Skip to content
2000
image of Nanocarrier-Based Therapies: A Breakthrough in Parkinson’s Disease Management

Abstract

Parkinson’s disease (PD) is one of the severe neurodegenerative disorders characterized by a deficiency of dopamine in the substantia nigra. The implicated factors for this include mitochondrial dysfunction, gut dysbiosis, and alteration in the signaling pathways. Overall, these events lead to the generation and aggregation of misfolding proteins, ., Lewy bodies. These aggregates contribute to the production of oxidative stress, inflammation, and neurotransmission imbalance. Hence, impaired cognition and body movements in the PD patients. There are several conventional treatments, such as synthetic drugs and herbal drugs, used to mitigate PD. Despite having enormous potential, their use is limited due to their low permeability, low solubility, and complexation in standardization. However, with the advancement in technology, different NDDS (Novel drug delivery systems) such as vesicular drug delivery systems, SNEDDS (Self-Nanoemulsifying Drug Delivery System), NPs (Nanoparticles), NLCs (Nano-structure lipid carrier), SLN (Solid lipid nanoparticles), quantum dots, and dendrimers have been explored to overcome the limitations of conventional treatments. Hence, the present review emphasizes a brief introduction to PD, pathogenesis of PD, signaling pathways, biomarkers, conventional treatments, need for NDDS, and Applications of NDDS in PD. Additionally, patents, clinical trials, and ongoing clinical trials are also covered in the present manuscript.

Loading

Article metrics loading...

/content/journals/cpd/10.2174/0113816128404289251010202113
2025-10-28
2026-01-27
Loading full text...

Full text loading...

References

  1. Poewe W. Seppi K. Tanner C.M. Halliday G.M. Brundin P. Volkmann J. Schrag A.E. Lang A.E. Parkinson disease. Nat. Rev. Dis. Primers 2017 3 1 17013 10.1038/nrdp.2017.13 28332488
    [Google Scholar]
  2. Bloem B.R. Okun M.S. Klein C. Parkinson’s disease. Lancet 2021 397 10291 2284 2303 10.1016/S0140‑6736(21)00218‑X 33848468
    [Google Scholar]
  3. Rocha E.M. Keeney M.T. Di Maio R. De Miranda B.R. Greenamyre J.T. LRRK2 and idiopathic Parkinson’s disease. Trends Neurosci. 2022 45 3 224 236 10.1016/j.tins.2021.12.002 34991886
    [Google Scholar]
  4. Baizabal-Carvallo J.F. Morgan J.C. Drug-induced tremor, clinical features, diagnostic approach and management. J. Neurol. Sci. 2022 435 120192 10.1016/j.jns.2022.120192 35220110
    [Google Scholar]
  5. Ma K.K.Y. Lin S. Mok V.C.T. Neuroimaging in vascular parkinsonism. Curr. Neurol. Neurosci. Rep. 2019 19 12 102 10.1007/s11910‑019‑1019‑7 31773419
    [Google Scholar]
  6. Church F.C. Treatment options for motor and non-motor symptoms of Parkinson’s disease. Biomolecules 2021 11 4 612 10.3390/biom11040612 33924103
    [Google Scholar]
  7. Stocchi F. Bravi D. Emmi A. Antonini A. Parkinson disease therapy: Current strategies and future research priorities. Nat. Rev. Neurol. 2024 20 12 695 707 10.1038/s41582‑024‑01034‑x 39496848
    [Google Scholar]
  8. Harris J.P. Burrell J.C. Struzyna L.A. Chen H.I. Serruya M.D. Wolf J.A. Duda J.E. Cullen D.K. Emerging regenerative medicine and tissue engineering strategies for Parkinson’s disease. NPJ Parkinsons Dis. 2020 6 1 4 10.1038/s41531‑019‑0105‑5 31934611
    [Google Scholar]
  9. Rajan R. Divya K.P. Kandadai R.M. Yadav R. Satagopam V.P. Madhusoodanan U.K. Agarwal P. Kumar N. Ferreira T. Kumar H. Sreeram Prasad A.V. Shetty K. Mehta S. Desai S. Kumar S. Prashanth L.K. Bhatt M. Wadia P. Ramalingam S. Wali G.M. Pandey S. Bartusch F. Hannussek M. Krüger J. Kumar-Sreelatha A. Grover S. Lichtner P. Sturm M. Roeper J. Busskamp V. Chandak G.R. Schwamborn J. Seth P. Gasser T. Riess O. Goyal V. Pal P.K. Borgohain R. Krüger R. Kishore A. Sharma M. Genetic architecture of Parkinson’s disease in the indian population: Harnessing genetic diversity to address critical gaps in parkinson’s disease research. Front. Neurol. 2020 11 524 10.3389/fneur.2020.00524 32655481
    [Google Scholar]
  10. Zirra A. Rao S.C. Bestwick J. Rajalingam R. Marras C. Blauwendraat C. Mata I.F. Noyce A.J. Gender differences in the prevalence of Parkinson’s disease. Mov. Disord. Clin. Pract. 2023 10 1 86 93 10.1002/mdc3.13584 36699001
    [Google Scholar]
  11. Simon D.K. Tanner C.M. Brundin P. Parkinson disease epidemiology, pathology, genetics, and pathophysiology. Clin. Geriatr. Med. 2020 36 1 1 12 10.1016/j.cger.2019.08.002 31733690
    [Google Scholar]
  12. Ryman S.G. Poston K.L. MRI biomarkers of motor and non-motor symptoms in Parkinson’s disease. Parkinsonism Relat. Disord. 2020 73 85 93 10.1016/j.parkreldis.2019.10.002 31629653
    [Google Scholar]
  13. Travagli R.A. Browning K.N. Camilleri M. Parkinson disease and the gut: New insights into pathogenesis and clinical relevance. Nat. Rev. Gastroenterol. Hepatol. 2020 17 11 673 685 10.1038/s41575‑020‑0339‑z 32737460
    [Google Scholar]
  14. Rani L. Mondal A.C. Emerging concepts of mitochondrial dysfunction in Parkinson’s disease progression: Pathogenic and therapeutic implications. Mitochondrion 2020 50 25 34 10.1016/j.mito.2019.09.010 31654753
    [Google Scholar]
  15. Li J. Long X. Hu J. Bi J. Zhou T. Guo X. Han C. Huang J. Wang T. Xiong N. Lin Z. Multiple pathways for natural product treatment of Parkinson’s disease: A mini review. Phytomedicine 2019 60 152954 10.1016/j.phymed.2019.152954 31130327
    [Google Scholar]
  16. See W.Z.C. Naidu R. Tang K.S. Cellular and molecular events leading to paraquat-induced apoptosis: Mechanistic insights into parkinson’s disease pathophysiology. Mol. Neurobiol. 2022 59 6 3353 3369 10.1007/s12035‑022‑02799‑2 35306641
    [Google Scholar]
  17. Klann E.M. Dissanayake U. Gurrala A. Farrer M. Shukla A.W. Ramirez-Zamora A. Mai V. Vedam-Mai V. The gut–brain axis and its relation to parkinson’s disease: A review. Front. Aging Neurosci. 2022 13 782082 10.3389/fnagi.2021.782082 35069178
    [Google Scholar]
  18. Chen S.J. Lin C.H. Gut microenvironmental changes as a potential trigger in Parkinson’s disease through the gut–brain axis. J. Biomed. Sci. 2022 29 1 54 10.1186/s12929‑022‑00839‑6 35897024
    [Google Scholar]
  19. MacMahon Copas A.N. McComish S.F. Fletcher J.M. Caldwell M.A. The pathogenesis of Parkinson’s disease: A complex interplay between astrocytes, microglia, and T lymphocytes? Front. Neurol. 2021 12 666737 10.3389/fneur.2021.666737 34122308
    [Google Scholar]
  20. Wang R. Ren H. Kaznacheyeva E. Lu X. Wang G. Association of glial activation and α-synuclein pathology in Parkinson’s disease. Neurosci. Bull. 2023 39 3 479 490 10.1007/s12264‑022‑00957‑z 36229715
    [Google Scholar]
  21. Roodveldt C. Bernardino L. Oztop-Cakmak O. Dragic M. Fladmark K.E. Ertan S. Aktas B. Pita C. Ciglar L. Garraux G. Williams-Gray C. Pacheco R. Romero-Ramos M. The immune system in Parkinson’s disease: What we know so far. Brain 2024 147 10 3306 3324 10.1093/brain/awae177 38833182
    [Google Scholar]
  22. Dutta D. Kundu M. Mondal S. Roy A. Ruehl S. Hall D.A. Pahan K. RANTES-induced invasion of Th17 cells into substantia nigra potentiates dopaminergic cell loss in MPTP mouse model of Parkinson’s disease. Neurobiol. Dis. 2019 132 104575 10.1016/j.nbd.2019.104575 31445159
    [Google Scholar]
  23. Qu Y. Li J. Qin Q. Wang D. Zhao J. An K. Mao Z. Min Z. Xiong Y. Li J. Xue Z. A systematic review and meta-analysis of inflammatory biomarkers in Parkinson’s disease. NPJ Parkinsons Dis. 2023 9 1 18 10.1038/s41531‑023‑00449‑5 36739284
    [Google Scholar]
  24. Kam T.I. Hinkle J.T. Dawson T.M. Dawson V.L. Microglia and astrocyte dysfunction in parkinson’s disease. Neurobiol. Dis. 2020 144 105028 10.1016/j.nbd.2020.105028 32736085
    [Google Scholar]
  25. Eser P. Kocabicak E. Bekar A. Temel Y. The interplay between neuroinflammatory pathways and Parkinson’s disease. Exp. Neurol. 2024 372 114644 10.1016/j.expneurol.2023.114644 38061555
