Contrast Enhanced Ultrasound with Therapeutic Modality

对比增强超声与治疗方式

• 批准号: 6796348
• 负责人: MARGARET A. WHEATLEY
• 金额: $ 17.75万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6796348
• 关键词: biodegradable product; bioimaging /biomedical imaging; biotransformation; cell line; contrast media; drug delivery systems; drug design /synthesis /production; neoplasm /cancer chemotherapy; neoplasm /cancer diagnosis; neoplastic cell; polymers; sound frequency; tissue /cell culture; ultrasonography

DESCRIPTION (provided by applicant): Recent advances in contrast agent (CA) development have expanded the range of diagnostic ultrasound (US), an imaging modality that has the advantage of being safe, real-time, inexpensive and portable. The challenge now becomes the differentiation of soft tissue metastases in organs such as the liver and breast, imaging of actual and potential disease states such as atherosclerotic plaque or regions of ischemia, and discrimination between malignant and benign. Moreover the potential of a therapeutic role for US, using imaging to guide and trigger drug delivery presents exciting new areas of research. The long-term objective is to develop a polymer-based US contrast agent with therapeutic capabilities. The goal is to both image and target release of a drug from the CA using the same US energy. The polymer CA should enhance the diagnostic image and aid the physician in locating diseased tissue. The agent must be non toxic, biocompatible, biodegradable and stable after injection for the duration of imaging. It must pass unimpeded through the capillary bed, (be less than -6 pm in diameter). The first aim is to develop a CA that is echogenic in the medical imaging range, (1-10 MHz) and stable in vivo giving a clear diagnostic image and have the potential to deliver a drug. The second is to attach a drug onto the surface of the CA and to use focused US to visualize and release the exact dose of drug at the time and location required. Specific Aim 1: To develop, optimize and characterize a biodegradable polymer CA with characteristics that enable it to function as a drug carrier and delivery system. Specific Aim 2: To characterize the degradation pattern of the hollow polymer microcapsules, with and without US of different frequencies. Specific Aim 3: To investigate incorporation of bioactive compounds into the polymer capsule shell. Determination will be made of the method which yields the greatest payload of the bioactive compound and which reduces any initial burst effect. Specific Aim 4: To determine the effects of ultrasound energy on the bioactive compound release rate and pattern from the contrast agent, the effect of ultrasound on the compound activity and the effect of payload on acoustic properties. To understand the effects of the ultrasound parameters, frequency, pressure and energy on the drug release profile, and investigate the mechanism of drug release, in order to better control the release profile. Specific Aim 5: Investigate acoustically-triggered drug delivery in vitro using tissue cultured breast cancer cell lines. Optimized drug-loaded capsules will be tested for efficacy of bioactive compound release by assessing cell damage in tissue cultures, compared with blank capsules and with US alone. These studies are a prelude to show feasibility prior to in vivo studies.

描述（由申请人提供）： 对比剂（CA）开发的最新进展扩大了诊断超声（US）的范围，这是一种成像模式，具有安全，实时，廉价和便携的优势。现在的挑战是在肝脏和乳房等器官中的软组织转移的分化，实际和潜在疾病状态的成像，例如动脉粥样硬化斑块或缺血区域，以及恶性和良性之间的歧视。此外，使用成像指导和触发药物提供了令人兴奋的新研究领域。长期目标是开发一种基于聚合物的美国对比剂，并具有治疗能力。目的是使用相同的美国能量从CA中的图像和目标释放。聚合物CA应增强诊断图像并帮助医生定位患病组织。在成像持续时间内注射后，该试剂必须无毒，生物相容性，可生物降解和稳定。它必须在毛细管床（直径小于-6 pm）中不受阻碍。第一个目的是开发一个在医学成像范围内具有回声的Ca，（1-10 MHz）并在体内稳定，提供明确的诊断图像，并具有输送药物的潜力。第二个是将药物连接到CA的表面上，并在所需的时间和位置使用聚焦我们可视化和释放精确的药物剂量。特定目的1：开发，优化和表征具有可生物降解的聚合物CA具有特征，使其能够充当药物载体和输送系统。特定目的2：表征有和没有不同频率的空心聚合物微胶囊的降解模式。特定目的3：研究将生物活性化合物掺入聚合物胶囊壳中。将确定该方法产生最大的生物活性化合物有效载荷，并降低任何初始爆发效果。特定目标4：确定超声能量对对比剂的生物活性复合释放速率和模式的影响，超声对复合活动的影响以及有效载荷对声学特性的影响。要了解超声参数，频率，压力和能量对药物释放曲线的影响，并研究药物释放的机理，以便更好地控制释放曲线。具体目标5：使用组织培养的乳腺癌细胞系在体外进行了触发的药物递送。与空白胶囊相比，通过评估组织培养物中的细胞损伤，将测试优化的药物胶囊的生物活性化合物释放功效，并与我们单独评估。这些研究是在体内研究之前显示可行性的前奏。