Repurposing copper diethyldithiocarbamate (CuET) in a polymeric nanofibrous patch for topical therapy of psoriasis.

The management of psoriasis remains challenging due to the limitations of current therapies. This study explores the repurposing of copper diethyldithiocarbamate (CuET)-a metabolite of the anti-alcoholism drug disulfiram-as a novel topical agent for psoriasis. To this end, we developed an advanced delivery platform by fabricating a CuET-loaded nanofiber patch via electrospinning of a polyvinylpyrrolidone/polyethylene glycol/citric acid (PVP/PEG/CA) blend. This rationally designed matrix provided optimal mechanical strength, moisture-activated adhesion, and precise local drug delivery performance, thereby addressing the application challenges associated with xerotic psoriatic skin. In an imiquimod-induced psoriasis mouse model, the nanofiber patch exhibited efficacy comparable to the that of clinical standard clobetasol propionate ointment, significantly alleviating clinical scores and epidermal hyperplasia. Mechanistically, the patch mediated a multimodal therapeutic action: it potently suppressed pathological angiogenesis (reducing CD31 + vessel density by 73.97%) and macrophage infiltration. Crucially, it normalized the dysregulated immune microenvironment by concurrently inhibiting key pro-inflammatory cytokines (IL-17A, IL-22, and IL-1β) and restoring the anti-inflammatory cytokine IL-10 to physiological levels, indicating a reset of the Th17/Treg balance. Comprehensive safety evaluation revealed no systemic toxicity. This work not only validates psoriasis as a new therapeutic indication for CuET but also presents a pioneering combined strategy of drug repurposing and material engineering, offering a safe and effective topical therapy that targets the core immune-vascular pathology of the disease.