Thermogelling Hydrogel for Sustained Topical Delivery of Quercetin for the Treatment of Atopic Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease clinically characterized by pruritus, dryness, and eczematous lesions, resulting from a combination of environmental, immunological, and genetic factors. In this study, the quercetin-loaded thermosensitive hydrogel (QU-THG) was developed using the cold method and optimized through a Box-Behnken design. The concentrations of Pluronic F-127 and DMSO, and stirring speed were selected as independent variables, and sol-gel transition temperature, gelation time, and viscosity were evaluated as responses. The optimized formulation contained 18% w/v Pluronic F-127, showed a gelation temperature of 3 ± 0.3 °C, a gelation time of 5.3 ± 0.8 min, and a viscosity of 78 ± 5.3 cPs. The hydrogel underwent a reversible sol-gel transition, forming in situ stable gel at physiological temperature and enhances skin residence time. In vitro release studies demonstrated 49.9 ± 5.23% quercetin release within 7 h and 92.5 ± 3.1% over 24 h, following a non-Fickian diffusion mechanism based on the Korsmeyer-Peppas model, indicating the combined influence of diffusion and polymer relaxation. Skin permeation studies revealed maximum permeation at 18% w/v Pluronic F-127, likely due to reduced micellar packing and improved thermodynamic activity of quercetin. In vivo studies confirmed a significant reduction in inflammation and accelerated skin recovery compared to the negative control. Clinical scoring further confirmed a highly significant difference (p < 0.0001) using one-way ANOVA followed by Tukey's post hoc test. The optimized QU-THG demonstrated controlled gelation, desirable rheological properties, and sustained drug release, resulting in improved therapeutic outcomes, thereby supporting its applicability as an effective topical system for atopic dermatitis management.