“…The chemical nature of the overcoating surfactant is of importance, because only polysorbates, not poloxamers (184, 188, 388, or 407), poloxamine 908, Cremophors (EZ or RH40) or polyoxyethylene(23)-laurylether, led to a CNS pharmacological effect of dalargin. 30 As the mechanism of action, it was hypothesized that polysorbate-coated nanoparticles were transported across the BBB via endocytosis by the brain capillary endothelial cells. 29 This endocytosis would be triggered by a serum protein, apolipoprotein E, reported to adsorb on polysorbate 20, 40, 60, or 80-coated nanoparticles after a 5-min Kreuter,29 this hypothesis raises questions, based on the following observations.…”