GINGER LOADED CHITOSAN NANOPARTICLES FOR THE MANAGEMENT OF  3–NITROPROPIONIC ACID-INDUCED HUNTINGTON’S DISEASE-LIKE SYMPTOMS IN MALE WISTAR RATS

R. M. AKILA; DONA MARIA SHAJI

doi:10.22159/ijpps.2022v14i1.42894

Authors

R. M. AKILA Department of Pharmaceutics, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences Coimbatore, Tamilnadu, India
DONA MARIA SHAJI Department of Pharmaceutics, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences Coimbatore, Tamilnadu, India

DOI:

https://doi.org/10.22159/ijpps.2022v14i1.42894

Keywords:

Huntington’s disease, Ginger loaded chitosan nanoparticles, Ionic gelation, 3-Nitro propionic acid

Abstract

Objective: The purpose of this research work is to enhance bioavailability and brain delivery of ginger through the development of ginger-loaded chitosan nanoparticles and evaluation of its neuroprotective potential against 3-Nitropropionic acid (3-NP) induced Huntington’s Disease model rats.

Methods: Ginger-loaded chitosan nanoparticles were developed as five different formulations (F1-F5) by the ionic gelation method. Based on their release, formulations F1 and F3 were chosen for physicochemical characterization. The neuroprotective activity of formulations F1 and F3 were evaluated by behavioural (Neurological scoring, Hanging wire test, Elevated plus maze test), biochemical (estimation of lipid peroxidation, glutathione, protein, superoxide dismutase, catalase) and neurochemical (estimation of acetylcholine esterase inhibition) tests in comparison with ginger extract in Huntington’s Disease (HD) model rats.

Results: Formulations F1 and F3 showed almost similar and significant controlled release. Formulation F1 showed spherical nanoparticles with optimum size range and negative zeta potential. The behavioural assessment revealed that there was an improvement in gait, movement, grip strength and memory in ginger-loaded chitosan nanoformulations administered to rats than ginger extract administered rats. Biochemical and neurochemical analyses also proved that ginger-loaded chitosan nanoformulations had greatly lowered the oxidative stress parameters such as malondialdehyde and protein carbonyls in comparison with ginger extract (p<0.05). The ginger nanoformulations had highly increased the activity of antioxidant enzymes such as superoxide dismutase, glutathione and catalase by reducing the formation of free radicals than ginger extract (p<0.05). The memory and cognition of ginger nanoformulations administered Wistar rats had highly improved than ginger extract administered Wistar rats (p<0.05 due to inhibition of acetylcholine esterase enzyme).

Conclusion: The current study indicated that ginger-loaded chitosan nanoparticles have a superior neuroprotective effect than their extract due to their nano size, which facilitates their entry across the blood-brain barrier and eventually improves the bioavailability of ginger.

Downloads

Download data is not yet available.

References

Ohlmeier C, Saum KU, Galetzka W, Beier D, Gothe H. Epidemiology and health care utilization of patients suffering from Huntington’s disease in germany: real-world evidence based on German claims data. BMC Neurol. 2019;19(1):318. doi: 10.1186/s12883-019-1556-3, PMID 31823737.

Bakr AF, Abdelgayed SS, EL-Tawil OS, Bakeer AM. Ginger extract and ginger nanoparticles; characterization and applications. Int J Vet Sci. 2020;9:203-9.

Manisha S, Nidhi S, Ramica S. Neuroprotective effect of Zingiber officinale in 3-NP-induced Huntington disease. IOSR J Pharm. 2012;2:61-70.

Miller PJ, Zaborszky L. 3-nitropropionic acid neurotoxicity: visualization by silver staining and implications for use as an animal model of Huntington’s disease. Exp Neurol. 1997 Jul;146(1):212-29. doi: 10.1006/exnr.1997.6522, PMID 9225755.

Vis JC, Verbeek MM, De Waal RM, Ten Donkelaar HJ, Kremer HP. 3-nitropropionic acid induces a spectrum of Huntington’s disease-like neuropathology in rat striatum. Neuropathol Appl Neurobiol. 1999 Dec;25(6):513-21. doi: 10.1046/j.1365-2990.1999.00212.x, PMID 10632901.

Re F, Gregori M, Masserini M. Nanotechnology for neurodegenerative disorders. Nanomedicine. 2012 Sep;8Suppl 1:S51-8. doi: 10.1016/j.nano.2012.05.007, PMID 22640910.

