紫杉醇隐形脂质体的制备及在小鼠体内的组织分布  

PREPARATION OF PACLITAXEL STEALTH LIPOSOMES AND ITS TISSUE DISTRIBUTION IN MICE

作　　者：阎家麒 王悦[2] 王九一[3] 

机构地区：[1]河南绿十字生物工程研究所,河南郑州450008 [2]中山医科大学肿瘤防治中心,广东广州510006 [3]河南省分析测试中心,河南郑州450003

出　　处：《药学学报》2000年第9期706-709,共4页Acta Pharmaceutica Sinica

摘　　要：目的　研究紫杉醇隐形脂质体的制备方法并考察其在小鼠体内的组织分布。方法　采用共沉淀和微流态化两步法制备紫杉醇隐形脂质体 ,用两亲性聚乙二醇 二硬脂酰磷脂酰乙醇胺 (PEG DSPE)修饰脂质体膜。以RP HPLC法测定小鼠组织内紫杉醇药物浓度。结果　隐形脂质体粒径≤ 10 0nm ,药物包封率≥ 98%。均以 5mg·kg-1经iv脂质体紫杉醇和游离紫杉醇 ,2 4h后紫杉醇隐形脂质体在血液中驻留 35 %以上 ,在肝脾组织中摄取不足 10 %。而膜材中不含PEG DSPE的紫杉醇传统脂质体在血液中驻留 10 % ,被单核吞噬细胞系统 (mononuclearphagocytesystem ,MPS)捕获了 5 0 %以上。证明紫杉醇隐形脂质体延长了在血循环中的时间并减少了MPS的吞噬。血液AUC隐形脂质体约为传统脂质体的 2 0倍。结论　采用共沉淀和微流态化法可制得包封率高、粒径小的脂质体 ,用PEG DSPE修饰磷脂膜可以增加隐形脂质体的AUC 。AIM To investigate the preparation of paclitaxel stealth liposomes and to observe its tissue distribution in mice. METHODS The paclitaxel stealth liposomes were prepared by coprecipitation and microfluidization in two steps. The amphipathic polyethylene glycol distearoyl phosphatidylethanolamine (PEG DSPE) was added to modify the quality of liposomes membrane. The RP HPLC was utilised for the determination of paclitaxel concentration in mice tissue. RESULTS Stealth liposomes (S liposomes) were ≤100 nm in mean diameter and encapsulated paclitaxel with ≥98% entrapping efficiency. Liposomal paclitaxel and free paclitaxel were injected intravenously at a dose of 5 mg paclitaxel·kg -1 to mice. Prolonged circulation and reduced mononuclear phagocyte system uptake were achieved. After 24 h, up to 35% of the injected dose remains in the blood and less than 10% is taken up by the two major organs of the mononuclear phagocyte system, liver and spleen, compared with 10% and up to 50%, respectively, for conventional liposomes (C liposomes) without amphipathic PEG DSPE. The value of the area under the curve (AUC) of blood was approximately 2 fold higher than that of paclitaxel C liposomes. CONCLUSION Coprecipitation and microfluidization methods can highly increase the entrapping efficiency and decrease the size of the S liposomes. The AUC of S liposomes was increased and long circulation time can be reached after modification of lipid membrane with PEG DSPE.

关 键 词：紫杉醇 隐形脂质体 组织分布 共沉淀 

分 类 号：R979.1[医药卫生—药品] R969.1[医药卫生—药学]