【作者】 罗奇志；

【导师】 陈建海；

【作者基本信息】 第一军医大学 ， 药剂学， 2002， 硕士

【摘要】 毫微粒是一类由天然或合成的高分子材料制成的粒径在1nm～1000nm的固态胶体颗粒，在体内易被巨噬细胞吞噬而集中分布在网状内皮系统(reticuloendothelial system，RES)丰富的肝、脾、淋巴等部位，以毫微粒作为载体制成的毫微粒给药系统具有靶向性、改变药物体内分布、控缓释药、降低药物毒副作用及提高药物生物利用度等诸多优点。 本研究选用聚氰基丙烯酸正丁酯作为载体材料，以丝裂霉素C(Mitomycin C，MMC)作为模药，经过多次实验探索，解决了国内外文献均报道以乳化聚合法制备聚氰基丙烯酸正丁酯毫微粒时，反应通常在酸性条件下进行，而丝裂霉素C在酸性条件中极不稳定这一矛盾，寻找到了在中性条件下用乳化聚合法制备丝裂霉素C-聚氰基丙烯酸正丁酯毫微粒的方法，并通过均匀设计优选了最佳制备工艺条件，对该毫微粒形态、粒径大小及其分布、包封率和载药量、体外释药规律、动物体内分布进行了研究。制备出了平均粒径 79.87±7.24nm，Span=1.60，包封率79.03％，载药量6.58％的毫微粒，体外释药符合对数动力学规律，动物体内分布实验表明小鼠尾静脉注射30min后，即有76.29％的药物浓集于肝脏。对于提高丝裂霉素C临床肝癌治疗效果，降低毒副作用具有应用前景。更多还原

【Abstract】 Nanoparticles are small polymeric particles in the nanometer size range. Usually They are easily taken up by phagocytic cells and accumulate in the organs of the reticuloendothelial system (RES) such as the liver,the spleen and the lympth. As a drug carrier system,it has the ability of tumor targeting,changing the biodistribution of drugs,controlled or sustained drug release,reducing the toxicity and enhancing the efficacy of drugs.In this article,polybutylcyanoacrylate was used as the polymeric carriers,and the model drugs we chosed was mitomycin C. After serials of experiments,we found a new method to prepare mitomycin C-polybutylcyanoacrylate nanoparticles in neutral pH aqueous medium,which solved the problem that polybutylcyanoacrylate nanoparticles usually were reported be prepared in low pH aqueous medium,while mitomycin C was unstable in such conditions.Technical conditions were determined by uniform design. The morphology,size and size distribution,encorperation rate,drug loading,release characteristics in vitro,biodistribution of mitomycin C-polybutylcyanoacrylate nanoparticles in mice were studied. The results showed that the average size was 79.87+ 7.24nm,span=1.60,encorporation rate was 79.03%,drug loading was 6.58%,the release characteristics in vitro was in accord with logarithmic kinetics,76.29% of the mitomycin C were accumulated in liver at 30min after iv MMC-PBCA-NP. The study showed a possibility of enhancing efficacy and reducing toxicity of mitomycin C.更多还原