Tissue-Clearing Techniques Enable Three-Dimensional Visualization of Aerosolized Model Compound and Lung Structure at the Alveolar Scale
Tissue-Clearing Techniques Enable Three-Dimensional Visualization of Aerosolized Model Compound and Lung Structure at the Alveolar Scale
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DOI：
10.1248/bpb.b17-00348
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发表时间：
2018-01-01
影响因子：
2
通讯作者：
Chono, Sumio
中科院分区：
文献类型：
--
作者：
Togami, Kohei;Kitayama, Anri;Chono, Sumio
在这项研究中，我们研究了组织清除技术在评估雾化药物的肺部分布方面的有用性。使用 MicroSprayer 将 TexasRed 右旋糖酐 (70kDa)（气雾化药物的药物载体模型化合物）的气雾剂制剂通过 MicroSprayer 向小鼠肺内给药，然后静脉内给予 DyLight 488 缀合的番茄凝集素，通过肺泡和支气管上皮细胞的荧光标记来可视化一般肺结构。组织透明化后进行激光扫描共聚焦显微镜，可以实现肺内德克萨斯红右旋糖酐的三维可视化，并评估其在肺泡尺度的分布，而无需制备薄组织切片。这些发现表明组织清除技术可用于评估肺内分布和肺部药物输送系统的开发。
In this study, we examined the usefulness of a tissue-clearing technique for the evaluation of the lung distribution of aerosolized drugs. An aerosol formulation of TexasRed dextran (70kDa), a model compound of drug carrier for aerosolized drugs, was administered intrapulmonarily to mice using a MicroSprayer, and then DyLight 488-conjugated tomato lectin was administered intravenously to visualize general lung structure via the fluorescent labeling of alveolar and bronchial epithelial cells. Tissue clearing followed by laser scanning confocal microscopy enabled the three-dimensional visualization of intrapulmonary TexasRed dextran and the evaluation of its distribution at the alveolar scale without the preparation of thin tissue sections. These findings suggest that tissue-clearing techniques are useful for the evaluation of intrapulmonary distribution and development of pulmonary drug delivery systems.