Lucas Engelhardt1, Martina Röhm2,3, Chrystelle Mavoungou4, Katharina Schindowski4, Annette Schafmeister4, Ulrich Simon1. 1. Scientific Computing Centre Ulm, Ulm University, Helmholtzstraße 20, 89081, Ulm, Germany. 2. Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany. HBC-UU@mail.de. 3. Faculty of Medicine, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany. HBC-UU@mail.de. 4. Institute of Applied Biotechnology, Biberach University of Applied Sciences, Hubertus-Liebrecht-Strasse 35, 88400, Biberach, Germany.
Abstract
PURPOSE: Aerosol particle deposition in the human nasal cavity is of high interest in particular for intranasal central nervous system (CNS) drug delivery via the olfactory cleft. The objective of this study was the development and comparison of a numerical and experimental model to investigate various parameters for olfactory particle deposition within the complex anatomical nasal geometry. METHODS: Based on a standardized nasal cavity, a computational fluid and particle dynamics (CFPD) model was developed that enables the variation and optimization of different parameters, which were validated by in vitro experiments using a constructed rapid-prototyped human nose model. RESULTS: For various flow rates (5 to 40 l/min) and particle sizes (1 to 10 μm), the airflow velocities, the calculated particle airflow patterns and the particle deposition correlated very well with the experiment. Particle deposition was investigated numerically by varying particle sizes at constant flow rate and vice versa assuming the particle size distribution of the used nebulizer. CONCLUSIONS: The developed CFPD model could be directly translated to the in vitro results. Hence, it can be applied for parameter screening and will contribute to the improvement of aerosol particle deposition at the olfactory cleft for CNS drug delivery in particular for biopharmaceuticals.
PURPOSE: Aerosol particle deposition in the human nasal cavity is of high interest in particular for intranasal central nervous system (CNS) drug delivery via the olfactory cleft. The objective of this study was the development and comparison of a numerical and experimental model to investigate various parameters for olfactory particle deposition within the complex anatomical nasal geometry. METHODS: Based on a standardized nasal cavity, a computational fluid and particle dynamics (CFPD) model was developed that enables the variation and optimization of different parameters, which were validated by in vitro experiments using a constructed rapid-prototyped human nose model. RESULTS: For various flow rates (5 to 40 l/min) and particle sizes (1 to 10 μm), the airflow velocities, the calculated particle airflow patterns and the particle deposition correlated very well with the experiment. Particle deposition was investigated numerically by varying particle sizes at constant flow rate and vice versa assuming the particle size distribution of the used nebulizer. CONCLUSIONS: The developed CFPD model could be directly translated to the in vitro results. Hence, it can be applied for parameter screening and will contribute to the improvement of aerosol particle deposition at the olfactory cleft for CNS drug delivery in particular for biopharmaceuticals.
Entities:
Keywords:
CFPD; nasal airflow; nose-to-brain drug delivery; olfactory cleft; standardized human nasal cavity
Authors: Michael C Veronesi; Mosa Alhamami; Shelby B Miedema; Yeonhee Yun; Miguel Ruiz-Cardozo; Michael W Vannier Journal: Am J Nucl Med Mol Imaging Date: 2020-02-25