# Engineering nitric oxide releasing polymer with immobilized thrombin inhibitor for blood contacting applications

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2020 · $382,500

## Abstract

Project Summary/Abstract
After decades of research, an ideal non-thrombogenic and antibacterial surface is still yet to be identified and
remains an unsolved problem. Blood-material interactions are critical to the success of implantable medical
devices including simple catheters, stents and grafts, insulation materials for electrical leads of pacemakers
and defibrillators, and complex extracorporeal artificial organs, which are used in thousands of patients every
day. There are two major limiting factors to clinical application of blood contacting materials: 1) platelet
activation and thrombosis, and 2) infection.
Over the last five years we have demonstrated that surface nitric oxide (NO) release can prevent platelet
activation and bacterial infection. This technology is based on the fact that NO secretion by the normal
endothelium prevents clotting by preventing platelet adhesion and activation. Further, NO released within the
sinus cavities, and by neutrophils and macrophages, functions as a potent natural antimicrobial and antiviral
agent. Recently we discovered that all of the positive effects of NO release can be achieved from polymers
doped with the NO donor molecule S-nitroso-N-acetylpenicillamine (SNAP), which is nontoxic, inexpensive,
and easy to synthesize. Nitric oxide release alone can inhibit platelet function locally at the polymer/blood
interface, but it does not prevent fibrin formation, which plays a key role in a clot formation. Argatroban is a
direct thrombin inhibitor that prevents fibrin formation. Argatroban is synthetic, easily available, non-allergenic,
and FDA approved for intravenous administration. Recently we have also shown that immobilizing the
thrombin inhibitor, argatroban, to NO-releasing surfaces preserves platelets and reduces clot formation in a 4 h
animal model significantly better than the NO-releasing surfaces alone. The goal of this proposal is to
develop, optimize, and evaluate a novel polymer coating that will combine agents that inhibit platelet
adhesion and activation via NO release as well as inhibit the fibrin formation using the immobilized
argatroban. The new coatings will be applicable to any blood-contacting device; however, this proposal will
focus on studying the combined effect of NO release and argatroban in long-term (up to 30 d) intravascular
catheter-type devices.

## Key facts

- **NIH application ID:** 9883033
- **Project number:** 5R01HL134899-04
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Hitesh Handa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883033

## Citation

> US National Institutes of Health, RePORTER application 9883033, Engineering nitric oxide releasing polymer with immobilized thrombin inhibitor for blood contacting applications (5R01HL134899-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9883033. Licensed CC0.

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