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.

Public Health Relevance

The nasal route for direct drug-aerosol delivery is an attractive approach to combat various pathological conditions. 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. Specifically, different geometric nose-to-trachea configurations addressing subject-variability, air-particle-mucus interactions affecting drug-aerosol transport/deposition, and mucociliary clearance with drug transport and absorption dynamics for different nasal inlet conditions can be simulated and analyzed.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01FD006537-02
Application #
9771360
Study Section
Special Emphasis Panel (ZFD1)
Program Officer
Walenga, Ross
Project Start
2018-09-01
Project End
2021-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
North Carolina State University Raleigh
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695