The DOI matches its Crossref record; 246 of the 255 references it cites were found in a registry or an index.
Nasal mucociliary clearance as a factor in nasal drug delivery
Abstract
The nasal mucociliary clearance system transports the mucus layer that covers the nasal epithelium towards the nasopharynx by ciliary beating. Its function is to protect the respiratory system from damage by inhaled substances. Impairment of nasal mucociliary clearance can result in diseases of the upper airways. Therefore, it is important to study the effects of drugs and drug excipients on nasal mucociliary clearance. A large number of methods are used to assess mucociliary clearance. These methods study the effects of drug and excipients on the mucociliary system in vitro or in vivo in animals and humans. In some cases, the results of different in vitro and in vivo measurements do not correlate well. In vitro methods, especially ciliary beat frequency measurements, have been demonstrated to be valuable tools for toxicity screening. However, in vivo studies are essential to confirm the safety of nasal drug formulations. Nasal mucociliary clearance also has implications for nasal drug absorption. Drugs are cleared rapidly from the nasal cavity after intranasal administration, resulting in fast systemic drug absorption. Several approaches are discussed to increase the residence time of drug formulations in the nasal cavity, resulting in improved nasal drug absorption. However, more experimental evidence is needed to support the conclusion that this improved absorption is caused by a longer residence time of the nasal drug formulation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Samples taken from 30 minutes onwards, however, cannot reflect spiking, as substances that are not absorbed across the nasal membrane are transported to the back of the throat, and then swallowed within 15 minutes [14].”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [14]
In the citing paper
“Hence, taking saliva samples at 15 minutes creates the risk of collecting saliva that is ‘spiked’ with IN-OT (indeed this may be why other saliva studies have chosen 30 minutes as their first measurement, as this allows almost double the length of time of average mucociliary transport [14]).”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [14]
In the citing paper
“This process of clearing substances from the nasal cavity to the back of the throat, called mucociliary transport, takes 12–15 minutes in healthy individuals [14].”
From Salivary oxytocin concentrations in males following intranasal administration of oxytocin: a double-blind, cross-over study (2015) · cites this paper as [14]
Citations
Cites
The Lung: Scientific Foundations
(1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-115-6-503_2 · Cited by 1,183
Mucociliary Clearance in the Airways
Wanner, A., Salathe, M. A., & O’Riordan, T. G. (1996) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.154.6.8970383 · Cited by 738
Adenosine Triphosphate-Induced Sliding of Tubules in Trypsin-Treated Flagella of Sea-Urchin Sperm
Summers, K. E., & Gibbons, I. R. (1971) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.68.12.3092 · Cited by 700
Chitosan as a Novel Nasal Delivery System for Peptide Drugs
Illum, L., Farraj, N. F., & Davis, S. S. (1994) · Pharmaceutical Research · doi:10.1023/a:1018901302450 · Cited by 630
The Propulsion of Mucus by Cilia
Sleigh, M. A., Blake, J. R., & Liron, N. (1988) · American Review of Respiratory Disease · doi:10.1164/ajrccm/137.3.726 · Cited by 580
Satir, P. (1968) · The Journal of Cell Biology · doi:10.1083/jcb.39.1.77 · Cited by 556
Ciliary activity of cultured rabbit tracheal epithelium: beat pattern and metachrony
Sanderson, M. J., & Sleigh, M. A. (1981) · Journal of Cell Science · doi:10.1242/jcs.47.1.331 · Cited by 358
Clinical aspects of mucociliary transport.
