Repurposing copper diethyldithiocarbamate (CuET) in a polymeric nanofibrous patch for topical therapy of psoriasis.
Source: PubMed, NCBI / U.S. National Library of Medicine
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 psori
Abstract
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.