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

• 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
• 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

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）：无法定位动脉瘤程度和组成的传统手段和治疗动脉疾病受到阻碍。使用靶向回声脂质体（ELIP）的新技术正在被探索以克服这些问题的可能解决方案。 ELIP是封闭水分和气态空间的磷脂囊泡。可以将治疗剂（例如药物或基因）加载到ELIP中。此外，已经可以看到，暴露于脉冲超声波后，可以从ELIP中释放出治疗性，并可以送到附近的组织。封装的气体可通过临床超声扫描仪对ELIP进行成像，并通过气态成核进行治疗。该提案的主要目的是开发技术，这些技术将提供空间解决的无创反馈，用于使用ELIP超声介导的治疗效果到动脉壁。为了实现这一目标，将研究两个具体目标。 1）被动超声阵列记录的无罪误ELIP的声学发射将与释放抗炎（Rosiglitazone-cyclodextrin）相关。随后，将创建排放的空间图和相关的治疗释放。 2）被无罪的ELIP的被动成像将与将治疗性递送到离体猪动脉相关。这些研究的成功完成将极大地促进辛辛那提大学和德克萨斯州健康科学中心 - 霍斯顿大学的荷兰和麦克弗森实验室的长期目标，以触发和增强治疗性，以改善生理性心血管流动。 公共卫生相关性：该提案旨在开发用于超声介导的局部释放的被动气态图像，并增强了使用回声脂质体进行动脉粥样硬化治疗的抗炎药的递送。