Author(s):
Prakash D. Jadhav, Atish B. Velhal, Vivekkumar K. Redasani, Sanjivani T. Rathod
Email(s):
sanjivanirathod43@gmail.com
DOI:
10.52711/2231-5691.2026.00002 
Address:
Prakash D. Jadhav, Atish B. Velhal, Vivekkumar K. Redasani, Sanjivani T. Rathod*
Department of Pharmaceutics, YSPM’s Yashoda Technical Campus, Satara 415011, Maharashtra, India.
*Corresponding Author
Published In:
Volume - 16,
Issue - 1,
Year - 2026
ABSTRACT:
The second most prevalent neurological condition in the world is Parkinson's disease (PD). Dopamine-deficit symptoms, including bradykinesia, postural instability, muscular rigidity, and resting tremors, are its hallmarks. This disease is caused by a variety of endogenous and exogenous causes, including as oxidative stress, genetics, mitochondrial malfunction, aging, inflammation, and various neurotoxins. Oxidative stress (OS) has been identified as the main cause of PD. More specifically, dopamine is converted into reactive oxygen species (ROS) such as hydrogen peroxide as a result of oxidative stress. Therefore, addressing dopamine deficiency is the main objective of most PD therapies. Extensive research on the development of novel neuroprotective pharmaceutical candidates suggests that natural items, such as plant extracts and their bioactive compounds, may hold great potential as lead neuroprotective choices in the treatment of PD. One way to improve the delivery of antioxidants to the brain is to use the nose-to-brain route, which involves delivering the antioxidant in specific nasal formulations and letting it enter the central nervous system (CNS) mainly through the olfactory nerve channel. We have focused on recent advancements in the research of herbal medicines and the bioactive components they contain that are used in cellular and animal neurotoxic models of PD in order to help future clinical trials. Although numerous studies have investigated the neuroprotective potential of natural compounds in Parkinson’s disease, limited attention has been given to effective delivery strategies for targeting these agents to the brain. Most existing research overlooks the challenge of brain accessibility, focusing either on conventional drugs or natural products in isolation. Nose-to-brain drug delivery offers a direct route to the brain via the olfactory pathway, bypassing the blood–brain barrier. This review highlights its potential to enhance the efficacy of natural neuroprotective compounds for Parkinson’s disease therapy.
Cite this article:
Prakash D. Jadhav, Atish B. Velhal, Vivekkumar K. Redasani, Sanjivani T. Rathod. Intranasal Delivery of Natural Compounds: A Promising approach for Parkinson’s Disease therapy. Asian Journal of Pharmaceutical Research. 2026; 16(1):12-0. doi: 10.52711/2231-5691.2026.00002
Cite(Electronic):
Prakash D. Jadhav, Atish B. Velhal, Vivekkumar K. Redasani, Sanjivani T. Rathod. Intranasal Delivery of Natural Compounds: A Promising approach for Parkinson’s Disease therapy. Asian Journal of Pharmaceutical Research. 2026; 16(1):12-0. doi: 10.52711/2231-5691.2026.00002 Available on: https://asianjpr.com/AbstractView.aspx?PID=2026-16-1-2
REFERENCES:
1. Phani S, Loike JD, Przedborski S. Neurodegeneration and inflammation in Parkinson's disease. Parkinsonism and Related Disorders. 2012 Jan 1; 18:S207-9.doi.org/10.1016/S1353-8020(11)70064-5
2. Sharma, R., Kabra, A., Rao, M. M., and Prajapati, P. K. Herbal and holistic solutions for neurodegenerative and depressive disorders: Leads from Ayurveda. Curr. Pharm. Des. 2018; 27 (3), 2597– 2608.
3. Illum L. Nasal drug delivery: possibilities, problems and solutions. J Control. Rel. 2003; 87: 187-198
4. Modi G, Pillay V, Choonara YE, et al. Nanotechnological applications for the treatment of neurodegenerative disorders. Prog Neurobiol 2009; 88:272–85.
