Background: Microbial infections of wounds are a central problem of military deployments and combat. War wounds typically result from high-velocity gunshot, shrapnel, blast injuries including devastating wounds from improvised explosive devices (IEDs), and burns. Microorganisms in the soil and air together with bacteria generally present on the body may contaminate wounds essentially immediately after injury. Soldiers sustaining war wounds in a battlefield situation often lack an effective way to prevent and treat these life-threatening infections. Additional complications not addressed by conventional therapies include the emergence of antibiotic resistant strains of bacteria, poor activity against a wide range of pathogens, and inability to prevent or control long-lasting inflammatory responses that interfere with wound healing particularly after severe burns. Bacterial pathogens have caused life-threatening infections in casualties of the ongoing wars in Afghanistan and Iraq, leading to disability and death in soldiers even after minor wounds. Therefore, new, more effective and easy-to-apply treatments are urgently needed for effective prevention of wound infection at the time of injury on the battlefield, during evacuation, and after hospitalization.

Objective/Hypothesis: The overall objective of the proposed project is to develop a novel, safe, and rapidly effective treatment for war wounds and burns based on nanoemulsion (NE) formulations that have antimicrobial activity against a broad range of pathogens including antibiotic resistant strains. We will evaluate the hypothesis that new NE compounds of varying composition will prevent infection including multidrug-resistant, spore-forming, and biofilm-forming bacterial strains while reducing inflammation in animal wound and burn models.

Plan for this Project: NEs are safe and broadly active antimicrobial oil-in-water emulsions consisting of nanometer-sized droplets (200-600 nm). NE compounds are under evaluation in humans for particular skin infections such as herpes viral and fungal (dermatophyte) infections. Our previous findings indicate that many of the bacterial pathogens isolated from infected wounds sustained by US soldiers in Iraq and Afghanistan would be inactivated by the nanoemulsion technology. Additional analysis in our laboratories indicates that these early compounds are highly stable over a wide range of temperatures potentially enabling easy, immediate, and painless application in liquid or spray-on form for treatment of wounds and burns. Based on this knowledge, we plan to derive additional new NE compounds specifically effective for treatment of war wounds and burns. We will optimize and test a panel of 10 new NE formulations for activity against a broad spectrum of bacteria, fungi, and spores using laboratory culture techniques to ensure the ability to kill these organisms at concentrations that later can be achieved safely in wounds and burns. Finally, we will test the efficacy and safety of the NE treatment in animals using well-established models for infected wounds and burns.

Impact: We intend to develop a new generation of wound and burn treatments that will provide effective protection against most infections including those caused by antibiotic-resistant pathogens or bacteria that organize at the wound site into harmful higher-order microbial communities termed "biofilms." Successful completion of the project plan will enable rapid translation of the NE technology to evaluate prevention of wound and burn infection in US Food and Drug Administration-approved human clinical trials. A broadly effective nanoemulsion-based wound treatment that can be safely and easily applied at the time of injury without causing pain or adversely interfering with wound healing would have great value to prevent infection, increase survival, and enable more rapid healing of wounded US military personnel.

Project Task Area: The proposal will address a specific request from the US Department of Defense for development of antimicrobial countermeasures for polytrauma and blast injury.