Skip to content
2000
Volume 25, Issue 4
  • ISSN: 1871-5249
  • E-ISSN: 1875-6166

Abstract

Brain-related Neurodegenerative Disorders (NDD) are the leading cause of low life expectancy globally. Brain-targeted drug delivery is required for treating most the NDD bypassing the blood-brain barrier, and hepatic first-pass metabolism. The nasal-brain drug delivery route has the advantage of locally enhancing drug delivery to the brain, mainly through the olfactory route rather than systemic circulation. To overcome the limitations of nasal-brain drug delivery, a nanocarrier approach and mucoadhesive polymers are needed. Notwithstanding these constraints, various nanotechnology techniques have been created, including polymeric micelles, liposomes, polymeric nanoparticles, solid lipid nanoparticles, & nano-emulsions. This review aims to explore the intranasal pathway for drug delivery through the nasal-brain lymphatic systems, considering brain anatomy and physiology along with a drug formulation design approach.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cnsamc/10.2174/0118715249329586240924105624
2024-10-15
2025-10-27

  • From This Site

    /content/journals/cnsamc/10.2174/0118715249329586240924105624
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. PrinceM. Comas-HerreraA. KnappM. GuerchetM. KaragiannidouM. World Alzheimer Report 2016. Improving healthcare for people living with dementia: Coverage, Quality and costs now and in the future.Alzheimer’s Disease International2016
     [Google Scholar]
  2. AgrawalM. SarafS. SarafS. AntimisiarisS.G. ChouguleM.B. ShoyeleS.A. AlexanderA. Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs.J. Control. Release201828113917710.1016/j.jconrel.2018.05.01129772289
     [Google Scholar]
  3. JamesS.L. AbateD. AbateK.H. AbayS.M. AbbafatiC. AbbasiN. AbbastabarH. Abd-AllahF. AbdelaJ. AbdelalimA. AbdollahpourI. AbdulkaderR.S. AbebeZ. AberaS.F. AbilO.Z. AbrahaH.N. Abu-RaddadL.J. Abu-RmeilehN.M.E. AccrombessiM.M.K. AcharyaD. AcharyaP. AckermanI.N. AdamuA.A. AdebayoO.M. AdekanmbiV. AdetokunbohO.O. AdibM.G. AdsuarJ.C. AfanviK.A. AfaridehM. AfshinA. AgarwalG. AgesaK.M. AggarwalR. AghayanS.A. AgrawalS. AhmadiA. AhmadiM. AhmadiehH. AhmedM.B. AichourA.N. AichourI. AichourM.T.E. AkinyemijuT. AkseerN. Al-AlyZ. Al-EyadhyA. Al-MekhlafiH.M. Al-RaddadiR.M. AlahdabF. AlamK. AlamT. AlashiA. AlavianS.M. AleneK.A. AlijanzadehM. Alizadeh-NavaeiR. AljunidS.M. AlkerwiA. AllaF. AllebeckP. AlouaniM.M.L. AltirkawiK. Alvis-GuzmanN. AmareA.T. AmindeL.N. AmmarW. AmoakoY.A. AnberN.H. AndreiC.L. AndroudiS. AnimutM.D. AnjomshoaM. AnshaM.G. AntonioC.A.T. AnwariP. ArablooJ. ArauzA. AremuO. ArianiF. ArmoonB. ÄrnlövJ. AroraA. ArtamanA. AryalK.K. AsayeshH. AsgharR.J. AtaroZ. AtreS.R. AusloosM. Avila-BurgosL. AvokpahoE.F.G.A. AwasthiA. Ayala QuintanillaB.P. AyerR. AzzopardiP.S. BabazadehA. BadaliH. BadawiA. BaliA.G. BallesterosK.E. BallewS.H. BanachM. BanoubJ.A.M. BanstolaA. BaracA. BarbozaM.A. Barker-ColloS.L. BärnighausenT.W. BarreroL.H. BauneB.T. Bazargan-HejaziS. BediN. BeghiE. BehzadifarM. BehzadifarM. BéjotY. BelachewA.B. BelayY.A. BellM.L. BelloA.K. BensenorI.M. BernabeE. BernsteinR.S. BeuranM. BeyranvandT. BhalaN. BhattaraiS. BhaumikS. BhuttaZ.A. BiadgoB. BijaniA. BikbovB. BilanoV. BililignN. Bin SayeedM.S. BisanzioD. BlackerB.F. BlythF.M. Bou-OrmI.R. BoufousS. BourneR. BradyO.J. BraininM. BrantL.C. BrazinovaA. BreitbordeN.J.K. BrennerH. BriantP.S. BriggsA.M. BrikoA.N. BrittonG. BrughaT. BuchbinderR. BusseR. ButtZ.A. Cahuana-HurtadoL. CanoJ. CárdenasR. CarreroJ.J. CarterA. CarvalhoF. Castañeda-OrjuelaC.A. Castillo RivasJ. CastroF. Catalá-LópezF. CercyK.M. CerinE. ChaiahY. ChangA.R. ChangH-Y. ChangJ-C. CharlsonF.J. ChattopadhyayA. ChattuV.K. ChaturvediP. ChiangP.P-C. ChinK.L. ChitheerA. ChoiJ-Y.J. ChowdhuryR. ChristensenH. ChristopherD.J. CicuttiniF.M. CiobanuL.G. CirilloM. ClaroR.M. Collado-MateoD. CooperC. CoreshJ. CortesiP.A. CortinovisM. CostaM. CousinE. CriquiM.H. CromwellE.A. CrossM. CrumpJ.A. DadiA.F. DandonaL. DandonaR. DarganP.I. DaryaniA. Das GuptaR. Das NevesJ. DasaT.T. DaveyG. DavisA.C. DavitoiuD.V. De CourtenB. De La HozF.P. De LeoD. De NeveJ-W. DegefaM.G. DegenhardtL. DeiparineS. DellavalleR.P. DemozG.T. DeribeK. DervenisN. Des JarlaisD.C. DessieG.A. DeyS. DharmaratneS.D. DinberuM.T. DiracM.A. DjalaliniaS. DoanL. DokovaK. DokuD.T. DorseyE.R. DoyleK.E. DriscollT.R. DubeyM. DubljaninE. DukenE.E. DuncanB.B. DuraesA.R. EbrahimiH. EbrahimpourS. EchkoM.M. EdvardssonD. EffiongA. EhrlichJ.R. El BcheraouiC. El Sayed ZakiM. El-KhatibZ. ElkoutH. ElyazarI.R.F. EnayatiA. EndriesA.Y. ErB. ErskineH.E. EshratiB. EskandariehS. EsteghamatiA. EsteghamatiS. FakhimH. Fallah OmraniV. FaramarziM. FareedM. FarhadiF. FaridT.A. FarinhaC.S.E. FarioliA. FaroA. FarvidM.S. FarzadfarF. FeiginV.L. FentahunN. FereshtehnejadS-M. FernandesE. FernandesJ.C. FerrariA.J. FeyissaG.T. FilipI. FischerF. FitzmauriceC. FoigtN.A. ForemanK.J. FoxJ. FrankT.D. FukumotoT. FullmanN. FürstT. FurtadoJ.M. FutranN.D. GallS. GanjiM. GankpeF.G. Garcia-BasteiroA.L. GardnerW.M. GebreA.K. GebremedhinA.T. GebremichaelT.G. GelanoT.F. GeleijnseJ.M. Genova-MalerasR. GeramoY.C.D. GethingP.W. GezaeK.E. GhadiriK. Ghasemi FalavarjaniK. Ghasemi-KasmanM. GhimireM. GhoshR. GhoshalA.G. GiampaoliS. GillP.S. GillT.K. GinawiI.A. GiussaniG. GnedovskayaE.V. GoldbergE.M. GoliS. Gómez-DantésH. GonaP.N. GopalaniS.V. GormanT.M. GoulartA.C. GoulartB.N.G. GradaA. GramsM.E. GrossoG. GugnaniH.C. GuoY. GuptaP.C. GuptaR. GuptaR. GuptaT. GyawaliB. HaagsmaJ.A. HachinskiV. Hafezi-NejadN. Haghparast BidgoliH. HagosT.B. HailuG.B. Haj-MirzaianA. Haj-MirzaianA. HamadehR.R. HamidiS. HandalA.J. HankeyG.J. HaoY. HarbH.L. HarikrishnanS. HaroJ.M. HasanM. HassankhaniH. HassenH.Y. HavmoellerR. HawleyC.N. HayR.J. HayS.I. Hedayatizadeh-OmranA. HeibatiB. HendrieD. HenokA. HerteliuC. HeydarpourS. HibstuD.T. HoangH.T. HoekH.W. HoffmanH.J. HoleM.K. Homaie