A polymyxin and cellulase based smart hydrogel for localized infection treatment and biofilm eradication

Polymyxins are credited as the last line of defense against the clinical multi-resistant Gram-negative pathogen infections. However, their clinical use is limited by high nephrotoxicity and neurotoxicity, and less effectiveness against mature biofilms. In this work, the polymyxins including polymyxin B and polymyxin E were crosslinked with oxidized dextran via the acid labile Schiff base linkage. The generated hydrogel can release the polymyxins upon bacterial infection in an on-demand manner, which may alleviate adverse effects of the antibiotics. Moreover, a multifunctional hydrogel is generated by introducing the enzyme cellulase into the polymyxin hydrogel via the same Schiff base chemistry. The prepared gel can effectively degrade the mature biofilm, sensitizing the polymyxins in the treatment of biofilm-associated infections both in vitro and in vivo. This study provides an effective strategy to reduce the side effects of polymyxins and enhance their sensitivity against the mature biofilm-associated localized infections.