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image of Temperature-sensitive Hydrogel: An Effective Treatment for Nasal Drug Delivery Targeting the Brain

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 via nasal administration, aiming to provide a reference for the development of therapeutic drugs for cerebral diseases and their clinical application. A graphical summary.

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2025-05-06
2025-09-15

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References

  1. Goldstein L.B. Introduction for focused updates in cerebrovascular disease. Stroke 2020 51 3 708 710 10.1161/STROKEAHA.119.024159 32078448
    [Google Scholar]
  2. Creekmore B.C. Watanabe R. Lee E.B. Neurodegenerative disease tauopathies. Annu. Rev. Pathol. 2024 19 1 345 370 10.1146/annurev‑pathmechdis‑051222‑120750 37832941
    [Google Scholar]
  3. Mao Z. Tian L. Liu J. Wu Q. Wang N. Wang G. Wang Y. Seto S. Ligustilide ameliorates hippocampal neuronal injury after cerebral ischemia reperfusion through activating PINK1/Parkin-dependent mitophagy. Phytomedicine 2022 101 154111 10.1016/j.phymed.2022.154111 35512628
    [Google Scholar]
  4. Wang L. Liu C. Wang L. Tang B. Astragaloside IV mitigates cerebral ischaemia-reperfusion injury via inhibition of P62/Keap1/Nrf2 pathway-mediated ferroptosis. Eur. J. Pharmacol. 2023 944 175516 10.1016/j.ejphar.2023.175516 36758783
    [Google Scholar]
  5. Beirami E. Oryan S. Seyedhosseini Tamijani S.M. Ahmadiani A. Dargahi L. Intranasal insulin treatment alleviates methamphetamine induced anxiety-like behavior and neuroinflammation. Neurosci. Lett. 2017 660 122 129 10.1016/j.neulet.2017.09.026 28917981
    [Google Scholar]
  6. Lu Q. Xiang H. Zhu H. Chen Y. Lu X. Huang C. Intranasal lipopolysaccharide administration prevents chronic stress-induced depression- and anxiety-like behaviors in mice. Neuropharmacology 2021 200 108816 10.1016/j.neuropharm.2021.108816 34599975
    [Google Scholar]
  7. Zhao Z. Nelson A.R. Betsholtz C. Zlokovic B.V. Establishment and dysfunction of the blood-brain barrier. Cell 2015 163 5 1064 1078 10.1016/j.cell.2015.10.067 26590417
    [Google Scholar]
  8. Alahmari A. Blood-Brain Barrier Overview: Structural and Functional Correlation. Neural Plast. 2021 2021 1 10 10.1155/2021/6564585 34912450
    [Google Scholar]
  9. Sánchez de Medina A. Serrano-Rodríguez J.M. Díez de Castro E. García-Valverde M.T. Saitua A. Becero M. Muñoz A. Ferreiro-Vera C. Sánchez de Medina V. Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations. Equine Vet. J. 2023 55 6 1094 1103 10.1111/evj.13923 36624043
    [Google Scholar]
  10. Kadry H. Noorani B. Cucullo L. A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS 2020 17 1 69 10.1186/s12987‑020‑00230‑3 33208141
    [Google Scholar]
  11. Erdő F. Bors L.A. Farkas D. Bajza Á. Gizurarson S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res. Bull. 2018 143 155 170 10.1016/j.brainresbull.2018.10.009 30449731
    [Google Scholar]
  12. Gonçalves J. Alves G. Fonseca C. Carona A. Bicker J. Falcão A. Fortuna A. Is intranasal administration an opportunity for direct brain delivery of lacosamide? Eur. J. Pharm. Sci. 2021 157 105632 10.1016/j.ejps.2020.105632 33152466