RadE. HoogarP. HosgoodH.D. HosseiniS.M. HosseinzadehM. HostiucM. HostiucS. HotezP.J. HoyD.G. HsairiM. HtetA.S. HuG. HuangJ.J. HuynhC.K. IburgK.M. IkedaC.T. IleanuB. IlesanmiO.S. IqbalU. IrvaniS.S.N. IrvineC.M.S. IslamS.M.S. IslamiF. JacobsenK.H. JahangiryL. JahanmehrN. JainS.K. JakovljevicM. JavanbakhtM. JayatillekeA.U. JeemonP. JhaR.P. JhaV. JiJ.S. JohnsonC.O. JonasJ.B. JozwiakJ.J. JungariS.B. JürissonM. KabirZ. KadelR. KahsayA. KalaniR. KanchanT. KaramiM. Karami MatinB. KarchA. KaremaC. KarimiN. KarimiS.M. KasaeianA. KassaD.H. KassaG.M. KassaT.D. KassebaumN.J. KatikireddiS.V. KawakamiN. KaryaniA.K. KeighobadiM.M. KeiyoroP.N. KemmerL. KempG.R. KengneA.P. KerenA. KhaderY.S. KhafaeiB. KhafaieM.A. KhajaviA. KhalilI.A. KhanE.A. KhanM.S. KhanM.A. KhangY-H. KhazaeiM. KhojaA.T. KhosraviA. KhosraviM.H. KiadaliriA.A. KiirithioD.N. KimC-I. KimD. KimP. KimY-E. KimY.J. KimokotiR.W. KinfuY. KisaA. Kissimova-SkarbekK. KivimäkiM. KnudsenA.K.S. KocarnikJ.M. KochharS. KokuboY. KololaT. KopecJ.A. KosenS. KotsakisG.A. KoulP.A. KoyanagiA. KravchenkoM.A. KrishanK. KrohnK.J. Kuate DefoB. Kucuk BicerB. KumarG.A. KumarM. KyuH.H. LadD.P. LadS.D. LafranconiA. LallooR. LallukkaT. LamiF.H. LansinghV.C. LatifiA. LauK.M-M. LazarusJ.V. LeasherJ.L. LedesmaJ.R. LeeP.H. LeighJ. LeungJ. LeviM. LewyckaS. LiS. LiY. LiaoY. LibenM.L. LimL-L. LimS.S. LiuS. LodhaR. LookerK.J. LopezA.D. LorkowskiS. LotufoP.A. LowN. LozanoR. LucasT.C.D. LucchesiL.R. LuneviciusR. LyonsR.A. MaS. MacarayanE.R.K. MackayM.T. MadottoF. Magdy Abd El RazekH. Magdy Abd El RazekM. MaghavaniD.P. MahotraN.B. MaiH.T. MajdanM. MajdzadehR. MajeedA. MalekzadehR. MaltaD.C. MamunA.A. MandaA-L. ManguerraH. ManhertzT. MansourniaM.A. MantovaniL.G. MapomaC.C. MaravillaJ.C. MarcenesW. MarksA. Martins-MeloF.R. MartopulloI. MärzW. MarzanM.B. Mashamba-ThompsonT.P. MassenburgB.B. MathurM.R. MatsushitaK. MaulikP.K. MazidiM. McAlindenC. McGrathJ.J. McKeeM. MehndirattaM.M. MehrotraR. MehtaK.M. MehtaV. Mejia-RodriguezF. MekonenT. MeleseA. MelkuM. MeltzerM. MemiahP.T.N. MemishZ.A. MendozaW. MengistuD.T. MengistuG. MensahG.A. MeretaS.T. MeretojaA. MeretojaT.J. MestrovicT. MezerjiN.M.G. MiazgowskiB. MiazgowskiT. MillearA.I. MillerT.R. MiltzB. MiniG.K. MirarefinM. MirrakhimovE.M. MisganawA.T. MitchellP.B. MitikuH. MoazenB. MohajerB. MohammadK.A. MohammadifardN. Mohammadnia-AfrouziM. MohammedM.A. MohammedS. MohebiF. MoitraM. MokdadA.H. MolokhiaM. MonastaL. MoodleyY. MoosazadehM. MoradiG. Moradi-LakehM. MoradinazarM. MoragaP. MorawskaL. Moreno VelásquezI. Morgado-Da-CostaJ. MorrisonS.D. MoschosM.M. Mountjoy-VenningW.C. MousaviS.M. MrutsK.B. MucheA.A. MuchieK.F. MuellerU.O. MuhammedO.S. MukhopadhyayS. MullerK. MumfordJ.E. MurhekarM. MusaJ. MusaK.I. MustafaG. NabhanA.F. NagataC. NaghaviM. NaheedA. NahvijouA. NaikG. NaikN. NajafiF. NaldiL. NamH.S. NangiaV. NansseuJ.R. NascimentoB.R. NatarajanG. NeamatiN. NegoiI. NegoiR.I. NeupaneS. NewtonC.R.J. NgunjiriJ.W. NguyenA.Q. NguyenH.T. NguyenH.L.T. NguyenH.T. NguyenL.H. NguyenM. NguyenN.B. NguyenS.H. NicholsE. NingrumD.N.A. NixonM.R. NolutshunguN. NomuraS. NorheimO.F. NorooziM. NorrvingB. NoubiapJ.J. NouriH.R. Nourollahpour ShiadehM. NowrooziM.R. NsoesieE.O. NyasuluP.S. OdellC.M. Ofori-AsensoR. OgboF.A. OhI-H. OladimejiO. OlagunjuA.T. OlagunjuT.O. OlivaresP.R. OlsenH.E. OlusanyaB.O. OngK.L. OngS.K. OrenE. OrtizA. OtaE. OtstavnovS.S. ØverlandS. OwolabiM.O. P AM. PacellaR. PakpourA.H. PanaA. Panda-JonasS. ParisiA. ParkE-K. ParryC.D.H. PatelS. PatiS. PatilS.T. PatleA. PattonG.C. PaturiV.R. PaulsonK.R. PearceN. PereiraD.M. PericoN. PesudovsK. PhamH.Q. PhillipsM.R. PigottD.M. PillayJ.D. PiradovM.A. PirsahebM. PishgarF. Plana-RipollO. PlassD. PolinderS. PopovaS. PostmaM.J. PourshamsA. PoustchiH. PrabhakaranD. PrakashS. PrakashV. PurcellC.A. PurwarM.B. QorbaniM. QuistbergD.A. RadfarA. RafayA. RafieiA. RahimF. RahimiK. Rahimi-MovagharA. Rahimi-MovagharV. RahmanM. RahmanM.H. RahmanM.A. RahmanS.U. RaiR.K. RajatiF. RamU. RanjanP. RantaA. RaoP.C. RawafD.L. RawafS. ReddyK.S. ReinerR.C. ReinigN. ReitsmaM.B. RemuzziG. RenzahoA.M.N. ResnikoffS. RezaeiS. RezaiM.S. RibeiroA.L.P. RobertsN.L.S. RobinsonS.R. RoeverL. RonfaniL. RoshandelG. RostamiA. RothG.A. RoyA. RubagottiE. SachdevP.S. SadatN. SaddikB. SadeghiE. Saeedi MoghaddamS. SafariH. SafariY. Safari-FaramaniR. SafdarianM. SafiS. SafiriS. SagarR. SahebkarA. SahraianM.A. SajadiH.S. SalamN. SalamaJ.S. SalamatiP. SaleemK. SaleemZ. SalimiY. SalomonJ.A. SalviS.S. SalzI. SamyA.M. SanabriaJ. SangY. SantomauroD.F. SantosI.S. SantosJ.V. Santric MilicevicM.M. Sao JoseB.P. SardanaM. SarkerA.R. SarrafzadeganN. SartoriusB. SarviS. SathianB. SatpathyM. SawantA.R. SawhneyM. SaxenaS. SaylanM. SchaeffnerE. SchmidtM.I. SchneiderI.J.C. SchöttkerB. SchwebelD.C. SchwendickeF. ScottJ.G. SekerijaM. SepanlouS.G. Serván-MoriE. SeyedmousaviS. ShabaninejadH. ShafieesabetA. ShahbaziM. ShaheenA.A. ShaikhM.A. Shams-BeyranvandM. ShamsiM. ShamsizadehM. SharafiH. SharafiK. SharifM. Sharif-AlhoseiniM. SharmaM. SharmaR. SheJ. SheikhA. ShiP. ShibuyaK. ShigematsuM. ShiriR. ShirkoohiR. ShishaniK. ShiueI. ShokranehF. ShomanH. ShrimeM.G. SiS. SiabaniS. SiddiqiT.J. SigfusdottirI.D. SigurvinsdottirR. SilvaJ.P. SilveiraD.G.A. SingamN.S.V. SinghJ.A. SinghN.P. SinghV. SinhaD.N. SkiadaresiE. SlepakE.L.N. SliwaK. SmithD.L. SmithM. Soares FilhoA.M. SobaihB.H. SobhaniS. SobngwiE. SonejiS.S. SoofiM. SoosaraeiM. SorensenR.J.D. SorianoJ.B. SoyiriI.N. SposatoL.A. SreeramareddyC.T. SrinivasanV. StanawayJ.D. SteinD.J. SteinerC. SteinerT.J. StokesM.A. StovnerL.J. SubartM.L. SudaryantoA. SufiyanM.B. SunguyaB.F. SurP.J. SutradharI. SykesB.L. SylteD.O. Tabarés-SeisdedosR. TadakamadlaS.K. TadesseB.T. TandonN. TassewS.G. TavakkoliM. TaveiraN. TaylorH.R. Tehrani-BanihashemiA. TekalignT.G. TekelemedhinS.W. TekleM.G. TemesgenH. TemsahM-H. TemsahO. TerkawiA.S. TeweldemedhinM. ThankappanK.R. ThomasN. TilahunB. ToQ.G. TonelliM. Topor-MadryR. TopouzisF. TorreA.E. Tortajada-GirbésM. TouvierM. Tovani-PaloneM.R. TowbinJ.A. TranB.X. TranK.B. TroegerC.E. TruelsenT.C. TsilimbarisM.K. TsoiD. Tudor