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Development and evaluation of stability and ultrasound response of DSPC-DPSG-based freeze-dried microbubbles
Journal of Liposome Research ( IF 4.4 ) Pub Date : 2019-01-28 , DOI: 10.1080/08982104.2018.1556294 Johan Unga 1 , Daiki Omata 1 , Nobuki Kudo 2 , Soki Ueno 2 , Lisa Munakata 1 , Tadamitsu Shima 1 , Ryo Suzuki 1 , Kazuo Maruyama 1
Journal of Liposome Research ( IF 4.4 ) Pub Date : 2019-01-28 , DOI: 10.1080/08982104.2018.1556294 Johan Unga 1 , Daiki Omata 1 , Nobuki Kudo 2 , Soki Ueno 2 , Lisa Munakata 1 , Tadamitsu Shima 1 , Ryo Suzuki 1 , Kazuo Maruyama 1
Affiliation
Abstract It is known that Phosphatidyl choline-Phosphatidyl glycerol mixtures can be used for liposome formulations, making them less leaky than liposomes with only one lipid. We hypothesized that this might also be the case for bubbles, which can be used as ultrasound (US) contrast agents. Therefore, we have compared a series of mixed distearoyl phosphatidylcholine-distearoyl phosphatidylglycerol (DSPC-DPSG) bubbles and with bubbles containing either DSPC or DSPG (and distearoyl ethanolamine-polyethyleneglycol 2000, DSPE-PEG2k). Here, we describe the development, examination of stability in vitro and attenuation of broad frequency US pulses. Novel lipid-stabilized freeze-dried formulations for US applications, using the phospholipids DSPC, DSPG, and PEGylated DSPE-PEG2k and perfluoropropane gas were developed. It was found that the bubbles could effectively be preserved by freeze-drying and then re-constituted by addition of water. Average bubble sizes were around 2 µm for all bubbles after re-constitution. Bubble stability was assessed by evaluating the decay of the US backscattering signal in vitro. Bubbles containing DSPG were more stable than bubbles with only DSPC. The composition DSPC:DSPG:DSPE-PEG2k 30:60:10 (molar ratio) was the most stable with an effective half-life of 9.12 min, compared to bubbles without DSPG, which had half-life of 2.05 min. Bubble attenuation of US depended highly on the compositions. Bubbles without DSPG had the highest attenuation indicating higher oscillation the most but were also destroyed by higher energy US. No bubbles with DSPG showed any indication of destruction but all had increased attenuations to varying degrees, DSPC:DSPG:DSPE-PEG2k 45:45:10 showed the least attenuation.
中文翻译:
基于DSPC-DPSG的冻干微泡稳定性和超声响应的开发与评价
摘要 众所周知,磷脂酰胆碱-磷脂酰甘油混合物可用于脂质体制剂,使其比仅含一种脂质的脂质体泄漏更少。我们假设气泡也可能是这种情况,气泡可用作超声 (US) 造影剂。因此,我们比较了一系列混合二硬脂酰磷脂酰胆碱-二硬脂酰磷脂酰甘油 (DSPC-DPSG) 气泡和含有 DSPC 或 DSG(以及二硬脂酰乙醇胺-聚乙二醇 2000,DSPE-PEG2k)的气泡。在这里,我们描述了体外稳定性的开发、检查和宽频 US 脉冲的衰减。使用磷脂 DSPC、DSPG 和聚乙二醇化 DSPE-PEG2k 和全氟丙烷气体开发了适用于美国应用的新型脂质稳定冻干制剂。发现通过冷冻干燥可以有效地保留气泡,然后通过加水重新构成气泡。重构后所有气泡的平均气泡尺寸约为 2 µm。通过在体外评估美国反向散射信号的衰减来评估气泡稳定性。含有DSPG 的气泡比只含有DSPG 的气泡更稳定。DSPC:DSPG:DSPE-PEG2k 30:60:10(摩尔比)的组合物最稳定,有效半衰期为 9.12 分钟,相比之下,不含 DSG 的气泡的半衰期为 2.05 分钟。US 的气泡衰减高度依赖于组合物。没有DSPG的气泡衰减最高,表明振荡幅度最大,但也被更高能量的US破坏。
更新日期:2019-01-28
中文翻译:
基于DSPC-DPSG的冻干微泡稳定性和超声响应的开发与评价
摘要 众所周知,磷脂酰胆碱-磷脂酰甘油混合物可用于脂质体制剂,使其比仅含一种脂质的脂质体泄漏更少。我们假设气泡也可能是这种情况,气泡可用作超声 (US) 造影剂。因此,我们比较了一系列混合二硬脂酰磷脂酰胆碱-二硬脂酰磷脂酰甘油 (DSPC-DPSG) 气泡和含有 DSPC 或 DSG(以及二硬脂酰乙醇胺-聚乙二醇 2000,DSPE-PEG2k)的气泡。在这里,我们描述了体外稳定性的开发、检查和宽频 US 脉冲的衰减。使用磷脂 DSPC、DSPG 和聚乙二醇化 DSPE-PEG2k 和全氟丙烷气体开发了适用于美国应用的新型脂质稳定冻干制剂。发现通过冷冻干燥可以有效地保留气泡,然后通过加水重新构成气泡。重构后所有气泡的平均气泡尺寸约为 2 µm。通过在体外评估美国反向散射信号的衰减来评估气泡稳定性。含有DSPG 的气泡比只含有DSPG 的气泡更稳定。DSPC:DSPG:DSPE-PEG2k 30:60:10(摩尔比)的组合物最稳定,有效半衰期为 9.12 分钟,相比之下,不含 DSG 的气泡的半衰期为 2.05 分钟。US 的气泡衰减高度依赖于组合物。没有DSPG的气泡衰减最高,表明振荡幅度最大,但也被更高能量的US破坏。