Wanner, A. (1977) · PubMed · doi:10.1164/arrd.1977.116.1.73 · Cited by 356
McMartin, C., Hutchinson, L. E. F., Hyde, R. J., & Peters, G. E. (1987) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.2600760709 · Cited by 349
Goblet Cells Secretion And Mucogenesis
Verdugo, P. (1990) · Annual Review of Physiology · doi:10.1146/annurev.ph.52.030190.001105 · Cited by 298
Research works printed but not linked: 10
- Lansley, 1990, Changes in the duration of the effective, recovery and rest phases of the ciliary beat cycle induced by intracellular cAMP and Ca2+, J. Cell Biol., 111, 170a
- Sanderson, 1993, Measurement of the temperospatial dynamics of intercellular calcium signalling with digital fluorescence microscopy, Am. Lab., 25, 29
- Coles, 1983, Effect of topical nasal medications on human nasal ciliary function, Eur. J. Respir. Dis., 126, 121
- Su, 1994, Surface–response study of the effect of pH and tonicity on ciliary activity, STP Pharma. Sci., 4, 82
- King, 1974, On the transport of mucus and its rheological simulants in ciliated system, Am. Rev. Respir. Dis., 110, 740
- Klimek, 1995, Therapeutic management of mucociliary transport disturbances in allergic rhinitis, Eur. Respir. J., 8, 1298
- Hermens, 1987, The in vitro effect of morphine, fentanyl and sufentanil on ciliary beat frequency of human nasal epithelial tissue, Acta Pharm. Technol., 33, 88
- Gizurarson, 1990, Animal models for intranasal drug delivery studies, Acta Pharm. Nord., 2, 105
- Parr, 1983, Nasal delivery of drugs, Pharm. Int., 4, 202
- Ridley, 1995, The effect of posture on nasal clearance of bioadhesive starch microspheres, STP Pharma. Sci., 5, 442
Cited by
Sorted by citations
Items 401–466 of 466
Nasal versus sublingual routes for emergency drug administration
Debe, M. S., Khan, S. A., Ahmed, I. S., Hussain, Z., Uddin, M. N., & Rawas‐Qalaji, M. (2025) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2025.103903 · Cited by 2
Complete Review on Nasal Drug Delivery Systems
Kumari, N., Kalyanwat, R., & Singh, V. K. (2013) · Cited by 1
Sino-Nasal Status in Patients with Chronic Obstructive Pulmonary Disease
Singh, A. K., Gupta, S. K., Jain, V., Mishra, M. K., & Ojha, T. (2022) · The Indian Journal of Chest Diseases and Allied Sciences · doi:10.5005/ijcdas-58-2-99 · Cited by 1
Nose-to-Brain Targeted Drug Delivery Bypassing the Blood-Brain Barrier
Pandey, M. (2022) · Advances in bioinformatics and biomedical engineering book series · doi:10.4018/978-1-7998-8908-3.ch007 · Cited by 1
der Glas, S. M. D.-V., & Hafner, A. (2015) · Springer eBooks · doi:10.1007/978-3-319-15814-3_8 · Cited by 1
Cytochrome P450-mediated drug metabolizing activity in the nasal mucosa
Dhamankar, V. (2013) · doi:10.17077/etd.9ozi7j61 · Cited by 1
Nasal Delivery of Peptide and Nonpeptide Drugs
Thomas, C., & Ahsan, F. (2010) · Pharmaceutical Sciences Encyclopedia · doi:10.1002/9780470571224.pse355 · Cited by 1
Polymer-based delivery systems for support and delivery of bacteriophages
Brown, A. M. (2014) · doi:10.31274/etd-180810-2525 · Cited by 1
Nasal delivery system for peptide drugs: market trend and technology development
Morita, T., & Yamahara, H. (2006) · Drug Delivery System · doi:10.2745/dds.21.426 · Cited by 1
Spray Away Allergies – Modeling Intranasal Drug Delivery
Hannanta‐anan, P., Krupa, O., & Yi, J. J. (2012) · eCommons (Cornell University)
AN OVER VIEW: MICROSPHERES AS A NASAL DRUG DELIVERY SYSTEM Review Article
Chaudhari, A., & Mumbai, N. (2010)
Review Article Emerging Trends in Novel Drug Delivery System: Intra Nasal Drug Delivery
Buvaneswari, G. (2016)
Jamoh, A. (2016) · IOSR Journal of Dental and Medical Sciences · doi:10.9790/0853-150755961
Júnior, S. R. D. S. (2018) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2018.tde-24082018-141104
Aleysae, N. A. (2019) · Emergency Care Journal · doi:10.4081/ecj.2019.8320
Obulesu, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-819882-7.00008-8
Mucoadhesive Systems: Drug Delivery
