Cationic beta-lactoglobulin nanoparticles as a bioavailability enhancer: Effect of surface properties and size on the transport and delivery in vitro

BLG (beta-lactoglobulin) and CBLG (cationic BLG developed by our lab) were evaluated as potential nutraceutical/drug carriers. The cationic corona conferred CBLG with superior integrity and drug retention under gastrointestinal conditions, at most 40-fold higher mucoadhesion, up to 30-fold greater transepithelial permeation and, at most 285% higher cellular uptake, compared to BLG. Furthermore, the more hydrophilic CBLG species exhibited better mucoadhesion, while the more hydrophobic one exhibited higher cellular uptake. Intriguingly, protein molecules were more cytotoxic and exhibited up to 175% higher tight junction-opening capacity than did protein nanoparticles, whereas the nanoparticles displayed up to 770% higher mucoadhesion, greater transepithelial permeation and elevated cellular uptake. Finally, all these surface properties and performances were significantly altered as CBLG bound to serum proteins. Possible mechanisms underlying these findings are discussed in detail. This research sheds some light on the development of protein-based nanoencapsulants and their performance upon oral administration.