Skip to content
2000
image of In-vivo, In-vitro, and Ex-vivo Experimental Models for Nose‐to‐brain Drug Delivery

Abstract

This article reviews various experimental models to determine pharmacological and physiological factors affecting intranasal to brain delivery. Administering drugs directly from the nasal cavity to the brain has great potential for treating Central Nervous System (CNS) disorders. Various preclinical models, such as and are used to study the transport of drugs after intranasal administration. The use of and intranasal models provides an opportunity to study the physiological and pharmacological aspects that may impact the transport of drugs the nasal epithelium. These models can help in understanding the mechanisms of drug absorption from the intranasal region. Developing and employing cost-efficient pharmacokinetic models for intranasal drug administration that exhibit an effective relationship can boost the development of drugs and improve economic and ecological factors by reducing the need for animal experimentation. Thus, reducing both the duration and costs. The present review article aims to offer a comprehensive summary of the various experimental models. Furthermore, it does a comprehensive assessment of data gathered from several studies and emphasizes the pros and cons of each model.

Loading

Article metrics loading...

/content/journals/ddl/10.2174/0122103031378584250829054818
2025-09-02
2026-02-02
Loading full text...

Full text loading...

References

  1. Chen Y. Zhang C. Huang Y. Ma Y. Song Q. Chen H. Jiang G. Gao X. Intranasal drug delivery: The interaction between nanoparticles and the nose-to-brain pathway. Adv. Drug Deliv. Rev. 2024 207 115196 10.1016/j.addr.2024.115196 38336090
    [Google Scholar]
  2. Ghosh A. Majie A. Karmakar V. Chatterjee K. Chakraborty S. Pandey M. In-depth mechanism, challenges, and opportunities of delivering therapeutics in brain using intranasal route. AAPS PharmSciTech 2024 25 5 1 23 [May;]
    [Google Scholar]
  3. Koo J. Lim C. Oh K.T. Recent advances in intranasal administration for brain-targeting delivery: A comprehensive review of lipid-based nanoparticles and stimuli-responsive gel formulations. Int. J. Nanomedicine 2024 19 1767 1807 10.2147/IJN.S439181 38414526
    [Google Scholar]
  4. Huang Q. Chen Y. Zhang W. Xia X. Li H. Qin M. Gao H. Nanotechnology for enhanced nose-to-brain drug delivery in treating neurological diseases. J. Control. Release 2024 366 519 534 10.1016/j.jconrel.2023.12.054 38182059
    [Google Scholar]
  5. Xu D. Song X.J. Chen X. Wang J.W. Cui Y.L. Advances and future perspectives of intranasal drug delivery: A scientometric review. J. Control. Release 2024 367 366 384 10.1016/j.jconrel.2024.01.053 38286336
    [Google Scholar]
  6. Sicard R.M. Frank-Ito D.O. Parameter characteristics in intranasal drug delivery: A key to targeting medications to the olfactory airspace. Clin. Biomech. (Bristol, Avon) 2024 114 106231 10.1016/j.clinbiomech.2024.106231 38507865
    [Google Scholar]
  7. Haasbroek-Pheiffer A. Van Niekerk S. Van der Kooy F. Cloete T. Steenekamp J. Hamman J. in vitro and ex vivo experimental models for evaluation of intranasal systemic drug delivery as well as direct nose‐to‐brain drug delivery. Biopharm. Drug Dispos. 2023 44 1 94 112 10.1002/bdd.2348 36736328
    [Google Scholar]
