Development, characterization and evaluation of nanocarrier based formulations of antipsoriatic drug “acitretin” for skin targeting

Abstract

Acitretin, a 2nd generation retinoid, is a drug of choice for the treatment of severe psoriasis. Presently, only capsule formulation for oral administration is commercially available and associated with limitations of severe systemic side effects. In the present study, carrier elastic liposomal and ethosomal based topical gel formulations were developed, optimized, and characterized in-vitro, ex-vivo, and in-vivo to provide effective skin targeting of acitretin. In-vitro characterization exhibited nanometric vesicle size range (591 ± 16 and 360 ± 14 nm), high encapsulation efficacy (94.7 ± 2.1% and 91.2 ± 1.6%), optimum viscosity (1152 and 1320 cP), thixotropic behavior and good storage stability of the developed formulation. Ex-vivo skin permeation and deposition studies carried on four different biological membranes (rat, mice, porcine ear, and human cadaver skin) showed higher skin deposition of prepared carrier-based gels in comparison to plain acitretin gel. Better skin localization potential was also confirmed by mechanistic studies using Confocal Laser Scanning Microscopy and Scanning Electron Microscopy analysis. In-vivo antipsoriatic activity demonstrated the better therapeutic efficacy of carrier-based formulations. Thus, developed formulation seems to be a safe and promising alternative to oral route for effective topical delivery of acitretin with improved pharmacological activity and no systemic toxicity.