In Vitro Pulmonary Cell Culture in Pharmaceutical Inhalation Aerosol Delivery: 2-D, 3-D, and In Situ Bioimpactor Models

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Abstract
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. 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. This manuscript evaluates the currently available in vitro models and presents the challenges in developing reliable cellular tools to predict the deposition of inhalable particles in the lungs as a function of aerodynamic particle properties.