PEO-PPO-PEO嵌段共聚物作为药物载体的机理研究
文献类型：学位论文
| 作者 | 贾连伟 |
| 学位类别 | 博士 |
| 答辩日期 | 2012-06-01 |
| 授予单位 | 中国科学院研究生院 |
| 导师 | 郭晨 |
| 关键词 | PEO-PPO-PEO嵌段共聚物 胶团化 药物载体 二维红外相关光谱 核磁共振 |
| 其他题名 | Fundamental Study of PEO-PPO-PEO Block Copolymers in Biomedical Fields |
| 学位专业 | 化学工艺 |
| 中文摘要 | 聚氧乙烯–聚氧丙烯–聚氧乙烯（PEO–PPO–PEO）嵌段共聚物是一系列由不同的PPO/PEO嵌段比和分子量组成的水溶性非离子型表面活性剂。由于其良好的温度响应性和生物兼容性，PEO–PPO–PEO嵌段共聚物在疏水性药物增溶和控释、基因治疗等领域有着重要的应用。其作为药物载体应用的主要形式是利用形成的胶团结构对疏水性药物分子进行增溶、负载和控释，因此，深入研究嵌段共聚物在水溶液中的聚集行为、与不同类型分子之间的相互作用机理对其研究和实际应用具有重要意义。本论文主要利用傅立叶变换红外（FTIR）和核磁共振波谱（NMR）技术对以上问题进行了研究，主要包括以下四个方面研究内容： (1) 应用二维红外相关光谱研究了PEO-PPO-PEO嵌段共聚物在水溶液中的胶团化机理。随着温度的升高，PEO链段由gauche构象向trans构象转变，构象的转变引起PPO链段甲基和C-O键发生去水化，这些去水化基团引起不同分子间发生聚集而形成胶团结构。构象的转变是导致嵌段共聚物分子微环境变化和胶团化的初始原因。 (2) 利用NMR技术研究了PEO-PPO-PEO嵌段共聚物对抗氧化剂没食子酸丙酯的增溶和负载机理。没食子酸丙酯通过芳香氢与嵌段共聚物的PPO链段发生疏水相互作用而进入嵌段共聚物胶团内核，它的增溶使形成的胶团更加稳定。PEO-PPO-PEO嵌段共聚物能够对没食子酸丙酯起到增溶、保护和缓释作用。 (3) 利用NMR技术研究了PEO-PPO-PEO嵌段共聚物与细胞内重要的解毒/抗氧化分子谷胱甘肽的作用机理。谷胱甘肽Glu羧基基团能与嵌段共聚物PEO链段形成分子间氢键，而其巯基及其它位置不受相互作用的影响。由于Glu羧基基团是谷胱甘肽与相关蛋白作用的位点，嵌段共聚物与其的相互作用会对谷胱甘肽参与的一系列活动产生影响。 (4) 利用NMR和等温滴定微量热技术研究了PEO-PPO-PEO嵌段共聚物与六肽（GHRP-6）的作用机理。嵌段共聚物PPO链段的甲基与六肽甲基和芳香氢发生疏水作用，PEO链段与六肽的部分酰胺键和氨基发生分子间氢键作用，形成1：1复合聚集体。嵌段共聚物胶团体系能够对寡肽类药物分子进行负载和输送。 |
| 英文摘要 | PEO-PPO-PEO block copolymers are water soluble nonionic surfactants consisting of different PPO/PEO ratios and molecular weights. These copolymers have attracted renewed interest in drug delivery and gene therapy. Their aggregation behavior and interactions with hydrophobic drugs and biomolecules are of great importance for the copolymers in both fundamental research and practical applications. The aim of the thesis is attempting to reveal the aggregation behavior and interaction mechanism of PEO-PPO-PEO copolymers with biomolecules and drugs on a molecular level, with the aid of FTIR and NMR techniques. The main results are as follows: (1) The micellization mechanism of PEO-PPO-PEO block copolymer in aqueous solutions was studied by two-dimensional correlation FTIR spectroscopy. New insight into variation in the sequence of group associations was determined. The temperature-induced conformational changes were suggested the reason for micellization. (2) The interaction between PEO-PPO-PEO copolymers with propyl gallate was investigated by NMR technique. It was determined that aromatic protons of propy gallate interacted with PPO units of the copolymers, which contributed to its incorporation into the micelles. This study indicated that propyl gallate can be greatly solubilized, protected and controlled release by the copolymers. (3) In order to investigate the effect of PEO-PPO-PEO copolymers on glutathione (GSH)/glutathione-S-transferase (GST) detoxification system, interaction between the copolymers and GSH was studied by NMR measurements. It was revealed that GSH formed hydrogen bonds with EO units of the copolymers. This study suggests that GSH-transporting or utilizing systems may be affected by treatment of PEO-PPO-PEO copolymers. (4) Interaction between PEO-PPO-PEO copolymers and a hexapeptide, growth hormone releasing peptide-6 (GHRP-6), was investigated by NMR technique in order to study the potential use of the copolymers in peptide-drug delivery. It was determined that PEO-PPO-PEO copolymers and the peptide formed a complex in 1:1 stoichiometry, which implicated that PEO-PPO-PEO copolymers have great potential in delivering peptide-drugs. |
| 语种 | 中文 |
| 公开日期 | 2013-09-25 |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/1806]  |
| 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 | 贾连伟. PEO-PPO-PEO嵌段共聚物作为药物载体的机理研究[D]. 中国科学院研究生院. 2012. |
入库方式： OAI收割
来源：过程工程研究所
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