Department of Pharmaceutical Technology and Biopharmaceutics, University of Marburg, Marburg, Germany.
Eur J Pharm Biopharm. 2011 Apr;77(3):430-7. doi: 10.1016/j.ejpb.2010.12.007. Epub 2010 Dec 13.
Ultrasound contrast agents are widely used in clinical diagnosis. In recent years, the use of ultrasound contrast agents as therapeutic agents has gained a lot of attention. Of special interest are ultrasound-enhanced gene delivery in various tissues (e.g. cardiac, vascular, skeletal muscle and tumor tissue), ultrasound-enhanced protein delivery (e.g. insulin delivery) and ultrasound-enhanced delivery of small chemicals (e.g. doxorubicin, vancomycin). Commercially available ultrasound contrast agents such as SonoVue® or Optison® are ranged in a size of 2-8 μm. These micronscaled agents show a good ultrasound contrast enhancement and thus they are used for diagnostic imaging. But they are not suitable for targeted drug delivery to tumor tissues or blood clots because for these applications particles smaller than 700 nm are needed. In the present study, we developed new nanoscaled ultrasound contrast agents with a size between 70 and 300 nm. The lipid formulations show excellent contrast intensities using diagnostic ultrasound of about 1.4 MHz. The negatively charged colloidal dispersions are long-time stable under physiological conditions without loss of ultrasound reflectivity. The adjustable supramolecular organization of the carriers depends on the composition and varies from micellar to liposomal structures. The small size and the circulation stability of these systems make them promising for novel diagnostics and controlled drug release applications.
超声造影剂在临床诊断中被广泛应用。近年来，超声造影剂作为治疗剂的应用引起了广泛关注。特别值得关注的是各种组织（如心脏、血管、骨骼肌和肿瘤组织）中的超声增强基因传递、超声增强蛋白传递（如胰岛素传递）以及超声增强小分子传递（如阿霉素、万古霉素）。市售的超声造影剂，如 SonoVue®或 Optison®，粒径为 2-8 μm。这些微米级的造影剂具有良好的超声增强效果，因此被用于诊断成像。但它们不适合用于靶向递送到肿瘤组织或血栓，因为这些应用需要粒径小于 700nm 的颗粒。在本研究中，我们开发了新的纳米级超声造影剂，粒径在 70-300nm 之间。脂质制剂在约 1.4MHz 的诊断超声下表现出优异的对比强度。在生理条件下，带负电荷的胶体分散体具有长期稳定性，而不会损失超声反射率。载体的可调超分子结构取决于组成，从胶束到脂质体结构不等。这些系统的小尺寸和循环稳定性使它们有望用于新型诊断和控制药物释放应用。
