洛莫司汀脂质体的制备及药代动力学和组织分布学研究

摘要/Abstract

摘要： 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 ºC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(t1/2β) 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: 脂质体, 洛莫司汀, 被动靶向, 药代动力学, 缓释系统, 组织分布

Abstract: 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 ºC. 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.

Key words: Liposomes, Lomustine (CCNU), Passive targeting, Pharmacokinetics, Sustained release system, Tissue distribution

中图分类号:

R969.1

Supporting:

^*Corresponding author. Tel.: 86-531-88382015; fax:86-531-88382548

王金萍, 祝侠丽, 席延伟, 王德凤, 黄桂华^*. 洛莫司汀脂质体的制备及药代动力学和组织分布学研究[J]. .

Jin-Ping Wang, Xia-Li Zhu, Yan-Wei Xi, De-Feng Wang, Gui-Hua Huang^*. Preparation of lomustine loaded liposomes and studies of its pharmacokinetics and tissue distribution properties [J]. .

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