胆固醇-PEG修饰的酒石酸长春瑞滨脂质体研究

 目的 采用胆固醇-PEG制备酒石酸长春瑞滨长循环脂质体,并对其理化性质、体内药动学和药效学进行研究。方法 用主动载药技术制备胆固醇-PEG修饰的酒石酸长春瑞滨脂质体,用动态光散射法测定粒径,采用柱色谱法测定包封率,KM鼠进行药动学实验,S180/ KM小鼠为模型进行药效学实验。结果 脂质体平均粒径在（100±10）nm;胆固醇-PEG修饰的脂质体能高效包载酒石酸长春瑞滨,药脂摩尔比在1∶5～3∶5内包封率均大于95%;药动学实验表明,胆固醇-PEG2000的加入能够显著延长脂质体的体内循环时间;药效学实验表明,与空白组和游离药组相比,脂质体有明显抑瘤作用。结论 胆固醇-PEG修饰的酒石酸长春瑞滨脂质体具有较高包封率,能显著延长体内循环时间,并可提高酒石酸长春瑞滨的抗肿瘤活性。

Studies on Cholesterol-PEG Modified Long-Circulating Vinorelbine Tartrate Liposomes

OBJECTIVE To prepare the long-circulating vinorelbine tartrate liposomes and evaluate its physicochemical property, pharmacokinetics and pharmacodynamics in vivo. METHODS The long-circulating vinorelbine tartrate liposomes were prepared with "active loading" method. The mean diameter of liposomes was determined by dynamic light scattering (DLS) techniques. Column chromatography was employed for determining encapsulation efficiency. Plasma pharmacokinetics was evaluated in normal KM mice, and antitumor effect was determined in S180/KM mice. RESULTS The mean diameter of liposomes was 100±10 nm. The long-circulating vinorelbine tartrate liposomes modified by cholesterol-PEG loaded vinorelbine tartrate efficiently, and the entrapment efficiency was over 95% when the molar ratio of cholesterol-PEG to vinorelbine tartrate ranged from 1∶5 to 3∶5. The long-circulating vinorelbine tartrate liposomes significantly prolonged the residence time of vinorelbine tartrate in blood and had significant antitumor effects compared with control group and free vinorelbine group. CONCLUSION The long-circulating vinorelbine tartrate liposomes modified by cholesterol-PEG had a high encapsulation efficiency . It can significantly prolong the circulation time of vinorelbine tartrate in vivo and improve antitumor activity.