BOVINE SERUM-ALBUMIN LOADED POLY(LACTIDE-CO-GLYCOLIDE) MICROSPHERES -THE INFLUENCE OF POLYMER PURITY ON PARTICLE CHARACTERISTICS

To study the influence of polymer purity on microsphere characteristic s, bovine serum albumin (BSA) loaded biodegradable microspheres were p repared by spray drying using two samples of poly(lactide-co-glycolide ), PLG, (50:50, mwt = 35 and 69 kDa). Polymer properties were varied b y DL-lactide and glycolide addition or by ultrafiltration. While the e ffective drug loading was not affected by polymer purity, Tg was decre ased with increasing monomer and oligomer content. The removal of thes e low molecular weight substances by ultrafiltration led to a narrower molecular weight distribution compared to the untreated PLG. Concerni ng the polymer with the higher molecular weight, microsphere morpholog y was also strongly affected by polymer composition. In contrast to th e non-modified PLG, monomer addition yielded particles with a much smo other surface structure. Moreover, in vitro cytotoxicity of the micros pheres prepared from the polymer pretreated by ultrafiltration was sig nificantly reduced, whereas monomer addition caused a dramatic decreas e of cells surviving contact with the microsphere extract. The in vivo degradation rate of the ultrafiltered microspheres was decreased and as a result, protein release at later times was slowed down. Furthermo re, depending on the effective drug loading level, monomer addition re sulted in a decrease in the initial protein burst. It can be concluded that the effect of low molecular weight impurities in a polymer on mi crosphere characteristics and on cytotoxicity cannot be ignored. Their elimination is possible by ultrafiltration.