Polyacrylamide functionalized polysaccharide based nanocomposite semi-interpenetrating polymeric network hydrogel for pH-responsive controlled release of a model neuroprotective drug

The development of advanced drug delivery systems with enhanced stability, controlled release, and biocompatibility is critical for effective neuroprotective therapies. Here, we report a polyacrylamide-functionalized polysaccharide-based nanocomposite semi-interpenetrating polymer network (semi-IPN) hydrogel designed for pH-responsive delivery of the neuroprotective agent citicoline. The semi-IPN structure provides enhanced mechanical strength and tunable swelling, enabling precise and sustained pH-responsive drug release while minimizing burst effects. SEM analysis revealed a porous microstructure that facilitates efficient drug loading and diffusion, and XRD confirmed a semi-crystalline architecture contributing to mechanical stability. Cytotoxicity studies using 3T3 fibroblasts demonstrated excellent biocompatibility, with proliferation comparable to the control. Collectively, these results demonstrate that the developed hydrogel combines robust mechanical properties, tunable swelling, and controlled drug release, representing a promising platform for targeted and effective neuroprotective therapy.