  8. Wong C.Y.J. Baldelli A. Tietz O. van der Hoven J. Suman J. Ong H.X. Traini D. An overview of in vitro and in vivo techniques for characterization of intranasal protein and peptide formulations for brain targeting. Int. J. Pharm. 2024 654 123922 10.1016/j.ijpharm.2024.123922 38401871
    [Google Scholar]
  9. Bonaccorso A. Ortis A. Musumeci T. Carbone C. Hussain M. Di Salvatore V. Battiato S. Pappalardo F. Pignatello R. Nose-to-brain drug delivery and physico-chemical properties of nanosystems: Analysis and correlation studies of data from scientific Literature. Int. J. Nanomedicine 2024 19 5619 5636 10.2147/IJN.S452316 38882536
    [Google Scholar]
  10. Simhadri A. Dommeti M.D. Sana J. A comprehensive review on the nanotechnology-based intranasal drug delivery systems for brain targeting: Review article. J. Pharma Insights Res. 2024 2 4 015-023.Aug; 10.69613/fjsep132
    [Google Scholar]
  11. Boyuklieva R. Zagorchev P. Pilicheva B. Computational, in vitro, and in vivo models for nose-to-brain drug delivery studies. Biomedicines 2023 11 2198 10.3390/biomedicines11082198
    [Google Scholar]
  12. Ozkan C.K. Esim O. Savaser A. An up-to-date look at in vitro models of nose-to-brain drug delivery. Nanomaterials for Cancer Detection Using Imaging Techniques and Their Clinical Applications. Chaughule R.S. Patkar D.P. Ramanujan R.V. Cham Springer 2022 10.1007/978‑3‑031‑09636‑5_5
    [Google Scholar]
  13. Mercier C. Jacqueroux E. He Z. Hodin S. Constant S. Perek N. Boudard D. Delavenne X. Pharmacological characterization of the 3D MucilAir™ nasal model. Eur. J. Pharm. Biopharm. 2019 139 186 196 10.1016/j.ejpb.2019.04.002 30951820
    [Google Scholar]
  14. Zhao C. Cell culture: in vitro model system and a promising path to in vivo applications. J. Histotechnol. 2023 46 1 1 4 10.1080/01478885.2023.2170772 36691848
    [Google Scholar]
  15. Wang Y. Gao Y. Pan Y. Zhou D. Liu Y. Yin Y. Yang J. Wang Y. Song Y. Emerging trends in organ-on-a-chip systems for drug screening. Acta Pharm. Sin. B 2023 13 6 2483 2509 10.1016/j.apsb.2023.02.006 37425038
    [Google Scholar]
  16. Ingber D.E. Human organs-on-chips for disease modelling, drug development and personalized medicine. Nat. Rev. Genet. 2022 23 467 491 10.1038/s41576‑022‑00466‑9
    [Google Scholar]
  17. Chalak M. Hesaraki M. Mirbahari S.N. Yeganeh M. Abdi S. Rajabi S. Cell immortality: in vitro effective techniques to achieve and investigate its applications and challenges. Life 2024 14 3 417 10.3390/life14030417
    [Google Scholar]
  18. Mahieu L. in vitro modelling of bacterial pneumonia: A compar a ti v e analysis of widely applied complex cell culture models. FEMS Microbiol. Rev. 2024 48 7 10.1093/femsre/fuae007
    [Google Scholar]
  19. Moura J.A. Meldrum K. Doak S.H. Clift M.J.D. Alternative lung cell model systems for toxicology testing strategies: Current knowledge and future outlook. Semin. Cell Dev. Biol. 2023 147 70 82 10.1016/j.semcdb.2022.12.006 36599788
    [Google Scholar]
  20. Zhou Y. Duan Q. Yang D. in vitro human cell-based models to study airway remodeling in asthma. Biomed. Pharmacother. 2023 159 114218 10.1016/j.biopha.2023.114218 36638596
    [Google Scholar]
  21. Kanninen K.M. Lampinen R. Rantanen L.M. Odendaal L. Jalava P. Chew S. White A.R. Olfactory cell cultures to investigate health effects of air pollution exposure: Implications for neurodegeneration. Neurochem. Int. 2020 136 104729 10.1016/j.neuint.2020.104729 32201281
