STAR POLYMER UNIMOLECULAR MICELLES FOR DRUG DELIVERY

描述（由申请人提供）：拟继续开发用于肿瘤药理学治疗的新型药物递送载体。载体是具有亲脂性和亲水性链段的星星结构的聚合物，以促进难溶性药物的包封和复合物在生理流体中的溶解度。在水性环境中，该星星聚合物形成“单分子胶束”，其将包封的药物与外部环境屏蔽。单分子结构的稳定性将使包封的药物的早期降解最小化，减少药物过早释放的有害副作用，并促进位点特异性药物靶向所选组织。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的、良好控制的药物释放速率。II期计划的具体目标是a）合成一系列星星聚合物结构以开发结构-性质关系，B）使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封过程，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星聚合物胶束中是否增强癌症肿瘤的治疗。

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.