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In view of this, a dual\u2010layered microneedle system was developed for obesity treatment. Firstly, capsaicin (Cap) and mitochondrial uncoupler BAM15 were respectively co\u2010assembled with solutol HS\u201015 (HS) to obtain functionalized nanodrugs (HS@Cap NPs or HS@BAM15 NPs). Then they were integrated into the microneedle system (BC\u2010MNs). The BC\u2010MNs realize programmed controlled release of nanodrugs in subcutaneous tissue via transdermal delivery. HS@Cap NPs rapidly release at the needle tip to penetrate deep white adipose tissue and promote its browning. Sequentially, slowly released HS@BAM15 NPs then accumulate in beige adipocytes to enhance cell metabolism, achieving synergistic anti\u2010obesity effects. Finally, both in vitro and in vivo experiments analyzed and validated the therapeutic efficacy of this system for obesity. In summary, the above\u2010mentioned cascade co\u2010treatment strategy based on the microneedle drug delivery system provides a potential possibility for clinical management and treatment of obesity.<\/jats:p>","DOI":"10.1002\/adhm.71409","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:49:17Z","timestamp":1783327757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Programmed Drug\u2010Loaded and Penetration\u2010Delivery Functionalized Microneedle Patch for Synergistic Obesity Treatment"],"prefix":"10.1002","volume":"15","author":[{"given":"Feng","family":"Zeng","sequence":"first","affiliation":[{"name":"Research Center for Pharmaceutical Preparation and Nanomedicine Technology College of Pharmacy Chongqing Medical University  Chongqing P. R. 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