CAREER: Ultrasound-induced drug delivery through the blood-brain barrier

职业：超声波诱导药物穿过血脑屏障

• 批准号: 0644713
• 负责人: Elisa Konofagou
• 金额: $ 40万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0644713&HistoricalAwards=false
• 关键词: CAREER; Ultrasound; induced; drug; delivery

CBET-0644713 Konofagou The project will determine the range of intensities, frequencies and other parameters of focused ultrasound (FUS) that can be used to temporarily (i.e. reversibly) open the blood brain barrier (BBB) without concomitant thermal or mechanical damage to neurons and endothelial and other tissues. The preliminary work of the PI has demonstrated that via focused ultrasound (FUS) one can open the BBB in a controlled manner. The project will explore the possibilities under which the BBB can open reversibly, noninvasively, and with regional selectivity using FUS. The specific aims are: 1) understand transcranial ultrasound propagation and induced biological effects through an in-depth theoretical analysis; 2) Investigate the mechanisms under which FUS induces reversible BBB opening in hippocampal cells in vitro; and 3) Characterize the FUS method for optimized drug delivery in wildtype and Alzheimer's-disease affected mice. The project addresses very challenging topic-reversibly opening BBB and combines mathematical models to predict the localization of FUS and in vitro and in vivo experiments. The project utilizes ultrasound energy to temporarily open the blood brain barrier without damaging any tissue. Such modality would have a broad impact for treatments of central nervous system (CNS) diseases. The educational aims include introduction of a new course based on therapeutic use of ultrasound and ultrasound/tissue interaction and use of industrial internship at a graduate level.

CBET-0644713 KONOFAGOU该项目将确定可用于临时（即可逆地）打开血液脑屏障（BBB）的强度，频率和其他参数的范围，而无需对神经元和机械性损害神经元和内皮层和其他组织。 PI的初步工作表明，通过聚焦超声（FUS）可以以受控方式打开BBB。 该项目将探讨BBB可以使用FUS可逆，无创和区域选择性开放的可能性。具体目的是：1）通过深入的理论分析了解经颅超声传播和诱导的生物学效应； 2）研究FUS在体外诱导海马细胞中可逆的BBB开口的机制； 3）表征了在野生型和阿尔茨海默氏症中优化药物递送的FUS方法，影响了小鼠。该项目解决了非常具有挑战性的主题 - 可逆地打开BBB，并结合了数学模型，以预测FUS，体外和体内实验的定位。该项目利用超声能量暂时打开血脑屏障而不会损害任何组织。这种方式将对中枢神经系统（CNS）疾病的治疗产生广泛的影响。教育目的包​​括引入基于超声和超声/组织互动的治疗用途以及研究生级别的工业实习的新课程。