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

## TL;DR

This study develops a hydrogel system that can release curcumin oil to reduce inflammation and aid wound healing, with optimized mechanical and drug release properties.

## Contribution

A dual-crosslinked hydrogel system with controlled curcumin oil release and anti-inflammatory activity is developed and optimized using response surface methodology.

## Key findings

- The optimal hydrogel formulation achieved firmness of 1.27 ± 0.06 N and compressive strength of 41.91 ± 0.62 kPa.
- Curcumin oil was released at 82% cumulative over 360 min following Korsmeyer–Peppas kinetics.
- The hydrogel inhibited ROS and NO production and enhanced macrophage migration for wound closure.

## Abstract

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% w/w) and dialdehyde carboxymethyl cellulose (DCMC, 0.0125–0.0375% w/w) 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 (R2 = 0.9887, n = 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 (p < 0.001) and enhanced macrophage migration, increasing wound closure from 40–80% (p < 0.001). This dual-crosslinked hydrogel shows great potential for localized inflammatory pain relief.