Construction And Preliminary Pharmacodynamics Of Glycyrrhiza Flavone Nanosponge Drug Delivery System Based On Cyclodextrin Modification Technology

Glycyrrhiza flavonoids is a sort of flavonoids extracted from Glycyrrhiza uralensis,which has a wide range of pharmacological effects.However,recent studies have found that its water solubility is poor,which affects its bioavailability in vivo and limits its clinical application.In order to improve its solubility and dissolution,this paper taking Glycyrrhiza flavonoids as model drug,prepared Glycyrrhiza flavonoids cyclodextrin nanosponge based on the modification technology of cyclodextrin,optimized the preparation process,and studied its physicochemical properties and preliminary pharmacodynamics.This research realized the combination of cyclodextrin nanosponge and the effective part of traditional Chinese medicine,we expect to provide the universality and feasibility of applying this technology to the effective part of traditional Chinese medicine.Firstly,a method for in vitro analysis of Glycyrrhiza flavonoids was established.The contents of flavonoids and glycyrrhizin in crude drug were determined by UV and HPLC,respectively.Under the guidance of the Chinese Pharmacopoeia(2015edition),a method was established to determine the dissolution of Glycyrrhiza flavone cyclodextrin nanosponge in vitro.At the same time,based on the consideration of the safety of medicine,a method for the determination of the key impurity phenol in the process by high performance liquid chromatography was established to meet the relevant requirements..Glycyrrhiza flavone cyclodextrin nanosponges were prepared by stirring-freeze drying method.On the basis of single factor test and the guidance of multi-index weight coefficient thinking,the preparation process was optimized by Box-Behnken response surface methodology,with drug loading and particle size as indicators and comprehensive score values as weights.Finally,the optimum preparation condition was stirring temperature 45 °C,stirring time 4.8 h,stirring speed 245 r·min-1,and the comprehensive score OD was 94.78 under the optimum conditions.Under this optimal condition,the process is verified,and the difference between the measured comprehensive score and the predicted value is small.The physicochemical properties of Glycyrrhiza flavone cyclodextrin nanosponge were investigated.The drug loading,average particle size and solubilization ratio were determined.The drug was characterized by visual measurement,scanning electron microscopy(SEM),differential scanning calorimetry(DSC),Fourier transform infrared spectroscopy(FT-IR)and X-ray diffraction(XRD).The dissolution properties in vitro were investigated.Finally,the influencing factors were tested to verify the stability of the preparation.The results showed that the drug loading,average particle size and solubilization ratio of Glycyrrhiza flavone cyclodextrin nanosponge were excellent.The results of visual measurement and scanning electron microscopy showed that the glycyrrhiza flavone cyclodextrin nanosponge had good morphology.Under different multiples of electron microscopy,the glycyrrhiza flavone cyclodextrin nanosponge showed different states.Differential scanning calorimetry(DSC),Fourier transform infrared spectroscopy(FTIR)and Xray diffraction(XRD)were used to verify the formation of Glycyrrhiza flavonoids cyclodextrin nanosponge,and the existence of Glycyrrhiza flavonoids in amorphous state in the cyclodextrin nanosponge.In vitro dissolution test showed that the release rate of Glycyrrhiza flavonoids cyclodextrin nanosponge was significantly different in different pH environments.Cyclodextrin nanosponge could significantly improve the dissolution rate of Glycyrrhiza flavonoids.Influencing factors test showed that the properties of Glycyrrhiza flavone cyclodextrin nanosponges were stable under high temperature(60 C)and strong light(4500 500Lx),but they should be sealed and preserved in a relatively dry environment.The primary pharmacodynamics of Glycyrrhiza flavonoids and nano-sponges were studied in four different aspects: the average weight change rate of mice,the area of colon ulcer,the wet weight coefficient of colon and the gross morphology and scoring of colon in mice,using 4% acetic acid to induce ulcerative colitis model in mice.The blank group,the model group,the glycyrrhiza flavonoids raw material group and the preparation group were set up respectively.The results confirmed that the glycyrrhiza flavone cyclodextrin nanosponge can be used in the treatment of ulcerative colitis and has a good curative effect.