DoE-oriented optimization of a chitosan-based nanoemulgel of clobetasol propionate for therapeutic intervention in...

Psoriasis is an inflammatory skin disease caused by immune-mediated inflammation. Clobetasol propionate (Cp), a steroid, reduces inflammation by binding the glucocorticoid receptor. This study aimed to optimize a Cp-loaded nanoemulsion (Cp-NE) with a focus on its cytocompatibility with HaCaT keratinocytes and physicochemical stability during storage. Optimization was performed using a Box-Behnken design. Cp-NE was loaded into a chitosan gel to prolong skin retention. The formulations were analyzed for globule size, PDI, ZP, and viscosity. In vitro, drug release and skin permeability were also assessed. The optimized Cp-NE had a globule size of 122 nm, a %EE of 89%, a PDI of 0.508, and a ZP of -28 mV. The Cp-NE gel had a pH of 6.13 and a viscosity of 6799 cps, making it suitable for topical use. In vitro, free Cp released 91% within 2 h; Cp-NE released 83.4% at 12 h, indicating sustained release, which was further extended in chitosan gel. The release followed Higuchi kinetics, confirming diffusion control. Skin permeation was higher with the Cp-NE gel than with the free drug. Cytocompatibility tests showed higher cell viability for Cp-NE. Cytokine assays in HaCaT cells showed significant reductions in IL-6 and TNF-α with Cp-NE and Cp-NE gel, indicating anti-inflammatory potential. MTT assays confirmed biocompatibility, supporting transdermal use. The results suggest that chitosan nanoemulsions improve drug delivery and biocompatibility and reduce inflammation. Stability studies showed excellent stability at 5 ± 3 °C and 25 ± 2 °C/60 ± 5% RH. The Cp-NE gel exhibited favorable physicochemical properties, sustained release, enhanced skin permeation, and stability, highlighting its potential for psoriasis treatment.