Clinical evaluation of the lightening effect of cytidine on hyperpigmented skin.

Abstract

Melanocytes, which reside in the basal layer of the epidermis, produce the pigment melanin in cytoplasmic organelles known as melanosomes. Melanosomes are transferred to keratinocytes which provide the color in our skin. Recently, Diwakar etal reported the crucial roles of protein glycosylation in both melanogenesis and melanosome transfer to keratinocytes, and each was inhibited by the nucleotide cytidine. The main objective of this study was to determine the clinical effects of topical application of cytidine to the hyperpigmented regions of the face in a group of human volunteers. A randomized, vehicle-controlled study was conducted for 12weeks on healthy Korean female subjects. Cytidine was formulated into the lotion at concentrations of 2%, 3%, and 4% (w/w) and compared to the vehicle control formulation. The clinical outcomes were evaluated by performing visual assessment grading, measuring melanin index, skin brightness, and skin color parameters. In vitro skin penetration studies were conducted using Franz cell chambers for the 2% cytidine test formulation. The test group showed significant improvements in the visual assessment scores, melanin index, skin brightness, and skin color compared to the control group. Although significant dose-dependent improvements were seen in the clinical study, the in vitro Franz cell studies indicated that the clinical efficacy and potency of cytidine might be further enhanced by formulating a better topical delivery system, which will be the goal of our future studies. This randomized, double-blind, 12-week clinical study successfully demonstrated the efficacy of cytidine on skin depigmentation in a dose-dependent manner.