Chen Si-ze, Wang Sen-ming, Zhang Ji-ren
Department of Radiotherapy, First Hospital Affiliated to Guangdong Pharmaceutical University, Guangzhou 510080, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2008 Mar;28(3):403-5.
To prepare long-circulating liposome (LCL) for sustained release of nolatrexed dihydrochloride and evaluate the effect of this preparation against the growth of hepatocarcinoma cells in mice.
The long-circulating nolatrexed dihydrochloride liposome was prepared by film dispersion-extrusion combined with ammonium sulphate gradient method. Amphipathic polyethylene glycol-distearoyl phosphatidylethanolamine (PEG-DSPE) was added to modify the property of the liposome membrane. The drug entrapment efficiency of the nolatrexed dihydrochloride-containing liposome was determined using UV detector with Sephadex G50. Electron microscopy and laser particle analyzer were employed to determine the size of the nolatrexed dihydrochloride liposome. For in vivo evaluation of the effect of the liposomal preparation, H22 mouse hepatoma carcinoma cells were transplanted subcutaneouly in mice in the axillary region of the right hind limb to induce growth of solid tumors, which were evaluated for tumor weight inhibition rate and tumor volume changes after administration of the LCL preparations.
The mean diameter of the long-circulating nolatrexed dihydrochloride liposomes was 109 nm, with an entrapment efficiency of 68.5%. In vivo antitumor experiment showed that both the common liposomal and LCL preparations of nolatrexed dihydrochloride produced antitumor effect in vivo, and the latter had weaker antitumor effect than free and common liposomal preparation of nolatrexed dihydrochloride, but in the long term, the LCL preparation showed stronger antitumor effect with a tumor weight inhibition rate of 41.68%.
LCL allows sustained release of nolatrexed dihydrochloride in vivo, and may effectively lengthen the relatively short half life of this drug after administration.
制备用于盐酸诺拉曲塞缓释的长循环脂质体（LCL），并评估该制剂对小鼠肝癌细胞生长的影响。
采用薄膜分散 - 挤压结合硫酸铵梯度法制备长循环盐酸诺拉曲塞脂质体。添加两亲性聚乙二醇 - 二硬脂酰磷脂酰乙醇胺（PEG - DSPE）修饰脂质体膜的性质。使用配备Sephadex G50的紫外检测器测定含盐酸诺拉曲塞脂质体的药物包封率。采用电子显微镜和激光粒度分析仪测定盐酸诺拉曲塞脂质体的大小。为了在体内评估脂质体制剂的效果，将H22小鼠肝癌细胞皮下移植到小鼠右后肢腋窝区域以诱导实体瘤生长，在给予LCL制剂后评估肿瘤重量抑制率和肿瘤体积变化。
长循环盐酸诺拉曲塞脂质体的平均直径为109nm，包封率为68.5%。体内抗肿瘤实验表明，盐酸诺拉曲塞的普通脂质体和LCL制剂在体内均产生抗肿瘤作用，且后者的抗肿瘤作用比盐酸诺拉曲塞游离制剂和普通脂质体制剂弱，但从长期来看，LCL制剂显示出更强的抗肿瘤作用，肿瘤重量抑制率为41.68%。
LCL可使盐酸诺拉曲塞在体内持续释放，并可能有效延长该药物给药后的相对较短半衰期。
