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Novel coatings releasing synergistic polyphenols promote vascular healing

新型涂层释放协同多酚促进血管愈合

基本信息

批准号：
8716232
负责人：
TAMMY R DUGAS
金额：
$ 22.37万
依托单位：
REQUISITE BIOMEDICAL, LLC
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8716232
关键词：
Address Americas Angioplasty Animal Model Animals Antiplatelet Drugs Area Arteries Biological Factors Blood Platelets Blood Vessels Blood coagulation Blood flow Cardiac Cardiovascular Diseases Cause of Death Cell Proliferation Clinical Clinical Trials Coagulation Process Consultations Coronary Coronary artery Data Development Devices Disadvantaged Drug Delivery Systems Drug Formulations Drug Kinetics Drug usage Endothelial Cells Endothelium Event FDA approved Family suidae Funding Generations Goals Healed Hyperplasia Implant Inflammation Injury Intervention Left Lesion Letters Licensing Lower Extremity Marketing Medical Medical Device Metals Modeling Oryctolagus cuniculus Outcome Patients Peripheral Peripheral arterial disease Pharmaceutical Preparations Phase Physicians Poison Procedures Process Property Quercetin Rattus Research Design Resveratrol Risk Rodent Model Safety Site Small Business Technology Transfer Research Smooth Muscle Myocytes Solutions Source Staging Stenosis Stents Testing Thrombosis Time Tubular formation United States Validation Wound Healing artery occlusion biomaterial compatibility clinically relevant commercial application commercialization graft failure healing high risk human FRAP1 protein implantation improved new technology novel phase 1 study phase 2 study polyphenol prevent public health relevance red wine research study response restenosis vascular smooth muscle cell proliferation

项目摘要

PROJECT SUMMARY Cardiovascular disease (CVD) remains the number one cause of death in the U.S. Left untreated, CVD can result in the occlusion of key arteries that can precipitate a major cardiac event. Clinicians routinely correct arterial blockages mechanically using a balloon expansion of the lesioned area and placement of a metallic stent to help keep the arteries open. However, the overstretch of the vessel that takes place during the intervention is damaging to the artery wall. This damage often precipitates a re-narrowing of the artery (restenosis) due to the proliferation of smooth muscle cells within the vascular wall. Drug-eluting stents (DES) were developed to inhibit smooth muscle cell proliferation, but have the disadvantage that while keeping the arteries open, they also prevent the relining of the vessel wall with a functional endothelial cell layer. This requires that patients undergo long-term treatment with dual anti-platelet therapies in order to prevent rare, but often fatal late-term clotting events at the site of the implant. The applicant has developed a new coating for the endovascular drug delivery of synergistic natural products that prevent the negative responses to angioplasty treatment that promote artery re-narrowing. However, unlike the drugs currently used for stent coatings, these compounds have been shown to actively accelerate endothelial wound healing. Moreover, our preliminary data utilizing a rat model of stenting and angioplasty showed that DES coated with resveratrol and quercetin (RQ-DES) dramatically reduced restenosis, while at the same time, accelerated re-endothelialization to complete the healing process. The significance of these new RQ-DES is that by promoting vascular healing (i.e., re-endothelialization), their use in vascular interventions could reduce the need for dual anti-platelet therapies, as well as provide for safer long term outcomes. In this phase I proposal, the applicant will utilize an FDA-accepted, clinically relevant rabbit model to test whether the RQ-DES promotes re-endothelialization compared to a commercial stent device. Complementary studies using other company funding will test whether the RQ- DES also reduces the extent of restenosis. These studies will set the stage for a larger phase II project aimed at fully characterizing the safety and efficacy of our coatings for further commercialization. Our commercialization efforts will be aimed at the use of an RQ coating for diverse applications, including coronary artery and peripheral artery diseases, as well as other applications in which neointimal hyperplasia contributes to clinical complications, such as in arteriovenous graft failure.

项目总结