Initiated Polymerization Of Fe <sub> 3 </ Sub> The O <sub> 4 </ Sub> / P (maa-co-nvp) Magnetic Composite Microspheres Preparation, Characterization And Drug Release

With development of the bio-engineering and biomedical research as well as some related fields, magnetic polymer microspheres as a new functional materials, have attracted more attention. The exploration for intelligentization, functionalization and applications of these microspheresin drug delivery, cell separation, cell markers, clinical diagnosis, biological sensing and the immobilized enzyme has been the hot research subject of magnetic polymer microspheres. Many studies have described methods to prepare the microspheres containing inorganic magnetic nanoparticles such as swelling method, embedding method, monomer polymerization. The monomer polymerization approaches also include suspension polymerization, emulsion polymerization, dispersion polymerization, etc. However, these polymerization methods do not come up to expectations to some extent, One important reason of which is that inorganic magnetic particles combine with organic polymer by the hydrogen bonds and/or other physical or chemical absorption mostly. which is apt to desorption, leading to unstable combination. People are exploring new ways to solve this problem. This study contains two areas focusing on preparation, construction and characterization, application of functional magnetic polymer microspheres. First, we design and construct a magnetic composite microsphere consisting of Fe3O4 nanoparticles chemical-covalently encapsulated with poly(methacrylic acid-co-N-vinyl pyrrolidone) (P(MAA-co-NVP)) cross-linked copolymers by a surface-initiated radical dispersion polymerization route. Second, we study pH responsiveness, environmental stability, magnetic rheological and caffeine drug release behavior of the Fe3O4/P(MAA-co-NVP) cross-linked magnetic composite microspheres.1. We prepared Fe3O4 nanoparticles by chemical coprecipitation and then amino groups were coated on the surface of magnetite nanoparticles via surface modification of 3-amino propyltriethyloxy silane (APTES). Next,1,1-methylene bis-(4-isocyanato-cyclohexane) (H12MDI)) was attached onto the surface of the APTES-modified Fe3O4 nanoparticles through an amide bond linkage formed by a hydrogen transfer chemical reaction between amino groups of the APTES-modified Fe3O4 and isocyanate groups of the H12MDI, introducing isocyanate groups (-NCO). Subsequently,2,2'-azobis[2-methyl-N-(2-hydroxyethyl) propionamide] (AMNHP) was tailored onto the surface of the H12MDI-functionalized Fe3O4 nanoparticles through an ester bond juncture, and Fe3O4 azo initiator was obtained by the treatment of surface isocyanate groups of functionalized magnetic nanoparticles with hydroxyl groups of the AMNHP. Fe3O4/P (MAA-co-NVP) cross-linked magnetic composite microspheres with core-shell structure were prepared by a surface-initiated radical dispersion polymerization route of of methyl methacrylate and N-vinyl pyrrolidone monomer. The content of azo initiator AMNHP introducing to the surface of Fe3O4 was analysised by DSC. observations by FT-IR, SEM, TEM and XRD indicated that the P(MAA-co-NVP)copolymer has successfully covered the Fe3O4 nanoparticles. It can be observed by TEM and SEM that the Fe3O4 particles prepared are of spherical shape and an average particle diameter is about 12 nm under the experimental condition. The distribution of unimproved Fe3O4 nanoparticles assumes an aggregation state. Fe3O4/P(MAA-co-NVP) miceospheres bear an obvious core-shell structure characteristic with good distribution. Thermal analysis (TGA) showed that Fe3O4/P (MAA-co-NVP) crosslinked microspheres have good thennal stability, and there are strong interactions between Fe3O4 as core and P (MAA-co-NVP) as shell, implying chemical bonds between them. The VSM analysis testifies that Fe3O4/P(MAA-co-NVP) magnetic microspheres are superparamagnetic.2. We analysis pH response of Fe3O4/P(MAA-co-NVP) crosslinked microspheres by the change in particle size of Fe3O4/P(MAA-co-NVP) crosslinked microspheres at different pH solution with a laser particle size analyzer. The results show that the magnetic microspheres bear good magnetic response. The invitro controlled release examination based on caffiene as the model drug exhibited that the release rate in pH 7.4 buffer solution was faster than in pH 1.4 buffer solution, corresponding to their pH swelling. This superior performance of Fe3O4/P(MAA-co-NVP) crosslinked microspheres can be applied to the drugs which stimulate the stomach and is absorpted in the intestinal.The kinetic modeling demonstrated that the drug release is controlled by a balance between copolymer chain relaxation and Fickian diffusion process, and the proposed carrier is suitable for a magnetic targeting drug delivery system.