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

  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。 

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

  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.