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2000
Volume 7, Issue 2
  • ISSN: 2666-7967
  • E-ISSN: 2666-7975

Abstract

Nasal administration of mucosal medications and vaccines is an alternate and promising method of drug and vaccine delivery. Mucosal pathways can be used selectively for various disorders due to many benefits. Many initiatives are now being made to yield effective medications and cutting-edge nasal delivery systems. The structure of the nasal cavity and key features were discussed in this review. With a focus on vaccine distribution, the benefits, successes, and difficulties of using the nasal route for medical purposes were examined. The strong result supports the benefits and security, of the safety of nasal medication and vaccination administration. This alternate path may help many unmet medical needs and may also make big vaccination drives or expensive, protracted chronic therapies possible. Today, despite some lingering criticism, the area of nasal medicine and vaccine delivery is expanding quickly, supported by recent advancements in nanotechnology, imaging, and administration devices. The variety of drugs that have been licensed for nasal delivery is expected to increase significantly.

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2024-10-07
2026-01-02
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References

  1. MachtD. The history of intravenous and subcutaneous administration of drugs.J. Am. Med. Assoc.1916LXVI1285686010.1001/jama.1916.02580380006003
    [Google Scholar]
  2. NornS. KruseP.R. KruseE. Traek af injektionens historie [On the history of injection].Dan. Medicinhist. Arbog2006341043
    [Google Scholar]
  3. BarsoumN. KleemanC. Now and then, the history of parenteral fluid administration.Am. J. Nephrol.2002222-328428910.1159/00006377512097754
    [Google Scholar]
  4. ShakyaA.K. ChowdhuryM.Y.E. TaoW. GillH.S. Mucosal vaccine delivery: Current state and a pediatric perspective.J. Control. Release201624039441310.1016/j.jconrel.2016.02.01426860287
    [Google Scholar]
  5. KraehenbuhlJ.P. NeutraM. Mucosal vaccines: Where do we stand?Curr. Top. Med. Chem.201313202609262810.2174/1568026611313666018624066889
    [Google Scholar]
  6. BakerJ.R.Jr FarazuddinM. WongP.T. O’KonekJ.J. The unfulfilled potential of mucosal immunization.J. Allergy Clin. Immunol.2022150111110.1016/j.jaci.2022.05.00235569567
    [Google Scholar]
  7. CzerkinskyC. HolmgrenJ. Topical immunization strategies.Mucosal Immunol.20103654555510.1038/mi.2010.5520861833
    [Google Scholar]
  8. SangolkarS.S. AdhaoV.S. MundheD.G. SawarkarH.S. Particle size determination of nasal drug delivery system: A review.Int. J. Pharm. Sci. Rev. Res.20121716673 https://globalresearchonline.net/journalcontents/v17-1/14.pdf
    [Google Scholar]
  9. FortunaA. AlvesG. SerralheiroA. SousaJ. FalcãoA. Intranasal delivery of systemic-acting drugs: Small-molecules and biomacromolecules.Eur. J. Pharm. Biopharm.201488182710.1016/j.ejpb.2014.03.00424681294
    [Google Scholar]
  10. BeuleA.G. Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses.GMS Curr. Top. Otorhinolaryngol. Head Neck Surg.20109Doc0710.3205/cto00007122073111
    [Google Scholar]
  11. WilsonW.R. AllansmithM.R. Rapid, atraumatic method for obtaining nasal mucus samples.Ann. Otol. Rhinol. Laryngol.197685339139310.1177/000348947608500311937966
    [Google Scholar]
  12. PiresA. FortunaA. AlvesG. FalcãoA. Intranasal drug delivery: How, why and what for?J. Pharm. Pharm. Sci.200912328831110.18433/J3NC7920067706
    [Google Scholar]
  13. ColeP. Nasal and oral airflow resistors. Site, function, and assessment.Arch. Otolaryngol. Head Neck Surg.1992118879079310.1001/archotol.1992.018800800120041642827
    [Google Scholar]
  14. SarkarM.A. Drug metabolism in the nasal mucosa.Pharm. Res.1992911910.1023/A:10189112066461589391
    [Google Scholar]
  15. MarasiniN. SkwarczynskiM. TothI. Intranasal delivery of nanoparticle-based vaccines.Ther. Deliv.20178315116710.4155/tde‑2016‑006828145824
    [Google Scholar]
  16. MarttinE. SchipperN.G.M. VerhoefJ.C. MerkusF.W.H.M. Nasal mucociliary clearance as a factor in nasal drug delivery.Adv. Drug Deliv. Rev.1998291-2133810.1016/S0169‑409X(97)00059‑810837578
    [Google Scholar]
  17. AlsarraI.A. HamedA.Y. AlanaziF.K. El MaghrabyG.M. Vesicular systems for intranasal drug delivery.Drug Delivery to the Central Nervous System Neuromethods.20094517520310.1007/978‑1‑60761‑529‑3_8
    [Google Scholar]
  18. CsabaN. Garcia-FuentesM. AlonsoM.J. Nanoparticles for nasal vaccination.Adv. Drug Deliv. Rev.200961214015710.1016/j.addr.2008.09.00519121350
    [Google Scholar]
  19. HjelmB.E. KilbourneJ. Herbst-KralovetzM.M. TLR7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines.Hum. Vaccin. Immunother.201410241041610.4161/hv.2714724280723
    [Google Scholar]
  20. FukuyamaS. HiroiT. YokotaY. Initiation of NALT organogenesis is independent of the IL-7R, LTbetaR, and NIK signaling pathways but requires the Id2 gene and CD3(-)CD4(+)CD45(+) cells.Immunity2002171314010.1016/S1074‑7613(02)00339‑412150889
    [Google Scholar]
  21. KiyonoH. FukuyamaS. NALT- versus PEYER’S-patch-mediated mucosal immunity.Nat. Rev. Immunol.20044969971010.1038/nri143915343369
    [Google Scholar]
  22. LiangB. HylandL. HouS. Nasal-associated lymphoid tissue is a site of long-term virus-specific antibody production following respiratory virus infection of mice.J. Virol.200175115416542010.1128/JVI.75.11.5416‑5420.200111333927
    [Google Scholar]
