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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

Road From Nose to Brain for Treatment of Alzheimer: The Bumps and Humps

Author(s): Rajesh Kumar, Monica Gulati*, Sachin Kumar Singh, Deepika Sharma and Omji Porwal*

Volume 19, Issue 9, 2020

Page: [663 - 675] Pages: 13

DOI: 10.2174/1871527319666200708124726

Price: $65

Abstract

Vulnerability of the brain milieu to even the subtle changes in its normal physiology is guarded by a highly efficient blood brain barrier. A number of factors i.e. molecular weight of the drug, its route of administration, lipophilic character, etc. play a significant role in its sojourn through the Blood Brain Barrier (BBB) and limit the movement of drug into brain tissue through BBB. To overcome these problems, alternative routes of drug administration have been explored to target the drugs to brain tissue. Nasal route has been widely reported for the administration of drugs for treatment of Alzheimer. In this innovative approach, the challenge of BBB is bypassed. Through this route, both the larger as well as polar molecules can be made to reach the brain tissues. Generally, these systems are either pH dependent or temperature dependent. The present review highlights the anatomy of nose, mechanisms of drug delivery from nose to brain, critical factors in the formulation of nasal drug delivery system, nasal formulations of various drugs that have been tried for their nasal delivery for treatment of Alzheimer. It also dives deep to understand the factors that contribute to the success of such formulations to carve out a direction for this niche area to be explored further.

Keywords: Brain targeting, Alzheimer, Nasal delivery, BBB, Olfactory, Intranasal.

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Graphical Abstract

[1]
Wen MM, El-Salamouni NS, El-Refaie WM, et al. Nanotechnology-based drug delivery systems for Alzheimer’s disease management: technical industrial and clinical challenges. J Control Release 2017; 245: 95-107.
[http://dx.doi.org/10.1016/j.jconrel.2016.11.025] [PMID: 27889394]
[2]
Lista S, Dubois B, Hampel H. Paths to Alzheimer’s disease prevention: from modifiable risk factors to biomarker enrichment strategies. J Nutr Health Aging 2015; 19(2): 154-63.
[http://dx.doi.org/10.1007/s12603-014-0515-3 PMID: 25651440]
[3]
Alzheimer’s Association. 2015 Alzheimer’s disease facts and figures. Alzheimers Dement 2015; 11(3): 332-84.
[http://dx.doi.org/10.1016/j.jalz.2015.02.003 PMID: 25984581]
[4]
Folch J, Petrov D, Ettcheto M, et al. Current research therapeutic strategies for Alzheimer’s disease treatment. Neural plasticity 2016; 20168501693
[5]
Fettelschoss A, Zabel F, Bachmann MF. Vaccination against Alzheimer disease: an update on future strategies. Hum Vaccin Immunother 2014; 10(4): 847-51.
[http://dx.doi.org/10.4161/hv.28183 PMID: 24535580]
[6]
Prince M, Comas-Herrera A, Knapp M, Guerchet M, Karagiannidou M. World Alzheimer report 2016: improving healthcare for people living with dementia: coverage, quality and costs now and in the future 2016 Available from: http://eprints.lse.ac.uk/67858/
[7]
Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement 2017; 13(4): 325-73.
[http://dx.doi.org/10.1016/j.jalz.2017.02.001]
[8]
Mohammadi M, Yazdanparast R. Modulation of H2O2-induced mitogen-activated protein kinases activation and cell death in SK-N-MC cells by EUK134, a salen derivative. Basic Clin Pharmacol Toxicol 2011; 108(6): 378-84.
[http://dx.doi.org/10.1111/j.1742-7843.2010.00664.x] [PMID: 21205220]
[9]
Di Stefano A, Iannitelli A, Laserra S, Sozio P. Drug delivery strategies for Alzheimer’s disease treatment. Expert Opin Drug Deliv 2011; 8(5): 581-603.
[http://dx.doi.org/10.1517/17425247.2011.561311 PMID: 21391862]
[10]
Brambilla D, Verpillot R, Le Droumaguet B, et al. PEGylated nanoparticles bind to and alter amyloid-beta peptide conformation: toward engineering of functional nanomedicines for Alzheimer’s disease. ACS Nano 2012; 6(7): 5897-908.
[http://dx.doi.org/10.1021/nn300489k PMID: 22686577]
[11]
Parihar MS, Hemnani T. Alzheimer’s disease pathogenesis and therapeutic interventions. J Clin Neurosci 2004; 11(5): 456-67.
[http://dx.doi.org/10.1016/j.jocn.2003.12.007 PMID: 15177383]
[12]
Agrawal M, Saraf S, Saraf S, et al. Recent advancements in the field of nanotechnology for the delivery of anti-Alzheimer drug in the brain region. Expert Opin Drug Deliv 2018; 15(6): 589-617.
