Jingliang Dong1, Yidan Shang1, Kiao Inthavong1, Hak-Kim Chan2, Jiyuan Tu3,4. 1. School of Engineering, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia. 2. Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia. 3. School of Engineering, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia. jiyuan.tu@rmit.edu.au. 4. Key Laboratory of Ministry of Education for Advanced Reactor Engineering and Safety, Institute of Nuclear and New Energy Technology, Tsinghua University, PO Box 1021, Beijing, 100086, China. jiyuan.tu@rmit.edu.au.
Abstract
PURPOSE: Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. METHODS: This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. RESULTS: The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. CONCLUSIONS: The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.
PURPOSE: Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. METHODS: This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. RESULTS: The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 μm. While for particles in the range of 10 nm to 2 μm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. CONCLUSIONS: The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.
Entities:
Keywords:
drug administration; nose-to-brain; numerical modelling; olfactory; particle deposition
Authors: Wafaa Alabsi; Maria F Acosta; Fahad A Al-Obeidi; Meredith Hay; Robin Polt; Heidi M Mansour Journal: Pharmaceutics Date: 2021-08-17 Impact factor: 6.321