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Expert Opin Drug Deliv. 2016 Jul;13(7):963-75. doi: 10.1517/17425247.2016.1171315. Epub 2016 Apr 11.

CSF, blood-brain barrier, and brain drug delivery.

Author information

1
a Brain Research Institute , University of California , Los Angeles , CA , USA.

Abstract

INTRODUCTION:

There are 2 misconceptions about the cerebrospinal fluid (CSF), the blood-brain barrier (BBB), and brain drug delivery, which date back to the discovery of a barrier between blood and brain over 100 years ago. Misconception 1 is that drug distribution into CSF is a measure of BBB transport. Misconception 2 is that drug injected into the CSF compartment distributes to the inner parenchyma of brain.

AREAS COVERED:

Drug distribution into the CSF is a function of drug transport across the choroid plexus, which forms the blood-CSF barrier, and not drug transport across the BBB, which is situated at the microvascular endothelium of brain. Drug injected into CSF undergoes rapid efflux to the blood compartment via bulk flow. Drug penetration into brain parenchyma from the CSF is limited by diffusion and drug concentrations in brain decrease exponentially relative to the CSF concentration.

EXPERT OPINION:

The barrier between blood and brain was discovered in 1913, when it was believed that the BBB was localized to the choroid plexus, and that nutrient flow from blood passed through the CSF en route to brain. These misconceptions are still widely held, and hinder progress in the development of technology for BBB drug delivery.

KEYWORDS:

Blood-brain barrier; brain drug delivery; cerebrospinal fluid; choroid plexus; diffusion; microvasculature

PMID:
27020469
DOI:
10.1517/17425247.2016.1171315
[Indexed for MEDLINE]

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