    [Google Scholar]
  13. Kashyap K. Shukla R. Drug delivery and targeting to the brain through nasal route: Mechanisms, applications and challenges. Curr. Drug Deliv. 2019 16 10 887 901 10.2174/1567201816666191029122740 31660815
    [Google Scholar]
  14. Feng Y. Xia W. Zhao P. Yi X. Tang A. Survey anatomy and histological observation of the nasal cavity of Tupaia belangeri chinensis (Tupaiidae, Scandentia, Mammalia). Anat. Rec. (Hoboken) 2022 305 6 1448 1458 10.1002/ar.24793 34605617
    [Google Scholar]
  15. Patel R. Nasal anatomy and function.Facial Plast Surg., 2017 33 1 003 008 10.1055/s‑0036‑1597950 28226365
    [Google Scholar]
  16. Keller L.A. Merkel O. Popp A. Intranasal drug delivery: Opportunities and toxicologic challenges during drug development. Drug Deliv. Transl. Res. 2022 12 4 735 757 10.1007/s13346‑020‑00891‑5 33491126
    [Google Scholar]
  17. Gabold B. Adams F. Brameyer S. Jung K. Ried C.L. Merdan T. Merkel O.M. Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins. Drug Deliv. Transl. Res. 2023 13 3 822 838 10.1007/s13346‑022‑01245‑z 36207657
    [Google Scholar]
  18. Lobaina Mato Y. Nasal route for vaccine and drug delivery: Features and current opportunities. Int. J. Pharm. 2019 572 118813 10.1016/j.ijpharm.2019.118813 31678521
    [Google Scholar]
  19. Balafas E.G. Papakyriakopoulou P.I. Kostomitsopoulos N.G. Valsami G.N. Intranasal administration of a polymeric biodegradable film to C57BL/6 mice. J. Am. Assoc. Lab. Anim. Sci. 2023 62 2 179 184 10.30802/AALAS‑JAALAS‑22‑000091 36898691
    [Google Scholar]
  20. Gizurarson S. The effect of cilia and the mucociliary clearance on successful drug delivery. Biol. Pharm. Bull. 2015 38 4 497 506 10.1248/bpb.b14‑00398 25739664
    [Google Scholar]
  21. Scherließ R. Nasal formulations for drug administration and characterization of nasal preparations in drug delivery. Ther. Deliv. 2020 11 3 183 191 10.4155/tde‑2019‑0086 32046624
    [Google Scholar]
  22. Hu X. Yue X. Wu C. Zhang X. Factors affecting nasal drug delivery and design strategies for intranasal drug delivery. Zhejiang Da Xue Xue Bao Yi Xue Ban 2023 52 3 328 337 10.3724/zdxbyxb‑2023‑0069 37476944
    [Google Scholar]
  23. Gray S.M. Barrett E.J. Insulin transport into the brain. Am. J. Physiol. Cell Physiol. 2018 315 2 C125 C136 10.1002/jnr.25192 36977654
    [Google Scholar]
  24. Freddi T.A.L. Ottaiano A.C. Lucio L.L. Corrêa D.G. Hygino da Cruz L.C. The trigeminal nerve: Anatomy and pathology. Semin. Ultrasound CT MR 2022 43 5 403 413 10.1053/j.sult.2022.04.002 36116853
    [Google Scholar]
  25. Crowe T.P. Greenlee M.H.W. Kanthasamy A.G. Hsu W.H. Mechanism of intranasal drug delivery directly to the brain. Life Sci. 2018 195 44 52 10.1016/j.lfs.2017.12.025 29277310
    [Google Scholar]
  26. Ottaiano A.C. Freddi T.A.L. Lucio L.L. The olfactory nerve: Anatomy and pathology. Semin. Ultrasound CT MR 2022 43 5 371 377 10.1053/j.sult.2022.04.001 36116849
    [Google Scholar]
  27. Helwany M. Bordoni B. Neuroanatomy, Cranial Nerve 1 (Olfactory). StatPearls. Treasure Island, FL StatPearls Publishing 2025
