title: Intestinal peptide and protein delivery: novel bioadhesive drug-carrier matrix shielding from enzymatic attack.
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 polymer-BBI conjugates described in this study seem to be very useful drug-carrier matrixes in overcoming the enzymatic barrier to orally administered peptide and protein drugs.
authors.affiliation: The Center of Pharmacy, Institute of Pharmaceutical Technology, University of Vienna, Austria. andreas.bernkop-schnuerch@univie.ac.at
authors.forename: A
authors.initials: A
authors.lastname: Bernkop-Schnürch
authors.forename: M
authors.initials: M
authors.lastname: Pasta
mesh_terms: D000269:Adhesives / Q000737:chemistry; D002686:Chitin / Q000031:analogs & derivatives / Q000737:chemistry; D048271:Chitosan; D004492:Edetic Acid / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000201:enzymology; D010455:Peptides / Q000008:administration & dosage*; D011108:Polymers; D011506:Proteins / Q000008:administration & dosage*; D013718:Tensile Strength; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000269:Adhesives; D010455:Peptides; D011108:Polymers; D011506:Proteins; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D002686:Chitin; D048271:Chitosan; D004492:Edetic Acid