Abstract
Semi-interpenetrating polymer networks (semi-IPNs) composed of poly-(2-(dimethylamino)-ethyl methacrylate) (PDMAEMA) and various concentrations of N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride (HTCC) (5, 10, and 25% w/w) were synthesized and evaluated as matrices for papain loading and sustained delivery. The incorporation of HTCC significantly influenced the structural, swelling, and release properties of the networks. Monomer conversion and gel fraction decreased with increasing HTCC content, reaching 91.26 and 81.36%, respectively, at 25% HTCC. Swelling studies revealed a nonlinear behavior, with the 5% HTCC sample exhibiting the highest swelling degree (458.33%), while pure PDMAEMA and the 25% HTCC formulation reached 219.78 and 168.23%, respectively. Papain release profiles, fitted to the Peppas-Sahlin model, showed diffusion-controlled kinetics, with k (1) values decreasing from 31.89 h(-m) (PDMAEMA) to 6.14 h(-m) (PDMAEMA/HTCC25%), indicating hindered diffusion in denser networks, which may be beneficial for a more sustained therapeutic release. Antibacterial assays confirmed the potent activity of HTCC-containing formulations against Staphylococcus aureus, with 25% HTCC demonstrating nearly complete inhibition (∼95%), while no significant inhibition was observed against Escherichia coli, indicating Gram-specific selectivity. Moreover, the 25% HTCC formulation maintained fibroblast viability above 70%, further supporting these hydrogels as bioactive wound dressings combining controlled delivery with antimicrobial activity.