STAR POLYMER UNIMOLECULAR MICELLES FOR DRUG DELIVERY

描述(由申请人提供)：建议继续开发一种用于肿瘤药物治疗的新型药物输送载体。该载体是一种星形结构的聚合物，具有亲脂性和亲水性，以促进难溶药物的包封性和复合体在生理液体中的溶解。在水环境中，星形聚合物形成“单分子胶束”，将被包裹的药物与外部环境隔绝。单分子结构的稳定性将最大限度地减少包裹药物的早期降解，减少过早药物释放的有害副作用，并促进特定部位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载量水平和可预测的、可控的药物释放速率。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发展结构-性能关系，b)利用这些结构来开发和优化模型抗癌药物依托泊苷的药物包裹工艺，以及c)通过在内布拉斯加大学医学中心进行的体外和体内测试，确定将抗癌药物掺入星形聚合物胶束是否能增强癌症的治疗。

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.