[http://dx.doi.org/10.1080/17425247.2018.1471058] [PMID: 29733231]
[13]
Nagpal K, Singh SK, Mishra DN. Drug targeting to brain: a systematic approach to study the factors, parameters and approaches for prediction of permeability of drugs across BBB. Expert Opin Drug Deliv 2013; 10(7): 927-55.
[http://dx.doi.org/10.1517/17425247.2013.762354 PMID: 23330786]
[14]
Begley DJ. Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol Ther 2004; 104(1): 29-45.
[http://dx.doi.org/10.1016/j.pharmthera.2004.08.001] [PMID: 15500907]
[15]
Brasnjevic I, Steinbusch HW, Schmitz C, Martinez-Martinez P, Initiative ENR. European NanoBioPharmaceutics research initiative. Delivery of peptide and protein drugs over the blood-brain barrier. Prog Neurobiol 2009; 87(4): 212-51.
[http://dx.doi.org/10.1016/j.pneurobio.2008.12.002] [PMID: 19395337]
[16]
Su Y, Sinko PJ. Drug delivery across the blood-brain barrier: why is it difficult? how to measure and improve it? Expert Opin Drug Deliv 2006; 3(3): 419-35.
[http://dx.doi.org/10.1517/17425247.3.3.419 PMID: 16640501]
[17]
Agrawal M, Ajazuddin , Tripathi DK, et al. Recent advancements in liposomes targeting strategies to cross Blood-Brain Barrier (BBB) for the treatment of Alzheimer’s disease. J Control Release 2017; 260: 61-77.
[http://dx.doi.org/10.1016/j.jconrel.2017.05.019 PMID: 28549949]
[18]
Lochhead JJ, Wolak DJ, Pizzo ME, Thorne RG. Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration. J Cereb Blood Flow Metab 2015; 35(3): 371-81.
[http://dx.doi.org/10.1038/jcbfm.2014.215 PMID: 25492117]
[19]
van Sorge NM, Doran KS. Defense at the border: the blood-brain barrier versus bacterial foreigners. Future Microbiol 2012; 7(3): 383-94.
[http://dx.doi.org/10.2217/fmb.12.1 PMID: 22393891]
[20]
Bitter C, Suter-Zimmermann K, Surber C. Nasal drug delivery in humans topical applications and the Mucosa Karger Publishers 2011; 40: 20-35.
[http://dx.doi.org/10.1159/000321044]
[21]
Jiang Y, Zhu J, Xu G, Liu X. Intranasal delivery of stem cells to the brain. Expert Opin Drug Deliv 2011; 8(5): 623-32.
[http://dx.doi.org/10.1517/17425247.2011.566267 PMID: 21417782]
[22]
Chapman CD, Frey WH II, Craft S, et al. Intranasal treatment of central nervous system dysfunction in humans. Pharm Res 2013; 30(10): 2475-84.
[http://dx.doi.org/10.1007/s11095-012-0915-1 PMID: 23135822]
[23]
Frey WH, Liu J, Chen X, et al. Delivery of 125I-NGF to the brain via the olfactory route. Drug Deliv 1997; 4(2): 87-92.
[http://dx.doi.org/10.3109/10717549709051878]
[24]
Chen X-Q, Fawcett JR, Rahman Y-E, Ala TA, Frey WH II, William H. Delivery of nerve growth factor to the brain via the olfactory pathway. J Alzheimers Dis 1998; 1(1): 35-44.
[http://dx.doi.org/10.3233/JAD-1998-1102 PMID: 12214010]
[25]
Lochhead JJ, Thorne RG. Intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev 2012; 64(7): 614-28.
[http://dx.doi.org/10.1016/j.addr.2011.11.002 PMID: 22119441]
[26]
Danielyan L, Schäfer R, von Ameln-Mayerhofer A, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol 2009; 88(6): 315-24.
[http://dx.doi.org/10.1016/j.ejcb.2009.02.001 PMID: 19324456]
[27]
Danielyan L, Schäfer R, von Ameln-Mayerhofer A, et al. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease. Rejuvenation Res 2011; 14(1): 3-16.
[http://dx.doi.org/10.1089/rej.2010.1130 PMID: 21291297]
[28]
Kulkarni AP, Govender DA, Kotwal GJ, Kellaway LA. Modulation of anxiety behavior by intranasally administered vaccinia virus complement control protein and curcumin in a mouse model of Alzheimer’s disease. Curr Alzheimer Res 2011; 8(1): 95-113.
[http://dx.doi.org/10.2174/156720511794604598 PMID: 21143157]
[29]
Hussain AA. Intranasal drug delivery. Adv Drug Deliv Rev 1998; 29(1-2): 39-49.
[http://dx.doi.org/10.1016/S0169-409X(97)00060-4] [PMID: 10837579]
[30]
Sood S, Jain K, Gowthamarajan K. Intranasal therapeutic strategies for management of Alzheimer’s disease. J Drug Target 2014; 22(4): 279-94.
