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Uptake and transport of B12-conjugated nanoparticles in airway epithelium

Fowler, Robyn; Vllasaliu, Driton; Falcone, Franco H.; Garnett, Martin; Smith, Bryan; Horsley, Helen; Alexander, Cameron; Stolnik, Snow

Authors

Robyn Fowler

Driton Vllasaliu

Franco H. Falcone

Martin Garnett

Bryan Smith

Helen Horsley

Cameron Alexander

Snow Stolnik snow.stolnik@nottingham.ac.uk



Abstract

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. Our work 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.

Journal Article Type Article
Publication Date Nov 28, 2013
Journal Journal of Controlled Release
Print ISSN 0168-3659
Electronic ISSN 1873-4995
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 172
Issue 1
APA6 Citation Fowler, R., Vllasaliu, D., Falcone, F. H., Garnett, M., Smith, B., Horsley, H., …Stolnik, S. (2013). Uptake and transport of B12-conjugated nanoparticles in airway epithelium. Journal of Controlled Release, 172(1), https://doi.org/10.1016/j.jconrel.2013.08.028
DOI https://doi.org/10.1016/j.jconrel.2013.08.028
Keywords Vitamin B12; Airway epithelium; Cubilin; Calu-3 cells; Epithelial nanoparticle transport
Publisher URL http://ac.els-cdn.com/S0168365913004975/1-s2.0-S0168365913004975-main.pdf?_tid=f71a492e-af8c-11e3-b0a2-00000aab0f6c&acdnat=1395250752_a4ff886f231438b6fa006dc974704dc1
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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