Development of an in vitro blood-brain barrier model based on immortalized porcine brain microvascular endothelial cells

Regina Lauer; Roland Bauer; Birgit Linz; Fritz Pittner; Guenther A. Peschek; Gerhard Ecker; Peter Friedl; Christian R. Noe

doi:10.1016/j.farmac.2003.11.007

Development of an in vitro blood-brain barrier model based on immortalized porcine brain microvascular endothelial cells

Regina Lauer
, Roland Bauer
, Birgit Linz
, Fritz Pittner
, Guenther A. Peschek
, Gerhard Ecker
, Peter Friedl
, Christian R. Noe

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Immortalized porcine brain microvessel endothelial cells (PBMEC/C1-2) were used to develop a model for measurement of blood-brain barrier permeation of central nervous system active drugs. Previous studies showed that a system using C6 astrocyte glioma conditioned medium leads to cell layers with transendothelial electrical resistance values up to 300 Ω cm² and a permeability coefficient P_e of 3.24 ± 0.14 × 10^-4 cm/min for U-[¹⁴C]sucrose, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro. However, commercially available inserts for the Transwell® system were not permeable for highly lipophilic compounds, such as diazepam. Systematic studies with different insert showed, that inserts with a pore width of 1 μm proved to be optimal for permeation studies of lipophilic compounds. Permeability studies with a set of three benzodiazepines further supported this finding.

Original language	English (US)
Pages (from-to)	133-137
Number of pages	5
Journal	Farmaco
Volume	59
Issue number	2
DOIs	https://doi.org/10.1016/j.farmac.2003.11.007
State	Published - Feb 2004
Externally published	Yes

Keywords

Benzodiazepines
Blood-brain barrier
Immortalized porcine brain microvascular endothelial cells
In vitro model

ASJC Scopus subject areas

Pharmaceutical Science
Drug Discovery

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10.1016/j.farmac.2003.11.007

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title = "Development of an in vitro blood-brain barrier model based on immortalized porcine brain microvascular endothelial cells",

abstract = "Immortalized porcine brain microvessel endothelial cells (PBMEC/C1-2) were used to develop a model for measurement of blood-brain barrier permeation of central nervous system active drugs. Previous studies showed that a system using C6 astrocyte glioma conditioned medium leads to cell layers with transendothelial electrical resistance values up to 300 Ω cm2 and a permeability coefficient Pe of 3.24 ± 0.14 {\texttimes} 10-4 cm/min for U-[14C]sucrose, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro. However, commercially available inserts for the Transwell{\textregistered} system were not permeable for highly lipophilic compounds, such as diazepam. Systematic studies with different insert showed, that inserts with a pore width of 1 μm proved to be optimal for permeation studies of lipophilic compounds. Permeability studies with a set of three benzodiazepines further supported this finding.",

keywords = "Benzodiazepines, Blood-brain barrier, Immortalized porcine brain microvascular endothelial cells, In vitro model",

author = "Regina Lauer and Roland Bauer and Birgit Linz and Fritz Pittner and Peschek, \{Guenther A.\} and Gerhard Ecker and Peter Friedl and Noe, \{Christian R.\}",

year = "2004",

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doi = "10.1016/j.farmac.2003.11.007",

language = "English (US)",

volume = "59",

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journal = "Farmaco",

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AU - Lauer, Regina

AU - Bauer, Roland

AU - Linz, Birgit

AU - Pittner, Fritz

AU - Peschek, Guenther A.

AU - Ecker, Gerhard

AU - Friedl, Peter

AU - Noe, Christian R.

PY - 2004/2

Y1 - 2004/2

N2 - Immortalized porcine brain microvessel endothelial cells (PBMEC/C1-2) were used to develop a model for measurement of blood-brain barrier permeation of central nervous system active drugs. Previous studies showed that a system using C6 astrocyte glioma conditioned medium leads to cell layers with transendothelial electrical resistance values up to 300 Ω cm2 and a permeability coefficient Pe of 3.24 ± 0.14 × 10-4 cm/min for U-[14C]sucrose, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro. However, commercially available inserts for the Transwell® system were not permeable for highly lipophilic compounds, such as diazepam. Systematic studies with different insert showed, that inserts with a pore width of 1 μm proved to be optimal for permeation studies of lipophilic compounds. Permeability studies with a set of three benzodiazepines further supported this finding.

AB - Immortalized porcine brain microvessel endothelial cells (PBMEC/C1-2) were used to develop a model for measurement of blood-brain barrier permeation of central nervous system active drugs. Previous studies showed that a system using C6 astrocyte glioma conditioned medium leads to cell layers with transendothelial electrical resistance values up to 300 Ω cm2 and a permeability coefficient Pe of 3.24 ± 0.14 × 10-4 cm/min for U-[14C]sucrose, which is in good agreement to published values and thus indicates the formation of tight junctions in vitro. However, commercially available inserts for the Transwell® system were not permeable for highly lipophilic compounds, such as diazepam. Systematic studies with different insert showed, that inserts with a pore width of 1 μm proved to be optimal for permeation studies of lipophilic compounds. Permeability studies with a set of three benzodiazepines further supported this finding.

KW - Benzodiazepines

KW - Blood-brain barrier

KW - Immortalized porcine brain microvascular endothelial cells

KW - In vitro model

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DO - 10.1016/j.farmac.2003.11.007

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EP - 137

JO - Farmaco

JF - Farmaco

IS - 2

ER -

Development of an in vitro blood-brain barrier model based on immortalized porcine brain microvascular endothelial cells

Abstract

Keywords

ASJC Scopus subject areas

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