    [Google Scholar]
  22. Bai S. Yang T. Abbruscato T.J. Ahsan F. Evaluation of human nasal RPMI 2650 cells grown at an air-liquid interface as a model for nasal drug transport studies. J. Pharm. Sci. 2008 97 3 1165 1178 10.1002/jps.21031 17628494
    [Google Scholar]
  23. Tan H.Y. Trier S. Rahbek U.L. Dufva M. Kutter J.P. Andresen T.L. A multi-chamber microfluidic intestinal barrier model using Caco-2 cells for drug transport studies. PLoS One 2018 13 5 e0197101 10.1371/journal.pone.0197101 29746551
    [Google Scholar]
  24. Eltanameli B. Piñeiro-Llanes J. Cristofoletti R. Recent advances in cell-based in vitro models for predicting drug permeability across brain, intestinal, and pulmonary barriers. Expert Opin. Drug Metab. Toxicol. 2024 20 6 439 458 10.1080/17425255.2024.2366390 38850058
    [Google Scholar]
  25. Lofts A. Campea M.A. Winterhelt E. Rigg N. Rivera N.P. Macdonald C. Frey B.N. Mishra R.K. Hoare T. In situ-gelling hydrophobized starch nanoparticle-based nanoparticle network hydrogels for the effective delivery of intranasal olanzapine to treat brain disorders. Int. J. Biol. Macromol. 2024 277 Pt 4 134385 10.1016/j.ijbiomac.2024.134385 39111489
    [Google Scholar]
  26. Callaghan P.J. Ferrick B. Rybakovsky E. Thomas S. Mullin J.M. Epithelial barrier function properties of the 16HBE14o- human bronchial epithelial cell culture model. Biosci. Rep. 2020 40 10 BSR20201532 10.1042/BSR20201532
    [Google Scholar]
  27. Li L. Tan L. Zhang Q. Cheng Y. Liu Y. Li R. Hou S. Nose-to-brain delivery of self-assembled curcumin-lactoferrin nanoparticles: Characterization, neuroprotective effect and in vivo pharmacokinetic study. Front. Bioeng. Biotechnol. 2023 11 1168408 10.3389/fbioe.2023.1168408 37051277
    [Google Scholar]
  28. sharifian, A.; Varshosaz, J.; Aliomrani, M.; Kazemi, M. Polydopamine coated surfactin micelles for brain delivery of ibudilast in multiple sclerosis: Design, optimization, in vitro and in vivo evaluation. J. Drug Deliv. Sci. Technol. 2024 95 105530 10.1016/j.jddst.2024.105530
    [Google Scholar]
  29. Abd-algaleel S.A. Metwally A.A. Abdel-Bar H.M. Kassem D.H. Hathout R.M. Synchronizing in silico, in vitro, and in vivo studies for the successful nose to brain delivery of an anticancer molecule. Mol. Pharm. 2021 18 10 3763 3776 10.1021/acs.molpharmaceut.1c00276 34460250
    [Google Scholar]
  30. 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]
  31. Hamzah M. Kassab H. Formulation and characterization of intranasal drug delivery of frovatriptan-loaded binary ethosomes gel for brain targeting. Nanotechnol. Sci. Appl. 2024 17 1 19 10.2147/NSA.S442951 38249545
    [Google Scholar]
  32. Pereira M.F. Shyti R. Testa G. In and out: Benchmarking in vitro, in vivo, ex vivo and xenografting approaches for an integrative brain disease modeling pipeline. Stem Cell Reports 2024 19 6 767 795 10.1016/j.stemcr.2024.05.004 38865969
    [Google Scholar]
  33. Yadav J. El Hassani M. Sodhi J. Lauschke V.M. Hartman J.H. Russell L.E. Recent developments in in vitro and in vivo models for improved translation of preclinical pharmacokinetics and pharmacodynamics data. Drug Metab. Rev. 2021 53 2 207 233 10.1080/03602532.2021.1922435 33989099
    [Google Scholar]
  34. Steger-Hartmann T. Raschke M. Translating in vitro to in vivo and animal to human. Curr. Opin. Toxicol. 2020 23-24 6 10 10.1016/j.cotox.2020.02.003
