The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
Insights into direct nose to brain delivery: current status and future perspective
Open accessAbstract
Now a day's intranasal (i.n) drug delivery is emerging as a reliable method to bypass the blood-brain barrier (BBB) and deliver a wide range of therapeutic agents including both small and large molecules, growth factors, viral vectors and even stem cells to the brain and has shown therapeutic effects in both animals and humans. This route involves the olfactory or trigeminal nerve systems which initiate in the brain and terminate in the nasal cavity at the olfactory neuroepithelium or respiratory epithelium. They are the only externally exposed portions of the central nervous system (CNS) and therefore represent the most direct method of noninvasive entry into the brain. This approach has been primarily used to explore therapeutic avenues for neurological diseases. The potential for treatment possibilities with olfactory transfer of drugs will increase as more effective formulations and delivery devices are developed. Recently, the apomorphine hydrochloride dry powders have been developed for i.n. delivery (Apomorphine nasal, Lyonase technology, Britannia Pharmaceuticals, Surrey, UK). The results of clinical trial Phase III suggested that the prepared formulation had clinical effect equivalent to subcutaneously administered apomorphine. In coming years, intranasal delivery of drugs will demand more complex and automated delivery devices to ensure accurate and repeatable dosing. Thus, new efforts are needed to make this noninvasive route of delivery more efficient and popular, and it is also predicted that in future a range of intranasal products will be used in diagnosis as well as treatment of CNS diseases. This review will embark the existing evidence of nose-to-brain transport. It also provides insights into the most relevant pre-clinical studies of direct nose-brain delivery and delivery devices which will provide relative success of intranasal delivery system. We have, herein, outlined the relevant aspects of CNS drugs given intranasally to direct the brain in treating CNS disorders like Alzheimer's disease, depression, migraine, schizophrenia, etc.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“It is non-invasive, painless, non-stressful, and relatively easy to perform without requiring a medical specialist [246,247,248].”
From Alzheimer's Disease: Treatment Strategies and Their Limitations. (2022) · cites this paper as [247]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Therapeutic Nanoparticles for Drug Delivery in Cancer
Cho, K., Wang, X., Nie, S., Chen, Z. (., & Shin, D. M. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1441 · Cited by 2,978
Micellar Nanocarriers: Pharmaceutical Perspectives
Torchilin, V. P. (2006) · Pharmaceutical Research · doi:10.1007/s11095-006-9132-0 · Cited by 1,910
Erythropoietin crosses the blood–brain barrier to protect against experimental brain injury
Brines, M. L., Ghezzi, P., Keenan, S., Agnello, D., de Lanerolle, N. C., Cerami, C., Itri, L. M., & Cerami, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.19.10526 · Cited by 1,402
Intranasal delivery to the central nervous system: Mechanisms and experimental considerations
Dhuria, S. V., Hanson, L. R., & Frey, W. H. (2010) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21924 · Cited by 1,239
Letchford, K., & Burt, H. M. (2006) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2006.11.009 · Cited by 1,200
Bymaster, F. P. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00298-6 · Cited by 725
Intranasal Drug Delivery: How, Why and What For?
Pires, A., Fortuna, A., Alves, G., & Falcão, A. (2009) · Journal of Pharmacy & Pharmaceutical Sciences · doi:10.18433/j3nc79 · Cited by 641
Effect of chitosan on epithelial permeability and structure
Dodane, V. (1999) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(99)00030-7 · Cited by 579
Tfelt‐Hansen, P. C., de Vries, P. W., & Saxena, P. R. (2000) · Drugs · doi:10.2165/00003495-200060060-00003 · Cited by 536
Nanotechnological advances for the delivery of cns therapeutics.
