Project Summary Drug administering has conventionally been through the process of ingestion or via invasive procedures. There is an efficient way of delivering drugs through the nasal cavity. The nasal route for direct drug- aerosol delivery is an attractive approach to combat various pathological conditions. For example, if rapid absorption of the delivered drugs can be ensured at the nasal epithelium through the mucus layer, this methodology enables fast onset of action avoiding formulation breakdown in the digestive system and first- pass metabolism and side effects. In order to simulate and analyze the fate of inhaled drug-aerosols in nasal cavities, including dissolution and absorption in the mucus layer, a validated and comprehensive computer simulation model is a very useful and cost-effective tool. Hence, based on the current research activities and the FDA funding opportunity, the specific aims are: (i) Development and validation of transient 3-D mucociliary clearance (MCC) and interactive particle transport/deposition models applied to different nasal geometries. (ii) Use of a representative configuration to simulate and analyze drug-aerosol transport, deposition, absorption and clearance; all subject to different inlet conditions and possibly obstructed nasal geometries. (iii) Writing of research papers as well as completion of a user’s manual in OpenFOAM. These research objectives can be achieved by developing and testing the proposed computational fluid- particle dynamics model in open-source software (ie, OpenFOAM). With the new easy-to-use numerical model different geometric nose-to-trachea configurations addressing subject-variability, air-particle- mucus interactions affecting drug-aerosol transport/deposition, and mucociliary clearance (MCC) with drug transport and absorption dynamics for different nasal inlet conditions will be simulated and analyzed.