In Vitro Pulmonary Cell Culture in Pharmaceutical Inhalation Aerosol Delivery: 2-D, 3-D, and In Situ Bioimpactor Models
In Vitro Pulmonary Cell Culture in Pharmaceutical Inhalation Aerosol Delivery: 2-D, 3-D, and In Situ Bioimpactor Models
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DOI：
10.2174/1381612822666160202142104
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发表时间：
2016-01-01
影响因子：
3.1
通讯作者：
Mansour, Heidi M.
中科院分区：
文献类型：
--
作者：
Acosta, Maria F.;Muralidharan, Priya;Mansour, Heidi M.
背景：用于肺部给药的非侵入性吸入气雾剂的使用持续增长。这是由于这种递送路线在治疗局部和全身疾病方面提供了许多独特的优势。配方药物的物理化学性质以及肺部的生理特性对微粒的沉积和吸收都起着关键作用。呼吸道和肺泡上皮是呼吸系统疾病治疗的靶点。然而，粒子在到达目标并产生效果之前必须克服生物障碍。方法：可吸入颗粒的体外气雾剂分散性能(即空气动力学尺寸和空气动力学尺寸分布)通过惯性撞击来量化，这是监管机构批准在患者身上作为上市药品使用的试验性药物吸入气雾剂制剂的要求。使用惯性撞击结合各种肺细胞的原位培养作为生物撞击器，在将空气动力学特性与肺细胞行为(包括存活和摄取)相关联方面具有独特的方面。这些细胞可以是共培养的，也可以是单独培养的，可以是三维多细胞球体或二维细胞单层，使用不同的条件进行培养，如气液界面培养(ALI)或液体覆盖培养(LCC)。结果：本文对目前可用的体外模型进行了评估，并提出了开发可靠的细胞工具来预测可吸入颗粒物在肺部的沉积作为空气动力学颗粒物特性函数的挑战。结论：随着体外实验方法的发展，基于空气动力学尺寸和空气动力学尺寸分布的气溶胶颗粒在整个呼吸道细胞水平上的机械、空气动力学和生物物理特性将得到更好的理解。
Background: The use of non-invasive inhaled aerosols for pulmonary drug delivery continues to grow. This is due to the many unique advantages this delivery route offers for the treatment of both local and systemic diseases. The physicochemical properties of the formulated drugs as well as the physiology of the lungs play a key role in both the deposition and absorption of the particles. The airway and the alveolar epithelium are targets for the treatment of respiratory diseases. However, particles have to overcome biological barriers before they reach their target and produce an effect. Methods: In vitro aerosol dispersion performance (i.e. aerodynamic size and aerodynamic size distribution) of inhalable particles is quantified by inertial impaction, as required by regulatory agencies for an investigational pharmaceutical inhalation aerosol formulation to be approved for use in patients as a marketed pharmaceutical product. Using inertial impaction in conjunction with cell cultures of various pulmonary cells in situ as bioimpactors has unique aspects in correlating aerodynamic properties with pulmonary cellular behavior including viability and uptake. These can be as co-culture or in single culture, as 3-D multicellular spheroids or 2-D cellular monolayer using different conditions to grow them, such as air-liquid interface culture (ALI) or in liquid covered culture (LCC). Results: evaluation of the currently available in vitro models and the challenges in developing reliable cellular tools to predict the deposition of inhalable particles in the lungs as a function of aerodynamic particle properties is presented in the manuscript. Conclusion: The mechanistic aerodynamic and biophysical properties of inhaled aerosol particles on the entire respiratory tract at the cellular level based on aerodynamic size and aerodynamic size distribution will be better understood with the development of in vitro methods which are described in this work.