title: Thiolated chitosans: development and in vitro evaluation of a mucoadhesive, permeation enhancing oral drug delivery system.
abstract: It was the aim of this study to develop a mucoadhesive, permeation enhancing delivery system for orally administered poorly absorbed drugs. Chitosan was modified by the immobilisation of thiol groups utilising 2-iminothiolane (Traut's reagent). The permeation enhancing effect of the resulting chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) in combination with the permeation mediator glutathione (GSH) was evaluated in Ussing chambers on freshly excised small intestinal mucosa from guinea pigs using rhodamine 123 as marker for passive drug uptake. The mucoadhesive properties of the chitosan-TBA conjugate adjusted to pH 3, 5 and 7 were evaluated via the rotating cylinder method and via tensile studies. Release studies were performed with tablets comprising 10% cefadroxil used as model drug, 10% GSH and 80% chitosan-TBA conjugate pH 3 in 100 mM phosphate buffer pH 6.8 at 37 degrees C. Results showed a 3-fold higher permeation enhancing effect of the chitosan-TBA conjugate/GSH system in comparison to unmodified chitosan. Mucoadhesion studies revealed that the lower the pH of the thiolated chitosan is, the higher are its mucoadhesive properties. Release studies showed a sustained release of both cefadroxil and GSH over several hours. This delivery system might represent a promising novel tool in order to improve the therapeutic efficacy of various drugs which are poorly absorbed from the gastrointestinal tract.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens University Innsbruck, Innrain 52, Jösef Möller Haus, A-6020 Innsbruck, Austria. andreas.bernkop@uibk.ac.at
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
authors.forename: Davide
authors.initials: D
authors.lastname: Guggi
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Pinter
mesh_terms: D000269:Adhesives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D048271:Chitosan; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D006168:Guinea Pigs; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000269:Adhesives; D013438:Sulfhydryl Compounds; D002686:Chitin; D048271:Chitosan