May Donovan J, Allen John S, Ferrara Katherine W
University of California, Davis, Biomedical Engineering Department, 95616, USA.
IEEE Trans Ultrason Ferroelectr Freq Control. 2002 Oct;49(10):1400-10. doi: 10.1109/tuffc.2002.1041081.
Localized delivery could decrease the systemic side effects of toxic chemotherapy drugs. The unique delivery agents we examine consist of microbubbles with an outer lipid coating, an oil layer, and a perfluorobutane gas core. These structures are 0.5-12 microm in radius at rest. Oil layers of these acoustically active lipospheres (AALs) range from 0.3-1.5 microm in thickness and thus the agents can carry a large payload compared to nano-scale drug delivery systems. We show that triacetin-based drug-delivery vehicles can be fragmented using ultrasound. Compared with a lipid-shelled contrast agent, the expansion of the drug-delivery vehicle within the first cycle is similar, and a subharmonic component is demonstrated at an equivalent radius, frequency, and driving pressure. For the experimental conditions explored here, the pulse length required for destruction of the drug-delivery vehicle is significantly greater, with at least five cycles required, compared with one cycle for the contrast agent. For the drug-delivery vehicle, the observed destruction mechanism varies with the initial radius, with microbubbles smaller than resonance size undergoing a symmetric collapse and producing a set of small, equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents larger than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.
局部给药可以降低毒性化疗药物的全身副作用。我们研究的独特给药载体由具有外层脂质包膜、油层和全氟丁烷气体核心的微泡组成。这些结构在静止时半径为0.5 - 12微米。这些声学活性脂质球（AALs）的油层厚度在0.3 - 1.5微米之间，因此与纳米级药物递送系统相比，这些载体可以携带大量的有效载荷。我们表明，基于三醋精的药物递送载体可以通过超声破碎。与脂质壳造影剂相比，药物递送载体在第一个周期内的膨胀相似，并且在相同的半径、频率和驱动压力下显示出一个次谐波成分。对于此处探索的实验条件，与造影剂只需一个周期相比，破坏药物递送载体所需的脉冲长度明显更长，至少需要五个周期。对于药物递送载体，观察到的破坏机制随初始半径而变化，小于共振尺寸的微泡经历对称坍塌并产生一组大小相等的小碎片。在共振尺寸和两倍共振尺寸之间，表面波变得可见，并且振荡变得不对称。对于大于两倍共振半径的载体，破坏机制变为夹断，其中一个碎片包含大部分原始体积。
