Transport of Liposome Encapsulated Drugs in Voxelized Computational Model of Human Brain Tumors.

ABSTRACT

There are many obstacles in the transport of chemotherapeutic drugs to tumor cells that lead to irregular and non-uniform uptake of drugs inside tumors. The study of these transport problems will help with accurate prediction of drug transport and optimizing treatment strategy. To this end, liposome mediated drug delivery has emerged as an excellent anticancer therapy due to its ability to deliver drugs at site of action and reducing the chances of side effects to the healthy tissues. In this paper, a computational fluid dynamics (CFD) model based on realistic vasculature of human brain tumor is presented. This model utilizes dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) data to account for heterogeneity in tumor vasculature. Porosity of the interstitial space inside the tumor and normal tissue is determined voxel-wise by processing the DCE-MRI images by general tracer kinetic model (GTKM). The CFD model is applied to predict transport of two different types of liposomes (stealth and conventional) in tumors. The amount of accumulated liposomes is compared with accumulated free drug (doxorubicin) in the interstitial space. Simulation results indicate that stealth liposomes accumulate more and remain for longer periods of time in tumors as compared with conventional liposomes and free drug. The present model provides us a qualitative and quantitative examination on the transport and deposition of liposomes as well as free drugs in actual human brain tumors.