Methotrexate-Loaded Nano emulsion Gel Formulations for Enhanced Topical Delivery: A Comprehensive Review

Abstract

Methotrexate (MTX) is a widely used therapeutic agent for the management of psoriasis and other inflammatory skin disorders; however, its systemic administration is often associated with significant adverse effects, including hepatotoxicity, bone marrow suppression, and gastrointestinal complications. Topical delivery of MTX offers a promising alternative by targeting the drug directly to affected skin regions while minimizing systemic exposure. Nevertheless, the physicochemical properties of MTX, particularly its hydrophilicity and poor skin permeability, limit its effectiveness in conventional topical formulations.

Nanoemulsion-based gel systems have emerged as an advanced drug delivery strategy to overcome these limitations. Nanoemulsions, characterized by nanoscale droplet size and enhanced solubilization capacity, facilitate improved skin penetration through multiple mechanisms, including disruption of the stratum corneum and transappendageal transport. Incorporation of nanoemulsions into gel matrices further enhances bioadhesion, prolongs residence time, and enables sustained drug release, thereby improving therapeutic efficacy and patient compliance.

This review comprehensively discusses the formulation strategies, physicochemical characterization, in vitro and in vivo evaluation, and mechanistic advantages of MTX-loaded nanoemulsion gels. It highlights their superior skin permeation, controlled drug release, enhanced localization, and reduced systemic toxicity compared to conventional formulations. Additionally, the article addresses current challenges, including scalability, long-term stability, and regulatory considerations, while outlining future perspectives such as combination therapies and smart delivery systems.

Overall, MTX-loaded nanoemulsion gels represent a promising and innovative approach for the topical treatment of psoriasis and related dermatological conditions, with the potential to improve therapeutic outcomes and safety profiles.