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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.


Transwell system applied to measure the transport of nanoparticles across in vitro blood-brain barriers. A porous membrane, upon which the in vitro blood-brain barrier model is grown, separates two compartments. The nanoparticles are added to the upper compartment, and the number of nanoparticles that passes through to the lower compartment is measured.
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f0001: Transwell system applied to measure the transport of nanoparticles across in vitro blood-brain barriers. A porous membrane, upon which the in vitro blood-brain barrier model is grown, separates two compartments. The nanoparticles are added to the upper compartment, and the number of nanoparticles that passes through to the lower compartment is measured.

Mentions: The “classical” approach to measure transport across the blood-brain barrier, or barriers in general, is by utilizing (some form of) transwell system (Fig. 1). Briefly, the barrier is grown on a support filter which separates 2 different compartments. The filter is porous, thus allowing transport through it, at least in principle. The choice of support filter is important, both for ensuring the formation of a good barrier and potentially to allow/minimize (depending upon application) cell migration through the filter, but will not be covered here. Once a barrier has formed, transport through the barrier of a molecule/nanoparticle is measured by replacing the solution in the upper compartment with one including the object of interest. Subsequently, the amount that has transported through to the lower compartment is measured, e.g., by sampling the lower compartment and analyzing it optically, radioactively or using mass spectrometry. Based upon the amount in the lower chamber, the transport through the barrier is then quantified,36e.g., in terms of a permeability coefficient.Figure 1.


Quantitative analysis of nanoparticle transport through in vitro blood-brain barrier models
Transwell system applied to measure the transport of nanoparticles across in vitro blood-brain barriers. A porous membrane, upon which the in vitro blood-brain barrier model is grown, separates two compartments. The nanoparticles are added to the upper compartment, and the number of nanoparticles that passes through to the lower compartment is measured.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f0001: Transwell system applied to measure the transport of nanoparticles across in vitro blood-brain barriers. A porous membrane, upon which the in vitro blood-brain barrier model is grown, separates two compartments. The nanoparticles are added to the upper compartment, and the number of nanoparticles that passes through to the lower compartment is measured.
Mentions: The “classical” approach to measure transport across the blood-brain barrier, or barriers in general, is by utilizing (some form of) transwell system (Fig. 1). Briefly, the barrier is grown on a support filter which separates 2 different compartments. The filter is porous, thus allowing transport through it, at least in principle. The choice of support filter is important, both for ensuring the formation of a good barrier and potentially to allow/minimize (depending upon application) cell migration through the filter, but will not be covered here. Once a barrier has formed, transport through the barrier of a molecule/nanoparticle is measured by replacing the solution in the upper compartment with one including the object of interest. Subsequently, the amount that has transported through to the lower compartment is measured, e.g., by sampling the lower compartment and analyzing it optically, radioactively or using mass spectrometry. Based upon the amount in the lower chamber, the transport through the barrier is then quantified,36e.g., in terms of a permeability coefficient.Figure 1.

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.