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Clinical treatment is limited by the short half\u2010lives and hydrophilicity of drugs, necessitating release curve optimization to maintain a stable therapeutic concentration for an extended period. This article utilizes natural biomaterials to design a core\u2010shell structured microneedle, combining the \u201cimmediate release\u201d and \u201cdelayed release\u201d module to achieve programmed drug release. Silk fibroin with a crystalline structure is used as the shell to ensure the harmlessness of the accessible areas, which can provide a release channel for 24\u00a0h. The cellulose in the core layer undergoes acetylation treatment, endowing it with the ability to regulate the diffusion flux of hydrophilic drugs. Further, the release kinetics can be tuned based on the crystallinity of the shell layer and the degree of acetylation in the core layer. In the melasma model, glutathione and tranexamic acid play a major role at 0\u20134\u00a0h and 4\u201324\u00a0h, respectively, with bioavailability increased to 264% and 172%. The synergistic effect reduces the generation and transfer of melanin, and restores skin color to near normal. Therefore, this core\u2010shell structure microneedle patch is expected to promote the long\u2010term clinical treatment of melasma.<\/jats:p>","DOI":"10.1002\/adhm.202502052","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T05:27:30Z","timestamp":1757482050000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Core\u2010Shell Structured Microneedle Patch With Adjustable Release of Kinetically for the Treatment of Melasma"],"prefix":"10.1002","volume":"15","author":[{"given":"Tianshuo","family":"Jia","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyu","family":"Geng","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Shao","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanai","family":"Chen","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohongfang","family":"Tan","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering Soochow University  Suzhou 215123 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhas C.","family":"Kundu","sequence":"additional","affiliation":[{"name":"I3Bs Research Institute on Biomaterials, Biodegrabilities, and Biomimetics University of Minho  AvePark \u2013 Barco Guimaraes 4805\u2010017 Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4188-2057","authenticated-orcid":false,"given":"Shenzhou","family":"Lu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for Modern Silk, College of Textile and Clothing Engineering Soochow University  Suzhou 215123 China"},{"name":"Shengzhou Silk Protein Biotechnology Application Research Institute  Shengzhou Zhejiang 312400 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.25259\/IJDVL_530_2021"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1337282"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1421499"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.4103\/idoj.idoj_495_22"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-51133-w"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7487452"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.17094"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/4413130"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.29271\/jcpsp.2021.05.502"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jocd.16707"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2025.106785"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116751"},{"key":"e_1_2_8_13_1","first-page":"110","volume":"14","author":"Hong J.","year":"2018","journal-title":"Phcog. 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