人参皂苷-Rg5固体脂质纳米粒的制备与抑瘤活性研究

Preparation of Ginsenoside-Rg5 Solid Lipid Nanoparticles and evaluation of anti-tumor activity in vitro

目的制备人参皂苷-Rg5(G-Rg5)固体脂质纳米粒(G-Rg5 SLNs),并评价其对人宫颈癌细胞(Hela)的抑制效果。方法采用热熔乳化超声-低温固化法制备G-Rg5 SLNs,以脂质质量浓度(X_(1))、乳化剂质量浓度(X_(2))和助乳化剂质量浓度(X_(3))作为自变量,以G-Rg5 SLNs的粒径分布(Y_(1))与药物包封率(Y_(2))作为评价指标,通过Box-Behnken实验设计优化G-Rg5 SLNs的处方,并采用透射电镜观察其微观形态,考察G-Rg5 SLNs的体外药物释放特性;通过四甲基偶氮唑盐比色(MTT)法比较G-Rg5原料药与G-Rg5 SLNs对Hela细胞的抑制效果。结果经Box-Behnken实验设计优化得到G-Rg5 SLNs的最优处方组成为:脂质质量浓度为19.0 mg·mL^(-1),乳化剂质量浓度为9.0 mg·mL^(-1),助乳化剂质量浓度为10.0 mg·mL^(-1),根据最优处方制备的3批G-Rg5 SLNs粒径分布为(212.9±12.3)nm,包封率为85.1%±2.6%,透射电镜照片显示,G-Rg5 SLNs呈圆球状,分布均匀;体外药物释放结果显示,G-Rg5 SLNs中的药物表现出双相释药特征;体外药效学研究表明,G-Rg5 SLNs对Hela细胞的抑制率显著高于G-Rg5原料药。结论将G-Rg5制备成固体脂质纳米粒,处方合理,工艺可行,体外抑制Hela效果显著,有待进一步通过动物体内药效学实验证实。

Objective To prepare Ginsenoside-Rg5 Solid Lipid Nanoparticles(G-Rg5 SLNs),and to evaluate its inhibitory effect on human cervical cancer cells(Hela)in vitro.Methods G-Rg5 SLNs were prepared by hot melt emulsification-ultrasonic and low temperature-solidification method.By using lipid concentration(X_(1)),emulsifier concentration(X_(2))and co-emulsifier concentration(X_(3))as independent variables,particle size distribution(Y_(1))and drug encapsulation efficiency(Y_(2))of G-Rg5 SLNs as evaluation indicators,the formulation of G-Rg5 SLNs was optimized through Box-Behnken experimental design.The microscopic morphology of G-Rg5 SLNs was evaluated,and the in vitro drug release characteristics of G-Rg5 SLNs were investigated.The inhibitory effects of G-Rg5 active pharmaceutical ingredients(API)and G-Rg5 SLNs on human cervical cancer cells were compared by MTT method.Results The optimal formulation composition of G-Rg5 SLNs was as follows:lipid concentration(X_(1))19.0 mg·mL^(-1),emulsifier concentration(X_(2))9.0 mg·mL^(-1),co-emulsifier concentration(X 3)10.0 mg·mL^(-1).3 batches of G-Rg5 SLNs were prepared according to the optimal formulation.The average particle size was(212.9±12.3)nm and the encapsulation efficiency was 85.1%±2.6%.Under transmission electron microscope,G-Rg5 SLNs were spherical distribution.The in vitro drug release showed the G-Rg5 SLNs exhibited biphasic release characteristics.The in vitro pharmacodynamic studies showed the inhibitory rate of G-Rg5 SLNs on human cervical cancer cells was significantly higher than that of G-Rg5 bulk drugs.Conclusion The G-Rg5 SLNs formulation and preparation process are reasonable and feasible.G-Rg5 SLNs can inhibite human cervical cancer cells significantly in vitro,and which could be further confirmed by animal pharmacodynamic experiments.