A smart hydrogel for on-demand delivery of antibiotics and efficient eradication of biofilms

Biofilm-associated infections are difficult to treat in the clinics because the bacteria embedded in biofilm are ten to thousand times more resistant to traditional antibiotics than planktonic ones. Here, a smart hydrogel comprised of aminoglycoside antibiotics, pectinase, and oxidized dextran was developed to treat local biofilm-associated infections. The primary amines on aminoglycosides and pectinase were reacted with aldehyde groups on oxidized dextran via a pH-sensitive Schiff base linkage to form the hydrogel. Upon bacterial infection, the increased acidity triggers the release of both pectinase and aminoglycoside antibiotics. The released pectinase efficiently degrades extracellular polysaccharides surrounding the bacteria in biofilm, and thus greatly sensitizes the bacteria to aminoglycosides. The smart hydrogel efficiently eradicated biofilms and killed the embedded bacteria both n tvitro and in vivo. This study provides a promising strategy for the treatment of biofilm-associated infections.