title: Development of Cetylpyridinium-Alginate Nanoparticles: A Binding and Formulation Study.
abstract: In this study the development of stable polyelectrolyte-surfactant complex nanoparticles composed of alginate and cetylpyridinium chloride (CPC), with and without ZnCl2, for therapeutic use, is investigated. The mechanism of CPC binding by alginate was analyzed using a cetylpyridinium cation (CP(+)) selective membrane electrode. The cooperative nature of the interaction between CP(+) and alginate was underlined by the sigmoidal shape of the binding isotherms. The presence of salts was shown to weaken interactions and, moreover, ZnCl2 reduced the cooperativity of binding. The CP(+) cations in the form of micellar associates acted as multivalent crosslinkers of the alginate chains where stable dispersions of CP-alginate nanoparticles were formed in water at CP(+)/alginate charge ratios from 0.2 to 0.8. Characterization of the nanoparticles showed hydrodynamic diameters from 140 to 200nm, a polydispersity index below 0.2, a negative zeta potential and spherical morphology. The entrapment efficiency of CPC was ∼94%, the loading capacity more than 50% and prolonged release over 7days were shown. The formulations with noted charge ratios resulted in stable CP-alginate nanoparticles with a potential of treating periodontal disease.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
authors.forename: Janja
authors.initials: J
authors.lastname: Mirtič
authors.affiliation: Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
authors.forename: Ksenija
authors.initials: K
authors.lastname: Kogej
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia.
authors.forename: Saša
authors.initials: S
authors.lastname: Baumgartner
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway.
authors.forename: Gro
authors.initials: G
authors.lastname: Smistad
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000 Ljubljana, Slovenia. Electronic address: julijana.kristl@ffa.uni-lj.si.
authors.forename: Julijana
authors.initials: J
authors.lastname: Kristl
authors.affiliation: School of Pharmacy, University of Oslo, P.O. Box 1068, Blindern, 0316 Oslo, Norway. Electronic address: marianne.hiorth@farmasi.uio.no.
authors.forename: Marianne
authors.initials: M
authors.lastname: Hiorth
mesh_terms: D000464:Alginates / Q000737:chemistry*; D002594:Cetylpyridinium / Q000737:chemistry / Q000493:pharmacokinetics*; D002712:Chlorides / Q000737:chemistry; D065546:Drug Liberation; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D017967:Zinc Compounds / Q000737:chemistry
chemical_list: D000464:Alginates; D002712:Chlorides; D006603:Hexuronic Acids; D008823:Micelles; D017967:Zinc Compounds; C016837:zinc chloride; D020723:Glucuronic Acid; D002594:Cetylpyridinium
keywords: Drug delivery; antiseptics; critical association concentration; micelles; periodontal disease; polyelectrolyte complexes