The bloodbrain barrier (BBB) controls and restricts the entry of therapeutic medications because it plays a critical role in protecting the brain from toxins.Nasal medicine administration allows for immediate drug delivery into the brain through the nose-to brain pathway.avoiding both the first pass impact and the blood-brain barrier. Various novel and promising formulation approaches have been explored for drug targeting to the brain by nasal administration. Nanoemulsions have the potential to avoid problems, including low solubility, poor bioavailability, slow onset of action, and enzymatic degradation. The present review highlights research scenarios of nanoemulsions for nose-to-brain delivery for the management of CNS ailments classified on the basis of brain disorders and further identifies the areas that remain unexplored. The significance of the total dose delivered to the target region, biodistribution studies, and long-term toxicity studies have been identified as the key areas of future research. Direct access to the brain through the nasal route is made possible by the maxillary and nasal nerves, which are located in the upper part of the nose cavity.Nanoemulsions are formulations used in the field of nanomedicine.They consist of emulsions (typically, oil in water), which are then combined with one or more surfactants and, in the end, cosurfactants that are added in the form of small, highly surface area droplets. Promising formulations for intranasal drug administration that can reach the brain are nanoemulsions.This review focuses the present situation in literature regarding the use of nanoemulsions for nose-to-brain targeting, with particular attention to recent publications. Nasal nanoemulsions appear to be effective, non-invasive and safe drug delivery systems to achieve brain targeting for the treatment of neurological diseases.

Keywords: Intranasal, Blood brain barrier,Drug delivery,Nanoemulsions, Brain delivery

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1. Prat Dneman R. The blood-brain barrier, Cold Spring Harbor perspectives in biology. 2015 Jan 1,7(1) a020412
2. Gloor S . M, Wachtel M, Boliger M.F, et.al. Molecular and cellular permeability control at the blood-brain barrier. Brain research reviews 2001 Oct 1:36:2-3) 258-64.
3. Zlokovic B.V The blood-brain barrier health and neurodegenerative disorders. Neuron. 2008 Jan 24:57(2):178-201 chronic
4. Banks WA From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nature reviews Drug discovery. 2016 Apr. 15(4) 275-92.
5. Kaushik A, Jayart R.D, Bhardwaj V, Nair M, Personalized nanomedicinefor CNS diseases. Drug discovery today. 2018 May 1:23(5): 1007-15. Dhuna SV, Hanson LR, LR, Frey F II WH. Intranasal delivery to the central nervous system mechanisms and experimental considerations. Journal of pharmaceutical sciences. 2010 Apr 1.99(4):1654-73
6. Bourganis V, Kammona O. et.al. Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics. European journal of pharmaceutics and biopharmaceutics. 2018 Jul 1:128-337-62
7. Lee D, Minko T. Nanotherapeutics for nose-to-brain drug delivery: an approach to bypass the blood brain barrier. Pharmaceutics. 2021 Nov 30;13(12):2049.
8. Pardeshi, C.V.; Belgamwar, V.S. Direct nose to brain drag delivery via integrated nerve pathways. bypassing the blood-brain barrier. An excellent platform for brain targeting. ExpertOpin. Drug Delivery. 2013, 10, 957-972
9. Delpiaz, A. Fogagnolo, M. Ferrato, L.; Capuzzo, A.: Pavan. B. Rassu, G. Salis, A., Giunchedi, P.; Guvini, E. Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries. Antiviral Res. 2015, 123, 146-157.
10. Ugwoke, M.L; Verbeke, N.; Kinget, R. The biopharmaceutical aspects of nasal mucuadhesive drugdelivery. J. Pharm. Pharmacol. 2001, 53,3-21
11. Quintana, D.S: Westlye, L.T., Rustan, G., Trill, N., Poppy, CL, Samevik, H: Tesli, M.; Reine, M.: Mahunoad, RA, Smerud, KT. et al. Low-kise oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior. A randomized four-way crossover trial with nasal cavity dimension assessment. Transl. Psychiatry 2015, 5, 602. 34.
12. Stützle, M.: Flamm, J.; Carle, S. Schindowski, K. Nose-to-brain delivery of insulin for Alzheimer's disease. Admet Dapk, 2015, 3, 190-202.
