Zhang Xuelan, Luo Mingyao, Wang Erhui, Zheng Liancun, Shu Chang
School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 10083, China; School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China.
Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
Comput Methods Programs Biomed. 2020 Oct;195:105556. doi: 10.1016/j.cmpb.2020.105556. Epub 2020 May 29.
Nanoparticle-mediated targeted drug delivery is a promising option for treatment of atherosclerosis. However, the drug targeting may be affected by multiple factors. Considerable attentions have been focused on the influences of external factors, e.g., magnetic field, drug-loaded particle, but internal factors, e.g., plaque morphology (stenosis degree and shoulder length), have not received any attention yet. Therefore, we investigate the impact of plaque morphology on magnetic nanoparticles targeting under the action of an external field.
Numerical simulation, based on Eulerian-Lagrangian coupled Fluid-Solid Interaction, is performed in ANSYS Workbench platform. Blood flow is solved by Navier-Stokes equation, particles are tracked by discrete phase model, and the incorporated effect is obtained by two-way method. Plaques with varying stenosis degrees and shoulder lengths are acquired by manually modifying the geometry of patient-specific. The quantified variables include targeted delivery efficiency (deposition+adhesive strength) of particles and plaque injury characterized by temporal-spatial averaged shear stress (TAWSS¯) during the process of drug transport, in which the critical deposition velocity is determined by plaques and particles, the DEFINE_DPM_BC and User Defined Memory are employed to evaluate whether the particles are deposited, and to store the total number and the adhesive strength of particles deposited on the plaque.
Results signify that, with an increment of plaque stenosis degree, the deposition of particle and the adhesive strength between particle and plaque decrease, while the TAWSS¯ increases. Furthermore, for the same stenosis degree, with the increase of plaque shoulder length, the deposition and the adhesive strength of particle increase, and the TAWSS¯ decreases.
Results demonstrates that the plaque with smaller stenosis degree or longer shoulder length may achieve a better treatment effect in view of the higher targeted delivery efficiency of particles and the lighter shear damage to plaque itself during the process of drug transport.
纳米颗粒介导的靶向药物递送是治疗动脉粥样硬化的一种有前景的选择。然而，药物靶向可能受到多种因素影响。相当多的注意力集中在外部因素的影响上，例如磁场、载药颗粒，但内部因素，例如斑块形态（狭窄程度和肩部长度）尚未受到任何关注。因此，我们研究了在外加磁场作用下斑块形态对磁性纳米颗粒靶向的影响。
基于欧拉 - 拉格朗日耦合流固相互作用在ANSYS Workbench平台上进行数值模拟。通过纳维 - 斯托克斯方程求解血流，用离散相模型跟踪颗粒，并通过双向方法获得耦合效应。通过手动修改特定患者的几何形状来获取具有不同狭窄程度和肩部长度的斑块。量化变量包括药物运输过程中颗粒的靶向递送效率（沉积 + 粘附强度）以及以时空平均剪应力（TAWSS¯）表征的斑块损伤，其中临界沉积速度由斑块和颗粒决定，使用DEFINE_DPM_BC和用户定义内存来评估颗粒是否沉积，并存储沉积在斑块上的颗粒总数和粘附强度。
结果表明，随着斑块狭窄程度的增加，颗粒的沉积以及颗粒与斑块之间的粘附强度降低，而TAWSS¯增加。此外，对于相同的狭窄程度，随着斑块肩部长度的增加，颗粒的沉积和粘附强度增加，而TAWSS¯降低。
结果表明，从颗粒更高的靶向递送效率以及药物运输过程中对斑块本身较轻的剪切损伤来看，狭窄程度较小或肩部长度较长的斑块可能实现更好的治疗效果。
