PREFORMULATION STUDIES WITH MELANOTAN-II - A POTENTIAL SKIN-CANCER CHEMOPREVENTIVE PEPTIDE

Melanotan-II (1) is a cyclic heptapeptide analogue of alpha-melanocyte -stimulating hormone (alpha-MSH) which tans the skin and is currently being evaluated for the prevention of sunlight-induced skin cancers. T he dissociation constants of 1 were determined using potentiometric ti tration and ultraviolet spectrophotometry. The pK(a1) (histidine) and pK(a2) (arginine) were estimated to be 6.54 and 11.72, respectively. T he apparent partition coefficient (PG) was measured at three pH values using both n-octanol and isooctane as the nonpolar phase. The PC(octa nol) and Delta log PC at pH 7.35 were 2.82 and 1.05, respectively. The se data, together with the observance of a bioavailability of 4.6% in the rat, indicate that 1 may be a suitable candidate for oral delivery . The data presented here are useful in developing an appropriate dosa ge form for 1.