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摘要：为了实现抗癌药物的靶向传输，使药物在达到病灶部位时实现零释放，以降低对正常组织细胞的损害，提高药效，通常需要制备出一种具有环境响应性的药物传输系统，该载药系统能够对肿瘤组织细胞的微环境（如温度，pH等）迅速做出响应，从而实现药物的控制释放。基于这种思路，我们对介孔二氧化硅进行了表面修饰，即在其表面包覆一层壳聚糖-聚甲基丙烯酸聚合物壳层，制备得到具有pH响应的介孔二氧化硅/壳聚糖-聚甲基丙烯酸（即MSN/CS-PMAA，MCP）复合微球。根据SEM、TEM、XRD的表征结果，证实了MSN具有单一有序的介孔结构。表面Zeta电位及蛋白吸附实验表明，CS修饰后的MCP微球能减少蛋白吸附量。本课题以阿霉素（DOX）为模型药物，研究所制备的复合微球的载药和释药行为。结果显示，该复合微球具有高的载药率和包封率。同时，药物释放实验也表明,所合成的复合微球具有pH响应的药物释放行为,与pH值等于7.4时相比，在较低的pH值（5.5）时，药物释放的速率明显更快。37799
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毕业论文关键词：靶向传输；pH响应；载药；控制释放；介孔二氧化硅
Preparation and drug release behavior of pH-responsive mesoporous silica nanoparticles
Abstract：To achieve targeted transport of anticancer drug and avoid leaking of drugs before arriving at he targeted area, to reduce damage to normal tissue cells and improve drug efficacy, an environment-responsive drug delivery systems is usually needed., This drug delivery system is sensitive to the microenvironment of tumor cells (such as temperature, pH, etc) rapidly, and then release drug controllable. Based on such research background above, polymer shell chitosan / poly (methacrylic acid) (CS-PMAA) was coated on mesoporous silica nanoparticles (MSN) to achieve a kind of pH-responsive composite microspheres. According to the results of SEM, TEM and XRD, the MSN has a single ordered mesoporous structure.. The surface Zeta potential and protein adsorption experiments showed that the MCP microspheres can reduce the protein adsorption capacity after being modified by CS. DOX was applied as a model drug to investigate the drug storage and release behavior. The results indicated that the composite microspheres exhibited an excellent drug loading capacity The cumulative release of DOX-loaded composite microspheres was pH dependent and the release rate was much faster at low pH 5.5than that of pH 7.4.
Key word：Targeted transport; pH-responsive; Drug loading; Controlled release; Mesoporous silica nanoparticles
目 录
1绪论 6
1.1 肿瘤的靶向治疗 6
1.2 介孔二氧化硅纳米材料 7
1.3 环境响应性介孔二氧化硅靶向药物传输系统 9
1.3.1 pH响应型药物输送系统 9
1.3.2 温敏型药物传输系统 10
1.3.3 氧化还原型药物传输系统 11
1.3.4 磁响应型药物传输系统 13
1.4 本课题的研究意义和主要内容 14
2 实验部分 15
2.1 原料和试剂 15
2.2 介孔二氧化硅纳米粒子(MSN)的制备及其表面修饰 15
2.2.1 MSNs的制备 15
2.2.2 pH响应性介孔二氧化硅/壳聚糖-聚甲基丙烯酸(MSN/CS-PMAA，MCP)复合微球的制备 16
2.3 材料基础理化性能测试与表征 16
2.3.1 介孔二氧化硅及其复合改性微球的微观形貌 16
2.3.2 傅立叶红外光谱分析（FT-IR） 16
2.3.3 X射线衍射分析（XRD） 17
2.3.4 Zeta电位分析 17
2.4 材料的载药及药物的释放行为研究 17