Study On Controlled Release System Of Natural Products And Properties Based On Cyclodextrin And Acyclic Cucurbituril

Although there are a large number of drug molecules or essential oil molecules in natural products with biological activity and practical value,many of them have drawbacks such as poor water solubility,poor stability,low-temperature volatility and without any selectivity,which greatly limit their further applications in biological medicine and other fields.The emergence of supramolecular encapsulation technology can significantly improve the above-mentioned defects of the guest molecule without modifying the structure of the guest.The host molecules can be further modified so that it can collapse and release of the guest under specific stimulus signals（such as p H and temperature,etc.）to achieve controlled release.Among many supramolecular carriers,cyclodextrin is an ideal carrier for the development of supramolecular controlled release system due to its excellent water solubility and biological safety.In addition,the up-and-coming star acyclic cucurbituril has also been widely studied in recent years due to its alterable cavity structure and strong binding ability.Based on this,three parts of studies were carried out in this thesis.In the first section,two tumor-targeted drug delivery carriers were constructed by linked p H-sensitive maleic anhydride derivatives to Mono-6-NH₂-β-Cyclodextrin for the controlled release of podophyllotoxin.Their inclusion behaviors and characteristics were studied by NMR,UV-Vis,XRD,DSC and SEM,the water solubility and in vitro p H response release of this inclusion system were also investigated.Besides,their cell uptake and cytotoxicity experiments were conducted.These studies confirmed that the water solubility of podophyllotoxin increased by 502.92 and 190.75 folds after formation of inclusion complexes with two p H sensitiveβ-CD derivatives,and two inclusion complexes could release podophyllotoxin in a simulated tumor’s weakly acidic environment and the release rate increased with the decrease of p H in solution,the inclusion complexes showed good anti-tumor activity and selectivity against tumor cells.In the second part,two main components of rose essential oil（geraniol and nerol）were encapsulated by using acyclic cucurbituril modified with benzene ring or naphthalene ring to improve their stability and to achieve heat-response release.Their inclusion behaviors and characteristics were investigated by NMR,Fluorescence Titration and FT-IR.The heat-release properties and thermal stability of the inclusion complexes were further investigated by NMR and TGA.The stoichiometry between two acyclic cucurbituril and geraniol（or nerol）were 1:1,and Ks ranged from reach 4～5 orders of magnitude.The release rate of inclusion complexes increased with the increase of temperature and heating time,the thermal stability of geraniol and nerol were significantly improved after formation of inclusion complexes with acyclic cucurbituril.In the third part,two bridged cyclodextrins with different chain lengths were designed and synthesized for encapsulation of cannabidiol.Their inclusion behaviors and characteristics were investigated by UV-Vis,XRD,SEM,NMR and TGA,and the water solubility of inclusion complexes were determined.Moreover,the in vitro antioxidant and anti-tumor activities of the inclusion complexes were studied.The stoichiometry between two bridged cyclodextrins with cannabidiol were 1:1,and the Ks values ranged from reach 5～6 orders of magnitude.The water solubility of cannabidiol increased by 6.76×10⁵ and 4.52×10⁵ folds after formation of inclusion complexes,the inclusion complexes show certain performance in vitro anti-oxidation and anti-tumor activity.