A nanocomposite hydrogel for co-delivery of multiple anti-biofilm therapeutics to enhance the treatment of bacterial biofilm-related infections.

The characteristics of biofilms have exacerbated the issue of clinical antibiotic resistance, rendering it a pressing challenge in need of resolution. The combination of biofilm-dispersing agents and antibiotics can eliminate biofilms and promote healing synergistically in infected wounds. In this study, we developed a novel nanocomposite hydrogel (NC gel) comprised of the poly(lactic acid)-hyperbranched polyglycerol (PLA-HPG) based bioadhesive nanoparticles (BNPs) and a hydrophilic carboxymethyl chitosan (CS) network. The NC gel was designed to co-deliver two biofilm-dispersing agents (an NO-donor SNO, and an α-amylase Am) and an antibiotic, cefepime (Cef), utilizing a synergistic anti-biofilm mechanism in which Am loosens the matrix structure and NO promotes the release of biofilm bacteria via quorum sensing, and Cef kills bacteria. The drug-loaded NC gel (SNO/BNP/CS@Am-Cef) demonstrated sustained drug release, minimal cytotoxicity, and increased drug-bacterial interactions at the site of infection. When applied to mice infected with methicillin-resistant Staphylococcus aureus (MRSA) biofilms in vivo, SNO/BNP/CS@Am-Cef enhanced biofilm elimination and promoted wound healing compared to traditional antibiotic treatments. Our work demonstrates the feasibility of the co-delivery of biofilm-dispersing agents and antibiotics using the NC gel and presents a promising approach for the polytherapy of bacterial biofilm-related infections.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)