Biomimetic Polydopamine Loaded with Janus Kinase Inhibitor for Synergistic Vitiligo Therapy via Hydrogel Microneedles

Abstract

Background Both oxidative stress and autoimmune responses play crucial roles in the development of vitiligo. Under oxidative stress, the apoptotic melanocytes exposure self-antigens and release high mobility group box 1 (HMGB1), triggering autoimmune activation and recruiting CD8+ T cells. This process further leads to the destruction of melanocytes, resulting in a lack of melanin granules. Additionally, oxidative stress induces keratinocytes to express and release T cell chemotactic factors, exacerbating vitiligo. The reduction of CD8+ T cells by safeguarding melanocytes and keratinocytes from oxidative stress may be contemplated as a promising approach for vitiligo therapy. Results In 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 effectively mitigates apoptosis in melanocytes, reducing the antigen presentation and release of HMGB1. Simultaneously, PDA alleviates oxidative stress in keratinocytes, leading to a reduction in the expression of chemotactic factors. JAKi, binding to JAK, significantly diminishes the activation of T cells. 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 noted in the dermal thickness within the treated skin area. Concurrently, a decrease in the abundance of immune cells, particularly the infiltration of CD8+ T cells, have been observed. Moreover, there is a notable reduction in interferon-γ (IFN-γ) levels, along with a substantial decrease in the chemotactic factors C-X-C motif chemokine ligand 10 (CXCL10) and C-X-C motif chemokine ligand 16 (CXCL16). Conclusions In summary, PDA-JAKi MN nanoplatform emerges as a promising therapeutic agent in vitiligo treatment.