Abstract
The most important obstacle to the drug delivery into the brain is the presence of the blood-brain barrier, which limits the traffic of substances between the blood and the nervous tissue. Therefore, adequate in vitro models need to be developed in order to characterize the penetration properties of drug candidates into the central nervous system. This review article summarizes the presently used and the most promising in vitro BBB models based on the culture of brain endothelial cells. Robust models can be obtained using primary porcine brain endothelial cells and rodent coculture models, which have low paracellular permeability and express functional efflux transporters, showing good correlation of drug penetration data with in vivo results. Models mimicking the in vivo anatomophysiological complexity of the BBB are also available, including triple coculture (culture of brain endothelial cells in the presence of pericytes and astrocytes), dynamic, and microfluidic models; however, these are not suitable for rapid, high throughput studies. Potent human cell lines would be needed for easily available and reproducible models which avoid interspecies differences.
| Original language | English |
|---|---|
| Pages (from-to) | 1949-1963 |
| Number of pages | 15 |
| Journal | Molecular Pharmaceutics |
| Volume | 11 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - júl. 7 2014 |
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ASJC Scopus subject areas
- Pharmaceutical Science
- Molecular Medicine
- Drug Discovery
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In vitro models of the blood-brain barrier for the study of drug delivery to the brain. / Wilhelm, I.; Krizbai, I.
In: Molecular Pharmaceutics, Vol. 11, No. 7, 07.07.2014, p. 1949-1963.Research output: Article
}
TY - JOUR
T1 - In vitro models of the blood-brain barrier for the study of drug delivery to the brain
AU - Wilhelm, I.
AU - Krizbai, I.
PY - 2014/7/7
Y1 - 2014/7/7
N2 - The most important obstacle to the drug delivery into the brain is the presence of the blood-brain barrier, which limits the traffic of substances between the blood and the nervous tissue. Therefore, adequate in vitro models need to be developed in order to characterize the penetration properties of drug candidates into the central nervous system. This review article summarizes the presently used and the most promising in vitro BBB models based on the culture of brain endothelial cells. Robust models can be obtained using primary porcine brain endothelial cells and rodent coculture models, which have low paracellular permeability and express functional efflux transporters, showing good correlation of drug penetration data with in vivo results. Models mimicking the in vivo anatomophysiological complexity of the BBB are also available, including triple coculture (culture of brain endothelial cells in the presence of pericytes and astrocytes), dynamic, and microfluidic models; however, these are not suitable for rapid, high throughput studies. Potent human cell lines would be needed for easily available and reproducible models which avoid interspecies differences.
AB - The most important obstacle to the drug delivery into the brain is the presence of the blood-brain barrier, which limits the traffic of substances between the blood and the nervous tissue. Therefore, adequate in vitro models need to be developed in order to characterize the penetration properties of drug candidates into the central nervous system. This review article summarizes the presently used and the most promising in vitro BBB models based on the culture of brain endothelial cells. Robust models can be obtained using primary porcine brain endothelial cells and rodent coculture models, which have low paracellular permeability and express functional efflux transporters, showing good correlation of drug penetration data with in vivo results. Models mimicking the in vivo anatomophysiological complexity of the BBB are also available, including triple coculture (culture of brain endothelial cells in the presence of pericytes and astrocytes), dynamic, and microfluidic models; however, these are not suitable for rapid, high throughput studies. Potent human cell lines would be needed for easily available and reproducible models which avoid interspecies differences.
KW - ABC transporter
KW - blood-brain barrier (BBB)
KW - cerebral endothelial cell
KW - drug delivery
KW - in vitro model
KW - SLC transporter
KW - tight junction
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U2 - 10.1021/mp500046f
DO - 10.1021/mp500046f
M3 - Article
C2 - 24641309
AN - SCOPUS:84900023528
VL - 11
SP - 1949
EP - 1963
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 7
ER -