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Abstract
Carrier systems for local gentamicin (GS) treatment based on collagen sponges and polymethylmethacrylate beads show pharmacokinetic disadvantages in their GS-release profiles. Therefore, poly(lactic-co-glycolic acid) (PLGA) microparticles were devised. None of the five poly(α-hydroxy acid)s tested resulted in the desired antibiotic release over approximately one week. However, preparing microparticles from a 50/50 blend of Resomer® RG 502H, an uncapped variety, and Resomer RG 503, an endcapped polymer, yielded the targeted liberation profile. The mechanism of GS release was investigated by analyzing water uptake and polymer molecular weight. Release of GS from RG 502H particles occurred instantaneously and coincided with substantial water penetration. Particles prepared from RG 503 started out at a higher molecular weight and since the endcapped polymer takes up less water, the decrease in molecular weight was delayed. The threshold of collapse was reached after two weeks, which coincided with water penetration and GS release. For the 50/50 RG 502H/RG 503 blend, this process was delayed for two to three days. Hydrolysis occurred at the same rate as for RG 502H due to the high water content as a consequence of the uncapped polymer fraction and renders GS release over one week with release limited to 30% in the first two days due to the endcapped polymer fraction of higher molecular weight. Thus, the mixture of endcapped and uncapped Resomer exhibits a new quality for adjusting drug release from poly(α-hydroxy acid)s.