Response Surface Optimization of Curcumin Oil-Loaded Dual-Crosslinked PVOH/CMC/Gellan Gum Hydrogels with Controlled Release and Anti-Inflammatory Activity

Wound-related inflammatory pain is a major contributor to wound healing success and requires wound-specific therapeutic platforms with minimal systemic adverse effects. This study builds a dual-crosslinked polyvinyl alcohol (PVOH)/carboxymethyl cellulose (CMC)/gellan gum hydrogel system with optimized mechanical strength and sustained anti-inflammatory drug delivery by developing predictive mathematical models using response surface methodology with central composite design. The effects of citric acid (5-15% <i>w</i>/<i>w</i>) and dialdehyde carboxymethyl cellulose (DCMC, 0.0125-0.0375% <i>w</i>/<i>w</i>) on mechanical properties were systematically evaluated. The optimal formulation (2.23 g low-acyl gellan gum, 1.00 g high-acyl gellan gum, 0.02% DCMC, 10.21% citric acid) achieved firmness of 1.27 ± 0.06 N, rupture strength of 24.24 ± 0.52 N, and compressive strength of 41.91 ± 0.62 kPa. Curcumin oil incorporation yielded 82% cumulative release over 360 min following Korsmeyer-Peppas kinetics (<i>R</i>² = 0.9887, <i>n</i> = 0.8773). Cell viability exceeded 70% throughout the release period, confirming biocompatibility. The hydrogel strongly inhibited reactive oxygen species (ROS) and nitric oxide (NO) production in lipopolysaccharide-stimulated macrophages (<i>p</i> < 0.001) and enhanced macrophage migration, increasing wound closure from 40-80% (<i>p</i> < 0.001). This dual-crosslinked hydrogel shows great potential for localized inflammatory pain relief.