This study was conducted to evaluate the effects of unsaturated fatty acids on ultraviolet-induced hyperpigmentation of the skin. An efficient lightening effect was observed following topical application of linoleic acid or alpha-linolenic acid to UV-stimulated hyperpigmented dorsal skin of brownish guinea pigs. The number of melanocytes in the treated skin was similar to the number in the skin of the pigmented control, indicating that the pigment-lightening effect was not due to depletion of melanocytes. In vitro experiments using cultured murine melanoma cells showed that melanin production was inhibited most effectively by alpha-linolenic acid, followed by linoleic acid and then by oleic acid. Furthermore, the turnover of the stratum corneum, which plays an important role in the removal of melanin pigment from the epidermis, was accelerated by linoleic acid and by alpha-linolenic acid. Taken together, the results suggest that the pigment-lightening effects of linoleic acid and alpha-linolenic acid are, at least in part, due to suppression of melanin production by active melanocytes, and to enhanced desquamation of melanin pigment from the epidermis.

Hyperpigmentation on faces is a highly anxiety-producing symptom, especially for women from the aspect of beauty. We previously reported the skin whitening effect of linoleic acid (LA), 1,2) the mechanism of the whitening effect involving a decrease in tyrosinase level by LA, 3) and clinical trials of liposomal LA for skin hyperpigmentary disorders, such as melasma.4) Although these reports described the whitening effect of LA in transdermal application, and the stabilization of LA by liposomal formulation, it was not confirmed whether LA encapsulated in liposomes enhanced the skin whitening effect. There have been number of reports that describe transdermal application using liposomes on cutaneous absorption, 5-7) on the transdermal delivey of encapsulated drugs 8) and on effective interaction of dermal skin cells with liposomes containing drugs in liposomes.9-11) The synergistic effect of liposomes on active reagents for whitening via transdermal application was also reported.12) Compared to those reagents previously reported, LA is not only effective in whitening but also quite safe.13) Although there are many examples of the transdermal applications of liposomal formulations, little is known about the enhancement of drug efficacy by liposomalization. From this point of view, we were interested in the possible enhancement of LA's whitening activity by encapsulating it in liposomes. The present study clearly demonstrated that LA encapsulation in liposomes significantly enhanced it's whitening efficacy by transdermal application for UV-induced hyperpigmented dorsal skin of brownish guinea pigs. We also observed enhanced whitening efficacy by liposomalization of LA in UV-induced hyperpigmented human skin. MATERIALS AND METHODSWhitening Assay UVB-induced hyperpigmentation was elicited on the backs of brownish guinea pigs weighing about 600 g each (Saitama Experimental Animal Supply Co., Japan) using a modification of the method reported by Imokawa et al.14) Guinea pigs were gently tethered, and four separate areas (2.5 cmϫ2 cm) on the back of each animal were exposed to UVB radiation (ToRex FL20S-E-30/DMR, Toshiba, Japan) three times a week (every other day) for two consecutive weeks. The UVB intensity was 2 mW/cm 2 , and total energy dose was 1 J/cm 2 per exposure. Groups of six or more animals were used in each experiment. The animals were then left for an additional week to allow the UVBinduced hyperpigmentation to stabilize. Test samples were then topically applied daily to the hyperpigmented areas (0.01 ml/cm 2 ) five times per week for 3 successive weeks. The degree of pigmentation was assessed as the L-value measured with a chromameter (CR-200, Minolta, Japan) once every week from the beginning of sample application. The animals were cared for according to the guidelines for the Care and Use of Laboratory Animals of the University of Shizuoka.In the case of human skin assay, persons being tested were 6 healthy men in their 20 s or 30 s. After obtaining informed consents from the volunteers, UVB-induced hyp...

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