乐伐替尼脂质体的制备及处方工艺优化研究  

Study on the preparation process and formulation optimization of liposomal lenvatinib

作　　者：周艳艳 朱柯武 沈润溥[1] 袁喜英 骆翔 ZHOU Yanyan;ZHU Kewu;SHEN Runpu;YUAN Xiying;LUO Xiang*(Shaoxing University,Shaoxing 312000,China;Zhejiang Novus Pharmceuticals Co.,Ltd.,Shaoxing 312000,China)

机构地区：[1]绍兴文理学院,浙江绍兴312000 [2]浙江创新生物有限公司,浙江绍兴312000

出　　处：《中国药剂学杂志（网络版）》2022年第1期1-13,39,共14页Chinese Journal of Pharmaceutics：Online Edition

基　　金：浙江省教育厅一般科研项目(Y201839799);绍兴文理学院校级重点科研项目(2018LG1002)。

摘　　要：目的乐伐替尼(Lenvatinib,Len)作为一种新型一线口服肝癌治疗药物,其仍然存在一些消化道不良反应。需要开发一种生物相容性好、肿瘤靶向性高的新型乐伐替尼药物制剂。方法以磷脂和胆固醇作为基本膜材,通过被动载药工艺和主动载药技术成功制备了Len脂质体,并以药物包封率为指标,优化了Len脂质体的处方工艺。通过动态光散射技术和透射电子显微镜成像,对Len脂质体粒径、电位与微观形态进行了表征。采用透析法对Len脂质体的体外释放行为进行考察。结果被动载药工艺与主动载药技术制备的Len脂质体包封率分别为27.6±3.1%和91.8±2.1%,药物含量分别为0.28±0.03 mg·mL^(-1)和0.92±0.02 mg·mL^(-1),平均粒径分别为191.3±15.2 nm和134.8±7.5 nm,Zeta电位分别为-7.7±3.1 mV和-12.6±2.3 mV。结论利用被动载药工艺和主动载药技术成功制备了两种Len脂质体,主动载药法制备的Len脂质体具有更高包封率和更显著的缓释效果,具有较好的临床应用潜力和产品开发价值。Objective Lenvatinib(Len),as a new oral first-line drug for hepatocellular carcinoma treatment,still has some gastrointestinal adverse reactions.It is necessary to develop a novel Len preparation with good biocompatibility and high tumor-targeting.Methods Len liposomes were successfully prepared by passive loading method and remote loading method with phospholipid and cholesterol as basic membrane materials.The preparation process and formulation of Len liposomes were optimized with encapsulation efficiency(EE)of Len as an index.The particle size,Zeta potential and morphology of Len liposomes were characterized by dynamic light scattering(DLS)and transmission electron microscopy(TEM).The in vitro release behavior of Len liposomes was measured by the dialysis method.Results The encapsulation efficiency,content,mean particle size,and Zeta potential of Len liposomes,which were prepared by passive loading method and remote loading method,were(27.6±3.1)%and(91.8±2.1)%,(0.28±0.03)mg·mL^(-1)and(0.92±0.02)mg·mL^(-1),(191.3±15.2)nm and(134.8±7.5)nm,(-7.7±3.1)mV and(-12.6±2.3)mV,respectively.Conclusion Two kinds of Len liposomes were successfully prepared by passive loading method and remote loading method.The Len liposomes prepared by remote loading method have higher encapsulation efficiency and more significant sustained release behavior,which has a potential application in clinical and in product development.

关 键 词：乐伐替尼脂质体 肝癌 被动载药法 PH梯度法 包封率 

分 类 号：R94[医药卫生—药剂学]