On-demand release of enrofloxacin-loaded chitosan oligosaccharide-oxidized hyaluronic acid composite nanogels for infected wound healing

In this study, enrofloxacin (ENR) was encapsulated by oxidized hyaluronic acid (OHA) containing aldehyde groups and chitosan oligosaccharide (COS) containing amino groups through Schiff's base reaction to achieve on-demand release in the micro-environment (pH 5.5 and HAase) of bacterial-infected wounds (Escherichia coli and Staphylococcus aureus). The formation mechanism, physicochemical characterization, responsive release performance, in vitro and in vivo antimicrobial activities, and in vivo regeneration in full-thickness wounds in a bacterial-infected mouse model of the ENR nanogels were systematically studied. According to the single-factor experiment and Design-Expert software, the optimized formula was 3.8 mg/mL COS, 0.5 mg/mL OHA, and 0.3 mg/mL ENR, respectively. The mean particle diameter, polydispersity index, zeta potential, loading capacity, and encapsulation efficiency were 35.6 ± 1.7 nm, −6.7 ± 0.5 mV, 0.25 ± 0.02, 30.4 % ± 1.3 %, and 76.3 % ± 2.6 %, respectively. The appearance, optical microscopy images, SEM, TEM, PXRD, and FTIR showed that the ENR nanogels were successfully prepared. The ENR nanogels exhibited obvious pH and HAase-responsiveness by swelling ratios and in vitro release and had stronger antibacterial activity with time-dependent and concentration-dependent effects, as well as accelerating infected wound healing. In vitro and in vivo biosafety studies suggested the great promise of ENR nanogels as biocompatible wound dressings for infected wounds.