Morphology, drug distribution, and in vitro release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method

Abstract

The surface and internal morphology, drug distribution and release kinetics at 22°C of polyesters such as PCL (polycaprolactone) and PLGA (poly(DL-lactic-co-glycolic acid)) 65:35 microspheres containing BSA (bovine serum albumin) have been investigated in order to understand the relationship amongst morphology, drug distribution and in vitro release profiles and to develop controlled release devices for marine fishes in tropical area. CLSM (confocal laser scanning microscope) micrographs reveal that the polyvinylalcohol (PVA as an emulsifier) concentration in the external water phase strongly influences drug distribution within microspheres and release profiles. The presence of PVA in the internal water phase enhances the stabilization of inner water droplets against coalescence. This results in a more uniform drug distribution and a slower BSA release. Different oil-phase volumes and polymer concentrations yield different solvent exchange and precipitation mechanisms, which lead to different morphologies. A low oil-phase volume yields microspheres with a porous matrix and defective skin surface, which gives a high initial BSA burst as well as a fast release profile. Microspheres fabricated from a low polymer concentration have less defective skin surface, but with a less tortuous inner matrix which results in a more rapid BSA release. A higher BSA loading yields a larger concentration gradient between the emulsion droplet and the continuous water phase as well as between the microspheres and the in vitro medium. The former results in a lower encapsulation efficiency, whereas the latter yields a faster initial burst and a more rapid release profile. High stirring speed can reduce microsphere size, but decreases the yield of microspheres. Copyright (C) 2000 Elsevier Science B.V.