Dynamics of Vascular Microbubbles and Microdroplets in Gas Embolotherapy

气体栓塞治疗中血管微泡和微滴的动力学

• 批准号: 8505588
• 负责人: JOSEPH L BULL
• 金额: $ 57万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-12 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8505588
• 关键词: Acoustics; Affect; Albumins; Animals; Apoptosis; Blood Vessels; Blood flow; Caliber; Catheters; Cell Death; Clinical; Clinical Trials; Dose; Drug Delivery Systems; Drug Formulations; Drug Transport; Embolism; Encapsulated; Fibroid Tumor; Fluorocarbons; Funding; Gases; Goals; Grant; Hypoxia; Image; Interruption; Knowledge; Lead; Lipids; Liquid substance; Malignant neoplasm of liver; Mechanics; Methodology; Microbubbles; Microcirculation; Modality; Necrosis; Outcome; Permeability; Primary carcinoma of the liver cells; Rattus; Renal carcinoma; Saline; Solid; Source; Staging; Study models; Testing; Therapeutic Embolization; Time; Tissues; Ultrasonography; Vascular System; Work; base; cancer therapy; cancer type; capillary bed; cremaster muscle; density; drug efficacy; in vivo; malignant breast neoplasm; minimally invasive; neoplastic cell; novel; novel strategies; particle; public health relevance; residence; tumor; tumor growth; vaporization

DESCRIPTION (provided by applicant): Embolotherapy involves the occlusion of blood flow for therapy, such as treatment of tumors or fibroids, and has traditionally used solid emboli.1 In our novel approach, gas bubbles, rather than solid particles are used for occlusion. The bubbles originate as < 6 ¿m-diameter albumin- or lipid- encapsulated liquid droplets of perfluorocarbon (PFC), mixed in saline,2, 3 and are injected into the vascular system. The droplets are small enough to pass through capillary beds, so they can circulate until the next stage of the therapy. By strategic placement of an ultrasound source, vaporization of the droplets, which we have termed Acoustic Droplet Vaporization (ADV), can be induced in or near the tumor. The resulting bubble volume is ~125-150 times the droplet volume, and the bubbles resulting from an approximately 5 ¿m droplet are large enough to lodge in the microcirculation and occlude blood flow to the tumor. This gas embolotherapy approach is minimally invasive, would allow selective delivery of gas emboli to the tumor or fibroid, and is well suited to repeated doses and long-term use. The first funding period of this grant was focused on understanding the underlying biofluid mechanics involved in ADV, transport, and lodging of these novel emboli. Now that we understand the bubble and droplet dynamics well enough to allow us to effectively target regions of healthy tissue for occlusion, we are ready to apply this knowledge to study the potential for lodged microbubbles to induce bioeffects that may lead to localized hypoxia and tissue necrosis. Successful treatment of cancer by the proposed methodology is one of our long-term goals, and understanding how lodged microbubbles affect tumors is essential to reaching that goal. Therefore, the specific aims of this renewal application are: 1. Characterize ADV of adherent droplets, and transport and lodging of resulting bubbles, including ability of functionalized droplets to increase residence time of resulting bubbles. 2. Characterize the ability of lodged bubbles to induce hypoxia. 3. Characterize the ability of lodged bubbles to induce hypoxia related changes in tumors. 4. Assess the ability of lodged bubbles to induce tumor cell apoptosis and to slow tumor growth.

描述（由适用提供）：栓塞疗法涉及治疗的血液流动的阻塞，例如治疗肿瘤或肌瘤，并且传统上使用了固体栓子。1在我们的新型方法中，气泡而不是实心颗粒用于闭合。气泡起源于<6€m直径的专辑量或脂质包裹的液滴（PFC），混合在盐水中，2,3，并注入血管系统中。液滴足够小，可以通过毛细管床，因此它们可以循环直至治疗的下一阶段。通过战略性放置超声源，可以在肿瘤中或附近诱导液滴的分散（我们称为声滴蒸发（ADV））。产生的气泡体积约为液滴体积的〜125-150倍，大约5滴小液滴产生的气泡足够大，可以在微循环中放置和偶尔血液流向肿瘤。这种气体栓塞方法的侵入性最低，可以选择性地递送气体栓塞到肿瘤或纤维，并且非常适合重复剂量和长期使用。该赠款的第一个融资时期的重点是了解这些新型栓子的ADV，运输和住宿所涉及的基本生物流体力学。现在，我们足够了解气泡和液滴动力学，使我们能够有效地靶向健康组织的区域以遮挡，我们准备应用这些知识来研究暴露的微泡的潜力，以诱导可能导致局部缺氧和组织坏死的生物效应。通过提议的方法成功治疗癌症是我们的长期目标之一，了解暴露的微泡如何影响肿瘤对于达到该目标至关重要。因此，此更新应用的具体目的是：1。表征粘附的液滴的ADV，以及所得气泡的运输和住宿，包括功能化液滴增加产生气泡的停留时间。 2。表征暴露气泡诱导缺氧的能力。 3。表征暴露气泡诱导肿瘤中缺氧相关变化的能力。 4。评估暴露气泡诱导肿瘤细胞凋亡和减慢肿瘤生长的能力。