Nanoparticle-Mediated Quercetin Delivery Mitigates Oxidative Stress in Diabetic Neuropathy in Experimental Animals

Neha Yadav; Parag Jain; Jhakeshwar Prasad

doi:10.65807/prob.sci.2026.3.1.2

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Probecell Science

Open Access | E-ISSN: 3049-1584

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Nanoparticle-Mediated Quercetin Delivery Mitigates Oxidative Stress in Diabetic Neuropathy in Experimental Animals

Author(s): Neha Yadav, Parag Jain, Jhakeshwar Prasad

Email(s): paragjain1510@gmail.com

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Published In: Volume - 3, Issue - 1, Year - 2026

DOI: 10.65807/prob.sci.2026.3.1.2

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ABSTRACT:
Diabetic neuropathy is an ascending neurodegenerative condition of diabetes mellitus, which is heralded by sensory dysfunction, motor disability, and chronic neuropathic pain largely due to oxidative stress and mitochondrial impairment caused by hyperglycemia. Quercetin, a naturally occurring flavonoid, exhibits strong antioxidant and neuroprotective effects; however, its clinical application is limited by its low water solubility, poor bioavailability, and short half-life. The focus of the current study was to formulate and optimise quercetin-loaded polymeric nanoparticles and to investigate their efficacy in the treatment of diabetic neuropathy using an experimental animal model. Nanoparticles of quercetin were prepared by employing the solvent evaporation method, yielding 10 formulations (F1–F10) with different drug: polymer ratios. All-round physicochemical characterisation indicated F5 as an optimised system with a minimum particle size (182.3 ± 4.8 nm), maximum encapsulation efficiency (89.6 ± 2.1%), appropriate zeta potential (−31.7 ± 1.4 mV) and a sustainable in-vitro drug release profile. In-vitro antioxidant tests showed that the free radical activity of F5 was significantly improved compared to that of quercetin. In streptozotocin-induced diabetic rats, F5 significantly improved behavioural changes, suppressed oxidative stress, and restored the endogenous antioxidant defence mechanism and the morphology of the peripheral nerve. Overall, these results suggest that nanoparticle-mediated delivery of quercetin significantly enhances its neuroprotective efficacy and provides a promising treatment for diabetic neuropathy.

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Cite this article:
Yadav, N., Jain, P., & Prasad, J. Nanoparticle-Mediated Quercetin Delivery Mitigates Oxidative Stress in Diabetic Neuropathy in Experimental Animals. Probecell Sci., 2026;3(1):11–23. 10.65807/prob.sci.2026.3.1.2DOI: https://doi.org/10.65807/prob.sci.2026.3.1.2

[1] Yang Y, Zhao B, Wang Y, Lan H, Liu X, Hu Y, et al. Diabetic neuropathy: cutting-edge research and future directions. Signal Transduct Target Ther 2025;10:132. https://doi.org/10.1038/s41392-025-02175-1.

[2] Armstrong DG, Fisher TK, Lepow B, White ML, Mills JL. Pathophysiology and Principles of Management of the Diabetic Foot. Mechanisms of Vascular Disease: A Reference Book for Vascular Specialists 2011:475–96. https://doi.org/10.1017/UPO9781922064004.027.

[3] Sandireddy R, Yerra VG, Areti A, Komirishetty P, Kumar A. Neuroinflammation and Oxidative Stress in Diabetic Neuropathy: Futuristic Strategies Based on These Targets. Int J Endocrinol 2014;2014:674987. https://doi.org/10.1155/2014/674987.

[4] Afzal S, Abdul Manap AS, Attiq A, Albokhadaim I, Kandeel M, Alhojaily SM. From imbalance to impairment: the central role of reactive oxygen species in oxidative stress-induced disorders and therapeutic exploration. Front Pharmacol 2023;14:1269581. https://doi.org/10.3389/fphar.2023.1269581.

