Synthesis Of Dual-Magnetic Responses Thermo-sensitivie Composite Microspheres For Controlled Drug Release

Dual-magnetic composite thermosensitive microspheres Fe₃O₄/poly（N-isopro-pylacrylamide）（Fe₃O₄/PNIPAM）, Fe₃O₄/poly（N-isopropylacrylamide-co-styrene）（Fe₃O₄/P（NIPAM-co-St）） and Fe₃O₄/poly（N-isopropylacrylamide-co-methacrylic acid）（Fe₃O₄/P（NIPAM-co-MAA）） which possess various diameter and lower critiealsolution temperature （LSCT） were prepared by seeded emulsion polymerization.Their structure, morphology and magnetic properties were characterized by wide-angle X-ray diffraction definition （WAXD）, fourier-transform infrared （FTIR）,transmission electron microscopy （TEM）, dynamic light scattering （DLS）,thermogravimetric analysis （TGA）, vibrating specimen magnetometer （VSM） andBET specific surface area analysis. Ultraviolet-visible light （UV-Vis） was employedto investigate the drug loading capability of microspheres using Rhodamine B （Rh B）as model drug. Under water tank and alternating magnetic field, the release behaviorof Rh B from Fe₃O₄/P（NIPAM-co-MAA） in simulated gastric juice and intestinalliquid was carefully investigated. The main results are summarized as follows:1. Magnetic Fe₃O₄nanoparticles were prepared by co-precipitation, and furtherencapsulated with poly（N-isopropylacrylamide） via seeded emulsion polymerizationto form Fe₃O₄/PNIPAM dual-magnetic polyeric thermosensitive microspheres withcore-shell structures and superparamagnetism. It can be confirmed from TEM thatFe₃O₄/PNIPAM polyeric microsphere is mono-dispersed and quasi-spherical with anaverage diameter of about200nm. The reaction parameters show notable influenceon the structure and morphology of microspheres, as a result, the diameter andmagnetite content of the microspheres decrease with decrease of monomerconcentration, increase of cross-linker concentration and emulsifier concentration.When15mg/mL NIPAM,7mg/mL MBA and8mg/mL SDBS was used duringsythesis, it is indicated that the diameters of microspheres is about202.4nm, theFe₃O₄content of microspheres is about21.82wt%, the saturated of microspheresmagnetization reaches15.64emu/g, and the LSCT is about33℃.2. On the basis of Fe₃O₄/PNIPAM, various polymer-units （hydrophilic orhydrophobic） were introduced onto thermosen-sitive poly（N-isopropylacrylamide） chains to form Fe₃O₄/P（NIPAM-co-St） and Fe₃O₄/P（NIPAM-co-MAA）. Resultsindicate that the diameters of composite microspheres Fe₃O₄/P（NIPAM-co-St） is243.6nm, Fe₃O₄content is about22.9wt%, the saturated magnetization intensityreaches17.42emu/g, and the LSCT is about32.3℃, respectively. Besides, thediameters of Fe₃O₄/P（NIPAM-co-MAA） is224.9nm, Fe₃O₄content of microspheresis about20.6wt%, the saturated magnetization intensity reaches16.48emu/g, and theLSCT is about37.7℃. The difference between LSCT of Fe₃O₄/P（NIPAM-co-St）and Fe₃O₄/P（NIPAM-co-MAA） indicates that LSCT of composite microspheres canbe controlled by introduction of different polymer-units （hydrophilic or hydrophobic）onto thermosensitive PNIPAM chains, and the LSCT moves to higher temperaturesas the contents of hydrophilic polymer-units increase.3. The results of drug loading showed that Fe₃O₄/PNIPAM, Fe₃O₄/P（NIPAM-co-MAA） and Fe₃O₄/P（NIPAM-co-St） possess excellent encapsulation capability usingRh B as model drug. The experimental results indicated that the encapsulationcapacity of Fe₃O₄/PNIPAM is much higher than that of Fe₃O₄/P（NIPAM-co-MAA）and Fe₃O₄/P（NIPAM-co-St）. Besides, the drug loading parameters show notableinfluence on the encapsulation capacity of Fe₃O₄/P（NIPAM-co-MAA）. As a result,the encapsulation capacity of the microspheres increases with enlarging of Rh Bconcentration, first increases and then decreases with increase of pH value. The bestRhB loading amount of microspheres is able to reach16.38mg/g.4. Under alternating magnetic field, the Rh B release amount reaches13.02mg/gin simulative gastric-juice, and10.47mg/g in simulative intestinal-juice, respectively.