  23. Frieke KuperC. KoornstraP.J. HameleersD.M.H. The role of nasopharyngeal lymphoid tissue.Immunol. Today199213621922410.1016/0167‑5699(92)90158‑41627250
    [Google Scholar]
  24. PerryM. WhyteA. Immunology of the tonsils.Immunol. Today199819941442110.1016/S0167‑5699(98)01307‑39745205
    [Google Scholar]
  25. BienenstockJ. McDermottM.R. Bronchus‐ and nasal‐associated lymphoid tissues.Immunol. Rev.20052061223110.1111/j.0105‑2896.2005.00299.x16048540
    [Google Scholar]
  26. CestaM.F. Normal structure, function, and histology of mucosa-associated lymphoid tissue.Toxicol. Pathol.200634559960810.1080/0192623060086553117067945
    [Google Scholar]
  27. HowieA.J. Scanning and transmission electron microscopy on the epithelium of human palatine tonsils.J. Pathol.19801302919810.1002/path.17113002057365575
    [Google Scholar]
  28. JahnsenF.L. GranE. HayeR. BrandtzaegP. Human nasal mucosa contains antigen-presenting cells of strikingly different functional phenotypes.Am. J. Respir. Cell Mol. Biol.2004301313710.1165/rcmb.2002‑0230OC12829449
    [Google Scholar]
  29. DebinA. KravtzoffR. SantiagoJ.V. Intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and CTL responses.Vaccine20022021-222752276310.1016/S0264‑410X(02)00191‑312034102
    [Google Scholar]
  30. PriceG.E. SoboleskiM.R. LoC.Y. Single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent H5N1, H3N2 and H1N1 viruses.PLoS One2010510e1316210.1371/journal.pone.001316220976273
    [Google Scholar]
  31. HemannE.A. KangS.M. LeggeK.L. Protective CD8 T cell-mediated immunity against influenza A virus infection following influenza virus-like particle vaccination.J. Immunol.201319152486249410.4049/jimmunol.130095423885108
    [Google Scholar]
  32. AguilarJ.C. LobainaY. MuzioV. Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen.Immunol. Cell Biol.200482553954610.1111/j.0818‑9641.2004.01278.x15479440
    [Google Scholar]
  33. RudinA. JohanssonE.L. BergquistC. HolmgrenJ. Differential kinetics and distribution of antibodies in serum and nasal and vaginal secretions after nasal and oral vaccination of humans.Infect. Immun.19986673390339610.1128/IAI.66.7.3390‑3396.19989632610
    [Google Scholar]
  34. KaetzelC.S. The polymeric immunoglobulin receptor: Bridging innate and adaptive immune responses at mucosal surfaces.Immunol. Rev.20052061839910.1111/j.0105‑2896.2005.00278.x16048543
    [Google Scholar]
  35. NizardM. DinizM.O. RousselH. Mucosal vaccines.Hum. Vaccin. Immunother.20141082175218710.4161/hv.2926925424921
    [Google Scholar]
  36. SigmundsdottirH. ButcherE.C. Environmental cues, dendritic cells and the programming of tissue-selective lymphocyte trafficking.Nat. Immunol.20089998198710.1038/ni.f.20818711435
    [Google Scholar]
  37. MoraJ.R. BonoM.R. ManjunathN. Selective imprinting of gut-homing T cells by Peyer’s patch dendritic cells.Nature20034246944889310.1038/nature0172612840763
    [Google Scholar]
  38. OgraP.L. KarzonD.T. Poliovirus antibody response in serum and nasal secretions following intranasal inoculation with inactivated poliovaccine.J. Immunol.19691021152310.4049/jimmunol.102.1.154303877
    [Google Scholar]
  39. JohanssonE.L. WassénL. HolmgrenJ. JertbornM. RudinA. Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans.Infect. Immun.200169127481748610.1128/IAI.69.12.7481‑7486.200111705923
    [Google Scholar]
  40. PrakkenB.J. van der ZeeR. AndertonS.M. van KootenP.J.S. KuisW. van EdenW. Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis.Proc. Natl. Acad. Sci. USA19979473284328910.1073/pnas.94.7.32849096385
    [Google Scholar]
  41. HagiwaraY. McGheeJ.R. FujihashiK. Protective mucosal immunity in aging is associated with functional CD4+ T cells in nasopharyngeal-associated lymphoreticular tissue.J. Immunol.200317041754176210.4049/jimmunol.170.4.175412574339
    [Google Scholar]
  42. FujihashiK. KiyonoH. Mucosal immunosenescence: New developments and vaccines to control infectious diseases.Trends Immunol.200930733434310.1016/j.it.2009.04.00419540811
    [Google Scholar]
  43. KogaT. McGheeJ.R. KatoH. KatoR. KiyonoH. FujihashiK. Evidence for early aging in the mucosal immune system.J. Immunol.200016595352535910.4049/jimmunol.165.9.535211046071
    [Google Scholar]
  44. KobayashiA. DonaldsonD.S. ErridgeC. The functional maturation of M cells is dramatically reduced in the Peyer’s patches of aged mice.Mucosal Immunol.2013651027103710.1038/mi.2012.14123360902
    [Google Scholar]
  45. LyckeN. Recent progress in mucosal vaccine development: Potential and limitations.Nat. Rev. Immunol.201212859260510.1038/nri325122828912
    [Google Scholar]
  46. GallichanW.S. RosenthalK.L. Long-lived cytotoxic T lymphocyte memory in mucosal tissues after mucosal but not systemic immunization.J. Exp. Med.199618451879189010.1084/jem.184.5.18798920875
    [Google Scholar]
  47. BelyakovI.M. DerbyM.A. AhlersJ.D. Mucosal immunization with HIV-1 peptide vaccine induces mucosal and systemic cytotoxic T lymphocytes and protective immunity in mice against intrarectal recombinant HIV-vaccinia challenge.Proc. Natl. Acad. Sci. USA19989541709171410.1073/pnas.95.4.17099465081
    [Google Scholar]
  48. KaravasiliC. FatourosD.G. Smart materials: In situ gel-forming systems for nasal delivery.Drug Discov. Today201621115716610.1016/j.drudis.2015.10.01626563428
    [Google Scholar]
  49. AmidiM. RomeijnS.G. VerhoefJ.C. N-Trimethyl chitosan (TMC) nanoparticles loaded with influenza subunit antigen for intranasal vaccination: Biological properties and immunogenicity in a mouse model.Vaccine200725114415310.1016/j.vaccine.2006.06.08616973248
    [Google Scholar]
