School of Mechanical Engineering, Sharif University of Technology, Tehran,Iran.
Curr Drug Deliv. 2021;18(10):1526-1532. doi: 10.2174/1567201818666210316111458.
The continuing inflammatory response entailed by atherosclerosis is categorised by a pathological surface expression of certain proteins over the endothelium, namely, P-selectins. Thus, to boost the efficiency of drug carriers, these proteins can be used as binding targets.
Delivery of particles in a specific size range, from 200 to 3200 nm, covered by P-selectin aptamers (PSA), to an atherosclerotic plaque in a pathologically high haematocrit (Hct) blood flow was simulated. The surface of the plaque was assumed to possess a pathologically high expression of P-Selectins.
An in-silico patient-specific model of a Left Anterior Descending (LAD) coronary artery considering the luminal unevenness was built and meshed using the finite element method.
The distribution of deposited particles over the plaque in high Hct blood was significantly more homogenous compared to that of particles that travelled in normal blood Hct. Moreover, in the high Hct, the increase in the particle size, from 800 nm forwards, had a trivial effect on the upsurge in the surface density of adhered particles (SDAs) over the targeted endothelium. Yet, in normal blood Hct (45% in this research), the increase in the particle diameter from 800 nm forwards resulted in a significant increase in the SDAs over the targeted plaque. Interestingly, unlike the adsorption pattern of particles in normal Hct, a significant distribution of deposited particles in the post-constriction region of the atherosclerotic plaque was observed.
Our findings provide insights into designing optimum carriers of anti-thrombotic/inflammatory drugs specifically for high blood Hct conditions.
动脉粥样硬化所涉及的持续炎症反应的特征是某些蛋白质在血管内皮上的病理性表面表达,即 P 选择素。因此,为了提高药物载体的效率,可以将这些蛋白质用作结合靶点。
模拟将载药颗粒(粒径范围为 200nm 至 3200nm)递送至载有 P 选择素适体(PSA)的动脉粥样硬化斑块中,此时血液中的红细胞压积(Hct)处于病理性高值。假设斑块表面具有病理性高表达的 P 选择素。
使用有限元方法对左前降支(LAD)冠状动脉进行了考虑管腔不均匀性的患者特定的体内模拟,并进行了网格划分。
与在正常 Hct 血液中输送的颗粒相比,在高 Hct 血液中沉积颗粒在斑块上的分布更加均匀。此外,在高 Hct 中,粒径从 800nm 增加时,对靶向内皮上附着颗粒的表面密度(SDA)的增加影响微不足道。然而,在正常 Hct(本研究中为 45%)中,粒径从 800nm 增加时,靶向斑块上的 SDA 显著增加。有趣的是,与正常 Hct 中颗粒的吸附模式不同,在动脉粥样硬化斑块的后缩窄区域观察到沉积颗粒的显著分布。
我们的研究结果为设计针对高 Hct 条件的抗血栓/炎症药物的最佳载体提供了思路。