Dual delivery of chloramphenicol and essential oil by poly-ε-caprolactone-Pluronic nanocapsules to treat MRSA-Candida co-infected chronic burn wounds

Methicillin-resistant Staphylococcus aureus (MRSA) and Candida co-infections in the context of burn wounds, leads to morbidity and mortality. Eradication of such difficult to treat complex infection needs concomitant effective topical administration of an antibiotic-antifungal cocktail. Application of the broad-spectrum antibiotic chloramphenicol (CAM) has been hindered owing to its hydrophobicity, poor dermal penetration, rapid degradation and toxicity issues. But, due to its lesser uses in the past, CAM continues to be active against a majority of currently predominant resistant bacterial strains. Additionally, the essential oil of Cymbopogon flexuous possesses strong, broad spectrum antimicrobial property and also acts as a synergistic enhancer when used in combination with antibiotics. But due to its highly volatile nature and instability in free form, topical administration has not been possible. Keeping this in mind, we co-encapsulate CAM with lemongrass essential oil in PCL-Pluronic composite nanocapsules (CAM-LEO-PCL-P NCs) and were successful in overcoming the limitations in drug administration and achieved a significant reduction in cytotoxicity than that of the free counterparts with increased therapeutic index. CAM-LEO-PCL-P NCs exhibited significantly enhanced in vitro antimicrobial activity against 22 microbial pathogens including ten clinical MRSA isolates and three Candida species. This therapeutic nanocapsule was able to penetrate into burn wounds and demonstrated pronounced wound healing ability against MRSA-Candida co-infected burn wounds of mice by significant reduction of the pathogen burden. It also helps in increased cellular proliferation and collagen synthesis in the wounded area with the reduction of inflammatory cytokines. We propose CAM-LEO-PCL-P NCs as a potential candidate to treat chronic wound infections.