RGD环肽介导的靶向脂质体体内药动学及荷瘤动物活体成像研究  

In vivo imaging in tumor-bearing animals and pharmacokinetics of PEGylated liposomes modified with RGD cyclopeptide

作　　者：涂柳晓[1] 徐月红[1] 汤晨懿[1] 邓礼荷[1] 吴传斌[1] 

机构地区：[1]中山大学药学院,广东广州510006

出　　处：《药学学报》2012年第5期646-651,共6页Acta Pharmaceutica Sinica

摘　　要：本文测定了大鼠单剂量(5 mg.kg1)尾静脉注射RGD环肽介导的羟基喜树碱(hydroxycamptothecin,HCPT)靶向脂质体(HCPT-RGD-LP)和HCPT长循环脂质体(HCPT-LP)的血药浓度,比较两组的药动学行为;研究了HCPT-LP及HCPT注射剂在正常小鼠血浆和心、肝、脾、肺、肾中的分布情况;采用人肝癌HepG2细胞移植裸鼠,以DiR为荧光探针,通过活体成像比较RGD环肽修饰的DiR靶向脂质体(DiR-RGD-LP)和DiR长循环脂质体(DiR-LP)在荷瘤裸鼠体内的分布。结果显示,HCPT-RGD-LP组和HCPT-LP组的主要药动学参数t1/2β、CL、Vc、AUC048 h、AUC0∞、MRT048 h和MRT0∞均无显著性差异(P>0.05);HCPT-LP在小鼠体内的循环时间明显长于HCPT注射剂,且药物在肝脏中的分布浓度较高;荷瘤裸鼠中,DiR-RGD-LP组肿瘤部位的荧光强度显著高于DiR-LP组,提示RGD环肽用于脂质体修饰能明显提高给药系统的肿瘤靶向性。The hydroxycamptothecin（HCPT） PEGylated liposomes（HCPT-LP） were modified with RGD cyclopeptide formed the tumor-targeting liposomes（HCPT-RGD-LP）.HCPT-LP and HCPT-RGD-LP were injected intravenously with single dose of 5 mg-kg-1 to rats.The drug concentration in plasma was determined and the pharmacokinetic behaviour was compared.The HCPT distribution in heart,liver,spleen,lung,kidney and plasma of mice was investigated following intravenous administration of HCPT-LP and HCPT injection.The nude mice implanted human hepatoma HepG2 cells were studied by in vivo imaging.The fluorescent probe was DiR and the nude mice were injected with DiR PEGylated liposomes（DiR-LP） and DiR-LP modified with RGD cyclopeptide（DiR-RGD-LP）.The results showed that there was no signi-cant difference（P 0.05） of main pharmacokinetic parameters t1/2β,CL,Vc,AUC0-48 h,AUC0-∞,MRT0-48 h,MRT0-∞ between HCPT-RGD-LP and HCPT-LP.HCPT-LP had a remarkably better long-circulating effect than HCPT injection in mice and the concentration of HCPT was highest in liver.The DiR accumulation in tumors of DiR-RGD-LP was higher than that of DiR-LP by the visualized fluorescence of in vivo imaging.It indicated that such PEGylated liposomes modified with RGD cyclopeptide could improve the tumor targeting efficacy.

关 键 词：RGD环肽 肿瘤靶向 脂质体 羟基喜树碱 药动学 活体成像 组织分布 

分 类 号：R943[医药卫生—药剂学]