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

Abstract

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 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.

DOI: 10.1371/journal.pone.0086806

Extracted Key Phrases

7 Figures and Tables

02040201520162017
Citations per Year

Citation Velocity: 12

Averaging 12 citations per year over the last 3 years.

Learn more about how we calculate this metric in our FAQ.

Cite this paper

@inproceedings{Novkov2014TransportRO, title={Transport Rankings of Non-Steroidal Antiinflammatory Drugs across Blood-Brain Barrier In Vitro Models}, author={Iveta Nov{\'a}kov{\'a} and Eva-anne Subileau and Stefan Toegel and Daniela Gruber and Bodo Lachmann and Ernst Urban and Christophe Chesn{\'e} and Christian Roland Noe and Winfried Neuhaus}, booktitle={PloS one}, year={2014} }