Computational Multi-Scale Modeling of Drug Delivery into an Anti-Angiogenic Therapy-Treated Tumor

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.