STAR POLYMER UNIMOLECULAR MICELLES FOR DRUG DELIVERY

用于药物输送的星形聚合物单分子胶束

• 批准号: 6799200
• 负责人: Fei Wang
• 金额: $ 38.53万
• 依托单位: EIC LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-08 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6799200
• 关键词: antineoplastics; calorimetry; chemical structure function; doxorubicin; drug design /synthesis /production; drug interactions; drug metabolism; drug vehicle; etoposide; fluorescence spectrometry; high performance liquid chromatography; interferometry; laboratory mouse; micelles; microcapsule; neoplasm /cancer chemotherapy; nuclear magnetic resonance spectroscopy; pharmacokinetics; polymers; transmission electron microscopy

DESCRIPTION (provided by applicant): The continued development of a novel drug delivery vehicle for pharmacological treatment of tumors is proposed. The vehicle is a star structured polymer having lipophilic and hydrophilic segments to promote both encapsulation of poorly soluble drugs and solubility of the complex in physiological fluids. In an aqueous environment the star polymer forms a "unimolecular micelle", which shields the encapsulated drug from the outer environment. The stability of the unimolecular structure will minimize early degradation of the encapsulated drug, decrease harmful side effects from premature drug release, and facilitate site-specific drug targeting to selected tissues. Each micelle will have an identical structure and molecular weight that will promote uniform drug loading levels and a predictable, well-controlled drug release rate. The specific aims in the Phase II program are a) to synthesize a range of star polymer structures to develop structure-property relationships, b) to use these structures to develop and optimize the drug encapsulation process for the model anticancer drug etoposide, and, c) by in vitro and in vivo testing at the University of Nebraska Medical Center, determine whether incorporation of anticancer drugs into star polymer micelle enhances therapy of cancer tumors.

描述（由申请人提供）：建议继续开发用于肿瘤药物治疗的新型药物递送载体。该载体是具有亲脂性和亲水性链段的星形结构聚合物，以促进难溶性药物的封装和复合物在生理液体中的溶解度。在水性环境中，星形聚合物形成“单分子胶束”，保护封装的药物免受外部环境的影响。单分子结构的稳定性将最大限度地减少封装药物的早期降解，减少药物过早释放造成的有害副作用，并促进特定位点的药物靶向选定的组织。每个胶束将具有相同的结构和分子量，这将促进均匀的药物负载水平和可预测、良好控制的药物释放速率。第二阶段计划的具体目标是a）合成一系列星形聚合物结构以开发结构-性能关系，b）利用这些结构开发和优化模型抗癌药物依托泊苷的药物封装工艺，以及c ）通过内布拉斯加大学医学中心的体外和体内测试，确定将抗癌药物掺入星形聚合物胶束中是否可以增强癌症肿瘤的治疗。