5. Davis SS. Further development in nasal drug delivery. Pharmaceutical Science and Technology Today. 1999; 2: 265-266.
6. Dominique D, Gilles P. Nasal administration: a tool for tomorrow’s systemic administration of drugs. Drug Dev. Ind. Pharm. 19; 1993: 101-122.
7. Alexander GE, DeLong MR, Strick PL. Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Ann Rev Neurosci. 1986; 9:357–81.
8. Middleton FA, Strick PL. Basal ganglia and cerebellar loops: motor and cognitive circuits. Brain Res Rev. 2000; 31:236–50.
9. Lapper SR, Bolam JP. Input from the frontal cortex and the parafascicular nucleus to cholinergic interneurons in the dorsal striatum of the rat. Neuroscience. 1992; 51:533–45.
10. Abercrombie ED, Zigmond MJ. Modification of central catecholaminergic systems by stress and injury: functional significance and clinical implications. In: Bloom EJ, Kupfer DJ, eds. Psychopharmacology: the fourth generation of progress. New York: Raven Press. 1995.
11. Gibb WR, Scott T, Lees AJ. Neuronal inclusions of Parkinson's disease. Movement disorders: Official Journal of the Movement Disorder Society. 1991; 6(1):2-11.
12. An Y, Tang L, Jiang X, et al. A photoelectrochemical immunosensor based on Au-doped TiO2 nanotube arrays for the detection of a-synuclein. Chemistry. 2010; 16:14439–46
13. Di Stefano A, Sozio P, Iannitelli A, Cerasa LS. New drug delivery strategies for improved Parkinson's disease therapy. Expert Opinion on Drug Delivery. 2009 Apr 1; 6(4):389-404.
14. Md S, Khan RA, Mustafa G, et al. Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: pharmacodynamic, pharmacokinetic and scintigraphy study in mice model. Eur J Pharm Biopharm. 2013; 48:393–405.
15. Md S, Haque S, Fazil M, et al. Optimised nanoformulation of bromocriptine for direct nose-to-brain delivery: biodistribution, pharmacokinetic and dopamine estimation by ultra-HPLC/mass spectrometry method. Expert Opin Drug Deliv. 2014; 11:827–42.
16. Jafarieh O, Md S, Ali M, et al. Design, characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting. Drug Dev Ind Pharm. 2014. [Epub ahead of print]. doi: 10.3109/03639045.2014.991400.
17. Sharma S, Lohan S, Murthy RSR. Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery. Drug Dev Ind Pharm. 2014; 40: 869–78.
18. Mittal D, Md S, Hasan Q, et al. Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route. Drug Deliv. 2014. [Epub ahead of print]. doi: 10.3109/10717544.2014.907372.
19. Wen Z, Yan Z, Hu K, et al. Odorranalectin-conjugated nanoparticles: preparation, brain delivery and pharmacodynamic study on Parkinson’s disease following intranasal administration. J Control Release. 2011; 151:131–8.
20. Gambaryan PY, Kondrasheva IG, Severin ES, et al. Increasing the efficiency of Parkinson’s disease treatment using a poly(lactic-coglycolic acid) (PLGA) based L-DOPA delivery system. Exp Neurobiol 2014; 23:246–52.
21. Zhao YZ, Li X, Lu CT, et al. Gelatin nanostructured lipid carriers-mediated intranasal delivery of basic fibroblast growth factor enhances functional recovery in hemiparkinsonian rats. Nanomedicine. 2014; 10:755–64.
22. 92. Pardeshi CV, Rajput PV, Belgamwar VS, et al. Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: application of factorial design approach. Drug Deliv. 2013; 20:47–56.
23. Sahin-Yilmaz A and Naclerio RM. Anatomy and physiology of the upper airway. Proc Am Thorac Soc. 2011; 8: 31–39
24. Mustafa G, Baboota S, Ahuja A, et al. Formulation development of chitosan coated intranasal ropinirole nanoemulsion for better management option of parkinson: an in vitro ex vivo evaluation. Curr Nanosci. 2014; 3:348–60.
