Comparison of Blood-Brain Barrier Models for in Vitro Biological Analysis: One-Cell Type vs Three-Cell Type

Abstract

Different types of in vitro blood-brain barrier (BBB) models have been constructed and applied for drug transport to evaluate the efficacy of nanocarrier-based drug delivery. However, the effectiveness of different types of BBB models has not been reported. In this paper, we developed two types of in vitro models: a one-cell type BBB model developed using only endothelial cells and a three-cell type BBB model obtained by coculturing endothelial, pericyte, and astrocyte cells. The nanoparticle transport mechanisms through the BBB and transport efficiencies of the Lactoferrin-attached silica nanoparticles were studied using both types of the in vitro BBB models. Compared with the one-cell type model, the PSi-Lf NPs exhibit relatively lower transport efficiency across the three-cell type BBB model. However, the effects of the nanoparticle size on the transport efficacies are consistent for both models. For both types of BBB models, the transport efficacies of the NPs are size-dependent, and the highest efficacies are achieved for PSi-Lf NPs with 25 nm in diameter. Our experimental results indicate that the one-cell type and three-cell type BBB models are equivalent for evaluating and optimizing nanoparticle transport across the BBB.