A Custom-Made Device for Reproducibly Depositing Pre-metered Doses of Nebulized Drugs on Pulmonary Cells in vitro.
A Custom-Made Device for Reproducibly Depositing Pre-metered Doses of Nebulized Drugs on Pulmonary Cells in vitro.
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DOI：
10.3389/fbioe.2021.643491
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发表时间：
2021
影响因子：
5.7
通讯作者：
Lehr CM
中科院分区：
文献类型：
--
作者：
Horstmann JC;Thorn CR;Carius P;Graef F;Murgia X;de Souza Carvalho-Wodarz C;Lehr CM
预先计量剂量（即暴露前和暴露后定义）在活肺上皮细胞的气液界面沉积仍然是开发气雾剂药物的重要但具有挑战性的任务。虽然有些设备允许在实验后或实验期间对沉积剂量进行定量，例如，重量计量，但仍然没有普遍接受的方法来沉积雾化药物或药物制剂的预计量小剂量，例如纳米药物。在这里，我们描述了一个简单的定制设备，允许连接到市售雾化器与标准细胞培养板。设计为紧密配合12孔Transwell®插入或单个24孔板的约12毫米开口，一定剂量的雾化液体可以直接沉积在肺细胞培养的气液界面（ALI）精确和可重复性（4.8%偏差）。沉积剂量可由雾化溶液的体积控制，可在20 ~ 200 μl范围内变化。整个雾化-沉积操作在30s后完成，并且在空间上是均匀的。经磷酸盐缓冲盐水（PBS）沉积后，人支气管上皮Calu-3细胞的活力和经上皮电阻（TEER）的屏障性能没有受到负面影响。该设备制造和使用简单，可以重复沉积计量剂量的雾化药物，以研究在ALI条件下生长的肺细胞培养物的相互作用。
The deposition of pre-metered doses (i.e., defined before and not after exposition) at the air–liquid interface of viable pulmonary epithelial cells remains an important but challenging task for developing aerosol medicines. While some devices allow quantification of the deposited dose after or during the experiment, e.g., gravimetrically, there is still no generally accepted way to deposit small pre-metered doses of aerosolized drugs or pharmaceutical formulations, e.g., nanomedicines. Here, we describe a straightforward custom-made device, allowing connection to commercially available nebulizers with standard cell culture plates. Designed to tightly fit into the approximately 12-mm opening of either a 12-well Transwell® insert or a single 24-well plate, a defined dose of an aerosolized liquid can be directly deposited precisely and reproducibly (4.8% deviation) at the air–liquid interface (ALI) of pulmonary cell cultures. The deposited dose can be controlled by the volume of the nebulized solution, which may vary in a range from 20 to 200 μl. The entire nebulization-deposition maneuver is completed after 30 s and is spatially homogenous. After phosphate-buffered saline (PBS) deposition, the viability and barrier properties transepithelial electrical resistance (TEER) of human bronchial epithelial Calu-3 cells were not negatively affected. Straightforward in manufacture and use, the device enables reproducible deposition of metered doses of aerosolized drugs to study the interactions with pulmonary cell cultures grown at ALI conditions.
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影响因子：
6.6
作者：
Ehrmann S;Schmid O;Darquenne C;Rothen-Rutishauser B;Sznitman J;Yang L;Barosova H;Vecellio L;Mitchell J;Heuze-Vourc'h N
通讯作者：
Heuze-Vourc'h N
影响因子：
5.8
作者：
Foster, KA;Avery, ML;Audus, KL
通讯作者：
Audus, KL
影响因子：
10
作者：
Ding, Yaobo;Weindl, Patrick;Schmid, Otmar
通讯作者：
Schmid, Otmar
影响因子：
17.1
作者：
Barosova, Hana;Maione, Anna G.;Rothen-Rutishauser, Barbara
通讯作者：
Rothen-Rutishauser, Barbara
DOI：
10.1016/j.ejpb.2010.10.003
发表时间：
2011-01-01
影响因子：
4.9
作者：
Hein, Stephanie;Bur, Michael;Lehr, Claus-Michael
通讯作者：
Lehr, Claus-Michael