CarL. TuzcuE.M. UkwajaK.N. UllahI. UndurragaE.A. UnutzerJ. UpdikeR.L. UsmanM.S. UthmanO.A. VaduganathanM. VaeziA. ValdezP.R. VarugheseS. VasankariT.J. VenketasubramanianN. VillafainaS. ViolanteF.S. VladimirovS.K. VlassovV. VollsetS.E. VosoughiK. VujcicI.S. WagnewF.S. WaheedY. WallerS.G. WangY. WangY-P. WeiderpassE. WeintraubR.G. WeissD.J. WeldegebrealF. WeldegwergsK.G. WerdeckerA. WestT.E. WhitefordH.A. WideckaJ. WijeratneT. WilnerL.B. WilsonS. WinklerA.S. WiyehA.B. WiysongeC.S. WolfeC.D.A. WoolfA.D. WuS. WuY-C. WyperG.M.A. XavierD. XuG. YadgirS. YadollahpourA. Yahyazadeh JabbariS.H. YamadaT. YanL.L. YanoY. YaseriM. YasinY.J. YeshanehA. YimerE.M. YipP. YismaE. YonemotoN. YoonS-J. YotebiengM. YounisM.Z. YousefifardM. YuC. ZadnikV. ZaidiZ. ZamanS.B. ZamaniM. ZareZ. ZelekeA.J. ZenebeZ.M. ZhangK. ZhaoZ. ZhouM. ZodpeyS. ZuckerI. VosT. MurrayC.J.L. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017.Lancet2018392101591789185810.1016/S0140‑6736(18)32279‑730496104
     [Google Scholar]
  4. FeiginV.L. NicholsE. AlamT. BannickM.S. BeghiE. BlakeN. CulpepperW.J. DorseyE.R. ElbazA. EllenbogenR.G. FisherJ.L. FitzmauriceC. GiussaniG. GlennieL. JamesS.L. JohnsonC.O. KassebaumN.J. LogroscinoG. MarinB. Mountjoy-VenningW.C. NguyenM. Ofori-AsensoR. PatelA.P. PiccininniM. RothG.A. SteinerT.J. StovnerL.J. SzoekeC.E.I. TheadomA. VollsetS.E. WallinM.T. WrightC. ZuntJ.R. AbbasiN. Abd-AllahF. AbdelalimA. AbdollahpourI. AboyansV. AbrahaH.N. AcharyaD. AdamuA.A. AdebayoO.M. AdeoyeA.M. AdsuarJ.C. AfaridehM. AgrawalS. AhmadiA. AhmedM.B. AichourA.N. AichourI. AichourM.T.E. AkinyemiR.O. AkseerN. Al-EyadhyA. Al-Shahi SalmanR. AlahdabF. AleneK.A. AljunidS.M. AltirkawiK. Alvis-GuzmanN. AnberN.H. AntonioC.A.T. ArablooJ. AremuO. ÄrnlövJ. AsayeshH. AsgharR.J. AtalayH.T. AwasthiA. Ayala QuintanillaB.P. AyukT.B. BadawiA. BanachM. BanoubJ.A.M. BarbozaM.A. Barker-ColloS.L. BärnighausenT.W. BauneB.T. BediN. BehzadifarM. BehzadifarM. BéjotY. BekeleB.B. BelachewA.B. BennettD.A. BensenorI.M. BerhaneA. BeuranM. BhattacharyyaK. BhuttaZ.A. BiadgoB. BijaniA. BililignN. Bin SayeedM.S. BlazesC.K. BrayneC. ButtZ.A. Campos-NonatoI.R. Cantu-BritoC. CarM. CárdenasR. CarreroJ.J. CarvalhoF. Castañeda-OrjuelaC.A. CastroF. Catalá-LópezF. CerinE. ChaiahY. ChangJ-C. ChatziralliI. ChiangP.P-C. ChristensenH. ChristopherD.J. CooperC. CortesiP.A. CostaV.M. CriquiM.H. CroweC.S. DamascenoA.A.M. DaryaniA. De la Cruz-GóngoraV. De la HozF.P. De LeoD. DemozG.T. DeribeK. DharmaratneS.D. DiazD. DinberuM.T. DjalaliniaS. DokuD.T. DubeyM. DubljaninE. DukenE.E. EdvardssonD. El-KhatibZ. EndresM. EndriesA.Y. EskandariehS. EsteghamatiA. EsteghamatiS. FarhadiF. FaroA. FarzadfarF. FarzaeiM.H. FatimaB. FereshtehnejadS-M. FernandesE. FeyissaG.T. FilipI. FischerF. FukumotoT. GanjiM. GankpeF.G. Garcia-GordilloM.A. GebreA.K. GebremichaelT.G. GelawB.K. GeleijnseJ.M. GeremewD. GezaeK.E. Ghasemi-KasmanM. GideyM.Y. GillP.S. GillT.K. GirmaE.T. GnedovskayaE.V. GoulartA.C. GradaA. GrossoG. GuoY. GuptaR. GuptaR. HaagsmaJ.A. HagosT.B. Haj-MirzaianA. Haj-MirzaianA. HamadehR.R. HamidiS. HankeyG.J. HaoY. HaroJ.M. HassankhaniH. HassenH.Y. HavmoellerR. HayS.I. HegazyM.I. HeidariB. HenokA. HeydarpourF. HoangC.L. HoleM.K. Homaie RadE. HosseiniS.M. HuG. IgumborE.U. IlesanmiO.S. IrvaniS.S.N. IslamS.M.S. JakovljevicM. JavanbakhtM. JhaR.P. JobanputraY.B. JonasJ.B. JozwiakJ.J. JürissonM. KahsayA. KalaniR. KalkondeY. KamilT.A. KanchanT. KaramiM. KarchA. KarimiN. KasaeianA. KassaT.D. KassaZ.Y. KaulA. KefaleA.T. KeiyoroP.N. KhaderY.S. KhafaieM.A. KhalilI.A. KhanE.A. KhangY-H. KhazaieH. KiadaliriA.A. KiirithioD.N. KimA.S. KimD. KimY-E. KimY.J. KisaA. KokuboY. KoyanagiA. KrishnamurthiR.V. Kuate DefoB. Kucuk BicerB. KumarM. LaceyB. LafranconiA. LansinghV.C. LatifiA. LeshargieC.T. LiS. LiaoY. LinnS. LoW.D. LopezJ.C.F. LorkowskiS. LotufoP.A. LucasR.M. LuneviciusR. MackayM.T. MahotraN.B. MajdanM. MajdzadehR. MajeedA. MalekzadehR. MaltaD.C. ManafiN. MansourniaM.A. MantovaniL.G. MärzW. Mashamba-ThompsonT.P. MassenburgB.B. MateK.K.V. McAlindenC. McGrathJ.J. MehtaV. MeierT. MelesH.G. MeleseA. MemiahP.T.N. MemishZ.A. MendozaW. MengistuD.T. MengistuG. MeretojaA. MeretojaT.J. MestrovicT. MiazgowskiB. MiazgowskiT. MillerT.R. MiniG.K. MirrakhimovE.M. MoazenB. MohajerB. Mohammad Gholi MezerjiN. MohammadiM. Mohammadi-KhanaposhtaniM. MohammadibakhshR. Mohammadnia-AfrouziM. MohammedS. MohebiF. MokdadA.H. MonastaL. MondelloS. MoodleyY. MoosazadehM. MoradiG. Moradi-LakehM. MoradinazarM. MoragaP. Moreno VelásquezI. MorrisonS.D. MousaviS.M. MuhammedO.S. MuruetW. MusaK.I. MustafaG. NaderiM. NagelG. NaheedA. NaikG. NajafiF. NangiaV. NegoiI. NegoiR.I. NewtonC.R.J. NgunjiriJ.W. NguyenC.T. NguyenL.H. NingrumD.N.A. NirayoY.L. NixonM.R. NorrvingB. NoubiapJ.J. Nourollahpour ShiadehM. NyasuluP.S. OgahO.S. OhI-H. OlagunjuA.T. OlagunjuT.O. OlivaresP.R. OnwujekweO.E. OrenE. OwolabiM.O. PaM. PakpourA.H. PanW-H. Panda-JonasS. PandianJ.D. PatelS.K. PereiraD.M. PetzoldM. PillayJ.D. PiradovM.A. PolanczykG.V. PolinderS. PostmaM.J. PoultonR. PoustchiH. PrakashS. PrakashV. QorbaniM. RadfarA. RafayA. RafieiA. RahimF. Rahimi-MovagharV. RahmanM. RahmanM.H.U. RahmanM.A. RajatiF. RamU. RantaA. RawafD.L. RawafS. ReinigN. ReisC. RenzahoA.M.N. ResnikoffS. RezaeianS. RezaiM.S. Rios GonzálezC.M. RobertsN.L.S. RoeverL. RonfaniL. RoroE.M. RoshandelG. RostamiA. SabbaghP. SaccoR.L. SachdevP.S. SaddikB. SafariH. Safari-FaramaniR. SafiS. SafiriS. SagarR. SahathevanR. SahebkarA. SahraianM.A. SalamatiP. Salehi ZahabiS. SalimiY. SamyA.M. SanabriaJ. SantosI.S. Santric