NANOTECHNOLOGY-DRIVEN THERAPEUTICS: ENHANCING BRAIN DRUG DELIVERY VIA NASAL PATHWAYS
DOI:
https://doi.org/10.22159/ijap.2025v17i2.52879Keywords:
Nasal delivery, Brain, Nanotechnology, Targeted, ChallengesAbstract
The use of nanotechnology in drug delivery and targeting has proven to be extremely valuable. The Nose-to-brain route of drug administration acts as a more encouraging alternative to the traditional routes of medications acting on the Central Nervous System (CNS). This approach overcomes the disadvantages of Blood Brain Barrier (BBB), hepatic first-pass metabolism, and systemic circulation. Thus, it is highly suitable for neurodegenerative diseases, brain tumors, and neurological disorders like Alzheimer’s disease, Parkinson's disease, epilepsy, and brain cancer. Anatomy and physiology of the nasal cavity, mechanisms of drug transport to the brain, and different nano-formulations that may enhance the delivery and efficacy of CNS targeted drugs are reviewed here. Nanotechnology has brought new drug delivery systems like nanoparticles, niosomes, liposomes, dendrimers, in-situ gels, nanoemulsions, and nanostructured lipid carriers capable of successfully delivering drugs across the olfactory and trigeminal nerve pathways. It also discusses challenges pertinent to drug delivery across the BBB and the therapeutic application of nose-to-brain delivery, the article also highlighted the nanoformulation development and the ongoing clinical trials along with the marketed formulations related to nose-to-brain delivery.
References
Hussain AA. Intranasal drug delivery. Adv Drug Deliv Rev. 1998;29(1-2):39-49. doi: 10.1016/s0169-409x(97)00060-4, PMID 10837579.
Alnasser S. A review on nasal drug delivery system and its contribution in therapeutic management. Asian J Pharm Clin Res. 2019;12(1):40. doi: 10.22159/ajpcr.2019.v12i1.29443.
Illum L. Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci. 2000;11(1):1-18. doi: 10.1016/s0928-0987(00)00087-7, PMID 10913748.
Alexander A, Agrawal M, Uddin A, Siddique S, Shehata AM, Shaker MA. Recent expansions of novel strategies towards the drug targeting into the brain. Int J Nanomedicine. 2019;14:5895-909. doi: 10.2147/IJN.S210876, PMID 31440051.
Mac Kinnon GE, Mac Kinnon NJ, Pharmacokinetics C, Larry Bauer PA, Larisa Cavallari PH, Francis Lam YW. Pharmacotherapy: A Pathophysiologic Approach; 2008.
Bonferoni MC, Rossi S, Sandri G, Ferrari F, Gavini E, Rassu G. Nanoemulsions for nose to brain drug delivery. Pharmaceutics. 2019;11(2):84. doi: 10.3390/pharmaceutics11020084, PMID 30781585.
Rassu G, Soddu E, Cossu M, Brundu A, Cerri G, Marchetti N. Solid microparticles based on chitosan or methyl-β-cyclodextrin: a first formulative approach to increase the nose to brain transport of deferoxamine mesylate. J Control Release. 2015 Mar 10;201:68-77. doi: 10.1016/j.jconrel.2015.01.025, PMID 25620068.
Zlokovic BV. Neurovascular pathways to neurodegeneration in alzheimers disease and other disorders. Nat Rev Neurosci. 2011;12(12):723-38. doi: 10.1038/nrn3114, PMID 22048062.
Kisler K, Nelson AR, Montagne A, Zlokovic BV. Cerebral blood flow regulation and neurovascular dysfunction in alzheimer disease. Nat Rev Neurosci. 2017;18(7):419-34. doi: 10.1038/nrn.2017.48, PMID 28515434.
Pardridge WM. Blood-brain barrier endogenous transporters as therapeutic targets: a new model for small molecule CNS drug discovery. Expert Opin Ther Targets. 2015;19(8):1059-72. doi: 10.1517/14728222.2015.1042364, PMID 25936389.
Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13-25. doi: 10.1016/j.nbd.2009.07.030, PMID 19664713.
