Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Neurotherapeutics. 2019 Jul;16(3):878-890. doi: 10.1007/s13311-019-00733-4.
Xenon (Xe) is a bioactive gas capable of reducing and stabilizing neurologic injury in stroke. The goal of this work was to develop lipid-shelled microbubbles for xenon loading and ultrasound-triggered release. Microbubbles loaded with either xenon (Xe-MB) or xenon and octafluoropropane (Xe-OFP-MB) (9:1 v/v) were synthesized by high-shear mixing. The size distribution and the frequency-dependent attenuation coefficient of Xe-MB and Xe-OFP-MB were measured using a Coulter counter and a broadband acoustic attenuation spectroscopy system, respectively. The Xe dose was evaluated using gas chromatography/mass spectrometry. The total Xe doses in Xe-MB and Xe-OFP-MB were 113.1 ± 13.5 and 145.6 ± 25.5 μl per mg of lipid, respectively. Co-encapsulation of OFP increased the total xenon dose, attenuation coefficient, microbubble stability (in an undersaturated solution), and shelf life of the agent. Triggered release of gas payload was demonstrated with 6-MHz duplex Doppler and 220-kHz pulsed ultrasound. These results constitute the first step toward the use of lipid-shelled microbubbles for applications such as neuroprotection in stroke.
氙气(Xe)是一种具有生物活性的气体,能够减轻和稳定中风引起的神经损伤。本研究旨在开发用于氙气负载和超声触发释放的脂质壳微泡。通过高剪切混合合成了负载氙气(Xe-MB)或氙气和八氟丙烷(Xe-OFP-MB)(9:1v/v)的微泡。使用库尔特计数器和宽带声学衰减光谱系统分别测量了 Xe-MB 和 Xe-OFP-MB 的粒径分布和频率相关衰减系数。使用气相色谱/质谱法评估 Xe 剂量。Xe-MB 和 Xe-OFP-MB 中的总 Xe 剂量分别为 113.1±13.5 和 145.6±25.5μl/每毫克脂质。OFP 的共包封增加了总氙剂量、衰减系数、微泡稳定性(在不饱和溶液中)和试剂的保质期。使用 6MHz 双工多普勒和 220kHz 脉冲超声证明了气体有效载荷的触发释放。这些结果是朝着将脂质壳微泡用于中风神经保护等应用的方向迈出的第一步。