Brüssler Jana, Marxer Elena, Becker Andreas, Schubert Rolf, Schümmelfeder Joachim, Nimsky Christopher, Bakowsky Udo
University of Marburg, Department of Pharmaceutical Technology and Biopharmaceutics, Ketzerbach 63, 35037 Marburg, Germany.
University of Marburg, Department of Pharmaceutical Technology and Biopharmaceutics, Ketzerbach 63, 35037 Marburg, Germany.
Colloids Surf B Biointerfaces. 2014 May 1;117:206-15. doi: 10.1016/j.colsurfb.2014.02.029. Epub 2014 Feb 28.
Ultrasound is a common tool for clinical diagnosis due to its safety and economic. Especially the addition of ultrasound contrast agents leads to a high diagnostic reliability. In recent years ultrasound has been used as a trigger for directed drug delivery or to enhance thrombolysis. We developed a nanoscaled ultrasound contrast agent (NUSCA) to improve these applications. In the future drugs can be incorporated into this contrast agent to achieve a combination of ultrasound diagnosis and therapy. The aim of the present study is to elucidate the structure of the nanoscaled lipid formulations and a potential dependence of the ultrasound contrast enhancement on this structure. Our NUSCA is based on the phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and the single-chained polyethylene glycol (40) stearate (PEG40S). In this study the effect of increasing concentrations of the single chained PEG40S on the structure of the lipid formulations was characterised using Dynamic Light Scattering, cryo-Transmission Electron Microscopy, Nuclear Magnetic Resonance spectroscopy, lipid monolayer studies and epifluorescence measurements. In addition, the ultrasound contrast enhancement for the formulations was determined in vitro. Dependence between structure and ultrasound contrast was found. All PEG40S concentrations lead to a mixture of liposomes and discoid micelles. With increasing PEG40S content the amount of micelles increased. Certain PEG40S concentrations lead to an ultrasound contrast superior to the contrast of the commercially available ultrasound contrast agent SonoVue(®).
由于超声具有安全性和经济性，它是临床诊断的常用工具。特别是添加超声造影剂后，诊断可靠性更高。近年来，超声已被用作定向药物递送的触发因素或增强溶栓作用。我们开发了一种纳米级超声造影剂（NUSCA）以改善这些应用。未来，药物可以掺入这种造影剂中，以实现超声诊断和治疗的结合。本研究的目的是阐明纳米级脂质制剂的结构以及超声造影增强对此结构的潜在依赖性。我们的NUSCA基于磷脂1,2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC）、1,2-二硬脂酰-sn-甘油-3-磷酸胆碱（DSPC）和单链聚乙二醇（40）硬脂酸酯（PEG40S）。在本研究中，使用动态光散射、低温透射电子显微镜、核磁共振光谱、脂质单层研究和落射荧光测量来表征单链PEG40S浓度增加对脂质制剂结构的影响。此外，在体外测定了制剂的超声造影增强。发现结构与超声造影之间存在依赖性。所有PEG40S浓度都会导致脂质体和盘状胶束的混合物。随着PEG40S含量的增加，胶束的数量增加。某些PEG40S浓度导致的超声造影效果优于市售超声造影剂声诺维（®）。
