A hyaluronic acid-based nanogel for the co-delivery of nitric oxide (NO) and a novel antimicrobial peptide (AMP) against bacterial biofilms

Biofilms are a global health concern because they are associated with chronic and recurrent infections as well as resistance to conventional antibiotics. The aim of this study was to prepare a nanogel for the co-delivery of NO and AMPs against bacteria and biofilms. The NO-releasing nanogel was prepared by crosslinking HA solution with divinyl sulfone and extensively characterized. The nanogel was found to be biocompatible, injectable and NO release from the gel was sustained over a period of 24 h. In vitro antibacterial studies showed that the NO-AMP-loaded nanogel exhibited a broad spectrum antibacterial/antibiofilm activity. The NO-releasing nanogel had a greater antibacterial effect when compared to NO alone with MIC values of 1.56, 0.78 and 0.39 μg/ml against Escherichia coli, Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa bacteria respectively. The antibiofilm results showed there was a 12.5 and 24-folds reduction in biofilms of MRSA, and P. aeruginosa respectively for catheters exposed to nanogel loaded with AMP/NO when compared to only NO, while a 7 and 9.4-folds reduction in biofilms of MRSA, and P. aeruginosa respectively was displayed by the nanogel loaded with only NO compared to only NO. The AMP/NO-releasing nanogel showed the potential to combat both biofilms and bacterial infections.