The Synthesis Of ?-cyclodextrin Polyrotaxanes And Their Biological Properties Study

Cancer is a serious threat to human health worldwide,and the mortality causing by cancer is increasing year by year.The treatment of cancer has been regarded as a worldwide problem for a long time.Chemotherapy is one of the most important methods in the mode of combined therapy of tumour.However,most of the chemotherapy drugs lack pharmacological specificity,and exhibit serious side effects.Nano drug carriers have lots of advantages in the field of drug delivery,such as improving the solubility and the stability of the hydrophobic drugs,controlling release of drugs,extending the time of drugs action,changing the mechanisms of the cellular membrane trafficking,improving the permeability of drugs,targeting delivery,delivering the drugs to the diseased region and realizing combination therapies by carrying multiple drugs,which can achieve the clinical goals that the traditional drug delivery methods can not achieve.Polyrotaxanes(PRs)are kind of nano drug carriers with small size,which are composed of the cyclodextrins(CD,host molecules)and the polymer axls(guest molecular).Compared with the traditional organic nano drug carriers,CD-based polyrotaxanes have numerous outstanding advantages,such as good biocompatibility,ease of chemical modification,the transferability of cyclodextrins on the molecular axis,the permeability and diffusibility in tumor tissues and the adjustable size.Therefore,polyrotaxanes have good applications in the field of drug delivery.Herein,we prepared the a-CD-based polyrotaxanes,and studied the preparation method,size,morphology characteristics and the applications of polyrotaxanes.Specific studying contents are as follows:1.We synthesized a-CD PRs with PEG(2000,4000,6000)end carboxylated as molecular axis and mono-(6-amino-6-O)-?-CD as capping agent.Nuclear magnetic resonance spectroscopy(NMR),Transmission electron microscopy(TEM),X-ray Powder diffraction(XRD)and Fourier infrared spectrum(FT-IR)were used to characterize the structures of the PRs.2.First,the water-soluble 1,2-bis(2-amino ethoxy)ethane was used to modify the PRs to realize the water soluble of polyrotaxanes.Then the antitumor drug 10-hydroxy camptothecin was modified by succinic anhydride,and the modification anticancer drug covalently coupled to polyrotaxanes via amidation reaction.The drug loading content(7.0%)was measured by the nin-hydrin.In vitro release experiments showed that the structure of the drug covalently attached to the surface of the drug carriers was stable,the drug release rate could be controlled effectively,and no drug burst phenomenon occured.At the same time,we studied the biological properties and applications of polyrotaxanes.