A Double-Layer Microneedle Patch Containing Methylprednisolone and Upadacitinib-Loaded Mesoporous Silica Nanocomposites for Psoriasis Treatment.

Psoriasis is promoted by signaling through the IL-23/IL-17 pathway. Existing oral or topical treatment regimens can hardly balance acute flare-ups with long-term maintenance. A dual-layer soluble microneedle (MN) that combines methylprednisolone (MP) and upadacitinib (UPA) was developed using an immediate-release-controlled-release spatiotemporal program to achieve rapid anti-inflammatory effects and sustained immunosuppression. The outer layer contains mechanically robust gelatin-polyvinyl alcohol (Gel-PVA) hydrogel loaded with MP, while the inner layer contains light-curable methyl acrylate hyaluronic acid (MeHA) to encapsulate UPA (UPA/SBA-15)-loaded mesoporous silica. The results revealed that the MNs penetrated the thickened stratum corneum, releasing 70% of MP within 2 h, and UPA release was sustained via SBA-15 mesopores over the next 48 h, significantly inhibiting IL-17A, IL-1β, IL-6, and TNF-α 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-free, precise, and low-toxicity transdermal glucocorticoid and JAK1 inhibitor delivery through synergistic effects of mechanical penetration and mesoporous sustained release, offering translational potential for personalized psoriasis treatment.