Quality by Design-Based Development and In Vitro–In Vivo Evaluation of Baicalin-Loaded Thermoresponsive Nanocomposite Hydrogel for Targeted Immunomodulatory Therapy in Chronic Plaque Psoriasis

Chronic plaque psoriasis is a persistent inflammatory skin disorder characterized by excessive keratinocyte proliferation and immune dysregulation. The present study aimed to develop a Quality by Design (QbD)–based baicalin-loaded thermoresponsive nanocomposite hydrogel for targeted topical immunomodulatory therapy. Baicalin nanoparticles were optimized using a three-factor Box–Behnken design to evaluate the influence of polymer, stabilizer, and nanoclay concentrations on particle size, polydispersity index, and encapsulation efficiency. The optimized formulation exhibited nanoscale particle size (~162 nm), narrow size distribution, and high drug entrapment. These nanoparticles were incorporated into a poloxamer-based thermoresponsive hydrogel that underwent sol–gel transition near skin temperature and demonstrated favourable rheological properties and spreadability. In vitro release studies revealed sustained drug release with reduced burst effect compared to free drug gel. Ex vivo permeation studies demonstrated enhanced dermal deposition and controlled transdermal flux. Cytocompatibility assessment using HaCaT and RAW 264.7 cells confirmed formulation safety. Furthermore, significant suppression of pro-inflammatory cytokines, including TNF-α and IL-6, indicated improved immunomodulatory potential. Overall, the QbD-guided nanocomposite hydrogel system demonstrated enhanced pharmaceutical and biological performance, supporting its potential as a localized therapeutic strategy for chronic plaque psoriasis.