乌索酸固体脂质纳米粒的制备及其抗肿瘤活性考察  

Preparation and in vitro Antitumor Activity of Ursolic Acid Solid Lipid Nanoparticles

作　　者：陆云华[1,2] 曹丽萍[1] 李茜[1] 张琼[1] 谢秀倩[1] 陈武[1,2] 张新[1] 

机构地区：[1]湖州师范学院生命科学学院药学系,浙江湖州313000 [2]宜春学院江西省天然药物活性成分研究重点实验室,江西宜春336000

出　　处：《中国实验方剂学杂志》2014年第19期1-5,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：浙江省自然科学基金项目(LY3H280011);江西教育厅科研项目(GJJ11601);全国大学生创新创业计划项目(201210347012)

摘　　要：目的:优选乌索酸固体脂质纳米粒的处方工艺并考察其理化性质及体外抗肿瘤活性。方法:采用薄膜分散法制备乌索酸固体脂质纳米粒,以包封率为指标,通过正交试验优选处方工艺;利用透射电镜、激光粒度测定仪等考察纳米粒的理化性质,通过MMT法检测其体外抗肿瘤活性。结果:最佳处方工艺为乌索酸90 mg,卵磷脂30 mg,硬脂酸10 mg,磷酸盐缓冲液浓度10 mmol·L-1;制备的乌索酸固体脂质纳米粒在透射电镜下呈球形或椭圆球形,平均粒径(184.7±18.3)nm,包封率(82.6±0.6)%,载药量(11.9±0.5)%,48 h体外累积释放率达81.21%,30 d内粒径与包封率均无明显变化。在5,10,20,40,80μmol·L-1时,乌索酸对人肝癌细胞株SMMC-7721的抑制率分别为(9.0±1.2)%,(15.7±2.8)%,(42.3±4.6)%,(78.7±6.9)%,(79.3±7.2)%;乌索酸固体脂质纳米粒的抑制率则分别为(9.0±1.3)%,(23.6±2.2)%,(59.3±6.1)%,(84.7±8.3)%,(85.0±8.1)%。结论:薄膜法分散法制备的乌索酸固体脂质纳米粒粒径适中、体外释放和稳定性良好,具有优良的抗肿瘤活性。Objective： To optimize formulation process of ursolic acid solid lipid nanoparticles and investigate its physicochemical properties and antitumor activity. Method： Ursolic acid solid lipid nanoparticles was prepared by film dispersion method, orthogonal test was adopted to optimize formulation process by taking encapsulation efficiency as index. Its physical and chemical properties were studied by transmission electron microscope and laser particle sizer/Zeta potential system, MMT was used to detect its in vitro anti-tumor activity. Result： The best formulation process was as following： ursolic acid 90 rag, lecithin 30 mg, stearic acid 10 mg, PBS concentration of 10 mmol · L^-1. These prepared nanoparticles showed spherical or ellipsoidal under transmission electron microscope, average particle size, encapsulation efficiency and drug loading were （184.7 ±18.3） nm, （82.6 ±0.6）% and （11.9 ±0.5）%, respectively; release was 81.2% at 48 h, particle size and encapsulation efficiency had no significant change in 30 d. When the concentration of ursolic acid were 5, 10,20, 40, 80 μmol ·L^-1, inhibition rates of ursolic acid on human hepatoma cell line SMMC-7721 were （9.0 ±1.2）%, （15.7±2.8）%, （42.3±4.6）%, （78.7±6.9）% and （79.3±7.2）%, inhibition rates ofursolic acid solid lipid nanoparticleswere （9.0±1.3）%, （23.6 ±2.2）%, （59.3 ±6.1）%, （84.7 ±8.3）% and （85.0 ±8.1 ）%, respectively. Conclusion： These prepared ursolic acid solid lipid nanoparticles have appropriate size, good in vitro release and stability with excellent antitumor activity.

关 键 词：乌索酸 脂质纳米粒 处方工艺 理化性质 抗肿瘤活性 

分 类 号：R283.6[医药卫生—中药学] R285.5[医药卫生—中医学]