RESUMO
AIM:To explore the therapeutic effect of dexamethasone Angelica sinensis polysaccharide prodrug(DEX-AP) on trinitrobenzene sulfonic acid(TNBS) induced ulcerative colitis(UC) in rats and its side effects.METHODS: The experimental UC rats were induced by clusis of the solution of TNBS in 45% alcoho1(50(mg?ml~(-1))).The UC rats were orally administrated with(0.25)(?mol?kg~(-1)?d~(-1)) DEX and(0.05),(0.25),(1.25)(?mol?kg~(-1)?d~(-1)) DEX-AP(calculated by carried DEX in DEX-AP) for 7 days,respectively.The rats were killed after the amount of peripheral blood lymphocyte was counted,then the spleen,thymus and colon were separated and weighted.After the ulcerative area of colon was calculated,the colonic myeloperoxidase(MPO) activity was determined and parts of colon were paraffin sectioned and examined under light microscope by HE stain.RESULTS: After the UC rats were administrated with different doses of DEX-AP for 7 days,the ulcerative area,the weight and the MPO activity of colon reduced significantly.The reduction of MPO activity was correlated to the dose of DEX-AP and the MPO activity with DEX-AP at the doses of(0.25),(1.25)(?mol?kg~(-1)?d~(-1)) reduced more significantly than that with DEX at the the dose of(0.25)(?mol?kg~(-1)?d~(-1)).The number of peripheral blood lymphocyte,spleen weight and thymus weight of UC rats reduced significantly at the dose of(0.25)(?mol?kg~(-1)?d~(-1)) DEX(P
RESUMO
AIM: To explore the transport and delivery of active drug from dexamethasone-angelica sinensis polysaccharides prodrug in the gastrointestinal tract of rats. METHODS: Dexamethasone and the prodrug were orally administered to rats at the dose of 1.96 mg?kg~ -1 (calculated by carried dexamethasone). The drugs in the plasma and contents of different parts of the rats' gastrointestinal tract were determined by high performance liquid chromatography (HPLC). RESULTS: Dexamethasone carried by the prodrug was mainly released in the contents and mucosa of cecum and colon after oral administration of the prodrug. The absorption of released dexamethasone was reduced significantly. The peak time, peak concentration and AUC were 7.2 h , 42 ?g?L~ -1 and 334 ?g?h?L~ -1 , respectively. However, free dexamethasone was found mainly in the contents and mucosa of the stomach, proximal and distal small intestine after oral administration. The peak time, peak concentration and AUC were 2.2 h, 2 120 ?g?L~ -1 and 11 875 ?g?h?L~ -1 , respectively. CONCLUSION: Dexamethasone can be specifically delivered to the cecum and colon by using dexamethasone- angelica sinensis polysaccharides prodrug. The absorption of dexamethasone was reduced significantly and the drug concentration in colon was increased significantly. The prodrug has a potential in the treatment of colitis.