Development of inherently echogenic liposomes as an ultrasonic contrast agent
Development of inherently echogenic liposomes as an ultrasonic contrast agent
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DOI：
10.1021/js950407f
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发表时间：
1996-05-01
影响因子：
3.8
通讯作者：
McPherson, DD
中科院分区：
文献类型：
--
作者：
AlkanOnyuksel, H;Demos, SM;McPherson, DD
超声造影剂已经被开发出来，用于改善血流和组织灌注量的评估。其中许多药剂本身并不具有声学反射(回声)功能，而且几乎所有药剂都不适合组织特异性靶向。本研究的目的是在不使用GAS或任何其他包封剂的情况下，研制适合于抗体偶联的声反射脂质体。以磷脂酰胆碱(PC)、磷脂酰乙醇胺(PE)、磷脂酰甘油(PG)和胆固醇(CH)为原料，采用脱水/复水法制备了回声脂质体。通过改变脂质成分，对处方进行了优化，以获得更高的声反射率。用20 MHz血管内超声成像导管对脂质体进行成像。回声水平用像素灰度级表示。冷冻蚀刻电子显微镜证实，特定浓度的PE和PG的存在改善了回声，这是因为它们对脂质体的形态产生了影响。脂质体经血液处理后，在室温和37℃的体外条件下仍能保持良好的声反射率。研究表明，脂质体注射到迷你葡萄酒模型后，在体内也能产生声反射。我们已经开发出稳定的、适合于组织特异性靶向的回声脂质体作为一种新型的造影剂。这种新型造影剂可用于超声图像增强和/或靶向病变部位的治疗。
Ultrasonic contrast agents have been developed for improved assessment of blood flow and tissue perfusion. Many of these agents are not inherently acoustically reflective (echogenic), and nearly all are not suitable for tissue specific targeting. The purpose of this study was to develop acoustically reflective liposomes, which are suitable for antibody conjugation, without using gas or any other agent entrapment. Echogenic liposomes were prepared from phosphatidylcholine (PC), phophatidylethanolamine (PE), phosphatidylglycerol (PG), and cholesterol (CH), using a dehydration/rehydration method. The formulation was optimized for higher acoustic reflectivity by varying the lipid composition. Liposomes were imaged with a 20 MHz intravascular ultrasonic imaging catheter. Echogenicity levels were expressed using pixel gray scale. The presence of PE and PG at specific concentrations improved echogenicity due to their effects on liposomal morphology as confirmed by freeze-etch electron microscopy. The acoustic reflectivity of liposomes was retained when liposomes were treated with blood at room temperature and 37 degrees C under in vitro conditions. It was demonstrated that the liposomes were also acoustically reflective in vivo after they were injected into a miniswine model. We have developed echogenic liposomes that are stable and suitable for tissue specific targeting as a novel contrast agent. This new contrast agent can be used for ultrasonic image enhancement and/or treatment of targeted pathologic sites.