    [Google Scholar]
  28. Maeng J. Lee K. Systemic and brain delivery of antidiabetic peptides through nasal administration using cell-penetrating peptides. Front. Pharmacol. 2022 13 1068495 10.3389/fphar.2022.1068495 36452220
    [Google Scholar]
  29. Wu D. Chen Q. Chen X. Han F. Chen Z. Wang Y. The blood–brain barrier: Structure, regulation and drug delivery. Signal Transduct. Target. Ther. 2023 8 1 217 10.1038/s41392‑023‑01481‑w 37231000
    [Google Scholar]
  30. Obermeier B. Daneman R. Ransohoff R.M. Development, maintenance and disruption of the blood-brain barrier. Nat. Med. 2013 19 12 1584 1596 10.1038/nm.3407 24309662
    [Google Scholar]
  31. Sun H. Hu H. Liu C. Sun N. Duan C. Methods used for the measurement of blood-brain barrier integrity. Metab. Brain Dis. 2021 36 5 723 735 10.1007/s11011‑021‑00694‑8 33635479
    [Google Scholar]
  32. Hajal C. Le Roi B. Kamm R.D. Maoz B.M. Biology and models of the blood–brain barrier. Annu. Rev. Biomed. Eng. 2021 23 1 359 384 10.1146/annurev‑bioeng‑082120‑042814 34255993
    [Google Scholar]
  33. Sweeney M.D. Zhao Z. Montagne A. Nelson A.R. Zlokovic B.V. Blood-brain barrier: From physiology to disease and back. Physiol. Rev. 2019 99 1 21 78 10.1152/physrev.00050.2017 30280653
    [Google Scholar]
  34. Matsumoto J. Stewart T. Banks W.A. Zhang J. The transport mechanism of extracellular vesicles at the blood-brain barrier. Curr. Pharm. Des. 2018 23 40 6206 6214 10.2174/1381612823666170913164738 28914201
    [Google Scholar]
  35. Sharma S. Dang S. Nanocarrier-based drug delivery to brain: Interventions of surface modification. Curr. Neuropharmacol. 2023 21 3 517 535 10.2174/1570159X20666220706121412 35794771
    [Google Scholar]
  36. Bashyal S. Thapa C. Lee S. Recent progresses in exosome-based systems for targeted drug delivery to the brain. J. Control. Release 2022 348 723 744 10.1016/j.jconrel.2022.06.011 35718214
    [Google Scholar]
  37. Vieira L.S. Wang J. Brain plasma membrane monoamine transporter in health and disease. Handb. Exp. Pharmacol. 2021 266 253 280 10.1007/164_2021_446 33751232
    [Google Scholar]
  38. Terstappen G.C. Meyer A.H. Bell R.D. Zhang W. Strategies for delivering therapeutics across the blood–brain barrier. Nat. Rev. Drug Discov. 2021 20 5 362 383 10.1038/s41573‑021‑00139‑y 33649582
    [Google Scholar]
  39. Yeruva T. Yang S. Doski S. Duncan G.A. Hydrogels for mucosal drug delivery. ACS Appl. Bio Mater. 2023 6 5 1684 1700 10.1021/acsabm.3c00050 37126538
    [Google Scholar]
  40. Almoshari Y. Novel hydrogels for topical applications: An updated comprehensive review based on source. Gels 2022 8 3 174 10.3390/gels8030174 35323287
    [Google Scholar]
  41. Mo F. Jiang K. Zhao D. Wang Y. Song J. Tan W. DNA hydrogel-based gene editing and drug delivery systems. Adv. Drug Deliv. Rev. 2021 168 79 98 10.1016/j.addr.2020.07.018 32712197
    [Google Scholar]
  42. Trombino S. Servidio C. Curcio F. Cassano R. Strategies for hyaluronic acid-based hydrogel design in drug delivery. Pharmaceutics 2019 11 8 407 10.3390/pharmaceutics11080407 31408954