MilicevicM.M. SarrafzadeganN. SartoriusB. SarviS. SathianB. SatpathyM. SawantA.R. SawhneyM. SchneiderI.J.C. SchöttkerB. SchwebelD.C. SeedatS. SepanlouS.G. ShabaninejadH. ShafieesabetA. ShaikhM.A. ShakirR.A. Shams-BeyranvandM. ShamsizadehM. SharifM. Sharif-AlhoseiniM. SheJ. SheikhA. ShethK.N. ShigematsuM. ShiriR. ShirkoohiR. ShiueI. SiabaniS. SiddiqiT.J. SigfusdottirI.D. SigurvinsdottirR. SilberbergD.H. SilvaJ.P. SilveiraD.G.A. SinghJ.A. SinhaD.N. SkiadaresiE. SmithM. SobaihB.H. SobhaniS. SoofiM. SoyiriI.N. SposatoL.A. SteinD.J. SteinM.B. StokesM.A. SufiyanM.B. SykesB.L. SylajaP.N. Tabarés-SeisdedosR. Te AoB.J. Tehrani-BanihashemiA. TemsahM-H. TemsahO. ThakurJ.S. ThriftA.G. Topor-MadryR. Tortajada-GirbésM. Tovani-PaloneM.R. TranB.X. TranK.B. TruelsenT.C. TsadikA.G. Tudor CarL. UkwajaK.N. UllahI. UsmanM.S. UthmanO.A. ValdezP.R. VasankariT.J. VasanthanR. VeisaniY. VenketasubramanianN. ViolanteF.S. VlassovV. VosoughiK. VuG.T. VujcicI.S. WagnewF.S. WaheedY. WangY-P. WeiderpassE. WeissJ. WhitefordH.A. WijeratneT. WinklerA.S. WiysongeC.S. WolfeC.D.A. XuG. YadollahpourA. YamadaT. YanoY. YaseriM. YatsuyaH. YimerE.M. YipP. YismaE. YonemotoN. YousefifardM. YuC. ZaidiZ. ZamanS.B. ZamaniM. ZandianH. ZareZ. ZhangY. ZodpeyS. NaghaviM. MurrayC.J.L. VosT. GBD 2016 Neurology Collaborators Global, regional, and national burden of neurological disorders, 1990–2016: A systematic analysis for the Global Burden of Disease Study 2016.Lancet Neurol.201918545948010.1016/S1474‑4422(18)30499‑X30879893
     [Google Scholar]
  5. WanneveichM. MoisanF. Jacqmin-GaddaH. ElbazA. JolyP. Projections of prevalence, lifetime risk, and life expectancy of Parkinson’s disease (2010‐2030) in France.Mov. Disord.20183391449145510.1002/mds.2744730145805
     [Google Scholar]
  6. BlankL.J. JetteN. Epilepsy research in 2022: Clinical advances.Lancet Neurol.2023221151710.1016/S1474‑4422(22)00486‑036517157
     [Google Scholar]
  7. OstromQ.T. GittlemanH. de BlankP.M. FinlayJ.L. GurneyJ.G. McKean-CowdinR. StearnsD.S. WolffJ.E. LiuM. WolinskyY. KruchkoC. Barnholtz-SloanJ.S. American brain tumor association adolescent and young adult primary brain and central nervous system tumors diagnosed in the United States in 2008-2012.Neuro-oncol.201618Suppl 1Suppl. 1i1i5010.1093/neuonc/nov29726705298
     [Google Scholar]
  8. KratzerT.B. SiegelR.L. MillerK.D. SungH. IslamiF. JemalA. Progress against cancer mortality 50 years after passage of the National Cancer Act.JAMA Oncol.20228115615910.1001/jamaoncol.2021.566834762103
     [Google Scholar]
  9. DingS. KhanA.I. CaiX. SongY. LyuZ. DuD. DuttaP. LinY. Overcoming blood–brain barrier transport: Advances in nanoparticle-based drug delivery strategies.Mater. Today20203711212510.1016/j.mattod.2020.02.00133093794
     [Google Scholar]
  10. GaoH. Progress and perspectives on targeting nanoparticles for brain drug delivery.Acta Pharm. Sin. B20166426828610.1016/j.apsb.2016.05.01327471668
     [Google Scholar]
  11. SelvarajK. GowthamarajanK. KarriV.V.S.R. Nose to brain transport pathways an overview: potential of nanostructured lipid carriers in nose to brain targeting.Artif. Cells Nanomed. Biotechnol.20184682088209529282995
     [Google Scholar]
  12. KambleM.S. BhaleraoK.K. BhosaleA.V. ChaudhariP.D. A review on nose-to-brain drug delivery.Int J Pharm Chem Sci.201321516525
     [Google Scholar]
  13. GuptaS. DhandaS. SandhirR. Anatomy and physiology of blood-brain barrier.Brain targeted drug delivery system.Elsevier201973110.1016/B978‑0‑12‑814001‑7.00002‑0
     [Google Scholar]
  14. CroweT.P. GreenleeM.H.W. KanthasamyA.G. HsuW.H. Mechanism of intranasal drug delivery directly to the brain.Life Sci.2018195445210.1016/j.lfs.2017.12.02529277310
     [Google Scholar]
  15. KashyapK. ShuklaR. Drug delivery and targeting to the brain through nasal route: Mechanisms, applications and challenges.Curr. Drug Deliv.2019161088790110.2174/156720181666619102912274031660815
     [Google Scholar]
  16. LiuQ. YangY. FanX. Microvascular pericytes in brain-associated vascular disease.Biomed. Pharmacother.202012110963310.1016/j.biopha.2019.10963331743876
     [Google Scholar]
  17. MichinagaS. KoyamaY. Dual roles of astrocyte-derived factors in regulation of blood-brain barrier function after brain damage.Int. J. Mol. Sci.201920357110.3390/ijms2003057130699952
     [Google Scholar]
  18. DanemanR. PratA. The blood-brain barrier.Cold Spring Harb. Perspect. Biol.201571a02041210.1101/cshperspect.a02041225561720
     [Google Scholar]
  19. MartinsP.P. SmythH.D.C. CuiZ. Strategies to facilitate or block nose-to-brain drug delivery.Int. J. Pharm.201957011863510.1016/j.ijpharm.2019.11863531445062
     [Google Scholar]
  20. BonferoniM.C. RossiS. SandriG. FerrariF. GaviniE. RassuG. GiunchediP. Nanoemulsions for “nose-to-brain” drug delivery.Pharmaceutics20191128410.3390/pharmaceutics1102008430781585
     [Google Scholar]
  21. KumarR. ThakurA. SinghP.K. BiswalS.S. KumarN. JhaC.B. SinghG. KaurC. WadhwaS. Drug delivery through nose: A noninvasive technique for brain targeting.J. Rep. Pharm. Sci.20209116817510.4103/jrptps.JRPTPS_59_19
     [Google Scholar]
  22. NagpalK. SinghS.K. MishraD.N. Drug targeting to brain: A systematic approach to study the factors, parameters and approaches for prediction of permeability of drugs across BBB.Expert Opin. Drug Deliv.201310792795510.1517/17425247.2013.76235423330786
     [Google Scholar]
  23. 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]
  24. Garcia-GarciaE. AndrieuxK. GilS. CouvreurP. Colloidal carriers and blood–brain barrier (BBB) translocation: A way to deliver drugs to the brain?Int. J. Pharm.2005298227429210.1016/j.ijpharm.2005.03.03115896933
     [Google Scholar]
  25. van TellingenO. Yetkin-ArikB. de GooijerM.C. WesselingP. WurdingerT. de VriesH.E. Overcoming the blood–brain tumor barrier for effective glioblastoma treatment.Drug Resist. Updat.20151911210.1016/j.drup.2015.02.00225791797
     [Google Scholar]
  26. SchaeferM.L. BöttgerB. SilverW.L. FingerT.E. Trigeminal collaterals in the nasal epithelium and olfactory bulb: A potential route for direct modulation of olfactory information by trigeminal stimuli.J. Comp. Neurol.2002444322122610.1002/cne.1014311840476
