Yan Chenxin, Xing Mengzhen, Zhang Suohui, Gao Yunhua
Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Polymers (Basel). 2023 Aug 4;15(15):3296. doi: 10.3390/polym15153296.
Excessive melanin deposition in the skin leads to various skin pigmentation diseases, such as chloasma and age spots. The deposition is induced by several factors, including tyrosinase activities and ultraviolet-induced oxidative stress. Herein, we propose a multi-component, multi-pathway drug combination, with glabridin, 3-O-ethyl-L-ascorbic acid, and tranexamic acid employed as, respectively, a tyrosinase inhibitor, an antioxidant, and a melanin transmission inhibitor. Considering the poor skin permeability associated with topical application, dissolving microneedles (MNs) prepared with hyaluronic acid/poly(vinyl alcohol)/poly(vinylpyrrolidone) were developed to load the drug combination. The drug-loaded microneedles (DMNs) presented outstanding skin insertion, dissolution, and drug delivery properties. In vitro experiments confirmed that DMNs loaded with active ingredients had significant antioxidant and inhibitory effects on tyrosinase activity. Furthermore, the production of melanin both in melanoma cells (B16-F10) and in zebrafish was directly reduced after using DMNs. Clinical studies demonstrated the DMNs' safety and showed that they have the ability to effectively reduce chloasma and age spots. This study indicated that a complex DMN based on a multifunctional combination is a valuable depigmentation product worthy of clinical application.
皮肤中黑色素过度沉积会导致各种皮肤色素沉着疾病，如黄褐斑和老年斑。这种沉积是由多种因素引起的，包括酪氨酸酶活性和紫外线诱导的氧化应激。在此，我们提出一种多组分、多途径的药物组合，分别使用光甘草定、3 - O - 乙基 - L - 抗坏血酸和氨甲环酸作为酪氨酸酶抑制剂、抗氧化剂和黑色素传递抑制剂。考虑到局部应用时皮肤渗透性较差，开发了用透明质酸/聚乙烯醇/聚乙烯吡咯烷酮制备的溶蚀微针（MNs）来负载该药物组合。载药微针（DMNs）具有出色的皮肤插入、溶解和药物递送性能。体外实验证实，负载活性成分的DMNs对酪氨酸酶活性具有显著的抗氧化和抑制作用。此外，使用DMNs后，黑色素瘤细胞（B16 - F10）和斑马鱼体内的黑色素生成均直接减少。临床研究证明了DMNs的安全性，并表明它们有能力有效减少黄褐斑和老年斑。这项研究表明，基于多功能组合的复合DMN是一种有价值的色素沉着减退产品，值得临床应用。
