【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℃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。更多还原

【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℃.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(t_1/2β) 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.更多还原