γ-聚谷氨酸磁性纳米复合颗粒的制备、表征及pH响应研究
文献类型：学位论文
| 作者 | 张菊花 |
| 学位类别 | 硕士 |
| 答辩日期 | 2008-06-10 |
| 授予单位 | 中国科学院过程工程研究所 |
| 授予地点 | 过程工程研究所 |
| 导师 | 刘会洲 |
| 关键词 | γ-PGA 磁性药物传输系统 γ-PGA/Fe3O4纳米复合载体 二级结构 pH |
| 其他题名 | Synthesis, Characterization and pH-response of γ-PGA/Magnetite Nanocomposite Particles |
| 学位专业 | 化学工艺 |
| 中文摘要 | γ-聚谷氨酸(γ-PGA)具有良好的生物相容性和生物可降解性，在体内可被降解为谷氨酸，对身体完全无毒，是非常好的药用高分子材料。聚谷氨酸与超顺磁性Fe3O4纳米颗粒结合可以得到具有靶向性的γ-聚谷氨酸/Fe3O4纳米复合材料，是集缓释、控释、靶向等特点为一身的非常有应用前景的药物载体。
本文主要开展了聚谷氨酸/Fe3O4纳米复合材料的制备和表征研究，内容包括以下几个方面：
首先，采用化学共沉淀法制备了粒径为9.7±2.0 nm，粒径分布较窄的超顺磁性Fe3O4纳米颗粒。在制备过程中加入PEG，在Fe3O4纳米颗粒表面形成了一层包覆膜。PEG可以稳定吸附在Fe3O4纳米颗粒表面，其空间位阻作用降低了表面能，从而形成了稳定的水基磁流体。
将上述PEG包覆的磁流体加入γ-聚谷氨酸溶液中，通过改变体系的pH及γ-聚谷氨酸分子量合成了不同包覆结构的γ-聚谷氨酸/Fe3O4纳米复合材料，并探讨了其形成机理。(a) 合成了“核-壳”结构和复合结构两种不同包覆结构的γ-聚谷氨酸/Fe3O4纳米复合微球。在酸性条件下，Fe3O4纳米颗粒表面的羟基与聚谷氨酸羧基进行酯化反应形成共价键，所以包覆比较紧密，形成“核-壳”结构；而在碱性条件下则为弱的氢键作用或范德华力，其包覆比较疏松，形成复合结构。(b) 反应体系的pH对微球磁性能也有影响。经磁性分析(AGM)表明，pH在1～2时，合成的颗粒比饱和磁化强度很小，为3.47 emu/g。当pH 4～5和12～13时合成的微球比饱和磁化强度比较高，分别为54.2 emu/g，69.4 emu/g。(c) γ-PGA分子量大小影响磁性微球大小。经透射电镜(TEM)分析，Fe3O4纳米颗粒分别与高、低分子量的γ-聚谷氨酸反应，得到了粒径在200～300 nm和100 nm左右的磁性微球。(d) 合成了新型、pH响应的智能型磁性网状水凝胶和磁性微球水凝胶。磁性网状水凝胶具有三维网状结构，而磁性微球水凝胶微球其表面是交联的片层结构。
γ-PGA的电离程度影响其二级结构的转变。应用傅立叶红外光谱法定量研究了pH对γ-PGA及聚γ-PGA/Fe3O4纳米复合微球二级结构的影响，结合傅立叶去卷积技术和二级导数法对原始谱带进行拟合计算了二级结构百分含量。研究发现，γ-PGA及γ-PGA磁性纳米复合微球的二级结构随pH变化趋势相同。聚谷氨酸磁性纳米微球的β-转角和β-折叠含量比较大，达65％以上，而α-螺旋与无规卷曲的含量很小，并且随着pH的增大，β-折叠含量减少，而β-转角的含量增加。
最后在上述二级结构研究基础上，分析了pH对γ-聚谷氨酸磁性复合微球在水溶液里的稳定性及分散性的影响。pH变化引起γ-PGA的构象变化，即γ-PGA的二级结构转变与γ-聚谷氨酸磁性复合微球在水溶液里的稳定性及分散性密切相关。用zeta电位仪和粒度分析仪考察了磁性微球在不同pH水溶液里稳定性及聚集行为。结果表明，当2 |
| 英文摘要 | γ-PGA is of particular interest in drug delivery applications because of its variety of properties such as high water soluable, biodegradable, biocompatable and non-toxic to human bodies. γ-PGA can be degraded to glutamic acid by γ-glutamyl transpeptidase, which is widely distributed in the whole body. Thus, magnetic γ-PGA carrers have great potential in drug delivery system for their targeting and controlling release behavior. In this work, a series of γ-PGA/Fe3O4 nanocomposites were synthesized, characterized and their pH-responsive behaivior also studied. First, the magnetite with a mean diameter of 9.7±2 nm and narrow distribution was prapared by co-precipitation methods. PEG was selected as surface treatment agent and added to the suspension of Fe3O4, the magnetite was coated with a nonionic surfactant through the hydrogen bonds or conordination bonds between PEG and Fe3O4 nanoparticles.A stable and well dispersed magnetite solution was formed due to the steric hindrance of PEG between the nanoparticles. The magenetite gels described above were then introduced into γ-PGA solution, resulting in forming different encapsulated structures under various pH conditions or by controlling the molecular weight of γ-PGA. The results showed that: (a) Two different kinds of structure, core-shell and composite structure, were obtained. In acidic solution, the