Passive Cavitation Image-Guided Ultrasound-Mediated Drug Delivery for Atheroma Th

被动空化图像引导超声介导的动脉粥样硬化药物输送

基本信息

批准号：
8155319
负责人：
Kevin Joseph Haworth
金额：
$ 5.35万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8155319
关键词：
Accounting Acoustics Air Anti-Inflammatory Agents Anti-inflammatory Arterial Fatty Streak Arteries Atherosclerosis Blood Vessels Cardiovascular Diseases Cardiovascular system Carotid Arteries Cause of Death Cessation of life Clinical Contrast Media Cyclodextrins Development Direct Costs Disease Dose Drug Delivery Systems Drug Formulations Elements Encapsulated Exposure to Facilities and Administrative Costs Family suidae Feedback Frequencies Funding Gases Genes Goals Health Sciences Image In Vitro Laboratories Lipid Bilayers Liposomes Liquid substance Maps Measurement Measures Mechanical Stress Mediating Methods Metric Microbubbles Modeling Monitor National Heart, Lung, and Blood Institute Nature Performance Pharmaceutical Preparations Phospholipids Physiologic pulse Physiological Protocols documentation Research Scheme Signal Transduction Site Solutions Spatial Distribution Staging Techniques Testing Texas Theoretical model Therapeutic Therapeutic Agents Tissues Translations Ultrasonic Transducer Ultrasonography United States United States National Institutes of Health Universities Use of New Techniques Vascular Diseases Vesicle Work aqueous base detector improved innovation mortality prevent public health relevance rosiglitazone targeted delivery

项目摘要

DESCRIPTION (provided by applicant): Traditional means to identify and treat arterial disease are hampered by an inability to localize atheroma extent and composition. New techniques using targeted echogenic liposomes (ELIP) are being explored as possible solutions to overcome these problems. ELIP are phospholipid vesicles enclosing both aqueous and gaseous spaces. Therapeutics, such as drugs or genes, can be loaded into the ELIP. Furthermore, it has been seen that upon exposure to pulsed ultrasound, the therapeutic can be released from the ELIP and made available for delivery to nearby tissue. The encapsulated gas allows the ELIP to be imaged with a clinical ultrasound scanner and the therapeutic to be delivered via cavitation nucleation. The principal aim of this proposal is to develop techniques that will provide spatially resolved, noninvasive feedback for ultrasound-mediated delivery of a therapeutic to an arterial wall using ELIP. To achieve this aim, two specific aims will be investigated. 1) The acoustic emissions of insonified ELIP, as recorded by a passive ultrasound array, will be correlated with release of an anti-inflammatory (rosiglitazone-cyclodextrin). Subsequently, a spatial map of the emissions, and correlated therapeutic release, will be created. 2) Passive imaging of the insonified ELIP will be correlated with the delivery of the therapeutic to an ex vivo porcine artery. Successful completion of these studies will contribute significantly to the long-term goals of the Holland and McPherson Labs at the Universities of Cincinnati and Texas Health Sciences Center-Houston to trigger and enhance the delivery of a therapeutic for improved physiologic cardiovascular flow. PUBLIC HEALTH RELEVANCE: The proposal seeks to develop passive cavitation images for ultrasound-mediated local release and enhanced delivery of an anti-inflammatory drug for atheroma treatment using echogenic liposomes.

描述（由申请人提供）：识别和治疗动脉疾病的传统方法因无法定位动脉粥样硬化的范围和成分而受到阻碍。正在探索使用靶向回声脂质体（ELIP）的新技术作为克服这些问题的可能解决方案。 ELIP 是包围水和气体空间的磷脂囊泡。药物或基因等治疗药物可以加载到 ELIP 中。此外，已经发现，在暴露于脉冲超声时，治疗剂可以从 ELIP 中释放出来，并可输送到附近的组织。封装的气体使得 ELIP 能够通过临床超声扫描仪进行成像，并通过空化成核来输送治疗剂。该提案的主要目的是开发一种技术，为使用 ELIP 以超声介导的方式向动脉壁输送治疗剂提供空间分辨、无创反馈。为了实现这一目标，将研究两个具体目标。 1) 由被动超声阵列记录的声发射 ELIP 的声发射将与抗炎药（罗格列酮-环糊精）的释放相关。随后，将创建排放和相关治疗释放的空间图。 2) 声穿透 ELIP 的被动成像将与治疗剂向离体猪动脉的递送相关。这些研究的成功完成将为辛辛那提大学和德克萨斯健康科学中心休斯顿的荷兰和麦克弗森实验室的长期目标做出重大贡献，即触发和加强治疗以改善生理心血管流量。公共健康相关性：该提案旨在开发被动空化图像，用于超声介导的局部释放和增强抗炎药物的输送，以使用回声脂质体治疗动脉粥样硬化。