Cargando…

A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions

The blood–brain barrier (BBB) limits movement of solutes from the lumen of the brain microvascular capillary system into the parenchyma. The unidirectional transfer constant, K(in), is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments...

Descripción completa

Detalles Bibliográficos
Autores principales: Sprowls, Samuel A., Saralkar, Pushkar, Arsiwala, Tasneem, Adkins, Christopher E., Blethen, Kathryn E., Pizzuti, Vincenzo J., Shah, Neal, Fladeland, Ross, Lockman, Paul R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160855/
https://www.ncbi.nlm.nih.gov/pubmed/34069733
http://dx.doi.org/10.3390/pharmaceutics13050756
_version_ 1783700377807355904
author Sprowls, Samuel A.
Saralkar, Pushkar
Arsiwala, Tasneem
Adkins, Christopher E.
Blethen, Kathryn E.
Pizzuti, Vincenzo J.
Shah, Neal
Fladeland, Ross
Lockman, Paul R.
author_facet Sprowls, Samuel A.
Saralkar, Pushkar
Arsiwala, Tasneem
Adkins, Christopher E.
Blethen, Kathryn E.
Pizzuti, Vincenzo J.
Shah, Neal
Fladeland, Ross
Lockman, Paul R.
author_sort Sprowls, Samuel A.
collection PubMed
description The blood–brain barrier (BBB) limits movement of solutes from the lumen of the brain microvascular capillary system into the parenchyma. The unidirectional transfer constant, K(in), is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments are available for the determination of K(in) for new drug candidates using both intravenous and in situ protocols. Additionally, the single uptake method can be used to determine K(in) in heterogeneous pathophysiological conditions such as stroke, brain cancers, and Alzheimer’s disease. In this review, we briefly cover the anatomy and physiology of the BBB, discuss the impact of efflux transporters on solute uptake, and provide an overview of the single-timepoint method for determination of K(in) values. Lastly, we compare preclinical K(in) experimental results with human parallels.
format Online
Article
Text
id pubmed-8160855
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-81608552021-05-29 A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions Sprowls, Samuel A. Saralkar, Pushkar Arsiwala, Tasneem Adkins, Christopher E. Blethen, Kathryn E. Pizzuti, Vincenzo J. Shah, Neal Fladeland, Ross Lockman, Paul R. Pharmaceutics Review The blood–brain barrier (BBB) limits movement of solutes from the lumen of the brain microvascular capillary system into the parenchyma. The unidirectional transfer constant, K(in), is the rate at which transport across the BBB occurs for individual molecules. Single and multiple uptake experiments are available for the determination of K(in) for new drug candidates using both intravenous and in situ protocols. Additionally, the single uptake method can be used to determine K(in) in heterogeneous pathophysiological conditions such as stroke, brain cancers, and Alzheimer’s disease. In this review, we briefly cover the anatomy and physiology of the BBB, discuss the impact of efflux transporters on solute uptake, and provide an overview of the single-timepoint method for determination of K(in) values. Lastly, we compare preclinical K(in) experimental results with human parallels. MDPI 2021-05-19 /pmc/articles/PMC8160855/ /pubmed/34069733 http://dx.doi.org/10.3390/pharmaceutics13050756 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Sprowls, Samuel A.
Saralkar, Pushkar
Arsiwala, Tasneem
Adkins, Christopher E.
Blethen, Kathryn E.
Pizzuti, Vincenzo J.
Shah, Neal
Fladeland, Ross
Lockman, Paul R.
A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions
title A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions
title_full A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions
title_fullStr A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions
title_full_unstemmed A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions
title_short A Review of Mathematics Determining Solute Uptake at the Blood–Brain Barrier in Normal and Pathological Conditions
title_sort review of mathematics determining solute uptake at the blood–brain barrier in normal and pathological conditions
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160855/
https://www.ncbi.nlm.nih.gov/pubmed/34069733
http://dx.doi.org/10.3390/pharmaceutics13050756
work_keys_str_mv AT sprowlssamuela areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT saralkarpushkar areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT arsiwalatasneem areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT adkinschristophere areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT blethenkathryne areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT pizzutivincenzoj areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT shahneal areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT fladelandross areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT lockmanpaulr areviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT sprowlssamuela reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT saralkarpushkar reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT arsiwalatasneem reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT adkinschristophere reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT blethenkathryne reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT pizzutivincenzoj reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT shahneal reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT fladelandross reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions
AT lockmanpaulr reviewofmathematicsdeterminingsoluteuptakeatthebloodbrainbarrierinnormalandpathologicalconditions