Impact of Nasal Delivery Devices on Olfactory Drug Deposition
Abstract
Nasal delivery offers a promising non-invasive approach for targeting therapeutics to the brain through the olfactory region. However, conventional nasal administration frequently produces predominant deposition in the anterior nasal cavity, limiting drug access to the olfactory epithelium. Nasal delivery devices play a critical role in overcoming these anatomical and aerodynamic barriers by controlling spray velocity, droplet or particle size, plume geometry, airflow, dose volume and administration direction. This review examines the impact of conventional and advanced nasal delivery devices on olfactory drug deposition, with particular emphasis on metered-dose sprays, nasal drops, nebulizers, powder devices, atomizers, breath-powered bidirectional systems and specialized nose-to-brain platforms. The influence of device design and administration parameters on regional deposition, mucosal retention and potential nose-to-brain transport is discussed. Computational fluid dynamics, nasal cast models, imaging techniques and experimental approaches used for deposition assessment are also reviewed. Emerging personalized and digitally optimized devices may provide improved and reproducible olfactory targeting for future CNS therapeutics.
Keywords: Olfactory deposition, nasal delivery devices, nose-to-brain delivery, intranasal drug delivery, olfactory targeting
Keywords:
Olfactory deposition, nasal delivery devices, nose-to-brain delivery, intranasal drug delivery, olfactory targetingDOI
https://doi.org/10.22270/jddt.v16i9.8009References
1. Khanfar MS, Alaboud SY, Khalil RW, Darweesh RS. Formulation and Characterization of Amisulpride-Poly (Lactic-Co-Glycolic Acid) Nanoparticles Coated with Chitosan for Intranasal Delivery. AAPS PharmSciTech. 2026;27(3):153. doi:10.1208/s12249-026-03405-7
https://doi.org/10.1208/s12249-026-03405-7 PMid:41872643
2. Zhai Z, Wang W, Wang G, et al. Rationalizing nose-to-brain drug delivery: Machine learning-guided optimization and mechanistic elucidation of olfactory deposition for nasal sprays. Journal of Controlled Release. 2026;392:114667. https://doi.org/10.1016/j.jconrel.2026.114667 PMid:41617015
3. DSouza AA, Kahan M, Yang A, Padmakumar S, Bleier BS, Amiji MM. Formulation considerations in enhancing olfactory mucosal deposition for nose-to-brain drug delivery. Drug Deliv Transl Res. 2026;16(8):2552-2577. https://doi.org/10.1007/s13346-026-02097-7 PMid:41865231 PMCid:PMC13346265
4. Wang H, Zhang Y, Zhang Y, et al. Evaluation of rayleigh jet atomizer for intranasal delivery of lipid nanoparticle-siRNA formulations: stability, deposition, and device performance. Int J Pharm. 2025;683:126084. https://doi.org/10.1016/j.ijpharm.2025.126084 PMid:40819710
5. Sunstrom N, Sunstrum FN. Wearable Devices for Subcutaneous Delivery of Large-Volume Biologics: Design, Use, and Regulatory Perspective. Biomedical Materials & Devices. 2026;4(4):4116-4135. https://doi.org/10.1007/s44174-025-00479-y
6. Sasaki K, Fukakusa S, Torikai Y, et al. Effective nose-to-brain drug delivery using a combination system targeting the olfactory region in monkeys. Journal of Controlled Release. 2023;359:384-399. https://doi.org/10.1016/j.jconrel.2023.06.005 PMid:37315691
7. Huang WH, Hung YW, Hung W, Lan MY, Yeh CF. Murine model of eosinophilic chronic rhinosinusitis with nasal polyposis inducing neuroinflammation and olfactory dysfunction. Journal of Allergy and Clinical Immunology. 2024;154(2):325-339.e3. https://doi.org/10.1016/j.jaci.2024.02.021 PMid:38494093