[http://dx.doi.org/10.3109/1061186X.2013.876644] [PMID: 24404923]
[31]
Fortuna A, Alves G, Serralheiro A, Sousa J, Falcão A. Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules. Eur J Pharm Biopharm 2014; 88(1): 8-27.
[http://dx.doi.org/10.1016/j.ejpb.2014.03.004 PMID: 24681294]
[32]
Grassin-Delyle S, Buenestado A, Naline E, et al. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol Ther 2012; 134(3): 366-79.
[http://dx.doi.org/10.1016/j.pharmthera.2012.03.003] [PMID: 22465159]
[33]
Jadhav KR, Gambhire MN, Shaikh IM, Kadam VJ, Pisal SS. Nasal drug delivery system-factors affecting and applications. Curr Drug Ther 2007; 2(1): 27-38.
[http://dx.doi.org/10.2174/157488507779422374]
[34]
Dhuria SV, Hanson LR, Frey WH II. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci 2010; 99(4): 1654-73.
[http://dx.doi.org/10.1002/jps.21924 PMID: 19877171]
[35]
Van den Berg MP, Merkus P, Romeijn SG, Verhoef JC, Merkus FW. Uptake of melatonin into the cerebrospinal fluid after nasal and intravenous delivery: studies in rats and comparison with a human study. Pharm Res 2004; 21(5): 799-802.
[http://dx.doi.org/10.1023/B:PHAM.0000026431.55383.69] [PMID: 15180337]
[36]
Al-Ghananeem AM, Traboulsi AA, Dittert LW, Hussain AA. Targeted brain delivery of 17 β-estradiol via nasally administered water soluble prodrugs. AAPS PharmSciTech 2002; 3(1): 40-7.
[http://dx.doi.org/10.1208/pt030105 PMID: 12919005]
[37]
Erdő F, Bors LA, Farkas D, Bajza Á, Gizurarson S. Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res Bull 2018; 143: 155-70.
[http://dx.doi.org/10.1016/j.brainresbull.2018.10.009] [PMID: 30449731]
[38]
Hirlekar RS, Momin AM. Advances in drug delivery from nose to brain: an overview. Curr Drug Ther 2018; 13(1): 4-24.
[http://dx.doi.org/10.2174/1574885512666170921145204]
[39]
Florence AT. The oral absorption of micro- and nanoparticulates: neither exceptional nor unusual. Pharm Res 1997; 14(3): 259-66.
[http://dx.doi.org/10.1023/A:1012029517394 PMID: 9098866]
[40]
Lockman PR, Mumper RJ, Khan MA, Allen DD. Nanoparticle technology for drug delivery across the blood-brain barrier. Drug Dev Ind Pharm 2002; 28(1): 1-13.
[http://dx.doi.org/10.1081/DDC-120001481 PMID: 11858519]
[41]
Ugwoke MI, Verbeke N, Kinget R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J Pharm Pharmacol 2001; 53(1): 3-21.
[http://dx.doi.org/10.1211/0022357011775145 PMID: 11206189]
[42]
Kumar M, Misra A, Babbar AK, Mishra AK, Mishra P, Pathak K. Intranasal nanoemulsion based brain targeting drug delivery system of risperidone. Int J Pharm 2008; 358(1-2): 285-91.
[http://dx.doi.org/10.1016/j.ijpharm.2008.03.029 PMID: 18455333]
[43]
Kumar M, Misra A, Mishra AK, Mishra P, Pathak K. Mucoadhesive nanoemulsion-based intranasal drug delivery system of olanzapine for brain targeting. J Drug Target 2008; 16(10): 806-14.
[http://dx.doi.org/10.1080/10611860802476504 PMID: 18988064]
[44]
Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf B Biointerfaces 2014; 113: 330-7.
[http://dx.doi.org/10.1016/j.colsurfb.2013.09.030 PMID: 24121076]
[45]
El-Hameed MA, Kellaway I. Preparation and in vitro characterisation of mucoadhesive polymeric microspheres as intra-nasal delivery systems. Eur J Pharm Biopharm 1997; 44(1): 53-60.
[http://dx.doi.org/10.1016/S0939-6411(97)00101-X]
[46]
Dalpiaz A, Scatturin A, Pavan B, Biondi C, Vandelli MA, Forni F. Poly(lactic acid) microspheres for the sustained release of antiischemic agents. Int J Pharm 2002; 242(1-2): 115-20.
[http://dx.doi.org/10.1016/S0378-5173(02)00179-5] [PMID: 12176233]
[47]
Leo E, Contado C, Bortolotti F, et al. Nanoparticle formulation may affect the stabilization of an antiischemic prodrug. Int J Pharm 2006; 307(1): 103-13.
