Zhu Xiaoxiang, Pack Daniel W, Braatz Richard D
a Department of Chemical Engineering , Massachusetts Institute of Technology , Cambridge , MA 02139 , USA.
Comput Methods Biomech Biomed Engin. 2014;17(3):187-98. doi: 10.1080/10255842.2012.672815. Epub 2012 Apr 18.
In-stent restenosis occurs in coronary arteries after implantation of drug-eluting stents with non-uniform restenosis thickness distribution in the artery cross section. Knowledge of the spatio-temporal drug uptake in the arterial wall is useful for investigating restenosis growth but may often be very expensive/difficult to acquire experimentally. In this study, local delivery of a hydrophobic drug from a drug-eluting stent implanted in a coronary artery is mathematically modelled to investigate the drug release and spatio-temporal drug distribution in the arterial wall. The model integrates drug diffusion in the coating and drug diffusion with reversible binding in the arterial wall. The model is solved by the finite volume method for both high and low drug loadings relative to its solubility in the stent coating with varied isotropic-anisotropic vascular drug diffusivities. Drug release profiles in the coating are observed to depend not only on the coating drug diffusivity but also on the properties of the surrounding arterial wall. Time dependencies of the spatially averaged free- and bound-drug levels in the arterial wall on the coating and vascular drug diffusivities are discussed. Anisotropic vascular drug diffusivities result in slightly different average drug levels in the arterial wall but with very different spatial distributions. Higher circumferential vascular diffusivity results in more uniform drug loading in the upper layers and is potentially beneficial in reducing in-stent restenosis. An analytical expression is derived which can be used to determine regions in the arterial with higher free-drug concentration than bound-drug concentration.
药物洗脱支架植入冠状动脉后会发生支架内再狭窄，动脉横截面的再狭窄厚度分布不均匀。了解动脉壁内药物的时空摄取情况有助于研究再狭窄的发展，但通过实验获取往往非常昂贵或困难。在本研究中，对植入冠状动脉的药物洗脱支架局部递送疏水性药物进行了数学建模，以研究药物释放及动脉壁内药物的时空分布。该模型整合了药物在涂层中的扩散以及药物在动脉壁内具有可逆结合的扩散。对于相对于其在支架涂层中的溶解度而言高载药量和低载药量的情况，采用有限体积法求解该模型，同时考虑了各向同性 - 各向异性的血管药物扩散率。观察到涂层中的药物释放曲线不仅取决于涂层药物扩散率，还取决于周围动脉壁的特性。讨论了动脉壁内空间平均游离药物和结合药物水平随时间对涂层和血管药物扩散率的依赖性。各向异性的血管药物扩散率导致动脉壁内平均药物水平略有不同，但空间分布差异很大。较高的周向血管扩散率导致上层药物负载更均匀，这可能有利于减少支架内再狭窄。推导了一个解析表达式，可用于确定动脉中游离药物浓度高于结合药物浓度的区域。
