甘露糖修饰的千金藤素聚合物胶束的制备及表征  

Preparation and Characterization of Mannose-Modified Cepharanthine Polymer Micelles

作　　者：陈怡莹 周益 罗丽琴 姜婕 程炳铎 李元增 程欣 马云淑 CHEN Yiying;ZHOU Yi;LUO Liqin;JIANG Jie;CHENG Bingduo;LI Yuanzeng;CHENG Xin;MA Yunshu(College of Chinese Medicine,Yunnan University of Chinese Medicine,Kunming 650500,China;Yunnan Province University External Drug Delivery System and Preparation Technology Research Key Laboratory,Kunming 650500,China;Yunnan Province Dai Medicine and Yi Medicine Primary Laboratory,Kunming 650500,China;Yunnan Province Nanyao Sustainable Utilization Primary Laboratory,Kunming 650500,China)

机构地区：[1]云南中医药大学中药学院,昆明650500 [2]云南省高校外用给药系统与制剂技术研究重点实验室,昆明650500 [3]云南省傣医药与彝医药重点实验室,昆明650500 [4]云南省南药可持续利用重点实验室,昆明650500

出　　处：《中国药学杂志》2024年第19期1834-1842,共9页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(82174065);云南省科技厅社会发展专项-重点研发计划项目资助(202303AC100025);云南省傣医药与彝医药重点实验室开放课题资助(202210ZD2207)。

摘　　要：目的制备千金藤素(cepharanthine,CEP)聚合物胶束,并对其进行表征。方法采用溶剂挥发法制备CEP聚合物胶束,在单因素考察的基础上,以包封率和载药量为指标,Box-Behnken响应面法进行制备工艺优化,并对其胶束的粒径分布、电位、体外释放等方面进行表征。结果CEP聚合物胶束的最佳工艺为:取甘露糖-聚乙二醇-聚乳酸羟基乙酸共聚物(MA-PEG-PLGA)50 mg,CEP 17.82 mg,溶解于0.25 mL丙酮中,逐滴加入14 mL的PBS溶液中,温度为60℃,以1000 r·min^(-1)的转速在磁力搅拌器上搅拌4 h,即得澄清的CEP聚合物胶束。优选得到的CEP聚合物胶束呈球形,平均粒径为(111.37±3.51)nm、多分散系数(PDI)为(0.21±0.01)、Zeta电位(-9.78±2.15)mV;体外释放结果显示,CEP原料药在10 h内快速释放,其胶束在72 h内分别释放(79.99±4.96)%和(71.66±2.62)%,说明制成胶束后,CEP能实现缓释释放。冻干剂考察结果发现,0.5%的泊洛沙姆188冻干后复溶后粒径变化最小;溶血试验结果显示,将CEP制成胶束后,溶血率明显降低。结论本研究的优选处方及工艺可以用于CEP-MA-PEG-PLGA聚合物胶束的制备,为后续CEP靶向制剂的研发奠定基础。OBJECTIVE To prepare cepharanthine(CEP)polymer micelles and characterize them.METHODS The CEP polymer micelles were prepared by solvent evaporation method.Based on the single factor investigation,the preparation process was optimized by Box-Behnken response surface method with the entrapment efficiency and drug loading as indicators,and the particle size distribution,potential and in vitro release of the micelles were characterized.RESULTS The optimum process of CEP polymer micelle was as follows:50 mg of MA-PEG-PLGA and 17.82 mg of CEP were dissolved in 0.25 mL of acetone,added dropwise into 14 mL of PBS solution at 60℃and stirred on a magnetic stirrer at a speed of 1000 r·min^(-1)for 4 hours to obtain a clear CEP polymer micelle.The optimized CEP polymer micelles are spherical,with an average particle size of(111.37±3.51)nm,a PDI of(0.21±0.01)and a Zeta potential of(-9.78±2.15)mV.In vitro release results showed that CEP was released rapidly within 10 h,and its micelles released(79.99±4.96)%and(71.66±2.62)%respectively within 72 h,indicating that CEP could be released slowly after being made into micelles.The results of freeze-drying agent investigation showed that 0.5%poloxamer 188 had the smallest change in complex particle size after freeze-drying.The results of hemolysis test showed that the hemolysis rate was obviously reduced after CEP was made into micelles.CONCLUSION The optimized formulation and technology in this study can be used for the preparation of CEP-MA-PEG-PLGA polymer micelles,which lays a foundation for the subsequent development of CEP targeted preparations.

关 键 词：千金藤素 聚合物胶束 甘露糖 Box-Behnken响应面法 冻干粉 

分 类 号：R944[医药卫生—药剂学]