ENZYME INHIBITION
Many non-invasively administered drugs such as therapeutic peptides or nucleic
acids are degraded on the mucosa by membrane bound enzymes strongly reducing
their bioavailability. In case of oral administration this ‘enzymatic
barrier’ is even more pronounced as an additional degradation caused by
luminally secreted enzymes takes place. Because of their capability to bind
Zn2+ ions via thiol groups, thiomers are potent inhibitors of most membrane
bound and secreted zinc-dependent enzymes. Due to this enzyme inhbitory effect, thiomers can sginificantly improve the bioavailability of non-invasively administered drugs.
Degradation of the peptide
drug leu-enkephalin by aminopeptidase N. Click on the graph to see the
improved drug stability in the presence of 0.5% thiomer. [Bernkop-Schnürch, A., Zarti, H., and Walker,
G.F. (2001) Thiolation of polycarbophil enhances its inhibition of soluble
and intestinal brush border membrane bound aminopeptidase N. J. Pharm. Sci., 90, 1907-1914].
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Hydrolysis of the substrate
hippuryl-L-phenylalanine (HPA) to L-phenylalanine (PA) and hippuric acid by
carboxypeptidase A. Click on the graph to
see the improved drug stability in the presence of 0.125% thiomer. [Bernkop-Schnürch, A. and Thaler, S.
(2000). Polycarbophil-cysteine conjugates as platforms for oral (poly)peptide
delivery systems. J. Pharm. Sci., 89, 901-909] |
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