s Development of Topical Gel of Methotrexate Incorporated Ethosomes and Salicylic Acid for the Treatment of Psoriasis

Background: There is an unmet need for optimized drug delivery system of psoriasis therapy because of various issues like adverse reaction, permeation problem associated with convention treatment (oral and topical) available for psoriasis. Objective: The goal was to develop an ethosomal gel of methotrexate (MTX)-incorporated ethosomes and salicylic acid (SA) and to evaluate and study its ethosomal gel potential in Imiquimod-induced psoriasis animal model to treat symptoms of psoriasis. Methods: MTX-SA ethosomal gel was prepared by the cold method given by Touitou et al. and optimized by comparing it with MTX ethosomal gel and drug solution. Particle size, zeta potential, entrapment efficiency, and ex-vivo study were selected as the critical quality checking attributes. Psoriatic Area and Severity Index (PASI) score & histopathological examination were done for checking Antipsoriatic potential of MTX-SA ethosomal gel by using the imiquimod-induced psoriasis model. Results: Optimized MTX-SA exhibited a particle size of 376.04 ± 3.47nm, EE(Entrapment efficiency) of 91.77 ± 0.02%. At the end of 24h, MTX-SA ethosomal gel exhibited a slow and prolonged release of MTX (26.13 ± 1.61% versus 6.97 ± 0.06%) compared to MTX drug solution. It also attributes of 43% retention study as compared to drug solution (13%). Besides, it essentially decreased the PASI score with the recuperation of normalcy of the mice's skin, while the MTX-SA gel displayed indications of gentle hyper and parakeratosis toward the completion of investigation when contrasted with the blank gel. Conclusion: The developed MTX-SA ethosomal gel formulation can be a promising alternative to existing MTX formulation in topically treating psoriasis.