Baswan Sudhir M, Leverett Jesse, Pawelek John
Global Discovery R&D, Amway Corporation, 7575 Fulton St E, Ada, 49355, Michigan, USA.
Department of Dermatology, Yale School of Medicine, New Haven, 06520, Connecticut, USA.
J Cosmet Dermatol. 2019 Feb;18(1):278-285. doi: 10.1111/jocd.12784. Epub 2018 Oct 5.
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 et al 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 12 weeks 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.
黑素细胞位于表皮基底层，在称为黑素小体的细胞质细胞器中产生色素黑色素。黑素小体被转移到角质形成细胞中，角质形成细胞赋予我们皮肤颜色。最近，迪瓦卡尔等人报道了蛋白质糖基化在黑素生成和黑素小体向角质形成细胞转移中的关键作用，并且每种作用都受到核苷酸胞苷的抑制。
本研究的主要目的是确定在一组人类志愿者中，将胞苷局部应用于面部色素沉着区域的临床效果。
对健康的韩国女性受试者进行了一项为期12周的随机、赋形剂对照研究。将胞苷配制成浓度为2%、3%和4%（w/w）的洗剂，并与赋形剂对照制剂进行比较。通过进行视觉评估分级、测量黑色素指数、皮肤亮度和皮肤颜色参数来评估临床结果。使用Franz细胞扩散池对2%胞苷测试制剂进行体外皮肤渗透研究。
与对照组相比，试验组在视觉评估评分、黑色素指数、皮肤亮度和皮肤颜色方面有显著改善。尽管在临床研究中观察到了显著的剂量依赖性改善，但体外Franz细胞研究表明，通过配制更好的局部给药系统，胞苷的临床疗效和效力可能会进一步提高，这将是我们未来研究的目标。
这项随机、双盲、为期12周的临床研究成功地证明了胞苷在皮肤色素脱失方面呈剂量依赖性的疗效。
