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PLGA/TiO2纳米药物缓释载体的研究
【作者】 蔡静；
【导师】 杨亚楠；
【作者基本信息】 长春工业大学 ， 高分子化学与物理， 2010， 硕士
【摘要】 本文将可生物降解材料乳酸和羟基乙酸的共聚物（PLGA）用不同的方法引入到TiO2纳米粒子表面上,制备了PLGA/TiO2纳米有机-无机杂化材料,目的是以此为载体吸附包裹胰岛素或其他药物,随着PLGA的降解,缓慢释放药物,以达到药物长效缓释的作用,同时提高药物缓释微球的载药量和包封率。研究工作如下：（1）用硅烷偶联剂氨丙基三乙氧基硅烷（KH550）对二氧化钛表面进行预处理,接着与带有高活性端基的聚乳酸-羟基乙酸共聚物（PLGA）反应,制备PLGA/TiO2有机-无机杂化纳米材料。通过研究表明,PLGA/TiO2有机-无机杂化纳米材料中PLGA通过酰胺键键合接枝到Ti02纳米粒子的表面；PLGA接枝量为13.2%左右；通过接枝低分子量的聚合物,纳米粒子的分散性得到较好的改善,无明显团聚现象。（2）通过实验将磺酸基引入PLGA分子链上,制得璜化PLGA,接着采用溶胶-凝胶技术,将璜化PLGA与二氧化钛凝胶反应,制备璜化PLGA/TiO2（SPLGA/TiO2）有机-无机杂化材料。研究表明,通过纳米Ti02表面羟基与PLGA的磺酸基上的氢离子的键合作用,低分子量的PLGA接枝到TiO2纳米粒子的表面；PLGA接枝量为20%左右；杂化材料纳米粒子分布均匀,无明显团聚现象；PLGA接枝在Ti02表面形成包裹层,有效的改善了TiO2的分散性和均一性。由细胞实验可知,PLGA/TiO2有机-无机杂化材料的生物相容性良好,适宜作为药物控制体系中的药物载体。（3）研究了PLGA/TiO2杂化材料载药缓释体系中的应用。首先用杂化材料纳米粒子吸附溶液中的BSA制备纳米级的药物颗粒,然后运用水包油包固体（S/0/W）乳化法将药物粒子用可生物降解的高分子材料PLGA包裹起来制成蛋白药物控制释放制剂,同时用纳米二氧化钛作为对比实验。通过紫外和SEM分析可知,纳米材料吸附蛋白药物后的产物仍为纳米粒子。与纯二氧化钛相比,在二氧化钛表面接枝PLGA后,杂化材料的BSA吸附量较高,由43.31%提高到81.34%。将两种材料吸附BSA后的药物粒子用水包油包固体乳化法制备成聚合物微球,均具有很高的包封率,大于90%；但杂化材料载药微球的载药量由9.71%提高到14.63%,包封率由90.51%提高到97.53%。且在体外释放行为中突释较小。
【Abstract】 In order to get high bioactive and good drug delivery carrier, novel nano bio-degradable and the organic-inorganic hybrid materials with nano-titanium dioxide. The surface modification process and PLGA was carried further to increase their interface compatibility. In addition, the materials behavior was characterized and analysis. and the hybrid materials biocompatibility and drug delivery carriers were studied(1) In the first step, the y-Aminopropyltriethoxysilane (KH550) was grafted on the surface of titanium dioxide, and then reacted with high activity-terminated poly(lactic-acid-glycolic-acid) (PLGA), prepared the PLGA/TiO2 organic-inorganic hybrid nano-materials. The research results shows that, the PLGA bonded through the amide bond grafted onto the surface of TiO2 nanoparticles in the PLGA/TiO2 organic-inorganic hybrid nano-materials, PLGA grafted amount of 13.2%, and the hybrid material dispersion had a better improve, and no obvious agglomeration.(2) First of all, PLGA was modified into sulfuric acid terminated, and reacted with titanium dioxide sol-gel through the sol-gel technology, perpetrated the PLGA/TiO2(SPLGA/TiO2) organic-inorganic hybrid materials. The Studies results show that, SPLGA/TiO2 organic-inorganic hybrid materials, sulfuric acid terminated PLGA was successful prepared and grafted on the surface of TiO2 nanoparticles through amide. PLGA grafted amount of about 20%, SEM photographs shows that hybrid materials has a good dispersion, no obvious agglomeration. PLGA grafted on TiO2 surface was formatted parcel layer, effectively improved the dispersion of TiO2 and homogeneity, and SPLGA/TiO2 organic-inorganic hybrid materials had excellent biocompatibility which we can see from the cells experiments and suit as a drug carriers in the drug control systems.(3) SPLGA/TiO2 microspheres were prepared by firstly absorbing model drug BSA onto SPLGA/TiO2 nano particles and then coating with PLGA via S/O/W method, compared with nano-TiO2. Using UV-Vis and TEM, the absorbing behaviors of BSA onto nano particles and the impact of preparation method on the drug loading efficiency and in vitro controlled drug release were studied. The results showed that the two kinds microspheres all had a high encapsulation efficiecy, greater than 90%. SPLGA/TiO2 nano particles had a higher BSA adsorption, increased from 43.31% to 81.34%. The SPLGA/TiO2 microspheres had a high drug loading and a smaller burst in vitro behavior.