    [Google Scholar]
  26. Bayati A. McPherson P.S. Alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: Mutations, propagation, aggregation, and the formation of inclusions. J. Biol. Chem. 2024 300 10 107742 10.1016/j.jbc.2024.107742 39233232
    [Google Scholar]
  27. Zheng Q. Liu H. Gao Y. Cao G. Wang Y. Li Z. Ameliorating mitochondrial dysfunction for the therapy of Parkinson’s disease. Small 2024 20 29 2311571 10.1002/smll.202311571 38385823
    [Google Scholar]
  28. Narendra D.P. Youle R.J. The role of PINK1–Parkin in mitochondrial quality control. Nat. Cell Biol. 2024 26 10 1639 1651 10.1038/s41556‑024‑01513‑9 39358449
    [Google Scholar]
  29. Kannan G. Paul B.M. Thangaraj P. Stimulation, regulation, and inflammaging interventions of natural compounds on nuclear factor kappa B (NF-kB) pathway: A comprehensive review. Inflammopharmacology 2025 33 1 145 162 10.1007/s10787‑024‑01635‑4 39776026
    [Google Scholar]
  30. Yu L. Hu X. Xu R. Zhao Y. Xiong L. Ai J. Wang X. Chen X. Ba Y. Xing Z. Guo C. Mi S. Wu X. Piperine promotes PI3K/AKT/mTOR-mediated gut-brain autophagy to degrade α-Synuclein in Parkinson’s disease rats. J. Ethnopharmacol. 2024 322 117628 10.1016/j.jep.2023.117628 38158101
    [Google Scholar]
  31. Zhao Y. Lin M. Zhai F. Chen J. Jin X. Exploring the role of ubiquitin-proteasome system in the pathogenesis of Parkinson’s disease. Pharmaceuticals 2024 17 6 782 10.3390/ph17060782 38931449
    [Google Scholar]
  32. Wang J. Zhao J. Zhao K. Wu S. Chen X. Hu W. The role of calcium and iron homeostasis in parkinson’s disease. Brain Sci. 2024 14 1 88 10.3390/brainsci14010088 38248303
    [Google Scholar]
  33. Chung See W.Z. Naidu R. Tang K.S. Paraquat and Parkinson’s disease: The molecular crosstalk of upstream signal transduction pathways leading to apoptosis. Curr. Neuropharmacol. 2024 22 1 140 151 10.2174/1570159X21666230126161524 36703582
    [Google Scholar]
  34. Kumar P. Patel R. Shah S.S. Aran K.R. Exploring the role of AMPK-JNK signaling pathways in Parkinson’s disease: Pathophysiology to therapeutic strategies. Neurosci. Behav. Physiol. 2025 55 1 86 100 10.1007/s11055‑025‑01750‑x
    [Google Scholar]
  35. Keshri P.K. Singh S.P. Unraveling the AKT/ERK cascade and its role in Parkinson disease. Arch. Toxicol. 2024 98 10 3169 3190 10.1007/s00204‑024‑03829‑9 39136731
    [Google Scholar]
  36. Ji M. Niu S. Mi H. Jiang P. Li Y. Vinpocetine improves dyskinesia in Parkinson’s disease rats by reducing oxidative stress and activating the Wnt/β‐catenin signaling pathway. Chem. Biol. Drug Des. 2024 103 1 14358 10.1111/cbdd.14358 37749299
    [Google Scholar]
  37. Singh G. Khatri D.K. MicroRNA-gene regulatory network of TLR signaling in neuroinflammation-induced Parkinson’s disease: A bioinformatics approach. Netw. Model. Anal. Health Inform. Bioinform. 2024 13 1 7 10.1007/s13721‑024‑00445‑6
    [Google Scholar]
  38. Liang H. Liu P. Wang Z. Xiong H. Yin C. Zhao D. Wu C. Chen L. TREM2 gene induces differentiation of induced pluripotent stem cells into dopaminergic neurons and promotes neuronal repair via TGF ‐β activation in 6‐OHDA ‐lesioned mouse model of Parkinson’s disease. CNS Neurosci. Ther. 2024 30 2 14630 10.1111/cns.14630 38348765
    [Google Scholar]
  39. Liu S. Liu T. Li J. Hong J. Moosavi-Movahedi A.A. Wei J. Type 2 diabetes mellitus exacerbates pathological processes of parkinson’s disease: Insights from signaling pathways mediated by insulin receptors. Neurosci. Bull. 2025 41 4 676 690 10.1007/s12264‑024‑01342‑8 39754628
    [Google Scholar]
  40. Wang L. Tian S. Ruan S. Wei J. Wei S. Chen W. Hu H. Qin W. Li Y. Yuan H. Mao J. Xu Y. Xie J. Neuroprotective effects of cordycepin on MPTP-induced Parkinson’s disease mice via suppressing PI3K/AKT/mTOR and MAPK-mediated neuroinflammation. Free Radic. Biol. Med. 2024 216 60 77 10.1016/j.freeradbiomed.2024.02.023 38479634
    [Google Scholar]
  41. Liu T. Li J. Sun L. Zhu C. Wei J. The role of ACE2 in RAS axis on microglia activation in Parkinson’s disease. Neuroscience 2024 553 128 144 10.1016/j.neuroscience.2024.06.024 38986737
    [Google Scholar]
  42. Kang M.K. Kim D.H. Anti-cancer effects of the Pandanus tectorius Parkinson extract: Reduction of YAP and TAZ levels via inhibition of the Hippo and Notch signaling pathways. Biomed. Sci. Lett. 2024 30 3 113 122 10.15616/BSL.2024.30.3.113
    [Google Scholar]
  43. Liu X. Li X. Li M. Jiang P. Zhuang L. Guan W. Naseem A. Chen Q. Zhang L. Kuang H. Yang B. Liu Y. The monoterpenoids of Paeoniae radix rubra alleviate dopaminergic neuronal injury of Parkinson’s disease by inhibiting Bach1 and activating Nrf2/ARE pathway. Food Biosci. 2025 63 105808 10.1016/j.fbio.2024.105808
    [Google Scholar]
  44. Turkistani A. Al-kuraishy H.M. Al-Gareeb A.I. Albuhadily A.K. Alexiou A. Papadakis M. Elfiky M.M. Saad H.M. Batiha G.E.S. Therapeutic potential effect of glycogen synthase kinase 3 beta (GSK-3β) inhibitors in Parkinson disease: Exploring an overlooked avenue. Mol. Neurobiol. 2024 61 9 7092 7108 10.1007/s12035‑024‑04003‑z 38367137
    [Google Scholar]
  45. Mitroshina E.V. Vedunova M.V. The role of oxygen homeostasis and the HIF-1 factor in the development of neurodegeneration. Int. J. Mol. Sci. 2024 25 9 4581 10.3390/ijms25094581 38731800
    [Google Scholar]
  46. Yan M. Sun Z. Zhang S. Yang G. Jiang X. Wang G. Li R. Wang Q. Tian X. SOCS modulates JAK-STAT pathway as a novel target to mediate the occurrence of neuroinflammation: Molecular details and treatment options. Brain Res. Bull. 2024 213 110988 10.1016/j.brainresbull.2024.110988 38805766
    [Google Scholar]
  47. Ravichandran N. Iyer M. Uvarajan D. Kirola L. Kumra S.M. Babu H.S. HariKrishnaReddy D. Vellingiri B. Narayanasamy A. New insights on the regulators and inhibitors of RhoA-ROCK signalling in Parkinson’s disease. Metab. Brain Dis. 2025 40 1 90 10.1007/s11011‑024‑01500‑x 39775342
    [Google Scholar]
  48. Magalhães P. Lashuel H.A. Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson’s disease and other synucleinopathies. NPJ Parkinsons Dis. 2022 8 1 93 10.1038/s41531‑022‑00357‑0 35869066
    [Google Scholar]
  49. Ganguly U. Singh S. Pal S. Prasad S. Agrawal B.K. Saini R.V. Chakrabarti S. Alpha-synuclein as a biomarker of Parkinson’s disease: Good, but not good enough. Front. Aging Neurosci. 2021 13 702639 10.3389/fnagi.2021.702639 34305577
    [Google Scholar]
  50. Brücke T. Brücke C. Dopamine transporter (DAT) imaging in Parkinson’s disease and related disorders. J. Neural Transm. 2022 129 5-6 581 594 10.1007/s00702‑021‑02452‑7 34910248
    [Google Scholar]
  51. Schirinzi T. Zenuni H. Grillo P. Bovenzi R. Guerrera G. Gargano F. Pieri M. Bernardini S. Biagio Mercuri N. Battistini L. Sancesario G.M. Tau and amyloid-β peptides in serum of patients with parkinson’s disease: Correlations With CSF levels and clinical parameters. Front. Neurol. 2022 13 748599 10.3389/fneur.2022.748599 35280296
    [Google Scholar]
  52. Surguchov A. Biomarkers in Parkinson’s disease. Neurodegenerative Diseases Biomarkers United States Humana Press 2022 173 10.1007/978‑1‑0716‑1712‑0_7
    [Google Scholar]
  53. Yan J. Feng X. Zhou X. Zhao M. Xiao H. Li R. Shen H. Identification of gut metabolites associated with Parkinson’s disease using bioinformatic analyses. Front. Aging Neurosci. 2022 14 927625 10.3389/fnagi.2022.927625 35959296
    [Google Scholar]
  54. Nabizadeh F. Pirahesh K. Valizadeh P. REM sleep behavior disorder and cerebrospinal fluid alpha-synuclein, amyloid beta, total tau and phosphorylated tau in Parkinson’s disease: A cross-sectional and longitudinal study. J. Neurol. 2022 269 9 4836 4845 10.1007/s00415‑022‑11120‑z 35426534
    [Google Scholar]
  55. Nabizadeh F. Pirahesh K. Khalili E. Olfactory dysfunction is associated with motor function only in tremor-dominant Parkinson’s disease. Neurol. Sci. 2022 43 7 4193 4201 10.1007/s10072‑022‑05952‑w 35166976