8. Mathias K, Petronilho F, Danielski LG. Nose-to-brain axis: mechanistic links between nasal microbiome dysbiosis, neuroinflammation, and brain disorders. Neuroscience. 2026;598:19-28. https://doi.org/10.1016/j.neuroscience.2026.01.039 PMid:41619875
9. Chiang H, Martin HL, Sicard RM, Frank-Ito DO. Olfactory drug delivery with intranasal sprays after nasal midvault reconstruction. Int J Pharm. 2023;644:123341. https://doi.org/10.1016/j.ijpharm.2023.123341 PMid:37611854 PMCid:PMC10621325
10. Peng H, Zhang J, Nie W, et al. Multiscale dynamics of respirable coal dust deposition in Miners’ Airways: Effects of respiratory intensity, particle size, and density on pulmonary retention. Powder Technol. 2026;468:121569. https://doi.org/10.1016/j.powtec.2025.121569
11. Kong X, Wang G, Wei S, et al. Macro-micro spray characteristics of nasal spray: Bridging physicochemical properties to precision olfactory delivery. Chinese Chemical Letters. 2026;37(10):112085. https://doi.org/10.1016/j.cclet.2025.112085
12. Seifelnasr A, Si XA, Xi J. Quantitative Investigation of Synthetic Mucus Effects on Spray Deposition in a 3D-Printed SLA Nasal Cavity Model. Pharm Res. 2025;42(7):1135-1152. https://doi.org/10.1007/s11095-025-03886-4 PMid:40562873
13. Wu S, Huang Y, Chen W, et al. Determinants of olfactory cleft targeting in intranasal aerosol delivery: a combined computational and experimental study. European Archives of Oto-Rhino-Laryngology. Published online June 6, 2026. https://doi.org/10.1007/s00405-026-10361-2
14. Ahmed K, Kumar Dubey M, Kumar A, Dubey S. Artificial intelligence and IoT driven system architecture for municipality waste management in smart cities: A review. Measurement: Sensors. 2024;36:101395. https://doi.org/10.1016/j.measen.2024.101395
15. Radzio J, Suprewicz Ł, Kuang D, et al. Reversibly-sealable microfluidic platform for multi-molecule gradient delivery to large adherent cell cultures. Biomed Microdevices. 2026;28(3):50. https://doi.org/10.1007/s10544-026-00831-z PMid:42307820 PMCid:PMC13275633
16. Seifelnasr A, Zare F, Si XA, Xi J. Optimized gravity-driven intranasal drop administration delivers significant doses to the ostiomeatal complex and maxillary sinus. Drug Deliv Transl Res. 2024;14(7):1839-1859. https://doi.org/10.1007/s13346-023-01488-4 PMid:38044376
17. Wang G, Yi H, Kong X, et al. A “three-in-one” nose-to-brain delivery strategy: intranasal vancomycin spray achieves simultaneous clearance of pneumococcal colonization, bacteremia, and meningitis. Int J Pharm. 2026;701:127148. https://doi.org/10.1016/j.ijpharm.2026.127148 PMid:42401303
18. Yan R, Zou C, Yang X, et al. Nebulized inhalation drug delivery: clinical applications and advancements in research. J Mater Chem B. 2025;13(3):821-843. https://doi.org/10.1039/D4TB01938E PMid:39652178
19. Salgado C, Guénée L, Černý R, Allémann E, Jordan O. Nano wet milled celecoxib extended release microparticles for local management of chronic inflammation. Int J Pharm. 2020;589:119783. https://doi.org/10.1016/j.ijpharm.2020.119783 PMid:32827674
20. Tao Y, Wang Z, Xu H, et al. Moisture-powered memristor with interfacial oxygen migration for power-free reading of multiple memory states. Nano Energy. 2020;71:104628. https://doi.org/10.1016/j.nanoen.2020.104628
21. Palmer JN, Adappa ND, Chandra RK, et al. Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2). J Allergy Clin Immunol Pract. 2024;12(4):1049-1061. https://doi.org/10.1016/j.jaip.2023.12.016 PMid:38244014
22. Yuan CS, Hsu CW, Cheng WH, Huang BY, Jiang Y. Optimizing the droplet size distribution of personal nebulizers to enhance the effectiveness of inhalation using 3D printing technology. J Drug Deliv Sci Technol. 2026;115:107667. https://doi.org/10.1016/j.jddst.2025.107667
