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针对冠状动脉左前降支粥样硬化斑块的患者特异性磁药物靶向的计算机模拟研究。

In silico study of patient-specific magnetic drug targeting for a coronary LAD atherosclerotic plaque.

机构信息

School of Mechanical Engineering, Sharif University of Technology, Tehran, Iran.

School of Mechanical Engineering, Sharif University of Technology, Tehran, Iran.

出版信息

Int J Pharm. 2019 Mar 25;559:113-129. doi: 10.1016/j.ijpharm.2018.12.088. Epub 2019 Jan 14.

Abstract

Coronary artery disease is the first cause of death across the world. Targeted delivery of therapeutics through controlled release of micro- and nano-particles remains a very capable approach to develop new strategies in treating restenosis and atherosclerotic plaques. In this research, to produce the arterial geometry, an image-processing was done using CT-scan images of a LAD coronary artery. After implementing the finite element mesh, the Fluid-Structure Interaction (FSI) simulation based on physiological boundary conditions was performed. Next, a Lagrangian description of particles dynamics in a non-Newtonian blood flow considering momentum equation of motion for each particle and the imposed external magnetic field was provided. Under the influence of the magnetic field, the optimal particle size scope for which the surface density of particles (SDP) adhered on the plaque lumen reaches its maximum was specified. Also, our results signify that applying a magnetic field can adversely affect the delivery of particles to the targeted site for near micron-size particles. Along with the evaluation of the Brownian and the gravitational forces on nanoparticles, the uniformity of the distribution of particles in the left coronary network with and without the presence of the magnetic field has been studied. In conclusion, the external magnetic field has increased the SDP adhered on the targeted surface by 49.4% and 59.7% for 400 and 600 nm particles, respectively.

摘要

冠状动脉疾病是全球首要致死原因。通过控制微纳米颗粒的释放来实现靶向药物输送,仍然是开发治疗再狭窄和动脉粥样硬化斑块新策略的一种非常有潜力的方法。在这项研究中,通过对左前降支冠状动脉的 CT 扫描图像进行图像处理,来生成动脉几何形状。在实现有限元网格后,基于生理边界条件进行了流固耦合(FSI)模拟。接下来,提供了在非牛顿血流中考虑每个粒子的运动方程和施加的磁场的情况下,粒子动力学的拉格朗日描述。在磁场的影响下,指定了最佳的粒子尺寸范围,在此范围内,粒子的表面密度(SDP)在斑块内腔上的附着达到最大值。此外,我们的结果表明,施加磁场会对近微米尺寸的粒子向靶向部位的输送产生不利影响。除了评估布朗运动和纳米粒子的重力外,还研究了存在和不存在磁场时,左冠状动脉网络中粒子的分布均匀性。总之,对于 400nm 和 600nm 粒子,外部磁场分别使附着在靶向表面的 SDP 增加了 49.4%和 59.7%。

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