Skip to content
2000
Volume 26, Issue 2
  • ISSN: 1389-2002
  • E-ISSN: 1875-5453

Abstract

The brain is highly protected by physiological barriers, in which the blood-brain barrier restricts the entry of most drugs. Intranasal drug delivery is a non-invasive way of drug delivery, which can cross the blood-brain barrier and achieve direct and efficient targeted delivery to the brain. Therefore, it has great potential in application to the treatment of brain diseases. Temperature-sensitive hydrogels undergo a solution-gel transition with temperature change, and the gel form has good mucosal adsorption properties in the nasal cavity, which is commonly used for targeted delivery of drugs for brain diseases. In this article, by introducing the transport mechanism of brain targeting after nasal administration, combined with the prescription design and basic performance study of temperature-sensitive nasal hydrogel, we summarized the research on the role that temperature-sensitive hydrogel plays brain targeting after nasal administration, aiming to provide a reference for the development of therapeutic drugs for cerebral diseases and their clinical application. A graphical summary.

Loading

Article metrics loading...

/content/journals/cdm/10.2174/0113892002365157250422114917
2025-05-06
2026-01-20
Loading full text...

Full text loading...

References

  1. GoldsteinL.B. Introduction for focused updates in cerebrovascular disease.Stroke202051370871010.1161/STROKEAHA.119.02415932078448
    [Google Scholar]
  2. CreekmoreB.C. WatanabeR. LeeE.B. Neurodegenerative disease tauopathies.Annu. Rev. Pathol.202419134537010.1146/annurev‑pathmechdis‑051222‑12075037832941
    [Google Scholar]
  3. MaoZ. TianL. LiuJ. WuQ. WangN. WangG. WangY. SetoS. Ligustilide ameliorates hippocampal neuronal injury after cerebral ischemia reperfusion through activating PINK1/Parkin-dependent mitophagy.Phytomedicine202210115411110.1016/j.phymed.2022.15411135512628
    [Google Scholar]
  4. WangL. LiuC. WangL. TangB. Astragaloside IV mitigates cerebral ischaemia-reperfusion injury via inhibition of P62/Keap1/Nrf2 pathway-mediated ferroptosis.Eur. J. Pharmacol.202394417551610.1016/j.ejphar.2023.17551636758783
    [Google Scholar]
  5. BeiramiE. OryanS. Seyedhosseini TamijaniS.M. AhmadianiA. DargahiL. Intranasal insulin treatment alleviates methamphetamine induced anxiety-like behavior and neuroinflammation.Neurosci. Lett.201766012212910.1016/j.neulet.2017.09.02628917981
    [Google Scholar]
  6. LuQ. XiangH. ZhuH. ChenY. LuX. HuangC. Intranasal lipopolysaccharide administration prevents chronic stress-induced depression- and anxiety-like behaviors in mice.Neuropharmacology202120010881610.1016/j.neuropharm.2021.10881634599975
    [Google Scholar]
  7. ZhaoZ. NelsonA.R. BetsholtzC. ZlokovicB.V. Establishment and dysfunction of the blood-brain barrier.Cell201516351064107810.1016/j.cell.2015.10.06726590417
    [Google Scholar]
  8. AlahmariA. Blood-Brain Barrier Overview: Structural and Functional Correlation.Neural Plast.2021202111010.1155/2021/656458534912450
    [Google Scholar]
  9. Sánchez de MedinaA. Serrano-RodríguezJ.M. Díez de CastroE. García-ValverdeM.T. SaituaA. BeceroM. MuñozA. Ferreiro-VeraC. Sánchez de MedinaV. Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations.Equine Vet. J.20235561094110310.1111/evj.1392336624043
    [Google Scholar]
  10. KadryH. NooraniB. CuculloL. A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity.Fluids Barriers CNS20201716910.1186/s12987‑020‑00230‑333208141
