Method for Pulmonary Administration Using Negative Pressure Generated by Inspiration in Mice
Method for Pulmonary Administration Using Negative Pressure Generated by Inspiration in Mice
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DOI：
10.3390/pharmaceutics12030200
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发表时间：
2020-03-01
期刊：
影响因子：
5.4
通讯作者：
Yamashita, Chikamasa
中科院分区：
文献类型：
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作者：
Oiso, Yuki;Akita, Tomomi;Yamashita, Chikamasa
在开发治疗呼吸系统疾病(如慢性阻塞性肺疾病)的吸入性药物时，需要在非临床试验中通过肺部给药。常用的给药方法需要在给药过程中施加压力，可能会导致肺损伤，因此我们将重点放在小鼠自身吸入液体药物上。本研究旨在探讨一种小鼠自吸负压肺给药方法。首先，为了确认液体药物进入肺部的准确性和肺损伤的可能性，癌症研究所(ICR)的小鼠通过负压法给四水亚甲基蓝或生理盐水。我们通过给予小鼠猪胰腺弹性蛋白酶和全反式维甲酸(ATRA)来评估药物分布和这种方法的有效性。结果，我们证实了染料的良好分布，并且没有损伤，如小鼠肺内血流中断或肺泡破坏。建立小鼠肺气肿模型后，计算平均线性截距(Lm)为78+/-4微米，并证实了全反式维甲酸的显著治疗作用。这些结果表明，这种负压给药方法可能适用于非临床试验中的肺部给药。
When developing inhaled medicines for respiratory diseases, such as chronic obstructive pulmonary disease, drugs need to be administered by pulmonary delivery to animals in non-clinical tests. Common methods require application of pressure during administration, and it may cause lung injury, so we focused on the inhalation of liquid medicines by mice themselves. This study aimed to evaluate a negative pressure method of pulmonary administration in mice by self-inhalation. First, to confirm the accuracy of delivery of liquid medicines into lungs and the potential for lung injury, Institute of Cancer Research (ICR) mice received methylene blue tetrahydrate or saline by the negative pressure method. We assessed drug distribution and usefulness of this method by administering porcine pancreatic elastase and all-trans-retinoic acid (ATRA) to mice. Consequently, we confirmed good distribution of the dye and no injury such as disruption of blood flow or destruction of alveoli in lungs of mice. Following production of the murine emphysema model, the mean linear intercept (Lm) was calculated as 78 +/- 4 mu m. Moreover, a significant therapeutic effect of administration of the ATRA was confirmed. These results suggest that this negative pressure method of administration may be useful for pulmonary administration in non-clinical tests.