  50. GilmoreJ.L. YiX. QuanL. KabanovA.V. Novel nanomaterials for clinical neuroscience.J. Neuroimmune Pharmacol.200832839410.1007/s11481‑007‑9099‑618210200
    [Google Scholar]
  51. FukuyamaY. TokuharaD. KataokaK. Novel vaccine development strategies for inducing mucosal immunity.Expert Rev. Vaccines201211336737910.1586/erv.11.19622380827
    [Google Scholar]
  52. LiangJ.L. TiwariT. MoroP. Prevention of pertussis, tetanus, and diphtheria with vaccines in the united states: Recommendations of the advisory committee on immunization practices (ACIP).MMWR Recomm. Rep.201867214410.15585/mmwr.rr6702a129702631
    [Google Scholar]
  53. BuonagurioD.A. BechertT.M. YangC.F. Genetic stability of live, cold-adapted influenza virus components of the FluMist®/CAIV-T vaccine throughout the manufacturing process.Vaccine200624122151216010.1016/j.vaccine.2005.11.00716413951
    [Google Scholar]
  54. AmbroseC.S. LukeC. CoelinghK. Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza.Influenza Other Respir. Viruses20082619320210.1111/j.1750‑2659.2008.00056.x19453395
    [Google Scholar]
  55. FioreA.E. UyekiT.M. BroderK. Prevention and control of influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010.MMWR Recomm. Rep.201059RR-816220689501
    [Google Scholar]
  56. CarterN.J. CurranM.P. Live attenuated influenza vaccine (FluMist®; Fluenz™): A review of its use in the prevention of seasonal influenza in children and adults.Drugs201171121591162210.2165/11206860‑000000000‑0000021861544
    [Google Scholar]
  57. CapeS. Safety and immunogenicity of dry powder measles vaccine administered by inhalation: A randomized controlled Phase I clinical trial.Vaccine201432506791679710.1016/j.vaccine.2014.09.071
    [Google Scholar]
  58. HinkulaJ. HagbomM. WahrenB. SchroderU. Safety and immunogenicity, after nasal application of HIV-1 DNA gagp37 plasmid vaccine in young mice.Vaccine200826405101510610.1016/j.vaccine.2008.03.09818482783
    [Google Scholar]
  59. TiwariS. VermaS.K. AgrawalG.P. VyasS.P. Viral protein complexed liposomes for intranasal delivery of hepatitis B surface antigen.Int. J. Pharm.20114131-221121910.1016/j.ijpharm.2011.04.02921540094
    [Google Scholar]
  60. DerrickS.C. KolibabK. YangA. MorrisS.L. Intranasal administration of Mycobacterium bovis BCG induces superior protection against aerosol infection with Mycobacterium tuberculosis in mice.Clin. Vaccine Immunol.201421101443145110.1128/CVI.00394‑1425143340
    [Google Scholar]
  61. LorenziJ.C.C. TromboneA.P.F. RochaC.D. Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis.BMC Biotechnol.20101017710.1186/1472‑6750‑10‑7720961459
    [Google Scholar]
  62. KrishnanV. AndersenB.H. ShoemakerC. Efficacy and immunogenicity of single-dose AdVAV intranasal anthrax vaccine compared to anthrax vaccine absorbed in an aerosolized spore rabbit challenge model.Clin. Vaccine Immunol.201522443043910.1128/CVI.00690‑1425673303
    [Google Scholar]
  63. WuY. WeiW. ZhouM. Thermal-sensitive hydrogel as adjuvant-free vaccine delivery system for H5N1 intranasal immunization.Biomaterials20123372351236010.1016/j.biomaterials.2011.11.06822192540
    [Google Scholar]
  64. FischerW.A.II KingL.S. LaneA.P. PekoszA. Restricted replication of the live attenuated influenza A virus vaccine during infection of primary differentiated human nasal epithelial cells.Vaccine201533364495450410.1016/j.vaccine.2015.07.02326196325
    [Google Scholar]
  65. CitronM.P. PatelM. PurcellM. A novel method for strict intranasal delivery of non-replicating RSV vaccines in cotton rats and non-human primates.Vaccine201836202876288510.1016/j.vaccine.2018.02.11029599087
    [Google Scholar]
  66. BallJ.P. SpringerM.J. NiY. Intranasal delivery of a bivalent norovirus vaccine formulated in an in situ gelling dry powder.PLoS One2017125e017731010.1371/journal.pone.017731028545100
    [Google Scholar]
  67. RiddleM.S. KaminskiR.W. WilliamsC. Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine.Vaccine201129407009701910.1016/j.vaccine.2011.07.03321787825
    [Google Scholar]
  68. VajdyM. SinghM. KazzazJ. Mucosal and systemic anti-HIV responses in Rhesus macaques following combinations of intranasal and parenteral immunizations.AIDS Res. Hum. Retroviruses200420111269128110.1089/aid.2004.20.126915588349
    [Google Scholar]
  69. MäkitaloB. LundholmP. HinkulaJ. Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen.J. Gen. Virol.20048582407241910.1099/vir.0.79869‑015269383
    [Google Scholar]
  70. Barré-SinoussiF. ChermannJ.C. ReyF. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).Science1983220459986887110.1126/science.61891836189183
    [Google Scholar]
  71. FuchsJD SobieszczykME HammerSM BuchbinderSP Lessons drawn from recent HIV vaccine efficacy trials.J Acquir Immune Defic Syndr201055Suppl 2)(Suppl. 2S1283110.1097/QAI.0b013e3181fbca0221406982
    [Google Scholar]
  72. BrolidenK. HinkulaJ. DevitoC. Functional HIV-1 specific IgA antibodies in HIV-1 exposed, persistently IgG seronegative female sex workers.Immunol. Lett.2001791-2293610.1016/S0165‑2478(01)00263‑211595287
    [Google Scholar]
  73. DevitoC. HinkulaJ. KaulR. Mucosal and plasma IgA from HIV-exposed seronegative individuals neutralize a primary HIV-1 isolate.AIDS200014131917192010.1097/00002030‑200009080‑0000610997395
    [Google Scholar]
  74. Leroux-RoelsG. MaesC. ClementF. Randomized Phase I: Safety, immunogenicity and mucosal antiviral activity in young healthy women vaccinated with HIV-1 gp41 P1 peptide on virosomes.PLoS One201382e5543810.1371/journal.pone.005543823437055
    [Google Scholar]
