title: S-protected thiolated chitosan: synthesis and in vitro characterization.
abstract: Purpose of the present study was the generation and evaluation of novel thiolated chitosans, so-named S-protected thiolated chitosans as mucosal drug delivery systems. Stability of all conjugates concerning swelling and disintegration behavior as well as drug release was examined. Mucoadhesive properties were evaluated in vitro on intestinal mucosa. Different thiolated chitosans were generated displaying increasing amounts of attached free thiol groups on the polymer, whereby more than 50% of these thiol groups were linked with 6-mercaptonicotinamide. Based on the implementation of this hydrophobic residue, the swelling behavior was 2-fold decreased, whereas stability was essentially improved. Their mucoadhesive properties were 2- and 14-fold increased compared to corresponding thiolated and unmodified chitosans, respectively. Release studies out of matrix tablets comprising the novel conjugates revealed a controlled release of a model peptide. Accordingly, S-protected thiomers represent a promising type of mucoadhesive polymers for the development of various mucosal drug delivery systems.
authors: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzenz-University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors: Sarah
authors: S
authors: Dünnhaupt
authors: Jan
authors: J
authors: Barthelmes
authors: Clemens C
authors: CC
authors: Thurner
authors: Claudia
authors: C
authors: Waldner
authors: Duangkamon
authors: D
authors: Sakloetsakun
authors: Andreas
authors: A
authors: Bernkop-Schnürch
mesh_terms: D018938:Caco-2 Cells; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D005300:Fertility Agents, Female / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000493:pharmacokinetics; D008954:Models, Biological; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013607:Tablets; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D005300:Fertility Agents, Female; D013438:Sulfhydryl Compounds; D013607:Tablets; D014867:Water; D048271:Chitosan; D016729:Leuprolide