[http://dx.doi.org/10.1016/j.ijpharm.2005.09.031 PMID: 16289882]
[48]
Jiang L, Gao L, Wang X, Tang L, Ma J. The application of mucoadhesive polymers in nasal drug delivery. Drug Dev Ind Pharm 2010; 36(3): 323-36.
[http://dx.doi.org/10.3109/03639040903170750] [PMID: 19735210]
[49]
Salamat-Miller N, Chittchang M, Johnston TP. The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev 2005; 57(11): 1666-91.
[http://dx.doi.org/10.1016/j.addr.2005.07.003 PMID: 16183164]
[50]
Ahuja A, Khar RK, Ali J. Mucoadhesive drug delivery systems. Drug Dev Ind Pharm 1997; 23(5): 489-515.
[http://dx.doi.org/10.3109/03639049709148498]
[51]
Crowe TP, Greenlee MHW, Kanthasamy AG, Hsu WH. Mechanism of intranasal drug delivery directly to the brain. Life Sci 2018; 195: 44-52.
[http://dx.doi.org/10.1016/j.lfs.2017.12.025 PMID: 29277310]
[52]
Merkus FW, Verhoef JC, Schipper NG, Marttin E. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Deliv Rev 1998; 29(1-2): 13-38.
[http://dx.doi.org/10.1016/S0169-409X(97)00059-8] [PMID: 10837578]
[53]
Vyas TK, Babbar AK, Sharma RK, Singh S, Misra A. Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting. J Pharm Sci 2006; 95(3): 570-80.
[http://dx.doi.org/10.1002/jps.20480 PMID: 16419051]
[54]
Einer-Jensen N, Hunter R. Counter-current transfer in reproductive biology. Reprod 2005; 129(1): 9-18.
[http://dx.doi.org/10.1530/rep.1.00278 PMID: 15615894]
[55]
El-Zaafarany GM, Soliman ME, Mansour S, Awad GA. Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies. Int J Pharm 2016; 503(1-2): 127-40.
[http://dx.doi.org/10.1016/j.ijpharm.2016.02.038 PMID: 26924357]
[56]
El-Zaafarany GM, Soliman ME, Mansour S, et al. A tailored thermosensitive PLGA-PEG-PLGA/emulsomes composite for enhanced oxcarbazepine brain delivery via the nasal route. Pharmaceutics 2018; 10(4): 217.
[http://dx.doi.org/10.3390/pharmaceutics10040217] [PMID: 30400577]
[57]
Romeo VD, deMeireles J, Sileno AP, Pimplaskar HK, Behl CR. Effects of physicochemical properties and other factors on systemic nasal drug delivery. Adv Drug Deliv Rev 1998; 29(1-2): 89-116.
[http://dx.doi.org/10.1016/S0169-409X(97)00063-X] [PMID: 10837582]
[58]
Pires A, Fortuna A, Alves G, Falcão A. Intranasal drug delivery: how, why and what for? J Pharm Pharm Sci 2009; 12(3): 288-311.
[http://dx.doi.org/10.18433/J3NC79 PMID: 20067706]
[59]
Frey IWH. Method for administering neurologic agents to the brain Google Patents 1997.
[60]
Thorne RG, Hanson LR, Ross TM, Tung D, Frey WH II. Delivery of interferon-β to the monkey nervous system following intranasal administration. Neurosci 2008; 152(3): 785-97.
[http://dx.doi.org/10.1016/j.neuroscience.2008.01.013 PMID: 18304744]
[61]
Frey IWH. Method for administering insulin to the brain Google Patents 2001.
[62]
Freiherr J, Hallschmid M, Frey WH II, et al. Intranasal insulin as a treatment for Alzheimer’s disease: a review of basic research and clinical evidence. CNS Drugs 2013; 27(7): 505-14.
[http://dx.doi.org/10.1007/s40263-013-0076-8 PMID: 23719722]
[63]
Alexander A. Ajazuddin, Patel RJ, Saraf S, Saraf S. Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives. J Control Release 2016; 241: 110-24.
[http://dx.doi.org/10.1016/j.jconrel.2016.09.017 PMID: 27663228]
[64]
Sunena, Singh SK, Mishra DN. Nose to brain delivery of galantamine loaded nanoparticles: in-vivo pharmacodynamic and biochemical study in mice. Curr Drug Deliv 2019; 16(1): 51-8.
[http://dx.doi.org/10.2174/1567201815666181004094707] [PMID: 30289074]
[65]
Hanafy AS, Farid RM, Helmy MW, ElGamal SS. Pharmacological, toxicological and neuronal localization assessment of galantamine/chitosan complex nanoparticles in rats: future potential contribution in Alzheimer’s disease management. Drug Deliv 2016; 23(8): 3111-22.
