title: Natural dendrimers: Synthesis and in vitro characterization of glycogen-cysteamine conjugates.
abstract: The aim of this study was to synthesize, characterize and evaluate the mucoadhesive properties of the first thiolated hyperbranched natural polysaccharide with biodegradability and biocompatibility features. In detail, glycogen-cysteamine conjugates were synthesized through a first step of oxidative ring opening applying increasing concentrations of sodium periodate, to obtain polymers with different degrees of oxidation, and a second step of reductive amination with a constant amount of cysteamine. The obtained glycogen-cysteamine conjugates were characterized regarding their content of free and total thiol groups by Ellman's assay, biocompatibility, swelling/erosion behavior, rheological synergism and mucoadhesive properties in comparison to the unmodified glycogen. The higher the concentration of periodate was, the higher was the content of total thiol groups being in the range of 255.7±12-1194.5±82μmol/g, biocompatibility remained unaffected by these structural changes. On the contrary, the mucoadhesive properties, evaluated by tensile, rheological synergism and rotating cylinder studies, appear to be influenced by the thiol groups concentration on the glycogen. In particular the glycogen-cysteamine conjugate exhibiting the highest degree of thiolation showed a 79-fold increase in viscosity over a time period of 8h, as well as, remained attached on freshly excised porcine mucosa 32-fold longer than the unmodified polymer. The higher was the amount of conjugated thiol groups, the higher was the water absorption capacity of glycogen-cysteamine tablets in Simulated Intestinal Fluid pH 6.8 (SIF). The introduction of thiol moieties on polymer changed the characteristics of the polysaccharide by improving mucoadhesion properties. Therefore, this work represents the first study describing thiolated natural dendrimers as potential platform useful to realize appropriate mucoadhesive nanocarrier systems suitable to prolong mucosal residence time.
authors.affiliation: Department of Pharmacy - Drug Sciences, University of Bari "Aldo Moro", Bari, Italy; Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Mara
authors.initials: M
authors.lastname: Perrone
authors.affiliation: Department of Pharmacy - Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Lopedota
authors.affiliation: ACRAF Angelini Research Centre, Pomezia, RM, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Liberati
authors.affiliation: ACRAF Angelini Research Centre, Pomezia, RM, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
authors.affiliation: Department of Pharmacy - Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Cutrignelli
authors.affiliation: Department of Pharmacy - Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Valentino
authors.initials: V
authors.lastname: Laquintana
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria.
authors.forename: Irene Pereira
authors.initials: IP
authors.lastname: de Sousa
authors.affiliation: Department of Pharmacy - Drug Sciences, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Franco
authors.affiliation: ACRAF Angelini Research Centre, Pomezia, RM, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Tongiani
authors.affiliation: Department of Pharmacy - Drug Sciences, University of Bari "Aldo Moro", Bari, Italy. Electronic address: nunzio.denora@uniba.it.
authors.forename: Nunzio
authors.initials: N
authors.lastname: Denora
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University of Innsbruck, Innsbruck, Austria. Electronic address: Andreas.Bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000269:Adhesives / Q000737:chemistry; D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D003543:Cysteamine / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006003:Glycogen / Q000737:chemistry*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D010084:Oxidation-Reduction; D011108:Polymers / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D012212:Rheology; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013552:Swine; D013607:Tablets / Q000737:chemistry; D014783:Viscosity
chemical_list: D000269:Adhesives; D050091:Dendrimers; D004337:Drug Carriers; D011108:Polymers; D011134:Polysaccharides; D013438:Sulfhydryl Compounds; D013607:Tablets; D003543:Cysteamine; D006003:Glycogen
keywords: Glycogen; Mucoadhesion; Rheology; Swelling studies; Tensile studies; Thiomer