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）： 造影剂 (CA) 开发的最新进展扩大了超声诊断 (US) 的范围，超声诊断是一种成像方式，具有安全、实时、廉价和便携的优点。现在的挑战是区分肝脏和乳房等器官中的软组织转移，对动脉粥样硬化斑块或缺血区域等实际和潜在疾病状态进行成像，以及区分恶性和良性。此外，利用成像引导和触发药物输送，美国的治疗作用的潜力提出了令人兴奋的新研究领域。长期目标是开发一种具有治疗能力的基于聚合物的超声造影剂。目标是使用相同的美国能量对药物从 CA 进行成像和靶向释放。聚合物CA应该增强诊断图像并帮助医生定位患病组织。该试剂必须是无毒的、生物相容的、可生物降解的并且在注射后在成像期间保持稳定。它必须畅通无阻地通过毛细管床（直径小于-6 pm）。第一个目标是开发一种在医学成像范围（1-10 MHz）内有回声且在体内稳定的 CA，可提供清晰的诊断图像，并具有输送药物的潜力。第二种是将药物附着在 CA 的表面上，并使用聚焦超声在所需的时间和位置可视化并释放精确剂量的药物。具体目标 1：开发、优化和表征可生物降解的聚合物 CA，其特性使其能够充当药物载体和递送系统。具体目标 2：表征中空聚合物微胶囊在有或没有不同频率 US 的情况下的降解模式。具体目标 3：研究将生物活性化合物掺入聚合物胶囊壳中。将确定产生生物活性化合物的最大有效负载并减少任何初始爆发效应的方法。具体目标 4：确定超声能量对生物活性化合物从造影剂释放速率和模式的影响、超声对化合物活性的影响以及有效负载对声学特性的影响。了解超声参数、频率、压力和能量对药物释放曲线的影响，探讨药物释放机理，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研究声学触发的体外药物递送。将通过评估组织培养物中的细胞损伤，与空白胶囊和单独使用 US 进行比较，来测试优化的载药胶囊的生物活性化合物释放功效。这些研究是体内研究之前展示可行性的前奏。