    [Google Scholar]
  43. Chen X. Li H. Lam K.Y. A multiphysics model of photo-sensitive hydrogels in response to light-thermo-pH-salt coupled stimuli for biomedical applications. Bioelectrochemistry 2020 135 107584 10.1016/j.bioelechem.2020.107584 32574995
    [Google Scholar]
  44. Wang Y. Zhang J. Zhang W. Zhang M. Pd-catalyzed C-C cross-coupling reactions within a thermoresponsive and pH-responsive and chelating polymeric hydrogel. J. Org. Chem. 2009 74 5 1923 1931 10.1021/jo802427k 19173610
    [Google Scholar]
  45. Zhu X. Yang C. Jian Y. Deng H. Du Y. Shi X. Ion-responsive chitosan hydrogel actuator inspired by carrotwood seed pod. Carbohydr. Polym. 2022 276 118759 10.1016/j.carbpol.2021.118759 34823783
    [Google Scholar]
  46. Akalp U. Bryant S.J. Vernerey F.J. Tuning tissue growth with scaffold degradation in enzyme-sensitive hydrogels: A mathematical model. Soft Matter 2016 12 36 7505 7520 10.1039/C6SM00583G 27548744
    [Google Scholar]
  47. Zhao Y. Liu X. Peng X. Zheng Y. Cheng Z. Sun S. Ding Q. Liu W. Ding C. A poloxamer/hyaluronic acid/chitosan-based thermosensitive hydrogel that releases dihydromyricetin to promote wound healing. Int. J. Biol. Macromol. 2022 216 475 486 10.1016/j.ijbiomac.2022.06.210 35810849
    [Google Scholar]
  48. Villa C. Martello F. Erratico S. Tocchio A. Belicchi M. Lenardi C. Torrente Y.P. (NIPAAM-co-HEMA) thermoresponsive hydrogels: An alternative approach for muscle cell sheet engineering. J. Tissue Eng. Regen. Med. 2017 11 1 187 196 10.1002/term.1898 24799388
    [Google Scholar]
  49. Bostan M.S. Senol M. Cig T. Peker I. Goren A.C. Ozturk T. Eroglu M.S. Controlled release of 5-aminosalicylicacid from chitosan based pH and temperature sensitive hydrogels. Int. J. Biol. Macromol. 2013 52 177 183 10.1016/j.ijbiomac.2012.09.018 23041667
    [Google Scholar]
  50. Li Y. Zhang L. Song Z. Li F. Xie D. Intelligent temperature-pH 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
  51. Kim A.R. Lee S.L. Park S.N. Properties and in vitro drug release of pH- and temperature-sensitive double cross-linked interpenetrat-ing polymer network hydrogels based on hyaluronic acid/poly (N-isopropylacrylamide) for transdermal delivery of luteolin. Int. J. Biol. Macromol, 2018 118 Part A 731 740 10.1016/j.ijbiomac.2018.06.061
  52. Lu L. Huang Z. Li X. Li X. Cui B. Yuan C. Guo L. Liu P. Dai Q. A high-conductive, anti-freezing, antibacterial and anti-swelling starch-based physical hydrogel for multifunctional flexible wearable sensors. Int. J. Biol. Macromol. 2022 213 791 803 10.1016/j.ijbiomac.2022.06.011 35679959
    [Google Scholar]
  53. Ilić-Stojanović S. Nikolić L. Nikolić V. Ristić I. Cakić S. Petrović S.D. Temperature-sensitive hydrogels as carriers for modulated delivery of acetaminophen. Gels 2023 9 9 684 10.3390/gels9090684 37754365
    [Google Scholar]
  54. Xian S. Webber M.J. Temperature-responsive supramolecular hydrogels. J. Mater. Chem. B Mater. Biol. Med. 2020 8 40 9197 9211 10.1039/D0TB01814G 32924052
    [Google Scholar]
  55. Yu Y. Cheng Y. Tong J. Zhang L. Wei Y. Tian M. Recent advances in thermo-sensitive hydrogels for drug delivery. J. Mater. Chem. B Mater. Biol. Med. 2021 9 13 2979 2992 10.1039/D0TB02877K 33885662