  75. BomselM. TudorD. DrilletA.S. Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges.Immunity201134226928010.1016/j.immuni.2011.01.01521315623
    [Google Scholar]
  76. MoserC. AmackerM. KammerA.R. RasiS. WesterfeldN. ZurbriggenR. Influenza virosomes as a combined vaccine carrier and adjuvant system for prophylactic and therapeutic immunizations.Expert Rev. Vaccines20076571172110.1586/14760584.6.5.71117931152
    [Google Scholar]
  77. BrekkeK. LindA. Holm-HansenC. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x) induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.PLoS One2014911e11255610.1371/journal.pone.011255625398137
    [Google Scholar]
  78. ShanL. DengK. ShroffN.S. Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation.Immunity201236349150110.1016/j.immuni.2012.01.01422406268
    [Google Scholar]
  79. CarcelainG. AutranB. Immune interventions in HIV infection.Immunol. Rev.2013254135537110.1111/imr.1208323772631
    [Google Scholar]
  80. KatlamaC. DeeksS.G. AutranB. Barriers to a cure for HIV: New ways to target and eradicate HIV-1 reservoirs.Lancet201338198832109211710.1016/S0140‑6736(13)60104‑X23541541
    [Google Scholar]
  81. ÅsjöB. StavangH. SørensenB. BaksaasI. NyhusJ. LangelandN. Phase I trial of a therapeutic HIV type 1 vaccine, Vacc-4x, in HIV type 1-infected individuals with or without antiretroviral therapy.AIDS Res. Hum. Retroviruses200218181357136510.1089/08892220232093543812487807
    [Google Scholar]
  82. KiepielaP. NgumbelaK. ThobakgaleC. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load.Nat. Med.2007131465310.1038/nm152017173051
    [Google Scholar]
  83. FalkebornT. BråveA. LarssonM. ÅkerlindB. SchröderU. HinkulaJ. Endocine™, N3OA and N3OASq; three mucosal adjuvants that enhance the immune response to nasal influenza vaccination.PLoS One201388e7052710.1371/journal.pone.007052723950951
    [Google Scholar]
  84. Lobaina MatoY. Nasal route for vaccine and drug delivery: Features and current opportunities.Int. J. Pharm.201957211881310.1016/j.ijpharm.2019.11881331678521
    [Google Scholar]
  85. IglesiasE. GarcíaD. CarrazanaY. Anti-HIV-1 and anti-HBV immune responses in mice after parenteral and nasal co-administration of a multiantigenic formulation.Curr. HIV Res.20086545246010.2174/15701620878586118618855656
    [Google Scholar]
  86. García-DíazD. RodríguezI. SantistebanY. Th2-Th1 shift with the multiantigenic formulation TERAVAC-HIV-1 in Balb/c mice.Immunol. Lett.20131491-2778410.1016/j.imlet.2012.11.00723183092
    [Google Scholar]
  87. MacdonaldN.E. HalperinB. ChapleE.B. ScottJ. KirkJ.M. KirkJ.M. Infectious disease management: Lessons from cuba.Can. J. Infect. Dis. Med. Microbiol.200617421722010.1155/2006/35191918382630
    [Google Scholar]
  88. LobainaY. MichelM.L. Chronic hepatitis B: Immunological profile and current therapeutic vaccines in clinical trials.Vaccine201735182308231410.1016/j.vaccine.2017.03.04928351734
    [Google Scholar]
  89. LobainaM.Y. Aguilar Rubido JC, Guillen Nieto GE. HeberNasvac, a novel therapeutic vaccine for chronic hepatitis B patients.Almanac Clin Med201644671371810.18786/2072‑0505‑2016‑44‑6‑713‑718
    [Google Scholar]
  90. Al MahtabM. AkbarS.M.F. AguilarJ.C. Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial).PLoS One2018138e020123610.1371/journal.pone.020123630133478
    [Google Scholar]
  91. LopezM. RodriguezE.N. LobainaY. MusacchioA. FalconV. GuillenG. Characterization of the size distribution and aggregation of virus-like nanoparticles used as active ingredients of the HeberNasvac therapeutic vaccine against chronic hepatitis B*.Adv Nat Sci: Nanosci Nanotechnol20178202500910.1088/2043‑6254/aa5e1d
    [Google Scholar]
  92. BetancourtA.A. DelgadoC.A.G. EstévezZ.C. Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens.Int. J. Infect. Dis.200711539440110.1016/j.ijid.2006.09.01017257877
    [Google Scholar]
  93. WHOWHO vaccine-preventable diseases: 2010 global summary.2010Available From: https://iris.who.int/bitstream/handle/10665/70535/WHO_IVB_2010_eng.pdf
  94. SkerryC.M. MahonB.P. A live, attenuated Bordetella pertussis vaccine provides long-term protection against virulent challenge in a murine model.Clin. Vaccine Immunol.201118218719310.1128/CVI.00371‑1021147936
    [Google Scholar]
  95. MielcarekN. DebrieA.S. RazeD. Live attenuated B. pertussis as a single-dose nasal vaccine against whooping cough.PLoS Pathog.200627e6510.1371/journal.ppat.002006516839199
    [Google Scholar]
  96. SkerryC.M. CassidyJ.P. EnglishK. Feunou-FeunouP. LochtC. MahonB.P. A live attenuated Bordetella pertussis candidate vaccine does not cause disseminating infection in gamma interferon receptor knockout mice.Clin. Vaccine Immunol.20091691344135110.1128/CVI.00082‑0919625486
    [Google Scholar]
  97. FeunouP.F. KammounH. DebrieA.S. MielcarekN. LochtC. Long-term immunity against pertussis induced by a single nasal administration of live attenuated B. pertussis BPZE1.Vaccine201028437047705310.1016/j.vaccine.2010.08.01720708998
    [Google Scholar]
  98. ThorstenssonR. TrollforsB. Al-TawilN. A phase I clinical study of a live attenuated Bordetella pertussis vaccine--BPZE1; a single centre, double-blind, placebo-controlled, dose-escalating study of BPZE1 given intranasally to healthy adult male volunteers.PLoS One201491e8344910.1371/journal.pone.008344924421886
    [Google Scholar]
  99. ScottB.A. YarchoanM. JaffeeE.M. Prophylactic vaccines for nonviral cancers.Annu. Rev. Cancer Biol.20182119521110.1146/annurev‑cancerbio‑030617‑050558
    [Google Scholar]
