[Nanoliposomal quercetin inhibits formation of malignant ascites of hepatocellular carcinoma].
OBJECTIVE
Quercetin is a potential chemotherapeutic drug with many biological activities. However, the insolubility of quercetin seriously limits its clinical use. This study was to investigate the biodistribution of quercetin encapsulated by pegylated nanoliposomes and its therapeutic efficacy on the formation of carcinomatous ascites of hepatocellular carcinoma in mice.


METHODS
Nanoliposomal quercetin was prepared with conventional rotary evaporation method. BALB/c mice inoculated with hepatocellular carcinoma cells (H22) at the anterior right subaxilla for twelve days were given intravascular injection with nanoliposomal quercetin at 1.5 mg/body (based on quercetin) at different time points. Then the levels of quercetin in the plasma, tumor tissues and normal organs were tested by high pressure liquid chromatography (HPLC). Various dosages of nanoliposomal quercetin were peritoneally given to tumor-bearing mice to determine the optimal dose. The tumor-bearing mice were treated intraperitoneally with 100 mg/kg nanoliposomal quercetin once a day for 14 days. The formation of malignant ascites, increase of body weight, survival time and peritoneal capillary permeability were assessed. Apoptotic cells in ascites were detected by flow cytometry.


RESULTS
Nanoliposomal quercetin was a spherical particle with 25% drug content (W/W) and 130+/-20 nm in diameter. Nanoliposomal quercetin effectively aggregated in tumor tissues and its half-life period was 4 h. Nanoliposome quercetin inhibited the formation of malignant ascites of hepatocellular carcinoma model in a dose-dependent manner. Moreover, 100 mg/kg nanoliposomal quercetin significantly enhanced the apoptosis of cancer cells in ascites, inhibited the increase of body weight, reduced peritoneal capillary permeability and prolonged the survival time of tumor-bearing mice compared with PBS control.


CONCLUSIONS
Nanoliposomal quercetin can effectively accumulate in tumor tissues and inhibit the formation of malignant ascites, thus it might be used as a potential antitumor drug which deserves future study.
Yuan
Zhi-Ping
ZP
State Key Laboratory of Biotherapy West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Chen
Li-Juan
LJ
Wei
Yu-Quan
YQ
Fan
Lin-Yu
LY
Tang
Ming-Hai
MH
Yang
Guang-Li
GL
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001201:Ascites / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D008081:Liposomes; D008113:Liver Neoplasms / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols; D011794:Quercetin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D011092:Polyethylene Glycols; D011794:Quercetin