     [Google Scholar]
  27. LochheadJ.J. ThorneR.G. Intranasal delivery of biologics to the central nervous system.Adv. Drug Deliv. Rev.201264761462810.1016/j.addr.2011.11.00222119441
     [Google Scholar]
  28. DuboisJ. Thomas-ChausséF. SoulezG. Common (cystic) lymphatic malformations: Current knowledge and management.Tech. Vasc. Interv. Radiol.201922410063110.1016/j.tvir.2019.10063131864533
     [Google Scholar]
  29. De MartiniL.B. SulmonaC. BrambillaL. RossiD. Cell-penetrating peptides as valuable tools for nose-to-brain delivery of biological drugs.Cells20231212164310.3390/cells1212164337371113
     [Google Scholar]
  30. HladkyS.B. BarrandM.A. Mechanisms of fluid movement into, through and out of the brain: Evaluation of the evidence.Fluids Barriers CNS20141112610.1186/2045‑8118‑11‑2625678956
     [Google Scholar]
  31. AlbayramM.S. SmithG. TufanF. TunaI.S. BostancıklıoğluM. ZileM. AlbayramO. Non-invasive MR imaging of human brain lymphatic networks with connections to cervical lymph nodes.Nat. Commun.202213120310.1038/s41467‑021‑27887‑035017525
     [Google Scholar]
  32. PardeshiC.V. BelgamwarV.S. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood–brain barrier: An excellent platform for brain targeting.Expert Opin. Drug Deliv.201310795797210.1517/17425247.2013.79088723586809
     [Google Scholar]
  33. SunB.L. WangL. YangT. SunJ. MaoL. YangM. YuanH. ColvinR.A. YangX. Lymphatic drainage system of the brain: A novel target for intervention of neurological diseases.Prog. Neurobiol.2018163-16411814310.1016/j.pneurobio.2017.08.00728903061
     [Google Scholar]
  34. ThiebaudN. MenetrierF. BelloirC. MinnA.L. NeiersF. ArturY. Le BonA.M. HeydelJ.M. Expression and differential localization of xenobiotic transporters in the rat olfactory neuro-epithelium.Neurosci. Lett.2011505218018510.1016/j.neulet.2011.10.01822015764
     [Google Scholar]
  35. HsuS.J. ZhangC. JeongJ. LeeS. McConnellM. UtsumiT. IwakiriY. Enhanced meningeal lymphatic drainage ameliorates neuroinflammation and hepatic encephalopathy in cirrhotic rats.Gastroenterology2021160413151329.e1310.1053/j.gastro.2020.11.03633227282
     [Google Scholar]
  36. ReinholzJ. LandfesterK. MailänderV. The challenges of oral drug delivery via nanocarriers.Drug Deliv.20182511694170510.1080/10717544.2018.150111930394120
     [Google Scholar]
  37. HomayunB. LinX. ChoiH.J. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals.Pharmaceutics201911312910.3390/pharmaceutics1103012930893852
     [Google Scholar]
  38. Üstündağ OkurN. YozgatlıV. OkurM.E. YoltaşA. SiafakaP.I. Improving therapeutic efficacy of voriconazole against fungal keratitis: Thermo-sensitive in situ gels as ophthalmic drug carriers.J. Drug Deliv. Sci. Technol.20194932333310.1016/j.jddst.2018.12.005
     [Google Scholar]
  39. ChoudhuryH. GorainB. KesharwaniP. Physiology of the biological barriers.Theory and Applications of Nonparenteral Nanomedicines.Elsevier2021799510.1016/B978‑0‑12‑820466‑5.00004‑1
     [Google Scholar]
  40. ArshadA. ArshadS. Alamgeer MahmoodA. Hussain AsimM. IjazM. Muhammad IrfanH. RubabM. AliS. Raza HashmiA. Zeta potential changing self-nanoemulsifying drug delivery systems: A newfangled approach for enhancing oral bioavailability of poorly soluble drugs.Int. J. Pharm.202465512399810.1016/j.ijpharm.2024.12399838490401
     [Google Scholar]
  41. LiT. VandesquilleM. KoukouliF. DudeffantC. YoussefI. LenormandP. GanneauC. MaskosU. CzechC. GrueningerF. DuyckaertsC. DhenainM. BayS. DelatourB. LafayeP. Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets.J. Control. Release201624311010.1016/j.jconrel.2016.09.01927671875
     [Google Scholar]
  42. ChenghuaG.U. AyalB.Z. Methods and compositions relating to modulation of the permeability of the blood brain barrier.Patent US20160120893A1,2014
  43. PardridgeW.M. Blood–brain barrier endogenous transporters as therapeutic targets: A new model for small molecule CNS drug discovery.Expert Opin. Ther. Targets20151981059107210.1517/14728222.2015.104236425936389
     [Google Scholar]
  44. ChoiM. KuT. ChongK. YoonJ. ChoiC. Minimally invasive molecular delivery into the brain using optical modulation of vascular permeability.Proc. Natl. Acad. Sci. USA2011108229256926110.1073/pnas.101879010821576460
     [Google Scholar]
  45. YuX.C. YangJ.J. JinB.H. XuH.L. ZhangH.Y. XiaoJ. LuC.T. ZhaoY.Z. YangW. A strategy for bypassing the blood-brain barrier: Facial intradermal brain-targeted delivery via the trigeminal nerve.J. Control. Release2017258223310.1016/j.jconrel.2017.05.00128476614
     [Google Scholar]
  46. HershD.S. WadajkarA.S. RobertsN. PerezJ.G. ConnollyN.P. FrenkelV. WinklesJ.A. WoodworthG.F. KimA.J. Evolving drug delivery strategies to overcome the blood brain barrier.Curr. Pharm. Des.20162291177119310.2174/138161282266615122115073326685681
     [Google Scholar]
  47. AgrawalM. Ajazuddin TripathiD.K. SarafS. SarafS. AntimisiarisS.G. MourtasS. Hammarlund-UdenaesM. AlexanderA. Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer’s disease.J. Control. Release2017260617710.1016/j.jconrel.2017.05.01928549949
     [Google Scholar]
  48. PoustforooshA. FarmarzS. NematollahiM.H. HashemipourH. PardakhtyA. Construction of Bio-conjugated nano-vesicles using non-ionic surfactants for targeted drug delivery: A computational supported experimental study.J. Mol. Liq.202236712058810.1016/j.molliq.2022.120588
     [Google Scholar]
  49. RabanelJ.M. FaivreJ. PakaG.D. RamassamyC. HildgenP. BanquyX. Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS.Eur. J. Pharm. Biopharm.20159640942010.1016/j.ejpb.2015.09.00426409200
     [Google Scholar]
  50. LiuW. YeA. LiuW. LiuC. HanJ. SinghH. Behaviour of liposomes loaded with bovine serum albumin during in vitro digestion.Food Chem.2015175162410.1016/j.foodchem.2014.11.10825577045
