Dong Jingliang, Shang Yidan, Inthavong Kiao, Chan Hak-Kim, Tu Jiyuan
School of Engineering, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW, 2006, Australia.
Pharm Res. 2017 Dec 29;35(1):5. doi: 10.1007/s11095-017-2280-6.
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.
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.
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.
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.
沿嗅觉和三叉神经通路进行鼻至脑给药为治疗中枢神经系统(CNS)疾病提供了一条替代途径。在实验中,颗粒沉积的表征仍然难以实现。应用替代数值方法来确定具有最大吸入剂量的合适气溶胶粒径。
本研究在数值上比较了两种针对嗅觉区域的气溶胶给药系统在真实人体鼻腔中的给药效率:气溶胶面罩系统和呼吸驱动双向系统。将稳定的吸入和呼出流速应用于两种给药系统。采用离散相颗粒跟踪方法来捕捉鼻腔中的气溶胶药物传输和沉积行为。详细分析了整体和区域沉积特征。
结果表明,呼吸驱动给药方法可以产生更好的嗅觉沉积,对于扩散的1纳米颗粒和惯性的10微米颗粒,嗅觉沉积分数达到峰值。而对于10纳米至2微米范围内的颗粒,未发现明显的嗅觉沉积,这表明治疗剂在靶向嗅觉沉积时应避免此尺寸范围。
呼吸驱动双向气溶胶给药方法在整体和局部均显示出更好的给药性能,并且可以在靶向嗅觉区域实现更高的给药剂量。