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首页> 外文会议>IEEE International Ultrasonics Symposium >Targeted drug delivery with focus ultrasound-induced blood-brain barrier opening Using acoustically-activated nanodroplets
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Targeted drug delivery with focus ultrasound-induced blood-brain barrier opening Using acoustically-activated nanodroplets

机译：Targeted drug delivery with focus ultrasound-induced blood-brain barrier opening Using acoustically-activated nanodroplets

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Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, indicating that contrast agent-dependent acoustic emission monitoring should be carried out. More homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FU-Sinduced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature.
机译：聚焦超声（FUS）在全身给药的微泡存在下已被证明可局部、瞬时和可逆地增加血脑屏障（BBB）的通透性，从而允许在脑内靶向输送治疗剂以治疗中枢神经系统疾病。目前，微泡是唯一用于促进FUS诱导的BBB开放的药物。然而，由于其微米大小的直径，它们被限制在血管内空间内，从而限制了微血管处或附近的输送效果。在本研究中，声激活的纳米液滴被用作一种新型造影剂来调节FUS诱导的BBB开放，以研究利用这些纳米级相移颗粒在脑内靶向给药的可行性。在临床相关压力下，使用纳米液滴在小鼠海马中实现了显著的右旋糖酐递送。与纳米液滴具有相同脂质壳组成和全氟丁烷核的传统微泡也用于比较FUS诱导的右旋糖酐递送的效率。结果发现，与微气泡相比，纳米液滴的BBB开启压力阈值较高，但稳定空化阈值较低，这表明应进行依赖造影剂的声发射监测。使用纳米液滴在靶向海马内实现更均匀的右旋糖酐递送，而不会引起惯性空化或损害安全性。我们的研究结果为开发FU诱导的BBB开放技术提供了一种新的方法，用于脑内潜在的血管外靶向药物递送，将潜在的药物递送区域扩展到脑血管之外。

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