Molecular Delivery System Laboratory Graduate School of Biomedical Engineering, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-0872, Japan.
Pharm Res. 2013 Jan;30(1):218-24. doi: 10.1007/s11095-012-0864-8. Epub 2012 Sep 1.
Liposomes encapsulating perfluoropropane gas, termed acoustic liposomes (ALs), which can serve both for ultrasound (US) imaging and US-mediated gene delivery, have been reported. However, the echogenicity of ALs decreases within minutes in vivo due to gas diffusion and leakage, hindering time-consuming procedures such as contrast-enhanced 3D US imaging and raising the need for improvement of their stability.
The stability of ALs preparations incorporating increasing ratios of anionic / unsaturated phospholipids, polyethylene glycol (PEG)ylated phospholipid and cholesterol was investigated by measurement of their reflectivity over time using a high-frequency US imaging system, both in vitro and in vivo.
The retention of echogenicity of ALs in vitro is enhanced with increasing molar ratios of PEGylated lipids. Addition of 10 molar percent of an anionic phospholipid resulted in a 31% longer half-life, while cholesterol had the opposite effect. Assessment of the stability of an optimized composition showed a more than 2-fold increase of the detection half-life in mice.
Presence of a PEG coating not only serves to provide "stealth" properties in vivo, but also contributes to the retention of the encapsulated gas. The optimized ALs reported here can be used as a contrast agent for lengthier imaging procedures.
包裹全氟丙烷气体的脂质体，称为声振脂质体（ALs），可同时用于超声（US）成像和 US 介导的基因传递，已有相关报道。然而，由于气体扩散和泄漏，ALs 的体内声振性在数分钟内降低，这阻碍了耗时的对比增强 3D US 成像等程序，并需要提高其稳定性。
通过使用高频 US 成像系统，在体外和体内测量 ALs 制剂中阴离子/不饱和磷脂、聚乙二醇（PEG）化磷脂和胆固醇的比例增加时的反射率，研究其稳定性。
PEG 化脂质摩尔比增加可增强 ALs 的体外声振性保持。添加 10 摩尔%的阴离子磷脂可使半衰期延长 31%，而胆固醇则产生相反的效果。对优化组成的稳定性评估表明，在小鼠中的检测半衰期增加了两倍以上。
PEG 涂层的存在不仅有助于在体内提供“隐形”特性，还有助于保留包裹的气体。这里报道的优化 ALs 可用作更长时间成像程序的造影剂。
