Available online on 15.09.2026 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2026 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access Full Text Article                                                   Review Article

Impact of Nasal Delivery Devices on Olfactory Drug Deposition

Niharika Sahu ², Ruchi Gupta¹, Rupesh Sahu³, Rahul Dev ¹, Dharmendra Sahu¹, Shiv Kumar Bhardwaj ^3*

¹ Gracious College of Pharmacy, Village-Belbhata, Abhanpur, Raipur-493661, Chhattisgarh, India

² Columbia College of Pharmacy, Columbia Professional University, Tekari, Near Vidhansabha Road, Raipur-493111, Chhattisgarh, India

³ Columbia Institute of Pharmacy, Columbia Professional University, Tekari, Near Vidhansabha Road, Raipur-493111, Chhattisgarh, India

Highlights

• Device parameters influence aerodynamic transport and olfactory deposition.
• Optimized plume geometry and airflow can reduce anterior nasal impaction.
• Formulation properties affect aerosolization, deposition and mucosal retention.
• Patient anatomy and technique influence regional nasal drug deposition. 
• Advanced devices may enhance olfactory targeting and nose-to-brain delivery.

1. Introduction

The nasal route has attracted considerable interest as a non-invasive pathway for delivering drugs to the central nervous system because the olfactory epithelium provides anatomical connectivity with the brain.¹ However, achieving therapeutically meaningful deposition in the olfactory region remains difficult because the nasal valve, turbinates, complex nasal geometry, mucus layer and mucociliary clearance can divert formulations toward the anterior cavity or nasopharynx.² Conventional nasal sprays generally produce greater deposition in the anterior and middle nasal regions, whereas specialized devices attempt to improve delivery toward the superior/posterior nasal cavity.³ Device-related parameters-including nozzle geometry, spray angle, plume width, droplet size, velocity, airflow and administration technique-therefore represent critical determinants of olfactory deposition.⁴ Recent research has increasingly shifted from simply selecting an intranasal formulation toward integrating formulation characteristics with device engineering and patient-specific administration.⁵ Advanced breath-powered, bidirectional, atomization-based and personalized devices offer opportunities for more reproducible olfactory targeting.⁶ 

2. Nasal anatomy and the olfactory target

The nasal cavity is anatomically organized into the vestibular, respiratory and olfactory regions, with the olfactory epithelium predominantly located in the superior nasal cavity around the olfactory cleft.⁷ This region is an important target for nose-to-brain delivery because its olfactory neurons provide a potential anatomical route toward the central nervous system.⁸ However, achieving selective and efficient olfactory deposition remains challenging because of the nasal valve, complex turbinate structure, narrow olfactory cleft, limited olfactory surface area, mucociliary clearance, inter-individual anatomical variability, anterior leakage or swallowing and device-dependent aerosol behavior.⁹

3. Device-dependent determinants of olfactory deposition

3.1 Droplet/particle size

Particle or droplet size strongly influences nasal deposition. Very large droplets tend to impact the anterior nasal cavity, whereas smaller particles may penetrate deeper into the nasal passage depending on airflow and aerodynamic characteristics. Human nasal-cast and computational studies have identified particle size and flow conditions as important variables governing olfactory deposition.¹⁰

3.2 Plume geometry

A narrow and appropriately directed plume can improve penetration toward the superior/posterior nasal cavity. Plume angle and spray direction therefore represent important device-design variables.¹¹ 

3.3 Airflow

Controlled airflow can transport aerosol beyond the nasal valve and improve posterior deposition. Breath-powered bidirectional devices are particularly relevant because exhaled airflow can facilitate movement toward the upper nasal regions while reducing unwanted pulmonary or oropharyngeal delivery.¹² 

3.4 Nozzle orientation

Nozzle position and insertion angle affect the trajectory of the emitted formulation. Incorrect orientation can increase anterior deposition and reduce access to the olfactory cleft.¹³

3.5 Administration technique

Head position, breathing pattern, dose volume, nostril selection and administration angle can substantially alter regional deposition. Thus, device performance cannot be considered independently of user technique.¹⁴ Figure 1 illustrates the key factors governing nasal drug deposition and potential nose-to-brain transport, highlighting the influence of device, formulation and patient parameters on aerodynamic transport, olfactory deposition, mucosal retention and subsequent delivery toward the central nervous system.

