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

Different types of in vitro blood-brain barrier (BBB) models have been constructed and applied for drug transport to evaluate the efficacy of nano-carrier 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: one-cell type BBB model developed using only endothelial cells and three-cell type BBB model obtained by co-culturing endothelial, pericyte and astrocyte cells. The nanoparticle transport mechanisms through BBB and transport efficiencies of the Lactoferrin attached silica nanoparticles were studied using both types of the in vitro BBB models. Compared with one-cell type model, the PSi-Lf NPs exhibit relatively lower transport efficiency across three-cell type BBB system. Moreover, 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 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 BBB.