复合空心磁性纳米粒子的制备、表征与药物输运应用

发布时间：2018-09-05 14:53

【摘要】：磁性铁氧化物纳米粒子在其表面进行修饰和包覆之后，可广泛应用于生物医学领域。如何降低“裸露”的磁性铁氧化物纳米粒子对机体的生物学毒性，并拓宽其在药物输运中的应用是近几年的研究热点。本论文正是从以上方面入手，选择了基于生物相容性的复合空心磁性Fe3O4粒子的制备、毒性评价和初步药物运输应用研究作为研究方向，从以下几个方面开展了工作： 1.采用乙二醇作为溶剂和还原剂，FeCl3·6H2O作为唯一铁铁离子源，，无水NaAc作为碱性结构指导试剂，合成粒径可控的Fe3O4磁性空心粒子。探讨了反应时间，FeCl3·6H2O和无水NaAc的之间的物质的量比等因素对磁性空心粒子的粒径、形貌结构、晶型和磁学性质等特征的影响，并综合扫描电子显微镜（SEM）、透射电子显微镜（TEM）、X射线衍射仪（XRD）和振动样品磁强计（VSM）等表征手段，主要研究结果如下：采用5mmol FeCl3·6H2O与40mmol无水NaAc量比，并反应10h时，所制备的Fe3O4纳米粒子的平均粒径约为222nm，饱和磁强度为125.00emu·g-1，其空心结构明显且具有良好的反尖晶石晶型。 2.采用APTES对上述制备好的磁性空心Fe3O4纳米粒子表面进行改性，然后采用化学交联法在纳米粒子表面包覆上聚丙烯酸（PAA），从而形成复合空心Fe3O4@PAA纳米粒子，并对包覆前后的粒子使用SEM、TEM、XRD、红外光谱（IR）、热重分析（TG）和VSM等多种表征手段进行对比表征。其中热重分析法研究结果发现：复合粒子包覆的PAA失重率约为25.2%，可初步估算制备的试样中PAA-Fe3O4的质量比（w/w）在40%左右。包覆后的复合粒子饱和磁强度（Ms）减少，说明APTES修饰层与PAA包覆层降低了其Ms，但复合Fe3O4@PAA磁粒具有很好的磁响应性。 3.研究考察了复合Fe3O4@PAA磁粒的细胞毒性与模拟药物输运结果。磁性空心Fe3O4纳米粒子和复合Fe3O4@PAA纳米粒子对酵母菌的毒性的评估检测实验对比发现：空心磁性Fe3O4纳米粒子的半致死浓度为0.100g/L，对应的半致死时间为1h；而Fe3O4@PAA复合纳米粒子在浓度为1.00g/L处理8小时后对酵母菌没有明显毒性。这说明磁粒在包覆PAA之后，可有效降低磁性纳米粒子固有的细胞毒性，提高其药物输运应用的生物相容性。在复合Fe3O4@PAA磁粒对模拟药物罗丹明（R6G）输运研究结果发现：吸附温度为30°C，吸附时间为30min，吸附浓度为0.15×10-1mol/L时，在pH为7.4的PBS缓冲溶液中，每克复合Fe3O4@PAA磁粒最大吸附量可达1011.1mg R6G。药物释放研究发现，在pH为7.4的PBS缓冲溶液中释放效果最好，在14小时后释放率达到93.0%；而在酸性条件下次之，约86.5%。这表明复合Fe3O4@PAA磁性纳米粒子具有较低的细胞毒性和优越的药物吸附与释放性能。
[Abstract]:Magnetic iron oxide nanoparticles can be widely used in biomedical field after their surface modification and coating. In recent years, how to reduce the biological toxicity of magnetic iron oxide nanoparticles and broaden their application in drug transportation has been a hot research topic in recent years. In this paper, the preparation, toxicity evaluation and preliminary drug transportation of composite hollow magnetic Fe3O4 particles based on biocompatibility were selected as the research direction. Work has been carried out from the following aspects: 1. 6H2O magnetic hollow particles with controllable particle size were synthesized by using ethylene glycol as solvent and FeCl 3 6H2O as the sole iron ion source and anhydrous NaAc as basic structure guidance reagent. The effects of reaction time and the ratio of FeCl _ 3 6H2O to anhydrous NaAc on the particle size, morphology, crystal form and magnetic properties of magnetic hollow particles were investigated. Scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM) were synthesized. The main results are as follows: the ratio of 5mmol FeCl3 6H2O to 40mmol is anhydrous NaAc, and the reaction time is 10 h. The average particle size of the prepared Fe3O4 nanoparticles is about 222nm, and the saturation magnetic intensity is 125.00emu g-1.The hollow structure of the nanoparticles is obvious and has a good antispinel crystal form. The surface of the prepared magnetic hollow Fe3O4 nanoparticles was modified by APTES, and then coated with polyacrylate (PAA), on the surface of the nanoparticles by chemical crosslinking method to form composite hollow Fe3O4@PAA nanoparticles. The particles before and after coating were characterized by SEM,TEM,XRD, IR (IR), thermogravimetric analysis (TGA) (TG) and VSM. The results of thermogravimetric analysis show that the weight loss rate of PAA coated by composite particles is about 25.2and the mass ratio of PAA-Fe3O4 (w / w) can be estimated to be about 40%. The saturation magnetic intensity (Ms) of the coated composite particles decreased, indicating that the APTES modified layer and the PAA coating layer decreased their Ms, but the composite Fe3O4@PAA particles had a good magnetic response. 3. The cytotoxicity of composite Fe3O4@PAA magnets and the results of drug delivery were investigated. The toxicity of magnetic hollow Fe3O4 nanoparticles and composite Fe3O4@PAA nanoparticles to yeast was evaluated and compared. The results showed that the half-lethal concentration of hollow magnetic Fe3O4 nanoparticles was 0.100 g / L and the corresponding half-lethal time was 1 h. However, Fe3O4@PAA nanoparticles were not toxic to yeast after 1.00g/L treatment for 8 hours. This shows that magnetic particles coated with PAA can effectively reduce the inherent cytotoxicity of magnetic nanoparticles and improve the biocompatibility of their drug delivery applications. The results of transport of the simulated drug Rhodamine (R6G) by composite Fe3O4@PAA magnetic particles show that when the adsorption temperature is 30 掳C, the adsorption time is 30 min, and the adsorption concentration is 0. 15 脳 10-1mol/L, the maximum adsorption capacity of the composite Fe3O4@PAA particles per gram can reach 1011.1mg R6G in the PBS buffer solution of pH 7.4. The release rate of drug release was 93.0 in PBS buffer solution with pH 7.4 after 14 hours, followed by 86.5 in acidic condition. The drug release was found to be the best in PBS buffer solution with pH 7.4, and the release rate reached 93.0 after 14 hours. This indicates that the composite Fe3O4@PAA magnetic nanoparticles have low cytotoxicity and excellent drug adsorption and release properties.
【学位授予单位】：湖南工业大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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