Methotrexate has been reported as an immunosuppressant and an antimetabolite widely used in the treatment of rheumatoid arthritis and psoriasis. However, it causes various toxicities and has low bioavailability when taken orally, thus, it is desirable that the drug be delivered transdermally. The water solubility and charged structure of methotrexate, however, limits its use via the transdermal route mainly due to the highly organized microstructure of the stratum corneum. Hence, various technologies, such as chemical enhancers, iontophoresis, electroporation, ultrasound and microneedles, either alone or in combination, are being explored to enhance its permeability by disrupting the barrier property of the skin. The present article discusses the past, present and future of transdermal delivery of methotrexate.
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