DEGRADATION IN VIVO OF CROSS-LINKED HYDROGELS FOR COLONIC-SITE DRUG DELIVERY
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Abstract
AIM To investigate the mechanism of degradation by cecal bacteria of cross-linked hydrogels for colonic-site drug delivery. METHODS Hydrogels that were incubated with cecal bacteria from rats for different time were washed repeatedly in distilled water till complete removal of bacteria. 15% NaOH solutions were added and heated till complete hydrolysis of the gels. The cleavage of azo bonds was monitored with a Lambda spectrophotometer. RESULTS The gels were degradable by ananerobes present in the colon. The rate of degradation was found to be related to the degree of swelling of the gels. The higher the degree of swelling, the higher the rate of degradation. The relation between the rate of degradation and the degree of swelling was attributed to the porosity and pore size of the networks. The lengths of hydrophobic side chains, the degree of cross-linking, the composition of structural units were shown to influence reduction of azo bonds. By changing the composition of structural units, the length of hydrophobic groups, it is possible to adjust the degree of swelling and thereby control the rate of degradation of the gels and the release of drugs. The study on the influence of electron carriers on the rate of degradation not only affirmed the hypothesis of extracellular reduction, but also appeared that there is an intracellular enzymatic component. Electron carriers function as exogeneous electron shuttles between azo compound and enzyme. CONCLUSION The above-mentioned results are of important significance for the development of carriers for the delivery of colon-specific drugs.
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