叶酸修饰的粉防己碱壳聚糖-硬脂酸纳米胶束的制备、表征及体外抗炎活性考察

Preparation,characterization and in vitro anti-inflammatory activity of tetrandrine-loaded chitosan-stearic acid nano micelles modified with folic acid

目的制备叶酸(FA)修饰的粉防己碱(TET)壳聚糖(CS)-硬脂酸(SA)纳米胶束(简称“FA-CS-SA/TET纳米胶束”),并进行表征和体外抗炎活性考察。方法采用超声法制备FA-CS-SA/TET纳米胶束,以包封率(EE)、载药量(DL)、粒径的综合评分为评价指标,FA-CS-SA与TET质量比、超声功率和超声次数为考察因素,根据正交实验确定最优制备工艺并验证;对以最优工艺制备的FA-CS-SA/TET纳米胶束进行表征,并考察其体外释放性能。以RAW264.7细胞为实验对象,考察其体外抗炎活性。结果最优制备工艺为FA-CS-SA与TET质量比2∶1,超声功率200W,超声200次。以最优工艺制备的FA-CS-SA/TET纳米胶束的EE为(98.86±0.30)%,DL为(28.57±0.34)%,平均粒径为(227.0±9.4)nm,多分散性指数为0.42±0.04,Zeta电位为(12.6±2.3)mV;该纳米胶束呈类圆形且分布均匀,其在0.5%十二烷基硫酸钠溶液中释放较快,72h内的累积释放度为(79.49±3.43)%,且其抗炎作用强于TET原料药。结论本研究成功制备了FA-CS-SA/TET纳米胶束,其载药性能良好,粒径均匀,且具有较好的体外抗炎活性。

OBJECTIVE To prepare tetrandrine(TET)-loaded chitosan(CS)-stearic acid(SA)nano micelles modified with folic acid(FA)(FA-CS-SA/TET nano micelles),characterize them and study the anti-inflammatory effect in vitro.METHODS FA-CS-SA/TET nano micelles were prepared by ultrasonic method;the preparation technology was optimized by orthogonal test and validation test was also performed with the mass ratio of FA-CS-SA to TET,ultrasound power and ultrasound times as the factors,using the comprehensive score of entrapment efficiency(EE),drug loading(DL)and particle size as evaluation index.FA-CS-SA/TET nano micelles prepared by the optimal technology were characterized,and their release performance in vitro was investigated.RAW264.7 cells were used as subjects to investigate their anti-inflammatory activity in vitro.RESULTS The optimal preparation technology included that the mass ratio of FA-CS-SA to TET was 2∶1,ultrasonic power was 200 W,and the ultrasonic frequency was 200 times.The parameters of FA-CS-SA/TET nano micelles prepared by optimized technology included that EE was(98.86±0.30)%,DL was(28.57±0.34)%,the average particle size was(227.0±9.4)nm,polydispersity index was 0.42±0.04,and the Zeta potential was(12.6±2.3)mV,respectively.The nano micelles were uniform in appearance and round in shape.The nano micelles were released quickly in 0.5%sodium dodecyl sulfate solution,with a cumulative release rate of(79.49±3.43)%within 72 hours,and its anti-inflammatory effect was stronger than that of TET raw materials.CONCLUSIONS FA-CS-SA/TET nano micelles are prepared successfully in the study,with good drug loading performance,uniform particle size,and good in vitro anti-inflammatory activity.