长循环紫杉醇微乳用于肿瘤小剂量化疗的研究  

Paclitaxel carried by long circulating microemulsions used for metronomic chemotherapy of cancer

作　　者：王俊平[1] 王玮[1] 赵丽妮[1] 

机构地区：[1]沈阳医学院药理学教研室,辽宁沈阳110034

出　　处：《药学学报》2009年第8期911-914,共4页Acta Pharmaceutica Sinica

基　　金：辽宁省教育厅资助项目(2004F068)

摘　　要：以聚乙二醇-二硬脂酰基磷脂酰乙醇胺(PEG-DSPE)为表面活性剂,以维生素E为油相,研制长循环紫杉醇微乳(paclitaxel carried by long circulating microemulsions,TXL-M),并评价其抗肿瘤作用。采用电子显微镜、激光粒度/zeta电位分析仪,观察了TXL-M的形态,测定了TXL-M的粒度分布和zeta电位。用昆明种小鼠评价了TXL-M的毒性。采用小剂量化疗方案和动物肿瘤模型,评价了TXL-M的抗肿瘤作用。通过测定给药后不同时间的血浆药物浓度和肿瘤中的药物含量,评价了TXL-M的长循环效果及其在肿瘤中的分布。结果表明,TXL-M呈圆球形,粒径为(98.6±11.2)nm,zeta电位为(?32.4±6.8)mV。采用小剂量给药方案,静脉注射后,与紫杉醇相比长循环微乳显著延长了紫杉醇的血液循环时间,显著提高了紫杉醇的抗肿瘤作用,同时显著减轻了紫杉醇的毒性。总之,TXL-M比紫杉醇更适用于肿瘤的小剂量化疗,有可能成为一种较好的抗肿瘤药物。Long circulating paclitaxel microemulsions （TXL-M） were prepared and its anticancer effect was evaluated in metronomic chemotherapy of cancer using animal tumor models. In TXL-M, paclitaxel was dissolved in vitamin E and polylene glycol derivative of distearoylphosphatidyl ethanolamine （PEG-DSPE） was used as surfactant. The shape and particle size distribution of TXL-M were evaluated using an electronic microscope and a laser size scanner. The toxicity comparisons of TXL-M and paclitaxel were conducted using mice. Its anticancer effect and long circulation were evaluated using animal tumor model in C57BL/6 mice. The average diameter of TXL-M was （98.6 ± 11.2） nm and its zeta potential was （-32.4 ± 6.8） mV. Compared with paclitaxel, TXL-M showed lower toxicity. When used in metronomic chemotherapy of cancer, TXL-M showed longer circulation time in the blood and greater anticancer effect than paclitaxel. Thus, TXL-M is a better candidate for metronomic chemotherapy of cancer than paclitaxel injection.

关 键 词：长循环紫杉醇微乳 小剂量化疗 毒性 抗肿瘤作用 

分 类 号：R943[医药卫生—药剂学]