【摘要】 目的：以两亲性药物分子甘草酸（GA）、疏水性药物姜黄素（CUR）和羟基喜树碱（HCPT）为材料，通过自组装形式构建GA、CUR和HCPT纳米粒递药系统（GA/CUR/HCPT-NPs），考察其制备工艺并进行质量评价。方法：采用反溶剂沉淀法和透析法相结合制备GA/CUR/HCPT-NPs，利用响应面Box-Behnken法对制备工艺进行优化，最终获得尺寸合适，稳定电荷，高载药量的GA/CUR/HCPT-NPs；并对优化出来的GA/CUR/HCPT-NPs进行核磁共振氢谱（1HNMR）、差示扫描量热法（DSC）、高分辨X射线衍射法（XRD）、傅里叶红外分光光度法（FTIR）、紫外分光光度法（UV）等表征和微观形态观察，并测定GA/CUR/HCPT-NPs中GA、CUR和HCPT含量大小。结果：得到的最优处方为去离子水体积30 mL，二甲基亚砜（DMSO）1 min内滴入去离子水，制备温度为40℃，确定GA、CUR、HCPT投药量分别为6.00 mg、10.03 mg、5.01 mg；测量GA/CUR/HCPT-NPs粒径为（146.37±0.15）nm，且带较高的稳定电荷-（34.43±0.77）mV,PDI为0.157±0.01，透射电子显微镜（TEM）和扫描电子显微镜（SEM）可观察到GA/CUR/HCPT-NPs是类球形或球形，并且均匀分布；1HNMR、DSC、XRD等证明了成功自组装成稳定的GA/CUR/HCPT-NPs，并且在7 d内4℃保存条件下稳定性良好；高效液相色谱（HPLC）测定GA/CUR/HCPT-NPs中GA、CUR、HCPT的载药量分别为57.19%、39.17%和3.07%。结论：本研究通过优化的反溶剂沉淀法结合透析法成功制备尺寸合适、均匀分布的GA/CUR/HCPT-NPs，为进一步实验奠定了基础。更多还原

【Abstract】 Objective: To construct the nano-drug delivery system(GA/CUR/HCPT-NPs) of glycyrrhizic acid(GA), curcumin(CUR) and hydroxycamptocampin(HCPT) with amphiphilic drug molecules GA, hydrophobic drug CUR and HCPT as materials by self-assembly, and to investigate its preparation technology as well as to evaluate its quality. Methods: GA/CUR/HCPT-NPs was prepared by the combination of anti-solvent precipitation method and dialysis method, and the preparation process was optimized by response surface methodology(Box-Behnken). Finally, the GA/CUR/HCPT-NPs with suitable size, stable charge and high drug loading was obtained, then the optimized GA/CUR/HCPT-NPs was characterized by H nuclear magnetic resonance spectrometer(1HNMR), differential scanning calorimetry(DSC), high-resolution X-ray diffractometer(XRD), Fourier transform infrared(FTIR) as well as ultraviolet-uisible spectropho(UV), and it’s micromorphology was observed.The contents of GA, CUR and HCPT in GA/CUR/HCPT-NPs were determined. Results: The optimal prescription was 30 m L deionized water, dimethyl sulfoxide(DMSO) was dropped into the deionized water within 1 min,the preparation temperature was 40 ℃, and the dosage of GA, CUR and HCPT was determined to be 6.00 mg,10.03 mg and 5.01 mg, respectively. The particle size of GA/CUR/HCPT-NPs was(146.37±0.15) nm, with a high stable charge of(-34.43±0.77) mV, and the polydispersity index(PDI) was 0.157±0.01. GA/CUR/HCPT-NPs was spherical and uniformly distributed under transmission electron microscopy(TEM) and scanning electron microscopy(SEM).1HNMR, DSC, XRD, etc. demonstrated that GA/CUR/HCPT-NPs had successful self-assembly, and had a great stability when stored at 4 ℃ within 7 days. The drug loading contents of GA, CUR, and HCPT in GA/CUR/HCPT-NPs determined by high-performance liquid chromatography(HPLC) were 57.19%, 39.17%, and3.07%, respectively. Conclusion: In this study, GA/CUR/HCPT-NPs with appropriate size and uniform distribution through optimized anti-solvent precipitation method combined with dialysis method is successfully prepared,which lays a foundation for further experiments.更多还原