    [Google Scholar]
  11. ErdőF. BorsL.A. FarkasD. BajzaÁ. GizurarsonS. Evaluation of intranasal delivery route of drug administration for brain targeting.Brain Res. Bull.201814315517010.1016/j.brainresbull.2018.10.00930449731
    [Google Scholar]
  12. GonçalvesJ. AlvesG. FonsecaC. CaronaA. BickerJ. FalcãoA. FortunaA. Is intranasal administration an opportunity for direct brain delivery of lacosamide?Eur. J. Pharm. Sci.202115710563210.1016/j.ejps.2020.10563233152466
    [Google Scholar]
  13. KashyapK. ShuklaR. Drug delivery and targeting to the brain through nasal route: Mechanisms, applications and challenges.Curr. Drug Deliv.2019161088790110.2174/156720181666619102912274031660815
    [Google Scholar]
  14. FengY. XiaW. ZhaoP. YiX. TangA. Survey anatomy and histological observation of the nasal cavity of Tupaia belangeri chinensis (Tupaiidae, Scandentia, Mammalia).Anat. Rec.202230561448145810.1002/ar.2479334605617
    [Google Scholar]
  15. PatelR. Nasal anatomy and function.Facial Plast Surg.201733(1), 003-008.10.1055/s‑0036‑159795028226365
    [Google Scholar]
  16. KellerL.A. MerkelO. PoppA. Intranasal drug delivery: Opportunities and toxicologic challenges during drug development.Drug Deliv. Transl. Res.202212473575710.1007/s13346‑020‑00891‑533491126
    [Google Scholar]
  17. GaboldB. AdamsF. BrameyerS. JungK. RiedC.L. MerdanT. MerkelO.M. Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins.Drug Deliv. Transl. Res.202313382283810.1007/s13346‑022‑01245‑z36207657
    [Google Scholar]
  18. Lobaina MatoY. Nasal route for vaccine and drug delivery: Features and current opportunities.Int. J. Pharm.201957211881310.1016/j.ijpharm.2019.11881331678521
    [Google Scholar]
  19. BalafasE.G. PapakyriakopoulouP.I. KostomitsopoulosN.G. ValsamiG.N. Intranasal administration of a polymeric biodegradable film to C57BL/6 mice.J. Am. Assoc. Lab. Anim. Sci.202362217918410.30802/AALAS‑JAALAS‑22‑00009136898691
    [Google Scholar]
  20. GizurarsonS. The effect of cilia and the mucociliary clearance on successful drug delivery.Biol. Pharm. Bull.201538449750610.1248/bpb.b14‑0039825739664
    [Google Scholar]
  21. ScherließR. Nasal formulations for drug administration and characterization of nasal preparations in drug delivery.Ther. Deliv.202011318319110.4155/tde‑2019‑008632046624
    [Google Scholar]
  22. HuX. YueX. WuC. ZhangX. Factors affecting nasal drug delivery and design strategies for intranasal drug delivery.Zhejiang Da Xue Xue Bao Yi Xue Ban202352332833710.3724/zdxbyxb‑2023‑006937476944
    [Google Scholar]
  23. GraySM BarrettEJ Insulin transport into the brain.Am. J. Physiol. Cell Physiol.20183152C125C13610.1002/jnr.2519236977654
    [Google Scholar]
  24. FreddiT.A.L. OttaianoA.C. LucioL.L. CorrêaD.G. Hygino da CruzL.C. The trigeminal nerve: Anatomy and pathology.Semin. Ultrasound CT MR202243540341310.1053/j.sult.2022.04.00236116853
    [Google Scholar]
  25. 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]
  26. OttaianoA.C. FreddiT.A.L. LucioL.L. The olfactory nerve: Anatomy and pathology.Semin. Ultrasound CT MR202243537137710.1053/j.sult.2022.04.00136116849
    [Google Scholar]
  27. HelwanyM. BordoniB. Neuroanatomy, Cranial Nerve 1 (Olfactory).StatPearls.Treasure Island, (FL)StatPearls Publishing2025
    [Google Scholar]
  28. MaengJ. LeeK. Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides.Front. Pharmacol.202213106849510.3389/fphar.2022.106849536452220
    [Google Scholar]