23. Casillas JEJ, Valle LF, Pham J, et al. Advancing Prostate Cancer Treatment: A Review of CT and MR-Guided Online Adaptive Radiotherapy Techniques. Semin Radiat Oncol. 2025;35(3):342-352. https://doi.org/10.1016/j.semradonc.2025.04.007 PMid:40516969
24. Economidou SN, Uddin MdJ, Marques MJ, et al. A novel 3D printed hollow microneedle microelectromechanical system for controlled, personalized transdermal drug delivery. Addit Manuf. 2021;38:101815. https://doi.org/10.1016/j.addma.2020.101815
25. Lobo S, Xi Z, Das D, Hadzimichalis NM, Creek JA. Intranasal Delivery: Formulation Factors and Insights Into User Experience. AAPS PharmSciTech. 2025;26(6):179. https://doi.org/10.1208/s12249-025-03171-y PMid:40593387
26. Keller LA, Merkel O, Popp A. Intranasal drug delivery: opportunities and toxicologic challenges during drug development. Drug Deliv Transl Res. 2022;12(4):735-757. https://doi.org/10.1007/s13346-020-00891-5 PMid:33491126 PMCid:PMC7829061
27. Maaz A, Blagbrough IS, De Bank PA. In Vitro Evaluation of Nasal Aerosol Depositions: An Insight for Direct Nose to Brain Drug Delivery. Pharmaceutics. 2021;13(7):1079. https://doi.org/10.3390/pharmaceutics13071079 PMid:34371770 PMCid:PMC8309016
28. Ma R, Sun S, Wang Y, et al. Optimizing topical delivery to the ostiomeatal complex after functional endoscopic sinus surgery using a bidirectional delivery method. Int J Pharm. 2025;686:126333. https://doi.org/10.1016/j.ijpharm.2025.126333 PMid:41187831
29. Wakayama K, Kurihara S, Kurashina Y. Narrow-width surface acoustic wave device-driven olfactory epithelium-targeted intranasal atomization. Int J Pharm. 2026;692:126630. https://doi.org/10.1016/j.ijpharm.2026.126630 PMid:41611042
30. Fong TYA, Thirugnanasampanthar M, Iley T, Parry M, Forbes B. The effect of spray properties and inspiratory flow rate on regional nasal deposition for pressure-swirl versus soft mist devices. Int J Pharm. 2026;700:126991. https://doi.org/10.1016/j.ijpharm.2026.126991 PMid:42208825
31. Cheng D, Pan T, Wang X, et al. An advanced inhalable dry powder, mucus-penetrating aerosol platform: Bridging Andrographolide delivery with clinical translation. Biomaterials. 2025;322:123401. https://doi.org/10.1016/j.biomaterials.2025.123401 PMid:40347852
32. Sosnowski TR, Florkiewicz E, Sosnowski K. Use of process intensification concepts for targeted delivery of inhaled aerosolized medicines. Chemical Engineering and Processing - Process Intensification. 2024;203:109902. https://doi.org/10.1016/j.cep.2024.109902
33. Cheepu M, Yenumula P, Shanmugam R. Progression in 3D printing families: laser, powder, nozzle-based techniques. In: Advances in 3D and 4D Printing of Medical Robots and Devices. Elsevier; 2025:57-73. https://doi.org/10.1016/B978-0-443-24861-0.00004-6
34. Pethappachetty P, Kumar B, Govindaraj A, et al. 3D Printing in Personalized Medicine: Revolutionizing Drug Delivery and Healthcare Applications. Biomedical Materials & Devices. 2026;4(4):4219-4240. https://doi.org/10.1007/s44174-025-00514-y
35. Li L, Relling ME, Islam S, et al. Optimization of nozzle geometry for virtual impaction across more than one decade in particle size. J Aerosol Sci. 2025;184:106516. https://doi.org/10.1016/j.jaerosci.2024.106516
36. Chaugule V, dos Reis LG, Fletcher DF, Young PM, Traini D, Soria J. A varying-swirl design concept for dry powder inhalers. J Aerosol Sci. 2023;171:106162. https://doi.org/10.1016/j.jaerosci.2023.106162
37. Weissburg M. Biologically Inspired Chemical Plume Tracking. In: 2026:285-314. https://doi.org/10.1007/978-3-032-11949-0_9
38. Comparative analysis of drug deposition patterns among three commercial nasal spray brands: A computational and experimental study.
