基因递送材料和用于药物输送的光敏性纳米材料的合成及性能的研究

发布时间：2018-06-23 15:28

本文选题：药物递送系统 + 光敏性　；参考：《河北大学》2017年硕士论文

【摘要】：药物递送系统在医学和药学领域受到越来越多的关注,因为它可以大幅提高各种治疗方案的效率。与传统的肿瘤治疗方法(化疗)相比,建立刺激响应型药物递送系统可以减少药物在递送过程中的降解,在血液循环过程中增加药物在肿瘤部位的堆积,达到在时间上和空间上释放药物的效果,同时可以减少药物对正常细胞的伤害。光响应型材料受到人们越来越多的关注,因为在刺激性因素中光是最有希望的选择,它可以通过改变光照时间、光照强度以及光束直径来控制药物的释放。基因治疗是一种将基因递送到细胞或组织用于遗传性疾病治疗的技术,目前已经广泛应用于癌症和传染性疾病的治疗。PEI是一种阳离子聚合物,由于其氨基基团较多,PEI的表面正电荷也较多,因此容易与带负电荷较多的分子如DNA因静电相互作用结合。而且它还可以通过破坏溶酶体膜进而从内涵体中逃逸,因此PEI被成功的用于体内和体外的基因递送实验。研究证明,随着分子量的增大,PEI的转染效率随之增大,但是毒性也会相应增加。为了提高转染效率同时降低毒性,很多课题组对分子量较小的PEI进行了修饰,达到提高转染效率的目的。一、本文设计了两种可以光致降解的药物递送系统。本文使用邻硝基卞醇和香豆素基团两种光敏基团,与乙醇胺和二甲基丙烯酰氯反应得到聚酯,通过乳液聚合的方法制备了光敏性的纳米粒。同时,为了考察它们的光致释放效应,将姜黄素和lapachone包载在纳米粒中。本文对纳米粒进行了紫外可见光谱(UV-Vis)、动态光散射(DLS)和扫描电镜的表征,同时考察了纳米粒在细胞内的摄取和光控释放能力。通过对这些性能的研究,本文得出结论,利用聚乙二醇二甲基丙烯酸酯作为交联剂,光照之后纳米粒粒径会增大,但是不会增大很多,同时可以释放包封的药物,达到一定的治疗效果。二、本文使用二硫化物作为交联剂将分子量较小的PEI连接成分子量较大的聚合物,当分子量较大的聚合物PEI-CL进入细胞后,二硫键在谷胱甘肽还原酶的作用下断裂,分子量减小,毒性随之减小,同时提高其转染效率。我们设计了PEI-CL聚合物,并使用红外光谱进行表征,并考察了它的转染效率。PEI-CL的转染效率明显高于PEI 1.8K。
[Abstract]:Drug delivery systems have received increasing attention in the medical and pharmaceutical fields because they can greatly improve the efficiency of various treatment schemes. Compared with traditional cancer therapy (chemotherapy), the establishment of stimulus-responsive drug delivery systems can reduce the degradation of drugs during delivery and increase the accumulation of drugs in tumor sites during blood circulation. Achieve the effect of releasing drugs in time and space, while reducing damage to normal cells. More and more attention has been paid to photo-responsive materials, because light is the most promising choice among the stimulative factors, which can control the release of drugs by changing the illumination time, light intensity and beam diameter. Gene therapy is a technology that delivers genes to cells or tissues for the treatment of genetic diseases. PEI is a cationic polymer that has been widely used in the treatment of cancer and infectious diseases. Because the amino groups of PEI have more positive surface charges, it is easy to interact with the negatively charged molecules such as DNA because of electrostatic interaction. And it can escape from the connotations by destroying the lysosomal membrane, so PEI has been successfully used in gene delivery experiments in vivo and in vitro. The results showed that the transfection efficiency of PEI increased with the increase of molecular weight, but the toxicity also increased. In order to improve the transfection efficiency and reduce the toxicity, many research groups modified PEI with small molecular weight to improve the transfection efficiency. First, two photodegradable drug delivery systems are designed. In this paper, two kinds of Guang Min groups, o-nitrobenol and coumarin, were used to react with ethanolamine and dimethacryloyl chloride to obtain polyester. Guang Min nanoparticles were prepared by emulsion polymerization. At the same time, curcumin and lapachone were encapsulated in nanoparticles to investigate their photo-release effects. The ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS) and scanning electron microscopy (SEM) were used to characterize the nanoparticles. Through the study of these properties, it is concluded that the size of the nanoparticles will increase after irradiation with polyethylene glycol dimethacrylate as crosslinking agent, but it will not increase much, and the encapsulated drugs can be released at the same time. To achieve a certain therapeutic effect. Secondly, using disulfide as crosslinking agent, PEI with small molecular weight was connected to polymer with high molecular weight. When PEI-CL, a polymer with higher molecular weight, entered the cell, the disulfide bond broke down under the action of glutathione reductase, and the molecular weight decreased. The toxicity decreased and the transfection efficiency was improved. PEI-CL polymer was designed and characterized by infrared spectroscopy. The transfection efficiency of PEI-CL was significantly higher than that of PEI 1.8K.
【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】：TB383.1;TQ460.1

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