山柰酚固体脂质纳米粒的制备及体外抗非小细胞肺癌作用研究  

Preparation of kaempferol loaded solid lipid nanoparticles and its anti-non-small-cell carcinoma effect in vitro

作　　者：刘金丽 马玉霏 侯甲福[2] 佟雷[2] LIU Jin-li;MA Yu-fei;HOU Jia-fu;TONG Lei(Affiliated Hongqi Hospital of Mudanjiang Medical University,Heilongjiang Mudanjiang 157000,China;School of Pharmacy,Mudanjiang Medical University,Heilongjiang Mudanjiang 157000,China)

机构地区：[1]牡丹江医学院附属红旗医院,黑龙江牡丹江157000 [2]牡丹江医学院药学院,黑龙江牡丹江157000

出　　处：《中国医院药学杂志》2022年第17期1798-1803,共6页Chinese Journal of Hospital Pharmacy

基　　金：黑龙江省自然科学基金项目(编号:SS2021H004);黑龙江省卫生健康委科研课题(编号:20211313020250)。

摘　　要：目的:制备山柰酚(kaemperol,KA)固体脂质纳米粒(KA-SLN),并评价其体外抗肿瘤效果。方法:首先建立KA的含量测定方法,并进行方法学考察,采用乳化超声分散法制备KA-SLN,测定其包封率、载药量、粒径及电位并拟合其体外释药方程,采用CCK-8法及溶血性试验评价空白载体及KA-SLN的体外安全性,采用CCK-8法评价A549细胞生存率变化,倒置光学显微镜下观察细胞形态学变化,采用Transwell法评价A549细胞迁移能力的变化,Hoechst染色法观察肿瘤细胞凋亡情况,平板克隆试验考察肿瘤细胞集落形成能力的变化。结果:所得制剂平均粒径(242±21)nm,包封率为(72.34±4.15)%,载药量为(3.29±0.21)%,空白载体无毒性,空白载体及KA-SLN体外无溶血性,释药规律符合Ritger-peppas方程,相对于KA,KA-SLN展示出更好地抑制肿瘤细胞增殖、迁移、集落形成作用及促肿瘤细胞凋亡效果。结论:通过将KA制成KA-SLN可以提高药物缓控释效果及体外抗肿瘤作用,且安全性较好,可进一步用于体内抗肿瘤研究。OBJECTIVE To prepare kaemperol loaded solid lipid nanoparticles(KA-SLN)and evaluate the antitumor effect.METHODS Firstly,the content determination method for KA was established,and KA-SLN was prepared by an emulsification ultrasonic dispersion method.The encapsulation rate,drug loading rate,particle size and Zeta potential of KA-SLN were determined,and the in vitro drug release equation was fitted.The safety of blank carrier and KA-SLN was evaluated by CCK-8 method and hemolytic test in vitro.CCK-8 method was used to evaluate the survival rate of A549 cells.The cell morphological changes were observed under an inverted microscope,the migration ability of A549 cells was evaluated by Transwell experiment,the apoptosis of tumor cells was observed by Hoechst staining,and the colony formation of tumor cells was investigated by plate cloning test.RESULTS The average particle size of the preparation was(242±21)nm,the encapsulation rate was(72.34±4.15)%,and the drug loading rate was(3.29±0.21)%.No apparent hemolysis appeared in vitro.The drug release was in line with the Ritger-peppas equation,and KA-SLN had better inhibitory effects on tumor cell proliferation,migration and colony formation,and showed better promoting effect on tumor cell apoptosis than free KA.CONCLUSION The preparation of KA-SLN can not only promote drug controlled release and antitumor performance in vitro,but also reduce toxicity of free KA,which is expected to be used for antitumor in vivo.

关 键 词：山柰酚 固体脂质纳米粒 非小细胞肺癌 细胞凋亡 

分 类 号：R943[医药卫生—药剂学]