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

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.

Keywords: biomolecular corona; blood-brain barrier; nanomedicine; nanoparticles; nanosafety; transwell systems.

Figure 1.

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.

Figure 2.

Potential issues with applying transwell systems to measure the transport of nanoparticles across in vitro blood-brain barriers.

Figure 3.

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.

Figure 4.

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. .