Zhang Guihua, Shinohara Naohide, Oshima Yutaka, Kobayashi Toshio, Imatanaka Nobuya, Kawaguchi Kenji, Gamo Masashi
National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki, 305-8569, Japan.
Chemicals Evaluation and Research Institute (CERI), Hita, Oita, Japan.
J Appl Toxicol. 2017 Apr;37(4):502-507. doi: 10.1002/jat.3386. Epub 2016 Oct 6.
Intratracheal administration methods are used to conduct toxicological assessments of inhaled nanoparticles (NPs), and gavage needles or microsprayers are common intratracheal delivery devices. The NP suspension is delivered in a liquid state via gavage needle and as a liquid aerosol via microsprayer. The differences in local pulmonary NP distribution (called the microdistribution) arising from the different states of the NP suspension cause differential pulmonary responses; however, this has yet to be investigated. Herein, using microbeam X-ray fluorescence microscopy, we quantitatively evaluated the TiO pulmonary microdistribution (per mesh: 100 μm × 100 μm) in lung sections from rats administered an intratracheal dose of TiO NPs (6 mg kg ) via gavage needle or microsprayer. The results revealed that: (i) using a microsprayer appears to reduce the variations in TiO content (ng mesh ) among rats (e.g., coefficients of variation, n = 3, microsprayer vs gavage needle: 13% vs 30%, for the entire lungs); (ii) TiO appears to be deposited less in the right middle lobes than in the rest of the lung lobes, irrespective of the chosen intratracheal delivery device; and (iii) similar TiO contents (ng mesh ) and frequencies are deposited in the lung lobes of rats administered TiO NPs via gavage needle or microsprayer. This suggests that the physical state of the administered NP suspension does not markedly alter TiO pulmonary microdistribution. The results of this investigation are important for the standardization of intratracheal administration methods. Copyright © 2016 John Wiley & Sons, Ltd.
气管内给药方法用于对吸入纳米颗粒(NP)进行毒理学评估,灌胃针或微型喷雾器是常见的气管内给药装置。NP悬浮液通过灌胃针以液态形式给药,通过微型喷雾器以液体气溶胶形式给药。NP悬浮液不同状态引起的局部肺部NP分布差异(称为微观分布)会导致不同的肺部反应;然而,这一点尚未得到研究。在此,我们使用微束X射线荧光显微镜,对通过灌胃针或微型喷雾器经气管给予TiO NP剂量(6 mg/kg)的大鼠肺切片中的TiO肺部微观分布(每网格:100μm×100μm)进行了定量评估。结果显示:(i)使用微型喷雾器似乎能减少大鼠之间TiO含量(ng/网格)的变化(例如,变异系数,n = 3,微型喷雾器与灌胃针相比:整个肺部分别为13%和30%);(ii)无论选择何种气管内给药装置,TiO在右中叶的沉积似乎都比在其他肺叶少;(iii)通过灌胃针或微型喷雾器给予TiO NP的大鼠肺叶中,TiO含量(ng/网格)和沉积频率相似。这表明所给药的NP悬浮液的物理状态不会显著改变TiO的肺部微观分布。本研究结果对于气管内给药方法的标准化具有重要意义。版权所有© 2016约翰·威利父子有限公司。