CSF, blood-brain barrier, and brain 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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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”
From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [134]
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.”
From AAVrh.10-Mediated APOE2 Central Nervous System Gene Therapy for APOE4-Associated Alzheimer's Disease (2018) · cites this paper as [86]
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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
- Publisher
- Informa UK Limited
- 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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