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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

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

Review Article

A Potential Strategy for Treating Parkinson's Disease Through Intranasal Nanoemulsions

Author(s): Krushna Shirsath and Yogeeta O. Agrawal*

Volume 22, Issue 8, 2023

Published on: 31 August, 2022

Page: [1137 - 1145] Pages: 9

DOI: 10.2174/1871527321666220622163403

open access plus

Abstract

Intranasal delivery has great potential to cross the blood-brain barrier and deliver the drug molecule into the central nervous system faster than the traditional methods. The olfactory neuronal and trigeminal pathways both are involved in intranasal delivery. The nano-technology is an innovative strategy for the nose to brain delivery. The mucoadhesive nanoemulsion formulation is a modified technology that increases the duration of drug accumulation and provides prolonged delivery at a targeted site. The nanoemulsion formulation oil, surfactant, and co-surfactant components maintain lower surface tension and particle coalescence. The globule dimension and zeta potential are affected in brain targeting. The globule size of the innovative formulation should be < 200 nm for drug permeation because, in humans, the average axon magnitude ranges from around 100 to 700 nm. Furthermore, modified technology of nanoemulsions like nanogel and nanoemulsion in-situ gel provide a great advantage to cure neurodegenerative disorders. Therefore, focusing on the innovative pharmaceutical approaches of nanoemulsion in intranasal drug delivery, the current review provides insight into the applications of nanoemulsion in neurodegenerative disorders like Parkinson's disease, which are due to the depletion of dopamine in substania nigra resulting in cardinal motor activity bradykinesia and tremors. The review also touches upon the pathways for intranasal delivery of nanoemulsion, the pathogenesis of Parkinson's disease, and the future direction of the research on intranasal nanoemulsion.

Keywords: Intranasal delivery, Parkinson's, Neurodegenerative disorder, Central Nervous System, Nanoemulsion, Nanogel.

