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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.


Role of biomolecular corona in nanoparticle interactions with the blood-brain barrier. (A) Corona-covered nanoparticle interacting with cells of the barrier vs. (B) bare nanoparticle. Only the former situation is expected to occur in vivo.
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f0003: Role of biomolecular corona in nanoparticle interactions with the blood-brain barrier. (A) Corona-covered nanoparticle interacting with cells of the barrier vs. (B) bare nanoparticle. Only the former situation is expected to occur in vivo.

Mentions: A different aspect – which clearly distinguishes nanoparticles from molecular species – of importance for how nanoparticles transport through the blood-brain barrier is the concept of biomolecular corona.49,50 The biomolecular corona refers to the adsorption of biomolecules from the environment onto the nanoparticle, forming a “corona” of biomolecules (Fig. 3A) that covers the original nanoparticle surface (Fig. 3B). The formation of such a corona is important to consider, because in any imaginable way a nanoparticle would come in contact with the blood-brain barrier in vivo, it would do so in the presence of a complex mixture of biomolecules in its environment, all of which could potentially adsorb. Indeed, proteins,49,51,52 lipids53-56 and sugars57,58 have all been found in the corona of different nanoparticles in animal-derived biological media, though the proteins are still the most studied. Furthermore, though which biomolecules adsorb differs, the same general phenomenon of a formation of corona is observed in many biological fluids,59 from blood serum50,52,60,61 to bronchoalveolar lavage fluid56 to urine.59 For nanoparticles approaching the blood-brain barrier, the corona formed in blood serum is perhaps the most important (but not the only; see below) to consider, and this is also the most well-studied.Figure 3.


Quantitative analysis of nanoparticle transport through in vitro blood-brain barrier models
Role of biomolecular corona in nanoparticle interactions with the blood-brain barrier. (A) Corona-covered nanoparticle interacting with cells of the barrier vs. (B) bare nanoparticle. Only the former situation is expected to occur in vivo.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f0003: Role of biomolecular corona in nanoparticle interactions with the blood-brain barrier. (A) Corona-covered nanoparticle interacting with cells of the barrier vs. (B) bare nanoparticle. Only the former situation is expected to occur in vivo.
Mentions: A different aspect – which clearly distinguishes nanoparticles from molecular species – of importance for how nanoparticles transport through the blood-brain barrier is the concept of biomolecular corona.49,50 The biomolecular corona refers to the adsorption of biomolecules from the environment onto the nanoparticle, forming a “corona” of biomolecules (Fig. 3A) that covers the original nanoparticle surface (Fig. 3B). The formation of such a corona is important to consider, because in any imaginable way a nanoparticle would come in contact with the blood-brain barrier in vivo, it would do so in the presence of a complex mixture of biomolecules in its environment, all of which could potentially adsorb. Indeed, proteins,49,51,52 lipids53-56 and sugars57,58 have all been found in the corona of different nanoparticles in animal-derived biological media, though the proteins are still the most studied. Furthermore, though which biomolecules adsorb differs, the same general phenomenon of a formation of corona is observed in many biological fluids,59 from blood serum50,52,60,61 to bronchoalveolar lavage fluid56 to urine.59 For nanoparticles approaching the blood-brain barrier, the corona formed in blood serum is perhaps the most important (but not the only; see below) to consider, and this is also the most well-studied.Figure 3.

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.