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| Content Provider | Springer Nature Link |
|---|---|
| Author | Booth, R. Kim, H. |
| Copyright Year | 2014 |
| Abstract | 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. |
| Starting Page | 2379 |
| Ending Page | 2391 |
| Page Count | 13 |
| File Format | |
| ISSN | 00906964 |
| Journal | Annals of Biomedical Engineering |
| Volume Number | 42 |
| Issue Number | 12 |
| e-ISSN | 15739686 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2014-08-13 |
| Publisher Place | Boston |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | BBB Central nervous system Drug discovery Endothelial cells Microsystems μBBB Biomedicine general Biomedical Engineering Biophysics and Biological Physics Mechanics Biochemistry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biomedical Engineering |
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