Medicines Research Unit, Aston Pharmacy School, Aston University, Birmingham, 894 60Y, UK.
J Biomed Nanotechnol. 2009 Dec;5(6):707-15. doi: 10.1166/jbn.2009.1087.
The aim of this study was to prepare gas-filled lipid-coated microbubbles as potential MRI contrast agents for imaging of fluid pressure. Air-filled microbubbles were produced with phospholipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) in the presence or absence of cholesterol and/or polyethylene-glycol distearate (PEG-distearate). Microbubbles were also prepared containing a fluorinated phospholipid, perfluoroalkylated glycerol-phosphatidylcholine, F-GPC shells encompassing perfluorohexane-saturated nitrogen gas. These microbubbles were evaluated in terms of physico-chemical characteristics such as size and stability. In parallel to these studies, DSPC microbubbles were also formulated containing nitrogen (N2) gas and compared to air-filled microbubbles. By preventing advection, signal drifts were used to assess their stability. DSPC microbubbles were found to have a drift of 20% signal change per bar of applied pressure in contrast to the F-GPC microbubbles which are considerably more stable with a lower drift of 5% signal change per bar of applied pressure. By increasing the pressure of the system and monitoring the MR signal intensity, the point at which the majority of the microbubbles have been damaged was determined. For the DSPC microbubbles this occurs at 1.3 bar whilst the F-GPC microbubbles withstand pressures up to 2.6 bar. For the comparison between air-filled and N2-filled microbubbles, the MRI sensitivity is assessed by cycling the pressure of the system and monitoring the MR signal intensity. It was found that the sensitivity exhibited by the N2-filled microbubbles remained constant, whilst the air-filled microbubbles demonstrated a continuous drop in sensitivity due to continuous bubble damage.
本研究旨在制备充入气体的脂质包覆微泡作为潜在的 MRI 对比剂，用于流体压力成像。在存在或不存在胆固醇和/或聚乙二醇二硬脂酸酯（PEG-硬脂酸酯）的情况下，用磷脂 1,2-二硬脂酰-sn-甘油-3-磷酸胆碱（DSPC）生产充气微泡。还制备了含有氟化磷脂、全氟烷基化甘油磷脂、全氟己烷饱和氮气包围的 F-GPC 壳的微泡。这些微泡在大小和稳定性等物理化学特性方面进行了评估。在进行这些研究的同时，还配制了含有氮气（N2）的 DSPC 微泡，并与充气微泡进行了比较。通过防止平流，信号漂移用于评估其稳定性。与 F-GPC 微泡相比，DSPC 微泡的信号漂移率为每施加 1 巴压力变化 20%，而 F-GPC 微泡的稳定性更高，每施加 1 巴压力变化 5%。通过增加系统压力并监测 MR 信号强度，确定了大多数微泡受损的点。对于 DSPC 微泡，这发生在 1.3 巴，而 F-GPC 微泡可承受高达 2.6 巴的压力。对于充气和 N2 填充微泡之间的比较，通过循环系统压力并监测 MR 信号强度来评估 MRI 灵敏度。结果发现，N2 填充微泡的灵敏度保持不变，而充气微泡由于连续的气泡损坏，灵敏度持续下降。