[5] Carrillo-Martinez EJ, Flores-Hernández FY, Salazar-Montes AM, Nario-Chaidez HF, Hernández-Ortega LD. Quercetin, a Flavonoid with Great Pharmacological Capacity. Molecules 2024, Vol 29, Page 1000 2024;29:1000. https://doi.org/10.3390/molecules29051000.

[6] Saikia L, Barbhuiya SAA, Saikia K, Kalita P, Dutta PP. Therapeutic Potential of Quercetin in Diabetic Neuropathy and Retinopathy: Exploring Molecular Mechanisms. Curr Top Med Chem 2024;24:2351–61. https://doi.org/10.2174/0115680266330678240821060623.

[7] Mirza MA, Mahmood S, Hilles AR, Ali A, Khan MZ, Zaidi SAA, et al. Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications—A Review. Pharmaceuticals 2023;16:1631. https://doi.org/10.3390/ph16111631.

[8] Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology 2018;16:71–71. https://doi.org/10.1186/s12951-018-0392-8.

[9] Kumar B, Jalodia K, Kumar P, Gautam HK. Recent advances in nanoparticle-mediated drug delivery. J Drug Deliv Sci Technol 2017;41:260–8. https://doi.org/10.1016/j.jddst.2017.07.019.

[10] Tefas LR, Tomuţă I, Achim M, Vlase L. Development and optimization of quercetin-loaded plga nanoparticles by experimental design. Clujul Medical 2015;88:214–23. https://doi.org/10.15386/cjmed-418.

[11] Kashif M, Ali M, Naz S, Amir J, Murad S, Atif M, et al. Formulation development and characterization of quercetin loaded poly caprolactone nanoparticles for tumors Desenvolvimento de formulações e caracterização de nanopartículas de policaprolactona carregadas de quercetina para tumores 2024;3:82–92. https://doi.org/10.14295/bjs.v3i2.494.

[12] Wu TH, Yen FL, Lin LT, Tsai TR, Lin CC, Cham TM. Preparation, physicochemical characterization, and antioxidant effects of quercetin nanoparticles. Int J Pharm 2008;346:160–8. https://doi.org/10.1016/j.ijpharm.2007.06.036.

[13] De Grandi D, Meghdadi A, LuTheryn G, Carugo D. Facile production of quercetin nanoparticles using 3D printed centrifugal flow reactors. RSC Adv 2022;12:20696. https://doi.org/10.1039/d2ra02745c.

[14] Melchior S, Codrich M, Gorassini A, Mehn D, Ponti J, Verardo G, et al. Design and advanced characterization of quercetin-loaded nano-liposomes prepared by high-pressure homogenization. Food Chem 2023;428:136680. https://doi.org/10.1016/j.foodchem.2023.136680.

[15] Suhailah, S. N., Arabia S. Quercetin nanoparticles: preparation and characterization. Indian Journal of Drugs 2014;2(3), 96–103.

[16] Lafta MZ, Hameed Al-Samarrai RR, Bouaziz M. Green synthesis of silver and gold nanoparticles using quercetin extracted from Arctium lappa by HPLC, Characterization and Estimation of antioxidant activity. Results Chem 2025;13:102028. https://doi.org/10.1016/j.rechem.2025.102028.

[17] Wang P, Keller AA. Natural and engineered nano and colloidal transport: Role of zeta potential in prediction of particle deposition. Langmuir 2009;25:6856–62. https://doi.org/10.1021/la900134f.

[18] Lalchandani DS, Chenkual L, Sonpasare K, Rajdev B, Naidu VGM, Chella N, et al. Optimization of atorvastatin and quercetin-loaded solid lipid nanoparticles using Box-Behnken design. Nanomedicine 2024;19:1541. https://doi.org/10.1080/17435889.2024.2364585.

[19] de Barros DPC, Santos R, Reed P, Fonseca LP, Oliva A. Design of Quercetin-Loaded Natural Oil-Based Nanostructured Lipid Carriers for the Treatment of Bacterial Skin Infections. Molecules 2022;27:8818. https://doi.org/10.3390/molecules27248818.

