Dermal drug delivery system that is required to localizes methotrexate (MTX) in the synovial joint is needed to treat inflammation in rheumatoid arthritis (RA). The present investigation aims at exploring the potential of fatty acid vesicles for the topical delivery of methotrexate. Vesicles were prepared by film hydration method using oleic acid as a fatty acid principal component. Developed vesicles were characterized for size, size distribution, shape, in vitro release, pH dependent, and storage stability. Interaction between MTX and oleic acid was investigated using differential scanning calorimetry. The MTX amount permeated through rat skin was three- to fourfold higher using oleic acid compared to those from plain drug solution or carbopol gel. At the end of the skin permeation assay using ufasomes, up to 50% of the administered dose was found in the skin. These results suggest that methotrexate encapsulated in oleic acid vesicles may be of value for the topical administration of MTX in the treatment of psoriasis. 1. Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology and complex multifactorial pathogenesis. It is characterized by progressive and irreversible damage of the synovial-lined joints, resulting in the loss of joint space, bone, and a decrease in joint function and deformity . RA is usually treated first with a nonsteroidal antiinflammatory drug (NSAID). However, current RA treatment favors early use of slow acting disease modifying anti-rheumatic drugs (DMARDs) because DMARDs have the potential to prevent or reduce joint damage. Therefore, they are used early in the treatment of RA and usually no later than 3 months after the commencement of NSAID treatment [2, 3]. Methotrexate (MTX) is one of the most frequently used DMARDs in the treatment of RA. Although the exact mechanism of action is still unclear, the efficacy of MTX is related to its cytotoxic and anti-inflammatory effects . When administered in low weekly oral doses, MTX effectively suppresses inflammation in RA . However, systemic toxicity effects such as stomatitis, nausea, bone marrowdepression, and liver toxicity can limit the oral use of this drug . To reduce these effects, clinical studies have been done with topical methotrexate [7, 8]. A major problem in topical administration of methotrexate is that the drug is hydrosoluble and is mostly in the dissociated form at physiological pH: its capacity for passive diffusion is thus limited. One of the possibilities for increasing the penetration of drugs through the skin is
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