A new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to evaluate pulmonary drug absorption for metered dose dry powder formulations
A new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to evaluate pulmonary drug absorption for metered dose dry powder formulations
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DOI：
10.1016/j.ejpb.2010.10.003
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发表时间：
2011-01-01
影响因子：
4.9
通讯作者：
Lehr, Claus-Michael
中科院分区：
文献类型：
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作者：
Hein, Stephanie;Bur, Michael;Lehr, Claus-Michael
由于涉及的过程很复杂，(I)气雾剂的产生和沉积，(Ii)药物从载体释放，以及(Iii)跨上皮气-血屏障的吸收，利用计量吸入器提供的气雾剂制剂通过肺上皮细胞和组织的体外模型进行的吸收研究并不是微不足道的。与肠粘膜不同，肺上皮只覆盖着一层薄薄的衬里液体。浸没式细胞培养系统不允许研究气溶胶颗粒的沉积及其对这一脆弱的上皮组织的影响。我们开发了一种新的药物气溶胶沉积装置(PADDOCC)，以模拟吸入单个计量气雾剂剂量及其随后在暴露于气液界面的滤器生长的肺上皮细胞单层上的沉积。使用含有硫酸沙丁胺醇或布地奈德的商用干粉吸入器，可以证明这些干粉气雾剂的沉积和随后通过CALU-3单层的药物传输的重复性。在开发新的干粉气雾剂配方的背景下，PADDOCC似乎是一个有用的工具，可以减少动物试验，并更快地转化为临床试验。(C)2010爱思唯尔B.V.保留所有权利。
Absorption studies with aerosol formulation delivered by metered dose inhalers across cell- and tissue-based in vitro models of the pulmonary epithelia are not trivial due to the complexity of the processes involved: (i) aerosol generation and deposition, (ii) drug release from the carrier, and (iii) absorption across the epithelial air-blood barrier. In contrast to the intestinal mucosa, pulmonary epithelia are only covered by a thin film of lining fluid. Submersed cell culture systems would not allow to studying the deposition of aerosol particles and their effects on this delicate epithelial tissue.We developed a new Pharmaceutical Aerosol Deposition Device on Cell Cultures (PADDOCC) to mimic the inhalation of a single metered aerosol dose and its subsequent deposition on filter-grown pulmonary epithelial cell monolayers exposed to an air-liquid interface. The reproducibility of deposition of these dry powder aerosols and subsequent drug transport across Calu-3 monolayers with commercially available dry powder inhalers containing salbutamol sulphate or budesonide could be demonstrated.In the context of developing new dry powder aerosol formulations, PADDOCC appears as a useful tool, allowing reducing animal testing and faster translation into clinical trials. (C) 2010 Elsevier B.V. All rights reserved.