13. Illum L. Nasal drug delivery-possibilities, problems, and solutions. J Control Release 2003:87:187-98.
14. Mahmoud, H. Al-awayeh, S: Bladi, S. Design and optimization of self-mano cruisfying drug delivery faatinaming disclвете. Ай. 1. Мыns. Manmad 2013, 7, 1482-150KL CrossRef 35. McClements, DA: Xian, H. Potential binlogical fate of ingested narcomadions: Influence ofparticle characteristics. Food Funct. 2012, 3, 202-229
15. V. Valenta, C. Lecithin-based samensions. J. Drug Delis. Sci. Tochaal, 2011, 21, 55-76. 49.
16. Vyas, T.K, Shatuwala, A. Aauji, M.M. Improved wal bulability and train warpet of an administration in penul nanakorn kensilations, Int. 1. Phann, 2008, 347, 95-101
17. Annem, A; Rizwan, M. Alana F.L., Ighel, Z. Khar, R.K. Agil. M. Tadeguak, 3. Хачмий(opening and selection: A technical aur. AAPS PharmöciTech 2009, 10, 09-76 31. f, C., Kate, V. Payghus, S.A. laveangama of slfet af non done sarfactant on propuntian onion. J. Nascenact. Chem. 2015, 3, 107-113.
18. Brisewitz, C. Steindler, A: Punkt A.: Wagner, T.: Lipp. R. Novel polosamer- shance the ineotiatul abnorption of active compounds lat. 1. Plan 2007, 329, 173-181 51. makly, VV., Chom, 5 Infaner of emalefier concmation ansion2014, 30, 11063-11074
19. Maber, F... Fendon, M.A., Zhou, Y. Kannul Haque, M., Rian, Y.H. Optimization of me shilling ramadosstag expertinental xture desigs. I. Food Sci. 2011, 36, C1108-C117
20. Combi, 1, Otto, A.; Plessis, I. Whey proteinpolysaccharide stabiliendomshine Effect polymer type and pli on release and topical delivery of salicylic acid. AAPSPhamSciTech 2014,15,188-000
21. Haggiest, N. Christensen, D.A. Kimusty, A.M., Nam, K.II. Cavitatum properties of block plynsabilized phase-shift nations wed is drug carriers. Uload Med. Biol. 2010, 36, 415-429 57
22. Zhang Y: Shang, Z: Gan. C. Dr. M.: Xa, S.; Song, IL: Lia, T. Nanoeraakkion for wohhikation Aabilization, and in vinnu micase of pterostilba final delivery, AAPS Pharaulic Tuch 2014, 15, 1000-1000
23. Bhan F. and Mallav 5. A Detailed review on nation drug delivery system, Bazermatiutalbum Pharmaceutical Sets and Row 2011, 2-1024x25000 39.
24. Bouchemal K.. Branom 3. Fesi 11., Puriet L. Namemalsu Bongкакалкиmakseliczem solvent, oil and surfactant printratten, Int Phamsacostes 2004; 0 247 10. K.
25. Briateon S. Foi H., Panier E Naemulaican Eemalditioning p muhsificanoo: obvent, unit, and surfactaн орчимонтов. Илиmational Journal of Pharmaceutics 2001, 200: 241
26. Guglielmine C orion for spinalapplicants, Clan Dermatol 2008; 26 341-6 62.
27. Huubing C. Dusrong D. Cheapves M., Duapheag M., Jingäng W. IHaiti X., Xiangliang Y.. Hydrogel trickened nanoemulsions system for topical delivery of Igophilic drugs. International Journal of Pharmaceutics 2008, 353 272.
28. Acharya, K. Pada Paschal, and Anna Lawan paranon and evaluation transal nicemails of carbamatepine Ajmal of home (2013)864-70
29. S. D. The epidemiology and rest of chronic and rothaслогу оpіверку. Проверенны(1996) 28:64-70.
30. Albani F, Mira R. and Baruzzi A. Carfunmauropone clined pharmaciingy a view hamp1995) 28235-244
31. Graves NM, Krid 1. and Joan SC. Relive biruvailability of rectally abuisine cahanapin ang in Дрібна (1985) 28-429-433
32. Kar M. Mara, A. Habhar, AK: Mishra, AK: Mishra, P. Pathak Katrana Main saguting drug delivery sync of riqit. J. P. 2006, 358, 295-201.
33. M. Misra, A. Mistes, A.K. Misha. F. Patuk. K. Mucodhesive namespace in drug delivery system perspring. A Dog Tages 2000, 16. 806-814 74.
34. Yu, C. Meng, 1. Chen. I, Tang, X. Permutation of ergusid mesylate huscam comahina forbanmhuing nasal chemistry be. 1. Pharm 2009, 375, 11-21. 79.
