Goraya Shoaib A, Ding Shengzhe, Arif Mariam K, Kong Hyunjoon, Masud Arif
Department of Civil and Environmental Engineering, University of Illinois Urbana-Champaign.
Department of Chemical and Biomolecular Engineering, University of Illinois Urbana-Champaign.
bioRxiv. 2024 Sep 12:2024.06.05.597680. doi: 10.1101/2024.06.05.597680.
Delivery of drug using nanocarriers tethered with vasculature-targeting epitopes aims to maximize the therapeutic efficacy of the drug while minimizing the drug side effects. Circadian rhythm which is governed by the central nervous system has implications for targeted drug delivery due to sleep-wake cycle changes in blood flow dynamics. This paper presents an advanced fluid dynamics modeling method that is based on viscous incompressible shear-rate fluid (blood) coupled with an advection-diffusion equation to simulate the formation of drug concentration gradients in the blood stream and buildup of concentration at the targeted site. The method is equipped with an experimentally calibrated nanoparticle-endothelial cell adhesion model that employs Robin boundary conditions to describe nanoparticle retention based on probability of adhesion, a friction model accounting for surface roughness of endothelial cell layer, and a dispersion model based on Taylor-Aris expression for effective diffusion in the boundary layer. The computational model is first experimentally validated and then tested on engineered bifurcating arterial systems where impedance boundary conditions are applied at the outflow to account for the downstream resistance at each outlet. It is then applied to a virtual geometric model of an arterial tree developed through MRI-based image processing techniques. These simulations highlight the potential of the computational model for drug transport, adhesion, and retention at multiple sites in virtual models. The model provides a virtual platform for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing the experimentation.
A novel integration of nanoparticle-based drug delivery framework with shear-rate dependent blood flow model is presented. The framework is comprised of a unique combination of mechanics-based dispersion model, an asperity model for endothelium surface roughness, and a stochastic nanoparticle-endothelial cell adhesion model. Simulations of MRI based carotid artery system showcase the effects of vessel geometry on nanoparticle adhesion and retention at the targeted site. Vessel geometry and target site location impact nanoparticle adhesion; curved and bifurcating regions favor local accumulation of drug. It is also shown that aligning drug administration with circadian rhythm and sleep cycle can enhance the efficacy of drug delivery processes. These simulations highlight the potential of the computational modeling for exploring circadian rhythm modulated blood flow for targeted drug delivery while minimizing the experimentation.
使用与血管靶向表位相连的纳米载体递送药物旨在在最大限度降低药物副作用的同时最大化药物的治疗效果。由中枢神经系统控制的昼夜节律因血流动力学的睡眠-觉醒周期变化而对靶向药物递送有影响。本文提出了一种先进的流体动力学建模方法，该方法基于粘性不可压缩剪切速率流体（血液）并结合平流扩散方程，以模拟血流中药物浓度梯度的形成以及靶向部位浓度的积累。该方法配备了一个经过实验校准的纳米颗粒-内皮细胞粘附模型，该模型采用罗宾边界条件基于粘附概率来描述纳米颗粒的滞留，一个考虑内皮细胞层表面粗糙度的摩擦模型，以及一个基于泰勒-阿里斯表达式用于边界层有效扩散的弥散模型。该计算模型首先经过实验验证，然后在工程化的分叉动脉系统上进行测试，在流出端应用阻抗边界条件以考虑每个出口处的下游阻力。然后将其应用于通过基于磁共振成像的图像处理技术开发的动脉树虚拟几何模型。这些模拟突出了该计算模型在虚拟模型中多个部位进行药物运输、粘附和滞留的潜力。该模型提供了一个虚拟平台，用于探索昼夜节律调节的血流以实现靶向药物递送，同时将实验降至最低。
提出了一种基于纳米颗粒的药物递送框架与剪切速率依赖性血流模型的新颖整合。该框架由基于力学的弥散模型、内皮表面粗糙度的粗糙模型和随机纳米颗粒-内皮细胞粘附模型的独特组合组成。基于磁共振成像的颈动脉系统模拟展示了血管几何形状对纳米颗粒在靶向部位的粘附和滞留的影响。血管几何形状和靶位点位置影响纳米颗粒的粘附；弯曲和分叉区域有利于药物的局部积累。还表明使药物给药与昼夜节律和睡眠周期同步可以提高药物递送过程的疗效。这些模拟突出了计算建模在探索昼夜节律调节的血流以实现靶向药物递送同时将实验降至最低方面的潜力。