Wong, H. L., Wu, X. Y., & Bendayan, R. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.10.007 · Cited by 488
Stahl, S. M., Grady, M. M., Moret, C., & Briley, M. (2005) · CNS Spectrums · doi:10.1017/s1092852900019726 · Cited by 471
Redzic, Z. B. (2011) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-8-3 · Cited by 455
Clarke's analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem material
Moffat, A. C., Osselton, M. D., Widdop, B., Galichet, L., & Clarke, E. G. C. (2004) · Pharmaceutical Press eBooks · Cited by 435
Intranasal nanoemulsion based brain targeting drug delivery system of risperidone
Kumar, M., Misra, A., Babbar, A. K., Mishra, A. K., Mishra, P., & Pathak, K. (2008) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2008.03.029 · Cited by 435
Lipid Nanoparticles with a Solid Matrix (SLN®, NLC®, LDC®) for Oral Drug Delivery
Muchow, M., Maincent, P., & Müller, R. H. (2008) · Drug Development and Industrial Pharmacy · doi:10.1080/03639040802130061 · Cited by 405
Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting
Fazil, M., Md, S., Haque, S., Kumar, M., Baboota, S., Sahni, J. K., & Ali, J. (2012) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2012.04.013 · Cited by 379
Self-citationWilson, B., Samanta, M. K., Santhi, K., Kumar, K. P. S., Paramakrishnan, N., & Suresh, B. (2008) · Brain Research · doi:10.1016/j.brainres.2008.01.039 · Cited by 363
Body Distribution of Camptothecin Solid Lipid Nanoparticles After Oral Administration
Yang, S., Zhu, J., Yu, L., Liang, B., & Yang, C. (1999) · Pharmaceutical Research · doi:10.1023/a:1018888927852 · Cited by 324
Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting
Wang, X., Chi, N., & Tang, X. (2008) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.07.005 · Cited by 307
Md, S., Khan, R. A., Mustafa, G., Chuttani, K., Baboota, S., Sahni, J. K., & Ali, J. (2012) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2012.12.007 · Cited by 307
Self-citationRevised estimate of the prevalence of multiple sclerosis in the united states
Anderson, D. W., Ellenberg, J. H., Leventhal, C. M., Reingold, S. C., Rodriguez, M., & Silberberg, D. H. (1992) · Annals of Neurology · doi:10.1002/ana.410310317 · Cited by 305
Zhang, Q., Jiang, X., Jiang, W., Lü, W., Su, L., & Shi, Z. (2004) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2004.01.039 · Cited by 285
Signaling pathways activated by interferons
Platanias, L. C., & Fish, E. N. (1999) · Experimental Hematology · doi:10.1016/s0301-472x(99)00109-5 · Cited by 270
Pharmacokinetic Optimisation of Benzodiazepine Therapy for Acute Seizures: Focus on Delivery Routes
Rey, E., Tr??luyer, J.-M., & Pons, G. (1999) · Clinical Pharmacokinetics · doi:10.2165/00003088-199936060-00003 · Cited by 265
Ross, T. M., Martinez, P. M., Renner, J. C., Thorne, R. G., Hanson, L. R., & Frey, W. H. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.02.011 · Cited by 242
Hanson, L. R., Roeytenberg, A., Martinez, P. M., Coppes, V. G., Sweet, D. C., Rao, R. J., Marti, D. L., Hoekman, J., Matthews, R. B., Frey, W. H., et al. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.149807 · Cited by 224
Brain targeting of risperidone-loaded solid lipid nanoparticles by intranasal route
Patel, S., Chavhan, S. S., Soni, H., Babbar, A. K., Mathur, R., Mishra, A. K., & Sawant, K. K. (2010) · Journal of drug targeting · doi:10.3109/1061186x.2010.523787 · Cited by 187
Intranasal Mucoadhesive Microemulsions of Clonazepam: Preliminary Studies on Brain Targeting
Vyas, T. K., Babbar, A. K., Sharma, R. K., Singh, S. S., & Misra, A. R. (2006) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.20480 · Cited by 186
Erythropoietin in the brain: can the promise to protect be fulfilled?
