title: Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation.
abstract: The aim of the present study was to evaluate the influence of the degree of modification and the polymer chain length on the mucoadhesive properties and the swelling behavior of thiolated chitosan derivatives obtained via a simple one-step reaction between the polymer and 2-iminothiolane. The conjugates differing in molecular mass of the polymer backbone and in the amount of immobilized thiol groups were compressed into tablets. They were investigated for their mucoadhesive properties on freshly excised porcine mucosa via tensile studies and the rotating cylinder method. Moreover, the swelling behavior of these tablets in aqueous solutions was studied by a simple gravimetric method. The obtained results demonstrated that the total work of adhesion of chitosan-TBA (=4-thio-butyl-amidine) conjugates can be improved by an increasing number of covalently attached thiol groups; a 100-fold increase compared to unmodified chitosan was observed for a medium molecular mass chitosan-TBA conjugate exhibiting 264 microM thiol groups per gram polymer. Also, the polymer chain length had an influence on the mucoadhesive properties of the polymer. The medium molecular mass polymer displayed a fourfold improved adhesion on the rotating cylinder compared to the derivative of low molecular mass. These results contribute to the development of new delivery systems exhibiting improved mucoadhesive properties.
authors.affiliation: Institute of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
authors.forename: Marta
authors.initials: M
authors.lastname: Roldo
authors.forename: Margit
authors.initials: M
authors.lastname: Hornof
authors.forename: Paolo
authors.initials: P
authors.lastname: Caliceti
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000269:Adhesives / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D000284:Administration, Oral; D000578:Amidines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D002197:Capillary Action; D048271:Chitosan / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007096:Imidoesters / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D009077:Mucins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000008:administration & dosage* / Q000138:chemical synthesis* / Q000737:chemistry; D013552:Swine; D013607:Tablets; D013718:Tensile Strength; D014867:Water / Q000378:metabolism
chemical_list: D000269:Adhesives; D000578:Amidines; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D007096:Imidoesters; D009077:Mucins; D011108:Polymers; D013438:Sulfhydryl Compounds; D013607:Tablets; D014867:Water; C005905:methyl 4-mercaptobutyrimidate; D048271:Chitosan