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

用于特定位点、图像引导药物输送的功能性聚合物基质

• 批准号: 7904385
• 负责人: Agata A Exner
• 金额: $ 5.87万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904385
• 关键词: Address; American Cancer Society; Bilateral; Biocompatible; Biological Assay; Biomedical Engineering; Cancer Biology; Carboplatin; Cell Death; Cell Line; Chemotherapy-Oncologic Procedure; Complex; Data; Development; Devices; Dose; Drug Delivery Systems; Drug Formulations; Drug Modulation; Evaluation; Exclusion; Functional Imaging; Funding; Gel; Glycolic-Lactic Acid Polyester; Grant; Hemorrhage; Hemostatic function; Image; Image Guided Biopsy; Imagery; In Vitro; Injectable; Injection of therapeutic agent; Interdisciplinary Study; Interventional radiology; Lactate Dehydrogenase; Large Intestine Carcinoma; Lead; Leg; Localized Malignant Neoplasm; Magnetic Resonance Imaging; Malignant Epithelial Cell; Malignant Neoplasms; Measurement; Measures; Medical Imaging; Metabolism; Metastatic Neoplasm to the Liver; Methods; Mitochondria; Modeling; Modification; Perfusion; Pharmaceutical Preparations; Pluronics; Polymers; Procedures; Property; Radiation therapy; Radiofrequency Interstitial Ablation; Rattus; Research; Research Personnel; Site; Sodium Chloride; Solid Neoplasm; System; Techniques; Therapeutic; Therapeutic Agents; Tissues; Treatment Efficacy; Trypan Blue; Ultrasonography; X-Ray Computed Tomography; base; cancer therapy; chemotherapy; copolymer; cytotoxicity; design; enzyme activity; experience; imaging modality; improved; in vivo; interdisciplinary approach; minimally invasive; multidisciplinary; physical property; programs; success; therapeutic evaluation; tissue phantom; tumor

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.

将治疗剂有效递送至其作用部位是具有挑战性的、多方面的生物工程 这个问题在癌症治疗中尤为复杂。我们建议开发一种微创的 通过使用多学科方法联合研究癌症化学疗法的药物递送系统， 癌症生物学、介入放射学和靶向药物递送。具体而言，该项目侧重于 用于图像引导的、位点特异性的化疗药物递送的功能性聚合物基质的开发 毒品这种全面的功能性递送系统将由1）生物可降解的、生物相容的， 可注射聚合物基质; 2）敏化和释放调节聚合物; 3）不透射线剂， 通过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， 特定的放置和表征;和4）适合于特定的治疗的活性剂或治疗剂， 应用，并将使用各种医疗成像模式进行微创放置， 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和通过超声对药物释放的调节。一旦 充分表征后，将组件组合到最终输送系统中， 将使用大鼠结肠直肠癌在体外定量该方法。优化后的设备将 用于将卡铂递送至实验大鼠肿瘤，以及所述药物的功效和作用机制。 系统将进行评估。这种多学科的伙伴关系将导致发展一种高度 用于癌症部位特异性治疗的有效递送系统，展示了医学成像的潜力 在化疗中，并导致对癌症和导致其根除的途径的增强理解。 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足够好， 证明，相同的概念可以应用于增强其他微创，图像引导 程序.例如，通过输送氯化钠来增强射频消融， 组织传导性，通过输送止血剂以控制 出血，以及产生用于放射治疗计划和指导的可生物降解的、不透射线的标记物。