Development of phosphorylated nanoparticles as zeta potential inverting systems

• Published in: European journal of pharmaceutics and biopharmaceutics 2015-11, Vol.97 (Pt A), p.250-256
• Main Authors: Perera, Glen, Zipser, Maximilian, Bonengel, Sonja, Salvenmoser, Willi, Bernkop-Schnürch, Andreas
• Format: Article
• Language: English
• Subjects: Alkaline Phosphatase - metabolism; Caco-2 Cells; Carboxymethylcellulose Sodium - chemistry; Chemistry, Pharmaceutical - methods; Chitosan - chemistry; Drug Delivery Systems; Humans; Intestinal alkaline phosphatase; Intestinal barriers; Intestines - metabolism; Mucus; Mucus - metabolism; Nanoparticles; Particle Size; Phosphates - chemistry; Phosphorylation; Phosphotyrosine; Phosphotyrosine - chemistry; Polymers - chemistry; Zeta potential
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2015.01.017

[Display omitted] •Two novel phosphorylated polymers were synthesized.•Nanoparticles were prepared by polyelectrolyte complexation of the two polymers.•These nanoparticles display appropriate characteristics for mucus permeation.•Enzymatic dephosphorylation of the nanoparticles leads to zeta potential inversion.•Novel polymers and corresponding nanoparticles do not show toxic effects. The objective of this study was to generate nanoparticles with a slightly negative zeta potential which switches to positive values under the influence of intestinal alkaline phosphatase in order to address two major physiological barriers (mucus and membrane barrier). Carboxymethyl cellulose and chitosan were modified with phosphotyrosine by means of a water-soluble carbodiimide and polyelectrolyte complexes were formed by mixing two polymer solutions in an appropriate ratio. Due to this modification, phosphate ions could potentially be released which would lead to a change in zeta potential. Their sizes were found to be between 200 and 300nm while their zeta potentials ranged from −8mV to −5mV prior to incubation with the enzyme. It could be shown that phosphate ions are released from the modified polymers and nanoparticles by isolated phosphatase and in a Caco-2 cell model. Incubation with phosphatase led to a change in zeta potential of the nanoparticles up to +8mV. As neither polymers nor particles display toxic properties within the resazurin assay, these nanoparticles appear to be useful tools in future drug delivery systems as they have appropriate properties regarding particle size and surface charge in order to overcome the mucus and the membrane barrier.