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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00966

Convection enhanced delivery: connection to and impact of interstitial fluid flow

  • 1Department of Biomedical Engineering and Mechanics, College of Engineering, Virginia Tech, United States
  • 2Department of Biomedical Engineering & Mechanics, College of Engineering, Virginia Tech, United States

Convection enhanced delivery (CED) is a method used to increase transport of therapeutics in and around brain tumors. CED works through locally applying a pressure differential to drive fluid flow throughout the tumor, such that convective forces dominate over diffusive transport. This allows therapies to bypass the blood brain barrier that would otherwise be too large or solely rely on passive diffusion. However, this also drives fluid flow out through the tumor bulk into surrounding brain parenchyma, which results in increased interstitial fluid (IF) flow, or fluid flow within extracellular spaces in the tissue. Interstitial fluid flow has been associated with altered transport of molecules, extracellular matrix rearrangement, and triggering of cellular motility through a number of mechanisms. Thus, the results of a simple method to increase drug delivery may have unintended consequences on tissue morphology. Clinically, prediction of dispersal of agents via convection enhanced delivery is important to catheter design, placement, and implementation to optimize contact of tumor cells with therapeutic agent. Prediction software can aid in this problem, yet we wonder if there is a better way to predict therapeutic distribution based simply on interstitial fluid flow pathways as determined from pre-intervention imaging. Overall, CED based therapy has seen limited success and we posit that integration and appreciation of altered IF flow may enhance outcomes. Thus, in this manuscript we both review current state of the art in CED and IF flow mechanistic understanding and relate these two elements to each other in a clinical context.

Keywords: Cancer, Convection-enhanced delivery, Interstitial flow (IF), Drug delivery, Glioma, transport

Received: 01 Mar 2019; Accepted: 11 Sep 2019.

Copyright: © 2019 Stine and Munson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jennifer M. Munson, Virginia Tech, Department of Biomedical Engineering & Mechanics, College of Engineering, Blacksburg, United States, jm4kt@vt.edu