The Synthesis Of Rattle-type Magnetic Composite Microspheres As Drug Carrier And Their Sustained-release Performance

In recent years,cancer has been a serious threat to human life and health,chemotherapy is the most conventional therapy for the cancer treatment.However,it makes the drug distribution all around the body,and the inevitable damage to normal tissues or cells,also the effective concentration and the effective residence time in the lesions may reach a higher level,so the side effects of chemotherapy often causes cancer treatment interruption or failure,which greatly limits the scope and effect of chemotherapy.The new controlled release drug delivery technology based on the new drug carrier has gradually becoming an important subject in the field of pharmacy all around the world.Among them,rattle-type magnetic microspheres as drug delivery carrier has become a focus of many researcher,with its advantage of its internal cavity can loading drugs,so the magnetic microspheres can releasing the drug at fixed point using an external magnetic field,and at the same time,drug carrier with a controllable shell structure can realize the quantitative or response release.So this kind of targeting drug carrier has great potential in the field of biological medicine.The rattle-type magnetic microspheres was the research object in this thesis,it aim to develop a synthesis method with a simple preparation process and a controllable structure,and use it as a drug carrier,to explore the relationship and rules of the drug release properties according to the composition and structure of the microspheres,and provide the basic theory and method of carrier for the development of new drugs carriers.At present,the general method for preparing rattle-type magnetic microspheres is that the magnetic microspheres are used as the core,and the complex process of two phase heterogeneous deposition and subsequent removal of the intermediate shell.Based on the analysis,this thesis proposes the use of non magnetic Fe₂O₃ as the template,and through the template corrosion and calcination reduction strategy to obtain rattle-type magnetic composite microspheres,using DOX as the drug model,and study the drug release properties.Specific research contents are as follows:?1?In order to avoid the complex multiple heterogeneous coating and removing process,the monodisperse Fe₂O₃ microspheres was used as the physical template,after coating a layer of SiO₂,the rattle-type Fe₂O₃@SiO₂ were obtained by using the etching strategy to make the Fe₂O₃ microspheres partial etched,then the rattle-type magnetic Fe₃O₄@SiO₂ composite microspheres was finally obtained through calcination which make the Fe₂O₃ reduced into magnetic Fe₃O₄.In the process of synthesis,on one hand using a non magnetic Fe₂O₃ microspheres can avoid the agglomeration for the magnetic attraction in coating process,so as to ensure the dispersibility of the product;on the other hand,the method avoided the complex shell coating and removing process just by etching the Fe₂O₃ microspheres to make some space.In addition,the method has the advantages of controllable shell thickness and cavity size,and the use of it as a drug carrier is beneficial to the study of the relationship between the cavity structure,the shell parameters and drug release properties.The results show that the rattle-type magnetic Fe₃O₄@SiO₂composite microspheres have a pH respond release property,and the drug loading is closely related to the size of the cavity,the release rate is affected by the shell thickness.The cytotoxicity experiments showed that the rattle-type magnetic Fe₃O₄@SiO₂ composite microspheres has good biocompatibility.?2?Through the analysis and research of the above experimental process,the Fe₂O₃ microspheres were prepared as chemical templates,namely one step preparation of rattle-type Fe₂O₃@PPy composite microspheres by use Fe₂O₃ release Fe³⁺and trigger pyrrole monomer in situ polymerization to form polypyrrole?PPy?shell,then the PPy shell and Fe₂O₃ core were transformed into C and Fe₃O₄ through calcination,finally the rattle-type magnetic Fe₃O₄@C composite microspheres was obtained.In this method,the shell formation process and template etching process are combined to further simplify the preparation process of rattle-type magnetic core shell composite microspheres.During the synthesis process,it can realize the controllable morphology and structure of the rattle-type magnetic Fe₃O₄@C composite microspheres through the regulation of various reaction parameters such as water alcohol ratio,hydrochloric acid,pyrrole dosage and reaction time.DOX was used as a drug model to investigate the effect on the sustained release properties for the shell thickness of the rattle-type magnetic Fe₃O₄@C composite microspheres and pH.The experimental results show that it has good biocompatibility,therefore,it is a promising drug targeting carrier material.