IN-VITRO CHARACTERIZATION AND IN-VIVO RELEASE PROFILE OF A POLY(D,L-LACTIDE-CO-GLYCOLIDE)-BASED IMPLANT DELIVERY SYSTEM FOR THE ALPHA-MSH ANALOG, MELANOTAN-I

Melanotan-I (MT-I) is a superpotent tridecapeptide capable of stimulat ing melanotropic activity. In order to overcome its short half-life in the systemic circulation, the biodegradable poly(D,L-lactide-co-glyco lide) (PLGA) copolymer was used to prepare an implant delivery system for MT-I. The implant was prepared by the hot melt-extrusion method. T he surface morphology of the PLGA implant was assessed using scanning electron microscopy. The lime-dependent changes in the molecular weigh t distribution of the copolymer and its erosion were monitored in orde r to help characterize the hydrolytic degradation processes occurring in vivo. The time required to reduce the weight-average molecular weig ht of PLGA to 50% of its initial value, as determined by size exclusio n chromatography, was about 12 days compared to 5 weeks for 50% erosio n of the copolymer mass to occur. The release of lactic acid from PLGA was also quantified simultaneously in order to characterize the degra dation, and the onset of increased lactic acid release was found to co incide with the onset of the tertiary phase of the MT-I release profil e in vivo in guinea pigs. The MT-I released from the depot implanted s ubcutaneously in guinea pigs exhibited a release profile extending ove r one month, in agreement with data from the in vitro studies. (C) 199 8 Elsevier Science B.V. All rights reserved.