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Existing oral or topical treatment regimens can hardly balance acute flare\u2010ups with long\u2010term maintenance. A dual\u2010layer soluble microneedle (MN) that combines methylprednisolone (MP) and upadacitinib (UPA) was developed using an immediate\u2010release\u2013controlled\u2010release spatiotemporal program to achieve rapid anti\u2010inflammatory effects and sustained immunosuppression. The outer layer contains mechanically robust gelatin\u2013polyvinyl alcohol (Gel\u2010PVA) hydrogel loaded with MP, while the inner layer contains light\u2010curable methyl acrylate hyaluronic acid (MeHA) to encapsulate UPA (UPA\/SBA\u201015)\u2010loaded mesoporous silica. The results revealed that the MNs penetrated the thickened stratum corneum, releasing 70% of MP within 2\u00a0h, and UPA release was sustained via SBA\u201015 mesopores over the next 48\u00a0h, significantly inhibiting IL\u201017A, IL\u20101\u03b2, IL\u20106, and TNF\u2010\u03b1 expression. In a psoriasis mouse model, the patch group revealed an approximately 90% Psoriasis Area and Severity Index (PASI) reduction, with normal pathological epidermal thickness achieved. Compared with those in the tacrolimus group (positive control group), serum and skin inflammatory factor levels were significantly lower, with no systemic toxicity. This MN platform achieves pain\u2010free, precise, and low\u2010toxicity transdermal glucocorticoid and JAK1 inhibitor delivery through synergistic effects of mechanical penetration and mesoporous sustained release, offering translational potential for personalized psoriasis treatment.<\/jats:p>","DOI":"10.1002\/mabi.202500530","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T03:50:50Z","timestamp":1763351450000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Double\u2010Layer Microneedle Patch Containing Methylprednisolone and Upadacitinib\u2010Loaded Mesoporous Silica Nanocomposites for Psoriasis Treatment"],"prefix":"10.1002","volume":"26","author":[{"given":"Die","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Therapy, School of Rehabilitation and Yunnan Key Laboratory of Plateau Thermal Medical Rehabilitation and Wellness Kunming 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