Saunders NR, Habgood MD, Mollgard K, Dziegielewska KM. The biological significance of brain barrier mechanisms: help or hindrance in drug delivery to the central nervous system? F1000Res. 2016;5:F1000. doi: 10.12688/f1000research.7378.1, PMID 26998242.
Engelhardt B, Sorokin L. The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol. 2009;31(4):497-511. doi: 10.1007/s00281-009-0177-0, PMID 19779720.
Morrison EE, Costanzo RM. Morphology of olfactory epithelium in humans and other vertebrates. Microsc Res Tech. 1992;23(1):49-61. doi: 10.1002/jemt.1070230105, PMID 1392071.
Law SL, Huang KJ, Chou HY. Preparation of desmopressin containing liposomes for intranasal delivery. J Control Release. 2001;70(3):375-82. doi: 10.1016/s0168-3659(00)00369-2, PMID 11182207.
Sosnik A, Das Neves J, Sarmento B. Mucoadhesive polymers in the design of nano drug delivery systems for administration by non parenteral routes: a review. Prog Polym Sci. 2014;39(12):2030-75. doi: 10.1016/j.progpolymsci.2014.07.010.
Mittal D, Ali A, Md S, Baboota S, Sahni JK, Ali J. Insights into direct nose to brain delivery: current status and future perspective. Drug Deliv. 2014;21(2):75-86. doi: 10.3109/10717544.2013.838713, PMID 24102636.
Djupesland PG, Messina JC, Mahmoud RA. The nasal approach to delivering treatment for brain diseases: an anatomic physiologic and delivery technology overview. Ther Deliv. 2014;5(6):709-33. doi: 10.4155/tde.14.41, PMID 25090283.
Serralheiro A, Alves G, Fortuna A, Falcao A. Intranasal administration of carbamazepine to mice: a direct delivery pathway for brain targeting. Eur J Pharm Sci. 2014;60(60):32-9. doi: 10.1016/j.ejps.2014.04.019, PMID 24813112.
Chapman CD, Frey WH, Craft S, Danielyan L, Hallschmid M, Schioth HB. Intranasal treatment of central nervous system dysfunction in humans. Pharm Res. 2013;30(10):2475-84. doi: 10.1007/s11095-012-0915-1, PMID 23135822.
Dhillon S. Rivastigmine transdermal patch: a review of its use in the management of dementia of the alzheimers type. Drugs. 2011;71(9):1209-31. doi: 10.2165/11206380-000000000-00000, PMID 21711064.
Carreiras MC, Mendes E, Perry MJ, Francisco AP, Marco Contelles J. The multifactorial nature of alzheimers disease for developing potential therapeutics. Curr Top Med Chem. 2013;13(15):1745-70. doi: 10.2174/15680266113139990135, PMID 23931435–70.
Onofri E, Mercuri M, Archer T, Rapp Ricciardi M, Ricci S. Legal medical consideration of alzheimers disease patients dysgraphia and cognitive dysfunction: a 6 month follow up. Clin Interv Aging. 2016;11:279-84. doi: 10.2147/CIA.S94750, PMID 27022252.
Mc Khann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of alzheimers disease: report of the nincds-adrda work group under the auspices of department of health and human services task force on alzheimers disease. Neurology. 1984;34(7):939-44. doi: 10.1212/wnl.34.7.939, PMID 6610841.
Hardy J. The amyloid hypothesis for alzheimers disease: a critical reappraisal. J Neurochem. 2009;110(4):1129-34. doi: 10.1111/j.1471-4159.2009.06181.x, PMID 19457065.
D Arrigo JS. Alzheimers disease brain injury and C.N.S. nanotherapy in humans: sonoporation augmenting drug targeting. Med Sci. 2017;5(4):29. doi: 10.3390/medsci5040029.
Trejo Lopez JA, Yachnis AT, Prokop S. Neuropathology of alzheimers disease. Neurotherapeutics. 2022;19(1):173-85. doi: 10.1007/s13311-021-01146-y, PMID 34729690.
Wilson B, Mohamed Alobaid BN, Geetha KM, Jenita JL. Chitosan nanoparticles to enhance nasal absorption and brain targeting of sitagliptin to treat alzheimers disease. J Drug Deliv Sci Technol. 2021 Feb;61:102176. doi: 10.1016/j.jddst.2020.102176.
