A THREE-DIMENSIONAL MODEL OF DRUG DELIVERY TO BRAIN TUMORS

Abstract

We have established a platform for three-dimensional simulation of drug delivery to tumors. The effects of pressure-induced convection, lymphatic drainage and the intracellular kinetics on drug distribution are also investigated. Simulations on systemic bolus injection and controlled release from polymers are conducted on two agents, (i.e., IgG and BCNU) which have significantly different molecular weights (MW), diffusivities and transvascular permeabilities. The determinant factor for systemic bolus injection is the half-life of drug in the plasma. Compared with systemic bolus injection, polymeric release gives higher local drug concentration with reduced systemic toxicity. The penetration depth of IgG is higher than that of BCNU since it depends more on tranvascular permeability than on diffusivity. The optimal location of polymer implantation for IgG is the viable zone. In contrast, the optimal location for BCNU is the necrotic core. For IgG, the lymphatic drainage greatly reduces the mean drug concentrations, while for BCNU, it only shows minor effect. For both cases, the binding of drug with tissue reduces the total drug concentrations and the effect depends significantly on the rate constant. This simulation platform can handle three-dimensional arbitrary geometry and hence is no longer limited to perfect shapes (spherical, cylindrical or slab), and can be used to get a more realistic prediction on interstitial pressure, velocity and drug distributions. The results provided here may serve as an aid for medical scientists to design better tumor treatment.