Electro-responsive paper patch for enhanced transdermal methotrexate delivery in psoriasis treatment

Abstract

Transdermal delivery of high-molecular-weight drugs like methotrexate (MTX) is significantly hindered in psoriatic skin. To overcome this barrier, we developed a wearable iontophoretic patch based on a polypyrrole-coated paper substrate for enhanced MTX loading and controlled release. Applying −1.2 V enabled efficient MTX release and permeation (20.8 ± 0.4 μg/cm2 over 2 h) while minimizing passive leakage. In an imiquimod (IMQ)-induced psoriasis mouse model, the patch significantly alleviated symptoms and demonstrated low systemic toxicity. Histological analysis confirmed both therapeutic efficacy and biocompatibility. This innovative paper-based iontophoretic platform offers a promising strategy for precise, patient-friendly management of psoriasis and other dermatological disorders. © 2025 Elsevier B.V.