The Inclusion Behaviors Of Cyclodextrins With Two Natural Molecules And The Optimized Synthetic Method Of Targeted Cyclodextrins

As its special molecular structure and property of low toxicity, cyclodextrins(CDs) could form inclusion complexes with drug molecules to improve the solubility, stability, safety and bioavailability of drug molecules. Therefore, cyclodextrins and their derivatives could be served as ideal drug carriers which widely used in pharmaceutical industry. Due to the chemical structure of cyclodextrins, the cyclodextrins are easily modified. Considering the fact that lots of biological receptors are overexpressed on the surface of most cancer cells and other focal cells, the related ligands which have a specific recognition to biological receptors could be chemically bound to cyclodextrins molecules, to construct drug carriers with targeting properties. In this dissertation, several cyclodextrin derivatives were synthesized, the host-guest inclusion behavior between cyclodextrin derivatives and norathyriol or foilc acid were investigated and characterized. In addition, the synthesis routes of folate-cyclodextrin conjugates were optimized.This dissertation was mainly consisted of four sections as follows:1. Firstly, several cyclodextrin derivatives were synthesized by chemical methods: Mono-6-OTs-β-CD, Mono-6-EN-β-CD, Mono-6-DIEN-β-CD, Mono-6-TRIEN-β-CD, Mono-6-N3-β-CD and Mono-6-NH2-β-CD. The chemical structure of these products were characterized by1H NMR.2. Inclusion complexes of norathyriol with β-cyclodextrin and its derivatives were prepared: Norathyriol/p-CD, Norathyriol/SBE-β-CD, Norathyriol/EN-β-CD and Norathyriol/EN-β-CD. The chemical structure of these inclusion complexes were characterized by XRD,1H and2D NMR. The stoichiometry and stability constants(Ks) for the inclusion complexation were measured by means of fluorescence spectra, and the stoichiometry for the inclusion complexation was determined by Job’s methods. In addition, the cytotoxicity of these complexes on human colon cancer cell lines HT-29, SW480, Lovo and HCT116were evaluated by MTT method.3. Inclusion complexes of folic acid with β-cyclodextrin and its derivatives were prepared: FA/NH2-β-CD,FA/EN-β-CD, FA/DIEN-β-CD and FA/TRIEN-β-CD. The stoichiometry for the inclusion complexation were measured by means of fluorescence spectra and Job’s methods. The chemical structure of these inclusion complexes were characterized by XRD,1H and2D NMR.4. The folate-cyclodextrin conjugates which synthesized by former method have two major faults:the low grafting percent of foilc acid and the impurities which hard to be removed. We optimized the synthesis route of folate-cyclodextrin conjugates to solve the problems and the congjugates were characterized by means of’H NMR, MS,XRD and SEM.