二氢卟吩e6脂质体在荷瘤小鼠体内的药动学及靶向性分析  

Pharmacokinetics and Targetability of Chlorin e6 Liposomes in Tumor-bearing Mice

作　　者：张祚德 王安元[1] 郝建冬 谢波[3] 凌家俊[1] 朱海媚 贺怡 田金洁 ZHANG Zuo-de;WANG An-yuan;HAO Jian-dong;XIE Bo;LING Jia-jun;ZHU Hai-mei;HE Yi;TIAN Jin-jie(School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China;EEC Bio-tech （ Guangzhou） Co. Ltd. , Guangzhou 510070, China;General Hospital of Guangzhou Military Command of PLA, Guangzhou 510010, China)

机构地区：[1]广州中医药大学中药学院,广州510006 [2]广州意斯生物工程科技有限公司,广州510070 [3]广州军区广州总医院,广州510010

出　　处：《中国实验方剂学杂志》2018年第13期71-77,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：广东省科技计划项目(2014A020210022)

摘　　要：目的：研究二氢卟吩e6（Ce6）磷酸盐缓冲液（PBS）溶液及其脂质体在荷瘤小鼠体内的药物动力学特性,并验证Ce6脂质体的肝脏靶向性和肿瘤靶向性。方法：荷瘤小鼠尾静脉注射Ce6溶液或其脂质体后,通过HPLC测定不同时间点血浆及组织中Ce6的质量浓度,流动相乙腈-0.2%磷酸盐（50∶50）,检测波长403 nm。采用DAS 2.1.1软件计算药动学参数,以8 h内相对摄取率（RE）来评价Ce6对主要器官的靶向性。结果：Ce6溶液和Ce6脂质体在荷瘤小鼠血浆中的药动学模式均符合二室模型,分布相半衰期（t1/2α）分别为1.516,0.507 h;消除相半衰期（t1/2β）分别0.457,1.366 h;清除率（CL）分别为0.178,0.067 L·h-1·kg-1;药时曲线下面积（AUC0-∞）分别为16.734,51.475 mg·h·L-1。在肝、脾、肿瘤组织中,RE分别为1.149,1.477和1.277。经统计学分析,Ce6溶液和Ce6脂质体的药动学结果有显著性差异（P〈0.05）。结论：Ce6脂质体在体内的药物代谢清除速度更缓慢,分布更迅速、广泛,并能选择性聚集于肝脏和肿瘤组织。Ce6脂质体制剂可继续开发以用于治疗肝癌。Objective： To study on the pharmacokinetics of chlorin e6（ Ce6） phosphate-buffered saline（ PBS） solution and its liposomes in tumor-bearing mice,and to verify the liver and tumor targeting of Ce6 liposomes. Method： After Ce6 solution or its liposomes were injected into tail vein of tumor-bearing mice,at different time points, the drug concentrations in serum and tissues of tumor-bearing mice were determined by HPLC,and the pharmacokinetic parameters were calculated by DAS 2. 1. 1 software,while the relative uptake rate（ RE） within 8 h was adopted to calculate the targeting performance of Ce6 on the main organs. Result： The pharmacokinetic models of Ce6 solution and its liposomes in plasma of tumor-bearing mice were consistent with the two-compartment model,their half time of distribution phase（ t1/2α） were 1. 516 h and 0. 507 h; their half time of elimination phase（ t1/2β） were 0. 457 h and 1. 366 h; clearance rates（ CLs） were 0. 178,0. 067 L·h-1·kg-1;their AUC0-∞were 16. 734,51. 475 mg·h·L-1,respectively. In liver,spleen and tumor tissues,the RE values were 1. 149,1. 477 and 1. 277,respectively. The statistical analysis showed that there was a significant difference in major pharmacokinetic parameters between Ce6 solution and Ce6 liposomes（ P 〈 0. 05）. Conclusion：Compared with Ce6 solution,Ce6 liposomes has a more slowly metabolic clearance in vivo,and it distributes more rapidly and widely,it also can selectively assemble in liver and tumor tissue,liposomal formulations of Ce6 may be further developed for the treatment of liver cancer.

关 键 词：二氢卟吩e6 脂质体 药代动力学 靶向性 组织分布 荷瘤小鼠 相对摄取率 

分 类 号：R22[医药卫生—中医基础理论] R289[医药卫生—中医学]