35. Yadav, S. Gashan, S.K. Puscacci, R. Av. MM. intranasal delivery of cationic natжения Encapsulated TNF siRNA in prevention of experimental neuroinffarxnution. Nanomedicine 2016. 12, 987
36. N., Akhur, S. hia. G.K.; Khan, 21; Kham, R.K. Aband. F. Artiepileptic inmunaal Amiloride kad Madhesive Development and safety assessment 1. bomed Nasomchandogy. 2011. T 143-143.
37. Jain Darshan, Tadavi Sandip, Patil Nishant, Pawar Sunil, Formulation & Evaluation of Quetipine fumarate loaded microemulsion, international journal Biology, Pharmacy and Allied Science, 2023,13 (9),3971-3982.
38. Buhalta, S. Pasak, K. Buffered forme to being delivery of siprasidone organochloridesPreformation and pharmacodynamic evaluation. Car Dog Deliv 2012, 9. 596-687
39. Mahajan, H.S.: Mahajan, M.S., Nerkar, PP., Agrawal, A. Nanoemulsions-based imranand ing delivery yam of sapisanir mesylate the brain targeting. Dog Detis, 2014, 21, 148-154
40. Pathak, R.; Dach, R.P. Mien, M. Nissarkar, M. Role of matoadheuve sadhesive polymers in enhancing delivery of nimodipine miconashion to brain via inmal route. Acta Pharm. Sis. B 2014, 4, 151-100
41. S. les, K: Gothamunjas, K. Оровникот of cumin samenuhr sanaal delivery wing design of experiment and its toxury semest. Colloids Surf. 8 Biointerfaces 2014, 113, 330-337.
42. Panger, R., Sharma, S.: Mostafa, G.; Ali. 1; Ba, S. Visu Eded overd nanomedicine fue brain targeting for the treatment of Parkinson's disesse by macing distress Nanotechnology 2014,25,485102.
43. M. Development of dusel pak mencecapulating tonepadyphenols for sose to brain delivery. Drug Delis, 2016, 21, 1444-1452.

The bloodbrain barrier (BBB) controls and restricts the entry of therapeutic medications because it plays a critical role in protecting the brain from toxins.Nasal medicine administration allows for immediate drug delivery into the brain through the nose-to brain pathway.avoiding both the first pass impact and the blood-brain barrier. Various novel and promising formulation approaches have been explored for drug targeting to the brain by nasal administration. Nanoemulsions have the potential to avoid problems, including low solubility, poor bioavailability, slow onset of action, and enzymatic degradation. The present review highlights research scenarios of nanoemulsions for nose-to-brain delivery for the management of CNS ailments classified on the basis of brain disorders and further identifies the areas that remain unexplored. The significance of the total dose delivered to the target region, biodistribution studies, and long-term toxicity studies have been identified as the key areas of future research. Direct access to the brain through the nasal route is made possible by the maxillary and nasal nerves, which are located in the upper part of the nose cavity.Nanoemulsions are formulations used in the field of nanomedicine.They consist of emulsions (typically, oil in water), which are then combined with one or more surfactants and, in the end, cosurfactants that are added in the form of small, highly surface area droplets. Promising formulations for intranasal drug administration that can reach the brain are nanoemulsions.This review focuses the present situation in literature regarding the use of nanoemulsions for nose-to-brain targeting, with particular attention to recent publications. Nasal nanoemulsions appear to be effective, non-invasive and safe drug delivery systems to achieve brain targeting for the treatment of neurological diseases.

Keywords: Intranasal, Blood brain barrier,Drug delivery,Nanoemulsions, Brain delivery

🔒 This is a subscription article

Full text is available to subscribers and institutional members. Please choose an option below to access it.

1. Prat Dneman R. The blood-brain barrier, Cold Spring Harbor perspectives in biology. 2015 Jan 1,7(1) a020412
2. Gloor S . M, Wachtel M, Boliger M.F, et.al. Molecular and cellular permeability control at the blood-brain barrier. Brain research reviews 2001 Oct 1:36:2-3) 258-64.
3. Zlokovic B.V The blood-brain barrier health and neurodegenerative disorders. Neuron. 2008 Jan 24:57(2):178-201 chronic
4. Banks WA From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nature reviews Drug discovery. 2016 Apr. 15(4) 275-92.
