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. The dissociation constants of 1 were determined using potentiometric titration and ultraviolet spectrophotometry. The pKa1 (histidine) and pKa2 (arginine) were estimated to be 6.54 and 11.72, respectively. The apparent partition coefficient (PC) was measured at three pH values using both n-octanol and isooctane as the nonpolar phase. The PC(octanol) and delta log PC at pH 7.35 were 2.82 and 1.05, respectively. These 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 dosage form for 1.
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Department of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, Tucson 85721.
Ugwu
S O
SO
Blanchard
J
J
Fang
X
X
Hruby
V J
VJ
Sharma
S
S
D000595:Amino Acid Sequence; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011199:Potentiometry; D051381:Rats; D012878:Skin Neoplasms / Q000517:prevention & control*; D013056:Spectrophotometry, Ultraviolet; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
D016588:Anticarcinogenic Agents; D010456:Peptides, Cyclic; C079282:melanotan-II; D000521:alpha-MSH