Bacterial enzyme-responsive hydrogels for triggered delivery of antibiotics to infected wounds.

Abstract

Wound infections are becoming increasingly difficult to treat due to rising antibiotic-resistant bacteria. β-Lactamase-producing bacteria are among the most common pathogens implicated in these infections. Here, we report a bacterial enzyme-responsive hydrogel formulated with a cephalosporin-derived, β-lactamase-cleavable crosslinker that undergoes selective degradation in the presence of bacterial β-lactamases. This degradation triggers the on-demand release of encapsulated ciprofloxacin-loaded liposomes, ensuring that antibiotic delivery occurs only at the site of infection. This selective degradation and release was demonstrated in both ex vivo and in vivo models of <i>Pseudomonas aeruginosa</i> wound infections. In a murine skin abrasion infection model, a single application of the hydrogel led to complete bacterial eradication and enhanced wound healing, outperforming a commercial silver-based hydrogel wound dressing. These responsive hydrogels did not induce ciprofloxacin resistance in non-β-lactamase-producing bacteria. These findings demonstrate that β-lactamase-responsive hydrogels provide a precise, infection-triggered antibiotic delivery platform that can improve the treatment of wound infections and mitigate antimicrobial resistance.