  29. WuD. ChenQ. ChenX. HanF. ChenZ. WangY. The blood–brain barrier: Structure, regulation and drug delivery.Signal Transduct. Target. Ther.20238121710.1038/s41392‑023‑01481‑w37231000
    [Google Scholar]
  30. ObermeierB. DanemanR. RansohoffR.M. Development, maintenance and disruption of the blood-brain barrier.Nat. Med.201319121584159610.1038/nm.340724309662
    [Google Scholar]
  31. SunH. HuH. LiuC. SunN. DuanC. Methods used for the measurement of blood-brain barrier integrity.Metab. Brain Dis.202136572373510.1007/s11011‑021‑00694‑833635479
    [Google Scholar]
  32. HajalC. Le RoiB. KammR.D. MaozB.M. Biology and models of the blood–brain barrier.Annu. Rev. Biomed. Eng.202123135938410.1146/annurev‑bioeng‑082120‑04281434255993
    [Google Scholar]
  33. SweeneyM.D. ZhaoZ. MontagneA. NelsonA.R. ZlokovicB.V. Blood-brain barrier: From physiology to disease and back.Physiol. Rev.2019991217810.1152/physrev.00050.201730280653
    [Google Scholar]
  34. MatsumotoJ. StewartT. BanksW.A. ZhangJ. The transport mechanism of extracellular vesicles at the blood-brain barrier.Curr. Pharm. Des.201823406206621410.2174/138161282366617091316473828914201
    [Google Scholar]
  35. SharmaS. DangS. Nanocarrier-based drug delivery to brain: Interventions of surface modification.Curr. Neuropharmacol.202321351753510.2174/1570159X2066622070612141235794771
    [Google Scholar]
  36. BashyalS. ThapaC. LeeS. Recent progresses in exosome-based systems for targeted drug delivery to the brain.J. Control. Release202234872374410.1016/j.jconrel.2022.06.01135718214
    [Google Scholar]
  37. VieiraL.S. WangJ. Brain plasma membrane monoamine transporter in health and disease.Handb. Exp. Pharmacol.202126625328010.1007/164_2021_44633751232
    [Google Scholar]
  38. TerstappenG.C. MeyerA.H. BellR.D. ZhangW. Strategies for delivering therapeutics across the blood–brain barrier.Nat. Rev. Drug Discov.202120536238310.1038/s41573‑021‑00139‑y33649582
    [Google Scholar]
  39. YeruvaT. YangS. DoskiS. DuncanG.A. Hydrogels for mucosal drug delivery.ACS Appl. Bio Mater.2023651684170010.1021/acsabm.3c0005037126538
    [Google Scholar]
  40. AlmoshariY. Novel hydrogels for topical applications: An updated comprehensive review based on source.Gels20228317410.3390/gels803017435323287
    [Google Scholar]
  41. MoF. JiangK. ZhaoD. WangY. SongJ. TanW. DNA hydrogel-based gene editing and drug delivery systems.Adv. Drug Deliv. Rev.2021168799810.1016/j.addr.2020.07.01832712197
    [Google Scholar]
  42. TrombinoS. ServidioC. CurcioF. CassanoR. Strategies for hyaluronic acid-based hydrogel design in drug delivery.Pharmaceutics201911840710.3390/pharmaceutics1108040731408954
    [Google Scholar]
  43. ChenX. LiH. LamK.Y. A multiphysics model of photo-sensitive hydrogels in response to light-thermo-pH-salt coupled stimuli for biomedical applications.Bioelectrochemistry202013510758410.1016/j.bioelechem.2020.10758432574995
    [Google Scholar]
  44. WangY. ZhangJ. ZhangW. ZhangM. Pd-catalyzed C-C cross-coupling reactions within a thermoresponsive and pH-responsive and chelating polymeric hydrogel.J. Org. Chem.20097451923193110.1021/jo802427k19173610
    [Google Scholar]
  45. ZhuX. YangC. JianY. DengH. DuY. ShiX. Ion-responsive chitosan hydrogel actuator inspired by carrotwood seed pod.Carbohydr. Polym.202227611875910.1016/j.carbpol.2021.11875934823783
    [Google Scholar]
  46. AkalpU. BryantS.J. VernereyF.J. Tuning tissue growth with scaffold degradation in enzyme-sensitive hydrogels: A mathematical model.Soft Matter201612367505752010.1039/C6SM00583G27548744