    [Google Scholar]
  35. Moore S.J. Smith J.D. Greenlee M.H.W. Nicholson E.M. Richt J.A. Greenlee J.J. Comparison of two US Sheep scrapie isolates supports identification as separate strains. Vet. Pathol. 2016 53 6 1187 1196 10.1177/0300985816629712 26936223
    [Google Scholar]
  36. Salameh T.S. Bullock K.M. Hujoel I.A. Niehoff M.L. Wolden-Hanson T. Kim J. Morley J.E. Farr S.A. Banks W.A. Central nervous system delivery of intranasal insulin: Mechanisms of uptake and effects on cognition. J. Alzheimers Dis. 2015 47 3 715 728 10.3233/JAD‑150307 26401706
    [Google Scholar]
  37. Micieli F. Santangelo B. Napoleone G. Di Dona F. Mennonna G. Vesce G. Intranasal fentanyl for acute severe pain episodes control in a dog. Vet. Anaesth. Analg. 2017 44 6 1400 1401 10.1016/j.vaa.2017.06.003 29174209
    [Google Scholar]
  38. Saccone P.A. Lindsey A.M. Koeppe R.A. Zelenock K.A. Shao X. Sherman P. Quesada C.A. Woods J.H. Scott P.J.H. Intranasal opioid administration in rhesus monkeys: PET imaging and antinociception. J. Pharmacol. Exp. Ther. 2016 359 2 366 373 10.1124/jpet.116.235192 27625351
    [Google Scholar]
  39. Terrance M. Gunawardena T. Ouyang H. Avolio J. Duan W. Thanikachalam S. Moraes T.J. Primary human nasal epithelial cell culture. Methods Mol. Biol. 2024 2725 213 223 10.1007/978‑1‑0716‑3507‑0_13 37856027
    [Google Scholar]
  40. Meng Q. Wang A. Hua H. Jiang Y. Wang Y. Mu H. Wu Z. Sun K. Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease. Int. J. Nanomedicine 2018 13 705 718 10.2147/IJN.S151474 29440896
    [Google Scholar]
  41. Sibinovska N. Žakelj S. Kristan K. Suitability of RPMI 2650 cell models for nasal drug permeability prediction. Eur. J. Pharm. Biopharm. 2019 145 85 95 10.1016/j.ejpb.2019.10.008 31639418
    [Google Scholar]
  42. Sibinovska N. Žakelj S. Trontelj J. Kristan K. Applicability of RPMI 2650 and Calu-3 cell models for evaluation of nasal formulations. Pharmaceutics 2022 14 2 369 10.3390/pharmaceutics14020369 35214101
    [Google Scholar]
  43. Furubayashi T. Inoue D. Nishiyama N. Tanaka A. Yutani R. Kimura S. Comparison of various cell lines and three-dimensional mucociliary tissue model systems to estimate drug permeability using an in vitro transport study to predict nasal drug absorption in rats. Pharmaceutics 2020 12 1 79 10.3390/pharmaceutics12010079 31963555
    [Google Scholar]
  44. Cirri M. Maestrelli F. Nerli G. Mennini N. D’ambrosio M. Luceri C. Development of a cyclodextrin-based mucoadhesive-thermosensitive in situ gel for clonazepam intranasal delivery. Pharmaceutics 2021 13 7 969 10.3390/pharmaceutics13070969
    [Google Scholar]
  45. Krieter P. Gyaw S. Chiang C.N. Crystal R. Skolnick P. Enhanced intranasal absorption of naltrexone by dodecyl maltopyranoside: Implications for the treatment of opioid overdose. J. Clin. Pharmacol. 2019 59 7 947 957 10.1002/jcph.1384 30698833
    [Google Scholar]
  46. Falconer J.L. Alt J.A. Grainger D.W. Comparing ex vivo and in vitro translocation of silver nanoparticles and ions through human nasal epithelium. Biomaterials 2018 171 97 106 10.1016/j.biomaterials.2018.04.013 29684679
    [Google Scholar]
  47. Leichner C. Baus R.A. Jelkmann M. Plautz M. Barthelmes J. Dünnhaupt S. Bernkop-Schnürch A. In vitro evaluation of a self-emulsifying drug delivery system (SEDDS) for nasal administration of dimenhydrinate. Drug Deliv. Transl. Res. 2019 9 5 945 955 10.1007/s13346‑019‑00634‑1 30877627