[http://dx.doi.org/10.3109/10717544.2016.1153748] [PMID: 26942549]
[66]
Hanafy AS, Farid RM, ElGamal SS. Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer’s disease management: preparation and detection in rat brain. Drug Dev Ind Pharm 2015; 41(12): 2055-68.
[http://dx.doi.org/10.3109/03639045.2015.1062897] [PMID: 26133084]
[67]
Li W, Zhou Y, Zhao N, Hao B, Wang X, Kong P. Pharmacokinetic behavior and efficiency of acetylcholinesterase inhibition in rat brain after intranasal administration of galanthamine hydrobromide loaded flexible liposomes. Environ Toxicol Pharmacol 2012; 34(2): 272-9.
[http://dx.doi.org/10.1016/j.etap.2012.04.012 PMID: 22613079]
[68]
Bhattacharya S, Maelicke A, Montag D. Nasal application of the galantamine pro-drug memogain slows down plaque deposition and ameliorates behavior in 5X familial Alzheimer’s disease mice. J Alzheimers Dis 2015; 46(1): 123-36.
[http://dx.doi.org/10.3233/JAD-142421 PMID: 25720404]
[69]
Yang Z-Z, Zhang Y-Q, Wang Z-Z, Wu K, Lou J-N, Qi X-R. Enhanced brain distribution and pharmacodynamics of rivastigmine by liposomes following intranasal administration. Int J Pharm 2013; 452(1-2): 344-54.
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.009 PMID: 23680731]
[70]
Fazil M, Md S, Haque S, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci 2012; 47(1): 6-15.
[http://dx.doi.org/10.1016/j.ejps.2012.04.013 PMID: 22561106]
[71]
Fine JM, Renner DB, Forsberg AC, et al. Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation. Neurosci Lett 2015; 584: 362-7.
[http://dx.doi.org/10.1016/j.neulet.2014.11.013 PMID: 25445365]
[72]
Bhavna Md S, Ali M, et al. Donepezil nanosuspension intended for nose to brain targeting: in vitro and in vivo safety evaluation. Int J Biol Macromol 2014; 67: 418-25.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.03.022 PMID: 24705169]
[73]
Espinoza LC, Silva-Abreu M, Clares B, et al. Formulation strategies to improve nose-to-brain delivery of donepezil. Pharmaceutics 2019; 11(2): 64.
[http://dx.doi.org/10.3390/pharmaceutics11020064] [PMID: 30717264]
[74]
Al Harthi S, Alavi SE, Radwan MA, El Khatib MM, AlSarra IA. Nasal delivery of donepezil HCl-loaded hydrogels for the treatment of Alzheimer’s disease. Sci Rep 2019; 9(1): 9563.
[http://dx.doi.org/10.1038/s41598-019-46032-y PMID: 31266990]
[75]
Qian S, Wong YC, Zuo Z. Development characterization and application of in situ gel systems for intranasal delivery of tacrine. Int J Pharm 2014; 468(1-2): 272-82.
[http://dx.doi.org/10.1016/j.ijpharm.2014.04.015 PMID: 24709220]
[76]
Muntimadugu E, Dhommati R, Jain A, Challa VGS, 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: 224-34.
[http://dx.doi.org/10.1016/j.ejps.2016.05.012 PMID: 27185298]
[77]
Vaz GR, Hädrich G, Bidone J, et al. Development of nasal lipid nanocarriers containing curcumin for brain targeting. J Alzheimers Dis 2017; 59(3): 961-74.
[http://dx.doi.org/10.3233/JAD-160355 PMID: 28731428]
[78]
Nasr M. Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery. Drug Deliv 2016; 23(4): 1444-52.
[http://dx.doi.org/10.3109/10717544.2015.1092619] [PMID: 26401600]
[79]
Chen X, Zhi F, Jia X, et al. Enhanced brain targeting of curcumin by intranasal administration of a thermosensitive poloxamer hydrogel. J Pharm Pharmacol 2013; 65(6): 807-16.
[http://dx.doi.org/10.1111/jphp.12043 PMID: 23647674]
[80]
Wang S, Chen P, Zhang L, Yang C, Zhai G. Formulation and evaluation of microemulsion-based in situ ion-sensitive gelling systems for intranasal administration of curcumin. J Drug Target 2012; 20(10): 831-40.
[http://dx.doi.org/10.3109/1061186X.2012.719230] [PMID: 22934854]
[81]
Lungare S, Hallam K, Badhan RK. Phytochemical-loaded mesoporous silica nanoparticles for nose-to-brain olfactory drug delivery. Int J Pharm 2016; 513(1-2): 280-93.
[http://dx.doi.org/10.1016/j.ijpharm.2016.09.042 PMID: 27633279]
[82]
Wu H, Li J, Zhang Q, et al. A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-β25−35-treated rats following intranasal administration. Eur J Pharm Biopharm 2012; 80(2): 368-78.
