磷脂组成对马钱子碱隐形脂质体药剂学性质与抗肿瘤作用的影响

Effect of phospholipid composition on pharmaceutical properties and anti-tumor activity of stealth liposomes containing brucine

目的:比较3种不同磷脂组成的马钱子碱隐形脂质体的药剂学性质以及抗肿瘤作用。方法:采用硫酸铵梯度法和隐形脂质体技术制备马钱子碱氢化大豆磷脂(hydrogenated soybean phosphatidylcholine,HSPC)、大豆磷脂(soybean phosphati-dylcholine,SPC)、复合磷脂(SPC-HSPC 3∶1)隐形脂质体,考察其形态学、粒径、包封率等药剂学性质。建立小鼠移植性肝癌H22模型,测定3种不同磷脂组成马钱子碱隐形脂质体的抑瘤率,并比较各组荷瘤小鼠的体重、免疫器官(脾和胸腺)指数。结果:马钱子碱复合磷脂隐形脂质体、HSPC隐形脂质体、SPC隐形脂质体的包封率分别为77.7%,64.8%,74.8%,粒径均小于100 nm。同剂量的马钱子碱复合磷脂,HSPC,SPC隐形脂质体的抑瘤率分别为57.88%,49.15%,23.37%。与阴性对照组相比,3组马钱子碱隐形脂质体对荷瘤小鼠体重、胸腺指数的影响均无统计学差异,此外,SPC组和HSPC组荷瘤小鼠脾指数有所提高,而复合磷脂组无统计学差异。结论:磷脂组成是影响马钱子碱隐形脂质体抗肿瘤效果的重要因素。

Objective ： To compare the pharmaceutical properties and the anti-tumor activities of three kinds of stealth liposomes prepared with different phospholipid composition containing brucine. Method ： Stealth liposomes with different phospholipids composition, such as soybean phosphatidycholine （SPC）,hydrogenated soybean phosphatidylcholine （HSPC） and the complex of SPC and HSPC,were prepared by ammonium sulfate transmembrane gradient method. Pharmaceutical properties such as shape,encapsulation efficiency and size of three stealth liposomes were compared intensively. Anti-tumor activity of SPC,HSPC and novel stealth liposomes composed of both SPC and HSPC were compared by established mouse liver cancer H22 model. Meanwhile,the mice body weight and immune organ weight were also compared. Result ： The encapsulation efficiency of novel,SPC and HSPC stealth liposomes were 77.7%,64.8%and 74.8%,respectively. The mean diameters of them were less than 100 nm. The tumor inhibition rate of novel,HSPC and SPC stealth liposomes were 57.88%,49.15%, 23.37%,respectively. The mice body weight,thymus gland index of three stealth liposomes group and spleen index of novel stealth liposomes group had no significant difference with the negative group while SPC and HSPC stealth liposomes group increased the spleen index. Conclusion ： Phospholipids composition is the key factor which determines the antitumor activity of brucine-loaded stealth liposomes.