Contemplating Novel W/O Emulsion Based Gel for Anti-Psoriatic Activity of Tofacitinib in Imiquimod-Induced Balb/C Mice Model

Abstract

Tyrosine kinase inhibitors like tofacitinib (TCB), are excellent examples of small molecular compounds that have demonstrated success in treating psoriasis. The current study aims to improve the efficacy of TCB and reduce its systemic adverse effects by developing a topical w/o emulgel formulation that will ameliorate the anti-psoriatic activity in a model of Imiquimod-induced BALB/c mice. In order to create w/o emulgel, the TCB was incorporated into the w/o emulsion using Peppermint oil, Transcutol P^®, and PEG-200 followed by converted into a gel by adding Carbopol 940. The final formulation was optimized by applying a 3-level, 3-factor Box-Behnken Design (BBD). The optimized formulation showed a viscosity of 560606.6 ± 80.8 cps (560 Pa.S), and firmness of 356 ± 48 g, and that was within the acceptable range with respect to the marketed emulgel preparation available for topical application. The developed TCB-emulgel also exhibited a controlled release profile, with 68.26 ± 8.33% release of TCB over 24 h and a 5-fold greater skin permeation as compared to normal TCB-gel. Apart from that, the application of TCB-emulgel on the diseased model results in a 3.3-times reduction in the PASI (Psoriasis Area Severity Index) scoring. Lastly, the epidermal reduction in histopathological evaluation, along with the reduction in TNF-α and Ki-67 levels observed in immunostaining, ensures the enhanced anti-psoriatic effect of the developed TCB-emulgel in comparison to the marketed product. To put it briefly, the findings of the study and the therapeutic effectiveness of the developed TCB-emulgel provide a strong basis for the clinical management of psoriasis in the future.

Keywords: W/O-Emulgel; histopathology; immunohistochemistry; psoriasis; tofacitinib.