5. Kaushik A, Jayart R.D, Bhardwaj V, Nair M, Personalized nanomedicinefor CNS diseases. Drug discovery today. 2018 May 1:23(5): 1007-15. Dhuna SV, Hanson LR, LR, Frey F II WH. Intranasal delivery to the central nervous system mechanisms and experimental considerations. Journal of pharmaceutical sciences. 2010 Apr 1.99(4):1654-73
6. Bourganis V, Kammona O. et.al. Recent advances in carrier mediated nose-to-brain delivery of pharmaceutics. European journal of pharmaceutics and biopharmaceutics. 2018 Jul 1:128-337-62
7. Lee D, Minko T. Nanotherapeutics for nose-to-brain drug delivery: an approach to bypass the blood brain barrier. Pharmaceutics. 2021 Nov 30;13(12):2049.
8. Pardeshi, C.V.; Belgamwar, V.S. Direct nose to brain drag delivery via integrated nerve pathways. bypassing the blood-brain barrier. An excellent platform for brain targeting. ExpertOpin. Drug Delivery. 2013, 10, 957-972
9. Delpiaz, A. Fogagnolo, M. Ferrato, L.; Capuzzo, A.: Pavan. B. Rassu, G. Salis, A., Giunchedi, P.; Guvini, E. Nasal chitosan microparticles target a zidovudine prodrug to brain HIV sanctuaries. Antiviral Res. 2015, 123, 146-157.
10. Ugwoke, M.L; Verbeke, N.; Kinget, R. The biopharmaceutical aspects of nasal mucuadhesive drugdelivery. J. Pharm. Pharmacol. 2001, 53,3-21
11. Quintana, D.S: Westlye, L.T., Rustan, G., Trill, N., Poppy, CL, Samevik, H: Tesli, M.; Reine, M.: Mahunoad, RA, Smerud, KT. et al. Low-kise oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior. A randomized four-way crossover trial with nasal cavity dimension assessment. Transl. Psychiatry 2015, 5, 602. 34.
12. Stützle, M.: Flamm, J.; Carle, S. Schindowski, K. Nose-to-brain delivery of insulin for Alzheimer's disease. Admet Dapk, 2015, 3, 190-202.
13. Illum L. Nasal drug delivery-possibilities, problems, and solutions. J Control Release 2003:87:187-98.
14. Mahmoud, H. Al-awayeh, S: Bladi, S. Design and optimization of self-mano cruisfying drug delivery faatinaming disclвете. Ай. 1. Мыns. Manmad 2013, 7, 1482-150KL CrossRef 35. McClements, DA: Xian, H. Potential binlogical fate of ingested narcomadions: Influence ofparticle characteristics. Food Funct. 2012, 3, 202-229
15. V. Valenta, C. Lecithin-based samensions. J. Drug Delis. Sci. Tochaal, 2011, 21, 55-76. 49.
16. Vyas, T.K, Shatuwala, A. Aauji, M.M. Improved wal bulability and train warpet of an administration in penul nanakorn kensilations, Int. 1. Phann, 2008, 347, 95-101
17. Annem, A; Rizwan, M. Alana F.L., Ighel, Z. Khar, R.K. Agil. M. Tadeguak, 3. Хачмий(opening and selection: A technical aur. AAPS PharmöciTech 2009, 10, 09-76 31. f, C., Kate, V. Payghus, S.A. laveangama of slfet af non done sarfactant on propuntian onion. J. Nascenact. Chem. 2015, 3, 107-113.
18. Brisewitz, C. Steindler, A: Punkt A.: Wagner, T.: Lipp. R. Novel polosamer- shance the ineotiatul abnorption of active compounds lat. 1. Plan 2007, 329, 173-181 51. makly, VV., Chom, 5 Infaner of emalefier concmation ansion2014, 30, 11063-11074
19. Maber, F... Fendon, M.A., Zhou, Y. Kannul Haque, M., Rian, Y.H. Optimization of me shilling ramadosstag expertinental xture desigs. I. Food Sci. 2011, 36, C1108-C117
20. Combi, 1, Otto, A.; Plessis, I. Whey proteinpolysaccharide stabiliendomshine Effect polymer type and pli on release and topical delivery of salicylic acid. AAPSPhamSciTech 2014,15,188-000
21. Haggiest, N. Christensen, D.A. Kimusty, A.M., Nam, K.II. Cavitatum properties of block plynsabilized phase-shift nations wed is drug carriers. Uload Med. Biol. 2010, 36, 415-429 57
22. Zhang Y: Shang, Z: Gan. C. Dr. M.: Xa, S.; Song, IL: Lia, T. Nanoeraakkion for wohhikation Aabilization, and in vinnu micase of pterostilba final delivery, AAPS Pharaulic Tuch 2014, 15, 1000-1000
23. Bhan F. and Mallav 5. A Detailed review on nation drug delivery system, Bazermatiutalbum Pharmaceutical Sets and Row 2011, 2-1024x25000 39.
