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Development of novel adenosine polymers for coating medical devices

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HL102891-01A1
Agency Tracking Number: R41HL102891
Amount: $182,972.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA10-051
Timeline
Solicitation Year: 2011
Award Year: 2011
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
1107 SNOW BERRY STREET
PARK CITY, UT 84098-
United States
DUNS: 011642789
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 MERVYN FORMAN
 (678) 843-5713
 formanm@bellsouth.net
Business Contact
 JILL BORLAND
Phone: (678) 843-5713
Email: jborland@sjha.org
Research Institution
 SAINT JOSEPH'S TRANSLATIONAL RESEARCH INSTITUTE
 
387 Technology Circle Suite 175
ATLANTA, GA 30313-
United States

 () -
 Domestic Nonprofit Research Organization
Abstract

DESCRIPTION (provided by applicant): Percutaneous coronary intervention (PCI) is the most frequently employed strategy to revascularize atherosclerotic stenosis of native coronary arteries and saphenous vein grafts. Tissue perfusion is frequently impairedfollowing PCI, particularly in patients with ST segment elevation myocardial infarction (STEMI). This results in the no-reflow phenomenon which is an important predictor of mortality. Adenosine is an endogenous nucleoside that attenuates many of the mechanisms responsible for the no-reflow phenomenon. Experimental and clinical studies have confirmed adenosine's efficacy in enhancing myocardial salvage and improving microvascular blood flow. Adensoine's full therapeutic potential is compromised due to its ultra short half life requiring large doses to obtain adequate blood levels at the target organ. Since the guidewire is the first PCI device that perturbs the vascular bed, we have developed the concept of elution of adenosine continuously via an adenosine-polymer-coated guidewire. We have developed a number of unique physiologic polymers in which adenosine can be covalently incorporated and placed on a guidewire. We tested out first generation polymers (LDI-glycerol and LDI-adenosine) in a small animal model and verified that it resulted in a substantial increase in blood flow. However in a large animal model the kinetic profile was too rapid for a typical interventional procedure (~45 mins). We have subsequently developed two new polymers, LDI- cysteineand LDI-PEG. Prior to initiating large animal studies in a Phase 2 study it is imperative we optimize the polymer structure, guidewire-coating methodology and kinetic release profile. We therefore propose the following studies with the new polymers to identify an ideal product. First we will develop and characterize the structure of the polymers and permutations thereof and evaluate numerous coating methodologies to optimize release kinetic profile. Second we will evaluate adenosine elution utilizing a temperature controlled recirculating water bath system and measure adenosine release serially with HPLC. Third we will determine if the selected polymer is safe for clinical use by employing NAMSA- based screening tests for cytotoxicity, pyrogenicity, hemolysis, and sensitization. Finally we will evaluate the stability and durability of the polymer with glass transition temperature experiments and by passing coated wires through simulated lesions. If the anti-no-reflow wire is shown to be effective in improving outcomes after interventional procedures it will represent a major advance in the treatment of patients with coronary artery disease undergoing PCI. This will have important societal benefits due to the large number of interventional procedures performed in the US each year for coronary artery disease. PUBLIC HEALTH RELEVANCE: The improved outcomes that may potentially occur with the device would have important societal benefits due to the large number of interventional procedures performed inthe US each year for atherosclerotic disease.

* Information listed above is at the time of submission. *

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