Figure 1. Anatomical and mechanistic basis of olfactory drug deposition

(Schematic illustration of nasal anatomy, conventional versus optimized deposition and the potential pathway of drug transport from the olfactory epithelium to the brain.)

4. Classification of nasal delivery devices

Table 1. Major nasal delivery devices and their deposition characteristics

5. Impact of conventional nasal devices

Conventional metered-dose nasal sprays are widely used because of their portability, dose reproducibility, ease of administration and rapid drug delivery.²⁴ However, the generated aerosol plume may undergo inertial impaction at the nasal valve and anterior nasal structures, resulting in predominant anterior deposition followed by mucociliary clearance or swallowing and consequently reducing drug exposure to the olfactory region.²⁵ Therefore, despite their established clinical utility, conventional nasal sprays have limited ability to achieve selective and efficient olfactory targeting.²⁶ Figure 2 highlights the major device, formulation and patient-related factors that influence aerodynamic drug transport within the nasal cavity, determining whether deposition occurs predominantly in the anterior region or is directed toward the superior/posterior olfactory region, thereby affecting mucosal retention and the potential for nose-to-brain drug transport.

6. Advanced devices for olfactory targeting

Table 2. Advanced device strategies for improving olfactory deposition

Figure 2. Device-formulation-deposition relationship

(Schematic representation of device, formulation and patient factors influencing aerodynamic transport, olfactory deposition, mucosal retention and potential nose-to-brain delivery).

7. Comparative evaluation of device performance

Table 3. Factors influencing olfactory deposition

8. Breath-powered and bidirectional delivery

Breath-powered and bidirectional nasal delivery systems are promising approaches for olfactory targeting, as they use controlled airflow rather than relying solely on mechanical spray momentum to transport formulations deeper into the nasal cavity.⁴⁵ Experimental evidence suggests that bidirectional administration can enhance deposition in the upper and posterior nasal regions compared with conventional unilateral spray delivery, with one study reporting approximately 32% upper-posterior deposition using a bidirectional device compared with 11% using a conventional spray pump.⁴⁶ Thus, these systems may help overcome a key limitation of conventional nasal delivery-insufficient penetration beyond the nasal valve.⁴⁷

9. Computational and experimental assessment

Table 4. Methods for evaluating olfactory drug deposition

10. Formulation-device interaction

Device optimization alone may not ensure enhanced olfactory deposition, as formulation characteristics-including viscosity, surface tension, density, particle size, muco-adhesion and rheological properties-also influence aerosolization and subsequent nasal transport.⁵⁶ Therefore, effective olfactory targeting requires coordinated optimization of both formulation and device attributes.⁵⁷ Recent studies combining machine-learning approaches with experimental optimization further suggest that formulation and spray characteristics can be jointly optimized to improve drug deposition in the olfactory region.⁵⁸

Table 5. Formulation-device interactions affecting olfactory deposition

11. Emerging personalized nasal delivery

A major future direction in olfactory drug delivery is the development of patient-specific nasal delivery systems, as considerable inter-individual variation in nasal anatomy can influence regional drug deposition and may limit the reproducibility of conventional devices.⁶⁷ Recent approaches have explored 3D-printed personalized devices designed to position drug-loaded formulations toward the olfactory region; however, their clinical translation still requires extensive human validation, particularly regarding drug-loading capacity and reproducibility.⁶⁸ In parallel, artificial intelligence (AI) and machine-learning (ML) techniques offer opportunities for individualized optimization by integrating patient anatomy, formulation properties, device parameters and deposition outcomes.⁶⁹ Such data-driven approaches may enable more precise prediction and optimization of olfactory deposition and support the development of anatomy-guided nasal delivery systems. Recent research has also demonstrated the potential of ML-assisted optimization of nasal spray characteristics for improving olfactory-region deposition.⁷⁰

12. Current challenges and future perspectives

A key challenge in evaluating nose-to-brain delivery is that an increase in brain drug concentration does not necessarily confirm direct olfactory transport, because systemically absorbed drug may also reach the brain through the circulation. Therefore, future research should prioritize standardized olfactory-deposition metrics, patient-specific nasal models, validated CFD simulations, device–formulation co-optimization, reproducible administration techniques, long-term nasal safety and human imaging and pharmacokinetic validation. In addition, AI-assisted device optimization and regulatory standardization are needed to improve the reproducibility and clinical translation of advanced nasal delivery systems. Establishing a clear correlation between olfactory deposition and actual CNS exposure will be particularly important for demonstrating therapeutic relevance. Overall, translation remains challenging because laboratory models may not adequately reproduce human nasal anatomy and physiology, while standardized methods for characterizing regional deposition are still limited.