  100. ÇuburuN. GrahamB.S. BuckC.B. Intravaginal immunization with HPV vectors induces tissue-resident CD8+ T cell responses.J. Clin. Invest.2012122124606462010.1172/JCI6328723143305
    [Google Scholar]
  101. SunY.Y. PengS. HanL. Local HPV recombinant vaccinia boost following priming with an HPV DNA vaccine enhances local HPV-Specific CD8+ T-cell-mediated tumor control in the genital tract.Clin. Cancer Res.201622365766910.1158/1078‑0432.CCR‑15‑023426420854
    [Google Scholar]
  102. SandovalF. TermeM. NizardM. Mucosal imprinting of vaccine-induced CD8+ T cells is crucial to inhibit the growth of mucosal tumors.Sci. Transl. Med.20135172172ra2010.1126/scitranslmed.300488823408053
    [Google Scholar]
  103. DecrausazL. PythoudC. Domingos-PereiraS. DerréL. JichlinskiP. Nardelli-HaefligerD. Intravaginal live attenuated Salmonella increases local antitumor vaccine-specific CD8+ T cells.OncoImmunology201321e2294410.4161/onci.2294423483225
    [Google Scholar]
  104. McMasterS.R. WilsonJ.J. WangH. KohlmeierJ.E. Airway-resident memory CD8 T cells provide antigen-specific protection against respiratory virus challenge through rapid IFN-gamma production.J. Immunol.2015195120320910.4049/jimmunol.140297526026054
    [Google Scholar]
  105. NizardM. RousselH. DinizM.O. Induction of resident memory T cells enhances the efficacy of cancer vaccine.Nat. Commun.2017811522110.1038/ncomms1522128537262
    [Google Scholar]
  106. SinghS. YangG. SchlunsK.S. AnthonyS.M. SastryK.J. Sublingual vaccination induces mucosal and systemic adaptive immunity for protection against lung tumor challenge.PLoS One201493e9000110.1371/journal.pone.009000124599269
    [Google Scholar]
  107. WakabayashiA. NakagawaY. ShimizuM. MoriyaK. NishiyamaY. TakahashiH. Suppression of an already established tumor growing through activated mucosal CTLs induced by oral administration of tumor antigen with cholera toxin.J. Immunol.200818064000401010.4049/jimmunol.180.6.400018322209
    [Google Scholar]
  108. Domingos-PereiraS. DerréL. Warpelin-DecrausazL. Intravaginal and subcutaneous immunization induced vaccine specific CD8 T cells and tumor regression in the bladder.J. Urol.2014191381482210.1016/j.juro.2013.08.00923954582
    [Google Scholar]
  109. AhmadS. CaseyG. CroninM. Induction of effective antitumor response after mucosal bacterial vector mediated DNA vaccination with endogenous prostate cancer specific antigen.J. Urol.2011186268769310.1016/j.juro.2011.03.13921683415
    [Google Scholar]
  110. Kim-SchulzeS. KimH.S. WainsteinA. Intrarectal vaccination with recombinant vaccinia virus expressing carcinoembronic antigen induces mucosal and systemic immunity and prevents progression of colorectal cancer.J. Immunol.2008181118112811910.4049/jimmunol.181.11.811219018004
    [Google Scholar]
  111. FinnO.J. Cancer Immunology.N. Engl. J. Med.2008358252704271510.1056/NEJMra07273918565863
    [Google Scholar]
  112. AhnB.N. KimS.K. ShimC.K. Proliposomes as an intranasal dosage form for the sustained delivery of propranolol.J. Control. Release199534320321010.1016/0168‑3659(94)00114‑A
    [Google Scholar]
  113. ShyuW.C. MayolR.F. PfefferM. PittmanK.A. GammansR.E. BarbhaiyaR.H. Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol.Biopharm. Drug Dispos.199314537137910.1002/bdd.25101405038218955
    [Google Scholar]
  114. YangC. GaoH. MitraA.K. Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir.J. Pharm. Sci.200190561762410.1002/1520‑6017(200105)90:5<617::AID‑JPS1018>3.0.CO;2‑511288106
    [Google Scholar]
  115. NagpalK. SinghS.K. MishraD.N. Chitosan nanoparticles: A promising system in novel drug delivery.Chem. Pharm. Bull. (Tokyo)201058111423143010.1248/cpb.58.142321048331
    [Google Scholar]
  116. VyasT.K. BabbarA.K. SharmaR.K. MisraA. Intranasal mucoadhesive microemulsions of zolmitriptan: Preliminary studies on brain-targeting.J. Drug Target.200513531732410.1080/1061186050024621716199375
    [Google Scholar]
  117. OzsoyY. GungorS. CevherE. Nasal delivery of high molecular weight drugs.Molecules20091493754377910.3390/molecules1409375419783956
    [Google Scholar]
  118. LochheadJ.J. ThorneR.G. FisherA.N. HinchcliffeM. NorburyH. Jabbal-GillI. Intranasal delivery of biologics to the central nervous system.Adv. Drug Deliv. Rev.201264761462810.1016/j.addr.2011.11.00222119441
    [Google Scholar]
  119. de LangeE.C.M. The mastermind approach to CNS drug therapy: Translational prediction of human brain distribution, target site kinetics, and therapeutic effects.Fluids Barriers CNS20131011210.1186/2045‑8118‑10‑1223432852
    [Google Scholar]
  120. MerkusF.W.H.M. van den BergM.P. Can nasal drug delivery bypass the blood-brain barrier?: Questioning the direct transport theory.Drugs R D.20078313314410.2165/00126839‑200708030‑0000117472409
    [Google Scholar]
  121. DjupeslandP.G. MessinaJ.C. MahmoudR.A. The nasal approach to delivering treatment for brain diseases: An anatomic, physiologic, and delivery technology overview.Ther. Deliv.20145670973310.4155/tde.14.4125090283
    [Google Scholar]
  122. SjölinderH. JonssonA.B. Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.PLoS One2010511e1403410.1371/journal.pone.001403421124975
    [Google Scholar]
  123. DandoS.J. Mackay-SimA. NortonR. Pathogens penetrating the central nervous system: Infection pathways and the cellular and molecular mechanisms of invasion.Clin. Microbiol. Rev.201427469172610.1128/CMR.00118‑1325278572
    [Google Scholar]
  124. PardridgeW.M. Drug transport across the blood-brain barrier.J. Cereb. Blood Flow Metab.201232111959197210.1038/jcbfm.2012.12622929442
    [Google Scholar]
