Olive Oil Based Methotrexate Loaded Topical Nanoemulsion Gel for the Treatment of Imiquimod Induced Psoriasis-like Skin Inflammation in an Animal Model

Abstract

Psoriasis, a chronic inflammatory illness, is on the rise and is linked to several other life-threatening diseases. The primary goal of this study was to create a nanoemulsion gel loaded with methotrexate and olive oil (MTX NEG). The formulation was evaluated for physicochemical characterization, entrapment efficiency, drug release kinetics, skin permeation studies and stability tests. In addition, the efficacy of MTX NEG against psoriasis was tested using imiquimod-induced psoriasis in a rat model. The final optimized MTX NEG was developed with a particle size of 202.6 ± 11.59 nm and a PDI of 0.233 ± 0.01, with a 76.57 ± 2.48% average entrapment efficiency. After 20 h, the release kinetics predicted a 72.47% drug release at pH 5.5. FTIR findings demonstrated that the optimized MTX NEG formulation effectively fluidized both the epidermis and dermis of the skin, potentially increasing drug permeability and retention. The application of Tween 80 and PEG 400, on the other hand, significantly enhanced these effects, as these are well known penetration enhancers. After 24 h, an average of 70.78 ± 5.8 μg/cm2 of methotrexate was permeated from the nanoemulsion gel with a flux value of 2.078 ± 0.42 μg/cm2/h, according to permeation measurements. Finally, in vivo experiments on rabbit skin revealed that the increased skin penetration of methotrexate-loaded nanoemulsion gel was not due to structural alterations in intercellular lipid layers in the stratum corneum. In vivo antipsoriatic studies on rats revealed that MTX NEG produced a PASI decrease that was extremely similar and even better than the 91% reduction seen in the MTX tablet group. According to the pharmacokinetic profile, Cmax was 8.5 μg/mL, Tmax was 12 h, and t1/2 was 15.5 ± 2.37 h. These findings reinforce that MTX-NEG based on olive oil could be a possible treatment for psoriasis and could decrease the remission of psoriasis-like symptoms.

Keywords

• psoriasis
• inflammation
• methotrexate
• topical delivery
• skin permeation