Functional Polymer Matrixes for Site-Specific, Image Guided Drug Delivery

描述（由申请人提供）：将治疗剂有效递送至其作用部位是一个具有挑战性的、多方面的生物工程问题，在癌症治疗中尤其复杂。我们建议开发一个微创药物输送系统的癌症化疗，通过使用多学科的方法联合研究癌症生物学，介入放射学和靶向药物输送。具体而言，该项目的重点是开发功能性聚合物基质，用于图像引导的、位点特异性的化疗药物递送。这种全面的功能性递送系统将由以下组成：1）可生物降解的、生物相容的、可注射的聚合物基质; 2）敏化和释放调节聚合物; 3）允许用计算机断层扫描或磁共振成像可视化以促进图像引导的、位点特异性放置和表征的不透射线的试剂;和4）适合于特定用途的活性剂或治疗剂。一旦充分表征，组分将被组合到最终的递送系统中，并且该方法的细胞毒性将使用大鼠结肠直肠癌在体外定量。然后将优化的装置用于将卡铂递送到实验大鼠肿瘤，并评估该系统的功效和作用机制。这种多学科的伙伴关系将导致开发一种用于癌症特定部位治疗的高效递送系统，展示医学成像在化疗中的潜力，并导致对癌症及其根除途径的进一步了解。虽然目前的焦点集中在癌症治疗上，但如果这种方法的疗效得到充分证明，同样的概念可以应用于增强其他微创图像引导手术。示例包括通过输送氯化钠以增加组织传导性来增强射频消融，通过输送止血剂以控制出血来提高图像引导活检的成功率，以及创建用于放射治疗计划和指导的可生物降解的不透射线标记物。

DESCRIPTION (provided by applicant): The efficient delivery of a therapeutic agent to its site of action is a challenging, multifaceted bioengineering problem that is particularly complex in the treatment of cancer. We propose to develop a minimally invasive drug delivery system for cancer chemotherapy by using a multidisciplinary approach uniting research in cancer biology, interventional radiology and targeted drug delivery. Specifically, this project focuses on the development of functional polymer matrixes for image guided, site-specific, delivery of chemotherapeutic drugs. This comprehensive, functional delivery system will consist of 1) a biodegradable, biocompatible, injectable polymer matrix; 2) a sensitizing and release-modulating polymer; 3) a radiopaque agent allowing visualization with computed tomography or magnetic resonance imaging to facilitate image guided, site- specific placement and characterization; and 4) an active agent, or therapeutic, suited to the specifd. Once adequately chracterized, the components will be combined into the final delivery system, and cytotoxicity of the approach will be quantified in vitro using a rat colorectal carcinoma. The optimized device will then be used to deliver carboplatin to experimental rat tumors and the efficacy and mechanism of action of the system will be assessed. This multidisciplinary partnership will result in the development of a highly effective delivery system for site-specific treatment of cancer, demonstrate the potential of medical imaging in chemotherapy, and lead to the of enhanced understanding of cancer and paths leading to its eradication. Although the present focus centers on cancer treatment, if the efficacy of this approach is sufficiently demonstrated, the same concepts can be applied to enhance other minimally invasive, image guided procedures. Examples include enhancing radiofrequency ablation by delivering sodium chloride to increase tissue conductivity, improving successes of image guided biopsy by delivering hemostasis agents to control bleeding, and creating biodegradable, radiopaque markers for radiation therapy planning and guidance.