Comparative in vitro study of different chitosan-complexing agent conjugates

In this study we analysed the bioadhesive properties and the enzyme inhibit ory effects of different chitosan-complexing agent conjugates. Etylenediami netetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA), re spectively, were covalently attached to chitosan by the formation of amide bonds between the primary amino group of the polymer and the carboxylic aci d 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 ami no 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 t o the chitosan-EDTA conjugate with 81.7 +/- 9.9 mN in the tensil studies de scribed 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 compar ative study should provide substantial knowledge for the development of bio adhesive polymers as auxiliary agents for the peroral administration of pep tide and protein drugs.