Enhanced Tacrolimus efficacy in psoriasis with innovative transethosomes: a promising preclinical study on Wistar rats.

Abstract

Aim: This study focuses on the formulation and evaluation of Tacrolimus-loaded transethosomes, which are then incorporated into a gel for topical application. The goal is to achieve deeper transdermal penetration, enhancing the treatment regimen.

Methods: Transethosomes were formulated using the cold method and optimized using 3² factorial design (DESIGN EXPERT^® Software) using different concentrations of lipid and ethanol. They were characterized for vesicle size, entrapment efficiency, zeta potential, and polydispersity index. The optimized batch was incorporated into the carbopol 940 gel base. In vitro and ex vivo permeation studies were carried out to determine the diffusion and release pattern. Skin irritancy and in vivo imiquimoid-induced anti-psoriatic activity were carried out on Wistar rats.

Results: The F1 batch, characterized by a low concentration of ethanol and lipids, demonstrated a vesicle size of 168 nm, an entrapment efficiency of 85%, a zeta potential of -36 mV, and a polydispersity index of 0.12. In vitro release studies indicated an 85.32% drug release and a 76.34% drug permeation after 24 h. The drug release adhered to zero-order kinetics, with the Korsmeyer-Peppas model suggesting a non-Fickian diffusion mechanism. In vivo studies of Tacrolimus-loaded transethosomal gel in an imiquimod-induced psoriasis-like rat model demonstrated significant therapeutic effects within seven days. Histopathological analysis showed reduced hyperkeratosis, epidermal hyperplasia, and inflammation, with fewer inflammatory cells in the dermis. Stability tests confirmed the formulation's integrity at 4 and 25 °C over 90 days.

Conclusion: The study's outcome revealed that tacrolimus-loaded transethosomes could effectively manage psoriasis.