Pharmacologic response of a controlled-release PLGA formulation for the alpha-melanocyte stimulating hormone analog, Melanotan-I.
OBJECTIVE
The objective of this study was to evaluate in vitro and in vivo the melanogenic activity of one-month duration Melanotan-I (MT-I) implants prepared using poly (D,L lactide-co-glycolide) polymer.


METHODS
The biological activity of the samples of MT-I released in vitro from the non-irradiated or gamma irradiated implants was measured using a frog skin bioassay. The effect of MT-I on skin pigmentation was measured using a Chroma meter (reflectometer) after subcutaneous administration of implants containing 4 mg MT-I to guinea pigs. Eumelanin, the black/brown melanin pigment, was quantified in skin biopsies as pyrrole-2, 3, 5-tricarboxylic acid using HPLC.


RESULTS
The MT-I released in vitro from implants after 24 hours exhibited 100% melanotropic activity in frog skins compared to an identical concentration of a freshly prepared MT-I standard. The reflectance readings demonstrated a prolonged skin darkening for up to three months as evidenced by the decrease in the luminance values from 0 to -4.82. A 2.5-fold increase in eumelanin levels was observed after one month and the increased pigmentation lasted for 3 months.


CONCLUSIONS
The melanogenic response to MT-I implants persisted for three months and the increase in pigmentation, especially the increased eumelanin levels, could provide protection from ultraviolet radiation.
Bhardwaj
R
R
Genzyme Corporation, Framingham, Massachusetts 01701, USA.
Hadley
M E
ME
Dorr
R T
RT
Dvorakova
K
K
Brooks
C
C
Blanchard
J
J
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D006168:Guinea Pigs; D019344:Lactic Acid; D008543:Melanins / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011758:Pyrroles / Q000378:metabolism; D011894:Rana pipiens; D012867:Skin / Q000737:chemistry; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D016588:Anticarcinogenic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D008543:Melanins; D011108:Polymers; D011758:Pyrroles; C041877:eumelanin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000521:alpha-MSH; C027756:MSH, 4-Nle-7-Phe-alpha-; C071226:pyrrole-2,3,5-tricarboxylic acid