Biocide loaded shear-thinning hydrogel with anti-biofilm efficacy cures topical infection

Abstract

The continuous intervention of multidrug-resistant (MDR) bacterial infections worsens and slows the dynamicity of natural wound healing processes. Fortunately, antibiotics, metal ions, or metal nanoparticle-loaded antimicrobial hydrogels have been developed to tackle infections at injury sites and speed up the healing process. Despite their success, these marketed released based hydrogels are still limited owing to their lack of broad-spectrum activity, inability to tackle biofilm-associated infections, susceptibility towards resistance development, fast release kinetics, and mild to moderate toxicity. To address these shortcomings, we report the development of a biocompatible, shear-thinning, injectable gellan-gelatin hydrogel loaded with a peptidomimetic potent biocide (ASAM-10). The hydrogel upon sustained biocide release (60% within 72 h), displays a broad-spectrum antibacterial activity with negligible in vitro (hemolysis < 20%) and in vivo toxicity (no adverse effects on dermal layer of mice). Besides tackling bacterial dormant subpopulation (1-6 Log reduction), the optimized hydrogel is able to disrupt the preformed bacterial biofilm and even kill the biofilm-trapped pathogens with enhanced pathogenicity. Above all, the lead hydrogel was proficient in tackling methicillin-resistant Staphylococcus aureus (MRSA) wound infections in a mouse model through its safe topical administration. Overall, the biocide-loaded hydrogel can be considered as a promising candidate to combat MDR chronic infections at the wound site.