Retro-convection enhanced drug delivery: a computational study.

Abstract

Retro-convection enhanced delivery (R-CED) is an emerging drug delivery method to overcome the blood brain barrier (BBB). We have developed a mathematical model to understand the fluid flow and mass transfer in the interstitium of brain tissue in R-CED therapy. The model was used to predict pressure distributions, fluid flow patterns, and drug concentration profiles. Some numerical results were obtained by computer simulations. Three kinds of microdialysis membranes used in R-CED protocols were analyzed in detail. While fluid flow was independent of the choice of membranes, mass transfer processes and drug distributions were found to be highly dependent on the choice of membranes. Sensitivity analysis on a variety of parameters and over a wide range of parameter values was carried out. Although R-CED turned out to be efficacious in generating fluid flows within the brain tissue, it did not favor a large effective treatment volume and needed to be re-examined and re-evaluated experimentally.