24. Bouchemal K.. Branom 3. Fesi 11., Puriet L. Namemalsu Bongкакалкиmakseliczem solvent, oil and surfactant printratten, Int Phamsacostes 2004; 0 247 10. K.
25. Briateon S. Foi H., Panier E Naemulaican Eemalditioning p muhsificanoo: obvent, unit, and surfactaн орчимонтов. Илиmational Journal of Pharmaceutics 2001, 200: 241
26. Guglielmine C orion for spinalapplicants, Clan Dermatol 2008; 26 341-6 62.
27. Huubing C. Dusrong D. Cheapves M., Duapheag M., Jingäng W. IHaiti X., Xiangliang Y.. Hydrogel trickened nanoemulsions system for topical delivery of Igophilic drugs. International Journal of Pharmaceutics 2008, 353 272.
28. Acharya, K. Pada Paschal, and Anna Lawan paranon and evaluation transal nicemails of carbamatepine Ajmal of home (2013)864-70
29. S. D. The epidemiology and rest of chronic and rothaслогу оpіверку. Проверенны(1996) 28:64-70.
30. Albani F, Mira R. and Baruzzi A. Carfunmauropone clined pharmaciingy a view hamp1995) 28235-244
31. Graves NM, Krid 1. and Joan SC. Relive biruvailability of rectally abuisine cahanapin ang in Дрібна (1985) 28-429-433
32. Kar M. Mara, A. Habhar, AK: Mishra, AK: Mishra, P. Pathak Katrana Main saguting drug delivery sync of riqit. J. P. 2006, 358, 295-201.
33. M. Misra, A. Mistes, A.K. Misha. F. Patuk. K. Mucodhesive namespace in drug delivery system perspring. A Dog Tages 2000, 16. 806-814 74.
34. Yu, C. Meng, 1. Chen. I, Tang, X. Permutation of ergusid mesylate huscam comahina forbanmhuing nasal chemistry be. 1. Pharm 2009, 375, 11-21. 79.
35. Yadav, S. Gashan, S.K. Puscacci, R. Av. MM. intranasal delivery of cationic natжения Encapsulated TNF siRNA in prevention of experimental neuroinffarxnution. Nanomedicine 2016. 12, 987
36. N., Akhur, S. hia. G.K.; Khan, 21; Kham, R.K. Aband. F. Artiepileptic inmunaal Amiloride kad Madhesive Development and safety assessment 1. bomed Nasomchandogy. 2011. T 143-143.
37. Jain Darshan, Tadavi Sandip, Patil Nishant, Pawar Sunil, Formulation & Evaluation of Quetipine fumarate loaded microemulsion, international journal Biology, Pharmacy and Allied Science, 2023,13 (9),3971-3982.
38. Buhalta, S. Pasak, K. Buffered forme to being delivery of siprasidone organochloridesPreformation and pharmacodynamic evaluation. Car Dog Deliv 2012, 9. 596-687
39. Mahajan, H.S.: Mahajan, M.S., Nerkar, PP., Agrawal, A. Nanoemulsions-based imranand ing delivery yam of sapisanir mesylate the brain targeting. Dog Detis, 2014, 21, 148-154
40. Pathak, R.; Dach, R.P. Mien, M. Nissarkar, M. Role of matoadheuve sadhesive polymers in enhancing delivery of nimodipine miconashion to brain via inmal route. Acta Pharm. Sis. B 2014, 4, 151-100
41. S. les, K: Gothamunjas, K. Оровникот of cumin samenuhr sanaal delivery wing design of experiment and its toxury semest. Colloids Surf. 8 Biointerfaces 2014, 113, 330-337.
42. Panger, R., Sharma, S.: Mostafa, G.; Ali. 1; Ba, S. Visu Eded overd nanomedicine fue brain targeting for the treatment of Parkinson's disesse by macing distress Nanotechnology 2014,25,485102.
43. M. Development of dusel pak mencecapulating tonepadyphenols for sose to brain delivery. Drug Delis, 2016, 21, 1444-1452.