    [Google Scholar]
  56. Jennings D. Huntwork-Rodriguez S. Henry A.G. Sasaki J.C. Meisner R. Diaz D. Solanoy H. Wang X. Negrou E. Bondar V.V. Ghosh R. Maloney M.T. Propson N.E. Zhu Y. Maciuca R.D. Harris L. Kay A. LeWitt P. King T.A. Kern D. Ellenbogen A. Goodman I. Siderowf A. Aldred J. Omidvar O. Masoud S.T. Davis S.S. Arguello A. Estrada A.A. de Vicente J. Sweeney Z.K. Astarita G. Borin M.T. Wong B.K. Wong H. Nguyen H. Scearce-Levie K. Ho C. Troyer M.D. Preclinical and clinical evaluation of the LRRK2 inhibitor DNL201 for Parkinson’s disease. Sci. Transl. Med. 2022 14 648 eabj2658 10.1126/scitranslmed.abj2658 35675433
    [Google Scholar]
  57. Senkevich K. Rudakou U. Gan-Or Z. New therapeutic approaches to Parkinson’s disease targeting GBA, LRRK2 and Parkin. Neuropharmacology 2022 202 108822 10.1016/j.neuropharm.2021.108822 34626666
    [Google Scholar]
  58. Kulkarni A. Preeti K. Tryphena K.P. Srivastava S. Singh S.B. Khatri D.K. Proteostasis in Parkinson’s disease: Recent development and possible implication in diagnosis and therapeutics. Ageing Res. Rev. 2023 84 101816 10.1016/j.arr.2022.101816 36481490
    [Google Scholar]
  59. Yang D. Xie H. Wu S. Ying C. Chen Y. Ge Y. Yao R. Li K. Jiang Z. Chen G. Neurofilament light chain as a mediator between LRRK2 mutation and dementia in Parkinson’s disease. NPJ Parkinsons Dis. 2023 9 1 132 10.1038/s41531‑023‑00572‑3 37699957
    [Google Scholar]
  60. Fu Y. Chen Y. Tian H. Liu H. Qi D. Wu E. Wang X. Identification of BAG5 as a potential biomarker for Parkinson’s disease patients with R492X PINK1 mutation. Front. Neurosci. 2022 16 903958 10.3389/fnins.2022.903958 35968372
    [Google Scholar]
  61. Solana-Manrique C. Sanz F.J. Torregrosa I. Palomino-Schätzlein M. Hernández-Oliver C. Pineda-Lucena A. Paricio N. Metabolic alterations in a Drosophila model of Parkinson’s disease based on DJ-1 deficiency. Cells 2022 11 3 331 10.3390/cells11030331 35159141
    [Google Scholar]
  62. Banait T. Wanjari A. Danade V. Banait S. Jain J. Role of high-sensitivity C-reactive protein (hs-CRP) in non-communicable diseases: A review. Cureus 2022 14 10 30225 10.7759/cureus.30225 36381804
    [Google Scholar]
  63. Liu T.W. Chen C.M. Chang K.H. Biomarker of neuroinflammation in Parkinson’s disease. Int. J. Mol. Sci. 2022 23 8 4148 10.3390/ijms23084148 35456966
    [Google Scholar]
  64. Muksuris K. Scarisbrick D.M. Mahoney J.J. III Cherkasova M.V. Noninvasive neuromodulation in Parkinson’s disease: Insights from animal models. J. Clin. Med. 2023 12 17 5448 10.3390/jcm12175448 37685514
    [Google Scholar]
  65. Mafuika S.N. Naicker T. Harrichandparsad R. Lazarus L. The potential of serum S100 calcium-binding protein B and glial fibrillary acidic protein as biomarkers for traumatic brain injury. Transl. Res. Anat. 2022 29 100228 10.1016/j.tria.2022.100228
    [Google Scholar]
  66. Kwon S.H. Park J.K. Koh Y.H. A systematic review and meta-analysis on the effect of virtual reality-based rehabilitation for people with Parkinson’s disease. J. Neuroeng. Rehabil. 2023 20 1 94 10.1186/s12984‑023‑01219‑3 37475014
    [Google Scholar]
  67. Hidalgo-Agudo R.D. Lucena-Anton D. Luque-Moreno C. Heredia-Rizo A.M. Moral-Munoz J.A. Additional physical interventions to conventional physical therapy in Parkinson’s disease: A systematic review and meta-analysis of randomized clinical trials. J. Clin. Med. 2020 9 4 1038 10.3390/jcm9041038 32272665
    [Google Scholar]
  68. Jost W.H. A critical appraisal of MAO-B inhibitors in the treatment of Parkinson’s disease. J. Neural Transm. (Vienna) 2022 129 5-6 723 736 10.1007/s00702‑022‑02465‑w 35107654
    [Google Scholar]
  69. Jenner P. Rocha J.F. Ferreira J.J. Rascol O. Soares-da-Silva P. Redefining the strategy for the use of COMT inhibitors in Parkinson’s disease: The role of opicapone. Expert Rev. Neurother. 2021 21 9 1019 1033 10.1080/14737175.2021.1968298 34525893
    [Google Scholar]
  70. Khan S.T. Ahmed S. Gul S. Khan A. Al-Harrasi A. Search for safer and potent natural inhibitors of Parkinson’s disease. Neurochem. Int. 2021 149 105135 10.1016/j.neuint.2021.105135 34271080
    [Google Scholar]
  71. Rascol O. Fabbri M. Poewe W. Amantadine in the treatment of Parkinson’s disease and other movement disorders. Lancet Neurol. 2021 20 12 1048 1056 10.1016/S1474‑4422(21)00249‑0 34678171
    [Google Scholar]
  72. Antonini A. Odin P. Pahwa R. Aldred J. Alobaidi A. Jalundhwala Y.J. Kukreja P. Bergmann L. Inguva S. Bao Y. Chaudhuri K.R. The long-term impact of levodopa/carbidopa intestinal gel on ‘off’-time in patients with advanced Parkinson’s disease: A systematic review. Adv. Ther. 2021 38 6 2854 2890 10.1007/s12325‑021‑01747‑1 34018146
    [Google Scholar]
  73. Yin R. The positive role and mechanism of herbal medicine in Parkinson’s disease. Oxid. Med. Cell. Longev. 2021 2021 9923331 10.1155/2021/9923331
    [Google Scholar]
  74. Jankovic J. Tan E.K. Parkinson’s disease: Etiopathogenesis and treatment. J. Neurol. Neurosurg. Psychiatry 2020 91 8 795 808 10.1136/jnnp‑2019‑322338 32576618
    [Google Scholar]
  75. Wang H.Y. Hao X. Lu R. Li T. Pu L. Liu W. Liang Z. Effects of trihexyphenidyl on prefrontal executive function and spontaneous neural activity in patients with tremor-dominant Parkinson’s disease: An fNIRS study. Parkinsonism Relat. Disord. 2022 105 96 102 10.1016/j.parkreldis.2022.11.012 36401901
    [Google Scholar]
  76. Friedman J.H. Koller W.C. Lannon M.C. Busenbark K. Swanson-Hyland E. Smith D. Benztropine versus clozapine for the treatment of tremor in Parkinson’s disease. Neurology 1997 48 4 1077 1080 10.1212/WNL.48.4.1077 9109903
    [Google Scholar]
  77. Nataraj J. Manivasagam T. Thenmozhi A.J. Essa M.M. Lutein protects dopaminergic neurons against MPTP-induced apoptotic death and motor dysfunction by ameliorating mitochondrial disruption and oxidative stress. Nutr. Neurosci. 2016 19 6 237 246 10.1179/1476830515Y.0000000010 25730317
    [Google Scholar]
  78. Baluchnejadmojarad T. Jamali-Raeufy N. Zabihnejad S. Rabiee N. Roghani M. Troxerutin exerts neuroprotection in 6-hydroxydopamine lesion rat model of Parkinson’s disease: Possible involvement of PI3K/ERβ signaling. Eur. J. Pharmacol. 2017 801 72 78 10.1016/j.ejphar.2017.03.002 28284752
    [Google Scholar]
  79. Antunes M.S. Cattelan Souza L. Ladd F.V.L. Ladd A.A.B.L. Moreira A.L. Bortolotto V.C. Silva M.R.P. Araújo S.M. Prigol M. Nogueira C.W. Boeira S.P. Hesperidin ameliorates anxiety-depressive-like behavior in 6-OHDA model of Parkinson’s disease by regulating striatal cytokine and neurotrophic factors levels and dopaminergic innervation loss in the striatum of mice. Mol. Neurobiol. 2020 57 7 3027 3041 10.1007/s12035‑020‑01940‑3 32458386
    [Google Scholar]
  80. Hung K.C. Huang H.J. Wang Y.T. Lin A.M.Y. Baicalein attenuates α-synuclein aggregation, inflammasome activation and autophagy in the MPP+-treated nigrostriatal dopaminergic system in vivo. J. Ethnopharmacol. 2016 194 522 529 10.1016/j.jep.2016.10.040 27742410
    [Google Scholar]
  81. Jiang M. Yun Q. Niu G. Gao Y. Shi F. Yu S. Puerarin prevents inflammation and apoptosis in the neurocytes of a murine Parkinson’s disease model. Genet. Mol. Res. 2016 15 4 1 9 10.4238/gmr.15047501 27808353
    [Google Scholar]
  82. Guo Y.J. Dong S.Y. Cui X.X. Feng Y. Liu T. Yin M. Kuo S.H. Tan E.K. Zhao W.J. Wu Y.C. Resveratrol alleviates MPTP‐induced motor impairments and pathological changes by autophagic degradation of α‐synuclein via SIRT1‐deacetylated LC3. Mol. Nutr. Food Res. 2016 60 10 2161 2175 10.1002/mnfr.201600111 27296520
    [Google Scholar]
  83. Song S. Nie Q. Li Z. Du G. Curcumin improves neurofunctions of 6-OHDA-induced parkinsonian rats. Pathol. Res. Pract. 2016 212 4 247 251 10.1016/j.prp.2015.11.012 26922613
    [Google Scholar]