25. Leopold, D. A. The Relationship Between Nasal Anatomy and Human Olfaction??? The Laryngoscope. 1988, 98 (11), 1232???1238. https://doi.org/10.1288/00005537-198811000-00015.
26. Thorne R.G., Emory C.R., Ala T.A. and Fery W.H., Quantitative analysis of the olfactory pathway for drug delivery to the brain. Brain Res. 1995; 692(1-2): 278- 282,
27. Dhuria, S. V.; Hanson, L. R.; Frey, W. H. Intranasal Delivery to the Central Nervous System: Mechanisms and Experimental Considerations. Journal of Pharmaceutical Sciences. 2010, 99 (4), 1654-1673. https://doi.org/10.1002/jps.21924.
28. Lochhead JJ and Thorne RG (2012) intranasal delivery of biologics to the central nervous system. Adv Drug Deliv Rev. 64: 614–628.
29. Thorne RG, Hanson LR, Ross TM, Tung D, and Frey WH II (2008) Delivery of interferon-beta to the monkey nervous system following intranasal administration. Neuroscience. 152: 785–797.
30. Bourganis, V.; Kammona, O.; Alexopoulos, A.; Kiparissides, C. Recent Advances in Carrier Mediated Nose-to-Brain Delivery of Pharmaceutics. European Journal of Pharmaceutics and Biopharmaceutics. 2018, pp 337-362. https://doi.org/10.1016/j.ejpb.2018.05.009
31. Casettari, L.; Illum, L. Chitosan in Nasal Delivery Systems for Therapeutic Drugs. Journal of Controlled Release. 2014, 190, 189- 200. https://doi.org/DOI 10.1016/j.jconrel.2014.05.003.
32. Pardeshi, C. V.; Belgamwar, V. S. Direct Nose to Brain Drug Delivery via Integrated Nerve Pathways Bypassing the BloodBrain Barrier: An Excellent Platform for Brain Targeting. Expert Opinion on Drug Delivery. 2013; 10(7): 957-972.
33. Renner, D. B.; Svitak, A. L.; Gallus, N. J.; Ericson, M. E.; Frey, W. H.; Hanson, L. R. Intranasal Delivery of Insulin via the Olfactory Nerve Pathway. Journal of Pharmacy and Pharmacology 2012. https://doi.org/10.1111/j.2042-7158.2012.01555.x.
34. Gottofrey, J.; Tjalve, H. Axonal Transport of Cadmium in the Olfactory Nerve of the Pike. Pharmacology and Toxicology. 1991; 69(4): 242-252. https://doi.org/10.1111/bcpt.1991.69.4.242.
35. Enrique Cometto-Muñiz, J.; Simons, C. Trigeminal Chemesthesis. In Handbook of Olfaction and Gustation: Third Edition; 2015; pp 1089-1112. https://doi.org/10.1002/9781118971758.ch50.
36. Johnson, N. J.; Hanson, L. R.; Frey, W. H. Trigeminal Pathways Deliver a Low Molecular Weight Drug from the Nose to the Brain and Orofacial Structures. Molecular Pharmaceutics. 2010; 7(3): 884-893. https://doi.org/10.1021/mp100029t
37. Nicholls, A. R.; Holt, R. I. G. Growth Hormone and Insulin-Like Growth Factor-1. Frontiers of Hormone Research. 2016; 47: 101- 114. https://doi.org/10.1159/000445173.
38. Illum, L. Nasal Drug Delivery - Possibilities, Problems and Solutions. In Journal of Controlled Release; 2003.
39. Illum, L. Transport of Drugs from the Nasal Cavity to the Central Nervous System. European Journal of Pharmaceutical Sciences. 2000. https://doi.org/10.1016/S0928-0987(00)00087-7.
