title: Thiomers: preparation and in vitro evaluation of a mucoadhesive nanoparticulate drug delivery system.
abstract: It was the aim of this study to develop a mucoadhesive nanoparticulate delivery system. Nanoparticles were generated by in situ gellation of the thiomer chitosan-4-thiobutylamidine (chitosan-TBA) with tripolyphosphate (TPP) followed by stabilization via the formation of inter- and intrachain disulfide bonds by oxidation with H(2)O(2) in various concentrations. Afterwards TPP was removed by exhaustive dialysis at pH 1-2. Incorporation of the model compound fluorescein diacetate (FDA) was achieved by incubation of this fluorescence marker, dissolved in acetonitrile, with aqueous particle suspensions for 1h at room temperature. Mucoadhesion studies were performed on porcine intestinal mucosa. Results showed that the preparation method described above leads to nanoparticles of a mean diameter of 268+/-15 nm and a FDA load of 2%. Due to the removal of the anionic crosslinker TPP, the zeta potential of the nanoparticles was raised from 4+/-1 up to 19+/-2 mV without loosing stability of the nanoparticles. The more H(2)O(2) was added to the particles, the more inter- and intrachain disulfide bonds were formed. The more thiol groups were oxidized within the particles, however, the lower was the improvement in mucoadhesive properties. Nevertheless, even when 91% of all thiol groups on the nanoparticles were oxidized, their mucoadhesive properties were still twice as high as the mucoadhesive properties of unmodified nanoparticles. Thiolated chitosan nanoparticles show a two-fold higher zeta potential (I), improved stability (II) and more than doubled mucoadhesive properties (III) than corresponding unmodified chitosan nanoparticles. Therefore, they seem to be advantageous over ionically crosslinked chitosan nanoparticles.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef-Möller-Haus, 6020 Innsbruck, Austria. andreas.bernkop@uibk.ac.at
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
authors.forename: Andrea
authors.initials: A
authors.lastname: Weithaler
authors.forename: Karin
authors.initials: K
authors.lastname: Albrecht
authors.forename: Alexander
authors.initials: A
authors.lastname: Greimel
mesh_terms: D000268:Adhesiveness; D000818:Animals; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D004220:Disulfides / Q000032:analysis / Q000737:chemistry; D016503:Drug Delivery Systems; D005452:Fluoresceins / Q000008:administration & dosage; D006861:Hydrogen Peroxide / Q000737:chemistry; D007413:Intestinal Mucosa / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction; D011122:Polyphosphates / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000032:analysis / Q000737:chemistry; D013552:Swine
chemical_list: D004220:Disulfides; D005452:Fluoresceins; D011122:Polyphosphates; D013438:Sulfhydryl Compounds; C493042:chitosan-4-thiobutylamidine; D002686:Chitin; D006861:Hydrogen Peroxide; C005692:triphosphoric acid; C018506:diacetylfluorescein