Acitretin-loaded nanoethosomal gel for the treatment of psoriasis: Formulation, optimization, in vitro, and in vivo assessment

Acitretin (ACT) is a second-generation systemic retinoid used to treat severe psoriasis. However, its poor aqueous solubility and systemic adverse effects make it impractical for oral administration. The primary objective of this research is to prepare, optimize, and evaluate a nanogel consisting of acitretin-loaded ethosomes (ACT-ETH) for its anti-psoriatic potential. A 3(2 )full factorial design was employed for optimization. Thin-film hydration was adopted to prepare ACT-ETH, and then their physicochemical characteristics were tested. The optimized ACT-ETH was converted into a carbopol gel and then evaluated for cytotoxicity, skin irritation, and anti-psoriatic properties. The vesicle size, zeta potential (ZP), and percent entrapment efficiency (% EE) of the optimal ACT-ETH are 147 +/- 2.15 nm, -11.5 +/- 0.25 mV, and 90.70 +/- 0.89%, respectively. The fluorescence microscopy study has shown that ethosomes may go deeper into the skin layers. Compared to plain gel, ACT-ETH gel greatly increased skin permeability and deposition in the ex-vivo skin permeation and deposition tests. The in vitro cytotoxicity investigation revealed that the cytotoxicity of ACT against normal cells (L-929) was significantly reduced by ACT-ETH gel compared to plain ACT gel. The skin irritation study proved that ACT-ETH gel was well tolerated and safe for use on the skin. The in vivo anti-psoriatic study showed that using ACT-ETH gel to treat psoriasis on the skin led to a significant improvement in the therapeutic response. Based on these results, ACT-ETH gel has the potential to increase the topical anti-psoriatic action of ACT by mitigating its known drawbacks. [Graphical Abstract]