Shehata MK, Ismail AA, Kamel MA. Nose to brain delivery of astaxanthin loaded nanostructured lipid carriers in rat model of alzheimers disease: preparation in vitro and in vivo evaluation. Int J Nanomedicine. 2023;18:1631-58. doi: 10.2147/IJN.S402447, PMID 37020692.
Kaur A, Nigam K, Srivastava S, Tyagi A, Dang S. Memantine nanoemulsion: a new approach to treat alzheimers disease. J Microencapsul. 2020;37(5):355-65. doi: 10.1080/02652048.2020.1756971, PMID 32293915.
Espinoza LC, Vacacela M, Clares B, Garcia ML, Fabrega MJ, Calpena AC. Development of a nasal donepezil loaded microemulsion for the treatment of alzheimers disease: in vitro and ex vivo characterization. CNS Neurol Disord Drug Targets. 2018;17(1):43-53. doi: 10.2174/1871527317666180104122347, PMID 29299992.
Shehata MK, Ismail AA, Kamel MA. Nose to brain delivery of astaxanthin loaded nanostructured lipid carriers in rat model of alzheimers disease: preparation in vitro and in vivo evaluation. Int J Nanomedicine. 2023;18:1631-58. doi: 10.2147/IJN.S402447, PMID 37020692.
Espinoza LC, Silva Abreu M, Clares B, Rodriguez Lagunas MJ, Halbaut L, Canas MA. Formulation strategies to improve nose to brain delivery of donepezil. Pharmaceutics. 2019;11(2):64. doi: 10.3390/pharmaceutics11020064, PMID 30717264.
Al Asmari AK, Ullah Z, Tariq M, Fatani A. Preparation characterization and in vivo evaluation of intranasally administered liposomal formulation of donepezil. Drug Des Dev Ther. 2016 Jan 12;10:205-15. doi: 10.2147/DDDT.S93937, PMID 26834457.
Zheng X, Shao X, Zhang C, Tan Y, Liu Q, Wan X. Intranasal H102 peptide loaded liposomes for brain delivery to treat alzheimers disease. Pharm Res. 2015;32(12):3837-49. doi: 10.1007/s11095-015-1744-9, PMID 26113236.
Rompicherla SK, Arumugam K, Bojja SL, Kumar N, Rao CM. Pharmacokinetic and pharmacodynamic evaluation of nasal liposome and nanoparticle based rivastigmine formulations in acute and chronic models of alzheimers disease. Naunyn Schmiedebergs Arch Pharmacol. 2021;394(8):1737-55. doi: 10.1007/s00210-021-02096-0, PMID 34086100.
Abbas H, Sayed NS, Youssef NA, ME Gaafar P, Mousa MR, Fayez AM. Novel luteolin loaded chitosan decorated nanoparticles for brain targeting delivery in a sporadic alzheimers disease mouse model: focus on antioxidant anti-inflammatory and amyloidogenic pathways. Pharmaceutics. 2022;14(5):1003. doi: 10.3390/pharmaceutics14051003, PMID 35631589.
Saraswathi TS, Mothilal M. Development of rivastigmine loaded self assembled nanostructures of nonionic surfactants for brain delivery. Int J Appl Pharm. 2021;13(5):205-15. doi: 10.22159/ijap.2021v13i5.42664.
Gao Y, Almalki WH, Afzal O, Panda SK, Kazmi I, Alrobaian M. Systematic development of lectin conjugated microspheres for nose to brain delivery of rivastigmine for the treatment of alzheimers disease. Biomed Pharmacother. 2021;141 Sep:111829. doi: 10.1016/j.biopha.2021.111829, PMID 34147904.
Tulbah AS, Elkomy MH, Zaki RM, Eid HM, Eissa EM, Ali AA. Novel nasal niosomes loaded with lacosamide and coated with chitosan: a possible pathway to target the brain to control partial onset seizures. Int J Pharm X. 2023;6:100206. doi: 10.1016/j.ijpx.2023.100206, PMID 37637477.
