Hyaluronic Acid/Chitosan/Glycerophosphate-Based In Situ-Forming Hydrogel for Accelerated Wound Healing

This study reports the use of an in situ-forming gel based on hyaluronic-chitosan-glycerophosphate for wound healing. Hydrogels with optimized thermoresponsive gelling, rheological, and prolonged drug release properties were developed and incorporated with ciprofloxacin and carvacrol. In vitro evaluations included rheological studies, swelling degree, degradation rates, morphological analysis, antioxidant effects, antimicrobial activity, and drug release studies. The effectiveness of the optimized hydrogel was assessed using an animal ischemic wound rabbit ear model. The incorporation of ciprofloxacin and carvacrol into the combined hydrogel system maintained the mechanical strength of the formula, with a G'/G″ ≈ ratio of approximately 15.6, interconnected porosity, and controlled swelling. It enhanced antimicrobial activity against both <i>S. aureus</i> and <i>E. coli</i>. In addition, the developed gel exhibited sustained release following the Higuchi diffusion kinetics. The quantitative wound area% indicated that on day 9, the mean wound area decreased from 81.8% for the control to 51.2% for the developed gel. The study findings demonstrate the suitability and potential of this system as multifunctional wound-healing formulations that promote moist healing, antimicrobial and antioxidant activities, while providing sustained therapeutic delivery over 24 h.