13. Conclusion

Nasal delivery devices are a critical determinant of olfactory drug deposition and consequently influence the potential effectiveness of nose-to-brain drug delivery. Conventional nasal sprays generally Favor anterior deposition, whereas specialized approaches-including breath-powered, bidirectional, atomization-based, powder and personalized devices-can improve transport toward the superior and posterior nasal cavity. Device parameters such as droplet size, plume geometry, spray velocity, nozzle orientation, airflow and dose volume must be optimized together with formulation properties and administration technique. Evidence from nasal-cast studies, CFD modeling, imaging and experimental investigations supports the concept that rational device engineering can substantially improve regional deposition. However, enhanced olfactory deposition should not automatically be interpreted as proof of direct brain delivery. Future progress will depend on patient-specific device design, formulation-device integration, standardized deposition assessment, AI-assisted optimization, and well-designed clinical studies. Thus, the future of olfactory drug delivery is likely to shift from conventional nasal administration toward precision, anatomy-guided and digitally optimized delivery systems.

Abbreviations:

AI : Artificial Intelligence
BBB : Blood Brain Barrier
CNS : Central Nervous System
CFD : Computational Fluid Dynamics
CT : Computed Tomography
CNS : Central Nervous System
CNSD : Central Nervous System Delivery
DP : Dry Powder
DPI : Dry Powder Inhaler
FDA : Food and Drug Administration
GIT : Gastrointestinal Tract
HPLC : High-Performance Liquid Chromatography
IV : Intravenous
LC-MS/MS : Liquid Chromatography-Tandem Mass Spectrometry
MD : Molecular Dynamics
ML : Machine Learning
MRI : Magnetic Resonance Imaging
N2B : Nose-to-Brain
NDD : Nasal Drug Delivery
NDS : Nasal Delivery System
PK : Pharmacokinetics
PD : Pharmacodynamics
PDE : Partial Differential Equation
PDI : Polydispersity Index
SEM : Scanning Electron Microscopy
TEM : Transmission Electron Microscopy
TGI : Trigeminal–Olfactory Interface
USP : United States Pharmacopeia
3D : Three-Dimensional

Declaration:

Ethics approval and consent to participate:

Ethical approval and informed consent were not applicable to this study because it was a narrative literature review that did not involve any original research involving human participants or animals.

Clinical Trial No:

As this manuscript is a narrative review based exclusively on previously published literature and does not involve any clinical trials, clinical trial registration was not required.

Consent for publication:

Clinical trial registration was not required because this manuscript is based solely on a narrative review of previously published literature and does not involve any clinical trials.

Availability of data and material:

Data availability was not applicable because this manuscript is a narrative review based solely on previously published literature and does not involve the generation or analysis of original datasets.

Funding:

The authors declare that no dedicated financial support was received from any governmental, commercial, or non-profit organization for the preparation of this review.

Declaration of competing interest: The authors declare that there are no conflicts of interest  

regarding  the publication of this manuscript.

Acknowledgements: 

The authors sincerely acknowledge the Principals of Columbia Institute of Pharmacy, Columbia Professional University, Raipur, Chhattisgarh, India and Gracious College of Pharmacy, Village Belbhata, Abhanpur, Raipur, Chhattisgarh, India, for their valuable encouragement, support and provision of the necessary infrastructure and library facilities that contributed to the successful completion of this review.

Authorship contribution statement:

Niharika Sahu: Writing -review & editing

Ruchi Gupta: Visualization, schematic design, graphical abstract development and figure illustration.

Rupesh Sahu: Literature review, data curation, validation & manuscript evaluation

Rahul Dev: Manuscript writing, review & editing and critical revision

Dharmendra Sahu: Concept development, methodology & critical review

Shiv Kumar Bhardwaj: Writing, methodology, visualization & final editing

References:

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