    [Google Scholar]
  47. ZhaoY. LiuX. PengX. ZhengY. ChengZ. SunS. DingQ. LiuW. DingC. A poloxamer/hyaluronic acid/chitosan-based thermosensitive hydrogel that releases dihydromyricetin to promote wound healing.Int. J. Biol. Macromol.202221647548610.1016/j.ijbiomac.2022.06.21035810849
    [Google Scholar]
  48. VillaC. MartelloF. ErraticoS. TocchioA. BelicchiM. LenardiC. TorrenteY.P. (NIPAAM-co-HEMA) thermoresponsive hydrogels: An alternative approach for muscle cell sheet engineering.J. Tissue Eng. Regen. Med.201711118719610.1002/term.189824799388
    [Google Scholar]
  49. BostanM.S. SenolM. CigT. PekerI. GorenA.C. OzturkT. ErogluM.S. Controlled release of 5-aminosalicylicacid from chitosan based pH and temperature sensitive hydrogels.Int. J. Biol. Macromol.20135217718310.1016/j.ijbiomac.2012.09.01823041667
    [Google Scholar]
  50. LiY. ZhangL. SongZ. LiF. XieD. Intelligent temperaturepH dual responsive nanocellulose hydrogels and the application of drug release towards 5-fluorouracil. Int. J. Biol. Macromol, 2022, 223(Part A), 11-16.10.1016/j.ijbiomac.2022.10.188
    [Google Scholar]
  51. KimA.R. LeeS.L. ParkS.N. Properties and in vitro drug release of pH- and temperature-sensitive double cross-linked interpenetrating polymer network hydrogels based on hyaluronic acid/poly (Nisopropylacrylamide) for transdermal delivery of luteolin. Int. J. Biol. Macromol, 2018, 118(Part A), 731-740.10.1016/j.ijbiomac.2018.06.061
    [Google Scholar]
  52. LuL. HuangZ. LiX. LiX. CuiB. YuanC. GuoL. LiuP. DaiQ. A high-conductive, anti-freezing, antibacterial and anti-swelling starch-based physical hydrogel for multifunctional flexible wearable sensors.Int. J. Biol. Macromol.202221379180310.1016/j.ijbiomac.2022.06.01135679959
    [Google Scholar]
  53. Ilić-StojanovićS. NikolićL. NikolićV. RistićI. CakićS. PetrovićS.D. Temperature-sensitive hydrogels as carriers for modulated delivery of acetaminophen.Gels20239968410.3390/gels909068437754365
    [Google Scholar]
  54. XianS. WebberM.J. Temperature-responsive supramolecular hydrogels.J. Mater. Chem. B Mater. Biol. Med.20208409197921110.1039/D0TB01814G32924052
    [Google Scholar]
  55. YuY. ChengY. TongJ. ZhangL. WeiY. TianM. Recent advances in thermo-sensitive hydrogels for drug delivery.J. Mater. Chem. B Mater. Biol. Med.20219132979299210.1039/D0TB02877K33885662
    [Google Scholar]
  56. RahmaniF. AtabakiR. BehrouziS. MohamadpourF. KamaliH. The recent advancement in the PLGA-based thermo-sensitive hydrogel for smart drug delivery.Int. J. Pharm.202363112248410.1016/j.ijpharm.2022.12248436509221
    [Google Scholar]
  57. ZhouW. DuanZ. ZhaoJ. FuR. ZhuC. FanD. Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing.Bioact. Mater.20221711710.1016/j.bioactmat.2022.01.00435386439
    [Google Scholar]
  58. GargA. AgrawalR. Singh ChauhanC. DeshmukhR. In-situ gel: A smart carrier for drug delivery.Int. J. Pharm.202465212381910.1016/j.ijpharm.2024.12381938242256
    [Google Scholar]
  59. ChenW.N. ShaikhM.F. BhuvanendranS. DateA. AnsariM.T. RadhakrishnanA.K. OthmanI. Poloxamer 188 (P188), A potential polymeric protective agent for central nervous system disorders: A systematic review.Curr. Neuropharmacol.202220479980810.2174/1570159X1966621052815580134077349
    [Google Scholar]
  60. ZarrintajP. RamseyJ.D. SamadiA. AtoufiZ. YazdiM.K. GanjaliM.R. AmirabadL.M. ZangeneE. FarokhiM. FormelaK. SaebM.R. MozafariM. ThomasS. Poloxamer: A versatile tri-block copolymer for biomedical applications.Acta Biomater.2020110376710.1016/j.actbio.2020.04.02832417265
