The interaction of carbon nanotubes with an in vitro blood-brain barrier model and mouse brain in vivo
Kafa, Houmam (King's College London. Institute of Pharmaceutical Science)
Wang, Julie Tzu-Wen (King's College London. Institute of Pharmaceutical Science)
Rubio, Noelia (King's College London. Institute of Pharmaceutical Science)
Venner, Kerrie (University College London. Institute of Neurology)
Anderson, Glenn (Great Ormond Street Hospital for Children (Londres))
Pach, Elzbieta (Institut Català de Nanociència i Nanotecnologia)
Ballesteros, Belén (Institut Català de Nanociència i Nanotecnologia)
Preston, Jane E. (King's College London. Institute of Pharmaceutical Science)
Abbott, N. Joan (King's College London. Institute of Pharmaceutical Science)
Al-Jamal, Khuloud T. (King's College London. Institute of Pharmaceutical Science)

Data:	2015
Resum:	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.
Ajuts:	European Commission 290023 Ministerio de Economía y Competitividad SEV-2013-0295
Nota:	Altres ajuts: KAJ thanks the members of the EU COST actions TD1004 (Theranostics Imaging and Therapy: An Action to Develop Novel Nanosized Systems for Imaging-Guided Drug Delivery and Biological Processes) for sponsoring HK's research stay at the ICN2 for the electron microscopy studies.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Transcytosis ; Transwells ; PBEC ; BBB model ; TEM ; STEM
Publicat a:	Biomaterials, Vol. 53 (June 2015) , p. 437-452, ISSN 1878-5905

DOI: 10.1016/j.biomaterials.2015.02.083
PMID: 25890741

16 p, 4.7 MB

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