Cell-Based in Vitro Blood–Brain Barrier Model Can Rapidly Evaluate Nanoparticles’ Brain Permeability in Association with Particle Size and Surface Modification

Abstract

The possibility of nanoparticle (NP) uptake to the human central nervous system is a major concern. Recent reports showed that in animal models, nanoparticles (NPs) passed through the blood–brain barrier (BBB). For the safe use of NPs, it is imperative to evaluate the permeability of NPs through the BBB. Here we used a commercially available in vitro BBB model to evaluate the permeability of NPs for a rapid, easy and reproducible assay. The model is reconstructed by culturing both primary rat brain endothelial cells and pericytes to support the tight junctions of endothelial cells. We used the permeability coefficient (Papp) to determine the permeability of NPs. The size dependency results, using fluorescent silica NPs (30, 100, and 400 nm), revealed that the Papp for the 30 nm NPs was higher than those of the larger silica. The surface charge dependency results using Qdots® (amino-, carboxyl-, and PEGylated-Qdots), showed that more amino-Qdots passed through the model than the other Qdots. Usage of serum-containing buffer in the model resulted in an overall reduction of permeability. In conclusion, although additional developments are desired to elucidate the NPs transportation, we showed that the BBB model could be useful as a tool to test the permeability of nanoparticles.

Pneumococcal meningitis is promoted by single cocci expressing pilus adhesin RrgA

“…This is also true for S. pneumoniae, an organism in which each individual bacterium only measures approximately 1 μm compared with a chain, which can be longer than 10 μm. It has previously been demonstrated that particles of small molecular size penetrate the BBB more easily than do larger molecules (23,24).…”

Aggregation is a critical cause of poor transfer into the brain tissue of intravenously administered cationic PAMAM dendrimer nanoparticles

“…[24][25][26] In another experiment, we performed the same test with dendrimer nanoparticles suspended in human serum instead of in the assay buffer and obtained very similar results (data not shown). These results suggest that low BBB permeability in vivo of cationic PAMAM dendrimer particles is unexpected because of prompt cellular internalization of the dendrimer particles in cultured cells as we observed.…”

Silver nanoparticles induce tight junction disruption and astrocyte neurotoxicity in a rat blood–brain barrier primary triple coculture model

“…However, the influence of nanoparticles on human health and brain has not been studied well. 24 Several studies have demonstrated that Ag-NPs can enter the CNS 25 and induce brain edema and neurotoxicity. 10,11,[26][27][28][29] Our previous studies showed that Ag-NPS and/or released Ag ions crossed the BBB and subsequently caused damage to astrocytes and neurons.…”