Cited by 511Barrier Structure and Function StudiesCerebrospinal fluid and hydrocephalusDrug Transport and Resistance Mechanisms

CSF, blood-brain barrier, and brain drug delivery

Pardridge, William M.·2016·Expert Opinion on Drug Delivery

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.

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Crossref · 10.1517/17425247.2016.1171315

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  • Intrathecal drug administration is a typical method for drug delivery into the entire ventricular system without passing through the blood-brain barrier.

    “For instance, intrathecal drug administration is a typical method for drug delivery into the entire ventricular system without passing through the BBB.134,135”
  • Targeting the large cerebral ventricles (intraventricular route) in the frontal lobe is an easy surgical task and is commonly used to deliver drugs to the CNS.

    “Targeting the large cerebral ventricles (intraventricular route) in the frontal lobe of the brain is an easy surgical task, and is commonly used to deliver drugs to the CNS.”

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Authors
Pardridge, W. M.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Pardridge, William M.
Venue
Expert Opinion on Drug Delivery
Published
2016-04-11
Volume
13
Issue
7
Pages
963-975
ISSN
  • 1742-5247 (ISSN-L)
  • 1744-7593
OpenAlex
W2314371091
Cited by
508
References
88
Citations by year
2026: 33 · 2025: 45 · 2024: 63 · 2023: 63 · 2022: 84 · 2021: 64 · 2020: 58 · 2019: 37 · 2018: 29 · 2017: 27 · 2016: 4
FWCI
2.83
Type
journal article
Language
en
Open access
closed
Locations
  • Expert Opinion on Drug Delivery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
cerebrospinal fluid, blood-brain barrier, brain drug delivery, choroid plexus, blood-CSF barrier, drug transport, bulk flow
MeSH terms
Animals, Biological Transport, Blood-Brain Barrier, Brain, Choroid Plexus, Humans, Drug Delivery Systems

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