Abo El Enin HA, Elkomy MH, Naguib IA, Ahmed MF, Alsaidan OA, Alsalahat I. Lipid nanocarriers overlaid with chitosan for brain delivery of berberine via the nasal route. Pharmaceuticals (Basel). 2022;15(3):281. doi: 10.3390/ph15030281, PMID 35337079.
Yasir M, Sara UV, Chauhan I, Gaur PK, Singh AP, Puri D. Solid lipid nanoparticles for nose to brain delivery of donepezil: formulation optimization by box behnken design in vitro and in vivo evaluation. Artif Cells Nanomed Biotechnol. 2018;46(8):1838-51. doi: 10.1080/21691401.2017.1394872.
Khatri DK, Preeti K, Tonape S, Bhattacharjee S, Patel M, Shah S. Nanotechnological advances for nose to brain delivery of therapeutics to improve the parkinson therapy. Curr Neuropharmacol. 2023;21(3):493-516. doi: 10.2174/1570159X20666220507022701, PMID 35524671.
Dimiou S, Lopes RM, Kubajewska I, Mellor RD, Schlosser CS, Shet MS. Particulate levodopa nose to brain delivery targets dopamine to the brain with no plasma exposure. Int J Pharm. 2022;618:121658. doi: 10.1016/j.ijpharm.2022.121658, PMID 35292396.
Melamed E, Hefti F, Wurtman RJ. Nonaminergic striatal neurons convert exogenous L-dopa to dopamine in parkinsonism. Ann Neurol. 1980;8(6):558-63. doi: 10.1002/ana.410080603, PMID 6260009.
Sharma S, Lohan S, Murthy RS. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo reversible gel of levodopa for brain delivery. Drug Dev Ind Pharm. 2014;40(7):869-78. doi: 10.3109/03639045.2013.789051, PMID 23600649.
Saha P, Kathuria H, Pandey MM. Nose to brain delivery of rotigotine redispersible nanosuspension: in vitro and in vivo characterization. J Drug Deliv Sci Technol. 2023;79:104049. doi: 10.1016/j.jddst.2022.104049.
Avhad PS, Gupta RA, Firke SN, Roge AB, Sarje SK, Raut AS. Formulation and evaluation of chitosan based polyelectrolyte complex of levodopa for nasal drug delivery. Int J Health Sci. 2022;S3:1316-27. doi: 10.53730/ijhs.v6nS3.5555.
Sridhar V, Gaud R, Bajaj A, Wairkar S. Pharmacokinetics and pharmacodynamics of intranasally administered selegiline nanoparticles with improved brain delivery in parkinsons disease. Nanomedicine. 2018;14(8):2609-18. doi: 10.1016/j.nano.2018.08.004, PMID 30171904.
Ahmad MZ, Sabri AH, Anjani QK, Dominguez Robles J, Abdul Latip N, Hamid KA. Design and development of levodopa loaded polymeric nanoparticles for intranasal delivery. Pharmaceuticals (Basel). 2022;15(3):370. doi: 10.3390/ph15030370, PMID 35337167.
Allegritti E, Battista S, Maggi MA, Marconi C, Galantini L, Giansanti L. Novel liposomal formulations for protection and delivery of levodopa: structure properties correlation. Int J Pharm. 2023;643:123230. doi: 10.1016/j.ijpharm.2023.123230, PMID 37454830.
Alipour S, Azari H, TIPS AF. In situ thermosensitive gel of levodopa: potential formulation for nose to brain delivery in parkinson disease. Trends Pharm Sci; 2020.
Scharfman HE. The neurobiology of epilepsy. Curr Neurol Neurosci Rep. 2007;7(4):348-54. doi: 10.1007/s11910-007-0053-z, PMID 17618543.
Gupta YK, Malhotra J. Antiepileptic drug therapy in the twenty first century. Indian J Physiol Pharmacol. 2000;44(1):8-23. PMID 10919091.
DE Sarro G, Spagnolo C, Gareri P, Gallelli L, DE Sarro A. Gabapentin potentiates the antiseizure activity of certain anticonvulsants in DBA/2 mice. Eur J Pharmacol. 1998;349(2-3):179-85. doi: 10.1016/s0014-2999(98)00193-9, PMID 9671096.
