Development of novel 5-fluorouracil carrier erythrocyte with pharmacokinetics and potent antitumor activity in mice bearing malignant ascites.

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.

• Authors: Guo-Ping Wang, Yong-Song Guan, Xin-Rong Jin, Sha-Sha Jiang, Ze-Jun Lu, Yang Wu, Yang Li, Mei Li, Feng Luo
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 25 Issue 5 Pg. 985-90 (May 2010) ISSN: 1440-1746 [Electronic] Australia
• PMID: 20546454 (Publication Type: Journal Article)

Chemical References

• Antimetabolites, Antineoplastic
• Drug Carriers
• Liposomes
• Fluorouracil

Topics

• Animals
• Antimetabolites, Antineoplastic (administration & dosage, blood, pharmacokinetics, pharmacology)
• Body Weight
• Cell Line, Tumor
• Chromatography, High Pressure Liquid
• Chromatography, Reverse-Phase
• Dialysis (methods)
• Drug Carriers
• Drug Compounding
• Erythrocyte Transfusion
• Erythrocytes (metabolism)
• Female
• Fluorouracil (administration & dosage, blood, pharmacokinetics, pharmacology)
• Injections, Intraperitoneal
• Liposomes
• Liver Neoplasms (blood, drug therapy, secondary)
• Mice
• Osmosis
• Peritoneal Neoplasms (blood, drug therapy, secondary)
• Time Factors