Aderibigbe BA, Naki T. Chitosan-based nanocarriers for nose to brain delivery. Appl Sci. 2019;9(11):2219. doi: 10.3390/app9112219.

Del Prado Audelo ML, Caballero Floran IH, Meza Toledo JA, Mendoza Munoz N, Gonzalez Torres M, Floran B, Cortes H, Leyva Gomez G. Formulations of curcumin nanoparticles for brain diseases. Biomolecules. 2019 Feb 8;9(2):56. doi: 10.3390/biom9020056, PMID 30743984.

Sandhir R, Yadav A, Mehrotra A, Sunkaria A, Singh A, Sharma S. Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington’s disease. NeuroMolecular Med. 2014 Mar;16(1):106-18. doi: 10.1007/s12017-013-8261-y, PMID 24008671.

Azalea DR, Mohambed M, Joji S, Sankar C, Mishra B. Design and evaluation of chitosan nanoparticles as novel drug carriers for the delivery of donepezil. Iran J Pharm Sci. 2012 Summer;8:155-64.

Akila RM, Saju SA. Design and characterization of biodegradable chitosan nanoparticles loaded with almotriptan malate for migraine therapy. Am J Pharm Health Res. 2018;6:1-15.

Khaira R, Sharma J, Saini V. Development and characterization of nanoparticles for the delivery of gemcitabine hydrochloride. Scientific World Journal. 2014. doi: 10.1155/2014/560962, PMID 24592173.

Patel PN, Patel LJ, Patel JK. Development and testing of novel tamoxifen citrate-loaded chitosan nanoparticles using ionic gelation method. Pharm Sin. 2011;2:17-25.

Selvaraj S, Niraimathi V, Nappinnai M. Formulation and evaluation of acyclovir loaded chitosan nanoparticles. Int J Pharm Sci Nanotechnol 2016;5:619-29.

Baby AAB, Sree N, Harsha K, Jayaveera N. Formulation and evaluation of levofloxacin nanoparticles by ionic gelation method. J Pharm Pharm Sci. 2012;1:7-15.

Nagarajan E, Shanmugasundaram P, Ravichandiran V, Vijayalakshmi A, Senthilnathan B, Masilamani K. Development and evaluation of chitosan-based polymeric nanoparticles of an antiulcer drug lansoprazole. J Appl Pharm Sci. 2015;5(4):20-5. doi: 10.7324/JAPS.2015.50404.

Remya PN, Damodharan N. Formulation, development and characterization of nimodipine loaded solid lipid nanoparticles. Int J Appl Pharm. 2020;12:265-71.

Patel BA, Arundell M, Parker KH, Yeoman MS, O’Hare D. Simple and rapid determination of serotonin and catecholamines in biological tissue using high-performance liquid chromatography with electrochemical detection. J Chromatogr B Anal Technol Biomed Life Sci. 2005;818(2):269-76. doi: 10.1016/j.jchromb.2005.01.008. PMID 15734169.

Ryan EP. Bioactive food components and health properties of rice bran. J Am Vet Med Assoc. 2011;238(5):593-600. doi: 10.2460/javma.238.5.593, PMID 21355801.

Kumar P, Kalonia H, Kumar A. Possible GABAergic mechanism in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity. Eur J Pharmacol. 2012;674(2-3):265-74. doi: 10.1016/j.ejphar.2011.11.030, PMID 22154757.

Wills ED. Mechanisms of lipid peroxide formation in animal tissues. Biochem J. 1966;99(3):667-76. doi: 10.1042/bj0990667, PMID 5964963.

Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70-7. doi: 10.1016/0003-9861(59)90090-6, PMID 13650640.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-75. doi: 10.1016/S0021-9258(19)52451-6, PMID 14907713.

King TE. Preparation of succinate dehydrogenase and reconstitution of succinate oxidase. Meth Enzymol. 1967;10:322-31. doi: 10.1016/0076-6879(67)10061-X.

Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys. 1978;186(1):189-95. doi: 10.1016/0003-9861(78)90479-4, PMID 24422.

Luck H. Catalase. In: Bergmeyer HU. editor. Methods of enzymatic analysis. New York: Academic Press; 1971. p. 885-93.

Nathiya S, Nandhini A, Senthilkumar. Neuroprotective role of Salacia oblonga extracts against aluminium chloride-indicative stress in rat cortex. J Pharm Res. 2015;5:4344-7.