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血栓形成调节动脉药物分发,用于药物排泄支架

Chao-Wei Hwang¹, Andrew D Levin, Michael Jonas

¹Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge 02139, USA. cwhwang@post.harvard.edu

|March 30, 2005

概括

药物释放支架上的血栓显著影响药物输送,导致不可预测的动脉吸收. 控制或去除凝块对于持续的药物沉积至关重要.

科学领域:

生物医学工程生物医学工程
心血管研究研究心血管研究
药物输送系统药物输送系统

背景情况:

药物释放支架 (DES) 用于将强效药物输送到动脉中.
支架在部署时可能会充满血栓 (凝块).
血栓对药物化和动脉吸收的影响尚未完全理解.

研究的目的:

为了研究血栓的组成和几何如何影响来自DES的帕克利塔塞尔运输.
为了确定血栓对药物化和动脉吸收的影响.
用体内数据验证计算模型.

主要方法:

评估了帕克利塔塞尔在各种凝块组合 (纤维素,纤维素红细胞,全血) 中的运输和保留.
利用计算建模来预测基于凝块和支架几何学的药物运输.
经过验证的模型预测,使用了一种新的小鼠模型,用于诱导血栓形成的支架性大动脉.

主要成果:

帕克利塔塞尔的扩散性随着凝块组织的变化而显著变化,在纤维素中最快,在全血凝块中最慢.
血细胞与帕克利塔塞尔结合,导致凝块中的保留率更高,特别是在生理性血液值时.
计算模型和老鼠研究表明,血栓几何决定药物吸收,要么减少 (动脉和支架之间的凝块),要么增加 (凝块覆盖支架).

结论:

支架上的血栓会导致药物吸收和沉积的大量变化.
凝块和支架之间的几何关系显著影响药物输送结果.
有效控制或去除血栓对于可预测的DES药物输送至关重要.

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