Transient interstitial fluid flow in brain tumors: Effect on drug delivery

Abstract

The presence of high interstitial pressure within the tumor's center [Baxter, L.T., Jain, R.K., 1989. Transport of fluid and macromolecules in tumors I role of interstitial pressure and convection. Microvascular Research 37, 77-104] poses severe problems to chemotherapy via systemic administration. Removal of the tumor core by surgery and subsequent insertion of drug-carrying polymers in the resection cavity may improve the treatment [Wang, C.H., Li, J., 1998. Three dimensional simulation of IgG delivery to tumors. Chemical Engineering Science 53 (20), 3579-3600]. The operation establishes a favorable pressure gradient towards the center of the tumor and thus creates flow reversal immediately after the operation. The simulation results of the transient flow field of interstitial fluid in the surgical cavity of a brain tumor are presented. The simulation is carried out using a computational fluid dynamics software, Fluent, with the model geometry constructed from magnetic resonance images (MRI) with reference to the Gliadel® wafers application [Sampath, P., Brem, H., 1998. Implantable slow-release chemotherapeutic polymers for the treatment of malignant brain tumors. Cancer control. Journal of Molecular and Cellular Cardiology 5 (2), 130-137]. The coupled mass and momentum equations are solved for the steady-state solutions of the pressure and velocity distributions at a cut section of a tumor. The steady-state solution thus obtained is then perturbed to compute the characteristic time scale of the variation in the interstitial fluid pressure and velocity in a surgical cavity immediately after surgery. Simulation results show that the flow field reaches an equilibrium state in less than 3 h. The surgery produces a transient enhancement of the drug delivery but the surgery alone is not capable of removing permanently the unfavorable pressure gradient against the delivery of drug to tumor. The presence of post-surgery edema increases the interstitial pressure and fluid velocity, thus causing higher relative toxicity in the surrounding normal tissues. Simulations employing complete 3D structure show qualitatively similar results with 2D simulation and hence the use of a cut section of the tumor for simplified model calculations is validated. © 2005 Elsevier Ltd. All rights reserved.