Improving ultrasound reflectivity and stability of echogenic liposomal dispersions for use as targeted ultrasound contrast agents
Improving ultrasound reflectivity and stability of echogenic liposomal dispersions for use as targeted ultrasound contrast agents
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DOI：
10.1002/jps.1142.abs
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发表时间：
2001-12-01
影响因子：
3.8
通讯作者：
MacDonald, RC
中科院分区：
文献类型：
--
作者：
Huang, SL;Hamilton, AJ;MacDonald, RC
最近开发了靶向回声脂质体分散体，用于超声增强内皮和动脉粥样硬化的血管活性和病理成分。声学和靶向性质所需的组分脂质包括磷脂酰胆碱、磷脂酰乙醇胺磷脂酰甘油（PG）和胆固醇（CH），最初以60：8：2：30摩尔%的比例。改变组分脂质、冻干、糖和冷冻条件以优化声学超声反射率和声学稳定性。采用脱水-再水化法制备脂质体分散体.改变脂质浓度（CH在1至40摩尔%的范围内，PG在1至16摩尔%的范围内）。糖的类型和浓度的变化进行了检查。检查冷冻条件和再冻干的影响。使用20 MHz血管内超声导管和计算机辅助视频密度测定法评估超声反射率。超声反射率在CH浓度为10摩尔%时进行了优化; PG浓度变化对回声反射性的初始值基本上没有影响。在CH浓度为10 - 15摩尔%和PG浓度大于4摩尔%的情况下观察到最佳的声学稳定性。用0.2 M甘露醇制成的制剂比用乳糖、海藻糖和蔗糖制成的制剂更能反射超声。低于-20 ℃的再冻干和冷冻温度增加了超声反射率。我们优化了回声脂质体分散体的超声特性，其条件提供了一些深入了解相关的脂质结构。现在开发的制剂比我们以前的制剂更稳定，声反射性更好。这推进了回声脂质分散体作为靶向超声造影剂用于普通超声以及心血管成像的发展。(C)2001 Wiley-Liss，Inc.和美国制药协会。
Targeted echogenic liposome dispersions for ultrasonic enhancement of vasoactive and pathological components of endothelium and atherosclerosis have recently been developed. The component lipids required for acoustic and targeting properties include phosphatidylcholine, phosphatidylethanolamine phosphatidylglycerol (PG), and cholesterol (CH), initially in a 60:8:2:30 mol % ratio. Component lipids, lyophilization, sugars, and freezing conditions were varied to optimize acoustic ultrasound reflectivity and acoustic stability. Echogenic liposome dispersions were made by using the dehydration - rehydration process. The lipid concentrations were varied (CH in the range 1 to 40 mol % and PG from 1 to 16 mol %). Variations in type and concentration of sugars were examined. The effect of freezing conditions and re-lyophilization was examined. Ultrasound reflectivity was assessed by using a 20-MHz intravascular ultrasound catheter and computer-assisted videodensitometry. Ultrasound reflectivity was optimized at a CH concentration of 10 mol %; PG concentration variation had essentially no effect on initial values of echogenicity. Optimal acoustic stability was observed with concentrations of 10-15 mol % CH and with a PG concentration greater than 4 mol %. Preparations made with 0.2 M mannitol were more ultrasound reflective than those made with lactose, trehalose, and sucrose. Re-lyophilization and freezing temperatures below -20 degreesC increased ultrasound reflectivity. We optimized the ultrasound properties of echogenic liposomal dispersions, the conditions of which provide some insight into the underlying lipid structures responsible. The preparations developed are now more stable and acoustically reflective than our previous preparations. This advances the development of echogenic lipid dispersions as targeted ultrasound contrast agents for use in general ultrasound as well as cardiovascular imaging. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.