Graphical Abstract

[1]
Feany MB, Dickson DW. Neurodegenerative disorders with extensive tau pathology: A comparative study and review. Ann Neurol 1996; 40(2): 139-48.
[http://dx.doi.org/10.1002/ana.410400204] [PMID: 8773594]
[2]
Poewe W, Seppi K, Tanner CM, et al. Parkinson’s disease. Nat Rev Dis Primers 2017; 3(1): 17013.
[http://dx.doi.org/10.1038/nrdp.2017.13] [PMID: 28332488]
[3]
Patel V, Chisholm D, Parikh R, et al. Addressing the burden of mental, neurological, and substance use disorders: Key messages from disease control priorities, 3rd ed. Lancet 2016; 387(10028): 1672-85.
[http://dx.doi.org/10.1016/S0140-6736(15)00390-6] [PMID: 26454360]
[4]
Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol 2015; 7(1): a020412.
[http://dx.doi.org/10.1101/cshperspect.a020412] [PMID: 25561720]
[5]
Moinuddin S, Hasan Razvi S, Fazil M, Mustaneer Akmal M, Syed Moinuddin C, Shanawaz Uddin M. Nasal drug delivery system: A innovative approach. Pharm Innov J 2019; 8(3): 169-77.
[6]
Singh Y, Meher JG, Raval K, et al. Nanoemulsion: Concepts, development and applications in drug delivery. J Control Release 2017; 252: 28-49.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.008] [PMID: 28279798]
[7]
Che Marzuki NH, Wahab RA, Abdul Hamid M. An overview of nanoemulsion: Concepts of development and cosmeceutical applications. Biotechnol Biotechnol Equip 2019; 33(1): 779-97.
[http://dx.doi.org/10.1080/13102818.2019.1620124]
[8]
Azeem A, Rizwan M, Ahmad FJ, et al. Nanoemulsion components screening and selection: A technical note. AAPS PharmSciTech 2009; 10(1): 69-76.
[http://dx.doi.org/10.1208/s12249-008-9178-x] [PMID: 19148761]
[9]
Chhajed S, Sangale S, Barhate SD. Advantageous nasal drug delivery system: A review. Int J Pharm Sci Res 2011; 2(6): 1322.
[10]
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]
[11]
Mygind N, Anggård A. Anatomy and physiology of the nosepathophysiologic alterations in allergic rhinitis. Clin Rev Allergy 1984; 2(3): 173-88.
[http://dx.doi.org/10.1007/BF02991098] [PMID: 6149007]
[12]
Wang Z, Xiong G, Tsang WC, Schätzlein AG, Uchegbu IF. Nose-to-brain delivery. J Pharmacol Exp Ther 2019; 370(3): 593-601.
[http://dx.doi.org/10.1124/jpet.119.258152] [PMID: 31126978]
[13]
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.
[http://dx.doi.org/10.3109/10717544.2013.838713] [PMID: 24102636]
[14]
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]
[15]
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]
[16]
Selvaraj K, Gowthamarajan K, Karri VVSR. Nose to brain transport pathways an overview: Potential of nanostructured lipid carriers in nose to brain targeting. Artif Cells Nanomed Biotechnol 2018; 46(8): 2088-95.
[PMID: 29282995]
[17]
Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis 2011; 128(6): 309-16.
[http://dx.doi.org/10.1016/j.anorl.2011.03.002] [PMID: 22100360]
[18]
Johnston M, Papaiconomou C. Cerebrospinal fluid transport: A lymphatic perspective. News Physiol Sci 2002; 17(6): 227-30.
[PMID: 12433975]
[19]
Bonferoni MC, Rossi S, Sandri G, et al. Nanoemulsions for “nose-to-brain” drug delivery. Pharmaceutics 2019; 11(2): 1-17.
[http://dx.doi.org/10.3390/pharmaceutics11020084] [PMID: 30781585]
[20]
Ahmad E, Feng Y, Qi J, et al. Evidence of nose-to-brain delivery of nanoemulsions: Cargoes but not vehicles. Nanoscale 2017; 9(3): 1174-83.
[http://dx.doi.org/10.1039/C6NR07581A] [PMID: 28009915]
[21]
Bhanushali RS, Gatne MM, Gaikwad RV, Bajaj AN, Morde MA. Nanoemulsion based intranasal delivery of antimigraine drugs for nose to brain targeting. Indian J Pharm Sci 2009; 71(6): 707.
[22]
Rinaldi F, Oliva A, Sabatino M, et al. Antimicrobial essential oil formulation: Chitosan coated nanoemulsions for nose to brain delivery. Pharmaceutics 2020; 12(7): 678.
[http://dx.doi.org/10.3390/pharmaceutics12070678] [PMID: 32709076]
[23]
Dasgupta N, Ranjan S, Gandhi M. Nanoemulsion ingredients and components. Environ Chem Lett 2019; 17(2): 917-28.
[http://dx.doi.org/10.1007/s10311-018-00849-7]
[24]
Nirale P, Paul A, Yadav KS. Nanoemulsions for targeting the neurodegenerative diseases: Alzheimer’s, Parkinson’s and Prion’s. Life Sci 2020; 245: 117394.
[http://dx.doi.org/10.1016/j.lfs.2020.117394] [PMID: 32017870]
[25]
Jaiswal M, Dudhe R, Sharma PK. Nanoemulsion: An advanced mode of drug delivery system. 3 Biotech 2015; 5(2): 123-7.
[26]