    [Google Scholar]
  61. RussoE. VillaC. Poloxamer hydrogels for biomedical applications.Pharmaceutics2019111267110.3390/pharmaceutics1112067131835628
    [Google Scholar]
  62. LeT.P. YuY. ChoI.S. SuhE.Y. KwonH.C. ShinS.A. ParkY.H. HuhK.M. Injectable poloxamer hydrogel formulations for intratympanic delivery of dexamethasone.J. Korean Med. Sci.20233817e13510.3346/jkms.2023.38.e13537128878
    [Google Scholar]
  63. WangT. MarkhamA. ThomasS.J. WangN. HuangL. ClemensM. RajagopalanN. Solution stability of poloxamer 188 under stress conditions.J. Pharm. Sci.201910831264127110.1016/j.xphs.2018.10.05730419275
    [Google Scholar]
  64. ElsenosyF.M. AbdelbaryG.A. ElshafeeyA.H. ElsayedI. FaresA.R. Brain targeting of duloxetine HCl via intranasal delivery of loaded cubosomal gel: In vitro characterization, ex vivo permeation, and in vivo biodistribution studies.Int. J. Nanomedicine2020159517953710.2147/IJN.S27735233324051
    [Google Scholar]
  65. PangL. ZhuS. MaJ. ZhuL. LiuY. OuG. LiR. WangY. LiangY. JinX. DuL. JinY. Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder.Acta Pharm. Sin. B20211172031204710.1016/j.apsb.2021.01.01434386336
    [Google Scholar]
  66. RiazM. ZamanM. HameedH. SarwarH.S. KhanM.A. IrfanA. ShazlyG.A. Paiva-SantosA.C. JardanY.A.B. Lamotrigine-loaded poloxamer-based thermo-responsive sol-gel: Formulation, in vitro assessment, ex vivo permeation, and toxicology study.Gels202391081737888390
    [Google Scholar]
  67. Diaz-SalmeronR. ToussaintB. HuangN. Bourgeois DucournauE. AlvisetG. Goulay DufaÿS. HillaireauH. Dufaÿ WojcickiA. BoudyV. Mucoadhesive poloxamer-based hydrogels for the release of HP-β-CD-complexed dexamethasone in the treatment of buccal diseases.Pharmaceutics202113111733477667
    [Google Scholar]
  68. MendonsaN.S. MurthyS.N. HashemnejadS.M. KunduS. ZhangF. RepkaM.A. Development of poloxamer gel formulations via hot-melt extrusion technology.Int. J. Pharm.20185371-212213110.1016/j.ijpharm.2017.12.00829253585
    [Google Scholar]
  69. ChenX. ZhiF. JiaX. ZhangX. AmbardekarR. MengZ. ParadkarA.R. HuY. YangY. Enhanced brain targeting of curcumin by intranasal administration of a thermosensitive poloxamer hydrogel.J. Pharm. Pharmacol.201365680781623647674
    [Google Scholar]
  70. LiC. LiC. LiuZ. LiQ. YanX. LiuY. LuW. Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan.Int. J. Pharm.20144741-212313310.1016/j.ijpharm.2014.08.02325138250
    [Google Scholar]
  71. AhirraoM. ShrotriyaS. In vitro and in vivo evaluation of cubosomal in situ nasal gel containing resveratrol for brain targeting.Drug Dev. Ind. Pharm.201743101686169310.1080/03639045.2017.133872128574732
    [Google Scholar]
  72. CorazzaE. di CagnoM.P. Bauer-BrandlA. AbruzzoA. CerchiaraT. BigucciF. LuppiB. Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin.Eur. J. Pharm. Sci.202217910629410.1016/j.ejps.2022.10629436116696
    [Google Scholar]
  73. RaviP.R. AdityaN. PatilS. CherianL. Nasal in-situ gels for delivery of rasagiline mesylate: Improvement in bioavailability and brain localization.Drug Deliv.201522790391010.3109/10717544.2013.86050124286183
    [Google Scholar]
  74. SalatinS. Alami-MilaniM. DaneshgarR. JelvehgariM. Box–Behnken experimental design for preparation and optimization of the intranasal gels of selegiline hydrochloride.Drug Dev. Ind. Pharm.201844101613162110.1080/03639045.2018.148338729932793
    [Google Scholar]