  84. Wongtrakul J. Thongtan T. Kumrapich B. Saisawang C. Ketterman A.J. Neuroprotective effects of Withania somnifera in the SH-SY5Y Parkinson cell model. Heliyon 2021 7 10 08172 10.1016/j.heliyon.2021.e08172 34765761
    [Google Scholar]
  85. Mani S. Sekar S. Barathidasan R. Manivasagam T. Thenmozhi A.J. Sevanan M. Chidambaram S.B. Essa M.M. Guillemin G.J. Sakharkar M.K. Naringenin decreases α-synuclein expression and neuroinflammation in MPTP-induced Parkinson’s disease model in mice. Neurotox. Res. 2018 33 3 656 670 10.1007/s12640‑018‑9869‑3 29427283
    [Google Scholar]
  86. Zhu Y.L. Sun M.F. Jia X.B. Cheng K. Xu Y.D. Zhou Z.L. Zhang P.H. Qiao C.M. Cui C. Chen X. Yang X.S. Shen Y.Q. Neuroprotective effects of Astilbin on MPTP-induced Parkinson’s disease mice: Glial reaction, α-synuclein expression and oxidative stress. Int. Immunopharmacol. 2019 66 19 27 10.1016/j.intimp.2018.11.004 30419450
    [Google Scholar]
  87. Del Fabbro L. Chrysin protects against behavioral, cognitive and neurochemical alterations in a 6-hydroxydopamine model of Parkinson's disease. Neurosci. Lett. 2019 706 158 163 10.1016/j.neulet.2019.05.036
    [Google Scholar]
  88. Wang J. Ni Q. Wang Y. Zhang Y. He H. Gao D. Ma X. Liang X.J. Nanoscale drug delivery systems for controllable drug behaviors by multi-stage barrier penetration. J. Control. Release 2021 331 282 295 10.1016/j.jconrel.2020.08.045 32866590
    [Google Scholar]
  89. Knox E.G. Aburto M.R. Clarke G. Cryan J.F. O’Driscoll C.M. The blood-brain barrier in aging and neurodegeneration. Mol. Psychiatry 2022 27 6 2659 2673 10.1038/s41380‑022‑01511‑z 35361905
    [Google Scholar]
  90. Reddy S. Tatiparti K. Sau S. Iyer A.K. Recent advances in nano delivery systems for blood-brain barrier (BBB) penetration and targeting of brain tumors. Drug Discov. Today 2021 26 8 1944 1952 10.1016/j.drudis.2021.04.008 33865978
    [Google Scholar]
  91. Piantino M. Louis F. Shigemoto-Mogami Y. Kitamura K. Sato K. Yamaguchi T. Kawabata K. Yamamoto S. Iwasaki S. Hirabayashi H. Matsusaki M. Brain microvascular endothelial cells derived from human induced pluripotent stem cells as in vitro model for assessing blood-brain barrier transferrin receptor-mediated transcytosis. Mater. Today Bio 2022 14 100232 10.1016/j.mtbio.2022.100232 35308041
    [Google Scholar]
  92. Abdul Razzak R. Florence G.J. Gunn-Moore F.J. Approaches to CNS drug delivery with a focus on transporter-mediated transcytosis. Int. J. Mol. Sci. 2019 20 12 3108 10.3390/ijms20123108 31242683
    [Google Scholar]
  93. Gavas S. Quazi S. Karpiński T.M. Nanoparticles for cancer therapy: Current progress and challenges. Nanoscale Res. Lett. 2021 16 1 173 10.1186/s11671‑021‑03628‑6 34866166
    [Google Scholar]
  94. Mitchell M.J. Billingsley M.M. Haley R.M. Wechsler M.E. Peppas N.A. Langer R. Engineering precision nanoparticles for drug delivery. Nat. Rev. Drug Discov. 2021 20 2 101 124 10.1038/s41573‑020‑0090‑8 33277608
    [Google Scholar]
  95. Begines B. Ortiz T. Pérez-Aranda M. Martínez G. Merinero M. Argüelles-Arias F. Alcudia A. Polymeric nanoparticles for drug delivery: Recent developments and future prospects. Nanomaterials 2020 10 7 1403 10.3390/nano10071403 32707641
    [Google Scholar]
  96. Zielińska A. Carreiró F. Oliveira A.M. Neves A. Pires B. Venkatesh D.N. Durazzo A. Lucarini M. Eder P. Silva A.M. Santini A. Souto E.B. Polymeric nanoparticles: Production, characterization, toxicology and ecotoxicology. Molecules 2020 25 16 3731 10.3390/molecules25163731 32824172
    [Google Scholar]
  97. Chen T. Liu W. Xiong S. Li D. Fang S. Wu Z. Wang Q. Chen X. Nanoparticles mediating the sustained puerarin release facilitate improved brain delivery to treat Parkinson’s disease. ACS Appl. Mater. Interfaces 2019 11 48 45276 45289 10.1021/acsami.9b16047 31638771
    [Google Scholar]
  98. Xiong S. Liu W. Li D. Chen X. Liu F. Yuan D. Pan H. Wang Q. Fang S. Chen T. Oral delivery of puerarin nanocrystals to improve brain accumulation and anti-parkinsonian efficacy. Mol. Pharm. 2019 16 4 1444 1455 10.1021/acs.molpharmaceut.8b01012 30811206
    [Google Scholar]
  99. Chen T. Li C. Li Y. Yi X. Wang R. Lee S.M.Y. Zheng Y. Small-sized mPEG–PLGA nanoparticles of Schisantherin A with sustained release for enhanced brain uptake and anti-parkinsonian activity. ACS Appl. Mater. Interfaces 2017 9 11 9516 9527 10.1021/acsami.7b01171 28247754
    [Google Scholar]
  100. Esteves M. Cristóvão A.C. Saraiva T. Rocha S.M. Baltazar G. Ferreira L. Bernardino L. Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model for Parkinson’s disease. Front. Aging Neurosci. 2015 7 20 10.3389/fnagi.2015.00020 25798108
    [Google Scholar]
  101. Zhao Y. Xiong S. Liu P. Liu W. Wang Q. Liu Y. Tan H. Chen X. Shi X. Wang Q. Chen T. Polymeric nanoparticles-based brain delivery with improved therapeutic efficacy of ginkgolide B in Parkinson’s disease. Int. J. Nanomedicine 2020 15 10453 10467 10.2147/IJN.S272831 33380795
    [Google Scholar]
  102. Ahmad M.Z. Sabri A.H.B. Anjani Q.K. Domínguez-Robles J. Abdul Latip N. Hamid K.A. Design and development of levodopa loaded polymeric nanoparticles for intranasal delivery. Pharmaceuticals 2022 15 3 370 10.3390/ph15030370 35337167
    [Google Scholar]
  103. Amina S.J. Guo B. A review on the synthesis and functionalization of gold nanoparticles as a drug delivery vehicle. Int. J. Nanomedicine 2020 15 9823 9857 10.2147/IJN.S279094 33324054
    [Google Scholar]
  104. Xue J. Liu T. Liu Y. Jiang Y. Seshadri V.D.D. Mohan S.K. Ling L. Neuroprotective effect of biosynthesised gold nanoparticles synthesised from root extract of Paeonia moutan against Parkinson disease – In vitro & In vivo model. J. Photochem. Photobiol. B 2019 200 111635 10.1016/j.jphotobiol.2019.111635 31671372
    [Google Scholar]
  105. da Silva Córneo E. de Bem Silveira G. Scussel R. Correa M.E.A.B. da Silva Abel J. Luiz G.P. Feuser P.E. Silveira P.C.L. Machado-de-Ávila R.A. Effects of gold nanoparticles administration through behavioral and oxidative parameters in animal model of Parkinson’s disease. Colloids Surf. B Biointerfaces 2020 196 111302 10.1016/j.colsurfb.2020.111302 32777662
    [Google Scholar]
  106. Liu L. Li M. Xu M. Wang Z. Zeng Z. Li Y. Zhang Y. You R. Li C.H. Guan Y.Q. Actively targeted gold nanoparticle composites improve behavior and cognitive impairment in Parkinson’s disease mice. Mater. Sci. Eng. C 2020 114 111028 10.1016/j.msec.2020.111028 32994016
    [Google Scholar]
  107. Prasher P. Sharma M. Mudila H. Gupta G. Sharma A.K. Kumar D. Bakshi H.A. Negi P. Kapoor D.N. Chellappan D.K. Tambuwala M.M. Dua K. Emerging trends in clinical implications of bio-conjugated silver nanoparticles in drug delivery. Colloid Interface Sci. Commun. 2020 35 100244 10.1016/j.colcom.2020.100244
    [Google Scholar]
  108. Gonzalez-Carter D.A. Leo B.F. Ruenraroengsak P. Chen S. Goode A.E. Theodorou I.G. Chung K.F. Carzaniga R. Shaffer M.S.P. Dexter D.T. Ryan M.P. Porter A.E. Silver nanoparticles reduce brain inflammation and related neurotoxicity through induction of H2S-synthesizing enzymes. Sci. Rep. 2017 7 1 42871 10.1038/srep42871 28251989
    [Google Scholar]
  109. Naz F. Rahul Fatima M. Naseem S. Khan W. Mondal A.C. Siddique Y.H. Ropinirole silver nanocomposite attenuates neurodegeneration in the transgenic Drosophila melanogaster model of Parkinson’s disease. Neuropharmacology 2020 177 108216 10.1016/j.neuropharm.2020.108216 32707222
    [Google Scholar]
  110. Devaraju Kuramkote Shivanna Gopinath G Hanumanthappa Ramesha Babu Ramesh Datura Stramonium leaves extract Silver Nanoparticles regulates PINK1 gene in Parkinson’s disease model of Drosophila melanogaster. Res. Square 2022 1 10.21203/rs.3.rs‑1807001/v1
    [Google Scholar]
  111. Ziental D. Czarczynska-Goslinska B. Mlynarczyk D.T. Glowacka-Sobotta A. Stanisz B. Goslinski T. Sobotta L. Titanium dioxide nanoparticles: Prospects and applications in medicine. Nanomaterials 2020 10 2 387 10.3390/nano10020387 32102185
