Crosslinking-regulated dual-network carboxymethyl chitosan/gelatin hydrogel for pH-responsive oral curcumin delivery

To enhance the gastrointestinal stability and oral bioavailability of curcumin, a pH-responsive dual-network hydrogel was constructed from a photocrosslinkable chitosan derivative and a lipoic-acid-modified gelatin derivative. The network was formed by thiol-ene photocrosslinking and reversible disulfide bonding, providing a tunable crosslinking structure for oral delivery. The hydrogel showed high water content (>90%), pronounced pH-dependent swelling, rapid swelling-deswelling at pH 7.4, and fast enzymatic degradation under multi-enzyme conditions. Rheology confirmed that the effective crosslink density increased with formulation crosslinking level. The less crosslinked hydrogel achieved a higher curcumin loading amount (188.98 ± 0.35 mg/g), whereas the more highly crosslinked formulation provided better control over sequential gastrointestinal release. Under simulated gastrointestinal conditions, premature release in gastric medium was markedly suppressed, with cumulative release below 13% at 2 h, followed by accelerated release in intestinal and colonic media. Release kinetics were best fitted by the Peppas-Sahlin model, indicating a dominant Fickian diffusion contribution. Together with antioxidant activity and hemocompatibility, these results demonstrate the potential of this chitosan-based hydrogel as a pH-responsive oral curcumin delivery platform.