In vitro evaluation of Poly( d, l-lactide-co-glycolide) polymer-based implants containing the α-melanocyte stimulating hormone analog, Melanotan-I

Abstract

The release of the melanotropic peptide, Melanotan-I (MT-I), from biodegradable implants of poly( d, l lactide-co-glycolide) (PLGA) copolymer was studied. The implants were prepared by a melt-extrusion method. The in vitro release of MT-I exhibited a triphasic profile with an initial rapid release followed by a secondary phase of slow release, then a tertiary phase of rapid release due to erosion of the polymer. The initial rapid release observed with PLGA (50:50 molar ratio of lactic/glycolic acid) polymers was less than 5% of the drug load and the tertiary phase commenced after about 3 weeks. The factors controlling the drug release are degradation and erosion of the polymer which may, in turn, be controlled by the physical properties of the polymer such as molecular weight and viscosity. The influence of viscosity (0.2–1.08 dl/g) of the polymer, on the release kinetics of MT-I were analyzed and the polymer having a viscosity of 0.6 dl/g was selected for preparing a 1-month implant system. Molecular weight distribution analysis indicated a biphasic rate of molecular weight reduction and within 12 days, the molecular weight had decreased to 50% of the initial value. The release rate was examined at different drug loading levels and in the presence of some hydrophilic additives. The effect of gamma radiation on the release kinetics of the peptide was analyzed to determine the optimal radiation sterilization dose for the PLGA implants. There was no significant difference in the total duration of MT-I release between the implants exposed to no radiation and the 2.5 Mrad dose selected.