Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 97, Issue -, Pages 250-256Publisher
ELSEVIER
DOI: 10.1016/j.ejpb.2015.01.017
Keywords
Mucus; Nanoparticles; Zeta potential; Intestinal alkaline phosphatase; Phosphotyrosine; Intestinal barriers
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Funding
- European Community's Seventh Framework Programme (FP7) [280761]
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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. (C) 2015 Elsevier B.V. All rights reserved.
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