title: Enzymatic biodegradation of hydrogels for protein delivery targeted to the small intestine.
abstract: Multiresponsive poly(methacrylic acid-co-N-vinylpyrrolidone) hydrogels were synthesized with biodegradable oligopeptide crosslinks. The oligopeptide crosslinks were incorporated using EDC-NHS zero-length links between the carboxylic acid groups of the polymer and free primary amines on the peptide. The reaction of the peptide was confirmed by primary amine assay and IR spectroscopy. The microgels exhibited pH-responsive swelling as well as enzyme-catalyzed degradation targeted by trypsin present in the small intestine, as demonstrated upon incubation with gastrointestinal fluids from rats. Relative turbidity was used to evaluate enzyme-catalyzed degradation as a function of time, and initial trypsin concentration controlled both the degradation mechanism as well as the extent of degradation. Trypsin activity was effectively extinguished by incubation at 70 °C, and both the microgels and degradation products posed no cytotoxic effect toward two different cell lines. The microgels demonstrated pH-dependent loading of the protein insulin for oral delivery to the small intestine.
authors: Department of Chemical Engineering, C0400, ‡Department of Biomedical Engineering, C0800, §College of Pharmacy, A1900, and #Institute for Biomaterials, Drug Delivery and Regenerative Medicine, C0800, The University of Texas at Austin , Austin, Texas 78712, United States.
authors: Jennifer M
authors: JM
authors: Knipe
authors: Frances
authors: F
authors: Chen
authors: Nicholas A
authors: NA
authors: Peppas
mesh_terms: D000818:Animals; D055162:Biocatalysis; D002460:Cell Line; D003692:Delayed-Action Preparations / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000737:chemistry*; D007421:Intestine, Small; D051379:Mice; D009842:Oligopeptides / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry*; D059748:Proteolysis; D051381:Rats; D014357:Trypsin / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D007328:Insulin; D009842:Oligopeptides; D011109:Polymethacrylic Acids; D014357:Trypsin