The present study develops a numerical model, which is the most complex one, in comparison to previous research to investigate drug delivery accompanied by the anti-angiogenesis effect. This paper simulates intravascular blood flow and interstitial fluid flow using a dynamic model. The model accounts for the non-Newtonian behavior of blood and incorporates the adaptation of the diameter of a heterogeneous microvascular network derived from modeling the evolution of endothelial cells toward a circular tumor sprouting from two-parent vessels, with and without imposing the inhibitory effect of angiostatin on a modified discrete angiogenesis model. The average solute exposure and its uniformity in solid tumors of different sizes are studied by numerically solving the convection-diffusion equation. Three different methodologies are considered for simulating anti-angiogenesis: modifying the capillary network, updating the transport properties, and considering both microvasculature and transport properties modifications. It is shown that anti-angiogenic therapy decreases drug wash-out in the periphery of the tumor. Results show the decisive role of microvascular structure, particularly its distribution, and interstitial transport properties modifications induced via vascular normalization on the quality of drug delivery, such that it is improved by 39% in uniformity by the second approach in R = 0.2 cm.
本研究构建了一个数值模型，相较于既往研究，该模型在探究伴随抗血管生成效应的药物递送机制方面最为复杂。本文采用动态模型模拟血管内血流与组织间液流动，该模型不仅考虑了血液的非牛顿流体特性，更通过改进的离散血管生成模型，模拟了从两条母血管向圆形肿瘤生长的内皮细胞演化过程，并纳入血管抑素抑制效应的影响，从而构建出具有异质性的微血管网络直径自适应体系。通过对流-扩散方程的数值求解，系统研究了不同尺寸实体瘤内的平均溶质暴露量及其分布均匀性。针对抗血管生成作用的模拟，本研究提出三种方法：修正毛细血管网络结构、更新传输特性参数、以及同时修正微血管结构与传输特性。研究表明，抗血管生成治疗能有效降低肿瘤外周区域的药物冲刷效应。结果显示，微血管结构（特别是其分布特征）以及通过血管正常化诱导的组织间传输特性改变，对药物递送质量具有决定性影响。在半径为0.2厘米的肿瘤模型中，采用第二种方法可使药物分布均匀性提升39%。
Computational Multi-Scale Modeling of Drug Delivery into an Anti-Angiogenic Therapy-Treated Tumor
肿瘤(癌症)患者之家