     [Google Scholar]
  51. BarbaraR. BellettiD. PederzoliF. MasoniM. KellerJ. BallestrazziA. VandelliM.A. TosiG. GrabruckerA.M. Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates.Int. J. Pharm.20175261-241342410.1016/j.ijpharm.2017.05.01528495580
     [Google Scholar]
  52. vA. CutinhoL.I. MouryaP. MaxwellA. ThomasG. RajputB.S. Approaches for encephalic drug delivery using nanomaterials: The current status.Brain Res. Bull.202015518419010.1016/j.brainresbull.2019.11.01731790722
     [Google Scholar]
  53. KongS.D. LeeJ. RamachandranS. EliceiriB.P. ShubayevV.I. LalR. JinS. Magnetic targeting of nanoparticles across the intact blood–brain barrier.J. Control. Release20121641495710.1016/j.jconrel.2012.09.02123063548
     [Google Scholar]
  54. WenM.M. El-SalamouniN.S. El-RefaieW.M. HazzahH.A. AliM.M. TosiG. FaridR.M. Blanco-PrietoM.J. BillaN. HanafyA.S. Nanotechnology-based drug delivery systems for Alzheimer’s disease management: Technical, industrial, and clinical challenges.J. Control. Release20172459510710.1016/j.jconrel.2016.11.02527889394
     [Google Scholar]
  55. ShahB. KhuntD. BhattH. MisraM. PadhH. Application of quality by design approach for intranasal delivery of rivastigmine loaded solid lipid nanoparticles: Effect on formulation and characterization parameters.Eur. J. Pharm. Sci.201578546610.1016/j.ejps.2015.07.00226143262
     [Google Scholar]
  56. TanX. KimG. LeeD. OhJ. KimM. PiaoC. LeeJ. LeeM.S. JeongJ.H. LeeM. A curcumin-loaded polymeric micelle as a carrier of a microRNA-21 antisense-oligonucleotide for enhanced anti-tumor effects in a glioblastoma animal model.Biomater. Sci.20186240741710.1039/C7BM01088E29340361
     [Google Scholar]
  57. AkelH. IsmailR. CsókaI. Progress and perspectives of brain-targeting lipid-based nanosystems via the nasal route in Alzheimer’s disease.Eur. J. Pharm. Biopharm.2020148385310.1016/j.ejpb.2019.12.01431926222
     [Google Scholar]
  58. OngW.Y. ShaliniS.M. CostantinoL. Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders.Curr. Med. Chem.201421374247425610.2174/092986732166614071610313025039773
     [Google Scholar]
  59. RajizadehM.A. MotamedyS. MirY. AkhgarandouzF. NematollahiM.H. NezhadiA. A comprehensive and updated review on the applications of vesicular drug delivery systems in treatment of brain disorders: A shelter against storms.J. Drug Deliv. Sci. Technol.20238910501110.1016/j.jddst.2023.105011
     [Google Scholar]
  60. BattagliaL. PancianiP.P. MuntoniE. CapucchioM.T. BiasibettiE. De BonisP. MiolettiS. FontanellaM. SwaminathanS. Lipid nanoparticles for intranasal administration: Application to nose-to-brain delivery.Expert Opin. Drug Deliv.201815436937810.1080/17425247.2018.142940129338427
     [Google Scholar]
  61. Santos-MoralesO. Díaz-MachadoA. Jiménez-RodríguezD. Pomares-IturraldeY. Festary-CasanovasT. González-DelgadoC.A. Pérez-RodríguezS. Alfonso-MuñozE. Viada-GonzálezC. Piedra-SierraP. García-GarcíaI. Amaro-GonzálezD. García-RodríguezJ.C. Sosa-TestéI. Lagarto-ParraA. Barrero-VieraL. David-BaldoM. Tamayo-RodríguezM. Rivero-VázquezI. González-GamizG. Martín-TrujilloA. Rodríguez-FernándezY. Ledo-de la LuzA.A. Álvarez-DelgadoM. Howland-ÁlvarezI. Cruz-GómezY. NeuroEPO Study Group Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: A randomized, parallel, open-label safety study.BMC Neurol.201717112910.1186/s12883‑017‑0908‑028676085
     [Google Scholar]
  62. ShrewsburySB SwardstromM SatterlyKH CampbellJ TugionoN GilliesJD Placebo/active controlled, safety, pharmaco-kinetic/dynamic study of INP105 (POD® olanzapine) in healthy adults.West J Emerg Med Integr Emerg Care with Popul Heal2019202
     [Google Scholar]
  63. TepperS.J. JohnstoneM.R. Breath-powered sumatriptan dry nasal powder: An intranasal medication delivery system for acute treatment of migraine.Med Devices201811147156
     [Google Scholar]
  64. IarkovA. BarretoG.E. GrizzellJ.A. EcheverriaV. Strategies for the treatment of Parkinson’s disease: Beyond dopamine.Front. Aging Neurosci.202012410.3389/fnagi.2020.0000432076403
     [Google Scholar]
  65. YetisginA.A. CetinelS. ZuvinM. KosarA. KutluO. Therapeutic nanoparticles and their targeted delivery applications.Molecules2020259219310.3390/molecules2509219332397080
     [Google Scholar]
  66. IslamS.U. ShehzadA. AhmedM.B. LeeY.S. Intranasal delivery of nanoformulations: A potential way of treatment for neurological disorders.Molecules2020258192910.3390/molecules2508192932326318
     [Google Scholar]
  67. TangS. WangA. YanX. ChuL. YangX. SongY. SunK. YuX. LiuR. WuZ. XueP. Brain-targeted intranasal delivery of dopamine with borneol and lactoferrin co-modified nanoparticles for treating Parkinson’s disease.Drug Deliv.201926170070710.1080/10717544.2019.163642031290705
     [Google Scholar]
  68. NovakP. Pimentel MaldonadoD.A. NovakV. Safety and preliminary efficacy of intranasal insulin for cognitive impairment in Parkinson disease and multiple system atrophy: A double-blinded placebo-controlled pilot study.PLoS One2019144e021436410.1371/journal.pone.021436431022213
     [Google Scholar]
  69. WangZ. XiongG. TsangW.C. SchätzleinA.G. UchegbuI.F. Nose-to-brain delivery.J. Pharmacol. Exp. Ther.2019370359360110.1124/jpet.119.25815231126978
     [Google Scholar]
  70. SarafS. AlexanderA. Nose-to-brain drug delivery approach: A key to easily accessing the brain for the treatment of Alzheimer’s disease.Neural Regen. Res.201813122102210410.4103/1673‑5374.24145830323136
     [Google Scholar]
  71. MusumeciT. BonaccorsoA. PuglisiG. Epilepsy disease and nose-to-brain delivery of polymeric nanoparticles: An overview.Pharmaceutics201911311810.3390/pharmaceutics1103011830871237
     [Google Scholar]
  72. GadhaveD.G. KokareC.R. Nanostructured lipid carriers engineered for intranasal delivery of teriflunomide in multiple sclerosis: Optimization and in vivo studies.Drug Dev. Ind. Pharm.201945583985110.1080/03639045.2019.157672430702966