[20] Yarjanli Z, Ghaedi K, Esmaeili A, Zarrabi A, Rahgozar S. The antitoxic effects of quercetin and quercetin-conjugated iron oxide nanoparticles (QNPs) against H2O2-induced toxicity in PC12 cells. Int J Nanomedicine 2019;14:6813. https://doi.org/10.2147/IJN.S212582.

[21] Marinova, G., & Batchvarov, V. (2011). Evaluation of the methods for determination of the free radical scavenger activity by DPPH. Bulgarian Journal of Agricultural Science, 17, 11–24.

[22] Baliyan S, Mukherjee R, Priyadarshini A, Vibhuti A, Gupta A, Pandey RP, et al. Determination of Antioxidants by DPPH Radical Scavenging Activity and Quantitative Phytochemical Analysis of Ficus religiosa. Molecules 2022;27:1326. https://doi.org/10.3390/molecules27041326.

[23] Gupta A, Singh S, Yadav A. Pharmacological evaluation of antidiabetic activity of Urginea indica in laboratory animals. Int J Nutr Pharmacol Neurol Dis 2015;5:63–8. https://doi.org/10.4103/2231-0738.153795.

[24] Akbarzadeh A, Norouzian D, Mehrabi MR, Jamshidi S, Farhangi A, Verdi AA, Mofidian SM, Rad BL. Induction of diabetes by Streptozotocin in rats. Indian Journal of Clinical Biochemistry : IJCB, 2007;22(2), 60–64. https://doi.org/10.1007/BF02913315

[25] Hu Y, Dong B, Liu L, Deng Y, Han R, Li C. Treatment-induced neuropathy of diabetes overlapping with chronic inflammatory demyelinating polyradiculoneuropathy after rapid glycemic correction: a case report. Front Endocrinol (Lausanne) 2025;16:1654872. https://doi.org/10.3389/fendo.2025.1654872.

[26] Li H, Li M, Fu J, Ao H, Wang W, Wang X. Enhancement of oral bioavailability of quercetin by metabolic inhibitory nanosuspensions compared to conventional nanosuspensions. Drug Deliv 2021;28:1226. https://doi.org/10.1080/10717544.2021.1927244.

[27] Ostovar M, Akbari A, Anbardar MH, Iraji A, Salmanpour M, Hafez Ghoran S, et al. Effects of Citrullus colocynthis L. in a rat model of diabetic neuropathy. J Integr Med 2020;18:59–67. https://doi.org/10.1016/j.joim.2019.12.002.

[28] Alshahrani S, Fernandez-Conti F, Araujo A, di Fulvio M. Rapid Determination of the Thermal Nociceptive Threshold in Diabetic Rats. J Vis Exp 2012:3785. https://doi.org/10.3791/3785.

[29] Notartomaso S, Scarselli P, Pietro P Di, Battaglia G, Llebaria A, Ciruela F, et al. Mechanical Allodynia Assessment in a Murine Neuropathic Pain Model. Bio Protoc 2018;8:e2671. https://doi.org/10.21769/bioprotoc.2671.

[30] Amin B, Hajhashemi V, Abnous K, Hosseinzadeh H. Ceftriaxone, a Beta-Lactam Antibiotic, Modulates Apoptosis Pathways and Oxidative Stress in a Rat Model of Neuropathic Pain. Biomed Res Int 2014;2014:937568. https://doi.org/10.1155/2014/937568.

[31] Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med 1990;9:515–40. https://doi.org/10.1016/0891-5849(90)90131-2.

[32] Kasznicki J, Kosmalski M, Sliwinska A, Mrowicka M, Stanczyk M, Majsterek I, et al. Evaluation of oxidative stress markers in pathogenesis of diabetic neuropathy. Mol Biol Rep 2012;39:8669. https://doi.org/10.1007/s11033-012-1722-9.

