AbstractA series of crosslinked hydrogel are developed to evaluate their applicability as efficient carriers for sustained release of ciprofloxacin (CFX) with bactericidal activity. The hydrogels are prepared from 2‐hydroxyethyl methacrylate (HEMA) and carboxymethyl‐chitosan (CMCS) using ethylene glycol dimethacrylate (EGDMA) as crosslinker to yield a semi‐interpenetrating polymer networks (semi‐IPNs) by a photoinitiated chemical method. Molecular weight and concentration of CMCS in the network are varied to optimize its properties as a wound dressing. PHEMA‐CMCS semi‐IPNs (HC‐IPNs) are characterized by their swelling ratio (Q), glass transition temperature (Tg), Young's moduli by mechanical compression submerged in water at different pHs at 37 °C, CFX delivery mimicking skin conditions, cell viability, biodegradability study and by their antibacterial activity. Results show that addition of CMCS results in pH sensitive behavior. HC‐IPNs show thermal reinforcement, and they are softer materials as compared to plain PHEMA hydrogels when submerged in water. The in vitro release of CFX suggests that the HC‐IPNs release the drug continuously up to 50 h. Unloaded HC‐IPNs show inhibition effects against Escherichia coli strain and show bacteriostatic effects against Staphylococcus aureus strain. Results suggest that HC‐IPNs probably be a potential candidate that can be applied as wound dressing for topical CFX controlled delivery.