甘草酸、姜黄素和羟基喜树碱自组装纳米粒递药系统的工艺优化研究  

Study on the process optimization of self-assembled nano-drug delivery system of glycyrrhizic acid,curcumin and hydroxycamptothecin

作　　者：冯丽珍 黄锦平 刘胜君 王瑶 黄冬怡 黄婷婷 廖伟菊 邓润芳 黄兴振[1] 靳荣华 FENG Lizhen;HUANG Jinping;LIU Shengjun;WANG Yao;HUANG Dongyi;HUANG Tingting;LIAO Weiju;DENG Runfang;HUANG Xingzhen;JIN Ronghua(College of Pharmacy,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,南宁530021

出　　处：《广西医科大学学报》2024年第4期598-607,共10页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.82360367);广西自然科学基金资助项目(No.2023GXNSFAA026316);广西生物活性分子研究与评价重点实验室资助项目。

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。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,whi

关 键 词：羟基喜树碱 姜黄素 甘草酸 无载体绿色纳米递药系统 工艺优化 

分 类 号：R914[医药卫生—药物化学]