A method for radiation-force localized drug delivery using gas-filled lipospheres
A method for radiation-force localized drug delivery using gas-filled lipospheres
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DOI：
10.1109/tuffc.2004.1320741
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发表时间：
2004-07-01
影响因子：
3.6
通讯作者：
Ferrara, KW
中科院分区：
文献类型：
--
作者：
Shortencarier, MJ;Dayton, PA;Ferrara, KW
我们已经开发了一种使用超声和声活性脂球（AALs）的方法，可用于将生物活性物质输送到血管内皮。AALs由一个被厚油壳包围的小气泡和最外层的脂质层组成。AALs类似于超声造影剂：它们可以使用超声辐射力进行无损偏转，并可以使用高强度超声脉冲进行碎片化。脂油复合物可用于携带高浓度的生物活性物质。优化的超声脉冲序列可以偏转；AALs向血管壁移动，然后破坏它们，使其内容物穿过血管内皮。本文介绍了一系列体外和离体实验的结果，证明了一种荧光模型药物的定位。在使用人类黑色素瘤细胞（A2085）单层的实验中，特定的辐射力-碎片离子超声脉冲序列使细胞荧光比单独没有超声波或碎片脉冲增加10倍以上，比单独辐射力脉冲增加50%。我们观察到染料转移仅限于超声聚焦区域的细胞，这表明应用辐射力脉冲使运载工具靠近细胞是运载工具碎片成功粘附到细胞膜上所必需的。我们还演示了在模拟血管和切除的大鼠盲肠中，流动AALs的染料转移。我们相信这种方法可以成功地用于体内给药。
We have developed a method using ultrasound and acoustically active lipospheres (AALs) that might be used to deliver bioactive substances to the vascular endothelium. The AALs consist of a small gas bubble surrounded by a thick oil shell and enclosed by an outermost lipid layer. The AALs are similar to ultrasound contrast agents: they can be nondestructively deflected using ultrasound radiation force, and fragmented with high-intensity ultrasound pulses. The lipid-oil complex might be used to carry bioactive substances at high concentrations. An optimized sequence of ultrasound pulses can deflect; the AALs toward a vessel wall then disrupt them, painting their contents across the vascular endothelium. This paper presents results from a series of in vitro and ex vivo experiments demonstrating localization of a fluorescent model drug. In experiments using a human melanoma cell (A2085) monolayer, a specific radiation force-fragment at ion ultrasound pulse sequence increased cell fluorescence more than 10-fold over no ultra-sound or fragmentation pulses alone, and by 50% over radiation force pulses alone. We observe that dye transfer is limited to cells that are in the region of ultrasonic focus, indicating that the application of radiation force pulses to bring the delivery vehicle into proximity with the cell is required for successful adhesion of the vehicle fragments to the cell membrane. We also demonstrate dye transfer from flowing AALs, both in a mimetic vessel and in excised rat cecum. We believe that this method could be successfully used for drug delivery in vivo.