    [Google Scholar]
  56. Rahmani F. Atabaki R. Behrouzi S. Mohamadpour F. Kamali H. The recent advancement in the PLGA-based thermo-sensitive hydrogel for smart drug delivery. Int. J. Pharm. 2023 631 122484 10.1016/j.ijpharm.2022.122484 36509221
    [Google Scholar]
  57. Zhou W. Duan Z. Zhao J. Fu R. Zhu C. Fan D. Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing. Bioact. Mater. 2022 17 1 17 10.1016/j.bioactmat.2022.01.004 35386439
    [Google Scholar]
  58. Garg A. Agrawal R. Singh Chauhan C. Deshmukh R. In-situ gel: A smart carrier for drug delivery. Int. J. Pharm. 2024 652 123819 10.1016/j.ijpharm.2024.123819 38242256
    [Google Scholar]
  59. Chen W.N. Shaikh M.F. Bhuvanendran S. Date A. Ansari M.T. Radhakrishnan A.K. Othman I. Poloxamer 188 (P188), A potential polymeric protective agent for central nervous system disorders: A systematic review. Curr. Neuropharmacol. 2022 20 4 799 808 10.2174/1570159X19666210528155801 34077349
    [Google Scholar]
  60. Zarrintaj P. Ramsey J.D. Samadi A. Atoufi Z. Yazdi M.K. Ganjali M.R. Amirabad L.M. Zangene E. Farokhi M. Formela K. Saeb M.R. Mozafari M. Thomas S. Poloxamer: A versatile tri-block copolymer for biomedical applications. Acta Biomater. 2020 110 37 67 10.1016/j.actbio.2020.04.028 32417265
    [Google Scholar]
  61. Russo E. Villa C. Poloxamer hydrogels for biomedical applications. Pharmaceutics 2019 11 12 671 10.3390/pharmaceutics11120671 31835628
    [Google Scholar]
  62. Le T.P. Yu Y. Cho I.S. Suh E.Y. Kwon H.C. Shin S.A. Park Y.H. Huh K.M. Injectable poloxamer hydrogel formulations for intratympanic delivery of dexamethasone. J. Korean Med. Sci. 2023 38 17 e135 10.3346/jkms.2023.38.e135 37128878
    [Google Scholar]
  63. Wang T. Markham A. Thomas S.J. Wang N. Huang L. Clemens M. Rajagopalan N. Solution stability of poloxamer 188 under stress conditions. J. Pharm. Sci. 2019 108 3 1264 1271 10.1016/j.xphs.2018.10.057 30419275
    [Google Scholar]
  64. Elsenosy F.M. Abdelbary G.A. Elshafeey A.H. Elsayed I. Fares A.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. Nanomedicine 2020 15 9517 9537 10.2147/IJN.S277352 33324051
    [Google Scholar]
  65. Pang L. Zhu S. Ma J. Zhu L. Liu Y. Ou G. Li R. Wang Y. Liang Y. Jin X. Du L. Jin Y. Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder. Acta Pharm. Sin. B 2021 11 7 2031 2047 10.1016/j.apsb.2021.01.014 34386336
    [Google Scholar]
  66. Riaz M. Zaman M. Hameed H. Sarwar H.S. Khan M.A. Irfan A. Shazly G.A. Paiva-Santos A.C. Jardan Y.A.B. Lamotrigine-loaded poloxamer-based thermo-responsive sol-gel: Formulation, in vitro assessment, ex vivo permeation, and toxicology study. Gels 2023 9 10 817 37888390
    [Google Scholar]
  67. Diaz-Salmeron R. Toussaint B. Huang N. Bourgeois Ducournau E. Alviset G. Goulay Dufaÿ S. Hillaireau H. Dufaÿ Wojcicki A. Boudy V. Mucoadhesive poloxamer-based hydrogels for the release of HP-β-CD-complexed dexamethasone in the treatment of buccal diseases. Pharmaceutics 2021 13 1 117 33477667
    [Google Scholar]
