含腙键结构聚乙二醇—聚己内酯嵌段共聚物胶束的制备及其pH诱导的释药行为

发布时间：2018-03-05 04:29

本文选题：腙键　切入点：聚合物胶束　出处：《河南大学》2014年硕士论文　论文类型：学位论文

【摘要】：本文设计合成了一系列主链含腙键的聚乙二醇-聚己内酯两亲性嵌段共聚物mPEGHydPCL (AB型)与mPEGHyd(PCL)2(AB2型)。以此制备可生物降解的pH敏感聚合物胶束。从粒径,形貌,临界胶束浓度(CMC),载药量以及体外释药等方面,考察聚合物胶束的性质。主要研究内容如下： (1)以含腙键的聚乙二醇大分子mPEGHyd, mPEGHyd-2做引发剂,通过开环聚合的方法合成一系列主链含腙键mPEGHydPCL (AB型),mPEGHyd(PCL)2(AB2型)的嵌段共聚物。采用IR、1H-NMR以及凝胶渗透色谱(GPC)对聚合物的结构与组成进行表征。 (2)采用自乳化溶剂蒸发法制备空白胶束与载药胶束。应用透射电子显微镜(TEM)观察胶束的形貌,发现聚合物胶束呈球形具有核壳结构,分布均一。采用动态光散射法(DLS)测定胶束的粒径及分布,实验表明,胶束粒径较小,分布较窄。采用芘荧光探针法测定聚合物胶束的临界胶束浓度(CMC),结果表明聚合物的分子结构与分子量对临界胶束浓度有影响,测得CMC值均小于6.03×10-4mg/mL。采用高效液相色谱(HPLC)法测定聚合物胶束的载药量,结果显示不同分子结构以及不同分子量的聚合物胶束的载药量存在差异。以紫杉醇(PTX)为模型药物,考察了载药胶束的体外释放行为。实验结果表明,含腙键聚合物胶束的体外药物释放具有pH依赖性。药物的释放速度随释放介质pH值的降低而加快。 (3)采用MTT法考察分析聚合物胶束的细胞毒性以及评价载药胶束对肿瘤细胞的抑制效果。实验结果显示,空白聚合物胶束对细胞几乎没有毒性。含腙键载药聚合物胶束对人肺腺癌细胞A549的抑制作用强于不含腙键的载药聚合物胶束。
[Abstract]:A series of poly (ethylene glycol / poly (caprolactone) amphiphilic block copolymers mPEGHydPCL AB type and mPEGHyd(PCL)2(AB2 type) with main chain Hydrazone bonds were designed and synthesized to prepare biodegradable pH sensitive polymer micelles. The properties of polymer micelles were investigated in the aspects of critical micelle concentration (CMC), drug loading and drug release in vitro. The main contents of this study were as follows:. MPEGHyd-2, a macromolecule of polyethylene glycol containing Hydrazone bond, was used as initiator. A series of block copolymers containing mPEGHydPCL (AB) type of Hydronic acid (mPEGHydPCL) were synthesized by ring-opening polymerization. The structure and composition of the polymers were characterized by IR 1H-NMR and gel permeation chromatography (GPC). (2) the blank micelles and drug-loaded micelles were prepared by the self-emulsifying solvent evaporation method. The morphology of the micelles was observed by transmission electron microscope (TEM). It was found that the polymer micelles were spherical and had core-shell structure. The particle size and distribution of micelles were measured by dynamic light scattering (DLSs). The experimental results showed that the particle size of micelles was small. The critical micelle concentration of polymer micelles was determined by pyrene fluorescence probe method. The results showed that the molecular structure and molecular weight of the polymer had an effect on the critical micelle concentration. The CMC values were less than 6.03 脳 10 ~ (-4) mg 路mL ~ (-1). High performance liquid chromatography (HPLC) was used to determine the drug loading of polymer micelles. The results showed that there were differences among different molecular structures and molecular weight of polymer micelles. The release behavior of drug-loaded micelles in vitro was investigated. The results showed that the drug release of the polymer micelles containing Hydrazone bond was pH dependent, and the release rate of the drug increased with the decrease of pH value of the release medium. The cytotoxicity of polymer micelles and the inhibitory effect of drug loaded micelles on tumor cells were investigated by MTT. Blank polymer micelles had almost no toxicity to cells. The inhibitory effect of Hydrazone conjugated polymer micelles on human lung adenocarcinoma cell line A549 was stronger than that of drug-carrying polymer micelles without Hydrazone bond.
【学位授予单位】：河南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

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