生姜细胞外囊泡样纳米粒载吴茱萸碱的处方工艺及体外释药研究  

Study on the Formulation and in vitro Release of Evodiamine-Loaded Ginger-Derived Extracellular Vesicle-Like Nanoparticles

作　　者：赵梦 刘卓雅 于嘉敏 王芮 范铭婕 乔宏志[1,2,3] ZHAO Meng;LIU Zhuo-ya;YU Jia-min;WANG Rui;FAN Ming-jie;QIAO Hong-zhi(School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Jiangsu Key Laboratory for Functional Substance of Chinese Medicine,Nanjing 210023,China;Jiangsu Engineering Research Center for Efficient Delivery System of TCM,Nanjing 210023,China)

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏省中药功效物质重点实验室,江苏南京210023 [3]江苏省中药高效给药系统工程技术研究中心,江苏南京210023

出　　处：《南京中医药大学学报》2022年第6期527-533,共7页Journal of Nanjing University of Traditional Chinese Medicine

基　　金：中央本级重大增减支项目(2060302-1907-04);中国科协青年人才托举工程项目(2017QNRC001);江苏省高等学校自然科学研究重大项目(20KJA360004);江苏省六大人才高峰项目(SWYY-057);江苏省研究生培养创新工程项目(SJCX20_0546,SJCX20_0547,SJCX20_0680)。

摘　　要：目的采用生姜细胞外囊泡样纳米粒(EVNs)来源脂质制备载吴茱萸碱(EVO)的脂质体,以改善其成药性。方法采用差速离心法分离生姜EVNs,筛选EVNs脂质的提取溶剂。薄膜分散法制备载EVO脂质体(EVO@Lipo),以包封率为指标,正交试验优化处方和制备工艺。采用粒度电位分析、差示量热扫描(DSC)、傅里叶变换红外光谱(FTIR)对EVO@Lipo进行表征,并考察EVO@Lipo的体外释药行为。结果筛选出三氯甲烷、甲醇-三氯甲烷、乙醇-二氯甲烷作为脂质的提取溶剂,正交试验优化确定载药脂质体的最优制备条件为采用甲醇-三氯甲烷(2∶1)提取脂质,药脂比为1∶50,超声条件60 W、15 min。制得的EVO@Lipo包封率为88.21%,平均粒径194.9 nm,PDI为0.22,Zeta电位为-35.3 mV,并证明EVO@Lipo并非药物和脂质的物理混合物。体外释放实验显示,EVO@Lipo能延缓药物的释放。结论EVNs来源脂质可装载疏水性药物EVO,提高其溶解性,并具有一定的缓释作用。OBJECTIVE Lipids from ginger-derived extracellular vesicle-like nanoparticles(EVNs)were extracted and used to prepare liposomes containing evodiamine(EVO)to improve its druggability.METHODS EVNs from ginger were separated by differential centrifugation,and the lipid extraction solvent was screened.Liposomes loaded with EVO(EVO@Lipo)were prepared by thin film dispersion method.The formulation and preparation process of liposome were optimized by orthogonal test with encapsulation rate as evaluation index.EVO@Lipo was characterized by particle size and potential analysis,differential calorimetry(DSC)and Fourier transform infrared spectroscopy(FTIR),and the drug release behavior of EVO@Lipo was investigated in vitro.RESULTS Trichloromethane,methanol-trichloromethane and ethanol-dichloromethane were screened as lipid extraction solvents.The optimized preparation conditions were methanol-trichloromethane(2∶1)as lipid extraction solvent,drug to lipid ratio of 1∶50,ultrasonic conditions of 60 W,15 min.The encapsulation efficiency of EVO@Lipo was 88.21%,the average particle size was 194.9 nm,the PDI was 0.22,and the Zeta potential was-35.3 mV.Accumulated evidence suggests that EVO@Lipo is not a physical mixture of drugs and lipids.In vitro release experiments showed that EVO@Lipo could delay drug release.CONCLUSION Lipids from ginger EVNs can be used to load hydrophobic drug EVO,improve its solubility,and have a certain sustained release effect.

关 键 词：细胞外囊泡样纳米粒 生姜 吴茱萸碱 脂质体 体外释放 

分 类 号：R283[医药卫生—中药学]