DESIGN AND EVALUATION OF ASHWAGANDHA CHITOSAN NANOPARTICLES FOR ENHANCED NEUROPROTECTION IN HUNTINGTON’S DISEASE

R. M. AKILA; M. K. NITHIN

doi:10.22159/ijpps.2025v17i8.54517

Authors

R. M. AKILA Department of Pharmaceutics, College of Pharmacy, Sri Ramakrishna Institute of Paramedical and Sciences, Coimbatore, Tamil Nadu, India
M. K. NITHIN Department of Pharmaceutics, College of Pharmacy, Sri Ramakrishna Institute of Paramedical and Sciences, Coimbatore, Tamil Nadu, India

DOI:

https://doi.org/10.22159/ijpps.2025v17i8.54517

Keywords:

Ashwagandha, Chitosan nanoparticles, Mutant huntingtin protein, Molecular docking, In vitro release kinetics

Abstract

Objective: To develop and evaluate Ashwagandha-loaded nanoparticles for targeted therapy in Huntington’s disease (HD), aiming to enhance neuroprotection and prevent brain atrophy caused by synthetic antipsychotic drugs.

Methods: Molecular docking studies were initially conducted using a variety of phytoconstituents of Ashwagandha extract against the mutant huntingtin (mHTT) protein. Ashwagandha-loaded chitosan nanoparticles have been developed using the ionic-gelation method. Subsequently, a pre-formulation study was conducted to evaluate drug-excipient compatibility using Fourier-transform infrared spectroscopy (FTIR). Upon confirming compatibility, Ashwagandha-loaded chitosan nanoparticles were formulated using the ionic gelation method. Among the formulations, F1 was selected based on in vitro release at pH 7.4. The optimized formulation (F1) was further characterized for particle size, zeta potential and entrapment efficiency. Drug release kinetics were also studied to understand the release mechanism.

Results: Molecular docking studies revealed that Withaferin A, a key bioactive compound of Ashwagandha exhibited a binding affinity comparable to that of tetrabenazine against the mutant huntingtin (mHTT) protein. FTIR analysis confirmed compatibility between the drug and excipients. The nano formulation F1 showed controlled drug release (76% at 6 h) in pH 7.4, making it suitable for brain-targeted delivery, and showed small particle size between 62.3 nm and 86.5 nm and entrapment efficiency (75.06%), indicating effective drug encapsulation in nanoparticulate form, potentially improving solubility and bioavailability. The kinetic studies revealed that the formulation F1 followed zero-order kinetics and provide evidence to the diffusion mechanism of drug release.

Conclusion: The Ashwagandha-loaded chitosan-based biodegradable nano formulation may serve as a suitable alternative to conventional synthetic antipsychotic drugs for Huntington’s disease by demonstrating comparable efficacy in targeting mutant huntingtin protein. It enhances brain-targeted neurotrophic delivery, promotes neurogenesis, and prevents brain atrophy in HD. However, further in vivo validation is required.

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References

1. Ho BC, Andreasen NC, Ziebell S, Pierson R, Magnotta V. Long term antipsychotic treatment and brain volumes: a longitudinal study of first episode schizophrenia. Arch Gen Psychiatry. 2011 Feb;68(2):128-37. doi: 10.1001/archgenpsychiatry.2010.199, PMID 21300943.

2. Krishna Raju AV, Somepalli V, Thanawala S, Shah R. Efficacy and anti-inflammatory activity of ashwagandha sustained release formulation on depression and anxiety induced by chronic unpredictable stress: in vivo and in vitro studies. J Exp Pharmacol. 2023 Jul 25;15:291-305. doi: 10.2147/JEP.S407906, PMID 37521489.

3. Cui X, Lin Q, Liang Y. Plant-derived antioxidants protect the nervous system from aging by inhibiting oxidative stress. Front Aging Neurosci. 2020 Jul;12(12):209. doi: 10.3389/fnagi.2020.00209, PMID 32760268.

4. Deshpande SH, Muhsinah AB, Bagewadi ZK, Ankad GM, Mahnashi MH, Yaraguppi DA. In silico study on the interactions, molecular docking dynamics and simulation of potential compounds from Withania somnifera (L.) dunal root against cancer by targeting KAT6A. Molecules. 2023 Jan 22;28(3):1117. doi: 10.3390/molecules28031117, PMID 36770785.

5. Akila RM, Maria Shaji D. Ginger loaded chitosan nanoparticles for the management of 3–nitropropionic acid induced huntingtons disease like symptoms in male Wistar rats. Int J Pharm Pharm Sci. 2022 Jan 1;14(1):28-36. doi: 10.22159/ijpps.2022v14i1.42894.

6. Md S, Alhakamy NA, Akhter S, Awan ZAY, Aldawsari HM, Alharbi WS. Development of polymer and surfactant-based naringenin nanosuspension for improvement of stability antioxidant and antitumour activity. J Chem. 2020 Jul 15;2020(2):1-10. doi: 10.1155/2020/3489393.

7. Remya PN, Damodharan N. Formulation development and characterization of nimodipine loaded solid lipid nanoparticles. Int J Appl Pharm. 2020;12(5):265-71. doi: 10.22159/ijap.2020v12i5.34342.

8. Patel PN, Patel LJ, Patel JK. Development and testing of novel tamoxifen citrate-loaded chitosan nanoparticles using ionic gelation method. Pharm Sin. 2011;2(4):17-25.

9. Ramaye Y, Dabrio M, Roebben G, Kestens V. Development and validation of optical methods for zeta potential determination of silica and polystyrene particles in aqueous suspensions. Materials (Basel). 2021;14(2):290. doi: 10.3390/ma14020290, PMID 33429974.

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

11. Patil Jayashri, Patil R. Formulation and evaluation of besifloxacin non-erodible ocular inserts. Int J Appl Pharm. 2022 Jan 7;14(1):148-55. doi: 10.22159/ijap.2022v14i1.43058.

12. Madhu S, Komala M, Pandian P. Formulation development and characterization of withaferin a loaded polymeric nanoparticles for alzheimers disease. Bio Nano Sci. 2021;11(2):559-66. doi: 10.1007/s12668-020-00819-w.

13. Foroozandeh P, Aziz AA. Insight into cellular uptake and intracellular trafficking of nanoparticles. Nanoscale Res Lett. 2018 Oct 25;13(1):339. doi: 10.1186/s11671-018-2728-6, PMID 30361809.

14. Bhattacharjee S. DLS and zeta potential: what they are and what they are not? J Control Release. 2016 Aug 10;235:337-51. doi: 10.1016/j.jconrel.2016.06.017, PMID 27297779.

15. Robbani S, Elya B, Iswandana R. Alpha glucosidase and dpp-iv inhibitory activities of ethanol extract from caesalpinia sappan andrographis paniculata and syzygium cumini. Pharmacogn J. 2022;14(3):702-9. doi: 10.5530/pj.2022.14.89.

16. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001 May;13(2):123-33. doi: 10.1016/s0928-0987(01)00095-1, PMID 11297896.