    [Google Scholar]
  48. Albarki M.A. Donovan M.D. Bigger or Smaller? Size and loading effects on nanoparticle uptake efficiency in the nasal mucosa. AAPS PharmSciTech 2020 21 8 294 10.1208/s12249‑020‑01837‑3 33099728
    [Google Scholar]
  49. Dolberg A.M. Reichl S. Expression analysis of human solute carrier (SLC) family transporters in nasal mucosa and RPMI 2650 cells. Eur. J. Pharm. Sci. 2018 123 277 294 10.1016/j.ejps.2018.07.040 30041030
    [Google Scholar]
  50. Giuliani A. Balducci A.G. Zironi E. Colombo G. Bortolotti F. Lorenzini, L in vivo nose-to-brain delivery of the hydrophilic antiviral ribavirin by microparticle agglomerates. Drug Deliv. 2018 25 1 376 387 10.1080/10717544.2018.1428242 29382237
    [Google Scholar]
  51. Thakkar H. Vaghela D. Patel B.P. Brain targeted intranasal in-situ gelling spray of paroxetine: Formulation, characterization and in-vivo evaluation. J. Drug Deliv. Sci. Technol. 2021 62 102317 10.1016/j.jddst.2020.102317
    [Google Scholar]
  52. Haroon H.B. Mukherjee D. Anbu J. Teja B.V. Thiolated chitosan-centella asiatica nanocomposite: A potential brain targeting strategy through nasal route. AAPS PharmSciTech 2021 22 8 251 10.1208/s12249‑021‑02131‑6 34668091
    [Google Scholar]
  53. Papakyriakopoulou P. Manta K. Kostantini C. Kikionis S. Banella S. Ioannou E. Christodoulou E. Rekkas D.M. Dallas P. Vertzoni M. Valsami G. Colombo G. Nasal powders of quercetin-β-cyclodextrin derivatives complexes with mannitol/lecithin microparticles for Nose-to-Brain delivery: in vitro and ex vivo evaluation. Int. J. Pharm. 2021 607 121016 10.1016/j.ijpharm.2021.121016 34411652
    [Google Scholar]
  54. Ladel S. Maigler F. Flamm J. Schlossbauer P. Handl A. Hermann R. Herzog H. Hummel T. Mizaikoff B. Schindowski K. Impact of glycosylation and species origin on the uptake and permeation of iggs through the nasal airway mucosa. Pharmaceutics 2020 12 11 1014 10.3390/pharmaceutics12111014 33114132
    [Google Scholar]
  55. de Souza Von Zuben E. Eloy J.O. Araujo V.H.S. Gremião M.P.D. Chorilli M. Insulin-loaded liposomes functionalized with cell-penetrating peptides: influence on drug release and permeation through porcine nasal mucosa. Colloids Surf. A Physicochem. Eng. Asp. 2021 622 126624 10.1016/j.colsurfa.2021.126624
    [Google Scholar]
  56. Abdulla N.A. Balata G.F. El-ghamry H.A. Gomaa E. Intranasal delivery of Clozapine using nanoemulsion-based in-situ gels: An approach for bioavailability enhancement. Saudi Pharm. J. 2021 29 12 1466 1485 10.1016/j.jsps.2021.11.006 35002385
    [Google Scholar]
  57. Gadhave D.G. Kokare C.R. Nanostructured lipid carriers engineered for intranasal delivery of teriflunomide in multiple sclerosis: Optimization and in vivo studies. Drug Dev. Ind. Pharm. 2019 45 5 839 851 10.1080/03639045.2019.1576724 30702966
    [Google Scholar]
  58. Zheng X. Sun K. Liu Y. Yin X. Zhu H. Yu F. Zhao W. Resveratrol-loaded macrophage exosomes alleviate multiple sclerosis through targeting microglia. J. Control. Release 2023 353 675 684 10.1016/j.jconrel.2022.12.026 36521687
    [Google Scholar]
  59. Zhao X. Sun L. Wang J. Xu X. Ni S. Liu M. Hu K. Nose to brain delivery of Astragaloside IV by β-Asarone modified chitosan nanoparticles for multiple sclerosis therapy. Int. J. Pharm. 2023 644 123351 10.1016/j.ijpharm.2023.123351 37640088
