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

有效地将治疗剂输送到作用部位是一项具有挑战性的、多方面的生物工程。 这是癌症治疗中特别复杂的问题。我们建议开发一种微创的 癌症化疗药物传递系统的多学科结合研究 癌症生物学、介入放射学和靶向给药。具体地说，这个项目关注的是 用于图像引导、定位、给药的功能性聚合物基质的开发 毒品。这种全面的、功能性的递送系统将包括1)可生物降解、生物兼容、 可注射聚合物基质；2)敏化和释放调节聚合物；3)允许 使用计算机断层扫描或磁共振成像进行可视化，以便于图像引导、现场 特定的位置和特征；以及4)适合特定位置的活化剂或治疗剂 应用程序，并将使用各种医学成像方式进行微创放置， 表征和治疗评价。使用传统的和基于图像的方法，我们将首先 评估载体基质的物理性质，以及通过超声波对药物释放的调节。一次 经过充分鉴定，这些成分将被结合到最终的给药系统中，并具有细胞毒性 该方法将在体外使用大鼠结直肠癌进行量化。然后，优化的设备将 卡铂对实验性大鼠肿瘤的缓释作用及其作用机制 将对系统进行评估。这一多学科的伙伴关系将导致高度 癌症定位治疗的有效传递系统，展示了医学成像的潜力 在化疗方面，并导致加强对癌症和根除癌症的途径的了解。 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足够 证明，同样的概念也可以应用于增强其他微创、影像引导 程序。例如，通过输送氯化钠来增加射频消融 组织传导性，通过向对照组输送止血剂提高影像引导下活检的成功率 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。

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 specific application and will use various medical imaging modalities for minimally invasive placement, characterization and therapeutic evaluation. Using traditional and imaging-based methods we will first assess the physical properties of the carrier matrix, and the modulation of drug release via ultrasound. Once adequately characterized, 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.