聚乙二醇-聚丙氨酸嵌段共聚物的合成与药物释放行为

发布时间：2018-02-04 03:08

  本文关键词： L/D-丙氨酸-N-羧基环内酸酐(NCA) 聚乙二醇 聚丙氨酸 药物释放　出处：《河北大学》2017年硕士论文　论文类型：学位论文

【摘要】：许多抗肿瘤药物如姜黄素、阿霉素都难溶于水,这极大地限制了它们在临床治疗方面的应用。聚合胶束是一种新型的药物载体,它可用于靶向、水溶性差的治疗药物。胶束具有疏水核心和亲水外壳,通过自组装,两亲性分子或表面活性剂在溶液中聚集成球形或其他结构的纳米尺寸胶体颗粒。与通常表面活性剂形成的胶束相比,聚合胶束更稳定,并且可以溶解大量疏水性化合物。由于外壳的亲水性和外径的纳米尺寸,聚合胶束在肿瘤组织中滞留时间延长,对肿瘤组织具有被动靶向性。因此,设积、制备不同结构的聚合胶束,探究抗肿瘤药物的控制释放与靶向规律成为当今生物医学领域中研究热点之一。本文主要分为以下几部分:一、在绪论部分简要介绍了聚合物胶束以及聚合物胶束的形成机理、制备方法、载药以及释放过程等。二、以L/D-丙氨酸、三光气为原料,首先合成了L-丙氨酸-N-羧基环内酸酐单体(LA-NCA)和D-丙氨酸-N-羧基-环内酸酐(DA-NCA)单体。以丙氨酸-N-羧基环内酸酐和氨基聚乙二醇单甲醚(MPEG-NH2)分别为单体和大分子引发剂,成功制备出聚乙二醇-聚丙氨酸嵌段共聚物(PEG-b-PA)。利用红外光谱、核磁光谱、凝胶渗透色谱对所制备的丙氨酸-N-羧基环内酸酐单体和PEG-b-PA进行了结构表征。三、采用透析法制备了基于PEG-b-PA的聚合物胶束,利用透射电子显微镜(TEM)观察了其形貌,聚合物胶束具有球形结构并且粒径大小均一,其尺寸约为20纳米。通过紫外-可见分光光度积测定了不同p H、透析时间、共聚物用量、药物用量等因素对聚合物胶束载药与释放的影响。结果表明:当L-丙氨酸与D-丙氨酸比例为1:0.25,单体与引发剂比例为70:1,透析时间为72小时时姜黄素的释放行为为缓释。
[Abstract]:Many antitumor drugs such as curcumin and adriamycin are insoluble in water which greatly limits their clinical application. Polymeric micelle is a new drug carrier which can be used for targeting. A poorly water-soluble therapeutic drug. Micelles have hydrophobic cores and hydrophilic shells that are self-assembled. Amphiphilic molecules or surfactants aggregate into spherical or other nano-sized colloidal particles in solution, and the polymeric micelles are more stable than those formed by conventional surfactants. Because of the hydrophilicity of shell and the nanometer size of outer diameter, the retention time of polymeric micelles in tumor tissues is prolonged, and the polymer micelles have passive targeting to tumor tissues. The preparation of polymeric micelles with different structures and the investigation of the controlled release and targeting of anti-tumor drugs have become one of the research hotspots in the biomedical field. This paper is mainly divided into the following parts: 1. In the introduction part, the formation mechanism, preparation method, drug loading and release process of polymer micelles and polymer micelles are briefly introduced. Secondly, L / D- alanine and triphosgene are used as raw materials. L- alanine-N-carboxylic anhydride monomers (La-NCA) and D- alanine-N-carboxyl-intracyclic anhydride (DA-NCA) were synthesized. Monomer. The monomer and macromolecular initiator were alanine -N-carboxylic anhydride and amino polyethylene glycol monomethyl ether (MPEG-NH2), respectively. Poly (ethylene glycol) -polyalanine block copolymer (PEG-b-PAA) was successfully prepared. The structure of alanine -N-carboxylic anhydride monomer and PEG-b-PA were characterized by gel permeation chromatography. Thirdly, the polymer micelles based on PEG-b-PA were prepared by dialysis. The morphology of the polymer micelles was observed by transmission electron microscopy (TEM). The polymer micelles have spherical structure and uniform particle size. Its size is about 20 nanometers. Different pH, dialysis time and the amount of copolymers were determined by UV-Vis spectrophotometry. The results showed that the ratio of L- alanine to D- alanine was 1: 0.25 and the ratio of monomer to initiator was 70: 1. The release behavior of curcumin was sustained when dialysis time was 72 hours.
【学位授予单位】：河北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O631;TQ460.1

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