Sohrabi Salman, Yunus Doruk Erdem, Xu Jiang, Yang Jie, Liu Yaling
Department of Mechanical Engineering & Mechanics, Lehigh University, Bethlehem, PA 18015, USA.
School of Mechanics and Engineering, Southwest Jiaotong University, Chengdu, China.
Microvasc Res. 2016 Nov;108:41-7. doi: 10.1016/j.mvr.2016.07.005. Epub 2016 Jul 14.
Quantitative understanding of nanoparticles transport and adhesion dynamic in microcirculation is very challenging due to complexity of fluid dynamics and imaging setup. In-vitro experiments within microfluidic channels showed the significant influence of shear rate, carrier size, particle-substrate chemistry and vessel geometry on particle deposition rate. However, there are few theoretical models that can accurately predict experimental results. We have developed a numerical model to predict nanoparticle transport and binding dynamics and verified with our previous in-vitro tests results. A binding probability function is used to simplify the carrier attachment and detachment processes. Our results showed that due to the complex dynamics of particle transport and adhesion mechanism, the correlation between binding probability and actual deposition rate is not linear. Using experimental data, it is shown that the binding probability of small particles changes slightly with shear rate whereas the chance of binding for big particles decreases exponentially with shear. Our particulate model also captured some phenomena that cannot be achieved by continuum approach such as accumulation of drug particles in close vicinity of vessel wall. In addition, the effects of channel geometry and antibody density on particle binding are discussed extensively. The results from our particulate approach agrees well with experimental data suggesting that it can be used as a simple, yet efficient predictive tool for studying drug carrier binding in microcirculation.
由于流体动力学和成像设置的复杂性,对纳米颗粒在微循环中的传输和粘附动力学进行定量理解极具挑战性。微流控通道内的体外实验表明,剪切速率、载体尺寸、颗粒 - 底物化学性质和血管几何形状对颗粒沉积速率有显著影响。然而,很少有理论模型能够准确预测实验结果。我们开发了一个数值模型来预测纳米颗粒的传输和结合动力学,并通过我们之前的体外测试结果进行了验证。使用一个结合概率函数来简化载体的附着和脱离过程。我们的结果表明,由于颗粒传输和粘附机制的复杂动力学,结合概率与实际沉积速率之间的相关性不是线性的。利用实验数据表明,小颗粒的结合概率随剪切速率变化不大,而大颗粒的结合机会随剪切呈指数下降。我们的颗粒模型还捕捉到了一些连续介质方法无法实现的现象,如药物颗粒在血管壁附近的积累。此外,还广泛讨论了通道几何形状和抗体密度对颗粒结合的影响。我们颗粒方法的结果与实验数据吻合良好,表明它可以作为一种简单而有效的预测工具,用于研究微循环中药物载体的结合。