well as immunological evaluation in C3H mice. PLGA microsphere encapsulation of the Hepatitis B surface antigen (HBsAg), a lipoprotein particle, resulted in good recoveries of protein mass, protein particle conformational integrity, and in vitro antigenicity. Some partial delipidation of the HBsAg, however, was observed. The loading and encapsulation efficiency of HBsAg into the PLGA microspheres were measured along with the morphology and size distribution of the vaccine-loaded PLGA microspheres. The in vitro release kinetics of HBsAg from the PLGA microspheres was evaluated and found to be affected by experimental conditions such as stirring rate. HBsAg showed enhanced storage stability at 37°C in the slightly acidic pH range reported to be found inside PLGA microspheres; thus, the antigen is relatively stable under conditions of temperature and pH that may mimic in vivo conditions. The immunogenicity of the microsphere formulations of HBsAg was compared with conventional aluminum adjuvant formulated HBsAg vaccine in C3H mice. Comparisons were made between aluminum formulations (one and two injections), PLGA microsphere formulations (single injection), and a mixture of aluminum and PLGA microsphere formulations (single injection). The nine-month serum antibody titers indicate that a single injection of a mixture of aluminum and PLGA-formulated HBsAg results in equal or better immune responses than two injections of aluminum-formulated HBsAg vaccine. Based on these invitro and in vivo studies, it is concluded that HBsAg can be successfully encapsulated and recovered from the PLGA microspheres and a mixture of aluminum-adjuvanted and PLGA-formulated HBsAg can auto-boost an immune response in manner comparable to multiple injections of an aluminum-formulated vaccine. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1019,1035, 2002 [source] Pharmacokinetic characterization of 14C-vascular endothelial growth factor controlled release microspheres using a rat modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2002Tae-Kyoung Kim The objectives of this study were to characterize the pharmacokinetics of vascular endothelial growth factor (VEGF) in poly(lactic-co-glycolic) acid (PLGA) microspheres using a rat model, and to develop a pharmacokinetic model for this controlled release formulation. 14C-VEGF was encapsulated using a solid-in-oil-in-water emulsification method. The microspheres were administered subcutaneously to rats and the pharmacokinetic parameters were compared with those of protein solutions. Intravenous administration of protein solutions resulted in short half-lives and subcutaneous administration resulted in rapid clearance from the subcutaneous tissue, with high plasma concentrations as expressed by rapid absorption and elimination. The subcutaneous administration of the VEGF microspheres produced low plasma concentrations and high subcutaneous concentrations over a period of 7 weeks. The area under the curve (AUC), the time required to achieve the maximum concentration (tmax), the maximum concentration (Cmax) in blood samples and the elimination rate constant (kel) values at the subcutaneous tissue site were selected to compare the pharmacokinetic characterization of VEGF microspheres with that of protein solutions. The in-vivo release profiles of the proteins were slower than the in-vitro release profiles and they followed the same trend as the in-vitro and in-vivo PLGA degradation rates. The PLGA microsphere degradation was the determinant step for VEGF release from the microspheres and its absorption at the subcutaneous site. Microspheres appear to be an attractive system for the localized rate-controlled delivery of VEGF. 14C-Methylation via reductive alkylation of VEGF did not affect its mitogenic activity, however approximately 25% activity was lost following release from PLGA microspheres. This loss of activity may be due to degradation in an acidic environment as a result of PLGA degradation. [source] Sedimentation field-flow fractionation and granulometric analysis of PLGA microspheresJOURNAL OF SEPARATION SCIENCE, JSS, Issue 15-16 2003Nathalie Faisant Abstract Sedimentation field flow fractionation operated in the steric hyperlayer mode was used to obtain fractions of defined characteristics from crude samples of poly(D,L-lactic-co-glycolic acid) microspheres which were polydisperse in size. In less than ten minutes, Sedimentation Field Flow Fractionation (SdFFF) separation yielded three analytical fractions of very different size and particle size distribution (PSD) characteristics, as determined by granulometric analyses (Coulter Counter® and image analysis of SEM). A crude sample (average size = 45 ,m, 105% size polydispersity index) was separated into fractions of 73 ,m, 56 ,m, 8 ,m average diameters which showed a PSD of 39%, 33%, 30%, respectively. Our results demonstrated that SdFFF used in conjunction with particle size analysis offers a new approach to laboratory scale production of drug vectors of a specified average size and reduced size dispersity. In the future, this could be used to select the most convenient particles for drug loading and release. [source] Development of New Microencapsulation Techniques Useful for the Preparation of PLGA MicrospheresMACROMOLECULAR RAPID COMMUNICATIONS, Issue 21 2006Hongkee Sah Abstract Summary: Intensive efforts were made to develop an efficient, novel microencapsulation system useful to encapsulate a model drug, risperidone, to PLGA microspheres. Methyl dichloroacetate was used as a dispersed solvent for the first time, since it possessed excellent solvency power on PLGA and readily underwent ammonolysis. A dispersed phase composed of methyl dichloroacetate, risperidone, and PLGA was emulsified in an aqueous phase to form an O/W emulsion. Adding ammonia solution into the emulsion rapidly converted methyl dichloroacetate into water-soluble dichloroacetamide and methanol. As a result, emulsion droplets were immediately transformed into hardened microspheres. The new microencapsulation system allowed us to make PLGA microspheres with a drug payload of >40 wt.-% and attain almost complete encapsulation efficiencies. In summary, preparing an O/W emulsion and subjecting the emulsion to ammonolysis led to development of an efficient, novel microencapsulation system. It was anticipated that the new system could make it possible to load other bioactive materials into microspheres made of various types of hydrophobic polymers. SEM micrographs of the external and internal morphology of PLGA/risperidone microspheres. [source] | ||||||||||