紫杉醇长循环脂质体用于肿瘤小剂量化疗的研究概要.PDFVIP

紫杉醇长循环脂质体用于肿瘤小剂量化疗的研究 王俊平，赵丽妮，王玮(沈阳医学院药理学教研室，沈阳 110034) 摘要：目的 研制紫杉醇长循环脂质体(paclitaxel stealth liposome ，PSL) 用于肿瘤小剂量化疗，评价其急性毒性和抗肿瘤 作用。方法 制备 PSL ，其中含有聚乙二醇-二硬脂酰基磷脂酰乙醇胺(PEG-DSPE)和油酸。PEG-DSPE 用于延长脂质体的 血液循环时间，油酸用于降低脂质体的粒度。利用激光粒度/Zeta 电位测定仪和 Sephadex G50 色谱柱，观察和测定了 PSL 的粒度分布、Zeta 电位和包封率。采用昆明种小鼠，比较了 PSL 与紫杉醇的急性毒性，并且评价了 PSL 的长循环效果。 采用小剂量给药方案，评价了 PSL 的抗肿瘤作用。结果 在 5%葡萄糖水溶液中，PSL 的粒径为(138.6±4.6)nm ，Zeta 电 位为(31.6±7.9)mV ，包封率可达(97.8±2.6)%(n=3) 。长循环脂质体显著延长了紫杉醇的血液循环时间，减轻了紫杉醇的急 性毒性，同时显著提高了紫杉醇的抗肿瘤作用。采用小剂量给药方案，PSL 的抗肿瘤作用显著高于紫杉醇注射液(P0.01) 。 结论 PSL 包封率高，粒度小，制备工艺简单。与紫杉醇注射液比较，PSL 更适用于肿瘤的小剂量化疗。 关键词：紫杉醇；长循环脂质体；小剂量化疗 中图分类号：R943.4 文献标志码：B 文章编号：1007-7693(2010)11-1069-04 Anticancer Effect of Paclitaxel Carried with Stealth Liposome Used for Metronomic Chemotherapy WANG Junping, ZHAO Lini, WANG Wei(Department of Pharmacology, Shenyang Medical College, Shenyang 110034, China) ABSTRACT: OBJECTIVE To prepare paclitaxel stealth liposome (PSL) used for metronomic chemotherapy and evaluate its acute toxicity and anticancer effect. METHODS PSL was prepared, in which oleic acid, vitamin E, cholesterol and PEG-DSPE(polylene glycol derivative of distearoylphosphatidyl ethanolamine, mean molecular weight of PEG 2000) were included. PEG-DSPE was used to extend the circulation time of PSL. Oleic acid was used to reduce the average particle size of PSL. PSL was characterized using laser light scattering instrument and Sephadex G50 column. The anticancer effect of PSL was evaluated using S180 tumor model and its acute toxicity was compared with that of free paclitaxel. RESULTS The average diameter of PSL was (138.6±4.6) nm and its Zeta potential was (31.6±7.9) mV while its loading efficiency was (97.8±2.6)%. Compared with free paclitaxel, PSL showed lower acute toxicity and greater anticancer effect. In metron