Seifelnasr Amr, Si Xiuhua April, Xi Jinxiang
Department of Biomedical Engineering, University of Massachusetts, Lowell, MA 01854, USA.
Department of Mechanical Engineering, California Baptist University, Riverside, CA 92504, USA.
Pharmaceutics. 2023 Jun 5;15(6):1657. doi: 10.3390/pharmaceutics15061657.
Nose-to-brain (N2B) drug delivery offers unique advantages over intravenous methods; however, the delivery efficiency to the olfactory region using conventional nasal devices and protocols is low. This study proposes a new strategy to effectively deliver high doses to the olfactory region while minimizing dose variability and drug losses in other regions of the nasal cavity. The effects of delivery variables on the dosimetry of nasal sprays were systematically evaluated in a 3D-printed anatomical model that was generated from a magnetic resonance image of the nasal airway. The nasal model comprised four parts for regional dose quantification. A transparent nasal cast and fluorescent imaging were used for visualization, enabling detailed examination of the transient liquid film translocation, real-time feedback on input effect, and prompt adjustment to delivery variables, which included the head position, nozzle angle, applied dose, inhalation flow, and solution viscosity. The results showed that the conventional vertex-to-floor head position was not optimal for olfactory delivery. Instead, a head position tilting 45-60° backward from the supine position gave a higher olfactory deposition and lower variability. A two-dose application (250 mg) was necessary to mobilize the liquid film that often accumulated in the front nose following the first dose administration. The presence of an inhalation flow reduced the olfactory deposition and redistributed the sprays to the middle meatus. The recommended olfactory delivery variables include a head position ranging 45-60°, a nozzle angle ranging 5-10°, two doses, and no inhalation flow. With these variables, an olfactory deposition fraction of 22.7 ± 3.7% was achieved in this study, with insignificant discrepancies in olfactory delivery between the right and left nasal passages. It is feasible to deliver clinically significant doses of nasal sprays to the olfactory region by leveraging an optimized combination of delivery variables.
经鼻至脑（N2B）给药相较于静脉给药方法具有独特优势；然而，使用传统鼻腔装置和方案向嗅觉区域的给药效率较低。本研究提出一种新策略，可在将剂量变异性和鼻腔其他区域的药物损失降至最低的同时，有效地向嗅觉区域输送高剂量药物。在一个由鼻气道磁共振图像生成的3D打印解剖模型中，系统评估了给药变量对鼻喷雾剂剂量学的影响。该鼻腔模型包括四个部分用于区域剂量量化。使用透明鼻模和荧光成像进行可视化，从而能够详细检查瞬态液膜移位、对输入效应的实时反馈以及对给药变量的快速调整，这些变量包括头部位置、喷嘴角度、给药剂量、吸入流量和溶液粘度。结果表明，传统的头顶至脚底头部位置并非嗅觉给药的最佳选择。相反，从仰卧位向后倾斜45 - 60°的头部位置可实现更高的嗅觉沉积和更低的变异性。需要分两次给药（250毫克）来移动在首次给药后经常积聚在前鼻孔的液膜。吸入气流的存在会降低嗅觉沉积，并将喷雾剂重新分布到中鼻道。推荐的嗅觉给药变量包括45 - 60°的头部位置、5 - 10°的喷嘴角度、两次给药且无吸入气流。通过这些变量，本研究实现了22.7±3.7%的嗅觉沉积分数，左右鼻腔之间的嗅觉给药差异不显著。通过利用优化的给药变量组合，向嗅觉区域输送具有临床意义剂量的鼻喷雾剂是可行的。
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