ULTRASOUND-STIMULATED PHASE-CHANGE CONTRAST AGENTS FOR TRANSEPITHELIAL DELIVERY OF MACROMOLECULES, TOWARD GASTROINTESTINAL DRUG DELIVERY
ULTRASOUND-STIMULATED PHASE-CHANGE CONTRAST AGENTS FOR TRANSEPITHELIAL DELIVERY OF MACROMOLECULES, TOWARD GASTROINTESTINAL DRUG DELIVERY
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DOI：
10.1016/j.ultrasmedbio.2019.02.004
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发表时间：
2019-07-01
影响因子：
2.9
通讯作者：
Papadopoulou, Virginie
中科院分区：
文献类型：
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作者：
Fix, Samantha M.;Koppolu, Bhanu P.;Papadopoulou, Virginie
胃肠道是大分子药物，尤其是生物制剂的难以传递的屏障。在此，我们证明了超声刺激的相变造影剂（PCCAs）可以短暂地破坏结直肠腺癌融合单层，并改善大分子模型药物的经上皮转运。在pcca存在的情况下进行超声治疗，我们实现了70 kda荧光素异硫氰酸酯-葡聚糖经上皮递送率最高为44 +/- 15%，而通过假对照单层的递送率可以忽略不计。在所有测试的分压（300-600 kPa）中，300 kPa时葡聚糖的输送效率最高。为了探索这一意想不到的发现，我们量化了各种超声暴露条件下产生的稳定和惯性空化能。一般来说，在30秒超声暴露期间，较低的压力导致更持久的空化活动，这可能解释了右旋糖酐递送效率的提高。因此，在这种应用中使用低沸点pcca的一个独特优势是，可以使用相同的低压脉冲来诱导汽化并提供最大的输送。(C) 2019世界超声医学与生物学联合会。版权所有。
The gastrointestinal (GI) tract presents a notoriously difficult barrier for macromolecular drug delivery, especially for biologics. Herein, we demonstrate that ultrasound-stimulated phase change contrast agents (PCCAs) can transiently disrupt confluent colorectal adenocarcinoma monolayers and improve the transepithelial transport of a macromolecular model drug. With ultrasound treatment in the presence of PCCAs, we achieved a maximum of 44 +/- 15% transepithelial delivery of 70-kDa fluorescein isothiocyanate-dextran, compared with negligible delivery through sham control monolayers. Among all tested rarefactional pressures (300-600 kPa), dextran delivery efficiency was consistently greatest at 300 kPa. To explore this unexpected finding, we quantified stable and inertial cavitation energy generated by various ultrasound exposure conditions. In general, lower pressures resulted in more persistent cavitation activity during the 30-s ultrasound exposures, which may explain the enhanced dextran delivery efficiency. Thus, a unique advantage of using low boiling point PCCAs for this application is that the same low-pressure pulses can be used to induce vaporization and provide maximal delivery. (C) 2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved.