Poly(butyl cyanoacrylate) nanoparticles overcoated with polysorbate 80 or other polysorbates were shown to enable the transport of bound drugs across the blood-brain barrier. Drugs that have successfully been transported across this barrier with the nanoparticles include the hexapeptide dalargin, loperamide, tubocurarine, and doxorubicin. The mechanism of this transport has not yet been fully elucidated. The most probable transport pathway seems to be endocytosis by the blood capillary endothelial cells following adsorption of blood plasma components, most likely apo E, after intravenous injection. These particles could interact with the LDL receptors on the endothelial cells and then be internalized. After internalization by the brain capillary endothelial cells, the drug might be released in these cells by desorption or degradation of the nanoparticles and diffuse into the residual brain. Alternatively, the nano-particles may be transcytosed across the endothelium as suggested for LDL particles (39). In any case the drug would be able to largely circumvent the efficient efflux pumps (P-glycoprotein, MOAT) that actively transport substances such as drugs out of the endothelial cells and are concentrated in the cell membranes adjacent to the brain capillaries.
In addition to these processes, polysorbates seem to be able to inhibit these efflux pumps. This inhibition could contribute to the brain transport properties of the nanoparticles. Although polysorbates are inefficient as inhibi tors of the efflux pumps when used intravenously in the form of a 1% solution, the adsorption of these surfactants to the nanoparticle surface may enhance their concentration in the endothelial cells, thus augmenting the brain transport of simultaneously bound drug.
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