[关键词]
[摘要]
目的 优化RGD环肽修饰的姜黄素(curcumin,Cur)/黄芩苷(baicalin,Bai)共递送靶向纳米脂质体(RGD-Cur/Bai-Lip)的制备工艺并进行表征评价。方法 采用乙醇注入法制备RGD-Cur/Bai-Lip,首先通过Plackett-Burman筛选实验确定超声时间、胆脂比、水合温度作为制备RGD-Cur/Bai-Lip的关键因素,然后采用Box-Behnken响应面法进行工艺优化,以姜黄素包封率、黄芩苷包封率、总载药量为考察指标,采用AHP-复相关系数法-拉开档次法进行多指标组合赋权以确定各指标权重系数并计算综合评分,从而确定RGD-Cur/Bai-Lip的最优处方及关键工艺参数。最后对其形态、粒径电位、稳定性、体外释放度及溶血性等进行表征评价。结果 优选得到的最佳工艺为胆脂比1:12,水合温度60℃,探头超声时间为10 min。RGD-Cur/Bai-Lip外观澄清透明,呈亮黄色,对光可视淡蓝色乳光,透射电子显微镜下观察形态圆整、分散均匀。平均粒径为(101.10±0.62)nm,多分散系数(PDI)为0.191 0±0.014 3,Zeta电位为(1.59±0.07)mV,姜黄素包封率为(94.28±4.51)%,黄芩苷包封率为(76.93±1.35)%,总载药量为(2.27±0.09)%。7 d内稳定性良好,无溶血性,并具有一定的缓释作用。结论 优化处方后制备的RGD-Cur/Bai-Lip包封率高,粒径分布均匀,7 d内较稳定,无溶血性,并具有一定的缓释作用,为RGD-Cur/Bai-Lip的后续抗肝纤维化体内外研究提供了制剂基础。
[Key word]
[Abstract]
Objective To optimize the preparation and characterization of curcumin/baicalin co-delivery targeting nanoliposomes (RGD-Cur/Bai-Lip) modified by RGD cyclopeptide. Methods RGD-Cur/Bai-Lip was prepared by ethanol injection. Ultrasonic time, bile-fat ratio and hydration temperature were determined by Plackett-Burman screening experiment as the key factors for the preparation of RGD-Cur/Bai-Lip. Then the process was optimized by Box-Behnken response surface method, with curcumin entrapment efficiency, baicalin entrapment efficiency and total drug loading as indexes. The AHP-multiple correlation coefficient method-open grade method was used to determine the weight coefficient of each index and calculate the comprehensive score, so as to determine the optimal prescription and key process parameters of RGD-Cur/Bai-Lip. Finally, its morphology, particle size potential, stability, in vitro release and hemolysis were characterized and evaluated. Results The optimum conditions were as follows:the ratio of bile to lipid was 1:12, the hydration temperature was 60℃, and the ultrasonic time of the probe was 10 min. The appearance of RGD-Cur/Bai-Lip was clear and transparent, bright yellow, light blue opalescent light. Under transmission electron microscope, RGD-Cur/Bai-Lip dispersed evenly with round shape. The average particle size was (101.10 ±0.62) nm, the dispersion coefficient (PDI) was 0.191 0 ±0.014 3, the Zeta potential was (1.59 ±0.07) mV, the entrapment efficiency of curcumin was (94.28 ±4.51)%, the entrapment efficiency of baicalin was (76.93 ±1.35)%, and the total drug loading was (2.27 ±0.09)%. It had good stability and no hemolysis within 7 d, and had a certain sustained release effect. Conclusion This method can effectively and reliably optimize the preparation process of RGD-Cur/Bai-Lip. After optimizing the prescription, the prepared RGD-Cur/Bai-Lip has high entrapment efficiency, uniform particle size distribution and good stability without hemolysis, which provides a preparation basis for the follow-up study of anti-hepatic fibrosis of RGD-Cur/Bai-Lip in vivo and in vitro.
[中图分类号]
R283.6
[基金项目]
湖南中医药大学中药学一流学科开放基金项目(2020ZYX09)