Delivery of drugs and macromolecules into the brain is a challenging problem, due in part to the blood-brain barrier. In this article, we focus on the possibilities and limitations of two infusion techniques devised to bypass the blood-brain barrier: convection enhanced delivery (CED) and retro-convection enhanced delivery (R-CED). CED infuses fluid directly into the interstitial space of brain or tumor, whereas R-CED removes fluid from the interstitial space, which results in the transfer of drugs from the vascular compartment into the brain or tumor. Both techniques have shown promising results for the delivery of drugs into large volumes of tissue. Theoretical approaches of varying complexity have been developed to better understand and predict brain interstitial pressures and drug distribution for these techniques. These theoretical models of flow and diffusion can only be solved explicitly in simple geometries, and spherical symmetry is usually assumed for CED, while axial symmetry has been assumed for R-CED. This perspective summarizes features of these models and provides physical arguments and numerical simulations to support the notion that spherical symmetry is a reasonable approximation for modeling CED and R-CED. We also explore the potential of multi-catheter arrays for delivering and compartmentalizing drugs using CED and R-CED.
Bibliographical noteFunding Information:
We thank E. Dy for assistance with experiments. This work was carried out with funding provided by NIH R01 CA107268-01. JPMM is a recipient of the NIGMS predoctoral fellowship, supported by the NIGMS-IMSD grant (R25-GM56847). GHH was a recipient of a predoctoral fellowship from the Whitaker Foundation. RAS acknowledges the University of Minnesota for granting a sabbatical which permitted his participation in this work.
- blood brain barrier
- convection enhanced delivery
- finite element analysis
- mathematical model
- retroconvection enhanced delivery