Study on the process optimization of self-assembled nano-drug delivery system of glycyrrhi-zic acid,curcumin and hydroxycamptothecin
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 precipita-tion 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 ob-tained,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 trans-form 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 prescrip-tion was 30 mL 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 micros-copy(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%,and 3.07%,respectively.Conclusion:In this study,GA/CUR/HCPT-NPs with appropriate size and uniform distribu-tion through optimized anti-solvent precipitation method combined with dialysis method is successfully prepared,which lays a foundation for further experiments.
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