Physical and Computational Models of Human Lung for Optimizing Respiratory Drug Delivery.

Respiratory drug particles aerosolized from the commercially available drug delivery devices may charge electrostatically. Investigations of the relevance of this charge on deposition in the human lung are just quite a few and they started early eighties though the aerosol science study is a decade old discipline. Additionally, the localized deposition of drug particles at desired sites such as inflamed tissue and appropriate receptors has been recognized by clinical investigators as being critical factors for the effective administration of respiratory drugs. To accomplish these tasks, it is imperative to undertake in vitro and in silico studies of medicinal drug aerosol administration with physical and computational models of human lung. In this dissertation, a Glass Bead Tracheobronchial Model (GBTBM) of human lung's tracheobronchial airways was designed, developed, and validated with the respiratory deposition data predicted by the International Commission on Radiological Protection (ICRP). The experimental data agreed with the United States Pharmacopeia approved Andersen Cascade Impactor (ACI) measurements. Additionally, a computational model (CM) for studying the respiratory deposition of engineered drug aerosol particles in the entire human respiratory airways was also developed and validated with ICRP data. Both the GBTBM and CM were based on widely used human lung's morphological dimensions specified in the Ewald R. Weibel's dichotomous lung morphometry model. The combined effects of particle aerodynamic size and electrostatic charge on the deposition of inhaled aerosols in a cast of human oral-pharyngeal-laryngeal (OPL) airways were investigated. The effects of both properties (size and charge) on the OPL airway deposition of metered dose inhaler (MDI) and dry powder inhaler (DPI) aerosols were also studied. Finally, the effect of electrostatic charge property on deposition of several asthma drugs in the OPL airways was also investigated. The 2-stage GBTBM simulated the surface area and the flow Reynolds number of the trachea, main, lobar and segmental bronchi of the human lung. Its major advantage with the ACI was its ability to simulate all five electromechanical deposition mechanisms of aerosols while the stages cutoff diameters are equal to the 3rd and the 4th stages of the ACI. The deposition of unipolarly charged particles on the OPL airways is about three times of the bipolarly charged particles. Modeling studies with CM revealed that by enhancing electrostatic charge 1.5 times, improvement in the deposition of drug aerosols in the respiratory airways can be achieved, which will compensate 67% of the reduction due to the absence of gravity.