Abstract
Integration of antimicrobial polymeric nanoparticles into hydrogel materials presents a promising strategy to address multidrug-resistant biofilm infections. Here we report an injectable hydrogel loaded with engineered cationic antimicrobial polymeric nanoparticles (PNPs) for the effective topical treatment of severe wound biofilm infections. The PNPs demonstrated biofilm penetration and disruption, resulting in the eradication of resistant and persister cells that reside within the biofilm. Significantly, PNPs did not elicit resistance development even after multiple exposures to sub-therapeutic doses. In vitro studies showed PNPs significantly reduced prolonged inflammation due to infection and promoted fibroblast migration. These PNPs were then incorporated into Poloxamer 407 (P407) hydrogels and utilized as an inert carrier for PNPs to provide a controlled and sustained topical release of the antimicrobial nanoparticles at the wound area. In vivo studies using a mature (4-day) wound biofilm infection in a murine model mimicking severe human wound infections demonstrated provided 99% bacterial biofilm clearance and significantly enhanced wound healing. Overall, this work demonstrated the efficacy and selectivity of the antimicrobial polymer-loaded hydrogel platform as a topical treatment for difficult-to-treat wound biofilm infections.