Maiese, K., Li, F., & Chong, Z. Z. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.09.006 · Cited by 178
Nasal Drug Delivery System-Factors Affecting and Applications
Jadhav, K. R., Gambhire, M., Shaikh, I. M., Kadam, V., & Pisal, S. (2007) · Current Drug Therapy · doi:10.2174/157488507779422374 · Cited by 177
Ghigo, E., Arvat, E., Gianotti, L., Imbimbo, B. P., Lenaerts, V., Deghenghi, R., & Camanni, F. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.3.8126144 · Cited by 163
Venlafaxine loaded chitosan NPs for brain targeting: Pharmacokinetic and pharmacodynamic evaluation
Haque, S., Md, S., Fazil, M., Kumar, M., Sahni, J. K., Ali, J., & Baboota, S. (2012) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2012.02.051 · Cited by 161
Self-citationRay, B., & Lahiri, D. K. (2009) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2009.06.012 · Cited by 150
Perry, C. M., & Markham, A. (1998) · Drugs · doi:10.2165/00003495-199855060-00020 · Cited by 149
Khan, S., Patil, K., Bobade, N. N., Yeole, P. G., & Gaikwad, R. V. (2009) · Journal of drug targeting · doi:10.3109/10611860903386938 · Cited by 138
Hartman, N. R., Yarchoan, R., Pluda, J. M., Thomas, R. V., Marczyk, K. S., Broder, S. E., & Johns, D. G. (1990) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1990.86 · Cited by 133
Fréret, T., Valable, S., Chazalviel, L., Saulnier, R., MacKenzie, E. T., Petit, E., Bernaudin, M., Boulouard, M., & Schumann‐Bard, P. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04699.x · Cited by 125
Nanoparticulate lipid dispersions for bromocriptine delivery: Characterization and in vivo study
Esposito, E., Mariani, P., Ravani, L., Contado, C., Volta, M., Bido, S., Drechsler, M., Mazzoni, S., Menegatti, E., Morari, M., et al. (2011) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2011.10.015 · Cited by 119
Wang, F. (2003) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(03)00341-7 · Cited by 119
Al-Ghananeem, A. M., Saeed, H. M., Florence, R. L., Yokel, R. A., & Malkawi, A. H. (2009) · Journal of drug targeting · doi:10.3109/10611860903483396 · Cited by 116
Preliminary brain-targeting studies on intranasal mucoadhesive microemulsions of sumatriptan
Vyas, T. K., Babbar, A. K., Sharma, R. K., Singh, S. S., & Misra, A. R. (2006) · AAPS PharmSciTech · doi:10.1208/pt070108 · Cited by 116
Intranasal mucoadhesive microemulsions of zolmitriptan: Preliminary studies on brain-targeting
Vyas, T. K., Babbar, A. K., Sharma, R. K., & Misra, A. R. (2005) · Journal of drug targeting · doi:10.1080/10611860500246217 · Cited by 113
Intranasal recombinant human erythropoietin protects rats against focal cerebral ischemia
Yu, Y.-P., Qiu-qin, X., Zhang, Q., Zhang, W., Zhang, L., & Wei, E.-Q. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.07.008 · Cited by 110
Denora, N., Trapani, A., Laquintana, V., Lopedota, A. A., & Trapani, G. (2009) · Current Topics in Medicinal Chemistry · doi:10.2174/156802609787521571 · Cited by 104
Micellar Nanocarriers: Potential Nose-to-Brain Delivery of Zolmitriptan as Novel Migraine Therapy
Jain, R. D., Nabar, S., Dandekar, P. P., & Patravale, V. B. (2010) · Pharmaceutical Research · doi:10.1007/s11095-009-0041-x · Cited by 97
Alam, M. I., Baboota, S., Ahuja, A., Ali, M., Ali, J., & Sahni, J. K. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.05.014 · Cited by 89
Self-citationCritchley, H., Davis, S. S., Farraj, N. F., & Illum, L. (1994) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.1994.tb03876.x · Cited by 82
Korbonits, M., Little, Forsling, M. L., Tringali, Costa, A. C., Navarra, Trainer, P. J., & Grossman (1999) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1999.00353.x · Cited by 78
Kosasa, T., Kuriya, Y., Matsui, K., & Yamanishi, Y. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00741-4 · Cited by 69
Schupf, N., Winsten, S., Patel, B. N., Pang, D. I., Ferin, M., Zigman, W. B., Silverman, W. P., & Mayeux, R. P. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.07.062 · Cited by 66
Mechanism of action of clonazepam in myoclonus in relation to effects on GABA and 5-HT.
