Description:
OBJECTIVE: Develop a biocompatible dressing material for the controlled delivery of analgesic drugs to burn wounds. DESCRIPTION: Thousands of U.S. military personnel have suffered serious burn wounds and other injuries during Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF), where burns have been identified as the primary cause of injury in 5% of all military personnel evacuated from those battlefields (1-2). Uncontrolled acute burn pain contributes to several sensory abnormalities including development of chronic pain (3-4). Burn patients report intense pain during procedures such as wound debridement, dressing changes and strenuous physical and occupational therapy. In fact procedural pain is the most common grievance reported by the burn population (5). Management of the intense pain that accompanies burn wounds relies heavily on systemically administered opioids, which produce many side effects including tolerance, hyperalgesia, hemodynamic instability, respiratory depression, and dependence (4). There is therefore a need to reduce quantities of opioid analgesics administered to burn patients. This need could be met through development of a topical analgesic wound dressing for severe combat-associated burn injuries that would reduce or eliminate the need for systemic treatment with opioids. Such dressings would also serve to protect the wound from infection and thereby aid in wound healing. This request addresses one of the new USAMRMC SBIR topics for FY14, which falls within the goals of the Clinical and Rehabilitative Medicine Research Program: Novel pharmaceutical approaches to alleviate the development of tolerance and physical dependence of opioids without diminishing opioids"analgesic effects. To further accelerate healing, active wound dressings have been developed that provide controlled local delivery of therapeutic agents, such as biological growth factors and antimicrobial agents, while keeping the wound surface moist, removing exudates, inhibiting bacterial invasion and allowing oxygen permeation. Active wound dressings would ideally maintain the local drug concentration at a constant optimum therapeutic dosage level from the moment of initial application until complete wound healing is achieved (i.e., zero-order kinetics). To be suitable for topical application to burns, the composite wound dressing materials must also be carefully selected for biocompatibility, mechanical strength and surface adhesion, and resistance to bacterial invasion so that clinicians can readily apply and remove them at appropriate times during therapy. Eventually the development of wound dressings that deliver combinations of analgesics and antimicrobials is planned. PHASE I: Identify and define a biocompatible material which can provide the controlled delivery of analgesic drugs. This material must be adaptable to a wound dressing format. Required Phase I deliverables will include determination of technical feasibility using appropriate in-vitro, and if possible in-vivo assays. Such assays would demonstrate the ability of a prototype material to act as a stable, biologically compatible depot for one or more of the opioid analgesics (morphine, methadone, fentanyl, meperidine, oxycodone), or other mainstay analgesics (ketamine, gabapentin) currently used for treatment of burn wounds in the military population. In addition, demonstration of relevant physical properties of the material, such as mechanical strength, surface adhesion, resistance to bacterial invasion, and capacity for controlled release of analgesics (including release kinetics), is expected. In addition, once proof of feasibility is achieved, applicants are required to provide specific plans for how they will test the material in a validated animal pain model in Phase II. No human testing will be proposed for the Phase I (6 month) period. Although the period of time is short, it is preferred that an animal model be used for some part of the feasibility studies in Phase I. PHASE II: The proposed study should demonstrate and validate the efficacy of the material tested in Phase I for pain control in an in-vivo model that replicates burn injury induced pain. The safety of the material in combination with one or more of analgesics listed above must be demonstrated with respect to biocompatibility, toxicity and immunogenicity. The ideal material would have physical properties allowing it to conform to any burn wound surface. This includes liquids, gels, bandages and other dry materials that upon wound contact would conform to the complex topography of the wound bed. Phase II deliverables will include development, testing and demonstration of a prototype analgesic wound dressing composed of the material in combination with one or more of the above listed analgesics. The product should be self-administrable in the field and take effect within minutes of application. In addition, the product should be easily removed (i.e. dressing changed) without causing damage to the wound bed or left in place (i.e. biodegradable). The product also needs to be shelf stable for long periods of time at all likely temperatures experienced in austere combat environments. All these requirements must be demonstrated during the Phase II period. PHASE III: In this phase it is expected that all pre-clinical testing and validation of the Phase II prototype product(s) will be finalized. Phase III will primarily consist of clinical trials designed to test the safety and efficacy of the Phase II product(s) in burn pain control. The focus of these trials will be on testing for combat-related wound care and/or civilian wound care that is similar to combat wounds. Phase III efforts will be directed towards technology transfer, preferably commercialization, of the product(s) from Phase II. This will include application for FDA approval. Commercialization efforts will include GMP manufacturing of sufficient materials for evaluation. The small business should have plans to secure funding from non-SBIR government sources and /or the private sector to develop or transition the prototypes into a viable product(s) for sale to the military and/or private sector markets. The end-state of this research will be the full development of one or more products consisting of biocompatible wound dressings that deliver sustained pain control, which can be used effectively in austere combat environments. Such products are also expected to have utility extending beyond the combat environment, into civilian burn wound care and emergency medicine applications.