[http://dx.doi.org/10.1016/j.ejpb.2011.10.012 PMID: 22061263]
[83]
Maurice T, Mustafa M-H, Desrumaux C, et al. Intranasal formulation of erythropoietin (EPO) showed potent protective activity against amyloid toxicity in the Aβ25−35 non-transgenic mouse model of Alzheimer’s disease. J Psychopharmacol (Oxford) 2013; 27(11): 1044-57.
[http://dx.doi.org/10.1177/0269881113494939 PMID: 23813967]
[84]
Gao X, Wu B, Zhang Q, et al. Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. J Control Release 2007; 121(3): 156-67.
[http://dx.doi.org/10.1016/j.jconrel.2007.05.026 PMID: 17628165]
[85]
Picone P, Ditta LA, Sabatino MA, et al. Ionizing radiation-engineered nanogels as insulin nanocarriers for the development of a new strategy for the treatment of Alzheimer’s disease. Biomaterials 2016; 80: 179-94.
[http://dx.doi.org/10.1016/j.biomaterials.2015.11.057] [PMID: 26708643]
[86]
Feng C, Zhang C, Shao X, et al. Enhancement of nose-to-brain delivery of basic fibroblast growth factor for improving rat memory impairments induced by co-injection of β-amyloid and ibotenic acid into the bilateral hippocampus. Int J Pharm 2012; 423(2): 226-34.
[http://dx.doi.org/10.1016/j.ijpharm.2011.12.008 PMID: 22193058]
[87]
Zhang C, Chen J, Feng C, et al. Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer’s disease. Int J Pharm 2014; 461(1-2): 192-202.
[http://dx.doi.org/10.1016/j.ijpharm.2013.11.049 PMID: 24300213]
[88]
Agrawal M, Saraf S, Saraf S, et al. Nose-to-brain drug delivery: an update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J Control Release 2018; 281: 139-77.
[http://dx.doi.org/10.1016/j.jconrel.2018.05.011 PMID: 29772289]
[89]
Zheng X, Shao X, Zhang C, et al. Intranasal H102 peptide-loaded liposomes for brain delivery to treat Alzheimer’s disease. Pharm Res 2015; 32(12): 3837-49.
[http://dx.doi.org/10.1007/s11095-015-1744-9 PMID: 26113236]
[90]
Liu Z, Jiang M, Kang T, et al. Lactoferrin-modified PEG-co-PCL nanoparticles for enhanced brain delivery of NAP peptide following intranasal administration. Biomaterials 2013; 34(15): 3870-81.
[http://dx.doi.org/10.1016/j.biomaterials.2013.02.003] [PMID: 23453061]
[91]
Elnaggar YS, Etman SM, Abdelmonsif DA, Abdallah OY. Intranasal piperine-loaded chitosan nanoparticles as brain-targeted therapy in Alzheimer’s disease: optimization, biological efficacy and potential toxicity. J Pharm Sci 2015; 104(10): 3544-56.
[http://dx.doi.org/10.1002/jps.24557]
[92]
Meng Q, Wang A, Hua H, et al. 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: 705-18.
[http://dx.doi.org/10.2147/IJN.S151474 PMID: 29440896]
[93]
Schiöth HB, Craft S, Brooks SJ, Frey WH II, Benedict C. Brain insulin signaling and Alzheimer’s disease: current evidence and future directions. Mol Neurobiol 2012; 46(1): 4-10.
[http://dx.doi.org/10.1007/s12035-011-8229-6 PMID: 22205300]
[94]
Reger MA, Watson GS, Green PS, et al. Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-β in memory-impaired older adults. J Alzheimers Dis 2008; 13(3): 323-31.
[http://dx.doi.org/10.3233/JAD-2008-13309 PMID: 18430999]
[95]
McNay EC, Ong CT, McCrimmon RJ, Cresswell J, Bogan JS, Sherwin RS. Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol Learn Mem 2010; 93(4): 546-53.
[http://dx.doi.org/10.1016/j.nlm.2010.02.002 PMID: 20176121]
[96]
Benedict C, Hallschmid M, Schmitz K, et al. Intranasal insulin improves memory in humans: superiority of insulin aspart. Neuropsychopharmacology 2007; 32(1): 239-43.
[http://dx.doi.org/10.1038/sj.npp.1301193 PMID: 16936707]
[97]
Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease--is this type 3 diabetes? J Alzheimers Dis 2005; 7(1): 63-80.
[http://dx.doi.org/10.3233/JAD-2005-7107 PMID: 15750215]
[98]
Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer’s disease: link to brain reductions in acetylcholine. J Alzheimers Dis 2005; 8(3): 247-68.
[http://dx.doi.org/10.3233/JAD-2005-8304 PMID: 16340083]
[99]
Benedict C, Frey WH II, Schiöth HB, Schultes B, Born J, Hallschmid M. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments. Exp Gerontol 2011; 46(2-3): 112-5.