  68. Mendonsa N.S. Murthy S.N. Hashemnejad S.M. Kundu S. Zhang F. Repka M.A. Development of poloxamer gel formulations via hot-melt extrusion technology. Int. J. Pharm. 2018 537 1-2 122 131 10.1016/j.ijpharm.2017.12.008 29253585
    [Google Scholar]
  69. Chen X. Zhi F. Jia X. Zhang X. Ambardekar R. Meng Z. Paradkar A.R. Hu Y. Yang Y. Enhanced brain targeting of curcumin by intranasal administration of a thermosensitive poloxamer hydrogel. J. Pharm. Pharmacol. 2013 65 6 807 816 23647674
    [Google Scholar]
  70. Li C. Li C. Liu Z. Li Q. Yan X. Liu Y. Lu W. Enhancement in bioavailability of ketorolac tromethamine via intranasal in situ hydrogel based on poloxamer 407 and carrageenan. Int. J. Pharm. 2014 474 1-2 123 133 10.1016/j.ijpharm.2014.08.023 25138250
    [Google Scholar]
  71. Ahirrao M. Shrotriya S. In vitro and in vivo evaluation of cubosomal in situ nasal gel containing resveratrol for brain targeting. Drug Dev. Ind. Pharm. 2017 43 10 1686 1693 10.1080/03639045.2017.1338721 28574732
    [Google Scholar]
  72. Corazza E. di Cagno M.P. Bauer-Brandl A. Abruzzo A. Cerchiara T. Bigucci F. Luppi B. Drug delivery to the brain: In situ gelling formulation enhances carbamazepine diffusion through nasal mucosa models with mucin. Eur. J. Pharm. Sci. 2022 179 106294 10.1016/j.ejps.2022.106294 36116696
    [Google Scholar]
  73. Ravi P.R. Aditya N. Patil S. Cherian L. Nasal in-situ gels for delivery of rasagiline mesylate: Improvement in bioavailability and brain localization. Drug Deliv. 2015 22 7 903 910 10.3109/10717544.2013.860501 24286183
    [Google Scholar]
  74. Salatin S. Alami-Milani M. Daneshgar R. Jelvehgari M. Box–Behnken experimental design for preparation and optimization of the intranasal gels of selegiline hydrochloride. Drug Dev. Ind. Pharm. 2018 44 10 1613 1621 10.1080/03639045.2018.1483387 29932793
    [Google Scholar]
  75. Li Q. Zhang Y. Hu J. Yuan B. Zhang P. Wang Y. Jin X. Du L. Jin Y. The improved brain-targeted drug delivery of edaravone temperature-sensitive gels by ultrasound for γ-ray radiation-induced brain injury. Pharmaceutics 2022 14 11 2281 10.3390/pharmaceutics14112281 36365100
    [Google Scholar]
  76. Liu Y. Li S. Wang Z. Wang L. Ultrasound in cellulose-based hydrogel for biomedical use: From extraction to preparation. Colloids Surf. B Biointerfaces 2022 212 112368 10.1016/j.colsurfb.2022.112368 35114437
    [Google Scholar]
  77. Bhaladhare S. Das D. Cellulose: A fascinating biopolymer for hydrogel synthesis. J. Mater. Chem. B Mater. Biol. Med. 2022 10 12 1923 1945 10.1039/D1TB02848K 35226030
    [Google Scholar]
  78. Uppuluri C.T. Ravi P.R. Dalvi A.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. 2021 606 120881 10.1016/j.ijpharm.2021.120881 34273426
    [Google Scholar]
  79. Uppuluri C.T. Ravi P.R. Dalvi A.V. Design and evaluation of thermo-responsive nasal in situ gelling system dispersed with piribedil loaded lecithin-chitosan hybrid nanoparticles for improved brain availability. Neuropharmacology 2021 201 108832 10.1016/j.neuropharm.2021.108832 34627852
    [Google Scholar]
