International Journal of Drug Delivery Technology
Volume 14, Issue 3

Study of Nootropic Effect of Improved Nano Formulation Version of Levodopa in a Rat Model of Parkinson’s Disease Induced by 6-Hydroxydopamine

Rawal VP*, Gangurde SA

School of Pharmaceutical Sciences, Sandip University, Mahiravani, Nashik, Maharashtra, India. 

Received: 20th February, 2024; Revised: 27th March, 2024; Accepted: 15th August, 2024; Available Online: 25th September, 2024 

ABSTRACT

Background: More studies on Parkinson’s disease (PD) symptoms have demonstrated that the condition is multifaceted. PD is associated with cognitive problems & motor impairments, which lower quality of life. 6-hydroxydopamine is a common rodent Parkinsonism neurotoxin. 6-OHDA may damage neurons by increasing oxidative stress from hydroxyl radical production during autoxidation. 6-OHDA and oxidative stress have been shown to impair memory in rats. Thus, 6-OHDA mimics rat Parkinsonian and cognitive decline.

Objective: To construct a stable and easily administered nano-formulation with enhanced bioavailability by adding Mucuna pruriens seed phytoactive Levodopa into Nanocochleates.

Materials and Methods: Free L-Dopa, nanoliposomes, and levodopa nanocochleates were tested in 6-OHDA-treated rats with PD on the 14th day following the 6-OHDA injection, open-field, morris-water-maze, and Y-maze tests assessed learning and memory.

Results: Oral LDNC may reduce 6-OHDA-induced catecholamine neurotoxicity, according to this study. In this 6-OHDA- induced PD model, the nano-formulation appeared to restore injured striatal cells via antioxidant and DA-enhancing pathways. Keywords: Parkinson’s disease, 6-hydroxydopamine, 6-OHDA, Levodopa, Nanocochleates.

International Journal of Drug Delivery Technology (2024); DOI: 10.25258/ijddt.14.3.43

How to cite this article: Rawal VP, Gangurde SA. Study of Nootropic Effect of Improved Nano Formulation Version of Levodopa in a Rat Model of Parkinson’s Disease Induced by 6-Hydroxydopamine. International Journal of Drug Delivery Technology. 2024;14(3):1560-1565.

