项目名称: 内部空腔功能化方法制备高效、低毒的树形高分子药物载体
项目编号: No.21274044
项目类型: 面上项目
立项/批准年度: 2013
项目学科: 数理科学和化学
项目作者: 程义云
作者单位: 华东师范大学
项目金额: 78万元
中文摘要: 阳离子树形高分子已被广泛应用于药物输送,基因治疗等生物医学领域,但是其纳米毒性严重制约了它们的临床应用可行性。本项目拟采用表面乙酰化、聚乙二醇化等方法降低阳离子树形高分子的毒性,并通过多种内部功能化方法将活性基团或荷电基团引入到乙酰化和聚乙二醇化修饰的树形高分子的内部空腔中,从而保持阳离子树形高分子的高载药性能,获得高效、低毒的树形高分子药物载体。通过将药物以前药或复合物的方式结合到树形高分子的内部空腔来提高药物在生理环境中的稳定性以及药物剂型的水溶性,实现可控的药物释放等。在此基础上,合成具有靶向功能且药物分子连接在树形高分子内部的多功能高效、低毒的药物载体。通过本项目的研究,为树形高分子材料进入临床应用奠定坚实的理论基础。
中文关键词: 树形高分子;药物递送;内部功能化;刺激响应;肿瘤治疗
英文摘要: Cationic dendrimers have been widely used in biomedical fields such as drug delivery and gene therapy. However, the cytotoxicity of cationic dendrimers limited their clinical applications. In this research program, we will synthesize acetylated or PEGylated dendrimers and introduce reactive functional groups or charged groups into interior pockets of the acetyalted or PEGylated dendrimers to obtain dendrimer drug carriers with high efficiency and low cytotoxicity. Drugs can be loaded within the pockets of prepared dendrimers through prodrugs or dendrimer/drug complexes to improve their stability in physiological conditions, to increase the solubility of the drug formulations, and to achieve a controlled drug release. And on that basis, we will conjugate targeting ligands on the surface of dendrimer and bind drug molecules to the interior pocekts of dendrimer to prepare multifunctinal drug carriers with high efficiency and low cytotoxicity. This project is a fundamental study to promote the clinical applications of dendrimers in a near future.
英文关键词: Dendrimers;Drug delivery;Interior functionalizaiton;Stimuli-responsive;Cancer therapy