title: The interaction of carbon nanotubes with an in vitro blood-brain barrier model and mouse brain in vivo.
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) in vitro using a co-culture BBB model comprising primary porcine brain endothelial cells (PBEC) and primary rat astrocytes, and in vivo 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 24 h. A complete crossing of the in vitro BBB model was observed after 48 h, 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 72 h was achieved using the co-culture model. f-MWNT exhibited significant brain uptake (1.1  ±  0.3% injected dose/g) at 5 min 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.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Houmam
authors.initials: H
authors.lastname: Kafa
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Julie Tzu-Wen
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Noelia
authors.initials: N
authors.lastname: Rubio
authors.affiliation: Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
authors.forename: Kerrie
authors.initials: K
authors.lastname: Venner
authors.affiliation: Histopathology Department, Great Ormond Street Hospital for Children, London WC1N 3JH, UK.
authors.forename: Glenn
authors.initials: G
authors.lastname: Anderson
authors.affiliation: ICN2 - Institut Catala de Nanociencia i Nanotecnologia, Campus UAB, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Pach
authors.affiliation: ICN2 - Institut Catala de Nanociencia i Nanotecnologia, Campus UAB, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Ballesteros
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Preston
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: N Joan
authors.initials: NJ
authors.lastname: Abbott
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. Electronic address: khuloud.al-jamal@kcl.ac.uk.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D018920:Coculture Techniques; D066298:In Vitro Techniques; D051379:Mice; D017348:Microscopy, Electron, Scanning Transmission; D037742:Nanotubes, Carbon / Q000633:toxicity; D004369:Pentetic Acid / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
chemical_list: D037742:Nanotubes, Carbon; D004369:Pentetic Acid
keywords: BBB model; PBEC; STEM; TEM; Transcytosis; Transwells