39. Warfield-McAlpine P, Fletcher DF, Zhang F, Inthavong K. Increasing airflow ventilation in a nasal maxillary ostium using optimised shape and pulsating flows. Biomech Model Mechanobiol. 2025;24(4):1343-1362. https://doi.org/10.1007/s10237-025-01971-6 PMid:40562978 PMCid:PMC12246003
40. Ghodsi SH, Zahmatkesh Z, Goharian E, Kerachian R, Zhu Z. Optimal design of low impact development practices in response to climate change. J Hydrol (Amst). 2020;580:124266. https://doi.org/10.1016/j.jhydrol.2019.124266
41. Jia W, Pang Y, Zhao C, et al. Low drug load, high retention mometasone furoate cream with polyglyceryl − 3 oleate as a chemical enhancer: Formulation development, in vivo and in vitro evaluation and molecular mechanisms. Int J Pharm. 2024;659:124284. https://doi.org/10.1016/j.ijpharm.2024.124284 PMid:38810934
42. Bedhiafi T, Idoudi S, Alhams AA, et al. Applications of polydopaminic nanomaterials in mucosal drug delivery. Journal of Controlled Release. 2023;353:842-849. https://doi.org/10.1016/j.jconrel.2022.12.037 PMid:36529384
43. Liu Z, Huang J, Li P, et al. High-precision inkjet 3D printing of curved multi-material structures: Morphology evolution and optimization. Addit Manuf. 2024;94:104497. https://doi.org/10.1016/j.addma.2024.104497
44. Candeloro BM, Oliveira NS, Franchi AC, et al. Systematic Review and Meta-analysis to Investigate the Effects of Cannabidiol on Blood Pressure: Examination of Randomized Triple- and Double-Blind Placebo Trials. Revista Brasileira de Farmacognosia. 2025;35(5):878-893. https://doi.org/10.1007/s43450-025-00680-6
45. Sinatra ST., Houston MC. Nutritional and Integrative Strategies in Cardiovascular Medicine. CRC Press; 2022. https://doi.org/10.1201/9781003137849
46. Bi-directional nasal drug delivery systems: A scoping review of nasal particle deposition patterns and clinical application.
47. Gallina A, Gallina M, Cona A, Vitulo P, Mularoni A, Provenzani A. Phage Therapy at the Crossroads Between Clinical Promise and Regulatory Challenge. Pharmaceuticals. 2026;19(1):162. https://doi.org/10.3390/ph19010162 PMid:41599759 PMCid:PMC12845414
48. Salmanipour S, Salmani Pour Avval S, Inthavong K, Hamishehkar H. Numerical Investigation to Improve Pulmonary Drug Delivery via Dry Powder Inhalers: A Review of In-Silico Modeling. Pharm Res. 2025;42(8):1251-1283. https://doi.org/10.1007/s11095-025-03906-3 PMid:40813932
49. Silva AC. Current Clinical Evidence on Nose-to-Brain Drug Delivery. Drug Discov Today. 2026;31(5):104765. https://doi.org/10.1016/j.drudis.2026.104765 PMid:42580438
50. Bailey DL, Hennessy TM, Willowson KP, et al. In vivo quantification of 177Lu with planar whole-body and SPECT/CT gamma camera imaging. EJNMMI Phys. 2015;2(1):20. https://doi.org/10.1186/s40658-015-0123-2 PMid:26501821 PMCid:PMC4573647
51. D’Angelo D, Kooij S, Verhoeven F, Sonvico F, van Rijn C. Fluorescence-enabled evaluation of nasal tract deposition and coverage of pharmaceutical formulations in a silicone nasal cast using an innovative spray device. J Adv Res. 2023;44:227-232. https://doi.org/10.1016/j.jare.2022.04.011 PMid:36725192
52. Zhang J, Hu Y, Qin H, et al. Flexible skull-conformal phased array for aberration-corrected transcranial focused ultrasound therapy. Ultrasonics. 2026;165:108089. https://doi.org/10.1016/j.ultras.2026.108089 PMid:41936163
53. Doub WH, Suman JM, Copley M, Goodey AP, Hosseini S, Mitchell JP. Laboratory Performance Testing of Aqueous Nasal Inhalation Products for Droplet/Particle Size Distribution: an Assessment from the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS). AAPS PharmSciTech. 2023;24(7):208. https://doi.org/10.1208/s12249-023-02665-x PMid:37817001
54. Nannu Shankar S, Vass WB, Lednicky JA, et al. The BioCascade-VIVAS system for collection and delivery of virus-laden size-fractionated airborne particles. J Aerosol Sci. 2024;175:106263. https://doi.org/10.1016/j.jaerosci.2023.106263 PMid:38680161 PMCid:PMC11044810
55. Yang T, Bai S. In Vitro to In Vivo Extrapolation for Drug Delivery to the Brain. Curr Pharmacol Rep. 2025;11(1):56. https://doi.org/10.1007/s40495-025-00437-8
