Abstract

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.

Highlights

  • Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology and complex multifactorial pathogenesis

  • Multilamellar oleic acid vesicles were prepared by film hydration method by varying oleic acid-to-MTX molar ratios

  • The studies carried out demonstrated no significant difference in the entrapment efficiency; the mean entrapment efficiency of the vesicles increased with an increase in the molar quantity of MTX up to 7 : 3 oleic acid to MTX ratio (51.0 ± 4.2%)

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Summary

Introduction

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology and complex multifactorial pathogenesis. 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. They are used early in the treatment of RA and usually no later than 3 months after the commencement of NSAID treatment [2, 3]. Systemic toxicity effects such as stomatitis, nausea, bone marrowdepression, and liver toxicity can limit the oral use of this drug [6] To reduce these effects, clinical studies have been done with topical methotrexate [7, 8].

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