RGD脂肪醇与17-AAG脂质体的制备及抗肿瘤活性研究

摘要

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.%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(RGDFOC12 liposomes-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)mV,外观形态为球形,包封率为80%以上。 RLAs在pH 5.4环境的累积释放百分数大于在pH 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。