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- W2076374009 abstract "The oral bioavailability of salmon calcitonin is strongly reduced due to the enzymatic degradation by luminally secreted serine proteases. Apart from being degraded by trypsin (EC 3.4.21.4) and chymotrypsin (EC 3.4.21.1), it was shown in this study that calcitonin is also digested by elastase (EC 3.4.21.36). It was therefore the aim of this study to generate polymeric excipients protecting perorally administered salmon calcitonin from degradation by these enzymes. Mediated by a carbodiimide trypsin and chymotrypsin inhibitor Bowman-Birk inhibitor (BBI) and elastase inhibitor elastatinal were each covalently attached to the mucoadhesive polymer chitosan. The share of the Bowman-Birk inhibitor in the resulting conjugate was 3.5+/-0.1% (w/w, mean+/-S.D., n=4) and that of elastatinal 0.5+/-0.03% (w/w, mean+/-S.D., n=4). Enzyme assays with synthetic substrates demonstrated a strong inhibitory effect of the chitosan-BBI conjugate towards trypsin and chymotrypsin as well as of the chitosan-elastatinal conjugate towards elastase. In an artificial intestinal fluid containing physiological concentrations of trypsin, alpha-chymotrypsin and elastase, calcitonin being incorporated in unmodified chitosan (0.5%, w/v) was degraded by 99.7+/-0.1% (mean+/-S.D., n=3) within 2h at 37 degrees C. On the contrary, incorporating the drug in chitosan-BBI conjugate and chitosan-elastatinal conjugate (1+1, 0.5%, w/v) led to a degradation of only 36.4+/-0.9% (mean+/-S.D., n=3). Hence, the chitosan-inhibitor conjugates described in this study seem to be promising tools for the oral delivery of salmon calcitonin." @default.
- W2076374009 created "2016-06-24" @default.
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- W2076374009 date "2003-02-18" @default.
- W2076374009 modified "2023-10-12" @default.
- W2076374009 title "In vitro evaluation of polymeric excipients protecting calcitonin against degradation by intestinal serine proteases" @default.
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- W2076374009 doi "https://doi.org/10.1016/s0378-5173(02)00631-2" @default.
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