scholarly journals Quantitative prediction of pharmacokinetic properties of drugs in humans: recent advance in in vitro models to predict the impact of efflux transporters in the small intestine and blood–brain barrier

2021 ◽  
Author(s):  
Yoshiki Hashimoto ◽  
Kazuyoshi Michiba ◽  
Maeda Kazuya ◽  
Hiroyuki Kusuhara
Keyword(s):  
Small Intestine ◽  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Quantitative Prediction ◽  
Efflux Transporters ◽  
Blood Brain ◽  
Pharmacokinetic Properties ◽  
The Impact

scholarly journals Biochemical‐ and Biophysical‐Induced Barriergenesis in the Blood–Brain Barrier: A Review of Barriergenic Factors for Use in In Vitro Models

2021 ◽  
Vol 1 (5) ◽  
pp. 2170051
Author(s):  
Christina L. Schofield ◽  
Aleixandre Rodrigo-Navarro ◽  
Matthew J. Dalby ◽  
Tom Van Agtmael ◽  
Manuel Salmeron-Sanchez
Keyword(s):  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Blood Brain Barrier ◽  
Early Stage ◽  
Molecular Transport ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cns Drugs ◽  
The Impact ◽  
The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

Understanding the Physiology of the Blood-Brain Barrier: In Vitro Models

Physiology ◽  
1998 ◽  
Vol 13 (6) ◽  
pp. 287-293 ◽  
Author(s):  
Gerald A. Grant ◽  
N. Joan Abbott ◽  
Damir Janigro
Keyword(s):  
Central Nervous System ◽  
Tissue Culture ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain ◽  
Brain Tissue Culture ◽  
The Brain

Endothelial cells exposed to inductive central nervous system factors differentiate into a blood-brain barrier phenotype. The blood-brain barrier frequently obstructs the passage of chemotherapeutics into the brain. Tissue culture systems have been developed to reproduce key properties of the intact blood-brain barrier and to allow for testing of mechanisms of transendothelial drug permeation.

Claudin-5 Expression in In Vitro Models of the Blood–Brain Barrier

2011 ◽  
pp. 347-354 ◽  
Author(s):  
Itzik Cooper ◽  
Katayun Cohen-Kashi-Malina ◽  
Vivian I. Teichberg
Keyword(s):  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain

Transport Studies Using Blood-Brain Barrier In Vitro Models: A Critical Review and Guidelines

2020 ◽  
Author(s):  
Ana R. Santa-Maria ◽  
Marjolein Heymans ◽  
Fruzsina R. Walter ◽  
Maxime Culot ◽  
Fabien Gosselet ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Critical Review ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Transport Studies ◽  
Blood Brain

scholarly journals Mechanisms of Glutamate Efflux at the Blood—Brain Barrier: Involvement of Glial Cells

2011 ◽  
Vol 32 (1) ◽  
pp. 177-189 ◽  
Author(s):  
Katayun Cohen-Kashi-Malina ◽  
Itzik Cooper ◽  
Vivian I Teichberg
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Glial Cells ◽  
Excitatory Amino Acid ◽  
Active Role ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Amino Acid Transporters ◽  
Blood Brain

At high concentrations, glutamate (Glu) exerts potent neurotoxic properties, leading to irreversible brain damages found in numerous neurological disorders. The accepted notion that Glu homeostasis in brain interstitial fluid is maintained primarily through the activity of Glu transporters present on glial cells does not take into account the possible contribution of endothelial cells constituting the blood-brain barrier (BBB) to this process. Here, we present evidence for the presence of the Glu transporters, excitatory amino-acid transporters (EAATs) 1 to 3, in porcine brain endothelial cells (PBECs) and show their participation in Glu uptake into PBECs. Moreover, transport of Glu across three in vitro models of the BBB is investigated for the first time, and evidence for Glu transport across the BBB in both directions is presented. Our results provide evidence that the BBB can function in the efflux mode to selectively remove Glu, via specific transporters, from the abluminal side (brain) into the luminal compartment (blood). Furthermore, we found that glial cells lining the BBB have an active role in the efflux process by taking up Glu and releasing it, through hemichannels, anion channels, and possibly the reversal of its EAATs, in close proximity to ECs, which in turn take up Glu and release it to the blood.

New approaches to in vitro models of blood–brain barrier drug transport

2003 ◽  
Vol 8 (20) ◽  
pp. 944-954 ◽  
Author(s):  
Tetsuya Terasaki ◽  
Sumio Ohtsuki ◽  
Satoko Hori ◽  
Hitomi Takanaga ◽  
Emi Nakashima ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Drug Transport ◽  
In Vitro Models ◽  
Brain Barrier ◽  
New Approaches ◽  
Blood Brain
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