Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 51, Issue 1, Pages 45-53Publisher
ELSEVIER
DOI: 10.1016/S0939-6411(00)00138-7
Keywords
reservoir-type microsphere; poly(lactic-co-glycolic acid); poly(lactic acid); phase separation; amphiphilic polymer; poly(ethylene glycol); polyvinylpyrrolidone; release modification
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The effects of various amphiphilic polymers on the kinetics of protein release from reservoir-type microspheres, prepared by a solid-in-oil-in-water emulsion-solvent evaporation method, were investigated. Bovine serum albumin (BSA), as a model protein, was firstly micronized through co-lyophilization with amphiphilic polymers, such as poly (ethylene glycol) (PEG), polyvinylpyrrolidone (PVP), and pluronic F68. This process was based on the aqueous phase separation of protein and amphiphilic polymer induced by freezing-condensation. Mixing of poly(lactic-co-glycolic acid) (PLGA) and poly(lactic acid) (PLA) (at a ratio of 4:6) in a methylene chloride solution provided a 'polymeralloy' structure, where the preformed solid BSA microparticles were selectively distributed in the inner PLGA-rich phase. The reservoir-type microspheres obtained through this process showed high entrapment efficiencies (more than 85%) and reduced initial burst releases (less than 10%). Although PVP did not modify the BSA release profile, PEG and pluronic F68 enhanced the BSA release, with no increase of the initial burst effect, responding to their loading percentage: 3% loading of PEG or pluronic F68 resulted in typical zero-order release kinetics. The abilities of these amphiphilic polymers to modify the protein release profile could be predicted from their partitioning characteristics in the polymer-alloys and in the methylene chloride/water system. (C) 2001 Elsevier Science B.V. All rights reserved.
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