Callicarpa nudiflora-Derived Extracellular Vesicle-Based Hydrogel Loaded with Apremilast for Enhanced Therapy of Psoriasis.

Apremilast (APST) is an effective medication for psoriasis, but its clinical application is limited by its exclusive availability as an oral tablet formulation and the associated systemic adverse effects. Hydrogel-based transdermal delivery offers a promising alternative for localized APST administration. To address this, Callicarpa nudiflora-derived extracellular vesicle-based hydrogel loaded with APST (APST-EV-Gel) was developed. APST was first loaded into Callicarpa nudiflora-derived extracellular vesicles (APST-EVs) with a drug loading of 17.14% ± 0.13% and an encapsulation efficiency of 41.49% ± 0.48%. The resulting APST-EVs were then embedded in a carbomer hydrogel to form APST-EV-Gel. Pharmacodynamic evaluation demonstrated that APST-EV-Gel significantly ameliorated skin lesions and reduced splenic inflammation in mice. The treatment also decreased infiltration of T-lymphocytes and neutrophils, downregulated the proliferation marker Ki67, and markedly lowered levels of the inflammatory cytokines TNF-α, IL-17, and IL-23. Furthermore, APST-EV-Gel promoted apoptosis in hyperproliferative keratinocytes, thereby contributing to disease alleviation. In conclusion, the combination of APST and EVs exerts superior therapeutic efficacy against psoriasis compared to monotherapy with either agent alone. APST-EV-Gel represents a promising topical therapeutic strategy for psoriasis.