Khunt D, Shah B, Misra M. Role of butter oil in brain targeted delivery of quetiapine fumarate microemulsion via intranasal route. J Drug Deliv Sci Technol 2017; 40: 11-20.
[http://dx.doi.org/10.1016/j.jddst.2017.05.004]
[27]
Hosny KM, Banjar ZM. The formulation of a nasal nanoemulsion zaleplon in situ gel for the treatment of insomnia. Expert Opin Drug Deliv 2013; 10(8): 1033-41.
[http://dx.doi.org/10.1517/17425247.2013.812069] [PMID: 23795561]
[28]
Lin H, Gebhardt M, Bian S, et al. Enhancing effect of surfactants on fexofenadine. HCl transport across the human nasal epithelial cell monolayer. Int J Pharm 2007; 330(1-2): 23-31.
[http://dx.doi.org/10.1016/j.ijpharm.2006.08.043] [PMID: 16997520]
[29]
Farago B, Richter D, Huang JS, Safran SA, Milner ST. Shape and size fluctuations of microemulsion droplets: The role of cosurfactant. Phys Rev Lett 1990; 65(26): 3348-51.
[http://dx.doi.org/10.1103/PhysRevLett.65.3348] [PMID: 10042846]
[30]
Cho YH, Kim S, Bae EK, Mok CK, Park J. Formulation of a cosurfactant-free O/W microemulsion using nonionic surfactant mixtures. J Food Sci 2008; 73(3): E115-21.
[http://dx.doi.org/10.1111/j.1750-3841.2008.00688.x] [PMID: 18387105]
[31]
Klossek ML, Marcus J, Touraud D, Kunz W. The extension of microemulsion regions by combining ethanol with other cosurfactants. Colloids Surf A Physicochem Eng Asp 2013; 427: 95-100.
[http://dx.doi.org/10.1016/j.colsurfa.2013.03.059]
[32]
Comfort C, Garrastazu G, Pozzoli M, Sonvico F. Opportunities and challenges for the nasal administration of nanoemulsions. Curr Top Med Chem 2015; 15(4): 356-68.
[http://dx.doi.org/10.2174/1568026615666150108144655] [PMID: 25579345]
[33]
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]
[34]
Bahadur S, Pardhi DM, Rautio J, Rosenholm JM, Pathak K. Intranasal nanoemulsions for direct nose-to-brain delivery of actives for cns disorders. Pharmaceutics 2020; 12(12): 1230.
[http://dx.doi.org/10.3390/pharmaceutics12121230] [PMID: 33352959]
[35]
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]
[36]
Abdou EM, Kandil SM, Miniawy HMFE. Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion. Int J Pharm 2017; 529(1-2): 667-77.
[http://dx.doi.org/10.1016/j.ijpharm.2017.07.030] [PMID: 28729175]
[37]
Opara J, Małecki A, Małecka E, Socha T. Motor assessment in Parkinson’s disease. Ann Agric Environ Med 2017; 24(3): 411-5.
[http://dx.doi.org/10.5604/12321966.1232774] [PMID: 28954481]
[38]
Singh V, Lalotra AS, Agrawal S, Mishra G. Nose-to-brain drug delivery via nanocarriers for the management of neurodegenerative disorders: Recent advances and future. Biol Sci 2021; 1(1): 19-34.
[http://dx.doi.org/10.55006/biolsciences.2021.1103]
[39]
Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson’s disease: A systematic review and meta-analysis. Mov Disord 2014; 29(13): 1583-90.
[http://dx.doi.org/10.1002/mds.25945] [PMID: 24976103]
[40]
Braak H, Braak E. Pathoanatomy of Parkinson’s disease. J Neurol 2000; 247(2) (Suppl. 2): II3-II10.
[PMID: 10991663]
[41]
Weintraub D, Comella CL, Horn S. Parkinson’s disease-Part 1: Pathophysiology, symptoms, burden, diagnosis, and assessment. Am J Manag Care 2008; 14(2) (Suppl.): S40-8.
[PMID: 18402507]
[42]
Jankovic J. Parkinson’s disease: Clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008; 79(4): 368-76.
[http://dx.doi.org/10.1136/jnnp.2007.131045] [PMID: 18344392]
[43]
Reichmann H, Brandt MD, Klingelhoefer L. The nonmotor features of Parkinson’s disease: Pathophysiology and management advances. Curr Opin Neurol 2016; 29(4): 467-73.
[http://dx.doi.org/10.1097/WCO.0000000000000348] [PMID: 27262147]
[44]
Bergman H, Deuschl G. Pathophysiology of Parkinson’s disease: From clinical neurology to basic neuroscience and back. Mov Disord 2002; 17(S3) (Suppl. 3): S28-40.
[http://dx.doi.org/10.1002/mds.10140] [PMID: 11948753]
[45]
Ellis JM, Fell MJ. Current approaches to the treatment of Parkinson’s disease. Bioorg Med Chem Lett 2017; 27(18): 4247-55.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.075] [PMID: 28869077]
[46]
Schapira AH. Present and future drug treatment for Parkinson’s disease. J Neurol Neurosurg Psychiatry 2005; 76(11): 1472-8.
[http://dx.doi.org/10.1136/jnnp.2004.035980] [PMID: 16227533]
[47]
Singh N, Pillay V, Choonara YE. Advances in the treatment of Parkinson’s disease. Prog Neurobiol 2007; 81(1): 29-44.
