Box-Behnken优化去氢骆驼蓬碱纳米结构脂质载体的处方及其抗肿瘤活性研究  

Optimization of harmine-loaded nanostructure lipid carriers by Box-Behnken design and its anticancer effect study

作　　者：刘媛媛[1] LIU Yuanyuan(Xianyang Vocational College,Xianyang,Shanxi,712000 P. R. China)

机构地区：[1]咸阳职业技术学院

出　　处：《华西药学杂志》2019年第4期337-342,共6页West China Journal of Pharmaceutical Sciences

摘　　要：目的通过Box-Behnken设计优化去氢骆驼蓬碱纳米结构脂质载体的处方,并评价其对小鼠接种人宫颈癌Hela细胞的抑制效果。方法采用乳化蒸发-低温固化法制备去氢骆驼蓬碱纳米结构脂质载体,以药物用量、脂质浓度、表面活性剂浓度作为自变量,粒径大小和包封率作为因变量,通过Box-Behnken设计优化去氢骆驼蓬碱纳米结构脂质载体的最佳处方,并考察其微观结构、粒径分布、Zeta电位以及体外释药规律;比较了去氢骆驼蓬碱纳米结构脂质载体与去氢骆驼蓬碱溶液对小鼠接种人宫颈癌Hela细胞的抑制效果。结果去氢骆驼蓬碱纳米结构脂质载体的最佳处方为:药物用量60mg、脂质浓度5.5mg·mL^-1、表面活性剂浓度1.5mg·mL^-1;所制备的纳米结构脂质载体呈球形或类球形分布,粒径为98.4±15.3nm,Zeta电位为-37.4±1.5mV,包封率为82.4%±2.5%;去氢骆驼蓬碱纳米结构脂质载体前期释药出现突释现象,后期释药较为缓慢、平稳;去氢骆驼蓬碱纳米结构脂质载体对小鼠接种人宫颈癌Hela细胞的抑制作用显著高于溶液。结论将去氢骆驼蓬碱制备成纳米结构脂质载体可以延长药物的释放时间,增强药物对人宫颈癌Hela细胞的抑制作用,对宫颈癌的治疗可能具有潜在的应用价值。OBJECTIVE To optimize harmine - loaded nanostructure lipid carriers ( HLNLC) by Box - Behnken design and to evaluate its inhibitory effect on human cervical cancer Hela cells. METHODS The HLNLC were prepared by the emulsion evaporation - low temperature solidification method. The harmine amount, lipid concentration and surfactant concentration were used as independent variables, while the particle size distribution and encapsulation efficiency as dependent variables. The optimal formulation of HLNLC were optimized by Box - Behnken design. The microstructure, particle size distribution, Zeta potential and in vitro release were investigated. The inhibitory effects of HLNLC and harmine solution on human cervical cancer Hela cells were compared. RESULTS The optimal formulation of HLNLC was as follows: The drug amount was 60 mg, the lipid concentration was 5. 5·mgL^-1,and the surfactant concentration was 1.5·mgL^-1. The TEM observed them as a spherical or spheroidal distribution. The particle size distribution was 98. 4 ± 15. 3 nm;Zeta potential was - 37. 4 ± 1. 5 mV;and the entrapment efficiency was 82. 4%± 2. 5%. The drug release of HLNLC showed a bursting phenomenon in the early stage,and it was slow and stable in the later stage. The inhibitory effect of the HLNLC on human cervical cancer Hela cells was more significant than that of harmaline solution. CONCLUSION The HLNLC can prolong the drug release time and enhance the inhibitory effect on human cervical cancer Hela cells. It may have potential application value in the treatment of cervical cancer.

关 键 词：去氢骆驼蓬碱 纳米结构脂质载体 BOX-BEHNKEN设计 乳化蒸发-低温固化法 体外释药 人宫颈癌HELA细胞 抑瘤活性 优化 

分 类 号：R94[医药卫生—药剂学] R96[医药卫生—药学]