A Predictive Open-Source Computer Model for Inhaled Nanoparticle Transport and Deposition in Subject-specific Upper Airways

CBET - 1232988

Understanding the transport mechanisms of inhaled natural and man-made nanoparticles and accurately predicting the deposition in realistic human airways are of great interest. Experimentally validated computer simulation results are needed to assess health effects of inhaled toxic nanoparticles appearing in the environment and now more frequently in the workplace, as well as the fate of administered nanodrugs for therapeutic purposes. The overall goal of this proposal is to develop a validated, comprehensive, public-access computer simulation model of inhaled air-particle dynamics and deposition/clearance for representative, subject-specific cases. The new computer model will produce realistic and accurate results to gain new physical insight and provide an array of useful applications. Examples include: health-care providers focusing on drug-aerosol targeting of lung tumors, federal regulators assessing toxic nanoparticle deposition from man-made sources, and scientists interested in nanoparticle clearance aspects.

The research plan calls for a combined computational and experimental approach to understand interrelated fluid-particle interaction mechanisms and to develop a predictive computer simulation model. Building on two decades of experience in lung-aerosol dynamics modeling and simulation by the PI and his Research Team, the novel submodels for two-way coupled fluid-structure interactions, non-spherical particle dynamics and air-mucus transport and particle clearance mechanism will be developed in the MAE Department at NC State University. The experimental work, focusing on nanomaterial depositions in the same subject-specific airway models, will be carried out at Mercer University.The anticipated results: (i) are related to technology innovation (i.e., applied to virtual testing of a patented smart inhaler system for optimal drug-aerosol delivery); (ii) have multiple applications (see broader impacts listed); and (iii) interface engineering and life sciences (e.g., health-care and/or environmental regulations).

Intellectual Merit: The proposed study will provide new physical insights, a better understanding and novel mathematical and computer models on air-mucus flow and particle transport, deposition and clearance of real-world nanoparticles (especially ellipsoids, carbon nanotubes, and nanofibers) in realistic, subject-specific human airways under realistic, cyclic breathing conditions with fluid-structure interactions. Open-access software and codes will be developed to predict both local and regional nanoparticle deposition/clearance in subject-specific human airways for environmental specialists, toxicologists, health-care providers, basically free-of-charge.

Broader Impacts: The developed codes and software are free and open to the public. They will be easily available and updated via a specific website along with manuals and simulation examples. Modern medical and environmental problems related to nanoparticle inhalation could be readily solved, for example,(a) primarily reliable particle-deposition data to analyze the impact of inhaled toxic nanoparticles or new drugs for pharmacokinetics modeling (b) also, virtual testing of the new methodology for controlled drug-aerosol inhalation using a patented smart inhaler system and (c) evaluating the effect of local airway obstruction, e.g., due to severe asthma, COPD, OSAS, or CF on air-particle flow. The proposed research activity also has other broader impacts on research/education via: (i) promoting the teaching and research training of undergraduate and graduate students; (ii) involvement of students from underrepresented groups; (iii) establishing research and education collaborations with students and faculty from an undergraduate institution to expand their masters-level course offerings and to potentially create a PhD-level engineering program.