Prevention of Restenosis and Intimal Hyperplasia with Nitric Oxide

BioCure has licensed technology from Rice University for delivery of nitric oxide from hydrogels. These hydrogels could be coated onto stents for delivery of NO at the site of restenosis, or applied directly to the injured vessel, or coated onto vascular grafts to prevent intimal hyperplasia.

:: Rationale

NO has multiple physiological roles at the cellular and tissue level. The roles of NO in vasodilation and as an antithrombotic agent in the vascular system are well known and for decades have been exploited clinically in the form of NO releasing drugs, such as nitroglycerin for angina. Local delivery of NO from medical devices such as vascular grafts and stents has potential to prevent intimal hyperplasia or restenosis by minimizing thrombus deposition as well as by retarding smooth muscle cell proliferation and enhancing endothelial cell proliferation. The hydrogels could further have cell adhesion peptides covalently attached thereto to further encourage endothelial cell binding and proliferation.

:: Technology Description

Fast crosslinking PVA based prepolymers (or the formed hydrogel), modified with amine groups, are exposed to NO gas. The amine groups act as nucleophiles and a complex forms between the prepolymers or hydrogel and NO. On exposure to physiological conditions, the NO is released by hydrolysis and is able to act at the site of delivery. PVA-NO hydrogels can be sterilized by filtration and shelf-life can be extended by storage at low temperature or low pH. The NO loading can be varied by altering the % amine substitution and the exposure time to NO gas.

:: Results to Date

Release of NO from PVA-NO hydrogels was observed over a period of approximately two days at physiological pH and temperature using the Griess assay. In vitro studies conducted to date have shown that NO modified gels inhibit smooth muscle cell proliferation and platelet adhesion and activation and support endothelial cell proliferation. These findings combined support the role of NO in prevention of restenosis. Future studies will be conducted to evaluate the efficacy of these materials in vivo.

NO Release from PVA - NO Hydrogel

:: Patent Position

Issued patents for the fast crosslinking PVA hydrogel system. Patents pending for use of the PVA hydrogel system for preformed biomedical articles and for nitric oxide producing hydrogel materials.

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