40. Edeling, M. A.; Smith, C.; Owen, D. Life of a Clathrin Coat: Insights from Clathrin and AP Structures. Nature Reviews Molecular Cell Biology. 2006, pp 32-44.
41. Miyamoto, M.; Natsume, H.; Iwata, S.; Ohtake, K.; Yamaguchi, M.; Kobayashi, D.; Sugibayashi, K.; Yamashina, M.; Morimoto, Y. Improved Nasal Absorption of Drugs Using Poly-L-Arginine: Effects of Concentration and Molecular Weight of Poly-L-Arginine on the Nasal Absorption of Fluorescein Isothiocyanate-Dextran in Rats. European Journal of Pharmaceutics and Biopharmaceutics. 2001, 52 (1), 21-30.
42. Van Itallie, C. M.; Anderson, J. M. Claudins And Epithelial Paracellular Transport. Annual Review of Physiology. 2006, 68 (1), 403-429.
43. Mistry, A.; Stolnik, S.; Illum, L. Nanoparticles for Direct Nose-to Brain Delivery of Drugs. International Journal of Pharmaceutics. 2009. https://doi.org/10.1016/j.ijpharm.2009.06.019.
44. Pardeshi CV, Belgamwar VS. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood–brain barrier: an excellent platform for brain targeting. Expert Opinion on Drug Delivery. 2013 Jul 1; 10(7):957-72.
45. Hamidovic A, Khafaja M, Brandon V, Anderson J, Ray G, Allan AM, and Burge MR (2017) Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial. Mol Psychiatry. 22: 1413–1421.
46. Pangeni R, Sharma S, Mustafa G, Ali J, Baboota S. Vitamin E loaded resveratrol nanoemulsion for brain targeting for the treatment of Parkinson’s disease by reducing oxidative stress. Nanotechnology. 2014 Nov 13; 25(48):485102.
47. Shadab; Alhakamy, N.A.; Aldawsari, H.M.; Asfour, H.Z. Neuroprotective and Antioxidant Effect of Naringenin-Loaded Nanoparticles for Nose-to-Brain Delivery. Brain Sci. 2019, 9, 275.
48. Gaba, B.; Khan, T.; Haider, F.; Alam, T.; Baboota, S.; Parvez, S.; Ali, J. 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, 1–20.
49. Rassu, G.; Porcu, E.P.; Fancello, S.; Obinu, A.; Senes, N.; Galleri, G.; Migheli, R.; Gavini, E.; Giunchedi, P. Intranasal Delivery of Genistein-Loaded Nanoparticles as a Potential Preventive System against Neurodegenerative Disorders. Pharmaceutics. 2018, 11, 8.
50. Babu, R.J.; Dayal, P.P.; Pawar, K.; Singh, M. Nose-to-brain transport of melatonin from polymer gel suspensions: A microdialysis study in rats. J. Drug Target. 2011, 19, 731–740.
51. Haney, M.J.; Klyachko, N.L.; Zhao, Y.; Gupta, R.; Plotnikova, E.G.; He, Z.; Patel, T.; Piroyan, A.; Sokolsky, M.; Kabanov, A.V.; et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J. Control. Release. 2015, 207, 18–30.
52. Wu, C.F.; Yang, J.Y.; Wang, F.; Wang, X.X. Resveratrol: Botanical origin, pharmacological activity and applications. Chin. J. Nat. Med. 2013, 11, 1–15.
53. Leonard, S.S.; Xia, C.; Jiang, B.-H.; Stinefelt, B.; Klandorf, H.; Harris, G.K.; Shi, X. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem. Biophys. Res. Commun. 2003, 309, 1017–1026.
54. Lou, H.; Jing, X.; Wei, X.; Shi, H.; Ren, D.; Zhang, X.-M. Naringenin protects against 6-OHDA- induced neurotoxicity via activation of the Nrf2/ARE signaling pathway. Neuropharmacology 2014, 79, 380–388.
