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

描述(由申请人提供)：有效地将治疗剂输送到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。我们建议采用多学科方法，结合癌症生物学、介入放射学和靶向给药的研究，开发一种用于癌症化疗的微创给药系统。具体地说，该项目专注于开发用于图像引导的、特定部位的化疗药物输送的功能性聚合物基质。这一全面的功能性递送系统将包括1)可生物降解、生物兼容、可注射的聚合物基质；2)敏化和释放调节聚合物；3)可通过计算机断层扫描或磁共振成像进行可视化的不透射线制剂，以便于图像引导、特定部位的定位和定征；以及4)适合具体情况的活性制剂或治疗性制剂。一旦充分表征，这些成分将被结合到最终的递送系统中，该方法的细胞毒性将在体外使用大鼠结直肠癌进行量化。然后，优化后的装置将被用于将卡铂输送到实验大鼠肿瘤，并将评估该系统的疗效和作用机制。这一多学科伙伴关系将导致开发一种用于癌症特定部位治疗的高效传递系统，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，但如果这种方法的有效性得到充分证明，同样的概念也可以应用于增强其他微创、图像引导的手术。例如，通过输送氯化钠以增加组织传导性来加强射频消融，通过输送止血剂来控制出血来提高图像引导活检的成功率，以及为放射治疗计划和指导创建可生物降解的不透射线的标记物。

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.