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Quantitative analysis of nanoparticle transport through in vitro blood-brain barrier models

View Article: PubMed Central - PubMed

ABSTRACT

Nanoparticle transport through the blood-brain barrier has received much attention of late, both from the point of view of nano-enabled drug delivery, as well as due to concerns about unintended exposure of nanomaterials to humans and other organisms. In vitro models play a lead role in efforts to understand the extent of transport through the blood-brain barrier, but unique features of the nanoscale challenge their direct adaptation. Here we highlight some of the differences compared to molecular species when utilizing in vitro blood-brain barrier models for nanoparticle studies. Issues that may arise with transwell systems are discussed, together with some potential alternative methodologies. We also briefly review the biomolecular corona concept and its importance for how nanoparticles interact with the blood-brain barrier. We end with considering future directions, including indirect effects and application of shear and fluidics-technologies.

No MeSH data available.


Indirect effects due to nanoparticle uptake in an in vitro blood-brain barrier. Despite the nanoparticles not being transported across the barrier (at least not to a significant degree), signaling takes place between the blood-brain barrier cells and astrocytic cells grown below them. Image adapted from ref. 86.
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f0004: Indirect effects due to nanoparticle uptake in an in vitro blood-brain barrier. Despite the nanoparticles not being transported across the barrier (at least not to a significant degree), signaling takes place between the blood-brain barrier cells and astrocytic cells grown below them. Image adapted from ref. 86.

Mentions: In a related arena, Case and colleagues have made the interesting observation that nanoparticles can cause signaling across cell barriers – without actually passing through the barrier.84,85 Such indirect effects have actually been observed also for the blood-brain barrier (Fig. 4), with signaling taking place between an in vitro blood-brain barrier and astrocytes grown below it.86 It is obviously imperative that studies on indirect effects are carried out with many of the issues discussed here in mind. For instance, if in vivo a nanoparticle is able to exert an indirect effect across the blood-brain barrier, but in vitro crosses an imperfect blood-brain barrier through holes in the barrier, what is actually an indirect effect could be misinterpreted as a direct effect. Obviously the opposite could also occur. One could imagine even more complicated scenarios, where in vivo signaling takes place but not to a significant extent, whereas the nanoparticle passes through holes in an imperfect barrier, picks up the signaling molecule on the other side of the barrier through adsorption, and subsequently delivers it to the receiving cells, at a higher dose. Such variations on the “trojan horse” effect87 could be a significant challenge to dissect, if imperfections in the barrier are not considered.Figure 4.


Quantitative analysis of nanoparticle transport through in vitro blood-brain barrier models
Indirect effects due to nanoparticle uptake in an in vitro blood-brain barrier. Despite the nanoparticles not being transported across the barrier (at least not to a significant degree), signaling takes place between the blood-brain barrier cells and astrocytic cells grown below them. Image adapted from ref. 86.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836482&req=5

f0004: Indirect effects due to nanoparticle uptake in an in vitro blood-brain barrier. Despite the nanoparticles not being transported across the barrier (at least not to a significant degree), signaling takes place between the blood-brain barrier cells and astrocytic cells grown below them. Image adapted from ref. 86.
Mentions: In a related arena, Case and colleagues have made the interesting observation that nanoparticles can cause signaling across cell barriers – without actually passing through the barrier.84,85 Such indirect effects have actually been observed also for the blood-brain barrier (Fig. 4), with signaling taking place between an in vitro blood-brain barrier and astrocytes grown below it.86 It is obviously imperative that studies on indirect effects are carried out with many of the issues discussed here in mind. For instance, if in vivo a nanoparticle is able to exert an indirect effect across the blood-brain barrier, but in vitro crosses an imperfect blood-brain barrier through holes in the barrier, what is actually an indirect effect could be misinterpreted as a direct effect. Obviously the opposite could also occur. One could imagine even more complicated scenarios, where in vivo signaling takes place but not to a significant extent, whereas the nanoparticle passes through holes in an imperfect barrier, picks up the signaling molecule on the other side of the barrier through adsorption, and subsequently delivers it to the receiving cells, at a higher dose. Such variations on the “trojan horse” effect87 could be a significant challenge to dissect, if imperfections in the barrier are not considered.Figure 4.

View Article: PubMed Central - PubMed

ABSTRACT

Nanoparticle transport through the blood-brain barrier has received much attention of late, both from the point of view of nano-enabled drug delivery, as well as due to concerns about unintended exposure of nanomaterials to humans and other organisms. In vitro models play a lead role in efforts to understand the extent of transport through the blood-brain barrier, but unique features of the nanoscale challenge their direct adaptation. Here we highlight some of the differences compared to molecular species when utilizing in vitro blood-brain barrier models for nanoparticle studies. Issues that may arise with transwell systems are discussed, together with some potential alternative methodologies. We also briefly review the biomolecular corona concept and its importance for how nanoparticles interact with the blood-brain barrier. We end with considering future directions, including indirect effects and application of shear and fluidics-technologies.

No MeSH data available.