染料木素MePEG-PLGA共聚物胶束在荷瘤小鼠中靶向性研究  

Study on Targetability of MePEG-PLGA Copolymer Micelles in Tumor-Bearing Mice

作　　者：王雪莹[1] 张翔珂 陈铭 董雨萌 张新宇 苏慧[2] 阎雪莹[2] WANG Xueying;ZHANG Xiangke;CHEN Ming;DONG Yumeng;ZHANG Xinyu;SU Hui;YAN Xueying(First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang,China;Heilongjiang University of Chinese Medicine,Harbin 150040,Heilongjiang,China)

机构地区：[1]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040 [2]黑龙江中医药大学,黑龙江哈尔滨150040

出　　处：《辽宁中医药大学学报》2023年第7期26-30,共5页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：黑龙江省自然科学基金项目(LH2020H096,LH2021H102);黑龙江省中医药管理局项目(ZHY 2020-112)。

摘　　要：目的 采用人肝癌SMMC-7721细胞移植裸鼠,研究染料木素MePEG-PLGA共聚物胶束在荷瘤小鼠体内的分布情况。方法 以FITC为荧光探针,采用HPLC定量和小动物活体成像技术监测染料木素MePEG-PLGA共聚物胶束在荷瘤小鼠体内的分布情况。结果 建立了简单可靠的高效液相色谱方法用来定量分析荷瘤小鼠心、肝、脾、肺、肾、肿瘤组织以及血浆中的染料木素(GEN)浓度,色谱柱为DIKMA Diamonsil(钻石C18,5μm,250 mm×4.6 mm),流动相为甲醇∶水=60∶40(V/V),检测波长为260 nm,流速为0.8 mL·min^(-1),柱温为35℃,进样量为10μL。荷瘤裸鼠的体内分布研究结果表明,GEN胶束在肿瘤部位的相对摄取率(RUE)可达到2.04,峰浓度比值(Ce)也高达1.68,明显高于其他器官(P<0.05),与乳剂相比能够明显提高药物在肿瘤部位的蓄积。小动物成像结果表明,尾静脉注射给药后4 h时GEN胶束在肿瘤部位聚集最多,明显高于其他组织。结论 染料木素MePEGPLGA共聚物胶束能够在肝肿瘤部位富集,可明显提高给药系统的肿瘤靶向性。Objective Human hepatoma SMMC-7721 cells were transplanted into nude mice to study the distribution of MePEG-PLGA copolymer micelles in tumor-bearing mice.Methods FITC was used as a fluorescence probe,and the distribution of MePEG-PLGA copolymer micelles in tumor-bearing mice was monitored by HPLC quantification and small animal imaging.Results A simple and reliable HPLC method was established for the quantitative analysis of GEN concentrations in the heart,liver,spleen,lung,kidney,tumor tissues and plasma of tumor-bearing mice.The chromatographic column was DIKMA Diamonsil(diamond C 18,5μm,250 mm×4.6 mm)with methanol∶water=60∶40(V/V),the detection wavelength was 260 nm,the flow rate was 0.8 mL·min^(-1),the column temperature was 35℃,and the injection volume was 10μL.The results of in vivo distribution study of tumorigene-bearing nude mice showed that the RUE value of GEN micelles at the tumor site could reach 2.04,and the Ce value was as high as 1.68,which was significantly higher than other organs(P<0.05).Compared with the emulsion group,the accumulation of GEN micelles at the tumor site could be significantly improved.The results of small animal imaging showed that GEN micelles accumulated the most in the tumor site at 4 h after tail vein injection,which was significantly higher than that in other tissues.Conclusion The MePEG-PLGA copolymer micelles can be enriched in the liver tumor site,which can significantly improve the tumor-targeting performance of the drug delivery system.

关 键 词：染料木素 MePEG-PLGA共聚物胶束 肿瘤靶向 组织分布 荷瘤小鼠 

分 类 号：R285[医药卫生—中药学]