Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound.
Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound.
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DOI：
10.1021/la2013705
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发表时间：
2011-09-06
期刊：
影响因子：
--
通讯作者：
Matsunaga TO
中科院分区：
文献类型：
--
作者：
Sheeran PS;Luois S;Dayton PA;Matsunaga TO
最近在以设计血管外超声造影剂为目的的声学液滴汽化领域的努力已经导致了高挥发性化合物十氯丁烷（DFB）的稳定的脂质封装的纳米液滴的开发。我们开发了两种产生DFB液滴的方法，第一种方法涉及冷凝DFB气体（沸点为−1.1°至−2° C），然后用HEPES缓冲液中的脂质制剂挤出。声学液滴蒸发微米级的脂质涂层液滴在诊断超声频率和机械指数光学确认。在我们的第二种配制方法中，我们证明了基于含有DFB的预形成微泡的冷凝的亚微米尺寸的脂质包覆的纳米液滴的配制。液滴通常在200 - 300 nm范围内，并且一旦蒸发就产生1 - 5微米量级的微泡，这与理想气体定律膨胀预测一致。这种方法的简单和有效的性质允许开发可用于成像、药物和基因递送以及治疗的各种不同制剂。据我们所知，这项研究是第一个证明通过微泡冷凝产生ADV试剂的方法和在生理温度下保持稳定的主要亚微米十氯丁烷液滴的制剂。最后，DFB纳米液滴的激活是使用FDA诊断成像指南内的压力来证明的，这可能会最大限度地减少对人类的生物效应。这种方法提供了一种新的手段，开发血管外造影剂的诊断和治疗应用。
Recent efforts in the area of acoustic droplet vaporization with the objective of designing extravascular ultrasound contrast agents has led to the development of stabilized, lipid-encapsulated nanodroplets of the highly volatile compound decafluorobutane (DFB). We have developed two methods of generating DFB droplets, the first of which involves condensing DFB gas (boiling point of −1.1° to −2° C) followed by extrusion with a lipid formulation in HEPES buffer. Acoustic droplet vaporization of micron-sized lipid-coated droplets at diagnostic ultrasound frequencies and mechanical indices were confirmed optically. In our second formulation methodology, we demonstrate the formulation of sub-micron sized lipid-coated nanodroplets based upon condensation of pre-formed microbubbles containing DFB. The droplets are routinely in the 200 – 300 nm range and yield microbubbles on the order of 1 – 5 microns once vaporized, consistent with ideal gas law expansion predictions. The simple and effective nature of this methodology allows for the development of a variety of different formulations that can be used for imaging, drug and gene delivery, and therapy. This study is the first to our knowledge to demonstrate both a method of generating ADV agents by microbubble condensation and formulation of primarily sub-micron droplets of decafluorobutane that remain stable at physiological temperatures. Finally, activation of DFB nanodroplets is demonstrated using pressures within the FDA guidelines for diagnostic imaging, which may minimize the potential for bioeffects in humans. This methodology offers a new means of developing extravascular contrast agents for diagnostic and therapeutic applications.
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DOI：
10.1002/0471475734.ch12
发表时间：
2005-01-01
期刊：
DRUG DELIVERY: PRINCIPLES AND APPLICATIONS
影响因子：
--
作者：
Ng, Ka-yun;Matsunaga, Terry O.
通讯作者：
Matsunaga, Terry O.
影响因子：
--
作者：
Mullin, Lee;Gessner, Ryan;Kwan, James;Kaya, Mehmet;Borden, Mark A.;Dayton, Paul A.
通讯作者：
Dayton, Paul A.
DOI：
10.1109/tuffc.2005.1503996
发表时间：
2005-07-01
影响因子：
3.6
作者：
Kripfgans, OD;Orifici, CM;Fowlkes, JB
通讯作者：
Fowlkes, JB
DOI：
10.1109/tuffc.2002.1009331
发表时间：
2002-06-01
影响因子：
3.6
作者：
Kripfgans, OD;Fowlkes, JB;Carson, PL
通讯作者：
Carson, PL
影响因子：
2.9
作者：
Landmark, Kristin Eitrem;Johansen, Per Wiik;Skotland, Tore
通讯作者：
Skotland, Tore