Development of a size-dependent aerosol deposition model utilising human airway epithelial cells for evaluating aerosol drug delivery
Development of a size-dependent aerosol deposition model utilising human airway epithelial cells for evaluating aerosol drug delivery
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DOI：
10.1177/026119290403200609
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发表时间：
2004-12-01
影响因子：
2.7
通讯作者：
Hickey, AJ
中科院分区：
文献类型：
--
作者：
Cooney, D;Kazantseva, M;Hickey, AJ
气雾剂递送至人呼吸道的气道，然后吸收，构成了不适合通过常规口服和肠胃外途径递送的化合物的替代给药途径。气雾剂药物递送的靶是气道上皮，即气管、支气管、细支气管和肺泡细胞，其成为药物沉积的部位。这些上皮层也作为吸入物质渗透的屏障。一个体外模型的气溶胶沉积和运输通过上皮细胞在人体气道可能是一个很好的预测体内处置。目前的初步研究开始一项调查，混合气溶胶输送的动力学和体外模拟肺模型的基础上，以评估跨人源性细支气管上皮细胞单层的一系列分子量标记物化合物的转运特性。使用Andersen活级联撞击器作为递送装置，用于将尺寸分离的颗粒沉积到小气道上皮细胞和Calu-3细胞的单层上。结果表明，这些细胞层可以承受放置在冲击器中，并且可以在从冲击器中取出后测试渗透性。
Aerosol delivery to the airways of the human respiratory tract, followed by absorption, constitutes an alternative route of administration for compounds unsuitable for delivery by conventional oral and parenteral routes. The target for aerosol drug delivery is the airways epithelium, i.e. tracheal, bronchial, bronchiolar and alveolar cells, which become the site of drug deposition. These epithelial layers also serve as a barrier to the penetration of inhaled material. An in vitro model for aerosol deposition and transport across epithelia in the human airways may be a good predictor of in vivo disposition. The present preliminary studies begin an investigation that blends the dynamics of aerosol delivery and the basis of an in vitro simulated lung model to evaluate the transport properties of a series of molecular weight marker compounds across human-derived bronchiolar epithelial cell monolayers. An Andersen viable cascade impactor was used as a delivery apparatus for the deposition of size-segregated particles onto monolayers of small airway epithelial cells and Calu-3 cells. it was shown that these cell layers can withstand placement in the impactor, and that permeability can be tested subsequent to removal from the impactor.