QbD-designed development and evaluation of bexarotene-loaded Cubosome gel for enhanced skin permeation in psoriasis treatment

Psoriasis is a chronic, immune-mediated, relapsing inflammatory skin disease, which is marked by epidermal hyperplasia, hyperkeratosis, and inflammatory cell infiltration. Bexarotene (BEX), a retinoid-based therapeutic agent, has shown promise in the management of psoriasis, however, effective topical delivery of bexarotene faces challenges due to low skin penetration and low retention of the drug at the target site. Therefore, this study aimed to develop and evaluate a sustained-release cubosome gel formulation of Bexarotene (BEX). Bexarotene-loaded cubic shaped liquid crystalline nanoparticles (BEX-CUBs) were prepared using a hot-emulsification technique using the Quality by Design approach, where the variables of the formulation were assessed using risk assessment studies. A Box-Behnken statistical design was employed to optimize BEX-CUBs for response variables like particle size, polydispersity index (PDI), and entrapment efficiency (EE%). The prepared cubosomeswere subjected to different physicochemical characterization counting Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC), X-ray diffraction (XRD), etc. The optimized batch exhibited a particle size of 126.5 nm, PDI of 0.11, and entrapment efficiency of 56.54%.The optimized cubosomes werefurther incorporated into Carbopol 940 gel and evaluated through in vitro, ex vivo, and in vivo studies . The cubosomal gel showed a sustained release pattern over 24h showing 4.3-fold enhanced permeation of drug in comparison to plain BEX gel. Histopathological analysis and PASI scores revealed that the anti-psoriatic efficacy of the BEX-CUBs gel was significantly improved compared to the conventional formulation. Moreover, this formulation explores the potential of drug-loaded cubosome in vivo study and illustrated higher efficacy than the free drug.