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理治疗的新型药物传递载体。该载体是一种星形结构的聚合物，具有亲脂和亲水的部分，以促进难溶性药物的包封和复合物在生理液体中的溶解度。在水环境中，星形聚合物形成“单分子胶束”，保护被封装的药物不受外部环境的影响。单分子结构的稳定性将最大限度地减少被封装药物的早期降解，减少药物过早释放带来的有害副作用，并有利于靶向特定部位的药物靶向选择组织。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装载水平和可预测的，良好控制的药物释放速度。II期项目的具体目标是a)合成一系列星形聚合物结构，以发展结构-性质关系，b)使用这些结构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)通过内布拉斯加州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是否能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.