     [Google Scholar]
  73. RassyD. BárcenaB. Pérez-OsorioI.N. EspinosaA. PeónA.N. TerrazasL.I. MenesesG. BesedovskyH.O. FragosoG. SciuttoE. Intranasal methylprednisolone effectively reduces neuroinflammation in mice with experimental autoimmune encephalitis.J. Neuropathol. Exp. Neurol.202079222623710.1093/jnen/nlz12831886871
     [Google Scholar]
  74. KhanR.S. DineK. BaumanB. LorentsenM. LinL. BrownH. HansonL.R. SvitakA.L. WesselH. BrownL. ShindlerK.S. Intranasal delivery of a novel amnion cell secretome prevents neuronal damage and preserves function in a mouse multiple sclerosis model.Sci. Rep.2017714176810.1038/srep4176828139754
     [Google Scholar]
  75. ChenC. ZhangM. WuY. ZhouC. LiuR. Intranasal delivering method in the treatment of ischemic stroke.Therapeutic Intranasal Delivery for Stroke and Neurological Disorders.SpringerCham2019758910.1007/978‑3‑030‑16715‑8_7
     [Google Scholar]
  76. SoodS. JainK. GowthamarajanK. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment.Colloids Surf. B Biointerfaces201411333033710.1016/j.colsurfb.2013.09.03024121076
     [Google Scholar]
  77. ZhangC. ChenJ. FengC. ShaoX. LiuQ. ZhangQ. PangZ. JiangX. Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer’s disease.Int. J. Pharm.20144611-219220210.1016/j.ijpharm.2013.11.04924300213
     [Google Scholar]
  78. DjupeslandP.G. Nasal drug delivery devices: Characteristics and performance in a clinical perspective—a review.Drug Deliv. Transl. Res.201331426210.1007/s13346‑012‑0108‑923316447
     [Google Scholar]
  79. RegerM.A. WatsonG.S. GreenP.S. BakerL.D. CholertonB. FishelM.A. PlymateS.R. CherrierM.M. SchellenbergG.D. FreyW.H.II CraftS. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-β in memory-impaired older adults.J. Alzheimers Dis.200813332333110.3233/JAD‑2008‑1330918430999
     [Google Scholar]
  80. HoekmanJ.D. HoR.J.Y. Effects of localized hydrophilic mannitol and hydrophobic nelfinavir administration targeted to olfactory epithelium on brain distribution.AAPS PharmSciTech201112253454310.1208/s12249‑011‑9614‑121519984
     [Google Scholar]
  81. MajgainyaS. SoniS. BhatP. Novel approach for nose-to-brain drug delivery bypassing blood brain barrier by pressurized olfactory delivery device.J. Appl. Pharm.20157314816310.21065/19204159.7.3.125
     [Google Scholar]
  82. HallschmidM. BenedictC. SchultesB. PerrasB. FehmH.L. KernW. BornJ. Towards the therapeutic use of intranasal neuropeptide administration in metabolic and cognitive disorders.Regul. Pept.20081491-3798310.1016/j.regpep.2007.06.01218442862
     [Google Scholar]
  83. BenedictC. HallschmidM. SchultesB. BornJ. KernW. Intranasal insulin to improve memory function in humans.Neuroendocrinology200786213614210.1159/00010637817643054
     [Google Scholar]
  84. SchillingT.M. Ferreira de SáD.S. WesterhausenR. StrelzykF. LarraM.F. HallschmidM. SavaskanE. OitzlM.S. BuschH.P. NaumannE. SchächingerH. Intranasal insulin increases regional cerebral blood flow in the insular cortex in men independently of cortisol manipulation.Hum. Brain Mapp.20143551944195610.1002/hbm.2230423907764
     [Google Scholar]
  85. XiaoC. DashS. StahelP. LewisG.F. Effects of intranasal insulin on triglyceride-rich lipoprotein particle production in healthy men.Arterioscler. Thromb. Vasc. Biol.20173791776178110.1161/ATVBAHA.117.30970528751575
     [Google Scholar]
  86. DashS. XiaoC. MorgantiniC. KoulajianK. LewisG.F. Intranasal insulin suppresses endogenous glucose production in humans compared with placebo in the presence of similar venous insulin concentrations.Diabetes201564376677410.2337/db14‑068525288674
     [Google Scholar]
  87. StockhorstU. de FriesD. SteingrueberH.J. ScherbaumW.A. Unconditioned and conditioned effects of intranasally administered insulin vs placebo in healthy men: A randomised controlled trial.Diabetologia20115461502150610.1007/s00125‑011‑2111‑y21461638
     [Google Scholar]
  88. DjupeslandP.G. SkrettingA. WinderenM. HolandT. Bi-directional nasal delivery of aerosols can prevent lung deposition.J. Aerosol Med.200417324925910.1089/jam.2004.17.24915625817
     [Google Scholar]
  89. DjupeslandP.G. SkrettingA. WinderenM. HolandT. Breath actuated device improves delivery to target sites beyond the nasal valve.Laryngoscope2006116346647210.1097/01.MLG.0000199741.08517.9916540911
     [Google Scholar]
  90. DaleO. NilsenT. LoftssonT. TønnesenH.H. KlepstadP. KaasaS. HolandT. DjupeslandP.G. Intranasal midazolam: A comparison of two delivery devices in human volunteers.J. Pharm. Pharmacol.201058101311131810.1211/jpp.58.10.000317034653
     [Google Scholar]
  91. DjupeslandP.G. DočekalP. GroupC.M.I. Czech Migraine Investigators Group Intranasal sumatriptan powder delivered by a novel breath-actuated bi-directional device for the acute treatment of migraine: A randomised, placebo-controlled study.Cephalalgia201030893394210.1177/033310240935931420656704
     [Google Scholar]
  92. YadavS. GattaccecaF. PanicucciR. AmijiM.M. Comparative biodistribution and pharmacokinetic analysis of cyclosporine-A in the brain upon intranasal or intravenous administration in an oil-in-water nanoemulsion formulation.Mol. Pharm.20151251523153310.1021/mp500837625785492
     [Google Scholar]
  93. HanafyA.S. FaridR.M. HelmyM.W. ElGamalS.S. Pharmacological, toxicological and neuronal localization assessment of galantamine/chitosan complex nanoparticles in rats: future potential contribution in Alzheimer’s disease management.Drug Deliv.20162383111312210.3109/10717544.2016.115374826942549
     [Google Scholar]
  94. PathakR. Prasad DashR. MisraM. NivsarkarM. Role of mucoadhesive polymers in enhancing delivery of nimodipine microemulsion to brain via intranasal route.Acta Pharm. Sin. B20144215116010.1016/j.apsb.2014.02.00226579378
     [Google Scholar]
