caa a22 4500 445312815 CHVBK 20180317142636.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s11095-010-0296-2 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0296-2 Convection and Retro-Convection Enhanced Delivery: Some Theoretical Considerations Related to Drug Targeting [Elektronische Daten] [J. Motion, Grace Huynh, Francis Szoka Jr., Ronald Siegel] ABSTRACT: 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. The Author(s), 2010 blood brain barrier nationallicence convection enhanced delivery nationallicence finite element analysis nationallicence mathematical model nationallicence retro-convection enhanced delivery nationallicence CED : convection enhanced delivery nationallicence ECF : extracellular eluid nationallicence i.c. : intracranial nationallicence ISF : interstitial fluid nationallicence PDE : partial differential equation nationallicence R-CED : retro-convection enhanced delivery nationallicence s.c. : subcutaneous nationallicence Motion J. Joint Graduate Group in Bioengineering, University of California at San Francisco and Berkeley, 94143-0446, San Francisco, California, USA aut Huynh Grace Joint Graduate Group in Bioengineering, University of California at San Francisco and Berkeley, 94143-0446, San Francisco, California, USA aut Szoka Jr. Francis Joint Graduate Group in Bioengineering, University of California at San Francisco and Berkeley, 94143-0446, San Francisco, California, USA aut Siegel Ronald Department of Pharmaceutics and Biomedical Engineering, University of Minnesota, 55455, Minneapolis, Minnesota, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 472-479 0724-8741 28:3<472 2011 28 11095 https://doi.org/10.1007/s11095-010-0296-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0296-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Motion J. Joint Graduate Group in Bioengineering, University of California at San Francisco and Berkeley, 94143-0446, San Francisco, California, USA aut NATIONALLICENCE 700 1- Huynh Grace Joint Graduate Group in Bioengineering, University of California at San Francisco and Berkeley, 94143-0446, San Francisco, California, USA aut NATIONALLICENCE 700 1- Szoka Jr Francis Joint Graduate Group in Bioengineering, University of California at San Francisco and Berkeley, 94143-0446, San Francisco, California, USA aut NATIONALLICENCE 700 1- Siegel Ronald Department of Pharmaceutics and Biomedical Engineering, University of Minnesota, 55455, Minneapolis, Minnesota, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/3(2011-03-01), 472-479 0724-8741 28:3<472 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer