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.