Goyal SN, Prajapati CP, Gore PR, Patil CR, Mahajan UB, Sharma C. Therapeutic potential and pharmaceutical development of thymoquinone: a multitargeted molecule of natural origin. Front Pharmacol. 2017;8:656. doi: 10.3389/fphar.2017.00656, PMID 28983249.
Pethe A, Hadke A, Agrawal S, Telange D. Intranasal formulation and characterization of chitosan microsphere for improving in vitro mucoadhesion residence time and absorption rate of pregabalin. Int J Appl Pharm. 2023;15(1):156-65. doi: 10.22159/ijap.2023v15i1.46359.
Shah P, Dubey P, Vyas B, Kaul A, Mishra AK, Chopra D. Lamotrigine loaded PLGA nanoparticles intended for direct nose to brain delivery in epilepsy: pharmacokinetic pharmacodynamic and scintigraphy study. Artif Cells Nanomed Biotechnol. 2021;49(1):511-22. doi: 10.1080/21691401.2021.1939709, PMID 34151674.
Tulbah AS, Elkomy MH, Zaki RM, Eid HM, Eissa EM, Ali AA. Novel nasal niosomes loaded with lacosamide and coated with chitosan: a possible pathway to target the brain to control partial onset seizures. Int J Pharm X. 2023;6:100206. doi: 10.1016/j.ijpx.2023.100206, PMID 37637477.
Nerli G, Robla S, Bartalesi M, Luceri C, D Ambrosio M, Csaba N. Chitosan coated niosomes for nose to brain delivery of clonazepam: formulation stability and permeability studies. Carbohydr Polym Technol Appl. 2023 Dec;6:100332. doi: 10.1016/j.carpta.2023.100332.
Nair SC, Vinayan KP, Mangalathillam S. Nose to brain delivery of phenytoin sodium loaded nano lipid carriers: formulation drug release permeation and in vivo pharmacokinetic studies. Pharmaceutics. 2021;13(10):1640. doi: 10.3390/pharmaceutics13101640, PMID 34683933.
Praveen A, Aqil M, Imam SS, Ahad A, Moolakkadath T, Ahmad FJ. Lamotrigine encapsulated intra nasal nanoliposome formulation for epilepsy treatment: formulation design characterization and nasal toxicity study. Colloids Surf B Biointerfaces. 2019;174:553-62. doi: 10.1016/j.colsurfb.2018.11.025, PMID 30502666.
Abdelmonem R, El Enin HA, Abdelkader G, Abdel Hakeem M. Formulation and characterization of lamotrigine nasal insert targeted brain for enhanced epilepsy treatment. Drug Deliv. 2023;30(1):2163321. doi: 10.1080/10717544.2022.2163321, PMID 36579655.
Taymouri S, Minaiyan M, Ebrahimi F, Tavakoli N. In vitro and in vivo evaluation of chitosan based thermosensitive gel containing lorazepam NLCs for the treatment of status epilepticus. IET Nanobiotechnol. 2020;14(2):148-54. doi: 10.1049/iet-nbt.2019.0156, PMID 32433032.
Alam T, Pandit J, Vohora D, Aqil M, Ali A, Sultana Y. Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy. Expert Opin Drug Deliv. 2015;12(2):181-94. doi: 10.1517/17425247.2014.945416, PMID 25164097.
Shrestha N, Khan S, Neupane YR, Dang S, Md S, Fahmy UA. Tailoring midazolam loaded chitosan nanoparticulate formulation for enhanced brain delivery via intranasal route. Polymers. 2020;12(11):2589. doi: 10.3390/polym12112589, PMID 33158148.
Ahmad N, Ahmad R, Alrasheed RA, Almatar HM, Al Ramadan AS, Amir M. Quantification and evaluations of catechin hydrate polymeric nanoparticles used in brain targeting for the treatment of epilepsy. Pharmaceutics. 2020;12(3):203. doi: 10.3390/pharmaceutics12030203, PMID 32120778.
