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

描述（由申请人提供）： 药物洗脱支架（DES）被认为是介入心脏病学的第三次革命。虽然从支架的药物递送已经导致在预防再狭窄方面的实质性改善，但是待递送的药物的类型和期望的释放动力学还没有很好地理解。DES领域仍处于婴儿阶段，需要开发具有更理想药物释放动力学的更好支架。获得控制支架药物释放动力学的能力以及了解释放药物的局部浓度与支架支柱间距的关系至关重要。本项目的目的是开发基于逐层（LBL）组装技术的新型药物包衣方法，并结合成熟的聚合物包衣方法。紫杉醇在LBL方法中用作模型药物。支架上的LBL组装仅需要几层。本项目基于以下假设：根据支架上支柱的密度，支架的不同区域应具有不同的药物释放曲线，以在支架周围组织中获得均匀的局部紫杉醇浓度。本课题的具体目标是：（1）制备紫杉醇长链组装块（紫杉醇微粒和紫杉醇负载的聚合物微球）;（2）在基底上构建药物洗脱层（不锈钢丝、板和支架），使用LBL组装和微加工的组合;（3）检查药物在LBL组件内作为时间函数的三维（3-D）分布，并检查药物释放曲线;和（4）用肝素修饰组装的结构单元以改善生物相容性并检查其对药物释放曲线的影响。本项目的意义在于基于LBL组装和微细加工的药物涂层方法可以为研究人员提供具有控制药物沿支架沿着局部释放曲线的能力的载药工具。随着越来越多的新药和新的支架设计被开发用于预防再狭窄，在支架周围组织中获得均匀的局部药物浓度的能力对于找到正确的药物及其最佳释放动力学将是至关重要的。

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.