Biomimetic polydopamine loaded with janus kinase inhibitor for synergistic vitiligo therapy via hydrogel microneedles.

backgroundBoth oxidative stress and autoimmune responses play crucial roles in the development of vitiligo. Under oxidative stress, the apoptotic melanocytes expose self-antigens and release high mobility group box 1 (HMGB1), triggering autoimmune activation and recruiting CD8

resultsIn this study, we introduce a novel therapeutic agent called PDA-JAKi, which is capable of both eliminating oxidative stress and inhibiting T cell activation. Specifically, we have incorporated the janus kinase inhibitor (JAKi) tofacitinib into antioxidant polydopamine (PDA) nanoparticles, resulting in the formation of uniform PDA-JAKi nanodrug. PDA-JAKi effectively mitigates oxidative stress-induced apoptosis in melanocytes, reducing the antigen presentation and release of HMGB1. In addition, PDA-JAKi simultaneously attenuates oxidative stress and blocks the IFN-γ-JAK-STAT pathway to reduce the expression of C-X-C motif chemokine ligand 9/10/16 (CXCL9/10/16) in keratinocytes. We precisely deliver this therapeutic agent to the dermis using microneedle (MN) patches, aiming to enhance therapeutic efficacy compared to traditional drug administration methods. After PDA-JAKi MN treatment, the symptoms of vitiligo in mice are alleviated, and the affected areas regain pigmentation. Enhancements have been observed in the dermal thickness, the numbers of melanocytes and the content of melanin within the treated skin area. Moreover, there is a notable reduction in reactive oxygen species (ROS) level. Concurrently, substantial decreases were noted in CD8

conclusionsIn summary, PDA-JAKi MN patches emerge as a promising therapeutic agent for vitiligo treatment.