Polyphosphate coatings: A promising strategy to overcome the polycation dilemma

• Published in: Journal of colloid and interface science 2021-04, Vol.587, p.279-289
• Main Authors: Le, Nguyet-Minh Nguyen, Steinbring, Christian, Le-Vinh, Bao, Jalil, Aamir, Matuszczak, Barbara, Bernkop-Schnürch, Andreas
• Format: Article
• Language: English
• Subjects: Anionic coating; Cell penetrating peptide; Lipid-based nanocarriers; Nanoemulsions; Polycation dilemma; Polyphosphate; Zeta potential changing system
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2020.12.019

[Display omitted] It was the aim of this study to develop a zeta potential changing drug delivery system by decorating lipid-based nanocarriers with a polycationic cell penetrating peptide (CPP) and subsequently masking these cationic substructures with polyphosphates. In order to anchor the CPP poly-l-lysine (PLL) on the surface of the oily droplets of an o/w nanoemulsion, stearic acid was covalently attached to the peptide. The resulting CPP-decorated oily droplets were coated with phytic acid and tripolyphosphate. The elimination of these polyphosphates due to cleavage by alkaline phosphatase was monitored by the release of monophosphate from the surface of the nanocarriers, by the change in zeta potential and by cellular uptake studies on Caco-2 cells. Polyphosphate coated PLL-decorated nanocarriers exhibited a pronounced conversion of zeta potential from −14.1 mV to +4.2 mV in case of tripolyphosphate coated nanocarriers and from −9.9 mV to −2.6 mV in case of phytic acid coated nanocarriers. The cellular uptake on Caco-2 cells of the polyphosphate coated nanocarriers was 4-fold improved compared to the control nanocarriers. Furthermore, confocal images showed that the majority of nanodroplets distributed in cytoplasm not being internalized into lysosomes. Polyphosphate coating of CPP-decorated nanocarriers seems to be a promising and simple strategy to overcome the polycation dilemma.