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

描述(由申请人提供)：传统的方法识别和治疗动脉疾病由于不能定位动脉粥样硬化的范围和成分而受到阻碍。使用靶向回声脂质体(ELIP)的新技术正在探索，作为克服这些问题的可能解决方案。ELIP是包裹水和气态空间的磷脂小泡。治疗药物，如药物或基因，可以加载到Elip中。此外，已经看到，一旦暴露在脉冲超声波下，治疗药物可以从ERIP释放并可用于输送到附近的组织。封装的气体允许使用临床超声扫描仪对ELIP进行成像，并通过空化成核传递治疗性药物。这项建议的主要目的是开发一种技术，这种技术将提供空间分辨的、非侵入性的反馈，用于使用ERIP将治疗药物输送到动脉壁。为了实现这一目标，将调查两个具体目标。1)被动超声阵列记录的声发射与抗炎药物(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地图。2)非电离化ERIP的被动成像将与将治疗药物输送到体外猪动脉相关。这些研究的成功完成将大大有助于辛辛那提大学的荷兰和麦克弗森实验室和德克萨斯健康科学中心休斯顿分校的长期目标，即触发和加强治疗药物的交付，以改善生理性心血管血流。 公共卫生相关性：该提案寻求开发被动空化成像，用于超声介导的局部释放，并使用回声脂质体增强抗炎药物的输送，用于动脉粥样硬化治疗。

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.