Formulation, Evaluation and Optimization of Acitretin Loaded Transethosomes for the Management of Psoriasis

Background

Psoriasis is a chronic inflammatory skin disorder characterized by the development of red, scaly patches (National Psoriasis Foundation). It affects a significant portion of the global population, with estimates suggesting around 2% worldwide and 0.44% in India. Acitretin, a second-generation retinoid derived from vitamin A, emerged as a recognized treatment for severe psoriasis following its approval by the US Food and Drug Administration (US-FDA) in 1997.

Aim

The objective of this study was to enhance the topical delivery of acitretin by formulating it into a transethosomal gel. Acitretin, being poorly water-soluble, has limited penetration into the deep layers of the skin. The incorporation of transethosomal technology in this formulation aims to enhance acitretin's penetration into the skin and potentially improve its bioavailability.

Method

Transethosomes were prepared using the cold method. A 17-batch Box-Behnken design (Design-Expert® software) was employed to optimize the formulation with varying concentrations of lipid, ethanol, and Tween 80. Entrapment efficiency, vesicle size, and zeta potential were determined to characterize the transethosomes. The optimized batch containing acitretin-loaded transethosomes was then incorporated into a xanthan gum gel base. In vitro and ex-vivo and flux studies were conducted to assess drug diffusion and release patterns. Additionally, the formulation's irritancy and anti-psoriatic activity were evaluated in-vivo using Wistar rats.

Results

The Box-Behnken design optimization identified a formulation with a combination of 38.1% ethanol, 1.9% lipid, and 0.3% Tween 80 as optimal. This formulation exhibited a vesicle size of 105 nm, an entrapment efficiency of 80.4%, and a zeta potential of -28.25 mV. An optimized transethosome-based gel formulation was developed for its potential application in psoriasis therapy. The gel underwent a comprehensive evaluation of its physicochemical properties (pH, viscosity, spreadability) and in-vitro antimicrobial efficacy against Staphylococcus aureus. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and zone of inhibition assays were employed, demonstrating the gel's potent antibacterial activity. In-vivo studies on Wistar rats were subsequently conducted to evaluate skin irritation and imiquimod-induced anti-psoriatic activity. A pharmacokinetic study further compared the bioavailability of the transethosome gel with a conventional gel formulation. Notably, the results revealed a significant enhancement in bioavailability with the Transethosomal formulation.

Conclusion

The acitretin-loaded transethosomal gel demonstrated enhanced skin penetration and efficacy in managing psoriasis, achieving better outcomes than conventional treatments, while maintaining biocompatibility and minimal local side effects such as erythema, edema, and irritation.