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Verfasst von:Balzer, Viktor [VerfasserIn]   i
 Poc, Pascal [VerfasserIn]   i
 Puris, Elena [VerfasserIn]   i
 Martin, Stefan [VerfasserIn]   i
 Aliasgari, Maryam [VerfasserIn]   i
 Auriola, Seppo [VerfasserIn]   i
 Fricker, Gert [VerfasserIn]   i
Titel:Re-evaluation of the hCMEC/D3 based in vitro BBB model for ABC transporter studies
Verf.angabe:Viktor Balzer, Pascal Poc, Elena Puris, Stefan Martin, Maryam Aliasgari, Seppo Auriola, Gert Fricker
E-Jahr:2022
Jahr:26 February 2022
Umfang:10 S.
Fussnoten:Gesehen am 26.07.2022
Titel Quelle:Enthalten in: European journal of pharmaceutics and biopharmaceutics
Ort Quelle:New York, NY [u.a.] : Elsevier, 1997
Jahr Quelle:2022
Band/Heft Quelle:173(2022) vom: Apr., Seite 12-21
ISSN Quelle:1873-3441
Abstract:The blood-brain barrier (BBB) represents one of the biggest hurdles for CNS related drug delivery, preventing permeation of most molecules, and therefore poses a major challenge for researchers in finding effective treatments for CNS diseases. The low permeability of molecules through the BBB is linked on one hand to the extreme tightness by tight junction (TJ) formation limiting the paracellular transport, and on the other hand to the presence of ATP-driven efflux pumps which actively transport unwanted compounds out of the brain. In this study we evaluated the applicability of the immortalized human cell line hCMEC/D3 for ABC transporter studies, focusing on the most expressed ABC transporters at the human BBB: P-glycoprotein (PGP, ABCB1), multidrug resistance protein 4 (MRP4, ABCC4) and breast cancer resistance protein (BCRP, ABCG2). Therefore, a two-step screening method was applied, consisting of a regular uptake assay (96-well format) and bidirectional transport studies, using a transwell system as in vitro simulation of the human BBB. In conclusion, the hCMEC/D3 based in vitro BBB model is well suited to screen drug candidates for ABC transporter interactions on the basis of a regular uptake assay, but in terms of transcellular permeability studies the cell line is limited by a lack of sufficient junctional tightness.
DOI:doi:10.1016/j.ejpb.2022.02.017
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1016/j.ejpb.2022.02.017
 Volltext: https://www.sciencedirect.com/science/article/pii/S0939641122000388
 DOI: https://doi.org/10.1016/j.ejpb.2022.02.017
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:ABC transporters
 BBB model
 Blood-brain barrier
 hCMEC/D3
 Transwell
 Uptake
 Validation
K10plus-PPN:1811673066
Verknüpfungen:→ Zeitschrift

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