The H2S-releasing multifunctional composite ionic liquid facilitates topical melittin delivery for psoriasis treatment through RONS scavenging and inflammation inhibition

Psoriasis, an immune-mediated disease, commonly utilizes topical drug administration in clinical treatments, yet the thickening of skin presents a challenge to conventional topical drug delivery methods. In this study, we have successfully developed a multifunctional composite ionic liquid (CIL) that enhances the local delivery of melittin (CIL@Mel) by modifying the fluidity of the stratum corneum and the structure of keratin. In addition, CIL@Mel can transport H 2 S to the psoriatic microenvironment, effectively regulating the redox imbalance within it. The in vivo experimental results demonstrated that CIL@Mel effectively mitigates the progression of psoriasis, provides relief from oxidative stress, reduces the production of inflammatory factors, and promotes the repolarization of macrophages. Computational simulations and experimental validation revealed that CIL@Mel exerts its effects by inhibiting the expression of EGFR, STAT3, IL-6, SRC, and HSP90AA1. In conclusion, this study unveils the transdermal promotion mechanism of CIL@Mel and validates its efficacy in psoriasis.