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Release mechanism and parameter estimation in drug-eluting stent systems : analytical solutions of drug release and tissue transport

机译:药物洗脱支架系统的释放机理和参数估计:药物释放和组织转运的分析解决方案

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摘要

Drug-eluting stents have significantly improved the treatment of coronary artery disease. They offer reduced rates of restenosis compared with their bare-metal predecessors and are the current gold standard in percutaneous coronary interventions. Drug-eluting stents have been approved for use in humans since 2002 and yet, despite the intensive research activity over the past decade, the drug release mechanism(s) and the uptake into the arterial wall are still poorly understood. While stent manufacturers have focussed primarily on empirical methods, several mathematical models have appeared in the literature considering the release problem, the uptake problem and also the coupled problem. However, two significant challenges that remain are in understanding the drug release mechanism(s) and also the determination of the various parameters characterising the system. These include drug diffusion coefficients and dissolution constants in the stent polymer coating as well as drug diffusion coefficients, binding/uptake rates and the magnitude of the transmural convection in the arterial wall. In this paper we attempt to address these problems. We provide analytical solutions which, when compared with appropriate experiments, may allow the various parameters of the system to be estimated via the inverse problem. The analytical solutions which we provide here for drug release in vitro may thus be used as a tool for providing insight into the mechanism(s) of release.
机译:药物洗脱支架显着改善了冠状动脉疾病的治疗。与裸机相比,它们的再狭窄率降低,并且是经皮冠状动脉介入治疗的当前金标准。自2002年以来,药物洗脱支架已被批准用于人体,尽管在过去十年中进行了深入研究,但对药物释放机制和对动脉壁的吸收仍知之甚少。虽然支架制造商主要关注经验方法,但考虑释放问题,吸收问题以及耦合问题,文献中出现了几种数学模型。然而,在理解药物释放机理以及确定表征系统的各种参数方面仍然存在两个重大挑战。这些因素包括支架聚合物涂层中的药物扩散系数和溶出常数,以及药物扩散系数,结合/摄取率和动脉壁中透壁对流的大小。在本文中,我们尝试解决这些问题。我们提供分析解决方案,当与适当的实验进行比较时,可以通过反问题来估算系统的各种参数。因此,我们在此处提供的用于体外药物释放的分析解决方案可以用作了解释放机理的工具。

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