56. Gholizadeh H, Cheng S, Kourmatzis A, et al. In vitro interactions of aerosol formulations with human nasal epithelium using real-time monitoring of drug transport in a nasal mucosa-on-a-chip. Biosens Bioelectron. 2023;223:115010. https://doi.org/10.1016/j.bios.2022.115010 PMid:36586150
57. Jain H, Prabhakar B, Shende P. Modulation of olfactory area for effective transportation of actives in CNS disorders. J Drug Deliv Sci Technol. 2022;68:103091. https://doi.org/10.1016/j.jddst.2021.103091
58. Zhang Y, Zhang Z, Zhang X, et al. Machine learning guided design and ablation behavior of ZrC-TaC-SiC ternary coatings. Corros Sci. 2026;260:113499. https://doi.org/10.1016/j.corsci.2025.113499
59. Camacho-Lie M, Antonio-Gutiérrez O, López-Díaz AS, López-Malo A, Ramírez-Corona N. Factors influencing droplet size in pneumatic and ultrasonic atomization and its application in food processing. Discover Food. 2023;3(1):23. https://doi.org/10.1007/s44187-023-00065-5
60. Hernández-Cid D, Pérez-González VH, Gallo-Villanueva RC, González-Valdez J, Mata-Gómez MA. Modeling droplet formation in microfluidic flow-focusing devices using the two-phases level set method. Mater Today Proc. 2022;48:30-40. https://doi.org/10.1016/j.matpr.2020.09.417
61. Ciloglu D. The airflow and the regional particle behavior in a human airway under the circulatory breathing conditions: A numerical study. J Drug Deliv Sci Technol. 2024;99:105978. https://doi.org/10.1016/j.jddst.2024.105978
62. Godasiaei SH, Kamali H. Water jet angle prediction in supersonic crossflows: Euler-Lagrange and machine learning approaches. The European Physical Journal Plus. 2024;139(3):251. https://doi.org/10.1140/epjp/s13360-024-05047-9
63. Samadian H, Kakaei N, Karami M, et al. Multi-effect formulation based on pH-Responsive psyllium Mucilage/Poly(vinyl alcohol) nanofibers for controlled delivery of mesalamine. J Drug Deliv Sci Technol. 2024;92:105348. https://doi.org/10.1016/j.jddst.2024.105348
64. Samadian H, Kakaei N, Karami M, et al. Multi-effect formulation based on pH-Responsive psyllium Mucilage/Poly(vinyl alcohol) nanofibers for controlled delivery of mesalamine. J Drug Deliv Sci Technol. 2024;92:105348. https://doi.org/10.1016/j.jddst.2024.105348
65. Xu Y, Harinck L, Lokras AG, et al. Leucine improves the aerosol performance of dry powder inhaler formulations of siRNA-loaded nanoparticles. Int J Pharm. 2022;621:121758. https://doi.org/10.1016/j.ijpharm.2022.121758 PMid:35483619
66. Haughney J, Lee AJ, McKnight E, Pertsovskaya I, O’Driscoll M, Usmani OS. Peak Inspiratory Flow Measured at Different Inhaler Resistances in Patients with Asthma. J Allergy Clin Immunol Pract. 2021;9(2):890-896. https://doi.org/10.1016/j.jaip.2020.09.026 PMid:33011302
67. Hejazi M, Alshammary AM, Edwards DJ, Golshahi L. Development of a predictive model for pediatric intranasal drug delivery with nasal sprays: Leveraging intersubject variability in anatomical dimensions, administration-related parameters, and airway patency. Comput Biol Med. 2025;187:109746. https://doi.org/10.1016/j.compbiomed.2025.109746 PMid:39879885 PMCid:PMC12435185
68. Rajendran J, Esfandyarpour R. Revolutionizing Personalized Health: The Frontier of Wearable Biomolecule Sensors Through 3D Printing Innovation. Biomedical Materials & Devices. 2025;3(2):818-834. https://doi.org/10.1007/s44174-024-00226-9
69. Agarwal B, Gaware S, More N, Shinde R, Shivakumar HN, Jagdale S. A review exploring the translational perspective of artificial intelligence in drug discovery and formulation development. Ann Pharm Fr. 2026;84(4):559-594. https://doi.org/10.1016/j.pharma.2026.01.007 PMid:41653969
70. Karthikeyan S, Raja S, Balasubramanian V, Rusho MA, Shankar K V. Integrating Machine Learning Approach into Plasma-Sprayed Lanthanum Zirconate Coatings for Thermal Barrier Applications. Journal of Thermal Spray Technology. 2026;35(4):955-979. https://doi.org/10.1007/s11666-026-02163-z
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