(T1330-03-16) Design of a Personalized Nasal Device (Matrix-Piston Device, MPD) for Nose-to-Brain Delivery: A 3D-Printing Application

Purpose: Designing, construction and in vitro evaluation of a novel 3D-printed device for the nasal delivery of biodegradable polymeric films to the olfactory region.

Methods: The Matrix-Piston nasal device (MPD) was designed with the Autodesk Fusion 360 software® considering the human anatomical features of the nasal cavity [1]. The MPD constructed using a FDM Creality® Ender-3 Pro printer of 220 x 220 x 250 mm printing area. The device consisted of two independent parts, the matrix and the piston (Figure 1), printed by different material each. PLA, TPU, ABS and FiberFlex (thermoplastic elastomer, TPE) were tested as candidates for the construction of these parts. MPD evaluation was performed using a non-realistic (NR) and a semi-realistic (SR) nasal simulator. The two simulators were printed based on the computer-aided design model from the Department of infectious diseases of the Hospital University of Strasbourg, in France [2]. The NR simulator was constructed using TPU filament for the left side, while the right side was made of PLA. For the SR simulator, the more flexible FiberFlex 40D material was employed for printing both sides, to stimulate the flexibility of humane nasal cavity. A hydroxypropyl-methyl cellulose-based drug-free film, containing polyethylene glycol 400 as plasticizer and methyl-β-cyclodextrin as permeation enhancer (1.5% w/w HPMC E50, 1.7% w/w PEG 400 and 0.8% w/w Me-β-CD in water), was placed on the MPD head of the matrix [3]. It was allowed to dry for 30 min, at room temperature (± 25 °C) and tested for its ability to be detached from the device and positioned on the artificial olfactory region of the simulator.

Results: PLA, TPU and FiberFlex 40D matrices were printed with inner and external diameters of its extensions equal to 2.7 mm and 4 mm, respectively. The TPU material was selected as the best material among the tested for the matrix construction. It was characterized by moderate flexibility and adequate durability, expecting to cause no irritation in the nasal cavity during administration. The functionality of the piston, expressed as the ability to fit in the TPU matrix and release the film formed on its head, revealed the ABS material as the most appropriate for the construction of the piston. The ABS piston had an extension with 2.2 mm diameter and 36 mm height. It could properly fit into the TPU matrix and presented the appropriate rigidity to release the film successfully from the head. The assembled MPD (Figure 2A) was assessed using NR and SR nasal simulators (Figure 2B). The evaluation test showed that the base fits to the nostril, at both sides of the simulators and the height of extension enables the head of the matrix to reach the targeted area (Figure 3A). Furthermore, the film was released successfully on the targeted area, after 3 rotations of the device (Figure 3B).

Conclusion: The present study introduces a realistic novel 3D-printed device for the personalized administration of nasal films. The development of personalized devices for nasal delivery with 3D-printing technologies, as applied in this work, can significantly improve the effectiveness of the IN formulations. The four tested materials to produce MPD have been extensively used in the development of medical devices and are FDA approved [4-6]. Moreover, the simulator has been characterized as highly realistic and anatomically accurate by the 85% and 95% respectively [7]. Hence, in vitro evaluation can be efficiently performed using nasal simulator models, however clinical studies on healthy volunteers are required to support the applicability of the device.

References: 1. Uzun A, Akbas H, Bilgic S, Emirzeoglu M, Bostanci O, Sahin B, Bek Y. The average values of the nasal anthropometric measurements in 108 young Turkish males. Auris Nasus Larynx. 2006; 33(1):31-5. doi: 10.1016/j.anl.2005.05.004
2. Sananès N, Lodi M, Koch A, Lecointre L, Sananès A, Lefebvre N, Debry C. 3D‑printed simulator for nasopharyngeal swab collection for COVID‑19, Eur Arch Otorhinolaryngol. 2021; 278(7): 2649–2651. doi: 10.1007/s00405-020-06454-1
3. Papakyriakopoulou P, Rekkas DM, Colombo G, Valsami G. Development and in vitro - ex vivo evaluation of novel polymer nasal donepezil films for potential nose-to-brain delivery using experimental design. 2022 [submitted]
4. Fang Z, Yonghao X, Xue G, Liujun J, Yuehao X, Yongquan G, Ai-ying Z, Zeng-guo F. Fabrication of heparinized small diameter TPU/PCL bi-layered artificial blood vessels and in vivo assessment in a rabbit carotid artery replacement model. Mater Sci Eng C. 2021;112628. doi: 10.1016/j.msec.2021.112628
5. DeStefano V, Khan S, Tabada A. Applications of PLA in modern medicine. Engineered Regeneration. 2020; 1: 76–87. doi: 10.1016/j.engreg.2020.08.002
6. Grady BP, Cooper SL, Robertson CG. Thermoplastic Elastomers. The Science and Technology of Rubber, 2013: 591–652.


(i) CAD models of 1) the matrix of MPD consisting of: A. the base handle, B. the base, C. the base extension, D. the head, where the film will be formed and 2) the piston consisting of: A. the base handle, B. the base and, C. the base extension. (ii) The two parts of the MPD assembled before and (iii) after the film release.


A. i) TPU Matrix, ii) ABS Piston, iii) assembled MPD, and B. Non-realistic (left) and semi-realistic (right) nasal simulator.


A. MPD fit into the 3D-printed nasal simulators: i) right side of NR, ii) left side of NR, iii) right side of SR, iv) left side of SR, and B. Successful positioning of the nasal film (in the green circle) on the olfactory area of the SR nasal simulator, using MPD.