REFERENCES

  1. Lev N, Barhum Y, Ben-Zur T, Melamed E, Steiner I, Offen D. Knocking Out DJ-1 Attenuates Astrocytes Neuroprotection Against 6-Hydroxydopamine Toxicity. Journal of Molecular Neuroscience. 2013 Mar 28;50(3):542–50.
  2. Kamal SJ, Khadhim HM. Effects of Irbesartan in induced Parkinson’s Disease in International Journal of Pharmaceutical Quality Assurance. 2021;12(1):31-39.
  3. Foyet HS, Hritcu L, Ciobica A, Stefan M, Kamtchouing P, Cojocaru Methanolic extract of Hibiscus asper leaves improves spatial memory deficits in the 6-hydroxydopamine-lesion rodent model of Parkinson’s disease. Journal of Ethnopharmacology. 2011 Jan;133(2):773–9.
  4. Himanshu, Bhaskar R, Sharma N, Mehta M, Singh A, Yashwant,Yadav NS, Khatik GL, Verma S.Development and Evaluation of Buccoadhesive Film of RopiniroleHydrochloride for the Treatment of Parkinson’s Disease, International Journal of Drug Delivery Technology 2017; 7(2); 106-112.
  5. Soto-Otero R, Méndez-Álvarez E, Hermida-Ameijeiras Á, Muñoz-Patiño AM, Labandeira-Garcia Autoxidation and Neurotoxicity of 6-Hydroxydopamine in the Presence of Some Antioxidants. Journal of Neurochemistry. 2002 Jan 18;74(4):1605–12.
  6. Bharath S, Hsu M, Kaur D, Rajagopalan S, Andersen JK. Glutathione, iron and Parkinson’s Biochemical Pharmacology. 2002 Sep;64(5-6):1037–48.
  7. Halliwell Roleof Free Radicalsinthe NeurodegenerativeDiseases. Drugs & Aging. 2001;18(9):685–716.
  8. Pessoa D, Nádia C, Pontes V, Eduardo C, Taciana F, Sarah Souza Escudeiro, et al. Behavioral and Neurochemical Effects of Alpha-Lipoic Acid in the Model of Parkinson’s Disease Induced by Unilateral Stereotaxic Injection of 6-Ohda in Rat. Evidence-based Complementary and Alternative Medicine. 2013 Jan 1;2013:1–13.
  9. Pulikkalpura H, Kurup R, Mathew PJ, Baby S. Levodopa in Mucuna pruriens and its degradation. Scientific Reports. 2015 Jun 9;5(1).
  10. Salvia-Trujillo L, Rojas-Graü MA, Soliva-Fortuny R, Martín- Belloso Use of antimicrobial nanoemulsions as edible coatings: Impact on safety and quality attributes of fresh-cut Fuji apples. Postharvest Biology and Technology. 2015 Jul;105:8–16.
  11. Baqir KA, Selman SM, Mohammed SB. Neuroprotective Effects of Taraxicum Officinale as an Antioxidant and Anti- neuroinflammatory Agent in Rotenone Induced Rat Model of Parkinson’s Disease. International Journal of Drug Delivery Technology. 2021;11(3):649-655.
  12. Munot N, Kandekar U, Giram PS, Khot K, Patil A, Cavalu S. A Comparative Study of Quercetin-Loaded Nanocochleates and Liposomes: Formulation, Characterization, Assessment of Degradation and In Vitro Anticancer Potential. Pharmaceutics. 2022 Jul 31;14(8):1601.
  13. Sriraksa N, Wattanathorn J, Muchimapura S, Tiamkao S, Brown K, Chaisiwamongkol Cognitive-Enhancing Effect of Quercetin in a Rat Model of Parkinson’s Disease Induced by 6-Hydroxydopamine. Evidence-Based Complementary and Alternative Medicine. 2012;2012:1–9.
  14. Hritcu L, Cioanca O, Hancianu M. Effects of lavender oil inhalation on improving scopolamine-induced spatial memory impairment in laboratory rats. Phytomedicine [Internet]. 2012 Apr;19(6):529–34. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0944711312000414
  15. Vorhees CV, Williams MT. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature Protocols. 2006 Jul 27;1(2):848–58.
  16. Misra HP, Fridovich The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. Journal of Biological Chemistry. 1972 May;247(10):3170–5.
  17. Moron M, Depierre J, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et Biophysica Acta (BBA) - General 1979 Jan 4;582(1):67–78.
  18. Sreejayan, Rao Nitric Oxide Scavenging by Curcuminoids. Journal of Pharmacy and Pharmacology. 1997 Jan;49(1):105–7.
  19. Beers RF, Sizer A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. Journal of Biological Chemistry. 1952 Mar;195(1):133–40.
  20. Grotto D, L.D. Santa Maria, Silvana Peterini Boeira, Valentini J, Mariele Feiffer Charão, Moro AM, et Rapid quantification of malondialdehyde in plasma by high performance liquid chromatography–visible detection. 2007 Jan 17;43(2):619–24.
  21. DaughadayWh, Oh L, Rosebrough Nj, Fields Determination of cerebrospinal fluid protein with the Folin phenol reagent. PubMed. 1952 Apr 1;39(4):663–5.
  22. Bothiraja C, Yojana BD, Pawar AP, Shaikh KS, Thorat UH. Fisetin-loaded nanocochleates: formulation, characterisation,in vitroanticancer testing, bioavailability and biodistribution Expert Opinion on Drug Delivery. 2013 Dec 3;11(1):17–29.
  23. Florio T. Dopamine denervation of specific striatal subregions differentially affects preparation and execution of a delayed response task in the rat. Behavioural Brain Research. 1999 Oct;104(1-2):51–62.
  24. De Leonibus E, Pascucci T, Lopez S, Oliverio A, Amalric M, Mele Spatial deficits in a mouse model of Parkinson disease. Psychopharmacology. 2007 Jul 11;194(4):517–25.
  25. Fukui K, Omoi NO, Hayasaka T, Shinnkai T, Suzuki S, Abe K, et al. Cognitive Impairment of Rats Caused by Oxidative Stress and Aging, and Its Prevention by Vitamin Annals of the New York Academy of Sciences. 2002 Apr;959(1):275–84.
  26. Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, et Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. Journal of neurochemistry [Internet]. 1989;52(2):381–9.
  27. S Poongothai, Srinivasan R, Rama A Correlative Dissolution Study of Oral Drug Delivery Systems through Reverse Phase- HPLC Analysis. International Journal of Pharmaceutical Quality Assurance. 2023 Sep 25;14(03):553–8.
  28. Williams MD, Van Remmen H, Conrad CC, Huang TT, Epstein CJ, Richardson A. Increased Oxidative Damage Is Correlated to Altered Mitochondrial Function in Heterozygous Manganese Superoxide Dismutase Knockout Mice. Journal of Biological Chemistry. 1998 Oct;273(43):28510–5.
  29. Spillantini M. Parkinson’s disease-mild cognitive impairment (PD-MCI) and Parkinson’s disease Dementia (PDD). Alzheimer’s & Dementia. 2012 Jul;8(4):P725.
  30. Moshahid Khan Mohd, Raza SS, Javed H, Ahmad A, Khan A, Islam F, et al. Rutin Protects Dopaminergic Neurons from Oxidative Stress in an Animal Model of Parkinson’s Disease. Neurotoxicity Research. 2011 Dec 23;22(1):1–15.