洛莫司汀脂质体的制备及其在大鼠体内的药动学  

Preparation of Lomustine Liposomes and Its Pharmacokinetics in Rats

作　　者：沈圆圆[1] 邱利焱[1] 金一[1] 杨巨飞[1] 施菁[2] 

机构地区：[1]浙江大学药学院,杭州310031 [2]浙江医学高等专科学校,杭州310053

出　　处：《中国药学杂志》2007年第1期53-57,共5页Chinese Pharmaceutical Journal

基　　金：浙江省科技计划项目(2003C33012)

摘　　要：目的研究洛莫司汀(CCNU)脂质体的制备方法并考察用聚乙二醇单甲醚(2000)胆固醇琥珀酸酯(PEGCHS)修饰前后的2种脂质体静脉给药后在大鼠体内的药动学。方法用改良逆相蒸发法制备普通和PEGCHS修饰的CCNU脂质体,测定包封率和粒径,静脉注射给药后,以格列苯脲为内标,采用高效液相色谱法测定血液中的药物含量;并采用3P87药动学程序进行数据处理。结果制备的洛莫司汀脂质体包封率高(>80%),平均粒径50 nm左右;CCNU PBS溶液、CCNU脂质体和用PEGCHS修饰的CCNU脂质体的t1/2α分别为0.061 8,0.093 1和0.153 1 h;t1/2β分别为0.087 9,0.416 2和1.002 1 h;AUC分别为13.520 7,86.911 3和166.640 6 mg.h.L-1。结论制备的CCNU脂质体包封率较高,粒径小;2种CCNU脂质体均可不同程度地增加CCNU的AUC,延长其在血液循环中的时间,并以用PEGCHS修饰的CCNU脂质体效果最好。OBJECTIVE To prepare lomustine（CCNU） liposomes and study their pharmacokinetics in rats after intravenous administration. METHODS To prepare CCNU liposomes by improved reverse-phase evaparation method. The entrapment efficiency and mean diameter were studied. After intravenous administration, the CCNU in plasma was detected by HPLC and the pharmacokinetic parameters were calculated by 3P87 pharmacokinetic program. RESULTS The entrapment efficiency of CCNU liposomes was above 80% and the mean diameter was about 50 nm. The t1/2α of CCNU solution,common CCNU liposomes,CCNU liposomes modified by PEGCHS were 0. 061 8 ,0.093 1 and 0. 153 1 h, respectively ; t1/2β were 0.087 9 ,0.416 2 和11 1.002 1 h, respectively;AUC were 13.520 7 ,86.911 3 and 166. 640 6 mg· h · L^-1, respectively. CONCLUSION The CCNU liposomes have high entrapment efficiency and small particle size. The two kinds of liposomes raise the AUC and prolonge the resident time of the drug in the blood circulating system, especially in PEG-L group.

关 键 词：洛莫司汀 脂质体 药动学 

分 类 号：R969[医药卫生—药理学]