Curdlan-Reinforced Chitosan/Polyacrylate Interpenetrating Hydrogels with Enhanced Mechanical Stability for Gastric Retention and pH-Responsive Drug Release.

Polysaccharide-based hydrogels for gastric retention face the inherent challenge of achieving effective retention through swelling while avoiding mechanical failure. Here, we introduce a strategy by incorporating curdlan into chitosan/sodium polyacrylate interpenetrating networks to reinforce the hydrogel and regulate swelling-induced transport behavior. Curdlan-reinforced chitosan/polyacrylate (CS/CUR/PAAS) hydrogels with varying curdlan content (0-4 wt.%) were synthesized and characterized. Optimal reinforcement was achieved with 2 wt.% curdlan, yielding an indentation hardness of ~80 kPa and an elastic modulus of ~63 kPa without compromising swelling capacity. Under acidic conditions (pH 1.2), the hydrogel swelled rapidly (~50-fold at 3 h; ~140-fold at 8 h) while maintaining structural integrity. Using a dynamic in vitro human stomach simulator (DHSI-IV), the optimized hydrogel demonstrated gastric retention for up to 5 h, with ~60% of the initial mass retained at 6 h. Metformin hydrochloride release followed diffusion-controlled kinetics (~69% over 8 h), governed primarily by pH with secondary shear modulation. Microstructural and rheological analyses revealed that acidic conditions regulated network expansion, viscoelastic relaxation, and pore formation, which in turn controlled transport pathways and drug release. The findings highlight that curdlan reinforcement stabilizes swelling behavior under acidic conditions, offering a robust and pH-responsive strategy for designing mechanically stable, gastric-retentive hydrogels.