Preparation And Application Of Multifunctional Polymer Drug Carriers

With the research development of nano-biotechnology,multi-functional and smart polymer microspheres have attracted more and more attentions.Especially in the field of cancer therapy,multi-functional polymer microspheres could be used as the drug carriers in the targeted drug delivery system,which has a broad potential application. Based on the research background,this thesis focused on the preparation > characterization and application of the multi-functional polymer drug carriers,which involves the following two parts.First,the magnetic thermo-sensitive micro-containers were prepared in a novel solvent-templated approach,and the products were used as the carriers to load anti-cancer drug Doxorubicin(DOX). Second,the magnetic thermo-sensitive micro-containers were further modified with the conjugation of cancer cell targeting agent folic acid.The products had response to the magnetic field,environmental temperature and recognization of cancer cells.The drug loading and in vitro releasing of these carriers were carefully investigated.And finally the multi-function drug carriers were applied in vitro cancer cell experiments to testify the targeting of the products.The results of each part are listed as follows:1)Based on the previous work,a new solvent-templated approach to the fabrication of magnetic thermo-sensitive micro-containers of Fe₃O₄ nanoparticles with poly(N-isopropylacrylamide) walls is presented.The micro-containers undergo a temperature-induced volume phase transition and present an impressive magnetic response.The micro-containers have a well-defined structure with a narrow size distribution.The wall thicknesses of the micro-containers can be controlled according to requirements.Compared to other preparation methods,the process is simple and reproducible.The magnetic saturation of these micro-containers is high enough to meet most requirements of bioapplications.To further investigate the potential application of these micro-containers,they are tested as drug carriers,with the drug loading and releasing processes carefully studied.The drug encapsulation efficiency and drug content in the carriers are pH-dependent,and the carriers have a maximal drug loading of about 50 wt%under alkaline conditions.The release of the drug from the micro-containers can be controlled by the environmental pH,temperature,and magnetic force.2)Based on the work of part one,the magnetic thermo-sensitive micro-containers were further modified by the conjugation of the targeting agent folic acid,which resulted in the multi-functional drug carriers.These products had response to magnetic field,environmental temperature and cancer cells.With well defined morphology and structure,temperature induced volume phase transition and high magnetic saturation,the products could be used to load anti-cancer drug DOX.The in vitro release of drugs was also investigated in two different conditions which were simulated physiological condition and simulated cancer cell interior condition. We found that DOX release much faster under a simulated cancer cell interior condition when compared to that under physiological condition.Finally,the multi-functional products were utilized in vitro cancer cell experiments to testify the targeting effect.The products exhibited good capability in recognizing cancer cells, which indicated that this carrier-drug complex could be used in cancer targeted drug deliver system.