    [Google Scholar]
  112. Hu Q. Guo F. Zhao F. Fu Z. Effects of titanium dioxide nanoparticles exposure on parkinsonism in zebrafish larvae and PC12. Chemosphere 2017 173 373 379 10.1016/j.chemosphere.2017.01.063 28129614
    [Google Scholar]
  113. Waris A. Din M. Ali A. Ali M. Afridi S. Baset A. Ullah Khan A. A comprehensive review of green synthesis of copper oxide nanoparticles and their diverse biomedical applications. Inorg. Chem. Commun. 2021 123 108369 10.1016/j.inoche.2020.108369
    [Google Scholar]
  114. Shahsavari M. Tajik S. Sheikhshoaie I. Garkani Nejad F. Beitollahi H. Synthesis of Fe3O4@copper(II) imidazolate nanoparticles: Catalytic activity of modified graphite screen printed electrode for the determination of levodopa in presence of melatonin. Microchem. J. 2021 170 106637 10.1016/j.microc.2021.106637
    [Google Scholar]
  115. Kazi M. Al-Swairi M. Ahmad A. Raish M. Alanazi F.K. Badran M.M. Khan A.A. Alanazi A.M. Hussain M.D. Evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for poorly water-soluble talinolol: Preparation, in vitro and in vivo assessment. Front. Pharmacol. 2019 10 459 10.3389/fphar.2019.00459 31118895
    [Google Scholar]
  116. Kumar R. Kumar R. Khurana N. Singh S.K. Khurana S. Verma S. Sharma N. Kapoor B. Vyas M. Khursheed R. Awasthi A. Kaur J. Corrie L. Enhanced oral bioavailability and neuroprotective effect of fisetin through its SNEDDS against rotenone-induced Parkinson’s disease rat model. Food Chem. Toxicol. 2020 144 111590 10.1016/j.fct.2020.111590 32710995
    [Google Scholar]
  117. Sharma S. Narang J.K. Ali J. Baboota S. Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson’s disease model. Nanotechnology 2016 27 37 375101 10.1088/0957‑4484/27/37/375101 27491690
    [Google Scholar]
  118. Satapathy M.K. Yen T.L. Jan J.S. Tang R.D. Wang J.Y. Taliyan R. Yang C.H. Solid lipid nanoparticles (SLNs): An advanced drug delivery system targeting brain through BBB. Pharmaceutics 2021 13 8 1183 10.3390/pharmaceutics13081183 34452143
    [Google Scholar]
  119. Kundu P. Das M. Tripathy K. Sahoo S.K. Delivery of dual drug loaded lipid based nanoparticles across the blood–brain barrier impart enhanced neuroprotection in a rotenone induced mouse model of Parkinson’s disease. ACS Chem. Neurosci. 2016 7 12 1658 1670 10.1021/acschemneuro.6b00207 27642670
    [Google Scholar]
  120. Uppuluri C.T. Ravi P.R. Dalvi A.V. Design, optimization and pharmacokinetic evaluation of Piribedil loaded solid lipid nanoparticles dispersed in nasal in situ gelling system for effective management of Parkinson’s disease. Int. J. Pharm. 2021 606 120881 10.1016/j.ijpharm.2021.120881 34273426
    [Google Scholar]
  121. Esposito E. Fantin M. Marti M. Drechsler M. Paccamiccio L. Mariani P. Sivieri E. Lain F. Menegatti E. Morari M. Cortesi R. Solid lipid nanoparticles as delivery systems for bromocriptine. Pharm. Res. 2008 25 7 1521 1530 10.1007/s11095‑007‑9514‑y 18172580
    [Google Scholar]
  122. Dang H. Meng M.H.W. Zhao H. Iqbal J. Dai R. Deng Y. Lv F. Luteolin-loaded solid lipid nanoparticles synthesis, characterization, & improvement of bioavailability, pharmacokinetics in vitro and vivo studies. J. Nanopart. Res. 2014 16 4 2347 10.1007/s11051‑014‑2347‑9
    [Google Scholar]
  123. Chauhan I. Yasir M. Verma M. Singh A.P. Nanostructured lipid carriers: A groundbreaking approach for transdermal drug delivery. Adv. Pharm. Bull. 2020 10 2 150 165 10.34172/apb.2020.021 32373485
    [Google Scholar]
  124. Neha S.L. Mishra A.K. Rani L. Paroha S. Dewangan H.K. Sahoo P.K. Design and evaluations of a nanostructured lipid carrier loaded with dopamine hydrochloride for intranasal bypass drug delivery in Parkinson’s disease. J. Microencapsul. 2023 40 8 599 612 10.1080/02652048.2023.2264386 37787159
    [Google Scholar]
  125. Hassan D.M. Chitosan-coated nanostructured lipid carriers for effective brain delivery of Tanshinone IIA in Parkinson’s disease: Interplay between nuclear factor-kappa β and cathepsin B. Drug Deliv. Transl. Res. 2023 37598133
    [Google Scholar]
  126. Kumar M. Bishnoi R.S. Shukla A.K. Jain C.P. Techniques for formulation of nanoemulsion drug delivery system: A review. Prev. Nutr. Food Sci. 2019 24 3 225 234 10.3746/pnf.2019.24.3.225 31608247
    [Google Scholar]
  127. Nehal N. Nabi B. Rehman S. Pathak A. Iqubal A. Khan S.A. Yar M.S. Parvez S. Baboota S. Ali J. Chitosan coated synergistically engineered nanoemulsion of Ropinirole and nigella oil in the management of Parkinson’s disease: Formulation perspective and In vitro and In vivo assessment. Int. J. Biol. Macromol. 2021 167 605 619 10.1016/j.ijbiomac.2020.11.207 33278450
    [Google Scholar]
  128. Gaba B. Khan T. Haider M.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 10.1155/2019/2382563 31111044
    [Google Scholar]
  129. Ramires Júnior O.V. Alves B.S. Barros P.A.B. Rodrigues J.L. Ferreira S.P. Monteiro L.K.S. Araújo G.M.S. Fernandes S.S. Vaz G.R. Dora C.L. Hort M.A. Nanoemulsion improves the neuroprotective effects of curcumin in an experimental model of Parkinson’s disease. Neurotox. Res. 2021 39 3 787 799 10.1007/s12640‑021‑00362‑w 33860897
    [Google Scholar]
  130. Gupta B.K. Kumar S. Kaur H. Ali J. Baboota S. Attenuation of oxidative damage by coenzyme Q10 loaded nanoemulsion through oral route for the management of Parkinson’s disease. Rejuvenation Res. 2018 21 3 232 248 10.1089/rej.2017.1959 28844183
    [Google Scholar]
  131. Kaur J. Gill G.S. Jeet K. Applications of carbon nanotubes in drug delivery: A comprehensive review. Characterization and Biology of Nanomaterials for Drug Delivery Amsterdam, Netherlands Elsevier 2019 113 135 10.1016/B978‑0‑12‑814031‑4.00005‑2
    [Google Scholar]
  132. Alimohammadi E. Nikzad A. Khedri M. Rezaian M. Jahromi A.M. Rezaei N. Maleki R. Potential treatment of Parkinson’s disease using new-generation carbon nanotubes: A biomolecular in silico study. Nanomedicine 2021 16 3 189 204 10.2217/nnm‑2020‑0372 33502255
    [Google Scholar]
  133. Zhang R. Wang S. Huang X. Yang Y. Fan H. Yang F. Li J. Dong X. Feng S. Anbu P. Gopinath S.C.B. Xin T. Gold-nanourchin seeded single-walled carbon nanotube on voltammetry sensor for diagnosing neurogenerative Parkinson’s disease. Anal. Chim. Acta 2020 1094 142 150 10.1016/j.aca.2019.10.012 31761041
    [Google Scholar]
  134. Ferrer-Lorente R. Lozano-Cruz T. Fernández-Carasa I. Miłowska K. de la Mata F.J. Bryszewska M. Consiglio A. Ortega P. Gómez R. Raya A. Cationic carbosilane dendrimers prevent abnormal α-synuclein accumulation in Parkinson’s disease patient-specific dopamine neurons. Biomacromolecules 2021 22 11 4582 4591 10.1021/acs.biomac.1c00884 34613701
    [Google Scholar]
  135. Posadas I. López-Hernández B. Clemente M.I. Jiménez J.L. Ortega P. de la Mata J. Gómez R. Muñoz-Fernández M.A. Ceña V. Highly efficient transfection of rat cortical neurons using carbosilane dendrimers unveils a neuroprotective role for HIF-1alpha in early chemical hypoxia-mediated neurotoxicity. Pharm. Res. 2009 26 5 1181 1191 10.1007/s11095‑009‑9839‑9 19191011
    [Google Scholar]
  136. Qushawy M. Alenzi A.M. Albalawi S.A. Alghamdi S.G. Albalawi R.F. Albalawi H.S. Review on different vesicular drug delivery systems (VDDSs) and their applications. Recent Pat. Nanotechnol. 2023 17 1 18 32 10.2174/1872210516666220228150624 35227188
    [Google Scholar]
  137. Cao Y. Dong X. Chen X. Polymer-modified liposomes for drug delivery: From fundamentals to applications. Pharmaceutics 2022 14 4 778 10.3390/pharmaceutics14040778 35456613
    [Google Scholar]
  138. Zhigaltsev I.V. Kaplun A.P. Kucheryanu V.G. Kryzhanovsky G.N. Kolomeichuk S.N. Shvets V.I. Yurasov V.V. Liposomes containing dopamine entrapped in response to transmembrane ammonium sulfate gradient as carrier system for dopamine delivery into the brain of parkinsonian mice. J. Liposome Res. 2001 11 1 55 71 10.1081/LPR‑100103170 19530919