  80. Ou G. Li Q. Zhu L. Zhang Y. Liu Y. Li X. Du L. Jin Y. Intranasal hydrogel of armodafinil hydroxypropyl-β-cyclodextrin inclusion complex for the treatment of post-traumatic stress disorder. Saudi Pharm. J. 2022 30 3 265 282 10.1016/j.jsps.2022.01.009 35498223
    [Google Scholar]
  81. El Taweel M.M. Aboul-Einien M.H. Kassem M.A. Elkasabgy N.A. Intranasal zolmitriptan-loaded bilosomes with extended nasal mucociliary transit time for direct nose to brain delivery. Pharmaceutics 2021 13 11 1828 10.3390/pharmaceutics13111828 34834242
    [Google Scholar]
  82. Anees E. Riaz M. Imtiaz H. Hussain T. Electrochemical corrosion study of chitosan-hydroxyapatite coated dental implant. J. Mech. Behav. Biomed. Mater. 2024 150 106268 10.1016/j.jmbbm.2023.106268 38039776
    [Google Scholar]
  83. Khan S. Patil K. Bobade N. Yeole P. Gaikwad R. Formulation of intranasal mucoadhesive temperature-mediated in situ gel containing ropinirole and evaluation of brain targeting efficiency in rats. J. Drug Target. 2010 18 3 223 234 10.3109/10611860903386938 20030503
    [Google Scholar]
  84. Teaima M.H. El Mohamady A.M. El-Nabarawi M.A. Mohamed A.I. Formulation and evaluation of niosomal vesicles containing ondansetron HCL for trans-mucosal nasal drug delivery. Drug Dev. Ind. Pharm. 2020 46 5 751 761 10.1080/03639045.2020.1753061 32250181
    [Google Scholar]
  85. Qi X.J. Liu X.Y. Tang L.M.Y. Li P.F. Qiu F. Yang A.H. Anti-depressant effect of curcumin-loaded guanidine-chitosan thermo-sensitive hydrogel by nasal delivery. Pharm. Dev. Technol. 2020 25 3 316 325 10.1080/10837450.2019.1686524 31661648
    [Google Scholar]
  86. Kamali H. Tafaghodi M. Eisvand F. Ahmadi-Soleimani S.M. Khajouee M. Ghazizadeh H. Mosafer J. 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. 2024 21 7 1024 1035 10.2174/1567201820666230724161205 37491854
    [Google Scholar]
  87. Kashif M.R. Sohail M. Khan S.A. Minhas M.U. Mahmood A. Shah S.A. Mohsin S. Chitosan/guar gum-based thermoreversible hydrogels loaded with pullulan nanoparticles for enhanced nose-to-brain drug delivery. Int. J. Biol. Macromol. 2022 215 579 595 10.1016/j.ijbiomac.2022.06.161 35779651
    [Google Scholar]
  88. Nafee N. Ameen A.E.R. Abdallah O.Y. Patient-friendly, olfactory-targeted, stimuli-responsive hydrogels for cerebral degenerative disorders ensured & 400% brain targeting efficiency in rats. AAPS PharmSciTech 2021 22 1 6 10.1208/s12249‑020‑01872‑0 33222021
    [Google Scholar]
  89. Hard S.A.A.A. Shivakumar H.N. Redhwan M.A.M. Development and optimization of in-situ gel containing chitosan nanoparticles for possible nose-to-brain delivery of vinpocetine. Int. J. Biol. Macromol. 2023 253 Pt 6 127217 10.1016/j.ijbiomac.2023.127217 37793522
    [Google Scholar]
  90. Palumbo F.S. Federico S. Pitarresi G. Fiorica C. Giammona G. Gellan gum-based delivery systems of therapeutic agents and cells. Carbohydr. Polym. 2020 229 115430 10.1016/j.carbpol.2019.115430 31826518
    [Google Scholar]
  91. Osmałek T. Froelich A. Tasarek S. Application of gellan gum in pharmacy and medicine. Int. J. Pharm. 2014 466 1-2 328 340 10.1016/j.ijpharm.2014.03.038 24657577
    [Google Scholar]
