The Preparation And Charaction Of Doxorubicin-Loaded Magentic Microparticle And The Study Of Its In Vito Release

Doxorubicin-loaded magnetic microparticles, using doxorubicin as model drug, Fe3O4 as core and vinylpyrrolidone as matix material, were prepared by inverse emulsion polymerization in this paper. The prepared doxorubicin-loaded magnetic microparticles were characterized by telescope electron microscopy(TEM) and environmental scanning electron microscopy(ESEM) for morphological properties, laser light scattering(LLS) for size and size distribution. The drug encapsulation efficiency (EE) and the drug release kinetics under in vitro conditions were also measured. The thesis consists of follow three sections:In the first part of this paper,the magnetic material Fe3O4 was synthesized by chemical precipitation reaction from FeCl2 and FeCl3. Took the particle size and the purity of Fe3O4 as criteria, the optimal manufacturing conditions and formulation were obtained by single factor test. The optimal manufacturing condition and formulation were determined as follows: the ratio of Fe3＋/Fe2+ was 1.6:1,reaction temperature was 80℃,the pH value was 11,the processing time was 3h. The Fe3O4 particles obtained from optimal manufacturing condition are mainly cubic particle with narrow particle size distribution. The average diameter is 19.8nm. The X-ray diffraction and IR indicate that the prepared power is pure cubic Fe3O4. In the second part of this paper, we have attempted to prepare doxorubicin-loaded magnetic microparticles by the method of inverse emulsion polymerization. In this section, the surfactant and the amount of inverse emulsion system's components were reseached by single factor test through observing the stability of emulsion. Then the soluble capacity of doxorubicin in the inverse emulsion system was investigated. Finally, the above mentioned emulsion with soluble doxorubicin was used to prepare doxorubicin-loaded magnetic microparticles. The results shows that Span80 and Tween80 is the suitable surfactant, and the stable inverse emulsion can be obtained only when the surfactant is kept more than 8％(wt), volume fraction of water phase to oil phase is less than 0.1 and the NVP momoner is not more than 1.5g. The maximal soluble capacity of doxorubicin was 2.25mg. The optimal manufacturing conditions are that surfactant content is 8% by mass, Fe3O4 is 0.07g, the iniatior is 0.06g, the reaction temperature is 60℃ and the stirring speed is kept at high speed. As shown by TEM,SEM and DLS, the such prepared doxorubicin-loaded magnetic microparticles have a smooth spherical surface with average size 500nm and a narrow unimodel size distribution. And IR result indicated that the magnetic microparticles consists of doxorubicin, Fe3O4 and polyvinylpyrrolidone. Finally, the drug encapsulation efficiency (EE) and the drug release kinetics under in vitro conditions were measured by high performance liquid chromatography with fluorescence detection (HPLC-FLD). The results are that, with the doxorubicin dosage increasing, the doxorubicin loading is increasing while the drug encapsulation efficiency is decreasing. Again the doxorubicin loading is decreasing with the matrix material dosage increasing, while the drug encapsulation efficiency is increasing.In the drug release kinetics investigation, influences of the content of drug, the microsphere size and the content of crossing-linker on the drug-release were studied. The results showed that the greater the drug loading the greater the burst- drug, and the faster the release. In addition, larger particles have a smaller initial burst release and longer sustained release time than those of the smaller particles and the lower content the crossing-linking used, the more quickly the drug released.