Release mechanisms from gentamicin loaded poly(lactic-co-glycolic acid) (PLGA) microparticles

Abstract

To provide local gentamicin delivery for 1 week based on a biodegradable system, poly(lactic-co-glycolic acid) (PLGA) microparticles were developed utilizing a 50/50 blend of Resomer® RG 502H, an uncapped variety of 13.5 kD, and Resomer® RG 503, an endcapped polymer of 36.2 kD. The liberation mechanism was investigated by analysis of morphological changes and thermal analysis focusing on the polymer glass transition temperature (Tg) and the mechanical properties. The release of gentamicin was related to a structural breakdown of the particles reaching a critical molecular weight. A Tg of < 37°C in the hydrated state was not indicative of collapse and agglomeration of the particles because the mechanical strength of the polymer structures in the rubbery state may still render sufficient support. As the gap between incubation temperature and Tg widened, the mechanical stability of the PLGA microparticles decreased and became decisive. Particles prepared with RG 502H show a lower ability to bear mechanical stress than RG 503 and 50/50 RG 502H/RG 503 microparticles. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 845–855, 2002