Nour SA, Abdelmalak NS, Naguib MJ, Rashed HM, Ibrahim AB. Intranasal brain targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization ex vivo determination of cytotoxicity in vivo biodistribution and pharmacodynamics studies. Drug Deliv. 2016;23(9):3681-95. doi: 10.1080/10717544.2016.1223216, PMID 27648847.
Liu S, Yang S, HO PC. Intranasal administration of carbamazepine loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain. Asian J Pharm Sci. 2018;13(1):72-81. doi: 10.1016/j.ajps.2017.09.001, PMID 32104380.
Patel RB, Patel MR, Bhatt KK, Patel BG, Gaikwad RV. Microemulsion based drug delivery system for transnasal delivery of carbamazepine: preliminary brain targeting study. Drug Deliv. 2016;23(1):207-13. doi: 10.3109/10717544.2014.908980, PMID 24825492.
Gieszinger P, Stefania Csaba N, Garcia Fuentes M, Prasanna M, Gaspar R, Sztojkov Ivanov A. Preparation and characterization of lamotrigine containing nanocapsules for nasal administration. Eur J Pharm Biopharm. 2020 Aug;153:177-86. doi: 10.1016/j.ejpb.2020.06.003, PMID 32531424.
Samia O, Hanan R, Kamal ET. Carbamazepine mucoadhesive nanoemulgel (MNEG) as brain targeting delivery system via the olfactory mucosa. Drug Deliv. 2012;19(1):58-67. doi: 10.3109/10717544.2011.644349, PMID 22191715.
Melamane S, Walker RB, Khamanga SM. Formulation optimization of smart thermosetting lamotrigine loaded hydrogels using response surface methodology box benhken design and artificial neural networks. Drug Dev Ind Pharm. 2020;46(9):1402-15. doi: 10.1080/03639045.2020.1791163, PMID 32795107.
WU MY, Yiang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem. 2018;46(4):1650-67. doi: 10.1159/000489241, PMID 29694958.
Campbell BC, DE Silva DA, Macleod MR, Coutts SB, Schwamm LH, Davis SM. Ischaemic stroke. Nat Rev Dis Primers. 2019;5(1):70. doi: 10.1038/s41572-019-0118-8, PMID 31601801.
Jurcau A, Simion A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion injuries: from pathophysiology to therapeutic strategies. Int J Mol Sci. 2021;23(1):14. doi: 10.3390/ijms23010014, PMID 35008440.
Gund GM, Jagtap MP, Ingale MV, Patil RY. Stroke: a brain attack. IOSR J Pharm. 2013;3.
Radak D, Katsiki N, Resanovic I, Jovanovic A, Sudar Milovanovic E, Zafirovic S, S, R Isenovic E. Apoptosis and acute brain ischemia in ischemic stroke. Curr Vasc Pharmacol. 2017;15(2):115-22. doi: 10.2174/1570161115666161104095522.
Ahmad N, Ahmad R, Naqvi AA, Alam MA, Ashafaq M, Abdur Rub R. Intranasal delivery of quercetin loaded mucoadhesive nanoemulsion for treatment of cerebral ischaemia. Artif Cells Nanomed Biotechnol. 2018;46(4):717-29. doi: 10.1080/21691401.2017.1337024, PMID 28604104.
Yan H, Zhang X, HU W, MA J, Hou W, Zhang X. Histamine H3 receptors aggravate cerebral ischaemic injury by histamine independent mechanisms. Nat Commun. 2014 Feb 25;5:3334. doi: 10.1038/ncomms4334, PMID 24566390.
YU S, LI D, Shi A, Long Y, Deng J, MA Y. Multidrug loaded liposomes prevent ischemic stroke through intranasal administration. Biomed Pharmacother. 2023;162:114542. doi: 10.1016/j.biopha.2023.114542, PMID 36989725.
Ahmad N, Ahmad R, Ahmad FJ, Ahmad W, Alam MA, Amir M. Poloxamer chitosan based naringenin nanoformulation used in brain targeting for the treatment of cerebral ischemia. Saudi J Biol Sci. 2020;27(1):500-17. doi: 10.1016/j.sjbs.2019.11.008, PMID 31889876.
