Preparation,Properties,Molecular Simulation And Anticancer Activity Of Two Kinds Of Cyclodextrin-drug Molecular Capsules

Villiers firstly discovered of cyclodextrins in 1891,scholars at home and abroad have carried out extensive exploration and research on cyclodextrins.Cyclodextrin and its derivatives,had significant advantages in enhancing drug stability,drug solubility,improving drug bioavailability and reducing side effects,it have been widely used in dozens of listed pharmaceutical preparations.At present,there have been more than 40 kinds of commercially available pharmaceutical products based on cyclodextrin complex,such as cefoxitin,nimesulide,diclofenac and insulin.The number of drug products have been increased year by year,a variety of infusion agents,injections have been approved to enter the clinical.Therefore,by making full use of the host/guest interaction between cyclodextrins and guest molecules,it was of great significance for the research and development of new drug dosage forms to research the pharmaceutical preparations of new CD and its derivatives.In this study,two kinds of drug/cyclodextrin molecular capsules(pseudolaric acid B/CD and naringin/CD)were prepared firstly by lyophilization method.By means of the combination of experimental analysis and theoretical calculation,the properties,molecular simulation and anticancer activity of the molecular capsules were studied.My main work was described as follows:The first part:the cyclodextrin and its inclusion mechanism and the experimental analysis and theoretical calculation method of the drug/cyclodextrin system were reviewed in this paper.The second part:pseudolaric acid B(PAB,Figure 1)was a natural product without obvious toxicity in vivo.An in-depth study on its pharmacological activity,may be expected to promote it to be new anti-cancer drugs.In this study,the preparation of PAB/CD molecular capsule drug delivery system,which could effectively improved the water solubility and laid the foundation for the design of new pharmaceutical preparation of PAB.PAB/CD molecular capsules were prepared,ultraviolet spectrum,infrared spectrum,X-ray diffraction,2D NMR,thermal analysis,scanning electron microscopy and molecular simulation methods were used to discuss the interaction,the inclusion model and anticancer activity of them.The results showed that the solubility and stability of PAB were improved,and the proliferation of breast cancer MDA-MB-231 cells was significantly inhibited.The third part:naringin(Figure 2)was a flavonoid glycosides,one of the active ingredients of Rhizoma drynariae,it could also be used as a preventive health care product,had a variety of healthy benefits.However,poor solubility(S0=0.6502 mg/mL),low oral bioavailability and the presence of a bitter taste,naringin required the development of suitable delivery systems.In this paper,molecular dynamics simulation,thermodynamic calculation and physical and chemical properties of naringin/CD molecular capsules were studied.Series naringin/CD molecular capsules were prepared.Combined methods of experimental analysis,molecular dynamics simulation,and thermo-dynamic calculation were used for the first time.The molecular interaction,the possible binding mode,solubilization and stabilization of naringin were discussed,individually.The results showed that the formation of naringin/HP-beta cyclodextrin molecular capsule,which greatly improved the water solubility and stability of naringin,and retained its physiological activity as well.The combined experimental and computational methods represent a prospective approach for further studies.