紫杉醇长循环脂质体用于肿瘤小剂量化疗的研究

Anticancer Effect of Paclitaxel Carried with Stealth Liposome Used for Metronomic Chemotherapy

关键词:  紫杉醇  长循环脂质体  小剂量化疗

Key words:  paclitexel  stealth liposome  metronomic chemotherapy

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(P<0.01)。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。

Abstract:

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 metronomic chemotherapy, PSL showed greater anticancer effect than free paclitaxel. CONCLUSION PSL, which showed high loading efficiency and small particle size, can be prepared easily and may become a better candidate for cancer metronomic chemotherapy than paclitaxel injection.