Reliable permeability assay system in a microfluidic device mimicking cerebral vasculatures
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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.
KeywordsBlood–brain barrier Microfluidics Cell trapping Permeability assay
This research was supported by a National Research Laboratory (NRL) Program grant (2011-0018607), a Converging Research Center Program grant (2011K000864) through the National Research Foundation and a grant (2009 K001282) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology (MEST) of Republic of Korea.
- N.J. Abbott, Drug Discov Today 1, 407 (2004)Google Scholar
- T.G. Papaioannou, C. Stefanadis, Hell. J. Cardiol. 46, 9 (2005)Google Scholar
- W.M. Pardridge, D. Triguero, J. Yang, P.A. Cancilla, J. Pharmacol. Exp. Ther. 253, 884 (1990)Google Scholar
- P.B.L. Pun, J. Lu, S. Moochhala, Free Radic. Biol. Med. 43, 348 (2009)Google Scholar