Jenner, P. G., Pratt, J. A., & Marsden, C. D. (1986) · PubMed · Cited by 61
First human studies with a high-molecular-weight iron chelator
Dragsten, P. R., Hallaway, P. E., Hanson, G. J., Berger, A. E., Bernard, B. K., & Hedlund, B. E. (2000) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(00)70021-7 · Cited by 58
Mustafa, G., Baboota, S., Ahuja, A., & Ali, J. (2012) · Current Nanoscience · doi:10.2174/157341312800620331 · Cited by 56
Self-citationZolmitriptan Intranasal: A Review of the Pharmacokinetics and Clinical Efficacy
Goadsby, P. J., & Yates, R. (2006) · Headache The Journal of Head and Face Pain · doi:10.1111/j.1526-4610.2006.00301.x · Cited by 54
The triptan formulations: a critical evaluation
BIGAL, M. E., Bordini, C. A., Antoniazzi, A. L. D. L., & Speciali, J. G. (2003) · Arquivos de Neuro-Psiquiatria · doi:10.1590/s0004-282x2003000200032 · Cited by 54
Khan, M. S., Patil, K., Yeole, P. G., & Gaikwad, R. V. (2009) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.61.05.0017 · Cited by 53
VENLAFAXINE INGESTION IS ASSOCIATED WITH RHABDOMYOLYSIS IN ADULTS: A CASE SERIES
WILSON, A. D., Howell, C., & Waring, W. S. (2007) · The Journal of Toxicological Sciences · doi:10.2131/jts.32.97 · Cited by 52
Future prospects of nanoparticles on brain targeted drug delivery
Chakraborty, C., Sarkar, B., Hsu, C. H., Wen, Z., Lin, C. S., & Shieh, P.-C. (2008) · Journal of Neuro-Oncology · doi:10.1007/s11060-008-9759-2 · Cited by 46
Formulation and Evaluation of Novel Micellar Nanocarrier for Nasal Delivery of Sumatriptan
Jain, R. D., Nabar, S., Dandekar, P. P., Hassan, P. A., Aswal, V. K., Talmon, Y., Shet, T., Borde, L. C., Ray, K., & Patravale, V. B. (2010) · Nanomedicine · doi:10.2217/nnm.10.28 · Cited by 46
Vautier, S., Lacomblez, L., Chacun, H., Picard, V., Gimenez, F., Farinotti, R., & Fernandez, C. (2005) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2005.09.009 · Cited by 45
The nose may help the brain: intranasal drug delivery for treating neurological diseases
Ying, W. (2007) · Future Neurology · doi:10.2217/14796708.3.1.1 · Cited by 39
Yu, H. M., & Kim, K. (2009) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2009.05.057 · Cited by 37
Transdermal Administration of Bromocriptine.
