【作者】 刘敏；

【导师】 张其清； 翁建；

【作者基本信息】 厦门大学 ， 生物医学工程， 2007， 硕士

【摘要】 透析法是近年来兴起的一种用于制备聚合物缓释纳米颗粒的新方法。其制备过程简单,可以避免表面活性剂的应用,有望应用于工业化生产,因此受到人们越来越多的关注,具有重要的研究意义和应用前景。但目前这种方法尚不完善,如纳米颗粒粒径分布宽、载药量低,纳米颗粒的控缓释性能差等问题亟待解决。聚乳酸(PLA)以其所特有的良好生物相容性和生物降解性在生物医学领域有着广泛的应用。表阿霉素(EPI)是一种广谱的抗肿瘤抗生素类药物,临床上主要剂型为注射用表阿霉素冻干粉。为了降低该药的给药量,减小毒副作用,本文以聚乳酸为药物载体,表阿霉素为模型药物,采用改进的透析法进行载表阿霉素聚乳酸纳米颗粒的制备和研究。具体内容摘要如下:1.聚乳酸纳米颗粒粒径的控制:通过改变透析方式、聚合物浓度、初始溶剂和初始水体积等各个参数使纳米颗粒的粒径得到了有效的控制,同时探讨了粒径变化的内在原因。2.聚乳酸纳米颗粒形成机制探讨:用扫描电镜、动态光散射和荧光探针法对透析过程中纳米颗粒的形态、粒径及状态进行了监测,结果表明纳米颗粒的形成主要分为三步:(1)PLA缔和物的形成;(2)PLA颗粒的形成与分裂;(3)PLA纳米颗粒的形成及固化。3.载药纳米颗粒的制备和性能研究:采用表阿霉素为模型药物,系统研究了透析过程各个参数对载药纳米颗粒载药量、包封率的影响,探讨了纳米颗粒的载药过程,同时对载药纳米颗粒的热学性质、药物分布和药物释放性能进行了研究。结果表明通过改进的透析法可以获得较高的载药量和包封率,所得到的纳米颗粒为球形、表面圆滑、药物分布均匀,且药物释放速度可以得到有效的控制。更多还原

【Abstract】 Dialysis method was developed to prepare polymer particles in recent years. Dialysis method is an acceptable simple and effective preparation method for surfactant-free particles, which is expected to apply in industrial production. However, a systematic and in-depth evaluation of the effects of dialysis conditions on properties of particles is still not available in literature.Polylactic acid (PLA) is under extensive research because of its unique and excellent biocompatibility and biodegradability, particularly in biomedical field. Epirubicin (EPI) is a broad-spectrum antitumor antibiotic drug. To reduce the amount of administration and side effects, EPI loaded nanoparticles were prepared by dialysis. This paper focused on controlling the size of PLA nanoparticles, formation mechanism of nanoparticles during preparation process, and properties of drug-loaded nanoparticles. The contents are summarized as follows:1. Particle size control: the size of the spheres could be well controlled by the preparation conditions such as the speed of dialysis, initial solvent, initial water content and polymer concentration and other parameters. The mechanism of size change was also studied.2. The formation process of PLA spheres was investigated by dynamic light scattering technique (DLS), scanning electron microscopy (SEM), fluorescence probe in situ. Based on these experimental results, it was proposed that the PLA spheres were formed in three steps: (1) complexing - individual PLA chains got complexed with each other in solution; (2) formation and disruption of PLA particles; (3) solidification of PLA spheres.3. Preparation and properties of EPI-loaded PLA nanoparticles: effects of dialysis process on drug content, encapsulation efficiency and drug loading process, in addition, thermal properties, drug distribution and drug release properties of drug-loaded nanoparticles were investigated in this thesis. The results showed that drug content and drug encapsulation ration were high, particle with spherical shape was formed, and the drug release rate could be well controlled with pH of solution, drug content and size of nanoparticles.更多还原