ABSTRACT
The crossing of the BBB using a targeted or a non targeted nanoparticle has been demonstrated both in vitro and in vivo (Fenart et al. 1999; Huwyler et al. 1996; Jallouli et al. 2007). Evidence of nanoparticle transfer by transcytosis across the BBB on physiological models where endothelial cells are linked by tight junctions has been observed in different studies. The mechanisms involved in transferrin transcytosis through the BBB on physiological in vitro BBB models remain controversial as either the clathrin or caveolae pathway might be involved, depending on the model used (Chang et al. 2009; Fenart and Cecchelli 2003; Visser et al. 2004). A study performed on an in vitro BBB model using a co-culture of endothelial cells and astrocytes showed that 90-nm Tf-NPs enter the endothelial cells using a cholesterol-dependent pathway (Fig. 4). Moreover, the uptake of these NPs was increased 20-fold by Tf targeting (targeting was inhibited with excess Tf suggesting that these Tf-NPs enter the cells via the TfR). One study further suggests that the Tf-NPs can specifi cally interact with the BBB via the TfR and are highly endocytosed via the caveolae pathway (Chang et al. 2009).