Donnelly, R. F., Ryan, E., Singh, T. R. R., & Woolfson, A. D. (2015) · Taylor & Francis eBooks · doi:10.1081/e-ebpp-120050247
Ludwig, A., & der Glas, S. M. D.-V. (2009) · Bohn Stafleu van Loghum eBooks · doi:10.1007/978-90-313-8032-9_30
(2000) · CRC Press eBooks · doi:10.1201/9780203483701.ch9
Li, H., Tian, M., Wang, C.-L., Zhou, J., Wang, Z.-G., Zhang, W., Qi, X., & Duan, L. (2023) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2023.104223
Nasal Delivery of Micro and Nano Encapsulated Drugs
Sarfraz, M., Mousa, S., Saoud, R. A., & Löbenberg, R. (2023) · Springer eBooks · doi:10.1007/978-3-031-23112-4_16
Vu, T. H. N., Morozkina, S. N., Snetkov, P., & Uspenskaya, M. V. (2023) · Advanced clinical pharmacy - research, development and practical applications/Advanced clinical pharmacy - research, development and practical applications · doi:10.1007/978-3-031-26908-0_16
Santos, S. R. D. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2022.tde-22062023-154055
Gonçalves, B. R., Melo, L. M., Novato, V. D. O. L., & Ferreira, V. D. R. S. (2023) · A pesquisa em saúde: desafios atuais e perspectivas futuras 6 · doi:10.22533/at.ed.60023171020
Guilherme, G. L., Morais, B. A. A. D., Freitas, F. A. B. D., Silva, I. L., Garcia, J. C. D. S., Telles, L. O., Dias, M. C., Aguiar, D. H., do Nascimento, A. F., Bomfim, G. F., et al. (2023) · A pesquisa em saúde: desafios atuais e perspectivas futuras 6 · doi:10.22533/at.ed.60023171016
PNEUMONIA ASSOCIADA À VENTILAÇÃO MECÂNICA: UMA REVISÃO DE CONCEITOS
Filho, J. C. C. P., Grossi, L. V. R., & Faustino, P. M. (2023) · A pesquisa em saúde: desafios atuais e perspectivas futuras 6 · doi:10.22533/at.ed.60023171014
Sampaio, L. A., Silva, F. M. L., & Mendes, C. R. (2023) · A pesquisa em saúde: desafios atuais e perspectivas futuras 6 · doi:10.22533/at.ed.60023171012
ORIENTAÇÃO SOBRE A ATIVIDADE FÍSICA COMO ALIADA NA DIMINUIÇÃO DA PRESSÃO ARTERIAL
Heckler, L., Fincatto, Y., Beal, S. D. B., dos Santos, L. B., Brandenburg, D. C. L., Ramos, M. G., Latrônico, F. C. N., Artifon, O. A. N., Nunes, R. D., Sebastiany, P. K., et al. (2023) · A pesquisa em saúde: desafios atuais e perspectivas futuras 6 · doi:10.22533/at.ed.60023171021
O USO DE CANNABIS SATIVA PARA TRATAMENTO DE ENDOMETRIOSE: UMA REVISÃO LITERÁRIA
da Silva, A. J., dos Santos, A. V. F., de Lira, A. C. L., da Silva, I. B. S., Barbosa, J. O. L., Baracho, E. F. D. S. S., do Nascimento, J. S. G., da Silva, R. C., de Melo, V. S. S., Maciel, E. V. M., et al. (2023) · A pesquisa em saúde: desafios atuais e perspectivas futuras 6 · doi:10.22533/at.ed.60023171017
O ESTRESSE OCUPACIONAL DOS TRABALHADORES DE ENFERMAGEM DECORRENTE DA PANDEMIA DA COVID 19
Maximiano, L. C. D. S., Dantas, L. A. L., Morais, L. G. D. S., de Faria, R. A., Freire, L. F. D. O., de Melo, F. B. T., de Mesquita, F. B. G., Soares, A. R. A., Martins, M. V., Duarte, K. I. S., et al. (2023) · A pesquisa em saúde: desafios atuais e perspectivas futuras 6 · doi:10.22533/at.ed.60023171010
10. LITERATURE REVIEW OF RESEARCH AND DEVELOPMENT OF PROBIOTIC TABLETS
Anh, N. N. Q., Xuân, Đ. T., & Chien, N. N. (2023) · Tạp chí Y học Cộng đồng · doi:10.52163/yhc.v64i13.865
(2023) · International Research Journal of Modernization in Engineering Technology and Science · doi:10.56726/irjmets47523
Bala, R., Malik, D. S., Madan, R., Jindal, S., & Kaur, V. (2024) · Drug Delivery Letters · doi:10.2174/0122103031273192240102054301
Biomedical Applications of Pectin
Sharma, H., Sarwan, J., Chaudhary, M., Chugh, R., & Bose, J. C. (2024) · doi:10.1002/9781119865452.ch12
Cavanagh, A. S., Kuter, N., Sollinger, B. I., Aziz, K. B., Turnbill, V., Martin, L. J., & Northington, F. J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.26.615156
“The stratified squamous, keratinized epithelium of the vestibule projects hairs, vibrissae, that filter inhaled particles affording rigorous protection to the nasal cavity but foreclosing the delivery of many large-molecule therapeutics 13, 14 .”
