The interaction of carbon nanotubes with an invitro blood-brain barrier model and mouse brain invivo

Abstract

Carbon nanotubes (CNTs) are a novel nanocarriers with interesting physical and chemical properties. Here we investigate the ability of amino-functionalized multi-walled carbon nanotubes (MWNTs-NH3+) to cross the Blood-Brain Barrier (BBB) invitro using a co-culture BBB model comprising primary porcine brain endothelial cells (PBEC) and primary rat astrocytes, and invivo following a systemic administration of radiolabelled f-MWNTs. Transmission Electron microscopy (TEM) confirmed that MWNTs-NH3+ crossed the PBEC monolayer via energy-dependent transcytosis. MWNTs-NH3+ were observed within endocytic vesicles and multi-vesicular bodies after 4 and 24h. A complete crossing of the invitro BBB model was observed after 48h, which was further confirmed by the presence of MWNTs-NH3+ within the astrocytes. MWNT-NH3+ that crossed the PBEC layer was quantitatively assessed using radioactive tracers. A maximum transport of 13.0±1.1% after 72h was achieved using the co-culture model. f-MWNT exhibited significant brain uptake (1.1±0.3% injected dose/g) at 5min after intravenous injection in mice, after whole body perfusion with heparinized saline. Capillary depletion confirmed presence of f-MWNT in both brain capillaries and parenchyma fractions. These results could pave the way for use of CNTs as nanocarriers for delivery of drugs and biologics to the brain, after systemic administration.