磁性复合粒子Fe₃O₄/SiO₂/β-CD的制备及其药物缓释行为研究

【作者】 郝丽；

【导师】 雷忠利；

【作者基本信息】 陕西师范大学 ， 高分子化学与物理， 2012， 硕士

【摘要】 随着生物医学和生物工程相关领域研究的发展,磁性复合微球自其问世以来,由于其特有磁响应性和易功能化特点以及广阔的应用前景,在国际上受到了广泛的关注,探索复合微球的功能化、智能化以及将这些微球应用于药物释放、生物大分子分离、生物传感和固定化酶等方面是复合微球一个重要研究的方向。磁性复合微球作为一种新型的功能材料在近几十年来得到了充分的发展。磁性复合微球是指通过适当的方法使有机物与无机磁性粒子结合形成具有一定磁性及特殊结构的复合微球。与常规微球相比,具有超顺磁性的磁性复合微球能够在外磁场的作用下迅速从混合物中分离出来,这为生物分离和检测方法提出了新的思路,也给功能材料的研发带来了新的发展方向。基于此,本文的研究工作主要围绕着功能性磁性复合微球的制备、表征及其用于药物释放的性能研究展开,具体涉及四氧化三铁磁性纳米粒子(Fe304)的制备及其表面改性、核-壳结构的磁性二氧化硅复合粒子(Fe304/8i02)的制备以及具有超顺磁性的复合微球(Fe304/Si02/β-CD)的制备,最后,将这种功能性磁性复合微球用于药物释放的性能研究。具体内容如下：1.采用化学共沉淀方法制备了具有超顺磁性的四氧化三铁纳米粒子,并使用柠檬酸对纳米粒子进行了改性,制备了电荷稳定的磁流体。利用改性后的磁流体作为种子,通过Stober法制备了具有核-壳结构的Fe304/Si02复合粒子,进一步使用红外(FT-IR)、X-射线衍射(XRD)、透射电镜(TEM)、激光粒度仪、EDX能谱、振动样品磁强计(VSM)对其产物进行了表征,证实了我们成功制备了具有超顺磁性的核-壳复合粒子。2.用硅烷偶联剂APTES对Fe304/Si02进行了修饰,使Fe304/Si02表面带氨基并改善了其与有机物的亲和力,用顺丁烯二酸酐将p-环糊精改性,使其改性为羧基-p-环糊精,利用氨基和羧基之间的反应制备了Fe304/Si02/β-CD磁性复合微球,通过TEM、激光粒度仪、VSM等对其进行了表征,结果表明该微球的粒径为120nm左右,水溶液中分散性较好,磁响应性能较好。3.以Fe3O4/SiO2/β-CD磁性复合微球为载体,咖啡因为模拟药物进行了药物释放研究,分别研究了载体在pH=7.4的缓冲溶液中的缓释行为和载药微球的环境稳定性。研究发现,该载体的载药量为28.83%,且具有明显的缓释效果,有很好的环境稳定性。结果表明,Fe304/Si02/β-CD磁性复合微球是一种合适的药物控制释放的载体。更多还原

【Abstract】 With the research development in the field of biomedicine and bioengineering, people are exploring various functional polymer microspheres, because of its peculiar magnetic response, functionalized and broad application prospects, which can serve as smart or intelligent tools for drug delivery, biomacromolecules purification, biosensor and enzyme immobilization, etc. Magnetic polymer microsphere has been fully developed as a new functional material in recent decades. Magnetic polymer microsphere is a kind of hybrid microsphere with magnetic property, which is composed of polymer and inorganic magnetic particles. The main advantage of magnetic polymeric microspheres over conventional polymeric microspheres is that, because of their super-paramagnetic properties, they can be rapidly separated from solution under magnetic field, which proposes a new approach for biological separation and detection, also brings new direction of development for researching functional materials.Based on the research background and the development trend of magnetic polymer microspheres, the research interest of this work focused in the preparation, characterization and properties for controlled release examination of magnetic polymer microspheres, which involves in four parts, i.e. the preparation and surface modification of magnetic microspheres, preparation of core-shell Fe3O4SiO2particles and preparation of magnetic polymer microspheres with super-paramagnetic. Finally, we used the functional magnetic polymer microspheres in the drug release research. The results of each part are listed as follows:1. Magnetite nanoparticles were prepared by chemical co-precipitation process. By modifying as-prepared super-paramagnetic magnetite nanoparticles with citric acid aqueous solution, stable magnetic fluid was obtained. Using the modified magnetic nanoparticles as seeds, core-shell structure silica-coated magnetite nanoparticles (Fe3O4/SiO2) were prepared via Stober method. Furtherly, the composite particles were characterized by FT-IR, XRD, TEM, EDX and VSM, it can be confirmed we prepared core-shell composite particles with super-paramagnetic successfully.2. By treating silica-coated magnetite nanoparticles with (3-aminopropyl) triethoxysilane (APTES) by a silanization reaction, amino-functionalized nanoparticles were prepared. And its affinity with organic matter was improved. At the same time, β-cyclodextrin was modified with maleic anhydride (MAH), carboxylic β-cyclodextrin was obtained. Fe3O4SiO2/β-CD magnetic polymer microspheres were prepared via the reaction between-NH2and-COOH. The obtained nanoparticles were characterized by TEM, laser particle size analyzer and VSM, and the results showed that the microspheres had an average size of120nm. The magnetic polymer microspheres had good distribution in aqueous solution, and exhibited good magnetic response.3. The invitro controlled release examination based on caffeine as the model drug and magnetic polymer microspheres Fe3O4SiO2/β-CD as the carrier, we researched the release rate in pH=7.4buffer solution and environmental stability. The results showed that loading efficiency was28.83%, had a significant release behaviour and good environmental stability. It can be confirmed that Fe3O4SiO2/β-CD magnetic polymer microspheres is a suitable drug carrier for controlled release.更多还原