Rigaut Clément, Deruyver Laura, Goole Jonathan, Haut Benoît, Lambert Pierre
Transfers, Interfaces and Processes (TIPs), École Polytechnique de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium.
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Pharmacie, Université Libre de Bruxelles, Brussels, Belgium.
Front Med Technol. 2022 Jun 27;4:924501. doi: 10.3389/fmedt.2022.924501. eCollection 2022.
Nose-to-brain delivery is a promising way to reach the central nervous system with therapeutic drugs. However, the location of the olfactory region at the top of the nasal cavity complexifies this route of administration. In this study, we used a 3D-printed replica of a nasal cavity (a so-called "nasal cast") to reproduce the deposition of a solid powder. We considered two different delivery devices: a unidirectional device generating a classical spray and a bidirectional device that relies on the user expiration. A new artificial mucus also coated the replica. Five parameters were varied to measure their influence on the powder deposition pattern in the olfactory region of the cast: the administration device, the instillation angle and side, the presence of a septum perforation, and the flow rate of possible concomitant inspiration. We found that the unidirectional powder device is more effective in targeting the olfactory zone than the bi-directional device. Also, aiming the spray nozzle directly at the olfactory area is more effective than targeting the center of the nasal valve. Moreover, the choice of the nostril and the presence of a perforation in the septum also significantly influence the olfactory deposition. On the contrary, the inspiratory flow has only a minor effect on the powder outcome. By selecting the more efficient administration device and parameters, 44% of the powder can reach the olfactory region of the nasal cast.
鼻脑给药是一种利用治疗药物抵达中枢神经系统的很有前景的方式。然而，鼻腔顶部嗅觉区域的位置使这种给药途径变得复杂。在本研究中，我们使用鼻腔的3D打印复制品（所谓的“鼻模”）来重现固体粉末的沉积情况。我们考虑了两种不同的给药装置：一种产生传统喷雾的单向装置和一种依靠使用者呼气的双向装置。一种新型人工黏液也覆盖在该复制品上。改变了五个参数以测量它们对鼻模嗅觉区域粉末沉积模式的影响：给药装置、滴注角度和方向、是否存在鼻中隔穿孔以及可能伴随的吸气流量。我们发现，单向粉末装置在靶向嗅觉区域方面比双向装置更有效。此外，将喷雾喷嘴直接对准嗅觉区域比对准鼻阀中心更有效。而且，鼻孔的选择和鼻中隔穿孔的存在也会显著影响嗅觉沉积。相反，吸气流对粉末沉积结果的影响较小。通过选择更有效的给药装置和参数，44%的粉末能够到达鼻模的嗅觉区域。
