Transdermal hydrogen therapy for psoriasis using cavity-embedded double-conical microneedles.

Psoriasis remains clinically incurable due to its complex etiology. Topical immunosuppressive therapies offer limited effectiveness partly because of poor skin permeability, and can cause severe side effects. To address these challenges, we developed a novel transdermal hydrogen therapy that targets the mutually-reinforcing coupling between oxidative stress and inflammation in psoriasis. Specifically, we designed a double-conical microneedle with high loading capacity and effective skin penetration to efficiently deliver MgH2 powders, enabling the sustained release of molecular hydrogen within the skin tissue. This minimally invasive, self-administrable treatment significantly outperformed calcipotriol cream, a current standard topical therapy. The transdermal hydrogen therapy greatly relieved oxidative damages, pro-inflammatory cytokine expression, immune cell infiltration, and ultimately mitigated keratinocyte hyperproliferation and systemic symptoms. Furthermore, the mechanistic investigations provide valuable insights into psoriasis pathogenesis. More broadly, this study demonstrates a new solution for treating inflammatory skin diseases and a new strategy for microneedle-based transdermal therapeutic delivery.