Yuan Zhi-Ping, Chen Li-Juan, Wei Yu-Quan, Fan Lin-Yu, Tang Ming-Hai, Yang Guang-Li
State Key Laboratory of Biotherapy West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
Ai Zheng. 2006 Aug;25(8):941-5.
BACKGROUND & 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.
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.
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.
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.
槲皮素是一种具有多种生物活性的潜在化疗药物。然而，槲皮素的不溶性严重限制了其临床应用。本研究旨在探讨聚乙二醇化纳米脂质体包裹的槲皮素在小鼠体内的生物分布及其对小鼠肝细胞癌癌性腹水形成的治疗效果。
采用常规旋转蒸发法制备纳米脂质体槲皮素。将接种了肝癌细胞（H22）的BALB/c小鼠右腋下前侧接种12天，在不同时间点以1.5mg/只（以槲皮素计）的剂量给小鼠血管内注射纳米脂质体槲皮素。然后用高压液相色谱法（HPLC）检测血浆、肿瘤组织和正常器官中槲皮素的含量。给荷瘤小鼠腹腔注射不同剂量的纳米脂质体槲皮素以确定最佳剂量。给荷瘤小鼠腹腔注射100mg/kg纳米脂质体槲皮素，每天1次，共14天。评估恶性腹水的形成、体重增加、生存时间和腹膜毛细血管通透性。通过流式细胞术检测腹水中的凋亡细胞。
纳米脂质体槲皮素为球形颗粒，药物含量为25%（W/W），直径为130±20nm。纳米脂质体槲皮素在肿瘤组织中有效聚集，半衰期为4小时。纳米脂质体槲皮素以剂量依赖的方式抑制肝细胞癌模型恶性腹水的形成。此外，与PBS对照组相比，100mg/kg纳米脂质体槲皮素显著增强了腹水中癌细胞的凋亡，抑制了体重增加，降低了腹膜毛细血管通透性，延长了荷瘤小鼠的生存时间。
纳米脂质体槲皮素可有效积聚在肿瘤组织中并抑制恶性腹水的形成，因此可能作为一种潜在的抗肿瘤药物值得进一步研究。
