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

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CSF, blood-brain barrier, and brain drug delivery

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

DOI 10.1517/17425247.2016.1171315

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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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Additional file 2 of Novel CSF biomarkers for diagnosis and integrated analysis of neuropsychiatric systemic lupus erythematosus: based on antibody profiling
Ni, J., Chen, C., Wang, S., Liu, X., Tan, L., Lu, L., Fan, Y., Hou, Y., Dou, H., & Liang, J. (2024) · Figshare · doi:10.6084/m9.figshare.26615767
Additional file 2 of Intracranial pressure elevation alters CSF clearance pathways
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Additional file 2 of Location matters: highly divergent protein levels in samples from different CNS compartments in a clinical trial of rituximab for progressive MS
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Additional file 6 of Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters
Laganà, M. M., Di Tella, S., Ferrari, F., Pelizzari, L., Cazzoli, M., Alperin, N. J., Jin, N., Zacà, D., Baselli, G., & Baglio, F. (2024) · Figshare · doi:10.6084/m9.figshare.26554403
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Additional file 1 of Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters
Laganà, M. M., Di Tella, S., Ferrari, F., Pelizzari, L., Cazzoli, M., Alperin, N. J., Jin, N., Zacà, D., Baselli, G., & Baglio, F. (2024) · Figshare · doi:10.6084/m9.figshare.26554388
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Additional file 2 of Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters
Laganà, M. M., Di Tella, S., Ferrari, F., Pelizzari, L., Cazzoli, M., Alperin, N. J., Jin, N., Zacà, D., Baselli, G., & Baglio, F. (2024) · Figshare · doi:10.6084/m9.figshare.26554391
Additional file 4 of Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters
Laganà, M. M., Di Tella, S., Ferrari, F., Pelizzari, L., Cazzoli, M., Alperin, N. J., Jin, N., Zacà, D., Baselli, G., & Baglio, F. (2024) · Figshare · doi:10.6084/m9.figshare.26554397
Additional file 1 of Location matters: highly divergent protein levels in samples from different CNS compartments in a clinical trial of rituximab for progressive MS
Bergman, J., Svenningsson, A., Liv, P., Bergenheim, T. A., & Burman, J. (2020) · Figshare · doi:10.6084/m9.figshare.12737196
Additional file 1 of Human brain solute transport quantified by glymphatic MRI-informed biophysics during sleep and sleep deprivation
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Additional file 4 of Novel CSF biomarkers for diagnosis and integrated analysis of neuropsychiatric systemic lupus erythematosus: based on antibody profiling
Ni, J., Chen, C., Wang, S., Liu, X., Tan, L., Lu, L., Fan, Y., Hou, Y., Dou, H., & Liang, J. (2024) · Figshare · doi:10.6084/m9.figshare.26615773
Additional file 5 of Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters
Laganà, M. M., Di Tella, S., Ferrari, F., Pelizzari, L., Cazzoli, M., Alperin, N. J., Jin, N., Zacà, D., Baselli, G., & Baglio, F. (2024) · Figshare · doi:10.6084/m9.figshare.26554400
Additional file 3 of Novel CSF biomarkers for diagnosis and integrated analysis of neuropsychiatric systemic lupus erythematosus: based on antibody profiling
Ni, J., Chen, C., Wang, S., Liu, X., Tan, L., Lu, L., Fan, Y., Hou, Y., Dou, H., & Liang, J. (2024) · Figshare · doi:10.6084/m9.figshare.26615770
Additional file 1 of Novel CSF biomarkers for diagnosis and integrated analysis of neuropsychiatric systemic lupus erythematosus: based on antibody profiling
Ni, J., Chen, C., Wang, S., Liu, X., Tan, L., Lu, L., Fan, Y., Hou, Y., Dou, H., & Liang, J. (2024) · Figshare · doi:10.6084/m9.figshare.26615764
Additional file 3 of Blood and cerebrospinal fluid flow oscillations measured with real-time phase-contrast MRI: breathing mode matters
Laganà, M. M., Di Tella, S., Ferrari, F., Pelizzari, L., Cazzoli, M., Alperin, N. J., Jin, N., Zacà, D., Baselli, G., & Baglio, F. (2024) · Figshare · doi:10.6084/m9.figshare.26554394
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Kordy, A., Arafa, K. K., Abdellatif, A., & El-sherbiny, I. M. (2026) · RSC Advances · doi:10.1039/d6ra02361d
FPR2 deficiency alleviates LPS-induced depressive-like behaviors in mice by suppressing the microglial CSF1/NLRP3 inflammasome pathway
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Authors: Pardridge, W. M.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Pardridge, William M.
ORCID: 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
DOI: 10.1517/17425247.2016.1171315
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
Health Sciences › Medicine › Clinical Neurology › 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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