Comparison of brain capillary endothelial cell-based and epithelial (MDCK-MDR1, Caco-2, and VB-Caco-2) cell-based surrogate blood-brain barrier penetration models

Éva Hellinger, S. Veszelka, Andrea E. Tóth, Fruzsina Walter, A. Kittel, Mónika Laura Bakk, Károly Tihanyi, Viktor Háda, Shinsuke Nakagawa, Thuy Dinh Ha Duy, Masami Niwa, M. Deli, Monika Vastag

Research output: Contribution to journalArticle

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Abstract

An accurate means of predicting blood-brain barrier (BBB) penetration and blood-brain partitioning of NCEs (new chemical entities) would fulfill a major need in pharmaceutical research. Currently, an industry-standard BBB drug penetration model is not available. Primary brain capillary endothelial cells, optionally co-cultured with astrocytes and/or pericytes, are the most valued models of BBB. For routine use, establishing and maintaining a co-culture system is too costly and labor intensive. Alternatively, non-cerebral cell lines such as MDCK-MDR1 are used, and most recently, the suitability of native and modified Caco-2 for predicting brain penetration has also come under investigation. This study provides comparative data on the morphology and functionality of the high integrity brain capillary endothelial BBB model (EPA: triple culture of brain capillary endothelial cells with pericytes and astrocytes) and the epithelial cell-based (native Caco-2, high P-glycoprotein expressing vinblastine-treated VB-Caco-2 and MDCK-MDR1) surrogate BBB models. Using a panel of 10 compounds VB-Caco-2 and MDCK-MDR1 cell lines show restrictive paracellular pathway and BBB-like selective passive permeability that makes them comparable to the rat brain BBB model, which gave correlation with the highest r2 value with in vivo permeability data. In bidirectional assay, the VB-Caco-2 and the MDCK-MDR1 models identified more P-glycoprotein drug substrates than the rat brain BBB model. While the complexity and predictive value of the BBB model is the highest, for the screening of NCEs to determine whether they are efflux substrates or not, the VB-Caco-2 and the MDCK-MDR1 models may provide a simple and inexpensive tool.

Original languageEnglish
Pages (from-to)340-351
Number of pages12
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume82
Issue number2
DOIs
Publication statusPublished - Oct 2012

Fingerprint

Caco-2 Cells
Blood-Brain Barrier
Endothelial Cells
Brain
Pericytes
Astrocytes
Permeability
Cell Line
Madin Darby Canine Kidney Cells
Vinblastine
P-Glycoprotein
Coculture Techniques
Pharmaceutical Preparations
Industry
Epithelial Cells

Keywords

  • Blood-brain barrier
  • Brain endothelial cell
  • MDCK-MDR1
  • P-glycoprotein
  • Surrogate BBB model
  • VB-Caco-2

ASJC Scopus subject areas

  • Biotechnology
  • Pharmaceutical Science

Cite this

Comparison of brain capillary endothelial cell-based and epithelial (MDCK-MDR1, Caco-2, and VB-Caco-2) cell-based surrogate blood-brain barrier penetration models. / Hellinger, Éva; Veszelka, S.; Tóth, Andrea E.; Walter, Fruzsina; Kittel, A.; Bakk, Mónika Laura; Tihanyi, Károly; Háda, Viktor; Nakagawa, Shinsuke; Dinh Ha Duy, Thuy; Niwa, Masami; Deli, M.; Vastag, Monika.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 82, No. 2, 10.2012, p. 340-351.

Research output: Contribution to journalArticle

Hellinger, Éva ; Veszelka, S. ; Tóth, Andrea E. ; Walter, Fruzsina ; Kittel, A. ; Bakk, Mónika Laura ; Tihanyi, Károly ; Háda, Viktor ; Nakagawa, Shinsuke ; Dinh Ha Duy, Thuy ; Niwa, Masami ; Deli, M. ; Vastag, Monika. / Comparison of brain capillary endothelial cell-based and epithelial (MDCK-MDR1, Caco-2, and VB-Caco-2) cell-based surrogate blood-brain barrier penetration models. In: European Journal of Pharmaceutics and Biopharmaceutics. 2012 ; Vol. 82, No. 2. pp. 340-351.
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