Scaling behavior of drug transport and absorption in in silico cerebral capillary networks

Abstract

Drug delivery to the brain is challenging due to the presence of the blood-brain barrier. Mathematical modeling and simulation are essential tools for the deeper understanding of transport processes in the blood, across the blood-brain barrier and within the tissue. Here we present a mathematical model for drug delivery through capillary networks with increasingly complex topologies with the goal to understand the scaling behavior of model predictions on a coarse-to-fine sequence of grids. We apply our model to the delivery of L-Dopa, the primary drug used in the therapy of Parkinson's Disease. Our model replicates observed blood flow rates and ratios between plasma and tissue concentrations. We propose an optimal network grain size for the simulation of tissue volumes of 1 cm3 that allows to make reliable predictions with reasonable computational costs.