Modeling the transport of drugs eluted from stents: physical phenomena driving drug distribution in the arterial wall
Modeling the transport of drugs eluted from stents: physical phenomena driving drug distribution in the arterial wall
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DOI：
10.1007/s10237-013-0546-4
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发表时间：
2014-04-01
影响因子：
3.5
通讯作者：
Barakat, Abdul I.
中科院分区：
文献类型：
--
作者：
Bozsak, Franz;Chomaz, Jean-Marc;Barakat, Abdul I.
尽管最近的数据表明药物洗脱支架（DES）的整体性能上级裸金属支架，但DES的长期安全性和有效性仍存在争议。近年来，与DES使用相关的晚期支架血栓形成风险也促使开发了一种新的有前景的治疗选择，即药物涂层球囊（DCB）。与DES相反，DES的药物选择通常是西罗莫司及其衍生物，DCB使用紫杉醇，因为西罗莫司的使用似乎不会导致令人满意的结果。由于西罗莫司和紫杉醇都是具有相似转运特性的高亲脂性药物，因此紫杉醇而不是西罗莫司在DCB中成功的原因尚不清楚。从DES或DCB洗脱的药物在动脉壁内转运的计算模型有望增强我们对这些器械性能的理解。本研究开发了一个计算模型的运输两种药物紫杉醇和西罗莫司洗脱DES在动脉壁。该模型考虑了动脉壁的多层结构，并采用可逆结合模型来描述药物与动脉壁成分的相互作用。目前的结果表明，紫杉醇在动脉壁中的运输主要是由对流，而西罗莫司的运输主要是由结合过程。这些显著差异表明DES的药物释放动力学应根据所用药物的类型进行调整。
Despite recent data that suggest that the overall performance of drug-eluting stents (DES) is superior to that of bare-metal stents, the long-term safety and efficacy of DES remain controversial. The risk of late stent thrombosis associated with the use of DES has also motivated the development of a new and promising treatment option in recent years, namely drug-coated balloons (DCB). Contrary to DES where the drug of choice is typically sirolimus and its derivatives, DCB use paclitaxel since the use of sirolimus does not appear to lead to satisfactory results. Since both sirolimus and paclitaxel are highly lipophilic drugs with similar transport properties, the reason for the success of paclitaxel but not sirolimus in DCB remains unclear. Computational models of the transport of drugs eluted from DES or DCB within the arterial wall promise to enhance our understanding of the performance of these devices. The present study develops a computational model of the transport of the two drugs paclitaxel and sirolimus eluted from DES in the arterial wall. The model takes into account the multilayered structure of the arterial wall and incorporates a reversible binding model to describe drug interactions with the constituents of the arterial wall. The present results demonstrate that the transport of paclitaxel in the arterial wall is dominated by convection while the transport of sirolimus is dominated by the binding process. These marked differences suggest that drug release kinetics of DES should be tailored to the type of drug used.