RGD脂肪醇与17-AAG脂质体的制备及抗肿瘤活性研究

发布时间：2018-05-17 01:30

本文选题：抗肿瘤 + -丙烯胺基--去甲氧基格尔德霉素(-AAG)　；参考：《首都医科大学学报》2015年02期

【摘要】：目的制备一种新的精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-脂肪醇(Arg-Gly-Asp-Phe-fatty alcohol,RGDFOC12)与17-丙烯氨基-17-去甲氧基格尔德霉素(17-allylamino-17-demethoxygeldanamycin,17-AAG)的脂质体(RGDFOC12liposomes-loaded 17-AAG,RLAs)。方法采用薄膜分散-探头超声法制备;采用激光纳米粒度仪、透射电镜和扫描电镜测定粒径,Zeta电位和外观形态;采用动态透析法测定药物释放;采用四甲基偶氮唑盐〔3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,MTT〕考察其对5种人肿瘤细胞株增生的抑制作用;通过瘤质量、存活数、体质量、脏器指数比评价其在小鼠体内抗肿瘤效果。结果制备得到的RLAs的粒径为(130.6±0.6)nm,Zeta电位为(-28.37±1.67)m V,外观形态为球形,包封率为80%以上。RLAs在p H 5.4环境的累积释放百分数大于在p H 7.4环境的累积释放百分数。RLAs在血浆中可稳定存在,12 h累积释放百分数为(15.85±0.71)%。RLAs对5种肿瘤细胞有抑制增生作用。RLAs对接种S180腹水瘤的ICR小鼠有抑制肿瘤生长作用。结论本研究制备了一种新的RLAs,制备方法简单、包封率高,具有较好的抗肿瘤活性。
[Abstract]:Objective to prepare a novel liposome RGDFOC12 and 17-allylamino-17-demethoxygeldanamycin 17-AAGG liposome, RGDFOC12 and 17-propenoamino-17-demethoxygeldanamycin 17-AAGG, respectively, which are arginine-glycin-aspartic acid-phenylalanine fatty alcohol (Arg-Gly-Asp-Phe-fatty alcohol) and 17-propenylamino-17-demethoxygeldanamycin (17-AAGN). Methods the particle size of Zeta potential and appearance were measured by laser nanocrystalline particle size analyzer, transmission electron microscope and scanning electron microscope, and the drug release was determined by dynamic dialysis method. The inhibitory effects of tetrazolium bromidede (MTT) on the proliferation of 5 human tumor cell lines were investigated by using tetrazolium bromidede tetrazolium 5-diphenyltetrazolium tetrazolium bromidede MTT, and its antitumor effect in mice was evaluated by tumor mass, survival number, body mass and viscera index ratio. Results the particle size of RLAs was 130.6 卤0.6nm, the Zeta potential was -28.37 卤1.67mV, and its appearance was spherical. The cumulative release percentage of RLAs in pH5.4 environment was higher than that in pH7.4 environment. RLAs could stably exist in plasma for 12 h. The cumulative release percentage of RLAs in plasma was 15.85 卤0.71)%.RLAs, which inhibited 5 kinds of tumor cells. RLAs inhibited the growth of ICR mice inoculated with S180 ascites tumor. Conclusion A new RLAswas prepared in this study. The preparation method is simple, the encapsulation efficiency is high, and it has good anti-tumor activity.
【作者单位】：首都医科大学化学生物学与药学院药剂学系;首都医科大学化学生物学与药学院药物化学系;
【基金】：“十二五”重大新药创制科技重大专项(2011ZX09302-007-01)~~
【分类号】：R943;R96

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