  92. Rajput A. Bariya A. Allam A. Othman S. Butani S.B. In situ nanostructured hydrogel of resveratrol for brain targeting: in vitro-in vivo characterization. Drug Deliv. Transl. Res. 2018 8 5 1460 1470 10.1007/s13346‑018‑0540‑6 29785574
    [Google Scholar]
  93. Gadhave D. Rasal N. Sonawane R. Sekar M. Kokare C. 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. 2021 167 906 920 10.1016/j.ijbiomac.2020.11.047 33186648
    [Google Scholar]
  94. Lavania K. Garg A. Ion-activated in situ gel of gellan gum containing chrysin for nasal administration in parkinson’s disease. Recent Adv. Drug Deliv. Formul. 2024 18 1 35 49 10.2174/0126673878279656231204103855 38058093
    [Google Scholar]
  95. Tao T. Zhao Y. Yue P. Dong W.X. Chen Q.H. Preparation of huperzine A nasal in situ gel and evaluation of its brain targeting following intranasal administration. Yao Xue Xue Bao 2006 41 11 1104 1110 17262956
    [Google Scholar]
  96. Galgatte U.C. Kumbhar A.B. Chaudhari P.D. Development of in situ gel for nasal delivery: Design, optimization, in vitro and in vivo evaluation. Drug Deliv. 2014 21 1 62 73 10.3109/10717544.2013.849778 24191774
    [Google Scholar]
  97. Howard E. Li M. Kozma M. Zhao J. Bae J. Self-strengthening stimuli-responsive nanocomposite hydrogels. Nanoscale 2022 14 48 17887 17894 10.1039/D2NR05408F 36448666
    [Google Scholar]
  98. Capella V. Rivero R.E. Liaudat A.C. Ibarra L.E. Roma D.A. Alustiza F. Mañas F. Barbero C.A. Bosch P. Rivarola C.R. Rodriguez N. Cytotoxicity and bioadhesive properties of poly-N-isopropylacrylamide hydrogel. Heliyon 2019 5 4 e01474 10.1016/j.heliyon.2019.e01474 31008402
    [Google Scholar]
  99. Kim S. Lee K. Cha C. Refined control of thermoresponsive swelling/deswelling and drug release properties of poly(N-isopropylacrylamide) hydrogels using hydrophilic polymer crosslinkers. J. Biomater. Sci. Polym. Ed. 2016 27 17 1698 1711 10.1080/09205063.2016.1230933 27573586
    [Google Scholar]
  100. Schilling A.L. Kulahci Y. Moore J. Wang E.W. Lee S.E. Little S.R. A thermoresponsive hydrogel system for long-acting corticosteroid delivery into the paranasal sinuses. J. Control. Release 2021 330 889 897 10.1016/j.jconrel.2020.10.062 33157189
    [Google Scholar]
  101. Tan Y. Liu Y. Liu Y. Ma R. Luo J. Hong H. Chen X. Wang S. Liu C. Zhang Y. Chen T. Rational design of thermosensitive hydrogel to deliver nanocrystals with intranasal administration for brain targeting in parkinson’s disease. Research, 2021 2021 2021/9812523 10.34133/2021/9812523 34888525
    [Google Scholar]
/content/journals/cdm/10.2174/0113892002365157250422114917
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Temperature-sensitive Hydrogel: An Effective Treatment for Nasal Drug Delivery Targeting the Brain
Bentham Science Publishers ; https://doi.org/10.2174/0113892002365157250422114917
/content/journals/cdm/10.2174/0113892002365157250422114917
/content/journals/cdm/10.2174/0113892002365157250422114917
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  • Article Type:     Review Article
Keywords: Basal-brain pathway ; Blood-brain barrier ; Brain targeting ; Drug delivery system ; Temperature-sensitive hydrogel

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