LI X, LI S, MA C, LI T, Yang L. Preparation of baicalin loaded ligand modified nanoparticles for nose to brain delivery for neuroprotection in cerebral ischemia. Drug Deliv. 2022;29(1):1282-98. doi: 10.1080/10717544.2022.2064564, PMID 35467483.
Bseiso EA, AbdEl Aal SA, Nasr M, Sammour OA, El Gawad NA. Nose to brain delivery of melatonin lipidic nanocapsules as a promising post ischemic neuroprotective therapeutic modality. Drug Deliv. 2022;29(1):2469-80. doi: 10.1080/10717544.2022.2104405, PMID 35892291.
Wang L, XU L, DU J, Zhao X, Liu M, Feng J. Nose to brain delivery of borneol modified tanshinone IIA nanoparticles in prevention of cerebral ischemia/reperfusion injury. Drug Deliv. 2021;28(1):1363-75. doi: 10.1080/10717544.2021.1943058, PMID 34180761.
Ahmad N, Ahmad R, Alam MA, Samim M, Iqbal Z, Ahmad FJ. Quantification and evaluation of thymoquinone loaded mucoadhesive nanoemulsion for treatment of cerebral ischemia. Int J Biol Macromol. 2016;88:320-32. doi: 10.1016/j.ijbiomac.2016.03.019, PMID 26976069.
Hansen JM, Charles A. Differences in treatment response between migraine with aura and migraine without aura: lessons from clinical practice and RCTs. J Headache Pain. 2019;20(1):96. doi: 10.1186/s10194-019-1046-4, PMID 31492106.
Edvinsson L, Haanes KA, Warfvinge K, Krause DN. CGRP as the target of new migraine therapies successful translation from bench to clinic. Nat Rev Neurol. 2018;14(6):338-50. doi: 10.1038/s41582-018-0003-1, PMID 29691490.
Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American migraine study II. headache. 2001;41(7):646-57. doi: 10.1046/j.1526-4610.2001.041007646.x, PMID 11554952.
Gargus JJ. Ion channel functional candidate genes in multigenic neuropsychiatric disease. Biol Psychiatry. 2006;60(2):177-85. doi: 10.1016/j.biopsych.2005.12.008, PMID 16497276.
Gupta S, Oosthuizen R, Pulfrey S. Treatment of acute migraine in the emergency department. Can Fam Physician. 2014;60(1):47-9. PMID 24452560.
M A Moskowitz. Basic mechanisms in vascular headache Pub Med. Neurol Clin. 1990 Nov;8(4):801-15.
Alastal A, Kwaik AD, Malkawi AA, Baltzley S, Al Ghananeem AM. Enhancing intranasal delivery and bioavailability of dihydroergotamine utilizing chitosan nanoparticles. J Clin Pharm Ther. 2023;2023:1-8. doi: 10.1155/2023/2284371.
Saleh A, Khalifa M, Shawky S, Bani Ali A, Eassa H. Zolmitriptan intranasal spanlastics for enhanced migraine treatment; formulation parameters optimized via quality by design approach. Sci Pharm. 2021;89(2):2. doi: 10.3390/scipharm89020024.
Esim O, Savaser A, Ozkan CK, Oztuna A, Goksel BA, Ozler M. Nose to brain delivery of eletriptan hydrobromide nanoparticles: preparation in vitro/in vivo evaluation and effect on trigeminal activation. J Drug Deliv Sci Technol. 2020 Oct;59:101919. doi: 10.1016/j.jddst.2020.101919.
Mostafa DA, Khalifa MK, Gad SS. Zolmitriptan brain targeting via intranasal route using solid lipid nanoparticles for migraine therapy: formulation characterization in vitro and in vivo assessment. Int J Appl Pharm. 2020;12(2):86-93. doi: 10.22159/ijap.2020v12i2.36812.
Deepika D, Dewangan HK, Maurya L, Singh S. Intranasal drug delivery of frovatriptan succinate loaded polymeric nanoparticles for brain targeting. J Pharm Sci. 2019;108(2):851-9. doi: 10.1016/j.xphs.2018.07.013, PMID 30053555.
