阿霉素复合脂质纳米圆盘的制备与性质研究

发布时间：2018-02-25 18:54

本文关键词： 阿霉素复合脂质纳米圆盘肿瘤治疗化学治疗药物缓释　出处：《哈尔滨工业大学》2014年硕士论文　论文类型：学位论文

【摘要】：肿瘤分为良性肿瘤和恶性肿瘤两种，恶性肿瘤又可称之为癌症。目前，癌症已经成为了发达国家人口死亡的最重要原因，并且是发展中国家人口死亡的第二大原因。随着我国经济的不断发展，近些年我国人民的生活方式也在不断发生着改变。一些人在较大的工作压力下，生活严重不规律，再加上环境的不断恶化，导致我国的癌症患者不断增加，在癌症治疗方面也面临着非常严峻的形势。针对癌症的传统化学治疗来讲，化学药剂虽然有效，但是其对机体正常细胞的损伤也特别大，甚至有些患者因为经受不住化疗药物的副作用而放弃了治疗。靶向药物治疗是指开发出多种纳米结构或者常用的基团作为药物的载体，对化疗药物进行靶向递送。靶向载体的引入极大改善了传统化学治疗的劣势，极有可能在不久的将来取代传统的化学治疗方法。但是随着研究的不断深入，我们也发现现有的载体系统自身还有一些问题需要解决：例如，怎样使药物定向富集到肿瘤组织处，减少在其他器官的聚集，减小毒副作用；如何增强药物释放的可控性和缓释性，提高药物的有效性等。所以还需对现有的载体系统进行进一步的完善，或者研制出一种新型的载体系统，克服之前载体系统的缺点，真正做到相容性好、稳定性强、毒副作用小和靶向性、缓释性强。本课题利用适当比例的长链（有机-无机复合脂质）和短链脂质（DHPC）合成有机-无机复合脂质纳米圆盘，该纳米圆盘作为一种脂质双层膜结构，是一种很好地生物膜模型，并且表面的硅氧烷网格结构增加了圆盘的稳定性，在生物方面具有广阔的应用前景。本课题选取的抗肿瘤药物为盐酸阿霉素，，并对盐酸阿霉素进行处理，合成疏水性阿霉素。盐酸阿霉素是一种蒽环类抗癌药物，可抑制RNA和DNA的合成，对RNA的作用最强，对多种肿瘤均有作用，属周期非特异性药物，对各种生长周期的肿瘤细胞都有杀灭作用。但该药毒性作用较为严重，所以有必要开发新的药物载体来包裹盐酸阿霉素，使他的毒副作用减小，稳定性增加。本课题利用合成的有机-无机复合脂质纳米圆盘包裹疏水性的抗肿瘤药物阿霉素。对合成载药粒子进行粒度、红外、透射电镜、扫描电镜表征，证明载药的复合脂质纳米圆盘被成功合成；初步探讨纳米圆盘对药物阿霉素的控制释放性能以及生物相容性。从而为复合脂质纳米圆盘应用于药物输送提供一定的理论基础。
[Abstract]:Tumors are divided into benign tumors and malignant tumors, which can also be called cancer. At present, cancer has become the most important cause of death in developed countries. It is also the second leading cause of death in developing countries. With the continuous development of our economy, the way of life of our people has been constantly changing in recent years. Some people live under heavy pressure of work, and their lives are very irregular. In addition, the deterioration of the environment leads to an increasing number of cancer patients in China, and also faces a very serious situation in cancer treatment. As for traditional chemotherapy for cancer, although the chemical agent is effective, it also causes great damage to the normal cells of the body. Some patients even give up treatment because they can't stand the side effects of chemotherapy drugs. Targeted drug therapy is the development of a variety of nanostructures or groups commonly used as drug carriers. Targeting delivery of chemotherapeutic drugs. The introduction of targeted vectors has greatly improved the disadvantages of traditional chemotherapy and is likely to replace traditional chemotherapy in the near future. We also found that the existing carrier system itself still has some problems to be solved: for example, how to concentrate the drug into tumor tissue, reduce the accumulation in other organs, and reduce the side effects; How to enhance the controllability and slow-release of drug release, and improve the effectiveness of drugs, etc. Therefore, it is necessary to further improve the existing carrier system, or develop a new carrier system to overcome the shortcomings of the previous carrier system. Good compatibility, strong stability, small toxicity and targeting, strong slow-release. In this paper, the organic-inorganic composite lipid nanodisc was synthesized by using proper proportion of long chain (organic-inorganic compound lipid) and short chain lipid (DHPC). As a kind of lipid bilayer membrane structure, the nano-disk is a very good biofilm model. The siloxane mesh structure on the surface increases the stability of the disc and has a broad prospect in biological application. In this study, adriamycin hydrochloride is selected as the antitumor drug, and doxorubicin hydrochloride is treated with doxorubicin hydrochloride. The synthesis of hydrophobic doxorubicin. Adriamycin hydrochloride is an anthracycline anticancer drug, which can inhibit the synthesis of RNA and DNA, and has the strongest effect on RNA. But the toxicity of the drug is serious, so it is necessary to develop a new drug carrier to encapsulate adriamycin hydrochloride to reduce its side effects. The stability was increased. In this study, the hydrophobic antitumor drug doxorubicin was encapsulated by the synthesized organic-inorganic composite lipid nanodisc. The particle size, infrared, transmission electron microscope and scanning electron microscope of the synthetic drug-loaded particles were characterized. It was proved that the drug loaded composite lipid nanodisc was successfully synthesized, and the controlled release performance and biocompatibility of the nano-disk to drug doxorubicin were discussed, which provided a theoretical basis for the application of the composite lipid nano-disc in drug delivery.
【学位授予单位】：哈尔滨工业大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R943

【参考文献】