  95. ElnaggarY.S.R. EtmanS.M. AbdelmonsifD.A. AbdallahO.Y. Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in Alzheimer’s disease: Optimization, biological efficacy, and potential toxicity.J. Pharm. Sci.2015104103544355610.1002/jps.24557
     [Google Scholar]
  96. NasrM. Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery.Drug Deliv.20162341444145210.3109/10717544.2015.109261926401600
     [Google Scholar]
  97. HaiderM.F. KhanS. GabaB. AlamT. BabootaS. AliJ. AliA. Optimization of rivastigmine nanoemulsion for enhanced brain delivery: In-vivo and toxicity evaluation.J. Mol. Liq.201825538439610.1016/j.molliq.2018.01.123
     [Google Scholar]
  98. JiangY. LiuC. ZhaiW. ZhuangN. HanT. DingZ. The optimization design of lactoferrin loaded HupA nanoemulsion for targeted drug transport via intranasal route.Int. J. Nanomedicine2019149217923410.2147/IJN.S21465731819426
     [Google Scholar]
  99. IqbalR. AhmedS. JainG.K. VohoraD. Design and development of letrozole nanoemulsion: A comparative evaluation of brain targeted nanoemulsion with free letrozole against status epilepticus and neurodegeneration in mice.Int. J. Pharm.2019565203210.1016/j.ijpharm.2019.04.07631051232
     [Google Scholar]
  100. RinaldiF. SeguellaL. GigliS. HaniehP.N. Del FaveroE. CantùL. PesceM. SarnelliG. MarianecciC. EspositoG. CarafaM. inPentasomes: An innovative nose-to-brain pentamidine delivery blunts MPTP parkinsonism in mice.J. Control. Release2019294172610.1016/j.jconrel.2018.12.00730529726
     [Google Scholar]
  101. SalemH.F. KharshoumR.M. Abou-TalebH.A. NaguibD.M. Brain targeting of resveratrol through intranasal lipid vesicles labelled with gold nanoparticles: In vivo evaluation and bioaccumulation investigation using computed tomography and histopathological examination.J. Drug Target.201927101127113410.1080/1061186X.2019.160855331094230
     [Google Scholar]
  102. FreyI.I.W.H. Method for administering insulin to the brain.Patent US6313093B1,2001
  103. FreyI.I.W.H. Method for administering neurologic agents to the brain.Patent US5624898A,2001
  104. DhuriaS.V. HansonL.R. FreyW.H.II Intranasal delivery to the central nervous system: Mechanisms and experimental considerations.J. Pharm. Sci.20109941654167310.1002/jps.2192419877171
     [Google Scholar]
  105. MadavY. WairkarS. Strategies for enhanced direct nose-to-brain drug delivery.Direct Nose-to-Brain Drug Delivery.Elsevier202116918410.1016/B978‑0‑12‑822522‑6.00014‑X
     [Google Scholar]
  106. FreyI.I.W.H. ThorneR.G. Method for administering agents to the central nervous system.Patent WO/2000/033814,2007
  107. FreyW. Method for administering brain-derived neurotrophic factor to the brain.Patent,2003
  108. VyasT. ShahiwalaA. MaratheS. MisraA. Intranasal drug delivery for brain targeting.Curr. Drug Deliv.20052216517510.2174/156720105358604716305417
     [Google Scholar]
  109. LevinB. Directed intranasal administration of pharmaceutical agents.Patent,2005
  110. WairkarS. TambeV.S. Lipid-based nanocarriers via nose-to-brain pathway for alzheimer’s and parkinson’s disease.Curr. Nanosci.202319332233710.2174/1573413718666220627140824
     [Google Scholar]
  111. MisraA. JoganiV. JinturkarK. VyasT. Recent patents review on intranasal administration for CNS drug delivery.Recent Pat. Drug Deliv. Formul.200821254010.2174/18722110878333142919075895
     [Google Scholar]
  112. ChoiY.M. KimK. Transnasal microemulsions containing diazepam.Patent WO2004110403A1,2005
  113. MoscatelliD Capasso PalmieroU BiffiA PevianiM MilazzoR CapotondoA. Compositions and methods for treating diseases and disorders of the central nervous system.Patent AU2017342555A1,2017
  114. WermelingD.P. Intranasal delivery of antiepileptic medications for treatment of seizures.Neurotherapeutics20096235235810.1016/j.nurt.2009.01.00219332330
     [Google Scholar]
  115. WermelingD.P.H. MillerJ.L. ArcherS.M. ManaligodJ.M. RudyA.C. Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration.J. Clin. Pharmacol.200141111225123110.1177/0091270012201277911697755
     [Google Scholar]
  116. WarnkenZ.N. SmythH.D.C. WattsA.B. WeitmanS. KuhnJ.G. WilliamsR.O.III Formulation and device design to increase nose to brain drug delivery.J. Drug Deliv. Sci. Technol.20163521322210.1016/j.jddst.2016.05.003
     [Google Scholar]
  117. ChatterjeeB. GorainB. MohananaiduK. SenguptaP. MandalU.K. ChoudhuryH. Targeted drug delivery to the brain via intranasal nanoemulsion: Available proof of concept and existing challenges.Int. J. Pharm.201956525826810.1016/j.ijpharm.2019.05.03231095983
     [Google Scholar]
  118. LeeS.K. ChungK.H. UllahI. KumarP. LeeS. Nose-to-brain drug delivery device.Patent US11097073B2,2021
  119. BahadurS. PardhiD.M. RautioJ. RosenholmJ.M. PathakK. Intranasal nanoemulsions for direct nose-to-brain delivery of actives for CNS disorders.Pharmaceutics20201212123010.3390/pharmaceutics1212123033352959
     [Google Scholar]
  120. PandeyV. GadevalA. AsatiS. JainP. JainN. RoyR.K. Formulation strategies for nose-to-brain delivery of therapeutic molecules.Drug delivery systems.Elsevier202029133210.1016/B978‑0‑12‑814487‑9.00007‑7
     [Google Scholar]
/content/journals/cnsamc/10.2174/0118715249329586240924105624
Loading
To Explore Nasal-Brain Lymphatic System for Brain-Targeted Drug Delivery and to Treat Neurodegenerative Diseases
Central Nervous System Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Central Nervous System Agents) 25, 437 (2025); https://doi.org/10.2174/0118715249329586240924105624
/content/journals/cnsamc/10.2174/0118715249329586240924105624
/content/journals/cnsamc/10.2174/0118715249329586240924105624
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Alzheimer’s disease; blood brain barrier; central nervous system; Drug delivery brain targeting; neurodegenerative disorders (NDD); Parkinson’s disease

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test