    [Google Scholar]
  60. Gadhave D. Gorain B. Tagalpallewar A. Kokare C. Intranasal teriflunomide microemulsion: An improved chemotherapeutic approach in glioblastoma. J. Drug Deliv. Sci. Technol. 2019 51 276 289 10.1016/j.jddst.2019.02.013
    [Google Scholar]
  61. Shingaki T. Inoue D. Furubayashi T. Sakane T. Katsumi H. Yamamoto A. Yamashita S. Transnasal delivery of methotrexate to brain tumors in rats: a new strategy for brain tumor chemotherapy. Mol. Pharm. 2010 7 5 1561 1568 10.1021/mp900275s 20695463
    [Google Scholar]
  62. de Oliveira Junior E.R. Nascimento T.L. Salomão M.A. da Silva A.C.G. Valadares M.C. Lima E.M. Increased nose-to-brain delivery of melatonin mediated by polycaprolactone nanoparticles for the treatment of glioblastoma. Pharm. Res. 2019 36 9 131 10.1007/s11095‑019‑2662‑z 31263962
    [Google Scholar]
  63. Chu L. Wang A. Ni L. Yan X. Song Y. Zhao M. Sun K. Mu H. Liu S. Wu Z. Zhang C. Nose-to-brain delivery of temozolomide-loaded PLGA nanoparticles functionalized with anti-EPHA3 for glioblastoma targeting. Drug Deliv. 2018 25 1 1634 1641 10.1080/10717544.2018.1494226 30176744
    [Google Scholar]
  64. Alex A.T. Joseph A. Shavi G. Rao J.V. Udupa N. Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery. Drug Deliv. 2016 23 7 2144 2153 10.3109/10717544.2014.948643 25544603
    [Google Scholar]
  65. Taki H. Kanazawa T. Akiyama F. Takashima Y. Okada H. Intranasal delivery of camptothecin-loaded Tat-modified nanomicells for treatment of intracranial brain tumors. Pharmaceuticals 2012 5 1092 1102 10.3390/ph5101092
    [Google Scholar]
  66. Savale S.K. Formulation and evaluation of quercetin nanoemulsions for treatment of brain tumor via intranasal pathway. 2021 Available from: www.ajbr.in
  67. Ullah I. Chung K. Bae S. Li Y. Kim C. Choi B. Nam H.Y. Kim S.H. Yun C.O. Lee K.Y. Kumar P. Lee S.K. Nose-to-brain delivery of cancer-targeting paclitaxel-loaded nanoparticles potentiates antitumor effects in malignant glioblastoma. Mol. Pharm. 2020 17 4 1193 1204 10.1021/acs.molpharmaceut.9b01215 31944768
    [Google Scholar]
  68. Saka R. Chella N. Khan W. Development of imatinib mesylate-loaded liposomes for nose to brain delivery: In vitro and in vivo evaluation. AAPS PharmSciTech 2021 22 5 192 10.1208/s12249‑021‑02072‑0 34184160
    [Google Scholar]
  69. Ahmad S. Khan I. Pandit J. Emad N.A. Bano S. Dar K.I. Rizvi M.M.A. Ansari M.D. Aqil M. Sultana Y. Brain targeted delivery of carmustine using chitosan coated nanoparticles via nasal route for glioblastoma treatment. Int. J. Biol. Macromol. 2022 221 435 445 10.1016/j.ijbiomac.2022.08.210 36067850
    [Google Scholar]
  70. Alaayedi M.H. Maraie N.K. Lomustine’s nanoemulsion as nose-to-brain drug delivery system for CNS tumor treatment. Saudi Pharm. J. 2023 31 8 101692 10.1016/j.jsps.2023.06.025 37457367
    [Google Scholar]
  71. Fraga Dias A. Dallemole D.R. Bruinsmann F.A. Lopes Silva L.F. Cruz-López O. Conejo-García A. Oliveira Battastini A.M. Campos J.M. Guterres S.S. Pohlmann A.R. Figueiró F. Development of bozepinib-loaded nanocapsules for nose-to-brain delivery: Preclinical evaluation in glioblastoma. Nanomedicine (Lond.) 2021 16 23 2095 2115 10.2217/nnm‑2021‑0164 34523353
    [Google Scholar]
