Gentamycin/poly (lactic acid) blends aimed at sustained release local antibiotic therapy administered per-operatively. III. The case of gentamycin sulfate in films prepared from high and low molecular weight poly ( DL-lactic acids)

Abstract

Biodegradable films were prepared by casting acetone solutions of high and low molecular weight poly ( dl-lactic acids), respectively PLA50P and PLA50p, on glass plates before drying. Under these conditions, PLA50p played the role of plasticizer for PLA50P, as shown from DSC and dynamic mechanical characteristics. Similar films were prepared which contained different loads of gentamycin sulfate (GS) in attempts to make a delivery system suitable for local antibiotic therapy administered per-operatively. Biphasic release profiles were obtained in pH = 7.4, 0.13 M phosphate buffer at 37°C with a small burst effect followed by a controlled release period which lasted for at least 45 days, depending on the film composition. Size exclusion chromatography (SEC) and assays of gentamycin and of l-lactic acid showed that the higher the amounts of PLA50p oligomers in the blend, the higher the release rate of gentamycin and the higher the degradation rate of the matrix. In the absence of PLA50p oligomers, the release of GS obeyed a t 1 2 kinetics law. In the presence of oligomers, a zero-order release was observed which was discussed with respect to the mechanisms of degradation of the PLA matrices. It was also found that the degradation rate of PLA depended on the presence of gentamycin. This dependence was assigned to interactions between carboxylic acid end-groups and the antibiotic as previously shown for PLA50 oligomers.