The Synthesis Of Mesoporous SiO₂/Fe₃O₄ Hollow Micropheres And Ibu Drug Immobization

In the controlled release drug delivery systems drugs can be slowly released with a specific rate in a certain medium. This system can overcome the defect of traditional drug delivery system such as frequent dosing and fluctuation of blood drug concentration. Polymer materials are scarcely used for drug carrier materials because of their obvious deficiencies such as low mechanical strength, unsatisfactory biocompatibility and toxicity. Inorganic mesoporous silica materials are suitable drug carrier materials duo to their tunable pore size, high specific surface area, good hydrothermal stability and physiological nontoxicity. In this thesis, the adjustment of pore size and the surface modification of mesoporous hollow composite microspheres were investigated and the influence of pore size and surface modification of the microspheres on the ibuprofen immobilization and release performance was also discussed.Mesoporous Fe3O4/Si O2 composite hollow microspheres with different pore structure were prepared by adjusting the amount of expanding agent(1,3,5 – trimethylbenzene, TMB). When the TMB/CTAB(hexadecyltrimethylammonium bromide) molar ratio reaches 3:1, the drug loading capacity of composite hollow microspheres is up to 816 mg/g, 2 ~ 3 times of that of traditional drug carrier material. Drug release in vitro shows that mesoporous microspheres without adding expanding agent have a good controlled release performance, with a release quantity of just 40% within 24 h, but the drug release rate is accelerated with the increase of pore size. The molecular structure and activity of the released ibuprofen remain intact.Amino-functionalized mesoporous hollow Fe3O4/Si O2 composite microspheres were prepared by post-grafting method and co-condensation method respectively. It can be found that the amino groups have been successfully functionalized on the mesoporous hollow microspheres by the different methods. The pore channels are apt to be blocked during the post-grafting procedure, leading to a substantial decrease of surface area, pore volume and pore size, and as a result the drug storage decreases sharply to 232mg/g, only a quarter of that of the non-functionalized mesoporous microspheres. The surface area and pore volume of the mesoporous hollow microspheres also decrease slightly for the co-condensation method. The drug storage is 430mg/g, 496mg/g and 506mg/g for the functionalized materials with an APTMS/TEOS(3-Aminopropyltrimethoxysilane/tetraethyl orthosilicate) molar ratio of 5%, 10% and 15%, respectively, slightly lower than those of the unfunctionalized materials but higher than those of the traditional drug carriers. Drug release in vitro shows that the release rate of the amino-functionalized samples decreases obviously. The functionalized materials with an APTMS/TEOS molar ratio of 15% have a good slow release performance, with a release quantity of only 30% within 48 h.In vitro drug storage of mesoporous hollow Fe3O4/Si O2 composite microspheres was analyzed by using Quasi-two kinetic model. It can be found that the adsorption performance of both functionalized and unfunctionalized samples is similar, reaching the maximum within 2 ~ 4 h. Their adsorption performance can be well fitted by the Quasi-two kinetic model, with a linear correlation coefficient larger than 0.999. Several common dynamic models were used to analyze the drug release data. It can be found that the Korsmeyer- Peppas model is the most suitable for fitting. The results show that the drug release of unfunctionalized mesoporous microspheres complies with Fick diffusion mechanism and the drug release rate depends on the rate of diffusion. The drug release of amino-functionalized microspheres does not obey Fick diffusion.