  72. Bruinsmann F.A. de Cristo Soares Alves A. de Fraga Dias A. Lopes Silva L.F. Visioli F. Raffin Pohlmann A. Figueiró F. Sonvico F. Stanisçuaski Guterres S. Nose-to-brain delivery of simvastatin mediated by chitosan-coated lipid-core nanocapsules allows for the treatment of glioblastoma in vivo. Int. J. Pharm. 2022 616 121563 10.1016/j.ijpharm.2022.121563 35151819
    [Google Scholar]
  73. Shah B. Khunt D. Misra M. Padh H. Formulation and in-vivo pharmacokinetic consideration of intranasal microemulsion and mucoadhesive microemulsion of rivastigmine for brain targeting. Pharm. Res. 2018 35 1 8 8 10.1007/s11095‑017‑2279‑z 29294189
    [Google Scholar]
  74. Espinoza L.C. Vacacela M. Clares B. Garcia M.L. Fabrega M.J. Calpena A.C. Development of a nasal donepezil-loaded microemulsion for the treatment of Alzheimer’s disease: In vitro and ex vivoCharacterization. CNS Neurol. Disord. Drug Targets 2018 17 1 43 53 10.2174/1871527317666180104122347 29299992
    [Google Scholar]
  75. Qian S. Wong Y.C. Zuo Z. Development, characterization and application of in situ gel systems for intranasal delivery of tacrine. Int. J. Pharm. 2014 468 1-2 272 282 10.1016/j.ijpharm.2014.04.015 24709220
    [Google Scholar]
  76. Muntimadugu E. Dhommati R. Jain A. Challa V.G.S. Shaheen M. Khan W. Intranasal delivery of nanoparticle encapsulated tarenflurbil: A potential brain targeting strategy for Alzheimer’s disease. Eur. J. Pharm. Sci. 2016 92 224 234 10.1016/j.ejps.2016.05.012 27185298
    [Google Scholar]
  77. Zameer S. Ali J. Vohora D. Najmi A.K. Akhtar M. Development, optimisation and evaluation of chitosan nanoparticles of alendronate against Alzheimer’s disease in intracerebroventricular streptozotocin model for brain delivery. J. Drug Target. 2021 29 2 199 216 10.1080/1061186X.2020.1817041 32876502
    [Google Scholar]
  78. Akel H. Csóka I. Formulation and in vitro comparison study between lipid-based and polymeric-based nanoparticles for nose-to-brain delivery of a model drug for Alzheimer’s disease. Proceedings 2021 78 51 10.3390/IECP2020‑08680
    [Google Scholar]
  79. Shehata M.K. Ismail A.A. Kamel M.A. Nose to brain delivery of astaxanthin-loaded nanostructured lipid carriers in rat model of Alzheimer’s disease: Preparation, in vitro and in vivo evaluation. Int. J. Nanomedicine 2023 18 1631 1658 10.2147/IJN.S402447 37020692
    [Google Scholar]
  80. Jojo G.M. Kuppusamy G. De A. Karri V.V.S.N.R. Formulation and optimization of intranasal nanolipid carriers of pioglitazone for the repurposing in Alzheimer’s disease using Box-Behnken design. Drug Dev. Ind. Pharm. 2019 45 7 1061 1072 10.1080/03639045.2019.1593439 30922126
    [Google Scholar]
  81. Tiozzo Fasiolo L. Manniello M.D. Bortolotti F. Buttini F. Rossi A. Sonvico F. Colombo P. Valsami G. Colombo G. Russo P. Anti-inflammatory flurbiprofen nasal powders for nose-to-brain delivery in Alzheimer’s disease. J. Drug Target. 2019 27 9 984 994 10.1080/1061186X.2019.1574300 30691325
    [Google Scholar]
  82. Mischley L.K. Conley K.E. Shankland E.G. Kavanagh T.J. Rosenfeld M.E. Duda J.E. White C.C. Wilbur T.K. De La Torre P.U. Padowski J.M. Central nervous system uptake of intranasal glutathione in Parkinson’s disease. NPJ Parkinsons Dis. 2016 2 1 16002 10.1038/npjparkd.2016.2 28725693
    [Google Scholar]
  83. Raman S. Khan A.A. Mahmood S. Nose to brain delivery of selegiline loaded PLGA/lipid nanoparticles: Synthesis, characterisation and brain pharmacokinetics evaluation. J. Drug Deliv. Sci. Technol. 2022 77 103923 10.1016/j.jddst.2022.103923
