title: Development of phosphorylated nanoparticles as zeta potential inverting systems.
abstract: 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 300 nm while their zeta potentials ranged from -8 mV to -5 mV 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 +8 mV. 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.
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Center for Chemistry and Biomedicine, Innsbruck, Austria.
authors: Glen
authors: G
authors: Perera
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Center for Chemistry and Biomedicine, Innsbruck, Austria.
authors: Maximilian
authors: M
authors: Zipser
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Center for Chemistry and Biomedicine, Innsbruck, Austria.
authors: Sonja
authors: S
authors: Bonengel
authors: Institute of Zoology, University of Innsbruck, Innsbruck, Austria.
authors: Willi
authors: W
authors: Salvenmoser
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Center for Chemistry and Biomedicine, Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
authors: Andreas
authors: A
authors: Bernkop-Schnürch
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D018938:Caco-2 Cells; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D053758:Nanoparticles; D010316:Particle Size; D010710:Phosphates / Q000737:chemistry; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*
chemical_list: D010710:Phosphates; D011108:Polymers; D019000:Phosphotyrosine; D048271:Chitosan; D000469:Alkaline Phosphatase; D002266:Carboxymethylcellulose Sodium
keywords: Intestinal alkaline phosphatase; Intestinal barriers; Mucus; Nanoparticles; Phosphotyrosine; Zeta potential