Novel Supramacromolecular Polymer Complexes Providing Controlled Nitric Oxide Release for Healing Wounds
To overcome these deficiencies, UofToronto researchers have developed a novel, stable and biocompatible system for generating a durable release of NO. This technology is based on the discovery that a supramacromolecular complex, based on interacting GSNO conjugated to 2 polymers through intermolecular hydrogen bonding, can stabilize the conjugated GSNO and provide a controlled release of NO for an extended duration, not achievable by any currently available system. Background Chronic non-healing wound conditions such as diabetic ulcers represent a major clinical problem which impair the quality of life for diabetic patients and often lead to amputations. In advanced wound healing therapies, recombinant growth factors and bioengineered skin substitutes have had limited success in treating such chronic wounds. Nitric oxide (NO), an important physiological mediator, has been shown to play a critical role in enhancing wound healing. In fact, several studies have linked impaired wound healing in diabetic ulcer patients to NO deficiency at the wound site. Indeed, topical administration of NO or NO donors has been shown to be beneficial in promoting tissue repair and healing of diabetic ulcers in animal models. However, this approach has been limited by the short duration of NO release, short half-life of NO in physiological fluid, and the intrinsic instability of available NO donors. Currently, materials that can achieve prolonged release of NO at the wound site are still lacking. Existing NO-releasing materials have been limited by their lack of efficacy and/or dermal toxicity. More recently, S-nitrosoglutathione (GSNO), an endogenous nitrosothiol, has attracted significant attention as a desirable NO donor for wound healing. It has been physically incorporated or covalently attached to various hydrophilic polymer carriers in an attempt to improve biocompatibility and prolong the NO release. However, these systems lack the desired stability since the S-NO bond in S-nitrosoglutathione is both thermally and photolytically labile and susceptible to hemolytic cleavage leading to the spontaneous release of NO and its rapid inactivation. Therefore, the NO release from these prior art systems can not be maintained for any extended period, generally not more than several hours. Technology To overcome these deficiencies, UofToronto researchers have developed a novel, stable and biocompatible system for generating a durable release of NO. This technology is based on the discovery that a supramacromolecular complex, based on interacting GSNO conjugated to 2 polymers through intermolecular hydrogen bonding, can stabilize the conjugated GSNO and provide a controlled release of NO for an extended duration, not achievable by any currently available system. Advantages
• The system is novel, stable and biocompatible for generating a durable release of NO.
• It provides a control release of NO, up to 9 days or more.
• This novel nitric oxide releasing polymer complex can be incorporated into dressings and bandages for wound treatment.
• All its functional components have had prior history of use in man and in approved drug products. Applications Wound care is one of the most profitable and rapidly growing market segments that is being driven by our aging population and continued advances in biotechnology. The global market for wound care is estimated at $4.2 billion (Kalorama Information, Wound Care Markets, Volume 1: Skin Ulcers, July 2007). There has been a lack of effective treatment options which has been increasing costs for treatment of skin ulcers. The goal of new product manufacturers is to offer products designed to improve healing rates and prevent wound formation. Our supramacromolecular complex invention has an immediate fit and application in the “Moist Dressings” category of the wound healing market, although there may be synergies and applications in other segments of the total market (such as Skin Ulcer Management) that have yet to be crystallized. Intellectual Property On behalf of the inventors TIG filed a Canadian Patent Application No. 2,599,082 entitled
“Supramacromolecular Polymer Complexes Providing Controlled Nitric Oxide Release for Healing Wounds” on August 27, 2007. Business Opportunity The current business opportunity is to outlicense the supramacromolecular complex system for specific wound healing applications to biotech and pharma companies that are working in the area of these applications. Inventors Drs. Ping Lee and Yan Li. Dr. Lee is a Professor and GlaxoSmithKline Chair in the Faculty of Pharmacy at University of Toronto. His expertise lies in the design, fabrication and testing of polymeric controlled release delivery systems.
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