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  • Title: Development of novel 5-fluorouracil carrier erythrocyte with pharmacokinetics and potent antitumor activity in mice bearing malignant ascites.
    Author: Wang GP, Guan YS, Jin XR, Jiang SS, Lu ZJ, Wu Y, Li Y, Li M, Luo F.
    Journal: J Gastroenterol Hepatol; 2010 May; 25(5):985-90. PubMed ID: 20546454.
    Abstract:
    BACKGROUND: To investigate pharmacokinetics and potency of antitumor activity of a novel 5-fluorouracil carrier erythrocyte (RBC-FU) in mice bearing malignant ascites. METHODS: RBC-FU was synthesized with a hyperosmotic technique. The entrapment efficiency of targeted carrier erythrocytes was determined by reverse dialysis method with high-performance liquid chromatography (HPLC) for analyzing the quantity of 5-fluorouracil (5-FU). After a H22 hepatocarcinoma malignant ascites model was established in Kunming mice, 5-FU encapsulated by carrier erythrocytes (for Group A) and 5-FU solution (for Group B) at 20 mg per kg were injected into the peritoneal cavity of the mice, respectively. Blood and ascites samples were collected at different times to detect 5-FU quantity by HPLC. Body weight and survival time of mice were recorded in Group A, B and the Control Group in which mice were injected with normal saline only. RESULTS: 5-FU was effectively encapsulated into erythrocytes, with an encapsulating effect as 55 +/- 0.50%. In Group A, the maximum concentration (Cmax) and the area under curve (AUC) in peritoneal exudates were significantly higher than those of Group B (P < 0.05). On the other hand, 5-FU level in serum was significantly lower than that in peritoneal exudates of Group A and B (P < 0.05). High drug levels in the abdominal cavity in Group A were maintained longer than those in Group B. Compared with that in Group B and the control, the quantity of malignant ascites in Group A had significant regression and the survival time was prolonged. CONCLUSION: The hyperosmotic method described here could be suitable for producing this novel RBC-FU as a liposomal drug of potential value for treating malignant ascites by intraperitoneal administration.
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