  125. FreiherrJ. HallschmidM. FreyW.H.II Intranasal insulin as a treatment for Alzheimer’s disease: A review of basic research and clinical evidence.CNS Drugs201327750551410.1007/s40263‑013‑0076‑823719722
    [Google Scholar]
  126. GraustellaA.J. MacLeodC. A critical review of the influence of oxytocin nasal spray on social cognition in humans: Evidence and future directions.Horm. Behav.201261341041810.1016/j.yhbeh.2012.01.00222265852
    [Google Scholar]
  127. BornJ. LangeT. KernW. McGregorG.P. BickelU. FehmH.L. Sniffing neuropeptides: A transnasal approach to the human brain.Nat. Neurosci.20025651451610.1038/nn0602‑84911992114
    [Google Scholar]
  128. DanielyanL. SchäferR. von Ameln-MayerhoferA. Intranasal delivery of cells to the brain.Eur. J. Cell Biol.200988631532410.1016/j.ejcb.2009.02.00119324456
    [Google Scholar]
  129. DanielyanL. SchäferR. von Ameln-MayerhoferA. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease.Rejuvenation Res.201114131610.1089/rej.2010.113021291297
    [Google Scholar]
  130. ThorneR.G. PronkG.J. PadmanabhanV. FreyW.H.II Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration.Neuroscience2004127248149610.1016/j.neuroscience.2004.05.02915262337
    [Google Scholar]
  131. DeadwylerS.A. PorrinoL. SiegelJ.M. HampsonR.E. Systemic and nasal delivery of orexin-A (Hypocretin-1) reduces the effects of sleep deprivation on cognitive performance in nonhuman primates.J. Neurosci.20072752142391424710.1523/JNEUROSCI.3878‑07.200718160631
    [Google Scholar]
  132. DhamaK. DhawanM. TiwariR. COVID-19 intranasal vaccines: Current progress, advantages, prospects, and challenges.Hum. Vaccin. Immunother.2022185204585310.1080/21645515.2022.204585335258416
    [Google Scholar]
  133. BleierB.S. RamanathanM.Jr LaneA.P. COVID-19 vaccines may not prevent nasal SARS-CoV-2 infection and asymptomatic transmission.Otolaryngol. Head Neck Surg.2021164230530710.1177/019459982098263333320052
    [Google Scholar]
  134. McLenonJ. RogersM.A.M. The fear of needles: A systematic review and meta‐analysis.J. Adv. Nurs.2019751304210.1111/jan.1381830109720
    [Google Scholar]
  135. OliveC. SunH.K. HoM.F. Intranasal administration is an effective mucosal vaccine delivery route for self-adjuvanting lipid core peptides targeting the group A streptococcal M protein.J. Infect. Dis.2006194331632410.1086/50558016826479
    [Google Scholar]
  136. PeekL.J. MiddaughC.R. BerklandC. Nanotechnology in vaccine delivery.Adv. Drug Deliv. Rev.200860891592810.1016/j.addr.2007.05.01718325628
    [Google Scholar]
  137. ButlerS.E. CrowleyA.R. NatarajanH. Features and functions of systemic and mucosal humoral immunity among SARS-CoV-2 convalescent individuals, medRxiv.Front. Immunol.20211161868510.3389/fimmu.2020.61868533584712
    [Google Scholar]
  138. YusufH. KettV. Current prospects and future challenges for nasal vaccine delivery.Hum. Vaccin. Immunother.2017131344510.1080/21645515.2016.123966827936348
    [Google Scholar]
  139. van de PavertS.A. MebiusR.E. New insights into the development of lymphoid tissues.Nat. Rev. Immunol.201010966467410.1038/nri283220706277
    [Google Scholar]
  140. KagnoffM.F. EckmannL. Epithelial cells as sensors for microbial infection.J. Clin. Invest.1997100161010.1172/JCI1195229202050
    [Google Scholar]
  141. HargreavesD.C. MedzhitovR. Innate sensors of microbial infection.J. Clin. Immunol.200525650351010.1007/s10875‑005‑8065‑416380814
    [Google Scholar]
  142. IllumL. Nanoparticulate systems for nasal delivery of drugs: A real improvement over simple systems?J. Pharm. Sci.200796347348310.1002/jps.2071817117404
    [Google Scholar]
  143. BurgdorfS. KautzA. BöhnertV. KnolleP.A. KurtsC. Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation.Science2007316582461261610.1126/science.113797117463291
    [Google Scholar]
  144. SansonettiP.J. Di SantoJ.P. Debugging how bacteria manipulate the immune response.Immunity200726214916110.1016/j.immuni.2007.02.00417307704
    [Google Scholar]
  145. SkwarczynskiM. TothI. Non-invasive mucosal vaccine delivery: Advantages, challenges and the future.Expert Opin. Drug Deliv.202017443543710.1080/17425247.2020.173146832059625
    [Google Scholar]
  146. LijekR.S. LuqueS.L. LiuQ. ParkerD. BaeT. WeiserJ.N. Protection from the acquisition of Staphylococcus aureus nasal carriage by cross-reactive antibody to a pneumococcal dehydrogenase.Proc. Natl. Acad. Sci. USA201210934138231382810.1073/pnas.120807510922869727
    [Google Scholar]
  147. PashineA. ValianteN.M. UlmerJ.B. Targeting the innate immune response with improved vaccine adjuvants.Nat. Med.200511S4Suppl.S63S6810.1038/nm121015812492
    [Google Scholar]
  148. LinehanJ.L. DileepanT. KashemS.W. KaplanD.H. ClearyP. JenkinsM.K. Generation of Th17 cells in response to intranasal infection requires TGF-β1 from dendritic cells and IL-6 from CD301b + dendritic cells.Proc. Natl. Acad. Sci. USA201511241127821278710.1073/pnas.151353211226417101
    [Google Scholar]
  149. WangS. LiuH. ZhangX. QianF. Intranasal and oral vaccination with protein-based antigens: Advantages, challenges and formulation strategies.Protein Cell20156748050310.1007/s13238‑015‑0164‑225944045
    [Google Scholar]
  150. Jabbal-GillI. Nasal vaccine innovation.J. Drug Target.2010181077178610.3109/1061186X.2010.52379021047271
    [Google Scholar]
  151. AfkhamiS. YaoY. XingZ. Methods and clinical development of adenovirus-vectored vaccines against mucosal pathogens.Mol. Ther. Methods Clin. Dev.201631603010.1038/mtm.2016.3027162933
    [Google Scholar]
