The In Situ Synthesis Of Magnetic Polymer Microspheres And Its Application

The hollow polyurea microspheres with ferric chloride as content were prepared by inverse miniemulsion polymerization with diethylenetriamine?DETA?,2,4-tolylene diisocyanate?TDI?as reactive monomer,and then the polyurea magnetic microspheres were synthesized via further adding reducing agent and precipitating agent to the above solution,finally the thermosensitive magnetic polymer microspheres were synthesized via miniemulsion polymerization with N-isopropylacrylamide?NIPAM?,methacrylicacid?MAA?,and the above polyurea magnetic microspheres as the basic materials.The drug loading capability of the thermosensitive magnetic polymer microspheres to the model drug Rhodamine B?Rh B?was characterized by Ultraviolet-visible spectrophotometry,and the drug release behavior of thermosensitive magnetic polymer microspheres in simulate intestines liquid was investigated.Firstly,the influence of stability and particle size of the inverse miniemulsion were studied.The results show that the stability and particle size of the inverse miniemulsion were influenced mainly by surfactant concentration,ultrasonic time and oil to water ratio.With 0.8 g Span 80 as surfactant,oil to water ratio 7:1,the stable inverse miniemulsion was prepared under ice water bath ultrasonic for 10 min,of which the particle size is about 360 nm measured by nanoparticle size analyzer.Secondly,the hollow polyurea microspheres were synthesized by interfacial polycondensation in inverse miniemulsion,and the superparamagnetic Fe₃O₄ nanoparticles were in situ synthesized in the inner cavities of the polyurea microspheres by chemical coprecipitation method.The effects of the adding method of monomer TDI,polar solvent and costabilizer on the morphology of the polyurea were investigated,and the influence of the type of reducer and its amount,the type of coprecipitation regent and the reaction temperature on the magnetic saturation intensity of the polyurea microspheres were studied.The polyurea magnetic microspheres were characterized by transmissionelectron microscopy?TEM?,fourier transform infrared spectroscopy?FT-IR?and vibrating specimen magnetometer?VSM?.The optimum preparation process of polyurea magnetic microspheres as follow: the reactive monomer 2?TDI?was added by semi continuous feeding method to the inverse miniemulsionmixed with DETA as reaction monomer 1,formamide as polar solvent,KNO3 as costabilizer,the mixture was allowed to react for 12 h at 30 °C and then added 2 mL hydrazine hydrate and 5 mL aqueous ammonia to the inverse miniemulsion was kept 30 min at 80 °C.The polyurea magnetic microspheres had been prepared with an average size of about 350 nm and its saturation magnetization was 43.9emu·g^-1.Furthermore,thermosensitive magnetic polymer microspheres were obtained by miniemulsion polymerizationon the basis of PU@Fe₃O₄polymer microspheres.The microspheres structure and properties were characterized by TEM,VSM and differential scanning calorimeter?DSC?,the results show that the size of the thermosensitive magnetic polymer microspheres was about 400 nm,its saturation magnetization was 13.6emu·g^-1 and the lowest critical solution temperature was about 42.6 °C.Finally,the drug loading and release properties in vitro of thermosensitive magnetic polymer microspheres were investigated with Rhodamine B as model drug.The results show that the maximum drug loading was 73.40 mg Rh B per 1.00 g of thermosensitive magnetic polymer microspheres when the fixed loading drug concentration was0.15×10-2 mol/L and the temperature was 30 °C,the loading drug time was 50 min in PBS buffer?pH 5.7?.The drug accumulated release rate of thermosensitive magnetic polymer microspheres at 44 °C was higher than that at 37 °C,and its cumulative drug release rates were 60% and 31%respectively after 14 hours.The above results indicated that the thermosensitive magnetic polymer microspheres showed good slow release performance.