[33] Vitolo M. Decomposition of hydrogen peroxide by catalase. World Journal of Pharmacy and Pharmaceutical Sciences, 2021;10, 47. https://doi.org/10.20959/wjpps20218-19552

[34] Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 2006;1:3159–65. https://doi.org/10.1038/nprot.2006.378.

[35] Kim TK. Understanding one-way ANOVA using conceptual figures. Korean J Anesthesiol 2017;70:22. https://doi.org/10.4097/kjae.2017.70.1.22.

[36] Galiero R, Caturano A, Vetrano E, Beccia D, Brin C, Alfano M, et al. Peripheral Neuropathy in Diabetes Mellitus: Pathogenetic Mechanisms and Diagnostic Options. International Journal of Molecular Sciences 2023, Vol 24, Page 3554 2023;24:3554. https://doi.org/10.3390/ijms24043554.

[37] Bodman MA, Dreyer MA, Varacallo MA. Diabetic Peripheral Neuropathy. The Diabetes Textbook: Clinical Principles, Patient Management and Public Health Issues, Second Edition 2024:923–37. https://doi.org/10.1007/978-3-031-25519-9_56.

[38] Qi W, Qi W, Xiong D, Long M. Quercetin: Its Antioxidant Mechanism, Antibacterial Properties and Potential Application in Prevention and Control of Toxipathy. Molecules 2022;27:6545. https://doi.org/10.3390/molecules27196545.

[39] Wang S, Yang H, Zheng J, Tong A, Mu S, Wang D, et al. Recent advances and prospects of nanoparticle-based drug delivery for diabetic ocular complications. Theranostics 2025;15:3551–70. https://doi.org/10.7150/thno.108691.

[40] Tomou EM, Papakyriakopoulou P, Saitani EM, Valsami G, Pippa N, Skaltsa H. Recent Advances in Nanoformulations for Quercetin Delivery. Pharmaceutics 2023;15:1656. https://doi.org/10.3390/pharmaceutics15061656.

[41] Nalini T, Basha K, Sadiq A, Kumari S. Fabrication and evaluation of nanoencapsulated quercetin for wound healing application. Polymer Bulletin, 2022;80. https://doi.org/10.1007/s00289-022-04094-5

[42] Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B. Antioxidant Strategies in the Management of Diabetic Neuropathy. Biomed Res Int 2015;2015:515042. https://doi.org/10.1155/2015/515042.

[43] Lawson MK. Improvement of Therapeutic Value of Quercetin with Chitosan Nanoparticle Delivery Systems and Potential Applications. Int J Mol Sci 2023;24:3293. https://doi.org/10.3390/ijms24043293.

[44] Zhang R, Gu M, Ma R, Li R, Xu S, Xu Z. Engineered Delivery Systems for Chinese Herbal Medicine in Peripheral Nerve Regeneration: Challenges, Advances, and Future Perspectives. Drug Des Devel Ther 2025;19:10195. https://doi.org/10.2147/DDDT.S563805.

[45] Ye G, Lin C, Zhang Y, Ma Z, Chen Y, Kong L, et al. Quercetin Alleviates Neuropathic Pain in the Rat CCI Model by Mediating AMPK/MAPK Pathway. J Pain Res 2021;14:1289. https://doi.org/10.2147/JPR.S298727.

[46] Kumawat M, Sharma TK, Singh I, Singh N, Ghalaut VS, Vardey SK, et al. Antioxidant Enzymes and Lipid Peroxidation in Type 2 Diabetes Mellitus Patients with and without Nephropathy. N Am J Med Sci 2013;5:213. https://doi.org/10.4103/1947-2714.109193.

[47] Ozdemir G, Ozden M, Maral H, Kuskay S, Cetinalp P, Tarkun I. Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria. Ann Clin Biochem 2005;42:99–104. https://doi.org/10.1258/0004563053492838.

[48] Lawson MK. Improvement of Therapeutic Value of Quercetin with Chitosan Nanoparticle Delivery Systems and Potential Applications. Int J Mol Sci 2023;24:3293. https://doi.org/10.3390/ijms24043293.

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