Skin Whitening Effect of Linoleic Acid Is Enhanced by Liposomal Formulations

Abstract

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...

The Effect of Component of Cream for Topical Delivery of Hesperetin

“…The change level of L* by blank cream (without drug but containing lecithin and linoleic acid of 2.5%) application was higher than that of non-treatment, although no significant difference was found in this study. The result was similar to previous research studies [15][16][17][18] that pointed out linoleic acid and lecithin have depigmentation effect, but the basal formulation influences their whitening effect.…”

“…Lecithin and linoleic acids are fatty acids and used in cosmetic products as depigmenting agents. [15][16][17][18] Both of them have also permeation enhancement effect for drugs such as piroxicam and ketoprofen. 6,[19][20][21] These four enhancers were used to improve the permeation of hesperetin in this study.…”

“…Therefore, a combination of enhancers may be able to create a synergistic effect and mitigate the irritation caused by formulation applied by decreasing the addition level of enhancers. Previous studies [15][16][17][18] reported that lecithin has an inhibitory effect on melanization, and linoleic acid can promote degradation of tyrosinase and skin turnover acceleration of melanin pigment, so they are used in cosmetic products as depigmenting agents and have benefit on photoprotective effect. Furthermore, lecithin and linoleic acid showed moderate enhancement effect for hesperetin in this study.…”

Sebumetric and mexametric evaluation of a fennel based cream

“…Linoleic acid is an unsaturated fatty acid and a major component of biological cell membranes. It is well known for having whitening effect on hyper pigmented skin 24 . Linoleic acid has been shown to speed up the degradation of tyrosinase which is involved in melanin synthesis and decrease tyrosinase levels.…”

Suppressed Permeation of Linoleic Acid in a Liposomal Formulation through Reconstructed Skin Tissue

“…[9][10][11] However, in the case of the skinwhitening effect of liposomal LA, liposomes enhanced the original efficacy of the drug. 12) Therefore the mechanism of the enhancement of the effect by encapsulating LA into liposomes attracts interest. Towards the goal to elucidate the mechanism, we investigated the dependence of the permeation rate of LA through skin tissue and lasting rate of LA in the skin surface and skin tissue on the formulation of LA, i.e., the conventional formulation without liposomes (non-liposomal LA) or liposomal formulation using a three-dimensional (3D) reconstructed skin model.…”