摘要
AIM: To synthesize dexamethasone-succinate-dextran(DSD) conjugate and to evaluate the potentiality of DSD forthe treatment of inflammatory bowel diseases.METHODS: Dexamethasone was attached to dextran(average molecular weight＝70 400 Dalton) using succinateanhydride in an anhydrous environment catalyzed by 4-dimethylaminopyridine and 1, 1′-carbonyldiimidazole. Thechemical structure of DSD was identified by UV, IR and NMR,and the in vivo drug release behavior of this prodrug wasinvestigated after oral administration of DSD suspension.RESULTS: The DSD conjugate was obtained in two stepsand the content of dexamethasone in DSD was 11.28 %.The dextran prodrug was stable in rat stomach and smallintestine and negligibly absorbed from these tracts. Four tonine hours after the oral administration, most of the prodrug(＞95 %) had moved to the cecum and colon, and was easilyhydrolyzed by an endodextranase. Recover ofdexamethasone from colon and cecum after administrationof DSD conjugate was 6-12 folds higher than the recoveryafter administration of unmodified dexamethasone(t＝2.74,P＜0.05). The preferential release of free dexamethasone incecum and colon over that in the small intestine wasstatistically significant (t＝2.27, P＜0.05).CONCLUSION: The results of this study indicate thatdextran conjugates may be useful in selectively deliveringglucocorticoids to the colon.
AIM:To synthesize dexamethasone-succinate-dextran (DSD)conjugate and to evaluate the potentiality of DSD for the treatment of inflammatory bowel diseases. METHODS:Dexamethasone was attached to dextran (average molecular weight=70 400 Dalton)using succinate anhydride in an anhydrous environment catalyzed by 4- dimethylaminopyridine and 1,1'-carbonyldiimidazole.The chemical structure of DSD was identified by UV,IR and NMR, and the in vivo drug release behavior of this prodrug was investigated after oral administration of DSD suspension. RESULTS:The DSD conjugate was obtained in two steps and the content of dexamethasone in DSD was 11.28%. The dextran prodrug was stable in rat stomach and small intestine and negligibly absorbed from these tracts.Four to nine hours after the oral administration,most of the prodrug (>95%)had moved to the cecum and colon,and was easily hydrolyzed by an endodextranase.Recover of dexamethasone from colon and cecum after administration of DSD conjugate was 6-12 folds higher than the recovery after administration of unmodified dexamethasone(t=2.74, P<0.05).The preferential release of free dexamethasone in cecum and colon over that in the small intestine was statistically significant(t=2.27,P<0.05).CONCLUSION: The results of this study indicate that dextran conjugates may be useful in selectively delivering glucocorticoids to the colon.
基金
the National Distinguished Youth Scientific Fund,No.39925039
