Influence of the Surface Properties on Nanoparticle-Mediated Transport of Drugs to the Brain

Poly(alkyl cyanoacrylate) nanoparticles enable the delivery of a number of drugs, including doxorubicin, loperamide, tubocurarine, the NMDA receptor antagonist MRZ 2/576, and the peptides dalargin and kytorphin across the blood-brain barrier (BBB) after coating with surfactants. However, only the surfactants polysorbate (Tween^®) 20, 40, 60 and 80, and some poloxamers (Pluronic^® F 68) can induce this uptake. The mechanism for the delivery across the BBB most likely is endocytosis via the LDL receptor by the endothelial cells lining the brain blood capillaries after injection of the nanoparticles into the blood stream. This endocytotic uptake seems to be mediated by the adsorption of apolipoprotein B and/or E adsorption from the blood. Thus, the nanoparticles could mimic lipoprotein particles and act as "Trojan Horses." The drug, then, may be released either within these cells followed by passive diffusion into the brain or be transported into the brain by transcytosis.