In vitro and in vivo degradation of double-walled polymer microspheres

Abstract

By exploiting the phenomenon of phase separation, double-walled microspheres consisting of a core of one polymer surrounded by a coating of a second polymer were formed using a modified process of solvent evaporation. This paper discusses the characterization and in vitro and in vivo degradation of these microspheres made of two biodegradable polymers with poly(lactic acid) (PLA) as the external layer and poly( 1,3-bis(p-carboxyphenoxypropane)-co-(sebacic anhydride)) 20:80 (P(CPP:SA)20:80) as the inner core. The microspheres degraded in vitro were analyzed by Fourier-transform infrared (FTIR) spectroscopy, gel permeation chromatography (GPC), differential scanning calorimetry (DSC), and optical and scanning electron microscopy (SEM). The same methods were used to characterize the microspheres used in the in vivo study before intramuscular implantation. The tissue containing the microspheres was explanted and studied histologically by optical microscopy and SEM. The microspheres from both studies showed the same patterns of degradation, albeit at slightly different rates. The polyanhydride was hydrolyzed into oligomers first, with the PLA degrading more slowly, decreasing in molecular weight and increasing in fragility over the course of the study. The main difference between the two studies was that in vitro the inner core of degrading polyanhydride was trapped by the outer layer of PLA, even as long as 187 days while after only 72 days in vivo the polyanhydride had disappeared.