活体成像系统检测甘草次酸修饰脂质体在小鼠体内的分布

目的:研究胆固醇-聚乙二醇-甘草次酸(Chol-PEG-GA)修饰脂质体(CPGL)在小鼠体内的长循环型和分布情况,为肝肿瘤的靶向治疗提供理论依据.方法:将普通脂质体(LP)和CPGL分别包裹荧光显像剂NIRD-15,通过NIRD-15跟踪检测LP和CPGL在小鼠体内分布情况.将小鼠随机分为LP组和CPGL组,分别尾静脉注射,与药物注射后5,10,15,30,60,120,180,360,600 min采用活体成像系统观察小鼠活体及离体器官中药物荧光强度.结果:尾静脉注射LP后随循环系统迅速分布到各器官,肝靶向性较差.尾静脉注射CPGL 15 min后,药物开始聚集在肝脏,600 min后在肝脏中的药物浓度仍显著高于LP组,说明用Chol-PEG-GA修饰的脂质体能主动靶向于肝细胞,并延长其在肝组织的滞留时间.结论:CPGL在体内有明显的长循环性和肝靶向性,延长其在体内的半衰期,减少药物代谢率,靶向到达肝脏,延长在肝脏的滞留时间.

In vivo Imaging System in Detecting Distribution of Liposomes Modified with Glycyrrhetinic Acid

Objective: To prove the long-circulating and distribution of liposome which is modified with choesterol-poly (ethylene glycol)₂₀₀₀-glycyrrhetinic acid (Chol-PEG-GA)(CPGL) in vivo and provide theoretical basis for targeting therapy of tumor. Method: The biodistribution of NIRD-15 labeled liposome was studied in mice by fluorescence animal imaging. The mice were randomly separated in conventional liposomes (LP) group and CPGL group. The fluorescence intensities in vivo and in isolated organs were measured 5,10,15,30,60,120,180,360,600 min after injection. Result: LP faded away quickly through metabolism in organs of body, transferred by circulation system, while few phenomenon of NIRD-15's enrichment in liver occurred. After injected CPGL into body, the content ratio of NIRD-15 in the body was increased slowly. The phenomenon of NIRD-15 enrichment occurred in the liver 15 min after administration, and the concentration was still higher than LP after 600 min, which suggested liposomes modified with Chol-PEG-GA can target to the liver and extend its residence time in liver. Conclusion: CPGL can control the release of the drug in vivo, prolong the biological half life, and improve the liver targeting effect.