Reliable permeability assay system in a microfluidic device mimicking cerebral vasculatures
0303 health sciences
Brain
Reproducibility of Results
600
Equipment Design
Hydrogen Peroxide
Microfluidic Analytical Techniques
Permeability
Rats
Tight Junctions
3. Good health
03 medical and health sciences
Pharmaceutical Preparations
Blood-Brain Barrier
Astrocytes
Culture Media, Conditioned
Human Umbilical Vein Endothelial Cells
Animals
Humans
Pharmacokinetics
Cells, Cultured
Chromatography, High Pressure Liquid
DOI:
10.1007/s10544-012-9680-5
Publication Date:
2012-07-21T14:21:00Z
AUTHORS (6)
ABSTRACT
Since most of the bioavailable drugs are impermeable through the blood-brain barrier (BBB), development of a rapid and reliable permeability assay system has been a challenge in drug discovery targeting central nervous system (CNS). Here, we designed a microfluidic device to monitor the drug permeability into the CNS. Human umbilical vein endothelial cells (HUVECs) were shortly (2 ~ 3 h) incubated with astrocyte-conditioned medium after being trapped on microholes in the microfluidic device and tested for chip-based permeability measurement of drugs. The measured permeability values were highly correlated with those measured by conventional in vitro methods and the brain uptake index representing the quantity of transported substances across the in vivo BBB of rats. Using the microfluidic device, we could easily monitor the effect of hydrogen peroxide on the trans-endothelial permeability, which are consistent with the finding that the same treatment disrupted the formation of tight junctions between endothelial cells. Considering relatively short period of time needed for endothelial cell culture and ability to monitor the BBB physiology continuously, we propose that this novel system can be used as an invaluable first-line tool for CNS-related drug development.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (31)
CITATIONS (120)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....