[http://dx.doi.org/10.1016/j.pneurobio.2006.11.009] [PMID: 17258379]
[48]
Dobkin RD, Menza M, Allen LA, et al. Cognitive-behavioral therapy for depression in Parkinson’s disease: A randomized, controlled trial. Am J Psychiatry 2011; 168(10): 1066-74.
[http://dx.doi.org/10.1176/appi.ajp.2011.10111669] [PMID: 21676990]
[49]
Pollak P, Fraix V, Krack P, et al. Treatment results: Parkinson’s disease. Mov Disord 2002; 17(S3) (Suppl. 3): S75-83.
[http://dx.doi.org/10.1002/mds.10146] [PMID: 11948759]
[50]
Stocchi F. The levodopa wearing-off phenomenon in Parkinson’s disease: Pharmacokinetic considerations. Expert Opin Pharmacother 2006; 7(10): 1399-407.
[http://dx.doi.org/10.1517/14656566.7.10.1399] [PMID: 16805724]
[51]
Chatterjee B, Gorain B, Mohananaidu K, Sengupta P, Mandal UK, Choudhury H. Targeted drug delivery to the brain via intranasal nanoemulsion: Available proof of concept and existing challenges. Int J Pharm 2019; 565: 258-68.
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.032] [PMID: 31095983]
[52]
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. Curr Nanosci 2012; 8(3): 348-60.
[http://dx.doi.org/10.2174/157341312800620331]
[53]
Zainol S, Mahiran B, Hamidon BB, et al. Formulation optimization of palm-based nanoemulsion containing levodopa, an Anti-Parkinson’s drug. Int J Mol Sci 2012; 13(10): 13049–13064.
[54]
Devi S, Kumar V, Singh SK, Dubey AK, Kim JJ. Flavonoids: Potential candidates for the treatment of neurodegenerative disorders. Biomedicines 2021; 9(2): 99.
[http://dx.doi.org/10.3390/biomedicines9020099] [PMID: 33498503]
[55]
Gaba B, Khan T, Haider MF, et al. Vitamin E loaded naringenin nanoemulsion via intranasal delivery for the management of oxidative stress in a 6-OHDA Parkinson’s disease model. BioMed Res Int 2019; 2019: 2382563.
[http://dx.doi.org/10.1155/2019/2382563] [PMID: 31111044]
[56]
Mandal S, Mandal SD, Chuttani K, Sawant KK, Subudhi BB. Neuroprotective effect of ibuprofen by intranasal application of mucoadhesive nanoemulsion in MPTP induced Parkinson model. J Pharm Investig 2016; 46(1): 41-53.
[http://dx.doi.org/10.1007/s40005-015-0212-1]
[57]
Choudhury H, Zakaria NF, Tilang PA, et al. Formulation development and evaluation of rotigotine mucoadhesive nanoemulsion for intranasal delivery. J Drug Deliv Sci Technol 2019; 54: 101301.
[http://dx.doi.org/10.1016/j.jddst.2019.101301]
[58]
Shah B. Microemulsion as a promising carrier for nose to brain delivery: Journey since last decade. J Pharm Investig 2021; 51(6): 611-34.
[http://dx.doi.org/10.1007/s40005-021-00528-w]
[59]
Wen MM. Olfactory targeting through intranasal delivery of biopharmaceutical drugs to the brain: Current development. Discov Med 2011; 11(61): 497-503.
[PMID: 21712015]
[60]
Rehman S, Nabi B, Zafar A, Baboota S, Ali J. Intranasal delivery of mucoadhesive nanocarriers: A viable option for Parkinson’s disease treatment? Expert Opin Drug Deliv 2019; 16(12): 1355-66.
[http://dx.doi.org/10.1080/17425247.2019.1684895] [PMID: 31663382]
[61]
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.
[http://dx.doi.org/10.3109/10717544.2014.908980] [PMID: 24825492]
[62]
Sengupta P, Chatterjee B. Potential and future scope of nanoemulgel formulation for topical delivery of lipophilic drugs. Int J Pharm 2017; 526(1-2): 353-65.
[http://dx.doi.org/10.1016/j.ijpharm.2017.04.068] [PMID: 28461261]
[63]
Jaiswal M, Kumar A, Sharma S. Nanoemulsions loaded carbopol® 934 based gel for intranasal delivery of neuroprotective Centella asiatica extract: In vitro and ex vivo permeation study. J Pharm Investig 2016; 46(1): 79-89.
[http://dx.doi.org/10.1007/s40005-016-0228-1]
[64]
Samia O, Hanan R, Kamal T. Carbamazepine Mucoadhesive Nanoemulgel (MNEG) as brain targeting delivery system via the olfactory mucosa. Drug Deliv 2012; 19(1): 58-67.
[http://dx.doi.org/10.3109/10717544.2011.644349] [PMID: 22191715]
[65]
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; 1-11.
[http://dx.doi.org/10.1155/2021/1546798]
[66]
Srivastava M, Kohli K, Ali M. Formulation development of novel in situ Nanoemulgel (NEG) of ketoprofen for the treatment of periodontitis. Drug Deliv 2016; 23(1): 154-66.
[http://dx.doi.org/10.3109/10717544.2014.907842] [PMID: 24786482]
[67]
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]
[68]
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]

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