55. Park, Y.J.; Ko, J.W.; Jeon, S.; Kwon, Y.H. Protective effect of Genistein against neuronal degeneration in ApoE-/-Mice fed a high-fat diet. Nutrients. 2016, 8, 692.
56. Sánchez-Barceló, E.J.; Mediavilla, M.; Tan, D.; Reiter, R. Clinical Uses of Melatonin: Evaluation of Human Trials. Curr. Med. Chem. 2010, 17, 2070–2095.
57. Pappolla, M.A.; Sos, M.; Omar, R.A.; Bick, R.J.; Hickson-Bick, D.L.M.; Reiter, R.J.; Efthimiopoulos, S.; Robakis, N.K. Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide. J. Neurosci. 1997, 17, 1683–1690.
58. Pappolla, M.A.; Bozner, P.; Soto, C.; Shao, H.; Robakis, N.K.; Zagorski, M.G.; Frangione, B.; Ghiso, J. Inhibition of Alzheimer β-Fibrillogenesis by Melatonin. J. Biol. Chem. 1998, 273, 7185–7188.
59. Matsubara, E.; Bryant-Thomas, T.; Quinto, J.P.; Henry, T.L.; Poeggeler, B.; Herbert, D.; Cruz-Sanchez, F.; Chyan, Y.-J.; Smith, M.A.; Perry, G.; et al. Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer’s disease. J. Neurochem. 2003, 85, 1101–1108.
60. Reiter, R. Melatonin, active oxygen species and neurological damage. Drug News Perspect. 1998, 11, 291–296.
61. Li, Y.; Zhao, X.; Zu, Y.; Wang, L.; Wu, W.; Deng, Y.; Zu, C.; Liu, Y. Melatonin-loaded silica coated with hydroxypropyl methylcellulose phthalate for enhanced oral bioavailability: Preparation, and in vitro-in vivo evaluation. Eur. J. Pharm. Biopharm. 2017, 112, 58–66.
62. Agu, R.U.; Valiveti, S.; Earles, D.C.; Klausner, M.; Hayden, P.J.; Wermeling, D.P.; Stinchcomb, A.L. Intranasal Delivery of Recombinant Human Parathyroid Hormone [hPTH (1–34)], Teriparatide in Rats. Endocr. Res. 2004, 30, 455–467.
63. Agu, R.U.; Valiveti, S.; Paudel, K.S.; Klausner, M.; Hayden, P.J.; Stinchcomb, A.L. Permeation of WIN 55, 212-2, a potent cannabinoid receptor agonist, across human tracheo-bronchial tissue in vitro and rat nasal epithelium in vivo. J. Pharm. Pharmacol. 2006, 58, 1459–1465.
64. Babu, R.J.; Dayal, P.; Singh, M. Effect of cyclodextrins on the complexation and nasal permeation of melatonin. Drug Deliv. 2008, 15, 381–388.
65. Haney, M.J.; Zhao, Y.; Li, S.; Higginbotham, S.M.; Booth, S.L.; Han, H.-Y.; Vetro, J.A.; Mosley, R.L.; Kabanov, A.V.; Gendelman, H.E.; et al. Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells. Nanomedicine. 2011, 6, 1215–1230.
66. Ambani, L.M.; Van Woert, M.H.; Murphy, S. Brain Peroxidase and Catalase in Parkinson Disease. Arch. Neurol. 1975, 32, 114–118.
67. Nandi, A.; Yan, L.-J.; Jana, C.K.; Das, N. Role of Catalase in Oxidative Stress- and Age-Associated Degenerative Diseases. Oxidative Med. Cell. Longev. 2019, 2019, 1–19.
68. Haney, M.J.; Zhao, Y.; Li, S.; Higginbotham, S.M.; Booth, S.L.; Han, H.-Y.; Vetro, J.A.; Mosley, R.L.; Kabanov, A.V.; Gendelman, H.E.; et al. Cell-mediated transfer of catalase nanoparticles from macrophages to brain endothelial, glial and neuronal cells. Nanomedicine. 2011; 6: 1215–1230.