Preparation of lomustine loaded liposomes and studies of its pharmacokinetics and tissue distribution properties  

洛莫司汀脂质体的制备及药代动力学和组织分布学研究(英文)

作　　者：王金萍[1] 祝侠丽[1] 席延伟[1] 王德凤[1] 黄桂华[1] 

机构地区：[1]山东大学药学院,山东济南250012

出　　处：《Journal of Chinese Pharmaceutical Sciences》2010年第5期353-362,共10页中国药学（英文版）

摘　　要：Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.脂质体是可静脉注射的靶向、控释给药系统。本研究的主要目的是制备洛莫司汀脂质体,评价其物理化学性质,并对其静脉注射后的组织靶向性进行研究。用薄膜分散法制备洛莫司汀脂质体,37℃磷酸盐缓冲溶液(pH=6.8)中考察体外释放特性,反相高效液相色谱法测定静脉注射洛莫司汀HP-β-CD包合物溶液和脂质体后组织中的药物浓度。该实验制备的洛莫司汀脂质体平均粒径为(189.8±28.5)nm,zeta电位(-19.13±0.12)mV。释放曲线符合Weibull方程。以新西兰兔为试验动物,分别静脉注射洛莫司汀溶液和脂质体,脂质体组的消除半衰期(t_(1/2β)显著增加。洛莫司汀脂质体在小鼠脑组织中的AUC、Te和Re明显提高。实验结果表明该脂质体对脑部有被动靶向效果。

关 键 词：Liposomes Lomustine （CCNU） Passive targeting PHARMACOKINETICS Sustained release system Tissue distribution 

分 类 号：R969.1[医药卫生—药理学]