摘要
目的优选甘草次酸修饰的莪术醇-芍药苷共载纳米脂质体(GA-Cur-PF-Lips)的制备工艺,并对其理化性质进行表征。方法采用乙醇注入法制备GA-Cur-PF-Lips,通过单因素考察和Box-Behnken响应面优化法优选其制备工艺;利用透射电镜观察其显微形态,采用马尔文激光粒径仪测定其粒径、多分散指数(polydispersity index,PDI)及Zeta电位,并对其体外释放度、溶血性进行考察。结果最佳工艺:脂质量85.19 mg,胆脂比1∶9.74,总投药量4.5 mg,导脂比1∶40,超声时间6.4 min(工作2 s、停2 s)。制得的GA-Cur-PF-Lips外观澄清并伴有淡蓝色乳光,透射电镜下观察呈类球形;其平均粒径为(101.1±0.25)nm,PDI为0.170±0.011,Zeta电位为(0.333±0.060)mV,莪术醇包封率为86.65%±1.11%,芍药苷包封率为47.85%±1.02%,总载药量为1.233%±0.022%;体外释放呈现缓释特征,且无明显的溶血作用。结论优化后的GA-Cur-PF-Lips包封率高、粒径小且分布均匀,无溶血性,且具有一定的缓释作用,可为GA-Cur-PF-Lips进一步研发为低毒高效的抗肝癌新药奠定基础。
Objective To optimize the preparation process of curcumol and paeoniflorin co-loaded nanoliposomes(GA-Cur-PF-Lips)modified with glycyrrhetinic acid,and to characterize the physicochemical properties.Methods GA-Cur-PF-Lips were prepared by ethanol injection,and the preparation process was optimized by single-factor investigation and Box-Behnken response surface optimization method.The microscopic morphology was observed by transmission electron microscopy,the particle size,polydispersion index(PDI)and Zeta potential were measured by Malvern laser particle size analyzer,and the release degree and hemolysis were investigated in vitro.Results The optimum process was as follows:lipid weight was 85.19 mg,the ratio of cholesterol to phospholipid was 1∶9.74,the total dosage was 4.5 mg,the ratio of the guiding molecule to the lipid mass was 1∶40 and the ultrasonic time was 6.4 min(on for 2 s,off for 2 s).The obtained GA-Cur-PF-Lips were clear with pale blue opalescence,and spherical in appearance under transmission electron microscope.The average particle size was(101.1±0.25)nm,the PDI was 0.170±0.011,the Zeta potential was(0.333±0.060)mV,the encapsulation rate of curcumol was 86.65%±1.11%,the encapsulation rate of paeoniflorin was 47.85%±1.02%,the total drug load was 1.233%±0.022%.Its in vitro release presented slow release characteristics,and there was no obvious hemolysis.Conclusion With high encapsulation rate,small particle size and uniform distribution,the optimized GA-Cur-PF-Lips have no obvious hemolysis,and have a certain sustained release effect.The experimental findings can lay a foundation for the further development of GA-Cur-PF-Lips as a new drug with low toxicity and high efficiency against liver cancer.
作者
曾盈蓉
蒋婉婷
彭程
雷雨菁
夏新华
ZENG Yingrong;JIANG Wanting;PENG Cheng;LEI Yujing;XIA Xinhua(College of Pharmacy,Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)
出处
《湖南中医药大学学报》
CAS
2023年第5期830-837,共8页
Journal of Hunan University of Chinese Medicine
基金
国家自然科学基金面上项目(81573621)
湖南省科技创新计划资助(2021RC4064)
湖南中医药大学研究生创新课题(2022CX70)。
