Controlled-Release Delivery System for the α-MSH Analog Melanotan-I Using Poloxamer 407

Abstract

The overall objective of these studies was to develop a controlled-release formulation of Melanotan-I (MT-I) containing poloxamer 407 (P407). Various aqueous formulations were evaluated containing MT-I and 25% w/v P407 alone, or with one of the following additives present, i.e., poly(vinylpyrrolidone) 10000 (PVP), methylcellulose (MC), or hydroxypropyl methylcellulose (HPMC). The in-vitro release profiles of MT-I from the P407 formulations and the dissolution of the gel were obtained simultaneously using a membraneless in-vitro model. These data were obtained at 37 degrees C and room temperature (24 degrees C). It was observed that the PVP-containing P407 formulations of MT-I accelerated the dissolution of gel and the release of the peptide compared to the control formulation. The formulations containing MC or HPMC exhibited the slowest dissolution rates and release of MT-I. The same rank order was observed for the dissolution and release profiles of MT-I from the various formulations at both temperatures. The in-vivo release kinetics of selected formulations were analyzed in guinea pigs following intraperitoneal administration. The plasma concentration-time profiles showed an extended release of the peptide formulated with gel compared to the intraperitoneal administration of MT-I in solution. On the basis of the in-vitro and in-vivo results, the P407 formulations of MT-I with MC or HPMC as an additive showed potential for use as a controlled-release delivery system for MT-I.