caa a22 4500 477126286 CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970701xx s 000 0 eng 10.1023/A:1012108118670 doi (NATIONALLICENCE)springer-10.1023/A:1012108118670 Novel Bioadhesive Chitosan-EDTA Conjugate Protects Leucine Enkephalin from Degradation by Aminopeptidase N [Elektronische Daten] [Andreas Bernkop-Schnürch, Christina Paikl, Claudia Valenta] Purpose. To develop a novel bioadhesive polymer that protects peptide drugs from luminal degradation by aminopeptidase N and to evaluate the system in vitro on porcine mucosa. Methods. EDTA was covalently bound to chitosan in order to combine the bioadhesive properties of the polymer with the well known capacity of EDTA to complexe metal ions which are essential for the enzymatic activity of proteases. The inhibitory effect of this polymer conjugate was evaluated by using leucine enkephalin (Leu enkephalin) as a model drug. The degree of Leu enkephalin degradation caused by aminopeptidase N (EC 3.4.11.2), as well as porcine mucosa, in the presence of the polymer conjugate, was quantified by HPLC analysis. Results. The chitosan-EDTA conjugate is capable of binding 2.01 ± 0.12 mmole of zinc per gram of polymer at pH 6.5 (n = 3; ± S.D.). As zinc is an essential co-factor for aminopeptidase N, enzyme activity (48 mU/ml) could be completely inhibited under the use of 1.0% chitosan-EDTA conjugate. The inhibitory effect of 1.0% chitosan-EDTA conjugate on the degradation of Leu enkephalin on porcine mucosa within 3 h at 37°C was even 2.9-fold higher than that of a recently developed zinc complexing bacitracin-poly(acrylic acid) conjugate of the same concentration. The novel polymer conjugate is more bioadhesive than unmodified chitosan and is easily hydratable in water and basic aqueous solutions exhibiting quick swelling properties. Conclusions. The bioadhesive polymer conjugate described here seems to be a useful tool in overcoming enzymatic degradation by aminopeptidase N. Plenum Publishing Corporation, 1997 inhibition of aminopeptidase N nationallicence chitosan nationallicence EDTA nationallicence Leucine enkephalin nationallicence brush border membrane bound enzymes nationallicence Bernkop-Schnürch Andreas Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria/Europe aut Paikl Christina Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria/Europe aut Valenta Claudia Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria/Europe aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 917-922 0724-8741 14:7<917 1997 14 11095 https://doi.org/10.1023/A:1012108118670 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012108118670 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bernkop-Schnürch Andreas Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria/Europe aut NATIONALLICENCE 700 1- Paikl Christina Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria/Europe aut NATIONALLICENCE 700 1- Valenta Claudia Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria/Europe aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/7(1997-07-01), 917-922 0724-8741 14:7<917 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer