Mechanism of polymeric nanoparticle-based drug transport across the blood-brain barrier (BBB)

In 1995 it was reported for the first time that nanoparticles could be used for the delivery of drugs across the blood-brain barrier (BBB) following intravenous injection. In vitro and in vivo experiments show that the underlying mechanism is receptor-mediated endocytosis followed by transcytosis. No opening of the tight junctions was observed. Due to the overcoating of the nanoparticles with polysorbate 80 or poloxamers 188, apolipoproteins A-I and/or E are adsorbed from the blood on to the particle surface after injection. These apolipoproteins mediate the interaction with LDL or scavenger receptors on the BBB followed by the above brain uptake processes. Likewise, covalent attachment of these apolipoproteins or of transferrin, insulin or antibodies against the respective receptors also enables a similar nanoparticle-mediated drug transport across the BBB. From these results it can be concluded that the nanoparticles act as "Trojan Horses" taking advantage of physiological receptor-mediated transport processes across the BBB.