Liposomal phage-antibiotic-functionalized chitosan-alginate wound dressing for preventing staphylococcal infection

Treating burn wound infections has become increasingly difficult due to the rise of multidrug-resistant bacterial pathogens, particularly Staphylococcus aureus. To address this growing challenge, the present research explores a dual-therapy approach combining a broad-range lytic S. aureus-specific bacteriophage (SAΦ) and gentamicin (GeN) via a liposomal delivery system. The prepared liposomal formulation (LF) was biophysically characterized and evaluated for physiochemical properties. It was subsequently used for functionalizing an advanced chitosan-alginate (CA) wound dressing for treating burn wound infections. The findings revealed that SAΦ1 was successful in eradicating preformed staphylococcal biofilms in vitro, and when combined with GeN, it showed synergistic antibacterial potential against S. aureus ATCC 43300. SAΦ1-GeN-loaded LF exhibited high encapsulation efficiency, desirable physicochemical properties, sustained release drug/phage, and maintained antibacterial activity for up to 28 days at 4°C. The liposomal SAΦ1-GeN functionalized CA dressing and LFs displayed potent antibacterial activity against S. aureus, maintaining a hemocompatible and biocompatible nature towards sheep erythrocytes and L929 cells in vitro, respectively. With the LF-functionalized wound dressing demonstrating non-allergenic properties, its therapeutic efficacy was validated in a thermal injury-infection model in vivo. Interestingly, liposomal SAΦ1-GeN functionalized CA dressing curtailed bacterial colonization and prevented staphylococcal infection at the wound site, preventing systemic infection in BALB/c mice. Also, it reduced the levels of inflammatory markers (myeloperoxidase and malondialdehyde) at the wound site and displayed pro-wound healing abilities with rapid skin re-epithelialization. In summary, this dual-agent delivery system holds strong potential to revolutionize the management of biofilm-associated staphylococcal wound infections, offering an improved solution to existing wound care products.