紫杉醇长循环脂质体及其抗肿瘤作用的研究

Preparation and anticancer effect of paclitaxel carried with stealth liposome

目的:探讨紫杉醇长循环脂质体(PSL)的急性毒性、抗肿瘤作用和稳定性。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/Ze-ta电位测定仪和SephadexG50色谱柱,观察和测定了PSL的粒度分布、Zeta电位和包封率。在冷藏(7℃)避光条件下保存1年,观察其理化性质的改变。结果:PSL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)。静脉注射后,与游离紫杉醇相比,长循环脂质体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急性毒性。在本试验条件下,保存1年,粒度、包封率几乎无改变,但紫杉醇含量下降8.2%。结论:PSL包封率高、粒度小,有可能成为一种较好的抗肿瘤药物。

Objective：To prepare stealth liposome to carry paclitaxel （PSP） and to evaluate its acute toxicity,anticancer effect and stability. Methods：PSP was prepared, in which oleie acid, cholesterol and PEG-DSPE （polylene glycol derivative of distearoylphosphatidyl ethanolamine, mean molecular weight of PEG：2000） were included. PEG-DSPE was used to enlarge the circulation time of PSP. Oleie acid was used to reduce its particle size disitribution. PSL was characterized using laser light scattering instrument and Sephadex G50 column. The anticaneer effect of PSP was evaluated using S180 tumor model and its acute toxicity was compared with that of free paclitaxel. The stability of PSP was monitored by particle size,loading efficiency and paclitaxel content changes of three batches of PSP stored at 7 ℃ in the dark for 1 year. Results：The average diameter of PSP was （138.6±4.6） nm and its Zeta potential was （-31.6±7.9） my while its loading efficiency was （97.8±2.6）%. Compared with free paelitaxel,PSP showed lower acute toxicity and greater antieaneer effect. When stored at 7℃ in the dark for 1 year, 8.2 % of the paclitaxel was decomposed while there were few changes in its size and Zeta potential. Conclusion：PSL may become a better anticaneer drug than paclitaxel injection. Futher study is needed to promote the stability of PSP.