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Cell-based in vitro blood-brain barrier model can rapidly evaluate nanoparticles' brain permeability in association with particle size and surface modification.

Hanada S, Fujioka K, Inoue Y, Kanaya F, Manome Y, Yamamoto K - Int J Mol Sci (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. hanada@ri.ncgm.go.jp.

ABSTRACT
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.

Show MeSH
Microscopy analysis of the BBB model. In (a) and (b), we stained by H&E after supplementation of the 30 nm silica and the MP silica, respectively; in (c–e), we confirmed red fluorescence of the silica accumulation in the BBB model’s cell layers by fluorescent microscopy (30, 100, and 400 nm).
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f2-ijms-15-01812: Microscopy analysis of the BBB model. In (a) and (b), we stained by H&E after supplementation of the 30 nm silica and the MP silica, respectively; in (c–e), we confirmed red fluorescence of the silica accumulation in the BBB model’s cell layers by fluorescent microscopy (30, 100, and 400 nm).

Mentions: To confirm the histology of the BBB cell layers, we executed hematoxylin and eosin (H&E) staining. In the vertical sections of the cell layers (Figure 2a,b), thinning of the endothelial cell layers was observed by exposure to the 30 nm NPs, compared with the MPs, indicating “loosening” of the tight junction of the BBB cell layers.


Cell-based in vitro blood-brain barrier model can rapidly evaluate nanoparticles' brain permeability in association with particle size and surface modification.

Hanada S, Fujioka K, Inoue Y, Kanaya F, Manome Y, Yamamoto K - Int J Mol Sci (2014)

Microscopy analysis of the BBB model. In (a) and (b), we stained by H&E after supplementation of the 30 nm silica and the MP silica, respectively; in (c–e), we confirmed red fluorescence of the silica accumulation in the BBB model’s cell layers by fluorescent microscopy (30, 100, and 400 nm).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3958822&req=5

f2-ijms-15-01812: Microscopy analysis of the BBB model. In (a) and (b), we stained by H&E after supplementation of the 30 nm silica and the MP silica, respectively; in (c–e), we confirmed red fluorescence of the silica accumulation in the BBB model’s cell layers by fluorescent microscopy (30, 100, and 400 nm).
Mentions: To confirm the histology of the BBB cell layers, we executed hematoxylin and eosin (H&E) staining. In the vertical sections of the cell layers (Figure 2a,b), thinning of the endothelial cell layers was observed by exposure to the 30 nm NPs, compared with the MPs, indicating “loosening” of the tight junction of the BBB cell layers.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Research Institute, National Center for Global Health and Medicine, Tokyo 162-8655, Japan. hanada@ri.ncgm.go.jp.

ABSTRACT
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.

Show MeSH