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Transport Rankings of Non-Steroidal Antiinflammatory Drugs across Blood-Brain Barrier In Vitro Models

Please always quote using this URN: urn:nbn:de:bvb:20-opus-119992
  • The aim of this work was to conduct a comprehensive study about the transport properties of NSAIDs across the blood-brain barrier (BBB) in vitro. Transport studies with celecoxib, diclofenac, ibuprofen, meloxicam, piroxicam and tenoxicam were accomplished across Transwell models based on cell line PBMEC/C1-2, ECV304 or primary rat brain endothelial cells. Single as well as group substance studies were carried out. In group studies substance group compositions, transport medium and serum content were varied, transport inhibitors verapamil andThe aim of this work was to conduct a comprehensive study about the transport properties of NSAIDs across the blood-brain barrier (BBB) in vitro. Transport studies with celecoxib, diclofenac, ibuprofen, meloxicam, piroxicam and tenoxicam were accomplished across Transwell models based on cell line PBMEC/C1-2, ECV304 or primary rat brain endothelial cells. Single as well as group substance studies were carried out. In group studies substance group compositions, transport medium and serum content were varied, transport inhibitors verapamil and probenecid were added. Resulted permeability coefficients were compared and normalized to internal standards diazepam and carboxyfluorescein. Transport rankings of NSAIDs across each model were obtained. Single substance studies showed similar rankings as corresponding group studies across PBMEC/C1-2 or ECV304 cell layers. Serum content, glioma conditioned medium and inhibitors probenecid and verapamil influenced resulted permeability significantly. Basic differences of transport properties of the investigated NSAIDs were similar comparing all three in vitro BBB models. Different substance combinations in the group studies and addition of probenecid and verapamil suggested that transporter proteins are involved in the transport of every tested NSAID. Results especially underlined the importance of same experimental conditions (transport medium, serum content, species origin, cell line) for proper data comparison.show moreshow less

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Metadaten
Author: Iveta Novakova, Eva-Anne Subileau, Stefan Toegel, Daniela Gruber, Bodo Lachmann, Ernst Urban, Christophe Chesne, Christian R. Noe, Winfried Neuhaus
URN:urn:nbn:de:bvb:20-opus-119992
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004)
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2014
Volume:9
Issue:1
Pagenumber:e86806
Source:PLoS ONE 9(1): e86806. doi:10.1371/journal.pone.0086806
DOI:https://doi.org/10.1371/journal.pone.0086806
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 612 Humanphysiologie
Tag:NSAIDs; astrocytes; diazepam; drug-drug interactions; glioma; permeability; scanning electron microscopy; transport inhibition assay
Release Date:2015/11/25
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung