齐墩果酸与羟基喜树碱共组装纳米粒的制备及体外抗肿瘤评价

Preparation and in Vitro Anti-Tumor Evaluation of Oleanolic Acid and Hydroxycamptothecin Co-Assembled Nanoparticles

关键词:  齐墩果酸  羟基喜树碱  共组装  纳米粒

Key words:  oleanolic acid  hydroxycamptothecin  co-assembly  nanoparticles

摘要:

目的 制备齐墩果酸与羟基喜树碱共组装纳米粒，优化其制备工艺，进行药剂学性质研究和体外抗肿瘤活性评价。方法 采用抗溶剂沉淀结合超声法制备齐墩果酸-羟基喜树碱共组装纳米粒(OA-HCPT NPs)；采用动态光散射法、扫描电子显微镜、傅里叶变换红外光谱等对OA-HCPT NPs的粒径、电位、形态、含量和稳定性进行研究；采用CCK-8法考察OA-HCPT NPs对结肠癌细胞HCT116及肺癌细胞A549的增殖抑制作用。结果 制备所得OA-HCPT NPs形态为类球形，粒径和电位分别为(245.1±16.4) nm、(-10.1±0.5) mV。傅里叶变换红外光谱结果表明OA-HCPT NPs较原料药及物理混合物特征峰发生明显变化。体外细胞毒性实验表明OA、HCPT对HCT116细胞及A549细胞均有抑制作用，且呈浓度依赖性，OA-HCPT NPs分别在20~100 μmol·L-1和10~50 μmol·L-1时对HCT116细胞及A549细胞的抑制作用显著增强(P<0.01，P<0.05)。结论 抗溶剂沉淀结合超声法制备OA-HCPT NPs方法可行，制剂平均粒径较小且分布均匀；OA-HCPT NPs对HCT116细胞及A549细胞的体外增殖抑制作用显著增强。

Abstract:

OBJECTIVE To construct oleanolic acid and hydroxycamptothecin co-assembled nanoparticles (OA-HCPT NPs), optimize their preparation, study their pharmaceutical properties and evaluate their anti-tumor efficacy in vitro. METHODS The OA-HCPT NPs were prepared by anti-solvent precipitation combined with ultrasound. The particle size, Zeta potential, morphology, content and stability of OA-HCPT NPs were studied by the dynamic light scattering, scanning electron microscopy and fourier transform infrared spectrometry. The inhibitory effect of OA-HCPT NPs on the proliferation of colon cancer HCT116 cells and lung cancer cell A549 was detected by CCK-8. RESULTS The OA-HCPT NPs was spherical in appearance, and the particle size and Zeta potential were (245.1±16.4) nm and (-10.1±0.5) mV, respectively. Fourier transform infrared spectrum results show that the characteristic peaks of OA-HCPT NPs are significantly different from that of raw materials and physical mixtures. In vitro cytotoxicity test showed that OA and HCPT inhibited both HCT116 cells and A549 cells in a concentration-dependent manner. OA-HCPT NPs significantly increased the inhibition of HCT116 cells and A549 cells at 20~100 μmol·L-1 and 10~50 μmol·L-1, respectively (P<0.01, P<0.05). CONCLUSION The OA-HCPT NPs could be obtained by a feasible anti-solvent precipitation combined with ultrasound method with small particle size and uniform size distribution. OA-HCPT NPs significantly enhanced the inhibitory effects on HCT116 cell and A549 cell proliferation in vitro.