    [Google Scholar]
  139. Kahana M. Weizman A. Gabay M. Loboda Y. Segal-Gavish H. Gavish A. Barhum Y. Offen D. Finberg J. Allon N. Gavish M. Liposome-based targeting of dopamine to the brain: A novel approach for the treatment of Parkinson’s disease. Mol. Psychiatry 2021 26 6 2626 2632 10.1038/s41380‑020‑0742‑4 32372010
    [Google Scholar]
  140. Marino A. Battaglini M. Desii A. Lavarello C. Genchi G. Petretto A. Ciofani G. Liposomes loaded with polyphenol-rich grape pomace extracts protect from neurodegeneration in a rotenone-based in vitro model of Parkinson’s disease. Biomater. Sci. 2021 9 24 8171 8188 10.1039/D1BM01202A 34617936
    [Google Scholar]
  141. Sela M. Poley M. Mora-Raimundo P. Kagan S. Avital A. Kaduri M. Chen G. Adir O. Rozencweig A. Weiss Y. Sade O. Leichtmann-Bardoogo Y. Simchi L. Aga-Mizrachi S. Bell B. Yeretz-Peretz Y. Or A.Z. Choudhary A. Rosh I. Cordeiro D. Cohen-Adiv S. Berdichevsky Y. Odeh A. Shklover J. Shainsky-Roitman J. Schroeder J.E. Hershkovitz D. Hasson P. Ashkenazi A. Stern S. Laviv T. Ben-Zvi A. Avital A. Ashery U. Maoz B.M. Schroeder A. Brain‐targeted liposomes loaded with monoclonal antibodies reduce alpha‐synuclein aggregation and improve behavioral symptoms in Parkinson’s disease. Adv. Mater. 2023 35 51 2304654 10.1002/adma.202304654 37753928
    [Google Scholar]
  142. Wang M. Li L. Zhang X. Liu Y. Zhu R. Liu L. Fang Y. Gao Z. Gao D. Magnetic resveratrol liposomes as a new theranostic platform for magnetic resonance imaging guided Parkinson’s disease targeting therapy. ACS Sustain. Chem. Eng. 2018 6 12 17124 17133 10.1021/acssuschemeng.8b04507
    [Google Scholar]
  143. Zarrin P. Dehghani Ashkezari M. Seifati S.M. Liposomal form of L-dopa and SH-Sy5y cell-derived exosomes modulate the tyrosine hydroxylase/dopamine receptor D2 signaling pathway in Parkinson’s rat models. J. Mol. Neurosci. 2021 71 12 2583 2592 10.1007/s12031‑021‑01853‑3 34125397
    [Google Scholar]
  144. Kauslya A. Borawake P.D. Shinde J.V. Chavan R.S. Niosomes: A novel carrier drug delivery system. J. Drug Deliv. Ther. 2021 11 1 162 170 10.22270/jddt.v11i1.4479
    [Google Scholar]
  145. Sita V.G. Jadhav D. Vavia P. Niosomes for nose-to-brain delivery of bromocriptine: Formulation development, efficacy evaluation and toxicity profiling. J. Drug Deliv. Sci. Technol. 2020 58 101791 10.1016/j.jddst.2020.101791
    [Google Scholar]
  146. Hatami Nemati S. Bigdeli M.R. Mortazavi Moghadam F. Sharifi K. Neuroprotective effects of niosomes loaded with thymoquinone in the cerebral ischemia model of male Wistar rats. Nanomedicine 2023 48 102637 10.1016/j.nano.2022.102637 36549552
    [Google Scholar]
  147. Daneshvar A. Jouzdani A.F. Firozian F. Asl S.S. Mohammadi M. Ranjbar A. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats. Open Life Sci. 2022 17 1 1174 1181 10.1515/biol‑2022‑0468 36185402
    [Google Scholar]
  148. Esposito E. Pecorelli A. Ferrara F. Lila M.A. Valacchi G. Feeding the Body Through the Skin: Ethosomes and Transethosomes as a New Topical Delivery System for Bioactive Compounds. Annu. Rev. Food Sci. Technol. 2024 15 1 53 78 10.1146/annurev‑food‑072023‑034528 38941493
    [Google Scholar]
  149. Kumar N. Ethosomes: A novel approach in transdermal drug delivery system. Inter. J. Pharm. Life Sci. 2020 11 5 6598 6608
    [Google Scholar]
  150. Mishra N. Development of intranasal deformable ethosomes of rasagiline mesylate for the effective management of parkinsonism. Int. J. Pharm. Biol. Sci. 2020 10 25 33
    [Google Scholar]
  151. Matharoo N. Mohd H. Michniak-Kohn B. Transferosomes as a transdermal drug delivery system: Dermal kinetics and recent developments. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 2024 16 1 1918 10.1002/wnan.1918 37527953
    [Google Scholar]
  152. Chen R.P. Chavda V.P. Patel A.B. Chen Z.S. Phytochemical delivery through transferosome (phytosome): An advanced transdermal drug delivery for complementary medicines. Front. Pharmacol. 2022 13 850862 10.3389/fphar.2022.850862 35281927
    [Google Scholar]
  153. ElShagea H.N. Makar R.R. Salama A.H. Elkasabgy N.A. Basalious E.B. Investigating the targeting power to brain tissues of intranasal rasagiline mesylate-loaded transferosomal in situ gel for efficient treatment of parkinson’s disease. Pharmaceutics 2023 15 2 533 10.3390/pharmaceutics15020533 36839855
    [Google Scholar]
  154. Langasco R. Fancello S. Rassu G. Cossu M. Cavalli R. Galleri G. Giunchedi P. Migheli R. Gavini E. Increasing protective activity of genistein by loading into transfersomes: A new potential adjuvant in the oxidative stress-related neurodegenerative diseases? Phytomedicine 2019 52 23 31 10.1016/j.phymed.2018.09.207 30599903
    [Google Scholar]
  155. Zheng Y. Oz Y. Gu Y. Ahamad N. Shariati K. Chevalier J. Kapur D. Annabi N. Rational design of polymeric micelles for targeted therapeutic delivery. Nano Today 2024 55 102147 10.1016/j.nantod.2024.102147
    [Google Scholar]
  156. Kotta S. Aldawsari H.M. Badr-Eldin S.M. Nair A.B. Yt K. Progress in polymeric micelles for drug delivery applications. Pharmaceutics 2022 14 8 1636 10.3390/pharmaceutics14081636 36015262
    [Google Scholar]
  157. Ghezzi M. Pescina S. Padula C. Santi P. Del Favero E. Cantù L. Nicoli S. Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions. J. Control. Release 2021 332 312 336 10.1016/j.jconrel.2021.02.031 33652113
    [Google Scholar]
  158. Wang F. Yang Z. Liu M. Tao Y. Li Z. Wu Z. Gui S. Facile nose-to-brain delivery of rotigotine-loaded polymer micelles thermosensitive hydrogels: In vitro characterization and in vivo behavior study. Int. J. Pharm. 2020 577 119046 10.1016/j.ijpharm.2020.119046 31982559
    [Google Scholar]
  159. Zhang L. Yang S. Huang L. Ho P.C.L. Poly (ethylene glycol)-block-poly (D, L-lactide) (PEG-PLA) micelles for brain delivery of baicalein through nasal route for potential treatment of neurodegenerative diseases due to oxidative stress and inflammation: An in vitro and in vivo study. Int. J. Pharm. 2020 591 119981 10.1016/j.ijpharm.2020.119981 33069896
    [Google Scholar]
  160. Arisoy S. Sayiner O. Comoglu T. Onal D. Atalay O. Pehlivanoglu B. In vitro and in vivo evaluation of levodopa-loaded nanoparticles for nose to brain delivery. Pharm. Dev. Technol. 2020 25 6 735 747 10.1080/10837450.2020.1740257 32141798
    [Google Scholar]
  161. Monge-Fuentes V. Biolchi Mayer A. Lima M.R. Geraldes L.R. Zanotto L.N. Moreira K.G. Martins O.P. Piva H.L. Felipe M.S.S. Amaral A.C. Bocca A.L. Tedesco A.C. Mortari M.R. Dopamine-loaded nanoparticle systems circumvent the blood–brain barrier restoring motor function in mouse model for Parkinson’s Disease. Sci. Rep. 2021 11 1 15185 10.1038/s41598‑021‑94175‑8 34312413
    [Google Scholar]
  162. Pahuja R. Seth K. Shukla A. Shukla R.K. Bhatnagar P. Chauhan L.K.S. Saxena P.N. Arun J. Chaudhari B.P. Patel D.K. Singh S.P. Shukla R. Khanna V.K. Kumar P. Chaturvedi R.K. Gupta K.C. Trans-blood brain barrier delivery of dopamine-loaded nanoparticles reverses functional deficits in parkinsonian rats. ACS Nano 2015 9 5 4850 4871 10.1021/nn506408v 25825926
    [Google Scholar]
  163. Pandey P.K. Sharma A.K. Rani S. Mishra G. Kandasamy G. Patra A.K. Rana M. Sharma A.K. Yadav A.K. Gupta U. MCM-41 nanoparticles for brain delivery: Better choline-esterase and amyloid formation inhibition with improved kinetics. ACS Biomater. Sci. Eng. 2018 4 8 2860 2869 10.1021/acsbiomaterials.8b00335 33435009
    [Google Scholar]
  164. Díaz-García D. Ferrer-Donato Á. Méndez-Arriaga J.M. Cabrera-Pinto M. Díaz-Sánchez M. Prashar S. Fernandez-Martos C.M. Gómez-Ruiz S. Design of mesoporous silica nanoparticles for the treatment of amyotrophic lateral sclerosis (als) with a therapeutic cocktail based on leptin and pioglitazone. ACS Biomater. Sci. Eng. 2022 8 11 4838 4849 10.1021/acsbiomaterials.2c00865 36240025
