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.

Grant Number: 5R01HL170574-03
NIH Institute/Center: NIH
Principal Investigator: Elizabeth Brisbois