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A structure-sensitive continuum model of arterial drug deposition

机译：动脉药物沉积的结构敏感连续模型

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The successful function of drug-eluting devices used in the treatment of atherosclerosis relies on the concentration and retention of the drug in the vessel wall. While drug deposition necessarily depends on the underlying tissue structure, conventional models do not account for the intrinsic structural complexity of arterial tissue and its impact on deposition. By employing only average bulk material properties, the capability to predict the potential for local toxicity or therapeutic failure is limited. To address these limitations, we have developed a model that accounts explicitly for variations in the tissue structure. The approach uses a laminate approximation of the underlying microscopic structure to specify an expression for the continuous spatial dependence of the effective macroscopic material properties. Based on this continuum description, we derive an analytic expression for drug uptake into arterial tissue under typical ex vivo experimental conditions. This expression is used to extract relevant material properties for pac-litaxel in bovine arteries based on available literature data. The best fit parameters are then used as the basis for numerical simulations of long-term deposition behavior from a stent with a pure paclitaxel coating. The results of these simulations are quantitatively consistent with previously reported in vivo observations. We also demonstrate that significant errors can arise in both the interpretation of experimental data and the prediction of drug deposition when structural heterogeneities are ignored. Establishing a robust deposition model can ultimately reduce empiricism in the design of drug-eluting devices, providing a facile means to guide the development and refinement of these technologies.
机译：用于治疗动脉粥样硬化的药物洗脱装置的成功功能取决于药物在血管壁中的浓度和保留率。虽然药物沉积必定取决于基础的组织结构，但常规模型并未考虑到动脉组织的固有结构复杂性及其对沉积的影响。通过仅采用平均散装材料特性，预测局部毒性或治疗失败潜力的能力受到限制。为了解决这些局限性，我们开发了一个模型，可以明确说明组织结构的变化。该方法使用底层微观结构的层状近似来指定有效宏观材料属性的连续空间依赖性表达式。基于此连续描述，我们得出在典型的离体实验条件下药物吸收到动脉组织中的分析表达。根据可用的文献数据，此表达式用于提取pac-紫杉醇在牛动脉中的相关物质特性。然后，将最佳拟合参数用作从纯紫杉醇涂层的支架进行长期沉积行为数值模拟的基础。这些模拟的结果在数量上与先前报道的体内观察结果一致。我们还证明，当忽略结构异质性时，在解释实验数据和预测药物沉积方面都可能出现重大错误。建立稳健的沉积模型最终可以减少药物洗脱设备设计中的经验，从而为指导这些技术的开发和完善提供了一种简便的方法。

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