[http://dx.doi.org/10.1016/j.exger.2010.08.026 PMID: 20849944]
[100]
Reger MA, Watson GS, Green PS, et al. Intranasal insulin improves cognition and modulates β-amyloid in early AD. Neurology 2008; 70(6): 440-8.
[http://dx.doi.org/10.1212/01.WNL.0000265401.62434.36] [PMID: 17942819]
[101]
De Felice FG, Vieira MN, Bomfim TR, et al. Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci 2009; 106(6): 1971-6.
[http://dx.doi.org/10.1073/pnas.0809158106 PMID: 19188609]
[102]
Lee C-C, Kuo Y-M, Huang C-C, Hsu K-S. Insulin rescues amyloid β-induced impairment of hippocampal long-term potentiation. Neurobiol Aging 2009; 30(3): 377-87.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.06.014] [PMID: 17692997]
[103]
Reger MA, Watson GS, Frey WH II, et al. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging 2006; 27(3): 451-8.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.03.016] [PMID: 15964100]
[104]
Craft S, Baker LD, Montine TJ, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol 2012; 69(1): 29-38.
[http://dx.doi.org/10.1001/archneurol.2011.233 PMID: 21911655]
[105]
Claxton A, Baker LD, Hanson A, et al. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer’s disease dementia. J Alzheimers Dis 2015; 44(3): 897-906.
[http://dx.doi.org/10.3233/JAD-141791 PMID: 25374101]
[106]
Benedict C, Hallschmid M, Hatke A, et al. Intranasal insulin improves memory in humans. Psychoneuroendocrinology 2004; 29(10): 1326-34.
[http://dx.doi.org/10.1016/j.psyneuen.2004.04.003] [PMID: 15288712]
[107]
Lehrer S, Rheinstein PH. A derangement of the brain wound healing process may cause some cases of Alzheimer’s disease. Discov Med 2016; 22(119): 43-6.
[PMID: 27585229]
[108]
Rosenbloom MH, Barclay TR, Pyle M, et al. A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein E4 carriers with mild-moderate Alzheimer’s disease. CNS Drugs 2014; 28(12): 1185-9.
[http://dx.doi.org/10.1007/s40263-014-0214-y PMID: 25373630]
[109]
Rangasamy SB, Corbett GT, Roy A, et al. Intranasal delivery of NEMO-binding domain peptide prevents memory loss in a mouse model of Alzheimer’s disease. J Alzheimers Dis 2015; 47(2): 385-402.
[http://dx.doi.org/10.3233/JAD-150040 PMID: 26401561]
[110]
Hayden MS, Ghosh S. NF-κB, the first quarter-century: remarkable progress and outstanding questions. Genes Dev 2012; 26(3): 203-34.
[http://dx.doi.org/10.1101/gad.183434.111 PMID: 22302935]
[111]
Oeckinghaus A, Hayden MS, Ghosh S. Crosstalk in NF-κB signaling pathways. Nat Immunol 2011; 12(8): 695-708.
[http://dx.doi.org/10.1038/ni.2065 PMID: 21772278]
[112]
May MJ, D’Acquisto F, Madge LA, Glöckner J, Pober JS, Ghosh S. Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex. Sci 2000; 289(5484): 1550-4.
[http://dx.doi.org/10.1126/science.289.5484.1550 PMID: 10968790]
[113]
Chonpathompikunlert P, Wattanathorn J, Muchimapura S. Piperine, the main alkaloid of Thai black pepper, protects against neurodegeneration and cognitive impairment in animal model of cognitive deficit like condition of Alzheimer’s disease. Food Chem Toxicol 2010; 48(3): 798-802.
[http://dx.doi.org/10.1016/j.fct.2009.12.009 PMID: 20034530]
[114]
Born J, Lange T, Kern W, McGregor GP, Bickel U, Fehm HL. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci 2002; 5(6): 514-6.
[http://dx.doi.org/10.1038/nn0602-849 PMID: 11992114]
[115]
Fehm HL, Smolnik R, Kern W, McGregor GP, Bickel U, Born J. The melanocortin melanocyte-stimulating hormone/adrenocorti-cotropin(4-10) decreases body fat in humans. J Clin Endocrinol Metab 2001; 86(3): 1144-8.
[PMID: 11238499]
[116]
Smolnik R, Perras B, Mölle M, Fehm HL, Born J. Event-related brain potentials and working memory function in healthy humans after single-dose and prolonged intranasal administration of adrenocorticotropin 4-10 and desacetyl-α-melanocyte stimulating hormone. J Clin Psychopharmacol 2000; 20(4): 445-54.
[http://dx.doi.org/10.1097/00004714-200008000-00009] [PMID: 10917406]
[117]
Hallschmid M, Smolnik R, McGregor G, Born J, Fehm HL. Overweight humans are resistant to the weight-reducing effects of melanocortin4-10. J Clin Endocrinol Metab 2006; 91(2): 522-5.