Değim, İ. T., Acartürk, F., Erdoğan, D., & Ünlü, N. L. (2003) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.26.501 · Cited by 34
Ehrenreich, H., Timner, W., & Sirén, A. (2004) · Transfusion and Apheresis Science · doi:10.1016/j.transci.2004.05.001 · Cited by 30
Lim, J. H., Kim, S. S., Boo, D. H., No, H., Kang, B. Y., Kim, E., Hwang, O., & Choi, H. J. (2009) · Neuroscience Letters · doi:10.1016/j.neulet.2008.12.056 · Cited by 26
Anderson, B. D., Morgan, M. E., & Singhal, D. (1995) · Pharmaceutical Research · doi:10.1023/a:1016299507382 · Cited by 20
Drug Targeting to the Brain - A Review
Jain, A., & Jain, S. (2011) · Current Nanoscience · doi:10.2174/157341311794480255 · Cited by 16
Nanostructured Lipid Carrier Containing CNS Acting Drug: Formulation, Optimization and Evaluation
Alam, M. I., Baboota, S., Ahuja, A., Ali, M., Ali, J., & Sahni, J. K. (2011) · Current Nanoscience · doi:10.2174/1573413711107061014 · Cited by 16
Self-citationFluoxetine for Cocaine Dependence in Methadone Maintenance
Balon, R. (1994) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-199410000-00016 · Cited by 9
Buspirone in the Treatment of Separation Anxiety in an Adolescent Boy
Balon, R. (1994) · The Canadian Journal of Psychiatry · doi:10.1177/070674379403900919 · Cited by 8
Research works printed but not linked: 5
- Dhanda DS, 2005, Drug Del Tech, 5, 64
- Ghigo E, 1994, J Clin Endocrinol Metab, 78, 693
- Jenner P, 1986, Adv Neurol, 43, 629
- Mustafa G, 2012, Curr Nanosci, 29, 293
- Putheti R, 2009, J Sci Tec, 4, 1
Cited by
Sorted by citations
Nanostructured lipid carriers for site-specific drug delivery
Khosa, A., Reddi, S., & Saha, R. N. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.04.055 · Cited by 622
Alzheimer's Disease: Treatment Strategies and Their Limitations.
Passeri, E., Elkhoury, K., Morsink, M., Broersen, K., Linder, M., Tamayol, A., Malaplate, C., Yen, F. T., & Arab-Tehrany, E. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232213954 · Cited by 689
Gänger, S., & Schindowski, K. (2018) · Pharmaceutics · doi:10.3390/pharmaceutics10030116 · Cited by 447
Progress in brain targeting drug delivery system by nasal route
Khan, A. R., Liu, M., Khan, M. W., & Zhai, G. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.09.001 · Cited by 402
Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics
Bourganis, V., Kammona, O., Alexopoulos, A., & Kiparissides, C. (2018) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2018.05.009 · Cited by 357
Metadata
- Authors
- Mittal, D., Ali, A., Md, S., Baboota, S., Sahni, J. K., & Ali, J.
- Affiliations
- Jamia Hamdard (IN)
- Corresponding author
- Ali, Javed
- Venue
- Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2013-10-09
- Volume
- 21
- Issue
- 2
- Pages
- 75-86
- ISSN
- 1071-7544 (ISSN-L)
- 1521-0464
- OpenAlex
- W2019126236
- Cited by
- 359
- References
- 70
- Citations by year
- 2026: 22 · 2025: 42 · 2024: 44 · 2023: 35 · 2022: 34 · 2021: 39 · 2020: 37 · 2019: 39 · 2018: 21 · 2017: 12 · 2016: 11 · 2015: 13 · 2014: 10
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Drug Delivery (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 › Surgery › Head and Neck Surgical Oncology
- Keywords
- intranasal drug delivery, nose-to-brain delivery, blood-brain barrier bypass, olfactory nerve, trigeminal nerve, olfactory epithelium, dry powder formulation, brain drug delivery, neurological disorders, Alzheimer's disease, depression, migraine, schizophrenia
- MeSH terms
- Administration, Intranasal, Animals, Blood-Brain Barrier, Brain, Central Nervous System Agents, Forecasting, Humans, Nasal Mucosa, Nose, Olfactory Mucosa, Drug Delivery Systems
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
