Uptake and transport of B12-conjugated nanoparticles in airway epithelium

Fowler, Robyn and Vllasaliu, Driton and Falcone, Franco H. and Garnett, Martin and Smith, Bryan and Horsley, Helen and Alexander, Cameron and Stolnik, Snow (2013) Uptake and transport of B12-conjugated nanoparticles in airway epithelium. Journal of Controlled Release, 172 (1). pp. 374-381. ISSN 0168-3659

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Non-invasive delivery of biotherapeutics, as an attractive alternative to injections, could potentially be achieved

through the mucosal surfaces, utilizing nanoscale therapeutic carriers. However, nanoparticles do not readily

cross the mucosal barriers,with the epitheliumpresenting a major barrier to their translocation. The transcytotic

pathway of vitamin B12 has previously been shown to ‘ferry’ B12-decorated nanoparticles across intestinal epithelial

(Caco-2) cells. However, such studies have not been reported for the airway epithelium. Furthermore, the presence

in the airways of the cell machinery responsible for transepithelial trafficking of B12 is not widely reported. Using a

combination of molecular biology and immunostaining techniques, our work demonstrates that the bronchial cell

line, Calu-3, expresses the B12-intrinsic factor receptor, the transcobalamin II receptor and the transcobalamin II carrier

protein. Importantly, the work showed that sub-200 nm model nanoparticles chemically conjugated to B12

were internalised and transported across the Calu-3 cell layers,with B12 conjugation not only enhancing cell uptake

and transepithelial transport, but also influencing intracellular trafficking. Ourwork therefore demonstrates that the

B12 endocytotic apparatus is not only present in this airway model, but also transports ligand-conjugated

nanoparticles across polarised epithelial cells, indicating potential for B12-mediated delivery of nanoscale carriers

of biotherapeutics across the airways.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1016/j.jconrel.2013.08.028
Depositing User: de Sousa, Mrs Shona
Date Deposited: 25 Mar 2014 11:50
Last Modified: 14 Oct 2017 19:02
URI: http://eprints.nottingham.ac.uk/id/eprint/2507

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