[http://dx.doi.org/10.1210/jc.2005-0906 PMID: 16317061]
[118]
Kosfeld M, Heinrichs M, Zak PJ, Fischbacher U, Fehr E. Oxytocin increases trust in humans. Nature 2005; 435(7042): 673-6.
[http://dx.doi.org/10.1038/nature03701 PMID: 15931222]
[119]
Yamasue H, Yee JR, Hurlemann R, et al. Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction. J Neurosci 2012; 32(41): 14109-17.
[http://dx.doi.org/10.1523/JNEUROSCI.3327-12.2012] [PMID: 23055480]
[120]
Domes G, Heinrichs M, Michel A, Berger C, Herpertz SC. Oxytocin improves “mind-reading” in humans. Biol Psychiatry 2007; 61(6): 731-3.
[http://dx.doi.org/10.1016/j.biopsych.2006.07.015 PMID: 17137561]
[121]
Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 2003; 54(12): 1389-98.
[http://dx.doi.org/10.1016/S0006-3223(03)00465-7] [PMID: 14675803]
[122]
Labuschagne I, Phan KL, Wood A, et al. Oxytocin attenuates amygdala reactivity to fear in generalized social anxiety disorder. Neuropsychopharmacology 2010; 35(12): 2403-13.
[http://dx.doi.org/10.1038/npp.2010.123 PMID: 20720535]
[123]
Guastella AJ, Einfeld SL, Gray KM, et al. Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biol Psychiatry 2010; 67(7): 692-4.
[http://dx.doi.org/10.1016/j.biopsych.2009.09.020 PMID: 19897177]
[124]
Pietrowsky R, Strüben C, Mölle M, Fehm HL, Born J. Brain potential changes after intranasal vs. intravenous administration of vasopressin: evidence for a direct nose-brain pathway for peptide effects in humans. Biol Psychiatry 1996; 39(5): 332-40.
[http://dx.doi.org/10.1016/0006-3223(95)00180-8 PMID: 8704064]
[125]
Derad I, Willeke K, Pietrowsky R, Born J, Fehm HL. Intranasal angiotensin II directly influences central nervous regulation of blood pressure. Am J Hypertens 1998; 11(8 Pt 1): 971-7.
[http://dx.doi.org/10.1016/S0895-7061(98)00095-8 PMID: 9715790]
[126]
Pietrowsky R, Thiemann A, Kern W, Fehm HL, Born J. A nose-brain pathway for psychotropic peptides: evidence from a brain evoked potential study with cholecystokinin. Psychoneuroendocrinology 1996; 21(6): 559-72.
[http://dx.doi.org/10.1016/S0306-4530(96)00012-1 PMID: 8983091]
[127]
Lalatsa A, Schatzlein AG, Uchegbu IF. Strategies to deliver peptide drugs to the brain. Mol Pharm 2014; 11(4): 1081-93.
[http://dx.doi.org/10.1021/mp400680d PMID: 24601686]
[128]
Ugwoke MI, Agu RU, Verbeke N, Kinget R. Nasal mucoadhesive drug delivery: background applications trends and future perspectives. Adv Drug Deliv Rev 2005; 57(11): 1640-65.
[http://dx.doi.org/10.1016/j.addr.2005.07.009 PMID: 16182408]
[129]
Aspden TJ, Mason JD, Jones NS, Lowe J, Skaugrud O, Illum L. Chitosan as a nasal delivery system: the effect of chitosan solutions on in vitro and in vivo mucociliary transport rates in human turbinates and volunteers. J Pharm Sci 1997; 86(4): 509-13.
[http://dx.doi.org/10.1021/js960182o PMID: 9109057]
[130]
Haffejee N, Du Plessis J, Müller DG, Schultz C, Kotzé AF, Goosen C. Intranasal toxicity of selected absorption enhancers. Pharmazie 2001; 56(11): 882-8.
[PMID: 11817176]
[131]
Callens C, Adriaens E, Dierckens K, Remon JP. Toxicological evaluation of a bioadhesive nasal powder containing a starch and Carbopol 974 P on rabbit nasal mucosa and slug mucosa. J Control Release 2001; 76(1-2): 81-91.
[http://dx.doi.org/10.1016/S0168-3659(01)00419-9] [PMID: 11532315]
[132]
Ingels KJ, Kortmann MJ, Nijziel MR, Graamans K, Huizing EH. Factors influencing ciliary beat measurements. Rhinology 1991; 29(1): 17-26.
[PMID: 2038652]
[133]
Rusznak C, Devalia JL, Lozewicz S, Davies RJ. The assessment of nasal mucociliary clearance and the effect of drugs. Respir Med 1994; 88(2): 89-101.
[http://dx.doi.org/10.1016/0954-6111(94)90020-5] [PMID: 8146420]

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