  75. LiQ. ZhangY. HuJ. YuanB. ZhangP. WangY. JinX. DuL. JinY. The improved brain-targeted drug delivery of edaravone temperature-sensitive gels by ultrasound for γ-ray radiation-induced brain injury.Pharmaceutics20221411228110.3390/pharmaceutics1411228136365100
    [Google Scholar]
  76. LiuY. LiS. WangZ. WangL. Ultrasound in cellulose-based hydrogel for biomedical use: From extraction to preparation.Colloids Surf. B Biointerfaces202221211236810.1016/j.colsurfb.2022.11236835114437
    [Google Scholar]
  77. BhaladhareS. DasD. Cellulose: A fascinating biopolymer for hydrogel synthesis.J. Mater. Chem. B Mater. Biol. Med.202210121923194510.1039/D1TB02848K35226030
    [Google Scholar]
  78. UppuluriC.T. RaviP.R. DalviA.V. Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease.Int. J. Pharm.202160612088110.1016/j.ijpharm.2021.12088134273426
    [Google Scholar]
  79. UppuluriC.T. RaviP.R. DalviA.V. Design and evaluation of thermo-responsive nasal in situ gelling system dispersed with piribedil loaded lecithin-chitosan hybrid nanoparticles for improved brain availability.Neuropharmacology202120110883210.1016/j.neuropharm.2021.10883234627852
    [Google Scholar]
  80. OuG. LiQ. ZhuL. ZhangY. LiuY. LiX. DuL. JinY. Intranasal hydrogel of armodafinil hydroxypropyl-β-cyclodextrin inclusion complex for the treatment of post-traumatic stress disorder.Saudi Pharm. J.202230326528210.1016/j.jsps.2022.01.00935498223
    [Google Scholar]
  81. El TaweelM.M. Aboul-EinienM.H. KassemM.A. ElkasabgyN.A. Intranasal zolmitriptan-loaded bilosomes with extended nasal mucociliary transit time for direct nose to brain delivery.Pharmaceutics20211311182810.3390/pharmaceutics1311182834834242
    [Google Scholar]
  82. AneesE. RiazM. ImtiazH. HussainT. Electrochemical corrosion study of chitosan-hydroxyapatite coated dental implant.J. Mech. Behav. Biomed. Mater.202415010626810.1016/j.jmbbm.2023.10626838039776
    [Google Scholar]
  83. KhanS. PatilK. BobadeN. YeoleP. GaikwadR. Formulation of intranasal mucoadhesive temperature-mediated in situ gel containing ropinirole and evaluation of brain targeting efficiency in rats.J. Drug Target.201018322323410.3109/1061186090338693820030503
    [Google Scholar]
  84. TeaimaM.H. El MohamadyA.M. El-NabarawiM.A. MohamedA.I. Formulation and evaluation of niosomal vesicles containing ondansetron HCL for trans-mucosal nasal drug delivery.Drug Dev. Ind. Pharm.202046575176110.1080/03639045.2020.175306132250181
    [Google Scholar]
  85. QiX.J. LiuX.Y. TangL.M.Y. LiP.F. QiuF. YangA.H. Anti-depressant effect of curcumin-loaded guanidine-chitosan thermo-sensitive hydrogel by nasal delivery.Pharm. Dev. Technol.202025331632510.1080/10837450.2019.168652431661648
    [Google Scholar]
  86. KamaliH. TafaghodiM. EisvandF. Ahmadi-SoleimaniS.M. KhajoueeM. GhazizadehH. MosaferJ. Preparation and evaluation of the in situ gel-forming chitosan hydrogels for nasal delivery of morphine in a single unit dose in rats to enhance the analgesic responses.Curr. Drug Deliv.20242171024103510.2174/156720182066623072416120537491854
    [Google Scholar]
  87. KashifM.R. SohailM. KhanS.A. MinhasM.U. MahmoodA. ShahS.A. MohsinS. Chitosan/guar gum-based thermoreversible hydrogels loaded with pullulan nanoparticles for enhanced nose-to-brain drug delivery.Int. J. Biol. Macromol.202221557959510.1016/j.ijbiomac.2022.06.16135779651
    [Google Scholar]
  88. NafeeN. AmeenA.E.R. AbdallahO.Y. Patient-friendly, olfactory-targeted, stimuli-responsive hydrogels for cerebral degenerative disorders ensured & 400% brain targeting efficiency in rats.AAPS PharmSciTech2021221610.1208/s12249‑020‑01872‑033222021
