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.docVIP

 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# 陈志鹏，肖璐，蔡宝昌** 5 10 15 20 25 30 （南京中医药大学 药学院，南京 210046） 摘要：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 5min、10min、15 min、30 min、60min、120min、180min、360min 及 600min 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 15min 后，药物开始聚集在肝脏，600min 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。 关键词：胆固醇-聚乙二醇-甘草次酸；脂质体；NIRD-15；肝靶向；活体成像 中图分类号：R965 In vivo imaging system in detecting distribution of liposomes modified with Glycyrrhetinic Acid CHENG Zhipeng, XIAO Lu, CAI Baochang (College of Pharmacy, Nanjing University of Chinese Medicine, NanJing 210046) Abstract: IOBJECTIVE 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. METHODS The biodistribution of NIRD-15 labeled liposome was studied in mice by flouroscence animal imaging. The mice were randomly separated in conventional liposomes(LP) group and CPGL group. The fluoresence intensities in vivo and in isolated organs were measured 5min、10min、15 min、30 min、60min、120min、180min、360min and 600min after injection. RESULTS LP faded away quickly through metabolism in organs of body, transferrd by circulation system,while few phenomeno of NIRD-15’s enrichment in liver ocurred. After injected CPGL into body, the concent ratio of NIRD-15 in the body was increased slowly. The phenomenon of NIRD-15 enrichment occurred in the liver 15min after administration, and the concentration was still higher than LP after 600min, which suggested liposomes modified with Chol-PEG-GA can target to the 35 liver and extend its residence time in liver. CONCLUSION CPGL can control the release of t