BackgroundInfluentialNasal Vaccine: A Special Prominence on SARS-CoV-2
Chattopadhyay, S., Nag, M., Bora, R., Maity, S. C., Mishra, D., Biswas, S., Bhattacharyya, S. P., Pal, R., & Alam, F. (2024) · Coronaviruses · doi:10.2174/0126667975293193240826093456
Desnita, R., Noviana, E., Zai, K., & Sulaiman, . N. S. (2025) · Science & Technology Indonesia · doi:10.26554/sti.2025.10.1.165-172
Similar effect of lidocaine and saline on ciliary beating of nasal epithelial cells in vitro
Savas, S. T., Tschanz, S. A., Latzin, P., Casaulta, C., & Müller, L. L. (2025) · Klinische Pädiatrie · doi:10.1055/a-2544-3857
“Therefore, the less invasive nasal brushing has been established as a good alternative to obtain airway epithelial cells [1– 3], e. g. for the diagnostics of primary ciliary dyskinesia (PCD) [4] or research about cystic fibrosis [5, 6].”
Mucin anchoring of SARS-CoV-2 neutralizing nanobinders increases intranasal antiviral efficacyPreprint
Gomes, J. R., Jacquelin, J., Donchet, A., Lejal, N., Nevers, Q., Klonjkowski, B., Poder, S. L., Delmas, B., & Meunier, N. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.10.648177
“%) with two layers: the upper one thought to be cleared in ~15 min and the inner defined by membrane-anchored mucins (Chen & Dulfano, 1978; Marttin et al , 1998).”
Intranasal Administration for Targeting Neurodegenerative Disorders
Tripathi, S. M., Mishra, S. K., Malviya, R., & Ojha, S. (2025) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815324846125010006
Mishra, R., Afzal, M., Hussain, M. S., Bhat, A. A., Thapa, R., Siddique, R., Patel, N. K., Rawat, S., Gupta, S., Singh, S. K., et al. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-30120-9.00011-8
Mucosal Drug Delivery System Current Trends and Future Direction
Patil, M. S. K. (2025) · International Journal for Research in Applied Science and Engineering Technology · doi:10.22214/ijraset.2025.72149
“GEPANTS” CGPR ANTAGONIST – A NEW CLINICAL APPROACH TO TREAT MIGRAINE AND NEUROPEPTIDES
Sharma, M., & ARORA, K. (2025) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2025v18i7.54791
Introduction: Exploring the promise of probiotic delivery systems
Patel, A., Hussain, I., Debnath, B., Ashique, S., Islam, A., Mojgani, N., & Asad, Y. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-27594-4.00024-3
Nasal In Situ Hydrogels: A Boon For Anti-Emetic Drug Delivery
Boraste, S. V., & Patil, S. K. (2025) · Critical Reviews in Therapeutic Drug Carrier Systems · doi:10.1615/critrevtherdrugcarriersyst.2025053412
Elucidating bioadhesive processes in nasal drug delivery systems
Armstrong, M. (2014) · UPT. Syiah Kuala University Library (Syiah Kuala University) · doi:10.48730/6nbf-yx94
Contradictory indications for rhinosinus surgery in children with rhinogenic headaches
Александровна, П. А., Polyakov, D. P., & Yunusov, A. S. (2025) · Russian Bulletin of Otorhinolaryngology · doi:10.17116/otorino202590061111
In Situ Gellable Hydrogels for Nasal Drug Delivery
Ourani-Pourdashti, S., Marashiyan, S. M., & Tabatabaei, S. N. (2026) · Springer eBooks · doi:10.1007/978-981-95-6619-8_5
Formulation, Optimization and Evaluation of In-Situ Nasal Gel Loaded with Clonazepam Liposomes
Bugadi, S., Koli, V., Shivsharan, U. S., & Mote, V. (2026) · Journal of Research in Pharmacy · doi:10.12991/jrespharm.1684423
Structure and Fate of Emulsomes Designed for the Nasal Delivery of Poorly Water - Soluble Drugs
Sahu, R., & Kapadia, R. (2026) · Research Journal of Pharmacy and Technology · doi:10.52711/0974-360x.2026.00209
Air Pollution as a Driver of Recurrent Upper-Airway Infections and Comorbid Health Issues
Hassan, A., Marinova, P., & Velikova, T. V. (2026) · Sinusitis · doi:10.3390/sinusitis10010009 · Cited by 1
“Its defense network comprises coordinated mechanisms, such as mucociliary clearance, epithelial tight junctions, and pattern recognition receptors, that detect and respond to microbial or chemical stimuli [13].”
