Crossing mucosal barriers for non-invasive protein delivery: a vitamin B12-mediated approach

Mucosal delivery of biotherapeutics as a non-invasive means of delivery could potentially be enhanced using nanoscale therapeutic carriers. However, nanoparticles do not readily cross the mucosal barriers, with the epithelium severely restricting their translocation into the systemic circulation. Translocation of nanocarriers across the mucosae may be improved by employing ligands capable of exploiting receptor-mediated cell uptake processes. This work explores the potential of vitamin B12 transport pathway for mucosal delivery of B12-decorated model nanoparticles and investigates the cell trafficking pathways involved in these processes. Cyanocobalamin (vitamin B12) was chemically modified to produce the α-ω-aminohexylcarbamate B12 derivative – as a suitable bioconjugate – which was then conjugated to fluorescent, carboxy-functional nanoparticles (