Layer-by-layer assembly for making drug-eluting stents

逐层组装制备药物洗脱支架

• 批准号: 6966086
• 负责人: KINAM PARK
• 金额: $ 37.16万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6966086
• 关键词: Raman spectrometry; biomaterial compatibility; biomaterial development /preparation; biomaterial interface interaction; biotechnology; clinical research; confocal scanning microscopy; drug vehicle; fluorescent dye /probe; heparin; human subject; microcapsule; packaging material; paclitaxel; pharmacokinetics; polymers; slow release drug; surface coating

DESCRIPTION (provided by applicant): The drug-eluting stent (DES) is known to be the third revolution in Interventional Cardiology. While drug delivery from stents has resulted in substantial improvement in prevention of restenosis, the types of drugs to be delivered and the desired release kinetics are not well understood. The DES field is still in its infant stage, and it requires development of better stents with more desirable drug release kinetics. It is critical to obtain the ability to control the drug release kinetics from stents and to understand the local concentrations of the released drug in relation to the strut spacing of a stent. The objective of this project is to develop novel drug coating methods based on the layer-by-layer (LBL) assembly technology, in conjunction with well-established polymer coating methods. Paclitaxel is used as the model drug in the LBL approach. Only several layers will be necessary for LBL assembly on the stents. This project is based on the hypothesis that different regions of a stent should have different drug release profiles based on the density of struts on the stent to obtain homogeneous local paclitaxel concentration in the tissue surrounding the stent. The specific aims of this project are: (1) to prepare paclitaxel-loaded LBL assembly blocks (paclitaxel microparticles and paclitaxel-loaded polymer microspheres); (2) to build drug-eluting layers on substrates (stainless steel wires, plates, and stents) using combination of LBL assembly and microfabrication; (3) to examine the three-dimensional (3-D) distribution of the drug inside the LBL assemblies as a function of time, and to examine the drug release profiles; and (4) to modify the assembled building blocks with heparin for improved biocompatibility and to examine its effect on drug release profiles. The significance of this project is that the drug coating methods based on LBL assembly and microfabrication can provide tools for researchers to load drugs with the ability to control the local drug release profiles along the stent. The ability to obtain homogeneous local drug concentration in the tissue surrounding the stent will be essential in finding the right drugs and their optimum release kinetics as more and more new drugs and new stent designs will be developed for the prevention of restenosis.

描述（由申请人提供）： 众所周知，洗脱支架（DES）是介入心脏病学的第三次革命。虽然从支架上输送药物已导致预防再狭窄，但要递送的药物类型，所需的释放动力学尚不清楚。 DES领域仍处于婴儿阶段，它需要开发具有更理想的药物释放动力学的更好支架。至关重要的是，获得从支架上控制药物释放动力学并了解释放药物的局部浓度的能力至关重要。该项目的目的是基于逐层（LBL）组装技术开发新型的药物涂料方法，并结合建立的聚合物涂料方法。紫杉醇用作LBL方法中的模型药物。在支架上的LBL组件只需要几层。该项目基于以下假设：支架的不同区域应基于支架上的支柱的密度具有不同的药物释放曲线，以在支架周围的组织中获得均匀的局部局部紫杉醇浓度。该项目的具体目的是：（1）制备负载紫杉醇的LBL组件（紫杉醇微粒和紫杉醇负载的聚合物微球）； （2）使用LBL组装和微加工的组合在底物（不锈钢线，板和支架）上建造药物洗脱层； （3）检查LBL组件内药物的三维（3-D）分布，并检查药物释放曲线； （4）用肝素修改组装的构建块，以提高生物相容性，并检查其对药物释放曲线的影响。该项目的意义在于，基于LBL组装和微加工的药物涂料方法可以为研究人员提供工具，以便在控制沿支架的局部药物释放曲线的能力中加载药物。在围绕支架周围的组织中获得均匀的局部药物浓度的能力对于找到合适的药物及其最佳释放动力学至关重要，因为越来越多的新药和新的支架设计将开发以预防再狭窄。