Dual antimicrobial-loaded biodegradable nanoemulsions for synergistic treatment of wound biofilms

Wound biofilm infections caused by multidrug-resistant (MDR) bacteria constitute a major threat to public health; acquired resistance combined with resistance associated with the biofilm phenotype makes combatting these infections challenging. Biodegradable polymeric nanoemulsions that encapsulate two hydrophobic antimicrobial agents (eugenol and triclosan) (TE-BNEs) as a strategy to combat chronic wound infections are reported here. The cationic nanoemulsions efficiently penetrate and accumulate in biofilms, synergistically eradicating MDR bacterial biofilms, including persister cells. Notably, the nanoemulsion platform displays excellent biocompatibility and delays emergence of resistance to triclosan. The TE-BNEs are active in an in vivo murine model of mature MDR wound biofilm infections, with 99% bacterial elimination. The efficacy of this system coupled with prevention of emergence of bacterial resistance highlight the potential of this combination platform to treat MDR wound biofilm infections.