    [Google Scholar]
  84. Ahmad M.Z. Sabri A.H.B. Anjani Q.K. Domínguez-Robles J. Abdul Latip N. Hamid K.A. Design and development of levodopa loaded polymeric nanoparticles for intranasal delivery. Pharmaceuticals 2022 15 3 370 10.3390/ph15030370 35337167
    [Google Scholar]
  85. Raj R. Wairkar S. Sridhar V. Gaud R. Pramipexole dihydrochloride loaded chitosan nanoparticles for nose to brain delivery: Development, characterization and in vivo anti-Parkinson activity. Int. J. Biol. Macromol. 2018 109 27 35 10.1016/j.ijbiomac.2017.12.056 29247729
    [Google Scholar]
  86. Mustafa G. Baboota S. Ahuja A. Ali J. Formulation development of chitosan coated intra nasal ropinirole nanoemulsion for better management option of parkinson: An in vitro ex vivo evaluation. Int. J. Biol. Macromol. 2015 157 605 10.1016/j.ijbiomac.2020.11.207
    [Google Scholar]
  87. 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]
  88. Sita V.G. Jadhav D. Vavia P. Niosomes for nose-to-brain delivery of bromocriptine: Formulation development, efficacy evaluation and toxicity profiling. J. Drug Deliv. Sci. Technol. 2020 58 101791 10.1016/j.jddst.2020.101791
    [Google Scholar]
  89. Harjot K. Nanoemulsion for migraine prophylaxis nasal drug delivery: Preparation, characterization and in vitro evaluation. Pharm. Nanotechnol. 2016 4 3 229 241 10.2174/2211738504666160601162604
    [Google Scholar]
  90. Shelke S. Pathan I. Shinde G. Agrawal G. Damale M. Chouthe R. Panzade P. Kulkarni D. Poloxamer-based in situ nasal gel of naratriptan hydrochloride deformable vesicles for brain targeting. Bionanoscience 2020 10 3 633 648 10.1007/s12668‑020‑00767‑5
    [Google Scholar]
  91. Suhagiya K. Borkhataria C.H. Gohil S. Manek R.A. Patel K.A. Patel N.K. Patel D.V. Development of mucoadhesive in-situ nasal gel formulation for enhanced bioavailability and efficacy of rizatriptan in migraine treatment. Results Chem. 2023 6 101010 10.1016/j.rechem.2023.101010
    [Google Scholar]
  92. Masjedi M. Azadi A. Heidari R. Mohammadi-Samani S. Nose-to-brain delivery of sumatriptan-loaded nanostructured lipid carriers: preparation, optimization, characterization and pharmacokinetic evaluation. J. Pharm. Pharmacol. 2020 72 10 1341 1351 10.1111/jphp.13316 32579251
    [Google Scholar]
  93. Ibrahim M.M. Basalious E.B. El-Nabarawi M.A. Makhlouf A.I.A. Sayyed M.E. Ibrahim I.T. Nose to brain delivery of mirtazapine via lipid nanocapsules: Preparation, statistical optimization, radiolabeling, in vivo biodistribution and pharmacokinetic study. Drug Deliv. Transl. Res. 2024 14 9 2539 2557 10.1007/s13346‑024‑01528‑7 38376620
    [Google Scholar]
  94. Li JC Zhang WJ Zhu JX Zhu N Zhang HM Wang X Preparation and brain delivery of nasal solid lipid nanoparticles of quetiapine fumarate in situ gel in rat model of schizophrenia. Int. J. Clin. Exp. Med. 2015 8 10 17590 17600 Oct 15;
    [Google Scholar]
  95. Gadhave D. Tupe S. Tagalpallewar A. Gorain B. Choudhury H. Kokare C. Nose-to-brain delivery of amisulpride-loaded lipid-based poloxamer-gellan gum nanoemulgel: In vitro and in vivo pharmacological studies. Int. J. Pharm. 2021 607 121050 10.1016/j.ijpharm.2021.121050 34454028
    [Google Scholar]
/content/journals/ddl/10.2174/0122103031378584250829054818
Loading
/content/journals/ddl/10.2174/0122103031378584250829054818
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