An approach for psoriasis of microneedle patch simultaneously targeting multiple inflammatory cytokines and relapse related T cells.

Abstract

Psoriasis is a chronic inflammatory skin disorder affecting approximately 125 million people globally. Topical medications are a cornerstone of current treatment protocols; however, their efficacy in mitigating inflammation is constrained by their predominantly single-target mechanisms. A significant challenge is the lack of pharmaceuticals specifically targeting CD8⁺ tissue resident memory T (CD8⁺ TRM) cells, which are the targets in psoriasis relapse. Consequently, relapse rates can soar to 90% post-treatment discontinuation. In this study, we successfully screened a specific macrophage membrane capable of targeting multiple inflammatory factors at psoriatic sites. This membrane was coextruded with etomoxir, a compound that targets CD8⁺ TRM cells. To enhance drug retention and penetration, we employed a delivery strategy involving PDA and microneedles, resulting in the synthesis of PDA-Etomoxir-Macrophage membrane@microneedle (PEM@m). In vivo, PEM@m exhibited superior efficacy in alleviating psoriasis symptoms and preventing relapse compared to the clinical drug calcipotriol (Cal). Mechanistically, PEM@m broadly inhibits inflammatory signals, and its reduction of CD8⁺ TRM cells can be associated with decreased activity in the pentose phosphate pathway (PPP). Our study offers a novel and promising approach for the definitive treatment of psoriasis.