去甲基斑蝥素N-乳糖酰壳聚糖纳米粒的吸收机制及小鼠抑瘤作用研究  

Study on Absorption Mechanism and Anti-tumor Pharmacodynamics in Mice of Norcantharidin Loaded N-Galactosylated Chitosan Nanoparticles

作　　者：贝永燕[1] 管敏[1] 周奕[1] 许静玉[1] 薛成文[1] 胡展红[1] 张学农[1,2] BEI Yong-yan;GUAN Min;ZHOU Yi;XU Jing-yu;XUE Cheng-wen;HU Zhan-hong;ZHANG Xue-nong(College of Pharmacy,Soochow University,Jiangsu Suzhou 215123,China;Suzhou Liyuan Medical Technology Co.,Ltd.,Jiangsu Suzhou 215002,China)

机构地区：[1]苏州大学药学院,江苏苏州215123 [2]苏州利元医药科技有限公司,江苏苏州215002

出　　处：《中国药房》2012年第1期26-28,共3页China Pharmacy

摘　　要：目的:研究去甲基斑蝥素N-乳糖酰壳聚糖纳米粒(NCTD-GC-NPs)的吸收机制和小鼠抑瘤作用。方法:以表观透过系数为指标,考察NCTD-GC-NPs(80μg·mL-1)及其分别与环孢素A(50μmol·L-1)、去氧胆酸钠(100mmol·L-1)、叠氮化钠(25mmol·L-1)、氧化苯胂(25mmol·L-1)联用后对结肠癌Caco-2细胞转运的影响;将接种肝癌细胞H22后的小鼠随机分为空白组、对照组(NCTD原料药2mg·kg-1)和NCTD-GC-NPs低、中、高剂量组(0.5、2、4mg·kg-1),每组10只,每日灌胃给药1次,连续给药8d,考察各组小鼠体重和抑瘤率。结果:环孢素A、去氧胆酸钠和叠氮化钠均能明显促进NCTD-GC-NPs在Caco-2细胞的转运(P<0.05或P<0.01),氧化苯胂对转运无明显影响;各组小鼠体重无明显变化;与对照组比较,NCTD-GC-NPs中、高剂量组的抑瘤率明显增强(P<0.05或P<0.01)。结论:NCTD-GC-NPs主要通过主动转运穿过小肠上皮细胞,能明显抑制肝癌肿瘤细胞H22的生长。OBJECTIVE： To study absorption mechanism and anti-tumor effect in mice of Norcantharidin loaded N-galactosylated chitosan nanoparticles （NCTD-GC-NPs）. METHODS： Using apparent coefficient as index, effects of NCTD-GC-NPs （80 μg.mL-1） combined with cyclosporin A （CyA, 50 μmol.L -1）, sodium deoxycholate （SDCh, 100 mmol·L-1）, NaN3 （25 mmol-L-1） or oxo- phenylarsine （25 mmol. L--1） on Caco-2 cell transport were investigated; after the vaccination of H22, mice were randomly divided into blank group, control group （NCTD raw material 2 mg. kg-1）, NCTD-GC-NPs high-dose, medium-dose and low-dose groups （0.5, 2, 4 mg.kg-1） with each group of 10 mice. Those groups were given medicine via i.g. once a day for consecutive 8 days. The body weight and anti-tumor rate were investigated during this experiment. RESULTS： CyA, SDCh and NaN3 could improved the transportation of NCTD-GC-NPs in Caco-2 cells significantly （P〈0.05 or P〈0.01）, while oxophenylarsine showed no obvious effect. The body weight of mice had no significant change. Compared with control group, the anti-tumor rate of NCTD-GC-NPs of medium-dose and high-dose groups were enhanced significantly （P〈 0.05 or P〈 0.01）. CONCLUSION： NCTD-GC-NPs may pass through intestinal epithelial cells primarily by active transport, which could inhibit the growth of hepatic carcinoma cell H22.

关 键 词：去甲基斑蝥素N-乳糖酰壳聚糖纳米粒 结肠癌Caco-2细胞 吸收机制 小鼠 肝癌细胞H22 抑瘤率 

分 类 号：R965[医药卫生—药理学] R966[医药卫生—药学]