Intestinal peptide and protein delivery: novel bioadhesive drug-carrier matrix shielding from enzymatic attack

Journal of Pharmaceutical Sciences
A Bernkop-Schnürch, M Pasta

Abstract

We have been developing a novel bioadhesive drug-carrier matrix that protects embedded therapeutic peptides and proteins from degradation by the most abundant intestinal proteases. Increasing amounts of the Bowman-Birk inhibitor (BBI) were thereby covalently linked to chitosan-EDTA. The bioadhesive properties of the resulting polymer-BBI conjugates and their inhibitory effect toward trypsin (EC 3.4.21.4), chymotrypsin (EC 3.4.21.1), elastase (3.4.21.36), carboxypeptidase A (EC 3.4.17.1), and aminopeptidase N (EC 3.4.11.2) were evaluated in vitro. Whereas unmodified chitosan-EDTA exhibited under our experimental conditions an adhesive strength of 54.4 +/- 7.7 mN, it was determined to be 21.0 +/- 3.8 mN for the comparably most adhesive polymer-BBI conjugate (mean +/- SD; n = 5). All polymer-BBI conjugates showed a strong inhibitory activity toward the serine proteases trypsin and chymotrypsin. However, the protective effect toward elastase was markedly lower. Due to the high binding affinity of chitosan-EDTA toward zinc, which represents an essential cofactor for carboxypeptidase A and aminopeptidase N, all polymer-BBI conjugates displayed additionally a strong protective effect toward these exopeptidases. The novel bioadhesive p...Continue Reading

References

Feb 1, 1985·International Journal of Peptide and Protein Research·Y Birk
Mar 1, 1982·Scandinavian Journal of Gastroenterology·E E McGuinnessK G Wormsley
Jul 1, 1993·The British Journal of Nutrition·Y C Ge, R G Morgan
Feb 1, 1997·Pharmaceutical Research·A Bernkop-Schnürch, M K Marschütz
Apr 1, 1997·Pharmaceutical Research·A LindahlH Lennernäs

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Citations

Mar 1, 2012·Journal of Materials Science. Materials in Medicine·Qingyi MengJiaxiang Wang
Nov 24, 2001·Advanced Drug Delivery Reviews·A Bernkop-Schnürch, C E Kast
Dec 22, 1999·International Journal of Pharmaceutics·A Bernkop-Schnürch
Jan 20, 2004·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Naima ZerroukPaola Mura
Feb 16, 2002·European Journal of Biochemistry·James P TamJin-Long Yang
Nov 10, 2001·Annual Review of Biomedical Engineering·N A PeppasJ Zhang
Jul 27, 2012·Therapeutic Delivery·Colin Thompson, Chidinma Ibie
Mar 4, 2000·Drug Development and Industrial Pharmacy·A Bernkop-SchnürchC Valenta
Sep 11, 2008·Journal of Pharmaceutical Sciences·Martin WerleAndreas Bernkop-Schnürch
Jul 29, 2006·The Journal of Pharmacy and Pharmacology·Shruti ChopraFarhan J Ahmad
Aug 24, 2001·The Journal of Pharmacy and Pharmacology·A K Singla, M Chawla
Sep 28, 2004·The Journal of Pharmacology and Experimental Therapeutics·Noha N SalamaNatalie D Eddington
Feb 14, 2002·Chemical Reviews·A Sood, R Panchagnula
Dec 9, 2004·Chemical Reviews·M N V Ravi KumarA J Domb

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