RGD脂肪醇与17-AAG脂质体的制备及抗肿瘤活性研究  

Preparation and anti-tumor activity of a novel liposome-loaded drug

作　　者：李雪梅[1] 王玉记[2] 吴建辉[2] 崔纯莹[1] 

机构地区：[1]首都医科大学化学生物学与药学院药剂学系,北京100069 [2]首都医科大学化学生物学与药学院药物化学系,北京100069

出　　处：《首都医科大学学报》2015年第2期172-177,共6页Journal of Capital Medical University

基　　金："十二五"重大新药创制科技重大专项(2011ZX09302-007-01)~~

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。Objective To prepare an Arg-Gly-Asp-Phe-fatty alcohol （ RGDFOC12 ） liposomes-loaded 17-allylamino-17-demethoxygeldanamycin（17-AAG）. Methods RGDFOC12 liposomes-loaded 17-AAG（RLAs） was prepared by film dispersion method and evaluated by particle size analysis, Zeta potential, encapsulation efficiency, the release in vitro, plasma stability, 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（ MTT） assay and the anti-tumor activity in vivo. Results The RLAs was stable colloidal dispersion system in spherical shape of （130.6±0.6）nm in diameter and the Zeta potential was （-28.37±1.67）mV. The release of RLAs in vitro showed that the released percentage of RLAs in pH 5. 4 is more than that in pH 7. 4. The MTT assay proved that RLAs inhibited the proliferation of cancer cells. The anti-tumor assay showed that RLAs inhibited tumor growth and reduced the toxicity. Conclusion The RLAs were prepared by film dispersion method. RLAs showed anti-tumor activity in vivo and good potential in cancer therapy.

关 键 词：抗肿瘤 17-丙烯胺基-17-去甲氧基格尔德霉素(17-AAG) 精氨酸-甘氨酸-天冬氨酸-苯丙氨酸-脂肪醇(RGDFOC12) 

分 类 号：R965.1[医药卫生—药理学]