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):1341-51. doi: 10.1111/jphp.13316, PMID 32579251.
Singh A, Ubrane R, Prasad P, Ramteke S. Preparation and characterization of rizatriptan benzoate loaded solid lipid nanoparticles for brain targeting. Mater Today Proc. 2015;2(9):4521-43. doi: 10.1016/j.matpr.2015.10.067.
Mandlik SK, Vidyapeeth B, Adhikari S, Ranpise NS. Formulation and in vitro characterization of chitosan biodegradable nanoparticles of zolmitriptan for migraine treatment pharmacie globale international journal of comprehensive pharmacy formulation and in vitro characterization of chitosan biodegradable nanoparticles of zolmitriptan for migraine treatment 2012.101. Asian J Pharm Clin Res. 2018;11(7):345-7.
Shelke S, Shahi S, Jalalpure S, Dhamecha D. Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan loaded nanoethosomes: formulation optimization evaluation and permeation studies. J Liposome Res. 2016;26(4):313-23. doi: 10.3109/08982104.2015.1132232, PMID 26758957.
Girotra P, Singh SK, Kumar G. Development of zolmitriptan loaded PLGA/poloxamer nanoparticles for migraine using quality by design approach. Int J Biol Macromol. 2016;85:92-101. doi: 10.1016/j.ijbiomac.2015.12.069, PMID 26724690.
Abla KK, Domiati S, El Majzoub R, Mehanna MM. Propranolol loaded limonene based microemulsion thermo responsive mucoadhesive nasal nanogel: design in vitro assessment ex vivo permeation and brain biodistribution. Gels. 2023;9(6):491. doi: 10.3390/gels9060491, PMID 37367161.
The genetics of cancer-NCI; 2024.
DE Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020;8(2):e180-90. doi: 10.1016/S2214-109X(19)30488-7, PMID 31862245.
Emami Nejad A, Najafgholian S, Rostami A, Sistani A, Shojaeifar S, Esparvarinha M. The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment. Cancer Cell Int. 2021;21(1):62. doi: 10.1186/s12935-020-01719-5, PMID 33472628.
Morsy AA, Ng WH. Re-do craniotomy for recurrent glioblastoma. CNS Oncol. 2015;4(2):55-7. doi: 10.2217/cns.15.4, PMID 25768328.
Colombo M, Figueiro F, DE Fraga Dias A, Teixeira HF, Battastini AM, Koester LS. Kaempferol loaded mucoadhesive nanoemulsion for intranasal administration reduces glioma growth in vitro. Int J Pharm. 2018;543(1-2):214-23. doi: 10.1016/j.ijpharm.2018.03.055, PMID 29605695.
Alex AT, Joseph A, Shavi G, Rao JV, Udupa N. Development and evaluation of carboplatin loaded PCL nanoparticles for intranasal delivery. Drug Deliv. 2016;23(7):2144-53. doi: 10.3109/10717544.2014.948643, PMID 25544603.
Khan A, Aqil M, Imam SS, Ahad A, Sultana Y, Ali A. Temozolomide loaded nano lipid based chitosan hydrogel for nose to brain delivery: characterization nasal absorption histopathology and cell line study. Int J Biol Macromol. 2018;116:1260-7. doi: 10.1016/j.ijbiomac.2018.05.079, PMID 29775717.
Madane RG, Mahajan HS. Curcumin loaded nanostructured lipid carriers (NLCs) for nasal administration: design characterization and in vivo study. Drug Deliv. 2016;23(4):1326-34. doi: 10.3109/10717544.2014.975382, PMID 25367836.
Chung K, Ullah I, Kim N, Lim J, Shin J, Lee SC. Intranasal delivery of cancer targeting doxorubicin loaded PLGA nanoparticles arrests glioblastoma growth. J Drug Target. 2020;28(6):617-26. doi: 10.1080/1061186X.2019.1706095, PMID 31852284.
Bayanati M, Khosroshahi AG, Alvandi M, Mahboobian MM. Fabrication of a thermosensitive in situ gel nanoemulsion for nose to brain delivery of temozolomide. J Nanomater. 2021;2021:1-11. doi: 10.1155/2021/1546798.
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