Numerical modeling of drug delivery in a dynamic solid tumor microvasculature.

The complicated capillary network induced by angiogenesis is one of the main reasons of unsuccessful cancer therapy. A multi-scale mathematical method which simulates drug transport to a solid tumor is used in this study to investigate how capillary network structure affects drug delivery. The mathematical method involves processes such as blood flow through vessels, solute and fluid diffusion, convective transport in extracellular matrix, and extravasation from blood vessels. The effect of heterogeneous dynamic network on interstitial fluid flow and drug delivery is investigated by this multi-scale method. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network and fluid flow in normal and tumor tissues. Finally, convection-diffusion equation is used to simulate drug delivery. Three approaches are used to simulate drug transport based on the developed mathematical method: without a vascular network, using a static vascular network, and a dynamic vascular network. The avascular approach predicts more uniform and higher drug concentration than vascular approaches since the simplified assumptions are implemented in this method. The dynamic network which uses more realistic assumptions predicts more irregular blood vessels, high interstitial pressure, and more heterogeneity in drug distribution than other two approaches. Crown