Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics

Abstract

Methotrexate (MTX), a well known drug for the treatment of cancer and rheumatoid arthritis, has gained prominence in the treatment of psoriasis over the period of years. However, the present mode of systemic administration through oral or parenteral route has always proposition, full of compromises. The toxicity of drug to the vital organs and physiological environment is the major concern. Also, its poor skin penetration is one major problem. Hence novel system based on lipid carriers has been considered here to overcome the barriers. Microemulsions (MEs) were prepared using pseudo-ternary phase diagram (PTPD) and they were characterized for various parameters such as size, shape (cryo-SEM), PDI, zeta potential, etc. The chosen MEs system (optimized) was then incorporated into secondary vehicles and characterized for rheological behavior, texture profile analysis, in vitro release, ex vivo permeation and drug distribution into different layers of skin. The developed formulations were further evaluated in ex vivo and in vivo such as cell line study, imiquimod-induced psoriatic model, allergic contact dermatitis, rat tail model (% orthokeratosis) and safety test (Draize test). The MEs based MTX gel has shown its potential in locating the drug at the desired domain of stratum corneum, epidermal and dermal layers of skin and reducing systemic absorption. Our results are suggestive of MEs potential as a novel carrier for topical delivery of MTX in topical therapeutic and safety approaches. In conclusion, developed MEs-based hydrogel has shown promising results in achieving effective delivery of MTX.

• Methotrexate
• microemulsions
• phospholipids
• psoriasis
• topical delivery
• transepidermal targeting

Acknowledgements

The authors also thank IPCA Pharmaceuticals Ltd. (Mumbai, India) for providing MTX as gift sample, Lipoid, Ludwigshafen, Germany for providing Hydrogenated soya phosphatidyl choline (HSPC). Department of Research, Jawaharlal Nehru Cancer Hospital & Research Centre, Bhopal, for providing facilities for cell line study.

Declaration of interest

The authors are grateful for the fellowship and grant provided by the UGC RNFS, and Human Resource Development Group, Council of Scientific & Industrial Research (HRDG, CSIR) New Delhi, India.

Supplementary material available online

Supplementary Tables S1-S3 and Figures S1 and S2