hydroxyl groups on the surface of PEG coated magnetites were chemically conjugated with carboxyl groups of γ-PGA, the magnetite nanoparticles were tightly embedded in γ-PGA chains and core-shell like structure was formed. While, in basic solution, the interaction between magnetite gel and γ-PGA was weak due to hydrogen bonds or van der Waals force. Thus, the nanoparticles were loosely dispersed in the spheres and formed composite structure. (b) pH also affected the magnetization properties of magnetic γ-PGA nanosperes. The AGM (Alternating Gradient Magnetometer) results showed that nanospheres were synthesized in pH range from 1 to 2, the saturation magnetization was 3.47 emu/g; when pH was 4～5, the saturation magnetization was 54.2 emu/g; when pH was 12～13, the saturation magnetization was 69.4 emu/g. (c) The size of magnetic nanospheres was affected by the molecular weight of γ-PGA through TEM analysis. Typically, γ-PGA with high or low molecular weight produced nanospheres of 200～300 nm or nanospheres around 100 nm, respectively. (d) A novel network γ-PGA/magnetite hydrogel and microspheral γ-PGA/magnetite hydrogel were synthesized. Hydrogels with network structures formed by the conjugation between magnetite nanoparticles and γ-PGA chains.While, the microspheres formed sheets or layers structures on their surfaces. Secondly, the conformational transitions of γ-PGA and magnetic γ-PGA nanospheres under various pH conditions were investigated by FTIR (Fourier transform infrared spectroscopy). The secondary structure contents were determined through the analysis of Fourier deconvolution spectra, secondary derivative spectra and the Gaussian cruve fitting of the original infrared spectra. The results showed that the trend of conformational transitions of γ-PGA and magnetic γ-PGA nanospheres were the same. The whole contents of β-sheet and β-turn were higher than 65%, while α-helix and random coil were low. The content of β-turn increased with increasing pH, while the β-sheet decreased. Finally, on the basis of conformation study, the stability and aggregation of magnetic γ-PGA nanospheres in the solutions with various pH were investigated. The zeta potential and particle size results showed that with the increase of pH (2～10), the zeta potential and particle size decreased, while both values increased when pH>10. At pH 10, both the minimum values of the zeta potential (-32 mV) and particle size (306 nm) were obtained. It was proposed that the electrostatic repulsion between magnetic γ-PGA nanospheres and the conformational transition of γ-PGA led up to such behavior. |
| 语种 | 中文 |
| 公开日期 | 2013-09-13 |
| 页码 | 75 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/1217]  |
| 专题 | 过程工程研究所_研究所（批量导入） |
| 推荐引用方式 GB/T 7714 | 张菊花. γ-聚谷氨酸磁性纳米复合颗粒的制备、表征及pH响应研究[D]. 过程工程研究所. 中国科学院过程工程研究所. 2008. |
入库方式： OAI收割
来源：过程工程研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。