Prevention of catheter related infections via photoactive nitric oxide delivery device

Project Summary/Abstract Currently, clinical applications of intravascular catheters suffer from major challenges: 1) infection; and 2) platelet activation and surface-induced thrombosis. Bacterial contamination of catheters causes more than 28,000 deaths per year in the United States, as well as costing the healthcare industry a staggering $2.3 billion. Thrombus formation can further lead to obstruction of blood vessels, catheter malfunction, or even life- threatening situations such as embolism. Commercial catheters with heparin-bonded surfaces are available to prevent clotting, but do little to prevent infections. In addition, antiseptics or antibiotics catheter coatings or lock solutions decrease the risk of bacterial infection, but do not prevent biofilm formation that shields bacteria from antibiotics. Therefore, there is a necessity and opportunity to develop device strategies for preventing infection and thrombosis on indwelling catheters for enhanced patency and safety. Our work and others have demonstrated that nitric oxide (NO) release from polymer surfaces can prevent platelet activation and bacterial infection. This technology mimics the vascular endothelial cells lining the blood vessels, as well as other cells in our bodies, producing NO locally to prevent clotting and bacterial biofilm. Recently we discovered that all of the positive effects can be achieved from polymers physically blended with the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP), which is nontoxic, inexpensive, and easy to synthesize. Active NO release from the NO donors in polymers reduces infection and thrombosis on catheters; however, the NO-release polymer strategy alone is limited by the finite reservoir of NO donor functionalities within the catheter wall which limits the duration of the NO availability/release. Our recent work has shown the potential of developing a catheter hub device that utilizes photoactive NO-releasing polymers with side glowing fiber optics that enables controllable NO release levels. The goal of this proposal is to develop a catheter hub device comprised of a polymer utilizing a NO donor covalently bonded to the polymer with side glowing fiber optics to provide photoactive NO-release (without leaching) to provide long-term, tunable NO-release at the catheter interface to provide potent broad-spectrum antimicrobial properties and reduce thrombosis by inhibiting platelet adhesion/activation. The new device will be applicable to any catheter device; however, this proposal will focus on studying the combined photoactive NO-releasing catheter hub device in long-term intravascular catheters for the prevention of infection and thrombosis. Successful completion of this project will allow progression to early clinical trials and the development of a new generation of devices that can be inserted within the lumen of indwelling catheters to prevent these complications while improving patient care.