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TARGETED DELIVERY OF INHALED PROTEINS
Citation:
Martonen, T B., J. D. Schroeter, Z. Z. Zhang, D. Hwang, AND J. S. Fleming. TARGETED DELIVERY OF INHALED PROTEINS. Presented at Respiratory Drug Delivery VIII, Tucson, AZ, May 12-16, 2002.
Description:
ETD-02-047 (Martonen) GPRA # 10108
TARGETED DELIVERY OF INHALED PROTEINS
T. B. Martonen1, J. Schroeter2, Z. Zhang3, D. Hwang4, and J. S. Fleming5
1Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC and Division of Pulmonary Diseases, Department of Medicine, University of North Carolina, Chapel Hill, NC; 2Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC; 3Department of Mechanical Engineering and Applied Mechanics, University of Rhode Island, Kingston, RI; 4IBM Corporation, Network Hardware Division, Research Triangle Park, NC; 5Department of Nuclear Medicine, Southampton General Hospital, Southampton, UK
Aerosol therapy protocols for protein delivery would be enhanced if drugs could be selectively deposited within human lungs to elicit optimum therapeutic effects. Herein, we shall address the delivery of aerosolized insulin. Inhaled macromolecules are transported by airstreams, and because air motion is affected by morphology, knowledge of airway dimensions and structure is seminal to the development of dosimetry models. To aid in the definition of targeted drug delivery protocols we present original three-dimensional computer models of the complete human respiratory system, and methodologies to describe airflow behavior using computational fluid dynamics (CFD) software packages. The morphologies of extrathoracic regions (consisting of the nasal, oral, pharyngeal, and laryngeal passages) are based on measurements from original silicone rubber casts. The tracheobronchial and pulmonary airways of lungs are described using morphometric data from the literature coupled with original measurements from cadaveric casts. The CFD computations are performed using commercially available codes, either CFX-F3D or FIDAP. By integrating the above morphological-CFD models, the trajectories of aerosolized insulin are determined. We have simulated human exposures in the medical arena. This permitted factors (e.g., particle size, tidal volume, breath-hold) affecting localized deposition patterns to be predicted, allowing insulin to be effectively targeted and, thereby, enhancing the efficacy of the inhaled drug.
DISCLAIMER: This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.
ACKNOWLEDGMENTS: Dr. J. Schroeter was funded by the EPA/UNC Toxicology Research Program, Training Agreement CT902908.