Cell-based in vitro blood-brain barrier model can rapidly evaluate nanoparticles' brain permeability in association with particle size and surface modification.
The possibility of nanoparticle (NP) uptake to the human central nervous system is a major concern. Recent reports showed that in animal models, nanoparticles (NPs) passed through the blood-brain barrier (BBB). For the safe use of NPs, it is imperative to evaluate the permeability of NPs through the BBB. Here we used a commercially available in vitro BBB model to evaluate the permeability of NPs for a rapid, easy and reproducible assay. The model is reconstructed by culturing both primary rat brain endothelial cells and pericytes to support the tight junctions of endothelial cells. We used the permeability coefficient (P(app)) to determine the permeability of NPs. The size dependency results, using fluorescent silica NPs (30, 100, and 400 nm), revealed that the Papp for the 30 nm NPs was higher than those of the larger silica. The surface charge dependency results using Qdots® (amino-, carboxyl-, and PEGylated-Qdots), showed that more amino-Qdots passed through the model than the other Qdots. Usage of serum-containing buffer in the model resulted in an overall reduction of permeability. In conclusion, although additional developments are desired to elucidate the NPs transportation, we showed that the BBB model could be useful as a tool to test the permeability of nanoparticles.
Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. hanada@ri.ncgm.go.jp.
Sanshiro
S
Hanada
Department of Molecular Cell Biology, The Jikei University School of Medicine, Tokyo 105-8461, Japan. kfujioka@jikei.ac.jp.
Kouki
K
Fujioka
Department of Anatomy, Toho University, 5-21-16 Omori-Nishi Ota-ku, Tokyo 143-8541, Japan. yuriko.inoue@med.toho-u.ac.jp.
Yuriko
Y
Inoue
Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. fkanaya@acc.ncgm.go.jp.
Fumihide
F
Kanaya
Department of Molecular Cell Biology, The Jikei University School of Medicine, Tokyo 105-8461, Japan. manome@jikei.ac.jp.
Yoshinobu
Y
Manome
Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. backen@ri.ncgm.go.jp.
Kenji
K
Yamamoto
D000818:Animals; D001812:Blood-Brain Barrier / Q000166:cytology / Q000378:metabolism*; D018929:Cell Culture Techniques; D042783:Endothelial Cells; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D020286:Pericytes; D010539:Permeability; D051381:Rats; D012822:Silicon Dioxide / Q000737:chemistry / Q000378:metabolism; D013499:Surface Properties
D012822:Silicon Dioxide