星点设计-效应面法优化莪术油纳米乳的处方工艺及其体外抗肿瘤活性研究

Preparation Technology Optimization of Zedoary Turmeric Oil Nano-emulsion by Central Composite Design-Response Surface Methodology and Its Antitumor Activity in vitro

目的:优化莪术油纳米乳(ZTO-NM)的处方工艺,并对其进行体外抗肿瘤活性研究。方法:首先采用星点设计-效应面法优化ZTO-NM的处方工艺,然后对最优处方制备的ZTO-NM进行理化性质考察。以肝癌细胞SMMC-7721为模型,采用MTT法检测ZTO-NM的体外抗肿瘤活性。结果:最佳处方工艺为:蓖麻油聚氧乙烯醚(EL-35)为0.72 g,聚乙二醇400(PEG-400)为0.40 g,油酸乙酯(EO)为0.24 g,ZTO为0.12 g,纯水为8.0 ml。采用最优处方工艺制得的ZTO-NM外观澄清透明、稳定性好,平均粒径为29.21 nm;透射电镜下显示其为类球形结构;ZTO-NM的包封率和载药量分别为(98.48±0.06)%和(7.99±0.01)%。与莪术油相比,ZTO-NM对SMMC-7721增殖的抑制作用更强(P<0.01),并具有浓度和时间依赖性细胞抑制作用。结论:本实验采用最优处方工艺制备的ZTO-NM的相关理化性质均符合纳米乳的质量要求,可为下一步莪术油多机制抗肿瘤研究提供一定的理论基础。

Objective:To optimize the technological conditions of zedoary turmeric oil nano-emulsion(ZTO-NM),and study its antitumor activity in vitro.Methods:Firstly,the formulation and preparing process of ZTO-NM were optimized by central composite design-response surface methodology,and then the physical-chemical properties of ZTO-NM prepared by the optimal formulation were investigated.Finally,the antitumor activity of ZTO-NM on SMMC-7721 liver tumor cells was detected by MTT assay.Results:The optimal formulation process was as follows:EL-35 was 0.72 g,PEG-400 was 0.40 g,EO was 0.24 g,ZTO was 0.12 g,and pure water was 0.8 ml.The ZTO-NM prepared by the optimal formulation and process had a clear,transparent,well-distributed and stable appearance,and the average particle size was 29.21 nm.The photos under a transmission electron microscope showed that it had quasi-spherical structure.The encapsulation efficiency and the drug loading of ZTO-NM were(98.48±0.06)% and(7.99±0.01)%,respectively.When compared with zedoary turmerie oil,ZTO-NM had much higher inhibition rate on SMMC-7721 cells in concentration-and time-dependent manners(P<0.01).Conclusion:The relevant physical and chemical properties and appearance of ZTO-NM prepared by the optimal formulae meet the quality requirements for nano-emulsion,and the preparation technology is stable.This study provides certain theoretical basis for further antitumor research of zedoary turmeric oil.