This Small Business Innovation Research (SBIR) Phase I project seeks to develop novel hyperosmotic nanoemulsions for the prevention and treatment of infected wounds. Wound infections, whether acute or chronic, affects millions of Americans and have significant monetary and physiologic impacts on patient quality of life. Current therapies that rely on antibiotics are becoming limited due to the frequency of antibiotic drug resistance. For example, the CDC estimates that drug resistance has increased 36% in the last twenty years. To reduce the reliance on broad spectrum antibiotics, this research aims to develop a new class (non-antibiotic) of topical therapeutics known as hyperosmotic nanoemulsions. The intellectual merit of the proposed technology is the novel mechanism of bactericidal action (for infection prevention/treatment) coupled to the concomitant acceleration in wound healing. This proposal is intended to define the optimal treatment dosage necessary to move the technology into human clinical testing.
The broader impact/commercial potential of this project is the applicability of hyperosmotic nanoemulsions to become a standard first option in wound management protocol. Currently, market products either mitigate the infection or reduce healing times. However, hyperosmotic nanoemulsions are intended to treat both the underlying infection and actively promote the stages of wound healing. This dual-fold action is poised to disrupt the market of advanced wound dressings, which is estimated to be $1.2B and growing 10% annually. Other markets that may be addressed with the proposed technology include topical acne, antiviral and antifungal segments. The proposed platform technology may ultimately prove to be an alternative or supplement to traditional drugs and reshape both veterinary and human clinical practice.
Wound healing is the intricate process that restores function to damaged skin. The process consists of the inflammatory, proliferative and remodeling phases that orchestrate dynamic cellular responses to regenerate the cutaneous barrier. However, microbial contamination of the wound site stimulates a deleterious inflammatory response impedes wound closure. Controlling contamination is critical for proper wound management and reduced burden on the healthcare system. Based on this concern, we developed a novel therapeutic platform for wound care called hyperosmotic nanoemulsions (HNE). The HNE therapy is intended as a topical prophylactic or infection treatment option for both acute and chronic wounds. The underlining value of the therapy is reduction of wound level bacteria without inhibiting the stages of wound healing. HNE is designed to permeate bacterial membranes and dehydrate the microbes. The therapy further increases wound closure by enhancing wound microcirculation and removal of bioburden. Based on prior positive data in rodent models, our goal in the current proposal was to further elucidate the HNE platform’s safety and efficacy in a more representative large animal model of wound healing. These research objectives can be broadly described as characterizing the dose-response characteristics of the HNE technology, assessing acute dermal toxicology, and formulating a product that is both aesthetically and functionally acceptable for clinical use. The Phase I results provided significant proof of concept data that demonstrates product safety and patient oriented benefits. The proposed HNE technology possesses very low acute and short-term tissue toxicity. The dose-response characteristics show no signs of increased tissue damage as a function of increasing concentration. Based on the pilot studies, we even expanded the dosage by over two-fold to what was originally proposed and still did not observe detrimental side effects. Additionally, the technology did not display any acute dermal irritation and is not a dermal sensitizing agent- even at the highest applied concentration. These results suggest the HNE platform to be highly safe for dermatological and wound care application. The HNE technology at all doses reduced wound level microbial load by >99.9% in the porcine model of partial thickness injury within 24hrs. These results are also statistically better than the untreated controls by ten-fold. The proposed mechanism of antimicrobial action is a combination of microbial inhibition and increased microcirculation that cleanses the wound of surface contaminants and bioburden. The technology also showed benefits in several areas of wound healing, such as an improved hemostatic response and the preservation of a moist wound microenvironment conducive for healing, especially during the inflammatory phase of wound healing. Therefore, we have shown that the HNE concept to be a feasible treatment option that does not incur noticeable side effects. Specifically, this data along with our previous pre-clinical data in rodents suggest that the HNE technology reduces superficial wound bacteria and provides a cleaner, healthier microenvironment for wound healing. Based on our survey of the wound care market and discussions with wound care firms, the HNE technology warrants further investigation due to its potential in improving patient outcomes and reducing the time/costs associated with medical treatment.
