title: Reliable permeability assay system in a microfluidic device mimicking cerebral vasculatures.
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.
authors: Department of Bio and Brain Engineering, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 305-701, Republic of Korea.
authors: Ju Hun
authors: JH
authors: Yeon
authors: Dokyun
authors: D
authors: Na
authors: Kyungsun
authors: K
authors: Choi
authors: Seung-Wook
authors: SW
authors: Ryu
authors: Chulhee
authors: C
authors: Choi
authors: Je-Kyun
authors: JK
authors: Park
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000166:cytology / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000166:cytology; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned; D004867:Equipment Design; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation* / Q000379:methods; D010539:Permeability; D004364:Pharmaceutical Preparations; D010599:Pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D004364:Pharmaceutical Preparations; D006861:Hydrogen Peroxide