    [Google Scholar]
  165. Swar S. Máková V. Stibor I. Effectiveness of diverse mesoporous silica nanoparticles as potent vehicles for the drug L-DOPA. Materials 2019 12 19 3202 10.3390/ma12193202 31574906
    [Google Scholar]
  166. Kaliyaperumal P. Renganathan S. Arumugam K. Aremu B.R. Engineered graphene quantum dot nanocomposite triggers α-synuclein defibrillation: Therapeutics against Parkinson’s disease. Nanomedicine 2023 47 102608 10.1016/j.nano.2022.102608 36228996
    [Google Scholar]
  167. Lin D. Li M. Gao Y. Yin L. Guan Y. Brain-targeted gene delivery of ZnO quantum dots nanoplatform for the treatment of Parkinson disease. Chem. Eng. J. 2022 429 132210 10.1016/j.cej.2021.132210
    [Google Scholar]
  168. Imamura Y. Okuzumi A. Yoshinaga S. Hiyama A. Furukawa Y. Miyasaka T. Hattori N. Nukina N. Quantum-dot-labeled synuclein seed assay identifies drugs modulating the experimental prion-like transmission. Commun. Biol. 2022 5 1 636 10.1038/s42003‑022‑03590‑8 35768587
    [Google Scholar]
  169. Henriquez G. Ahlawat J. Fairman R. Narayan M. Citric acid-derived carbon quantum dots attenuate paraquat-induced neuronal compromise in vitro and in vivo. ACS Chem. Neurosci. 2022 13 16 2399 2409 10.1021/acschemneuro.2c00099 35942850
    [Google Scholar]
  170. Ahlawat J. Narayan M. Multifunctional carbon quantum dots prevent soluble-to-toxic transformation of amyloid and oxidative stress. ACS Sustain. Chem. Eng. 2022 10 14 4610 4622 10.1021/acssuschemeng.1c08638
    [Google Scholar]
  171. Chen Y.B. Qiao T. Wang Y-Q. Cui Y-L. Wang Q-S. Hydrogen bond-enhanced nanogel delivery system for potential intranasal therapy of Parkinson’s disease. Mater. Des. 2022 219 110741 10.1016/j.matdes.2022.110741
    [Google Scholar]
  172. Chittasupho C. Tadtong S. Vorarat S. Imaram W. Athikomkulchai S. Samee W. Sareedenchai V. Thongnopkoon T. Okonogi S. Kamkaen N. Development of jelly loaded with nanogel containing natural l-dopa from Mucuna pruriens seed extract for neuroprotection in parkinson’s disease. Pharmaceutics 2022 14 5 1079 10.3390/pharmaceutics14051079 35631666
    [Google Scholar]
  173. Saha P. Singh P. Kathuria H. Chitkara D. Pandey M.M. Self-assembled lecithin-chitosan nanoparticles improved rotigotine nose-to-brain delivery and brain targeting efficiency. Pharmaceutics 2023 15 3 851 10.3390/pharmaceutics15030851 36986712
    [Google Scholar]
  174. Rukmangathen R. Yallamalli I.M. Yalavarthi P.R. Biopharmaceutical potential of selegiline loaded chitosan nanoparticles in the management of Parkinson’s disease. Curr. Drug Discov. Technol. 2019 16 4 417 425 10.2174/1570163815666180418144019 29669501
    [Google Scholar]
  175. Yuan H. Bai X.L. Hu Y.K. Fan W.Q. Ayeni E.A. Liao X. Ligand fishing of monoamine oxidase B inhibitors from Platycodon grandiflorus (Jacq.) A.DC. roots by the enzyme functionalised magnetic nanoparticles. Phytochem. Anal. 2023 34 1 67 75 10.1002/pca.3180 36254558
    [Google Scholar]
  176. Wang X. Zhao J. Wang W. Lu M. Qu A. Sun M. Gao X. Chen C. Kuang H. Xu C. Xu L. Electromagnetic field-enhanced chiral dimanganese trioxide nanoparticles mitigate Parkinson’s disease. Sci. China Chem. 2022 65 10 1911 1920 10.1007/s11426‑022‑1321‑0
    [Google Scholar]
  177. Turna Demir F. Demir E. Exposure to boron trioxide nanoparticles and ions cause oxidative stress, DNA damage, and phenotypic alterations in Drosophila melanogaster as an in vivo model. J. Appl. Toxicol. 2022 42 11 1854 1867 10.1002/jat.4363 35837816
    [Google Scholar]
  178. Jin M. Li N. Sheng W. Ji X. Liang X. Kong B. Yin P. Li Y. Zhang X. Liu K. Toxicity of different zinc oxide nanomaterials and dose-dependent onset and development of Parkinson’s disease-like symptoms induced by zinc oxide nanorods. Environ. Int. 2021 146 106179 10.1016/j.envint.2020.106179 33099061
    [Google Scholar]
  179. Akintunde J.K. Farai T.I. Arogundade M.R. Adeleke J.T. Biogenic zinc-oxide nanoparticles of Moringa oleifera leaves abrogates rotenone induced neuroendocrine toxicity by regulation of oxidative stress and acetylcholinesterase activity. Biochem. Biophys. Rep. 2021 26 100999 10.1016/j.bbrep.2021.100999 33948501
    [Google Scholar]
  180. Belal R. Gad A. Zinc oxide nanoparticles induce oxidative stress, genotoxicity, and apoptosis in the hemocytes of Bombyx mori larvae. Sci. Rep. 2023 13 1 3520 10.1038/s41598‑023‑30444‑y 36864109
    [Google Scholar]
  181. Mohammad Khan U.A. Saifi Z. Bora J. Warsi M.H. Abourehab M.A.S. Jain G.K. Kesharwani P. Ali A. Intranasal inorganic cerium oxide nanoparticles ameliorate oxidative stress induced motor manifestations in haloperidol-induced parkinsonism. Inflammopharmacology 2023 31 5 2571 2585 10.1007/s10787‑023‑01274‑1 37432554
    [Google Scholar]
  182. Çiçek B. Danışman B. Cerium oxide nanoparticles rescue dopaminergic neurons in Parkinson’s disease model of sh-sy5y cells via modulating NRF2 signaling and ameliorating apoptotic cell death. Arch. Basic Clin. Res. 2023 5 2 284 290 10.5152/ABCR.2023.23150
    [Google Scholar]
  183. Mohammad Khan U.A. Warsi M.H. Alkreathy H.M. Karim S. Jain G.K. Ali A. Intranasal cerium oxide nanoparticles improves locomotor activity and reduces oxidative stress and neuroinflammation in haloperidol-induced parkinsonism in rats. Front. Pharmacol. 2023 14 1188470 10.3389/fphar.2023.1188470 37324485
    [Google Scholar]
  184. Meenambal R. Kruk T. Gurgul J. Warszyński P. Jantas D. Neuroprotective effects of polyacrylic acid (PAA) conjugated cerium oxide against hydrogen peroxide- and 6-OHDA-induced SH-SY5Y cell damage. Sci. Rep. 2023 13 1 18534 10.1038/s41598‑023‑45318‑6 37898622
    [Google Scholar]
  185. Bonet-Aleta J. Garcia-Peiro J.I. Irusta S. Hueso J.L. Gold-platinum nanoparticles with core-shell configuration as efficient oxidase-like nanosensors for glutathione detection. Nanomaterials 2022 12 5 755 10.3390/nano12050755 35269243
    [Google Scholar]
  186. Salaramoli S. Amiri H. Joshaghani H.R. Hosseini M. Hashemy S.I. Bio-synthesized selenium nanoparticles ameliorate Brain oxidative stress in Parkinson disease rat models. Metab. Brain Dis. 2023 38 6 2055 2064 10.1007/s11011‑023‑01222‑6 37133801
    [Google Scholar]
  187. Turovsky E.A. Mal’tseva V.N. Sarimov R.M. Simakin A.V. Gudkov S.V. Plotnikov E.Y. Features of the cytoprotective effect of selenium nanoparticles on primary cortical neurons and astrocytes during oxygen–glucose deprivation and reoxygenation. Sci. Rep. 2022 12 1 1710 10.1038/s41598‑022‑05674‑1 35110605
    [Google Scholar]
  188. Khalil H.M.A. Azouz R.A. Hozyen H.F. Aljuaydi S.H. AbuBakr H.O. Emam S.R. Al-Mokaddem A.K. Selenium nanoparticles impart robust neuroprotection against deltamethrin-induced neurotoxicity in male rats by reversing behavioral alterations, oxidative damage, apoptosis, and neuronal loss. Neurotoxicology 2022 91 329 339 10.1016/j.neuro.2022.06.006 35753508
    [Google Scholar]
  189. Arabi F. Mansouri V. Ahmadbeigi N. Gene therapy clinical trials, where do we go? An overview. Biomed. Pharmacother. 2022 153 113324 10.1016/j.biopha.2022.113324 35779421
    [Google Scholar]
  190. Torres-Saavedra P.A. Winter K.A. An overview of phase 2 clinical trial designs. Int. J. Radiat. Oncol. Biol. Phys. 2022 112 1 22 29 10.1016/j.ijrobp.2021.07.1700
    [Google Scholar]
  191. Fan J. Lu W. Tan W. Liu X. Wang Y. Wang N. Zhuang L. Effectiveness of acupuncture for anxiety among patients with Parkinson disease. JAMA Netw. Open 2022 5 9 e2232133 e2232133 10.1001/jamanetworkopen.2022.32133 36129711
    [Google Scholar]
  192. Johansson M.E. Cameron I.G.M. Van der Kolk N.M. de Vries N.M. Klimars E. Toni I. Bloem B.R. Helmich R.C. Aerobic exercise alters brain function and structure in Parkinson’s disease: A randomized controlled trial. Ann. Neurol. 2022 91 2 203 216 10.1002/ana.26291 34951063
