title: Comparative in vitro study of different chitosan-complexing agent conjugates.
abstract: In this study we analysed the bioadhesive properties and the enzyme inhibitory effects of different chitosan-complexing agent conjugates. Etylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA), respectively, were covalently attached to chitosan by the formation of amide bonds between the primary amino group of the polymer and the carboxylic acid groups of the complexing agents. Whereas almost each primary amino groups of chitosan could be modified by EDTA, DTPA was bound to only 63.8 +/- 5.8% (n = 3; +/- SD) of the amino groups of chitosan. The remaining primary amino groups of the chitosan-DTPA conjugate lead to strongly reduced adhesive properties, with a maximum detachment force of 3.0 +/- 1.3 mN in contrast to the chitosan-EDTA conjugate with 81.7 +/- 9.9 mN in the tensil studies described here (n = 4; +/- SD). However, both polymer conjugates displayed an inhibitory effect towards the zinc-dependent proteases carboxypeptidase A (EC 3.4.17.1) and aminopeptidase N (EC 3.4.11.2). The results of this comparative study should provide substantial knowledge for the development of bioadhesive polymers as auxiliary agents for the peroral administration of peptide and protein drugs.
authors.affiliation: Center of Pharmacy, University of Vienna, Austria. andreas.bernkop-schnuerch@univie.ac.at
authors.forename: A
authors.initials: A
authors.lastname: Bernkop-Schnürch
authors.forename: J
authors.initials: J
authors.lastname: Freudl
mesh_terms: D000818:Animals; D018826:CD13 Antigens / Q000037:antagonists & inhibitors; D002240:Carbohydrate Sequence; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D043422:Carboxypeptidases A; D002614:Chelating Agents / Q000737:chemistry; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan; D004492:Edetic Acid / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D004369:Pentetic Acid / Q000737:chemistry; D013329:Structure-Activity Relationship; D013552:Swine; D014014:Tissue Adhesives / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: D002614:Chelating Agents; D004791:Enzyme Inhibitors; D014014:Tissue Adhesives; D002686:Chitin; D004369:Pentetic Acid; D048271:Chitosan; D004492:Edetic Acid; D002268:Carboxypeptidases; D018826:CD13 Antigens; D043422:Carboxypeptidases A