In vitro characterization and in vivo release profile of a poly(D,L-lactide-co-glycolide)-based implant delivery system for the α-MSH analog, melanotan-I

Melanotan-I (MT-I) is a superpotent tridecapeptide capable of stimulating melanotropic activity. In order to overcome its short half-life in the systemic circulation, the biodegradable poly(D,L-lactide-co-glycolide) (PLGA) copolymer was used to prepare an implant delivery system for MT-I. The implant was prepared by the hot melt-extrusion method. The surface morphology of the PLGA implant was assessed using scanning electron microscopy. The lime-dependent changes in the molecular weight distribution of the copolymer and its erosion were monitored in order to help characterize the hydrolytic degradation processes occurring in vivo. The time required to reduce the weight-average molecular weight of PLGA to 50% of its initial value, as determined by size exclusion chromatography, was about 12 days compared to 5 weeks for 50% erosion of the copolymer mass to occur. The release of lactic acid from PLGA was also quantified simultaneously in order to characterize the degradation, and the onset of increased lactic acid release was found to coincide with the onset of the tertiary phase of the MT-I release profile in vivo in guinea pigs. The MT-I released from the depot implanted subcutaneously in guinea pigs exhibited a release profile extending over one month, in agreement with data from the in vitro studies. (C) 1998 Elsevier Science B.V. All rights reserved.