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


CONCLUSIONS
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.
Wang
Guo-Ping
GP
Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China.
Guan
Yong-Song
YS
Jin
Xin-Rong
XR
Jiang
Sha-Sha
SS
Lu
Ze-Jun
ZJ
Wu
Yang
Y
Li
Yang
Y
Li
Mei
M
Luo
Feng
F
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001835:Body Weight; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D003956:Dialysis / Q000379:methods; D004337:Drug Carriers; D004339:Drug Compounding; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008081:Liposomes; D008113:Liver Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D051379:Mice; D009995:Osmosis; D010534:Peritoneal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D005472:Fluorouracil