This proposed SBIR research effort will lay the foundation for commercializing a new class of biomaterial for the prevention and treatment of infected skin wounds, thereby enhancing patient health through improved patient outcome and reduced patient morbidity. Specifically, we will focus on evaluating and developing a biomaterial comprised of a nitric oxide (NO)-releasing based on a commonly used medical polymer. Important to the current application, this polymer can be designed to releases NO at predefined levels and exhibits excellent antibacterial and anti-biofilm properties as evidenced by our preliminary data using both in vitro and ex vivo biofilm models where it significantly outperforms commercially available wound care dressings. Through the completion of research and development tasks during the Phase I/II efforts, we will have compiled a compelling data set that outlines the biocompatibility, the efficacy and the mode of action of the NO-releasing polymer in infection management and wound healing that supports its entry into the FDA's regulatory process. Nitric oxide-releasing technologies offer a compelling alternative to standard antimicrobial treatments and antibiotics currently used in to combat infection in wounds. Our preliminary data clearly demonstrate the potential clinical utility of the proposed NO-releasing polyemr in addressing microbial infection in general, and more importantly, prevention and treatment of microbial biofilms that plague chronic skin wounds. An important milestone for this Phase I project will be the development of prototype NO-releasing topical formulations that will serve as both a non-antibiotic prophylactic treatment against microbial infection and as a treatment for chronically infected wounds ? two unmet needs within the wound care field. Completion of the Phase I efforts will result in a compelling data set that outlines the efficacy and defines the minimal requirements for product formulation in terms of topical application. Together, these studies will help in the transition to broader Phase II studies designed to support entry of our product into the FDA's regulatory process. iFyber will address the efficacy of the NO-releasing technology through the Phase I aims and tasks outlined below:
AIM 1. Develop a series of prototype topical formulation guided by an ex-vivo dermal model system Task 1. Produce prototype NO-releasing topical formulations. Past R&D efforts have established that point-of-care (POC) compounding is a plausible strategy for an NO-based wound dressing; that is, POC formulation(s) that are mixed just prior to applying to a wound. Prototype formulations selection will be guided by efficacy testing in the ex vivo model (Task 2) and subsequently in pilot in vivo studies (Task 4). Task 2. Conduct ex vivo dermal model testing for formulation selection. The goal of this task is to evaluate the efficacy of the prototype formulations from Task 1 in an ex vivo porcine dermal model to define suitable antimicrobial and anti-biofilm semi-solid dressings for wounds. A main goal in this task will be to down-select formulations for pilot animal studies (Tasks 3 and 4).
AIM 2. Guide prototype development through pre-clinical pilot studies Task 3. Conduct in vivo testing on selected formulations. Most promising formulations identified through Task 1-2 will be evaluated in two pilot in vivo studies conducted in the laboratory of Dr. Steven Davis at the University of Miami. These studies will establish efficacy in biofilm prevention (study 1) and reduction in an existing biofilm-associated infection (study 2), and results of these studies will help to further down-select formulations for future Phase II development Task 4. Determine the baseline in vivo biocompatibility profile of the NO-releasing polymer. In addition to assessing infection prevention and anti-biofilm efficacy, the effects of candidate formulations on non-infected wounds will also be assessed with respect to the wound healing process; specifically, inflammatory response, erythema, re-epithelialization, granulation tissue formation, and initial molecular screens for healing and inflammatory processes.
Acute wounds as well as chronic, slow-healing wounds are aggravated by relentless microbial infections that promote remarkable tolerance to classical anti-infectious treatments, including systemic and topical antibiotics, and general topical biocides. The current SBIR research effort aims to advance the development of a new class of biomaterial for the prevention and treatment of both acute and chronic wound infections to improve treatment and patient health with improved outcomes.
