Annals of Biomedical Engineering

, Volume 42, Issue 12, pp 2379–2391 | Cite as

Permeability Analysis of Neuroactive Drugs Through a Dynamic Microfluidic In Vitro Blood–Brain Barrier Model

  • R. BoothEmail author
  • H. Kim


This paper presents the permeability analysis of neuroactive drugs and correlation with in vivo brain/plasma ratios in a dynamic microfluidic blood–brain barrier (BBB) model. Permeability of seven neuroactive drugs (Ethosuximide, Gabapentin, Sertraline, Sunitinib, Traxoprodil, Varenicline, PF-304014) and trans-endothelial electrical resistance (TEER) were quantified in both dynamic (microfluidic) and static (transwell) BBB models, either with brain endothelial cells (bEnd.3) in monoculture, or in co-culture with glial cells (C6). Dynamic cultures were exposed to 15 dyn/cm2 shear stress to mimic the in vivo environment. Dynamic models resulted in significantly higher average TEER (respective 5.9-fold and 8.9-fold increase for co-culture and monoculture models) and lower drug permeabilities (average respective decrease of 0.050 and 0.052 log(cm/s) for co-culture and monoculture) than static models; and co-culture models demonstrated higher average TEER (respective 90 and 25% increase for static and dynamic models) and lower drug permeability (average respective decrease of 0.063 and 0.061 log(cm/s) for static and dynamic models) than monoculture models. Correlation of the resultant logP e values [ranging from −4.06 to −3.63 log(cm/s)] with in vivo brain/plasma ratios (ranging from 0.42 to 26.8) showed highly linear correlation (R 2 > 0.85) for all model conditions, indicating the feasibility of the dynamic microfluidic BBB model for prediction of BBB clearance of pharmaceuticals.


BBB Central nervous system Drug discovery Endothelial cells Microsystems μBBB 



Microfluidic blood–brain barrier






Area under the curve


Brain/plasma ratio


Blood–brain barrier


Central nervous system






High performance liquid chromatography


Liquid chromatography-mass spectrometry


Lactate dehydrogenase




Phosphate buffered saline








Trans-endothelial electrical resistance


Zonal occludin-1



This project has been supported by the Utah Science Technology and Research Initiative (USTAR). Microfabrication was performed at the University of Utah Nano Fabrication Facility located in the Sorenson Molecular Biotechnology Building. CNS drugs were provided by Pfizer through the compound transfer program. LC–MS and HPLC–UV was performed at the University of Utah Health Sciences Center (HSC) Core Lab.


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Copyright information

© Biomedical Engineering Society 2014

Authors and Affiliations

  1. 1.Department of BioengineeringUniversity of UtahSalt Lake CityUSA
  2. 2.Department of Electrical and Computer EngineeringUniversity of UtahSalt Lake CityUSA

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