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Dextran hydrogels for colon-specific drug delivery. V. Degradation in human intestinal incubation models

1995; Elsevier BV; Volume: 3; Issue: 6 Linguagem: Inglês

10.1016/0928-0987(95)00023-6

1879-0720

Lene Simonsen, Lars Hovgaard, Preben Bo Mortensen, H.V. BRØNDSTED,

Digestive system and related health

In the present study degradation of dextran hydrogels, potential drug carriers for colon-specific drug delivery, was studied in simulated small intestinal juices as well as in a human colonic fermentation model. Dextran hydrogels were shown to be stable when incubated at 37°C with the small intestinal enzymes amyloglucosidase, invertase and pancreatin. After a 24 h incubation, less than 3.3% of free glucose was released. However, the hydrogels were still intact as measured by the dry weight remaining. The fermentation of dextran hydrogels and several mono- and polysaccharides to short-chain fatty acids (SCFA) was investigated after anaerobic incubation in a human colonic fermentation model at 37°C for 0–72 h. In addition, the dextranase activity of the incubations was determined. The amounts and ratios of SCFA formed varied considerably in relation to the type of substrate fermented (glucose, maize starch, potato starch, cellulose, soluble dextran and dextran hydrogels). Detailed SCFA analysis demonstrated that fermentable saccharides resulted in an increased SCFA production, in contrast to the metabolic inert polysaccharide, cellulose. The hydrogels were found to be completely degraded in the human colonic fermentation model. An increased crosslinking density or a decreased degree of hydration resulted in a lower degradability. The pH of the incubations were found to be inversely proportional to the SCFA production as a result of the increased acid formation.