Exploring the skin permeability potential of cubosomal hydrogels for the keratosis-like skin conditions

Abstract

Actinic keratosis (AK) is a chronic skin condition caused primarily by prolonged sun exposure, leading to the development of uneven, scaly patches on sun-exposed areas like the face, chest, and neck. Traditional treatments often encounter challenges such as poor skin permeability and formulation stability. This study investigates the potential of cubosomal hydrogels for enhancing the treatment of AK, focusing on their permeability, and effectiveness. Cubosomes, a type of liquid crystalline nanoparticle, are known for their controlled release and improved skin penetration capabilities. We formulated tretinoin-loaded cubosomes and incorporated them into carbopol-based hydrogels, referred to as cubogels, to address issues related to stability and ease of application. The formulation of tretinoin-loaded cubosomes was optimized, resulting in particles with a size of 69.5 nm, a polydispersity index of 0.312, and an entrapment efficiency of 82.13%. These cubosomes were then dispersed in hydrogels made with varying concentrations of Carbopol 940 (0.5%, 1.0%, and 1.5%). The cubogels were evaluated for physical properties, including appearance, pH, viscosity, spreadability, and drug content uniformity. The hydrogels exhibited good homogeneity and appropriate pH levels, with CG2 (1.0% Carbopol) showing the best spreadability and drug content uniformity. Ex-vivo studies using goat ear pinna demonstrated that CG2 provided the highest steady-state flux and permeability coefficient, indicating superior skin penetration. The cumulative drug permeation over 24 hours was also higher for CG2 compared to the other formulations. In conclusion, the incorporation of cubosomes into hydrogels significantly enhances the stability and skin permeability of tretinoin, offering a promising approach for the treatment of actinic keratosis. Future studies should focus on clinical evaluation to confirm these findings and further optimize the formulation for broader therapeutic applications.