含胺基修饰beta-环糊精的可降解两亲性聚酯的合成及其对蛋白质和抗癌药物的控制释放

发布时间：2017-12-27 18:08

本文关键词：含胺基修饰beta-环糊精的可降解两亲性聚酯的合成及其对蛋白质和抗癌药物的控制释放　出处：《天津理工大学》2015年硕士论文　论文类型：学位论文

【摘要】：反相胶束最大的优点是其具有一个水性内环境,能够保持生物分子(如蛋白质,多肽)的生物活性,且能够使生物分子选择性的增溶。因此,将反相胶束体系应用于药物载体方面的研究具有非常重要的意义。以线型聚乙二醇(MPEG)和四臂聚乙二醇(4-arm PEG)为引发剂,辛酸亚锡为催化剂,丙交酯(D,L-LA)和乙交酯(GA)按不同比例混合,通过开环聚合,合成一系列聚乙二醇-聚乙丙交酯(PEG-PLGA)共聚物,然后用丁二酸酐将高分子末端羟基活化成羧基,并在4-二甲氨基吡啶(DMAP)和N,N'-二环己基碳酰亚胺(DCC)的脱水缩合作用下,分别与乙二胺环糊精(CDen)和桥联环糊精(BCDen)反应,合成一系列与β-环糊精偶联的聚乙二醇-聚乙丙交酯共聚物。所得共聚物的化学结构由核磁共振氢谱和傅利叶红外光谱确定。β-CD具有低毒性,一定的亲水性和空腔,这可以通过其芳香基团与牛血清白蛋白(BSA)的烷基链之间的相互作用,将其与BSA相连。而且,β-CD与PEG-PLGA之间不会形成超分子网络结构。因此用PEG-PLGA-β-CD共聚物制备反相胶束,在有机溶剂中包封BSA,并提高其载药量(LC)和包封率(EE)。接下来,我们采用一步法,利用这些反相胶束制备了蛋白多孔膜。实验证明,以这些反相胶束制备的多孔膜,具有有序的多孔结构,且蛋白质位于薄膜的连续相。采用乳化的方法用聚氨酯制备DOX载药纳米粒子,并对非载药和载药纳米粒子,进行体外细胞相容性和抗肿瘤活性测定,以及体外细胞摄取实验。实验结果表明,非载药聚氨酯胶束几乎是无毒的,载药聚氨酯胶束能够将药物传递到细胞核内,且具有较高的抗肿瘤活性。
[Abstract]:The biggest advantage of reverse micelles is that it has an aqueous inner environment, which can maintain biological activity of biomolecules, such as proteins and peptides, and make selective solubilization of biomolecules. Therefore, it is of great significance to apply the reverse micelle system in the research of drug carrier. Linear polyethylene glycol (MPEG) and four (4-arm PEG) glycol as initiator, stannous octoate as catalyst, the lactide (D, L-LA) and glycolide (GA) mixture in different proportion, through ring opening polymerization, synthesis of a series of polyethylene glycol PLGA copolymer (PEG-PLGA), and then use the small two the activation of terminal hydroxyl polymer anhydride into carboxyl group, and in two a 4- aminopyridine (DMAP) and N, N'- Dicyclohexylcarbodiimide (DCC) dehydration condensation, respectively with ethylenediamine (CDen) and cyclodextrin bridged cyclodextrins (BCDen) reaction, synthesis of a series of polyethylene glycol with beta cyclodextrin conjugated PLGA copolymer. The chemical structure of the obtained copolymer was determined by nuclear magnetic resonance (NMR) and Fourier Fourier infrared spectroscopy. Beta -CD has low toxicity, certain hydrophilicity and cavities, which can be connected to BSA through the interaction between its aromatic groups and the alkyl chains of bovine serum albumin (BSA). Moreover, the structure of the supramolecular network is not formed between the beta -CD and the PEG-PLGA. Therefore, reverse phase micelles were prepared by PEG-PLGA- beta -CD copolymers, and BSA was encapsulated in organic solvents, and their drug loading (LC) and encapsulation efficiency (EE) were improved. Then, we used one step method to prepare the protein porous membrane by using these reversed micelles. The experimental results show that the porous membrane prepared by these reversed micelles has an orderly porous structure and the protein is in the continuous phase of the film. DOX nanoparticles loaded with polyurethane were prepared by emulsification, and the cytocompatibility and antitumor activity in vitro and in vitro uptake experiments were carried out for non drug loaded and drug loaded nanoparticles. The experimental results show that the non drug loaded polyurethane micelles are almost non-toxic, and the drug loaded polyurethane micelles can deliver the drugs to the nucleus and have high anti-tumor activity.
【学位授予单位】：天津理工大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R943

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