  152. MalikJ.A. MullaA.H. FarooqiT. PottooF.H. AnwarS. RengasamyK.R.R. Targets and strategies for vaccine development against SARS-CoV-2.Biomed. Pharmacother.202113711125410.1016/j.biopha.2021.11125433550049
    [Google Scholar]
  153. GuoJ. MondalM. ZhouD. Development of novel vaccine vectors: Chimpanzee adenoviral vectors.Hum. Vaccin. Immunother.20181471679168510.1080/21645515.2017.141910829300685
    [Google Scholar]
  154. ChavdaV.P. VoraL.K. PandyaA.K. PatravaleV.B. Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management.Drug Discov. Today202126112619263610.1016/j.drudis.2021.07.02134332100
    [Google Scholar]
  155. van DoremalenN. PurushothamJ.N. SchulzJ.E. Intranasal ChAdOx1 nCoV-19/AZD1222 vaccination reduces viral shedding after SARS-CoV-2 D614G challenge in preclinical models.Sci. Transl. Med.202113607eabh075510.1126/scitranslmed.abh075534315826
    [Google Scholar]
  156. HassanA.O. KafaiN.M. DmitrievI.P. A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2.Cell20201831169184.e1310.1016/j.cell.2020.08.02632931734
    [Google Scholar]
  157. SinghC. VermaS. ReddyP. Phase III Pivotal comparative clinical trial of intranasal (iNCOVACC) and intramuscular COVID-19 vaccine (Covaxin®).NPJ Vaccines20238112510.1038/s41541‑023‑00717‑837596281
    [Google Scholar]
  158. CanSino Biologics IncPhase I/II Clinical Trial of Recombinant Novel Coronavirus (COVID-19) Vaccine (Adenovirus Type 5 Vector) for Inhalation.2023Available From: https://clinicaltrials.gov/ct2/show/NCT04840992
  159. Anhui Zhifei Longcom Biologic Pharmacy CoA Phase III Clinical Trial to Determine the Safety and Efficacy of ZF2001 for Prevention of COVID-19.2022Available From: https://clinicaltrials.gov/ct2/show/NCT04646590
  160. Altimmune IncNasoVAX in Patients With Early Coronavirus Infectious Disease 2019 (COVID-19).2022Available From: https://clinicaltrials.gov/ct2/show/NCT04442230
  161. KingR.G. Silva-SanchezA. PeelJ.N. Single-Dose Intranasal Administration of AdCOVID Elicits Systemic and Mucosal Immunity against SARS-CoV-2 and Fully Protects Mice from Lethal Challenge.Vaccines (Basel)20219888197610.3390/vaccines908088134452006
    [Google Scholar]
  162. FluGen IncFocused on efficacy-M2SR: 40th Annual J.P. Morgan Healthcare Conference.2022Available From: https://kvgo.com/baird-2021-global-healthcare-conference/flugen-inc-sept
  163. SarawarS. HattaY. WatanabeS. M2SR, a novel live single replication influenza virus vaccine, provides effective heterosubtypic protection in mice.Vaccine201634425090509810.1016/j.vaccine.2016.08.06127595896
    [Google Scholar]
  164. RubinR. COVID-19 Vaccine Nasal Spray.JAMA2021326121138114610.1001/jama.2021.1499634581751
    [Google Scholar]
  165. WangY. XingM. ZhouD. Coronavirus disease-19 vaccine development utilizing promising technology.Curr. Opin. HIV AIDS202015635135810.1097/COH.000000000000064832969973
    [Google Scholar]
  166. RuckwardtT.J. MorabitoK.M. PhungE. Safety, tolerability, and immunogenicity of the respiratory syncytial virus prefusion F subunit vaccine DS-Cav1: A phase 1, randomised, open-label, dose-escalation clinical trial.Lancet Respir. Med.20219101111112010.1016/S2213‑2600(21)00098‑933864736
    [Google Scholar]
  167. TandonR. JoshiA. Current Status of Intranasal COVID-19 Vaccine, its Usage and Efficacy: A Narrative Review.J. Clin. Diagn. Res.2023175LE07LE1010.7860/JCDR/2023/63348.17943
    [Google Scholar]
  168. GroenJ. Intravacc.2021Available From: http://www.intravacc.nl/news/intravacc-announces-positive-preclinical-data-intranasal-sars-cov-2-candidate-vaccine/
  169. KoshyS.T. CheungA.S. GuL. GravelineA.R. MooneyD.J. Liposomal delivery enhances immune activation by STING agonists for cancer immunotherapy.Adv. Biosyst.201711-2160001310.1002/adbi.20160001330258983
    [Google Scholar]
  170. MeyerM.J. AuraVax Therapeutics licences intranasal vaccine adjuvant technology from Massachusetts General Hospital.2021Available From: http://www.oindpnews.com/2021/01/auravax therapeutics-licences-intranasal-vaccine-adjuvant-technology-from massachusetts-general-hospital/
  171. MitchellJ.P. BerlinskiA. CanisiusS. Urgent appeal from International Society for Aerosols in Medicine (ISAM) during COVID-19: Clinical decision makers and governmental agencies should consider the inhaled route of administration: A statement from the ISAM Regulatory and Standardization Issues Networking Group.J. Aerosol Med. Pulm. Drug Deliv.202033423523810.1089/jamp.2020.162232589076
    [Google Scholar]
  172. ParkinsK. SaNOtize’s ‘revolutionary’ COVID-19 nasal spray bolstered by Phase II trial data.Available From: https://www.clinicaltrialsarena.com/news/sanotize-nasal-spray-reduces-covid-19-viral-load-uk-clinical-trail/
  173. WeinbergerB. LaskinD.L. HeckD.E. LaskinJ.D. The toxicology of inhaled nitric oxide.Toxicol. Sci.200159151610.1093/toxsci/59.1.511134540
    [Google Scholar]
  174. ÅkerströmS. GunalanV. KengC.T. TanY.J. MirazimiA. Dual effect of nitric oxide on SARS-CoV replication: Viral RNA production and palmitoylation of the S protein are affected.Virology200939511910.1016/j.virol.2009.09.00719800091
    [Google Scholar]
  175. Businesswire. UK Clinical Trial Confirms SaNOtize’s Breakthrough Treatment for COVID-19.2021Available From: https://www.businesswire.com/news/home/20210315005197/en/UK-Clinical-Trial-Confirms-SaNOtize%E2%80%99s-Breakthrough-Treatment-for-COVID-19
  176. Sanotize Research and Development CorpNitric Oxide Releasing Solutions to Prevent and Treat Mild/Moderate COVID-19 Infection (NOCOVID).2021Available From: https://clinicaltrials.gov/ct2/show/NCT04337918
