Hybrid hydrogels for bacteriocin delivery to infected wounds

Superficial infections in chronic wounds can prevent the wound healing process by the development of persistent infections and drug-resistant biofilms. Topically applied antimicrobial formulations with stabilized and controlled release offer significant benefits for the effective treatment of wound infections. Bacteriocins are the antimicrobial peptides (AMPs) produced by bacteria that are viable alternatives to antibiotics owing to their natural origin and low propensity for resistance development. Herein, we developed a hybrid hydrogel composed of Pluronic F127 (PF127), ethylenediaminetetraacetic acid (EDTA) loaded liposomes, glutathione (GSH), and the bacteriocin Garvicin KS (GarKS) referred to as "GarKS gel". The GarKS gel exhibited suitable viscosity and rheological properties along with controlled release behavior (up to 9 days) for effective peptide delivery following topical application. Potent in vitro antibacterial and anti-biofilm effects of GarKS gel were evident against the Gram-positive bacterium Staphylococcus aureus. The in vivo treatment of methicillin resistant S. aureus (MRSA) infected mouse wounds suggested potent antibacterial effects of the GarKS gel following multiple applications of once-a-day application for three consecutive days. Altogether, these results provide proof-of-concept for the successful development of AMP loaded topical formulation for effective treatment of wound infections.