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 impacting approximately 125 million people worldwide. Topical medications play an important role in the existing treatment regimen, while commercially available topical drugs’ efficacy in providing anti-inflammatory effects is limited due to the predominantly single-target. Furthermore, a pressing issue is the absence of pharmaceutical agents specifically targeting CD8+ tissue resident memory T (CD8+ TRM) cells (the target for psoriasis relapse). Consequently, the relapse rate following cessation of existing treatments can reach as high as 90%. In this study, a specific macrophage membrane was effectively screened for its ability to target multiple inflammatory factors at the site of psoriasis, and was subsequently coextruded with etomoxir, a compound that specifically targets CD8+ TRM cells. Additionally, a delivery strategy utilizing PDA and microneedles was chosen to enhance drug retention and penetration. Ultimately, a novel formulation, PDA-Etomoxir-Macrophage membrane@microneedle (PEM@m), was successfully synthesized. In vivo, PEM@m demonstrated superior efficacy in alleviating psoriasis symptoms and preventing relapse compared to the clinical drug calcipotriol (Cal). From a mechanistic standpoint, PEM@m exhibits a wide-ranging inhibitory impact on inflammatory signals. Moreover, its elimination of CD8+ tissue-resident memory cells can be linked to a decrease in the pentose phosphate pathway (PPP). Our study provides a novel and promising strategy for the radical treatment of psoriasis.

Note:
Funding Information: The work was financially supported by grants from the National Natural Science Foundation of China (32371454, 81871315, 32271387, 82305232, 82304819, 82204954), National Key Research and Development Program of China (2018YFC1705305).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: All the animal procedures were authorized by the Ethics Committee of Yueyang Hospital affiliated to Shanghai University of Traditional Chinese Medicine (no. YYLAC-2022-160-9, YYLAC-2022-160-8).

Keywords: psoriasis, relapse prevention, Macrophage Membrane, etomoxir, microneedle