    [Google Scholar]
  89. HardS.A.A.A. ShivakumarH.N. RedhwanM.A.M. Development and optimization of in-situ gel containing chitosan nanoparticles for possible nose-to-brain delivery of vinpocetine.Int. J. Biol. Macromol.2023253Pt 612721710.1016/j.ijbiomac.2023.12721737793522
    [Google Scholar]
  90. PalumboF.S. FedericoS. PitarresiG. FioricaC. GiammonaG. Gellan gum-based delivery systems of therapeutic agents and cells.Carbohydr. Polym.202022911543010.1016/j.carbpol.2019.11543031826518
    [Google Scholar]
  91. OsmałekT. FroelichA. TasarekS. Application of gellan gum in pharmacy and medicine.Int. J. Pharm.20144661-232834010.1016/j.ijpharm.2014.03.03824657577
    [Google Scholar]
  92. RajputA. BariyaA. AllamA. OthmanS. ButaniS.B. In situ nanostructured hydrogel of resveratrol for brain targeting: in vitro-in vivo characterization.Drug Deliv. Transl. Res.2018851460147010.1007/s13346‑018‑0540‑629785574
    [Google Scholar]
  93. GadhaveD. RasalN. SonawaneR. SekarM. KokareC. Nose-to-brain delivery of teriflunomide-loaded lipid-based carbopol-gellan gum nanogel for glioma: Pharmacological and in vitro cytotoxicity studies.Int. J. Biol. Macromol.202116790692010.1016/j.ijbiomac.2020.11.04733186648
    [Google Scholar]
  94. LavaniaK. GargA. Ion-activated in situ gel of gellan gum containing chrysin for nasal administration in parkinson’s disease.Recent Adv. Drug Deliv. Formul.2024181354910.2174/012667387827965623120410385538058093
    [Google Scholar]
  95. TaoT. ZhaoY. YueP. DongW.X. ChenQ.H. Preparation of huperzine A nasal in situ gel and evaluation of its brain targeting following intranasal administration.Yao Xue Xue Bao200641111104111017262956
    [Google Scholar]
  96. GalgatteU.C. KumbharA.B. ChaudhariP.D. Development of in situ gel for nasal delivery: Design, optimization, in vitro and in vivo evaluation.Drug Deliv.2014211627310.3109/10717544.2013.84977824191774
    [Google Scholar]
  97. HowardE. LiM. KozmaM. ZhaoJ. BaeJ. Self-strengthening stimuli-responsive nanocomposite hydrogels.Nanoscale20221448178871789410.1039/D2NR05408F36448666
    [Google Scholar]
  98. CapellaV. RiveroR.E. LiaudatA.C. IbarraL.E. RomaD.A. AlustizaF. MañasF. BarberoC.A. BoschP. RivarolaC.R. RodriguezN. Cytotoxicity and bioadhesive properties of poly-N-isopropylacrylamide hydrogel.Heliyon201954e0147410.1016/j.heliyon.2019.e0147431008402
    [Google Scholar]
  99. KimS. LeeK. ChaC. Refined control of thermoresponsive swelling/deswelling and drug release properties of poly(N-isopropylacrylamide) hydrogels using hydrophilic polymer crosslinkers.J. Biomater. Sci. Polym. Ed.201627171698171110.1080/09205063.2016.123093327573586
    [Google Scholar]
  100. SchillingA.L. KulahciY. MooreJ. WangE.W. LeeS.E. LittleS.R. A thermoresponsive hydrogel system for long-acting corticosteroid delivery into the paranasal sinuses.J. Control. Release202133088989710.1016/j.jconrel.2020.10.06233157189
    [Google Scholar]
  101. TanY. LiuY. LiuY. MaR. LuoJ. HongH. ChenX. WangS. LiuC. ZhangY. ChenT. Rational design of thermosensitive hydrogel to deliver nanocrystals with intranasal administration for brain targeting in parkinson’s disease.Research202120212021/9812523.10.34133/2021/981252334888525
    [Google Scholar]
/content/journals/cdm/10.2174/0113892002365157250422114917
Loading
/content/journals/cdm/10.2174/0113892002365157250422114917
Loading

Data & Media loading...

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