  177. MuruganC RamamoorthyS KuppuswamyG MuruganRK SivalingamY SundaramurthyA COVID-19: A review of newly formed viral clades, pathophysiology, therapeutic strategies and current vaccination tasks.Int J Biol Macromol2021193Pt B116520010.1016/j.ijbiomac.2021.10.14434710479
    [Google Scholar]
  178. Monsalve-NaharroJ.A. Domingo-ChivaE. García CastilloS. Cuesta-MonteroP. Jiménez-VizueteJ.M. Inhaled nitric oxide in adult patients with acute respiratory distress syndrome.Farm. Hosp.201741229231210.7399/fh.2017.41.2.1053328236803
    [Google Scholar]
  179. VeroBiotechHome Use of GENOSYL® Delivery System (DS) to Administer GENOSYL® (nitric oxide) gas for Inhalation for the Treatment of Pulmonary Hypertension Complicated by COVID-19Infection Published in American Journal of Respiratory and Critical Care Medicine.2020
    [Google Scholar]
  180. TzotzosS.J. FischerB. FischerH. ZeitlingerM. Incidence of ARDS and outcomes in hospitalized patients with COVID-19: A global literature survey.Crit. Care202024151610.1186/s13054‑020‑03240‑732825837
    [Google Scholar]
  181. ShmuelK. DaliaM. TairL. YaakovN. Low pH Hypromellose (Taffix) nasal powder spray could reduce SARS-CoV-2 infection rate post mass-gathering event at a highly endemic community: An observational prospective open label user survey.Expert Rev. Anti Infect. Ther.202119101325133010.1080/14787210.2021.190812733759682
    [Google Scholar]
  182. MoakesR.J.A. DaviesS.P. StamatakiZ. GroverL.M. Formulation of a composite nasal spray enabling enhanced surface coverage and prophylaxis of SARS-CoV-2.BioRxiv202010.1101/2020.11.18.388645
    [Google Scholar]
  183. BullerF. Neurimmune and Ethris sign collaboration agreement to rapidly develop inhaled mRNA-based antibody therapy for the treatment of COVID-19.2020Available From: http://www.neurimmune.com/news/neurimmune-and-ethris-sign
  184. WindtreeTherapeutics Trial to Assess the Safety and Tolerability of Lucinactant for Inhalation in Premature Neonates.2019Available From: https://clinicaltrials.gov/ct2/show/NCT02074059
    [Google Scholar]
  185. DuvignaudA. LhommeE. OnaisiR. Inhaled ciclesonide for outpatient treatment of COVID-19 in adults at risk of adverse outcomes: A randomised controlled trial (COVERAGE).Clin. Microbiol. Infect.20222871010101610.1016/j.cmi.2022.02.03135304280
    [Google Scholar]
  186. ChavdaV.P. BaviskarK.P. VaghelaD.A. RautS.S. BedseA.P. Nasal sprays for treating COVID-19: A scientific note.Pharmacol. Rep.202375224926510.1007/s43440‑023‑00463‑736848033
    [Google Scholar]
  187. TemerozoJ.R. SacramentaQ. Fintelman-RodriquesN. The neuropeptides VIP and PACAP inhibit SARS-CoV-2 replication in monocytes and lung epithelial cells, decrease the production of proinflammatory cytokines, and VIP levels are associated with survival in severe COVID-19 patients.J. Leukoc. Biol.202211151107112110.1002/JLB.5COVA1121‑626R35322471
    [Google Scholar]
  188. RöslerB. HeroldS. Lung epithelial GM-CSF improves host defense function and epithelial repair in influenza virus pneumonia—a new therapeutic strategy?Mol. Cell Pediatr.201631294210.1186/s40348‑016‑0055‑527480877
    [Google Scholar]
  189. LiebowitzM.R. SalmanE. NicoliniH. RosenthalN. HanoverR. MontiL. Effect of an acute intranasal aerosol dose of PH94B on social and performance anxiety in women with social anxiety disorder.Am. J. Psychiatry2014171667568210.1176/appi.ajp.2014.1210134224700254
    [Google Scholar]
  190. LacroixM. RousseauF. GuilhotF. Novel insights into interleukin 6 (IL-6) cis- and trans-signaling pathways by differentially manipulating the assembly of the IL-6 signaling complex.J. Biol. Chem.201529045269432695310.1074/jbc.M115.68213826363066
    [Google Scholar]
  191. AmpioPharmaceuticals Inc.. Study of Ampion for the treatment of Adult COVID-19 patients requiring oxygen supplementation.2021Available From: https://clinicaltrials.gov/ct2/show/NCT04456452
  192. MonkP.D. MarsdenR.J. TearV.J. Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: A randomised, double-blind, placebo-controlled, phase 2 trial.Lancet Respir. Med.20219219620610.1016/S2213‑2600(20)30511‑733189161
    [Google Scholar]
  193. Pfizer. Long-term Safety Study of BHV-3500 (Zavegepant*) for the Acute Treatment of Migraine.2023Available From: https://clinicaltrials.gov/study/NCT04408794
  194. MutschM. ZhouW. RhodesP. Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland.N. Engl. J. Med.2004350989690310.1056/NEJMoa03059514985487
    [Google Scholar]
  195. IzurietaH.S. HaberP. WiseR.P. Adverse events reported following live, cold-adapted, intranasal influenza vaccine.JAMA2005294212720272510.1001/jama.294.21.272016333007
    [Google Scholar]
  196. StoweJ. AndrewsN. WiseL. MillerE. Bell’s palsy and parenteral inactivated influenza vaccine.Hum. Vaccin.20062311011210.4161/hv.279017012908
    [Google Scholar]
  197. Rowhani-RahbarA. KleinN.P. LewisN. Immunization and Bell’s palsy in children: A case-centered analysis.Am. J. Epidemiol.2012175987888510.1093/aje/kws01122411861
    [Google Scholar]
  198. Souvik Chattopadhyay. SouravChakraborty SumonSheel Nasal route: A breakthrough for drug delivery.J. Pharm. Negat. Results202213931533410.47750/pnr.2022.13.S09.038
    [Google Scholar]
  199. ChattopadhyayS. DasS. SarmaK.N. Nose-to-brain drug delivery: An update to the alternative path to successful targeted anti-migraine drugs.Int J Appl Pharm2021132677510.22159/ijap.2021v13i2.40404
    [Google Scholar]
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Keyword(s): Drug delivery; mucosal administration; nasal delivery; nasal route; SARS-CoV-2; vaccines
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