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KMID : 0369820070370010045
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Jorunal of Korean Pharmaceutical Sciences
2007 Volume.37 No. 1 p.45 ~ p.50
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In vitro Evaluation of Dextran-5-aminosalicylic Acid Conjugate as a Polymeric Colon-specific Prodrug of 5-aminosalicylic Acid
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Jung Yun-Jin
Jeon Hyun-Chu
Choi Dea-kyu
Kim Young-Mi
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Abstract
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Dextran-5-aminosalicylic acid conjugate (dextran-5-ASA) was in vitro-evaluated as a polymeric colon-spe- cific prodrug of 5-aminosalicy lic acid (5-ASA). Chemical stability of dextran-5-ASA in the pH 1.2 or 6.8 buffer solutions was investigated at 37for 6hrs. The dextran backbone was not degraded and no 5-ASA release was detecled. Moreover, dextran-5-ASA neither liberated 5-ASA in the homogenates of the small intestine of rats nor was transported across Caco- 2 cell monolayers, suggesting no significant loss of dextran-5-ASA during transit through the upper intestine. Furthermore, incubation of dextran-5-ASA IN 10% cecal contents of rats released about 37% and 55% of 5-ASA bound to dextran in 8 hr and 24hr, respectively. While that with either esterase or dextranase failed to liberate 5-ASA from the polymeric prodrug, incubation of dextran-5-ASA with both esterases and dextranse released 5-ASA up to about 24% of 5-ASA bound to dex- tran. These results suggest that, after oral administration of dextran-5-ASA, the polymeric prodrug is delivered specifically to and releases 5-ASA in the large intestine, and reveal that the 5-ASA release by cleavage of the ester bond requires pre- cedent depolymerization of the dextran backbone.
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KEYWORD
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Dextran-5-aminosalicylic acid conjugate, Colon-specific prodrug, 5-Aminosalicylic acid, Dextran, Polymeric prodrug, Inflammatory bowel disease
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