The Preparation Of Magnetic Microspheres/graphene Oxide Composites And Applications As Carriers For Drug Delivery

Magnetic nanomaterials have become a hotspot in the fields of material science and biomedicine due to its excellent properties of superparamagnetism,high coercivity,biocompatibility,and so on.In particular,magnetic Fe3O4 nanoparticles have been widely used in biomedical fields such as nuclear magnetic resonance(NMR),immobilized enzyme and drug carriers because of their unique properties.In this paper,the magnetic Fe3O4 microspheres was prepared by using a simple one-step hydrothermal synthesis;at the same time,the magnetic microsphere/graphene oxide(GO)composites was obtained by surface modification and combination with GO,which explored the applications in the field of targeted drug delivery.FeCl3·6H2O and anhydrous sodium acetate(NaAc)as raw materials,ethylene glycol(EG)as dispersing agent and reducing agent,Fe304 hollow microsphere was prepared under high temperature and high pressure using the method of hydrothermal synthesis.The Fe3O4 hollow microsphere was characterized by scanning electron microscopy(SEM),transmission electron microscopy(TEM),Fourier infrared spectrometer(FTIR),X-ray diffraction(XRD),particle size analysis and vibrating sample magnetometer(VSM)measurements.The results showed that Fe3O4 hollow microsphere was prepared when FeCl3·6H2O was 20 mmol,the reaction temperature was 200?,the reaction time was 10 h.The study found that Fe3O4 microsphere was self-assembly composed of 53 nm small particles and was inverse spinel structure.The average size of Fe3O4 nanoparticles was about 220 nm with narrow size distribution.And that the magnetic hysteresis loop at room temperature showed saturation magnetization of 78.16 emu g-1 and coerci,vity of 75 Oe,which was easy to realize magnetic separation.Furthermore,the micropore on the surface of the magnetic microsphere was favorable for drug loading and releasing.A new Fe3O4 microsphere was obtained by adding sodium tripolyphosphate on the basis of previous experimental conditions.The Fe3O4 microsphere with a diameter of about 250 nm was self-assembly composed of 35 nm small particles.The content of hydroxy group existed on the surface of the microsphere was increased by characterizing of infrared spectroscopy,it was advantageous to disperse and stabilize in aqueous solution.Then,Fe3O4@2-amino-5-sulfobenzonic acid microsphere(labeled S-Fe3O4 microspheres)was prepared by adding 2-amino-5-sulfobenzonic acid through the polymerization of monomers in the water dispersion system of the prepared microsphere.There were hydrophilic amino and sulfo groups on the surface of the microsphere.The dispersion stability of the S-Fe3O4 was investigated through sedimentation experimentation affected by the amount of 2-amino-5-sulfobenzoic acid and reaction temperature.The results showed that the S-Fe3O4 microsphere with better dispersion stability was prepared when the reaction temperature was 80?,2-amino-5-sulfobenzonic acid was 0.8 g·g-1,and the mixture was stirred with 0.05 g Fe3O4 in deionized water for about 9 h.And the saturation magnetization of S-Fe3o4 microspheres was 64.38 emu g-1.What's more,the microsphere had good biological safety,which was possible for the application in the field of biomedicine.The hollow microsphere was ammoniated using silane coupling agent(KH550),then hollow Fe3O4/GO microsphere was formed through electrostatic interaction with graphene oxide(GO).Their in vitro cytotoxicity to bovine mammary epithelial cells was investigated,and anticancer drug of 5-fluorouracil(5-FU)loaded and released from Fe3O4/GO under different pH conditions were also explored.The results showed that magnetic hollow Fe3O4/GO composites was obviously superparamagnetic,which was easy to realize the magnetic orientation in the presence of external magnetic field.In vitro cytotoxicity test confirmed that the relative cell survival rate was still 97%when the concentration of magnetic hollow Fe3O4/GO microsphere was 40 ?g·cm-3.So it had biological safety as drug carrier.When the initial concentration of 5-fluorouracil was 0.5 mg cm-3,the drug loading was 0.41 mg·cm-3.The drug release rate were 61%and 11%at the pH of 6.9 and 4.0 after 24 h respectively,which indicated that the acidic condition was favorable for the release of 5-FU.