Degradation and protein release properties of microspheres prepared from biodegradable poly(lactide-co-glycolide) and ABA triblock copolymers: influence of buffer media on polymer erosion and bovine serum albumin release

The aim of the present study was to investigate the influence of the chemic al insertion of poly(ethylene oxide), PEG, into a poly(lactide-co-glycolide ), PLG, backbone on the mechanisms of in vitro degradation and erosion of t he polymer. For this purpose microspheres prepared by a modified W/O/W doub le emulsion technique using ABA triblock copolymers, consisting of PLG A-bl ocks attached to central PEO B-blocks were compared with microspheres prepa red from PLG. Due to their molecular architecture the ABA triblock copolyme rs differed in their erosion and degradation behavior from PLG. Degradation occurred faster in the ABA polymers by cleavage of ester bonds inside the polymer backbone. Even erosion was shown to start immediately after incubat ion in different buffer media. By varying pH and ionic strength of the buff er it was found that both mass loss and molecular weight decay were acceler ated in alkaline and acidic pH in the case of the ABA triblock copolymers. Although the pH of the medium had a moderate influence on the degradation o f PLG, the molecular weight decay was not accompanied by a mass loss during the observation time. In a second set of experiments we prepared bovine se rum albumin, BSA, loaded microspheres from both polymers. The release of BS A from ABA microspheres under in vitro conditions parallels the faster swel ling and erosion rates. This could be confirmed by electron paramagnetic re sonance, EPRI measurements with spin labeled albumin where an influx of buf fer medium into the ABA microspheres was already observed within a few minu tes. In contrast, PLG microspheres revealed a burst release without any ero sion. The current study shows that the environmental conditions affected th e degradation and erosion of the pure polymer microspheres in the same way as the release of the model protein. This leads to the conclusion that the more favorable degradation profile of the ABA triblock copolymers was respo nsible for the improvement of the release profile. (C) 1999 Elsevier Scienc e B.V. All rights reserved.