Celastrol-Loaded Liposomal Hydrogel Microneedles for Safe and Effective Treatment of Psoriasis

Background: Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal hyperplasia and immune-inflammatory imbalance. Although celastrol (Cel) exhibits potent anti-inflammatory activity, its strong hydrophobicity and low local delivery efficiency limit its therapeutic application. Methods: To enhance its transdermal delivery and topical therapeutic efficacy, a Cel-loaded liposomal hydrogel microneedle system (Cel-lipo-MNs) was developed in this study. Cel-loaded liposomes were first prepared by the thin-film dispersion method, and Cel-lipo-MNs were subsequently fabricated using a multistep vacuum micromolding process combined with UV-induced photocrosslinking. Results: In vivo studies demonstrated that, in an imiquimod-induced psoriasis-like mouse model, Cel-lipo-MNs markedly alleviated erythema, scaling, and skin thickening, reduced PASI-like scores. Further investigation revealed that Cel-lipo-MNs significantly downregulated the serum levels of IL-17, IL-23, and IFN-γ, and exhibited superior therapeutic efficacy compared with free celastrol, conventional liposomes, and blank microneedles. Conclusions: These findings indicate that Cel-lipo-MNs can substantially enhance the therapeutic effect of celastrol against psoriasis-like skin lesions, possibly through suppression of the IL-23/IL-17 inflammatory axis and related immune-inflammatory responses, and provide a promising transdermal delivery strategy for topical psoriasis treatment.