Spray-freeze-drying aprepitant with hydroxypropyl cellulose increases nasal bioavailability
Rautenberg, A., Bühlbecker, P., Kožák, J., Chrétien, C., Pellequer, Y., Wunderling, K., Stoyanov, E., Pfeifer, A., & Lamprecht, A. (2026) · International Journal of Pharmaceutics X · doi:10.1016/j.ijpx.2026.100551
Nose-to-Brain Delivery of Biologicals
Torres, J., Correia, A. C., & Silva, A. C. (2025) · Springer handbooks · doi:10.1007/978-3-032-01636-2_8
Population Pharmacokinetics of Intranasal Amiloride in Healthy Volunteers
Jain, M., Kumar, S., Battaglia, M., Davies, S., Rower, J. E., Reilly, C. A., & Yellepeddi, V. (2026) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-026-01011-3
“This variability is biologically plausible and may reflect known sources of heterogeneity in intranasal drug delivery, including interindividual differences in nasal geometry, regional deposition, and mucociliary clearance [38].”
Mittal, K., Rathi, N., Tripathi, D., Sharma, N., Rajinikanth, P. S., & Pandey, P. K. (2026) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2026.116008
Farias, G., Bude, A., Karavas, N., Rossignol, C., Lantier, I., Suman, J., Aubrey, N., Dimier‐Poisson, I., & Epardaud, M. (2026) · Frontiers in Drug Delivery · doi:10.3389/fddev.2026.1875011
“…target (Hejazi et al., 2026), either through the mucociliary clearance mechanism that will eventually transport the vaccine to the nasopharynx (Marttin et al., 1998; Laube et al., 2024), or through localised immune responses within the turbinates themselves via disseminated lymphoid tissue…”
Klintz, L. P. I., & Reichl, S. (2026) · In vitro models · doi:10.1007/s44164-026-00145-7
Kim, Y. B., Yun, C.-O., & Yoon, A. R. (2026) · Drug Delivery · doi:10.1080/10717544.2026.2738285
“Alongside this physical filter, mucociliary clearance (MCC) acts as the primary kinetic constraint, functioning as a physiological defense mechanism that rapidly clears administered therapeutics toward the nasopharynx (Gizurarson 1993; Merkus et al. 1998).”
InfluentialNguyen, N., Yuan, M., & Wang, Y. (2026) · Pharmaceutical Research · doi:10.1007/s11095-026-04201-5
Chaturvedi, N., Mazumder, R., Dogra, A., Rani, A., & Joshi, A. (2026) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-026-11088-7
Thorat, V. P., & Paliwal, P. P. (2026) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-026-11086-9
Efficacy and Safety of Cyclodextrins in Nasal Drug Delivery
Merkus, F. W. H. M., van der Kuy, P. H. M., Marttin, E., Romeijn, S. G., & Verhoef, J. C. (1999) · Springer eBooks · doi:10.1007/978-94-011-4681-4_46
Self-citationStrategie formulative per la veicolazione nasale di farmaci
Saladini, B. (2014) · AMS Dottorato Institutional Doctoral Theses Repository (University of Bologna) · doi:10.6092/unibo/amsdottorato/6468
Metadata
- Authors
- Marttin, E., Schipper, N. G. M., Verhoef, J. C., & Merkus, F. W. H. M.
- Corresponding author
- Merkus, Frans W.H.M
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 1998-01
- Volume
- 29
- Issue
- 1-2
- Pages
- 13-38
- ISSN
- 0169-409X (ISSN-L)
- OpenAlex
- W2089895093
- Cited by
- 469
- References
- 255
- Citations by year
- 2026: 24 · 2025: 45 · 2024: 26 · 2023: 40 · 2022: 32 · 2021: 34 · 2020: 26 · 2019: 16 · 2018: 27 · 2017: 15 · 2016: 18 · 2015: 14 · 2014: 24 · 2013: 17 · 2012: 15
- FWCI
- 0.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Health Sciences › Medicine › Otorhinolaryngology › Sinusitis and nasal conditions
- Keywords
- nasal mucociliary clearance, intranasal drug delivery, ciliary beat frequency, mucus transport, pharmaceutical excipients, nasal drug absorption, residence time, toxicity screening, upper airway diseases, in vitro-in vivo correlation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review