    [Google Scholar]
  193. Hao Z. Zhang X. Chen P. Effects of ten different exercise interventions on motor function in Parkinson’s disease patients—a network meta-analysis of randomized controlled trials. Brain Sci. 2022 12 6 698 10.3390/brainsci12060698 35741584
    [Google Scholar]
  194. Ghodsi H. Rahimi H.R. Aghili S.M. Saberi A. Shoeibi A. Evaluation of curcumin as add-on therapy in patients with Parkinson’s disease: A pilot randomized, triple-blind, placebo-controlled trial. Clin. Neurol. Neurosurg. 2022 218 107300 10.1016/j.clineuro.2022.107300 35636380
    [Google Scholar]
  195. Chaudhuri S.E. Ben Chaouch Z. Hauber B. Mange B. Zhou M. Christopher S. Bardot D. Sheehan M. Donnelly A. McLaughlin L. Caldwell B. Benz H.L. Ho M. Saha A. Gwinn K. Sheldon M. Lo A.W. Use of Bayesian decision analysis to maximize value in patient-centered randomized clinical trials in Parkinson’s disease. J. Biopharm. Stat. 2023 1 20 10.1080/10543406.2023.2170400 36861942
    [Google Scholar]
  196. Hong C.T. Chan L. Chen K.Y. Lee H.H. Huang L.K. Yang Y.C.S.H. Liu Y.R. Hu C.J. Rifaximin modifies gut microbiota and attenuates inflammation in parkinson’s disease: Preclinical and clinical studies. Cells 2022 11 21 3468 10.3390/cells11213468 36359864
    [Google Scholar]
  197. Morel T. Outcome assessment in early-stage Parkinson’s disease (PD) clinical trials: Are legacy patient-reported outcome (PRO) instruments fit for purpose. Neurology 2022 98 1570 10.1212/WNL.98.18_supplement.1570
    [Google Scholar]
  198. Camilleri M. Subramanian T. Pagan F. Isaacson S. Gil R. Hauser R.A. Feldman M. Goldstein M. Kumar R. Truong D. Chhabria N. Walter B.L. Eskenazi J. Riesenberg R. Burdick D. Tse W. Molho E. Robottom B. Bhatia P. Kadimi S. Klos K. Shprecher D. Marquez-Mendoza O. Hidalgo G. Grill S. Li G. Mandell H. Hughes M. Stephenson S. Vandersluis J. Pfeffer M. Duker A. Shivkumar V. Kinney W. MacDougall J. Zasloff M. Barbut D. Oral ENT-01 targets enteric neurons to treat constipation in Parkinson disease: A randomized controlled trial. Ann. Intern. Med. 2022 175 12 1666 1674 10.7326/M22‑1438 36343348
    [Google Scholar]
  199. Kim H. Kim E. Yun S.J. Kang M.G. Shin H.I. Oh B.M. Seo H.G. Robot-assisted gait training with auditory and visual cues in Parkinson’s disease: A randomized controlled trial. Ann. Phys. Rehabil. Med. 2022 65 3 101620 10.1016/j.rehab.2021.101620 34896605
    [Google Scholar]
  200. Camille M. Liraglutide improves non-motor function and activities of daily living in patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial (P9-11.005). Neurology 2022 98 18 3068
    [Google Scholar]
  201. 31P-MRS imaging to assess the effects of cnm-au8 on impaired neuronal redox state in Parkinson's disease (REPAIR-PD), NCT03815916. https://clinicaltrials.gov/study/NCT03815916
  202. Sustained release oral formulation for treatment of Parkinson's disease, NCT05471609. https://clinicaltrials.gov/study/NCT05471609
  203. Safety, tolerability and symptomatic efficacy of the rock-inhibitor fasudil in patients with Parkinson's disease, NCT05931575. https://clinicaltrials.gov/study/NCT05931575
  204. Light therapy plus exercise to improve motor, non-motor symptoms and qol in Parkinson's disease, NCT06036433. https://clinicaltrials.gov/study/NCT06036433
  205. Evaluating safety, tolerability, and efficacy of autologous mitocell transplantation in subjects with idiopathic Parkinson's disease, NCT05094011. 2024 https://clinicaltrials.gov/study/NCT05094011
  206. Effect of folic acid in levodopa treated Parkinson's disease patients, NCT05959044. 2023 https://clinicaltrials.gov/study/NCT05959044
  207. Pre-Active PD: Looking at physical activity behavior change in Parkinson's disease, NCT05308238. 2025 https://clinicaltrials.gov/study/NCT05308238
  208. Study to assess the safety of mrx0029 or mrx0005 compared to placebo, in people with Parkinson's, NCT05832775. 2023 https://clinicaltrials.gov/study/NCT05832775
  209. A trial of fecal microbiome transplantation in Parkinson's disease patients, NCT04854291. 2024 https://clinicaltrials.gov/study/NCT04854291
  210. Effects of complementary therapies in people with mild to moderate Parkinson's disease, NCT05377073. 2022 https://clinicaltrials.gov/study/NCT05377073
  211. Adipose-derived stromal vascular fraction cells to treat Parkinson (SVFP1), NCT05699161. 2023 https://clinicaltrials.gov/study/NCT05699161
  212. Effect of doxycycline in levodopa treated Parkinson's disease patients, NCT05492019. 2022 https://clinicaltrials.gov/study/NCT05492019
  213. The efficacy of a remote cognitive remediation therapy (crt) program on Parkinson's disease, NCT04955275. 2022 https://clinicaltrials.gov/study/NCT04955275
  214. Parkinson's disease (PD) treated with focused ultrasound subthalamotomy at an early stage (EarlyFocus), NCT04692116. 2022 https://clinicaltrials.gov/study/NCT04692116
  215. The acute effect of cervical mobilization in Parkinson's disease, NCT04524143. 2021 https://clinicaltrials.gov/study/NCT04524143
  216. The effect and mechanism of transcutaneous auricular vagus nerve stimulation on gait impairments in PD, NCT05561348. 2022 https://clinicaltrials.gov/study/NCT05561348
  217. Chinese herbal medicine treatment as adjunct therapy for Parkinson's disease (HERB-PARK), NCT05001217. 2024 https://clinicaltrials.gov/study/NCT05001217
  218. The effect of multi-target magnetic stimulation on freezing gait in PD, NCT05174299. 2022 https://clinicaltrials.gov/study/NCT05174299
  219. Mahlia T.M.I. Syazmi Z.A.H.S. Mofijur M. Abas A.E.P. Bilad M.R. Ong H.C. Silitonga A.S. Patent landscape review on biodiesel production: Technology updates. Renew. Sustain. Energy Rev. 2020 118 109526 10.1016/j.rser.2019.109526
    [Google Scholar]
  220. Simmonds M.S.J. Fang R. Wyatt L. Bell E. Allkin B. Forest F. Wynberg R. da Silva M. Zhang B.G. Shi Liu J. Dong Qi Y. Demissew S. Biodiversity and patents: Overview of plants and fungi covered by patents. Plants People Planet 2020 2 5 546 556 10.1002/ppp3.10144
    [Google Scholar]
  221. Meyre M-E, Levy L, Pottier A. Nanoparticles for use for treating a neuronal disorder. US Patent 11497717B2 2018
  222. Karaborni S, Mao C, Gwozdz GT. Nanoparticle compositions of dimethyl fumarate. US Patent 20150079180A1 2014
  223. Sun Y, Liu L, Wang W, Jia L, Ge D, Shi W. Preparation method of ultra-small polydopamine/polydopamine cysteine nanoparticles. CN Patent 113307970B 2021
  224. Sun T. Application of gold cluster-containing substances in the preparation of drugs for the prevention and treating Parkinson's disease. CN Patent 107693538B 2017
  225. Cotin R, Kells PA, Kells PA, Bernard L. AADC polynucleotide for the treatment of Parkinson's disease. JP Patent 6878370B2 2018
  226. Kornberg R, Shachar Y, Chen T. Apparatus and method for cerebral microdialysis to treat neurological disease, including Alzheimer's, Parkinson's or multiple sclerosis. US Patent 11529443B2 2016
  227. Mccully JD, Levitsky S, Cowan DB, Emani SM, Del Nido PJ. Therapeutic use of mitochondria and combined mitochondrial agents. JP Patent 2023018100A 2017
  228. Koan D, Naviroshkan S, Chumakov I, Haji R. New therapeutic methods for the treatment of Parkinson's disease. JP Patent 6727259B2 2012
  229. Ding X, Liu Q, Sang Y. LRRK2 inhibitors for the treatment of Parkinson's disease. US Patent 10618901B2 2018
  230. Kotajere S, Kuzhikandahir EB. Novel D3 dopamine receptor agonist for treating dyskinesia in Parkinson's disease. JP Patent 6542847B2 2011
/content/journals/cpd/10.2174/0113816128404289251010202113
Loading
/content/journals/cpd/10.2174/0113816128404289251010202113
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: NDDS ; pathogenesis ; signaling pathway ; Parkinson's disease ; patents ; clinical trials
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test