Towards Stents with Drug-Eluting Tethered Polymers

具有药物洗脱系留聚合物的支架

• 批准号: 7365454
• 负责人: Douglas E Hirt
• 金额: $ 22.16万
• 依托单位: CLEMSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-15 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7365454
• 关键词: Adverse reactions; Affect; Arteries; Biocompatible; Blood; Blood flow; Cause of Death; Characteristics; Chemicals; Chemistry; Clinical Trials; Condition; Coronary Arteriosclerosis; Coronary Artery Bypass; Development; Diffusion; Disclosure; Disease; Drug Controls; Drug Delivery Systems; Drug Monitoring; Figs - dietary; Goals; Hydrolysis; Imaging Techniques; Invasive; Left; Metals; Numbers; Object Attachment; Outcome; Paclitaxel; Patients; Personal Satisfaction; Pharmaceutical Preparations; Physiological; Polymer Chemistry; Polymers; Population; Procedures; Process; Rate; Reaction; Recovery; Research; Resistance; Side; Sirolimus; Solvents; Stainless Steel; Steel; Stents; Stream; Structure; Surface; System; Technology; Thick; Time; United States; base; clinically relevant; concept; density; design; diabetic; dosage; drug efficacy; functional group; improved; innovation; interest; monolayer; nanocoating; novel; polymerization; spectroscopic imaging

DESCRIPTION (provided by applicant): Coronary artery disease is the single leading cause of death in the United States, and drug-eluting stents (DES) have been developed as a means to open blocked or occluded arteries to significantly improve blood flow and provide controlled drug release to minimize the body's reaction to the stent. Our long-term goal is to develop durable, drug-releasing nano-coatings that cannot be compromised during stent handling and insertion. The specific hypothesis is that crack- resistance polymer nanolayers can be grafted from a stent surface. The nanolayers provide carefully chosen chemical functional groups to which a clinically relevant amount of drug could be immobilized and then released over time once the stent is inserted into a stenotic artery. Our rationale for this study is that conventional DES polymer coatings 1) may crack during stent expansion; 2) cause some patients to have adverse reactions; and 3) require the polymer and drug to be miscible in a common solvent during the coating process, which limits the number of available drugs that can be used. Therefore, the emphasis of this proposed research is on the synthesis of durable nano-coatings and the characterization of release profiles of clinically relevant drugs (e.g., paclitaxel, rapamycin). The specific aims are to: 1. Demonstrate the surface-grafting of drug-containing polymer chains from stents We will use graft polymerization to grow polymer nanolayers from specially designed functional groups that attach covalently to stent surfaces. After polymerization, the side chains of the polymer will be reacted with clinically relevant drugs, and we will correlate the efficacy of drug attachment with polymer layer thickness and grafting density. 2. Evaluate drug elution from the tethered chains We will monitor the drug-elution characteristics under physiologic conditions using a microarray-based spectroscopic imaging technique. The time-dependent amount of drug released will be characterized as a function of polymer layer thickness and grafting density as well as the type of drug molecule. We will also investigate the use of biocompatible overlayers to control hydrolysis and diffusion rates. NARRATIVE Developments in drug-eluting stents (DES) would reduce the rate of revascularization and improve patient recovery using a procedure much less invasive and costly than coronary artery bypass grafting. Improved DES technology also expands the potential use to those cases that are currently less amenable to DES such as multivessel disease, especially for diabetic patients who represent a growing segment of our population.

描述（由申请人提供）：冠状动脉疾病是美国的单一主要死亡原因，并且已经开发出药物洗脱支架（DES），作为打开阻塞或遮挡动脉的一种手段，可显着改善血液流动，并提供受控药物释放，以最大程度地减少人体对支架的反应。我们的长期目标是开发耐用的，富含药物的纳米涂料，这些纳米涂料在支架处理和插入过程中无法妥协。特定的假设是裂纹 - 抗性聚合物纳米层可以从支架表面接枝。纳米层提供了精心选择的化学官能团，一旦支架插入狭窄动脉，就可以将临床上相关的药物固定并随时间释放。我们对这项研究的理由是传统的DES聚合物涂层1）在支架膨胀过程中可能破裂； 2）导致某些患者的反应不良； 3）要求在涂料过程中共同溶剂中的聚合物和药物可混杂，这限制了可以使用的可用药物的数量。因此，这项拟议的研究的重点是耐用纳米涂料的合成以及临床相关药物的释放谱的表征（例如，紫杉醇，雷帕霉素）。 具体目的是：1。证明从支架上的含药物聚合物链的表面修剪我们将使用移植聚合物化从共同设计的特殊设计的官能团中生长聚合物纳米层，这些官能团共同将其连接到支架表面上。聚合后，聚合物的侧链将与临床相关的药物反应，我们将将药物附着的疗效与聚合物层厚度和嫁接密度相关联。 2。评估束缚链中的药物洗脱，我们将使用基于微阵列的光谱成像技术在生理条件下监测药物的特征。释放的时间依赖性药物的特征是聚合物层厚度和嫁接密度以及药物分子的类型的函数。我们还将调查使用生物相容性叠加层来控制水解和扩散速率的使用。叙述 与冠状动脉搭桥术相比，使用药物洗脱支架（DES）的发展将降低血运重建率并改善患者的康复率。改进的DES技术还将潜在用途扩展到目前不太适合DES的情况，例如多系列疾病，尤其是对于代表我们人群越来越多的糖尿病患者而言。