Solid lipid nanoparticles enhance piracetam’s neuroprotective action in streptozotocin-induced cognitive dysfunction
Source abstract
Abstract
Abstract Diabetes-induced cognitive dysfunction remains an unaddressed medical concern across the globe with limited options left with conventional drug therapy. Piracetam, the first identified nootropic agent has been repurposed in the current study via solid-lipid nanoparticle against streptozotocin-induced cognitive dysfunction in rats. Experimental piracetam loaded solid-lipid nanoparticles (PSLNs) were developed by conventional nanoprecipitation method and characterized in terms of SEM, AFM, DLS, zeta potential, drug loading efficiency etc. In vivo efficacy of the selected PSLNs was analysed. Various biochemical parameters were analysed along with histopathology and brain pharmacokinetic studies. Experimental PSLNs were spherical, nanosized, homogenous (PDI: 0.21 ± 0.5) with − 38.2 ± 0.3 mV surface charge. Following administration, selected PSLNs brought significant improvement in behavioural and memory function as compared to plain piracetam and control rat groups. Modulation in key enzyme/ protein expression in terms of SOD, CAT, GSH was observed in vivo in PSLNs treated rats. Histopathology of brain tissue in AD rats indicated revival of normal tissue architecture in PSLNs treated group as compared to piracetam/control groups. Key brain pharmacokinetic parameters like AUC, AUMC, MRT etc. were substantially improved for PSLNs than plain piracetam, signifying higher accumulation and retention of the drug following nanoencapsulation. However, futuristic studies are necessary to establish PSLNs as a potent modality against diabetes-induced cognitive dysfunction in clinical settings.
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Research context
OpenAlex topics: Advanced Drug Delivery Systems · Neurological Disease Mechanisms and Treatments · Medicinal Plants and Neuroprotection
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (98)
Show source-provided references
1. Meng X, Du H, Li D, Guo Y, Luo P, Pan L, et al. Risk factors, pathological changes, and potential treatment of diabetes-associated cognitive dysfunction. J Diabetes. 2025;17:e70089. https://doi.org/10.1111/1753-0407.70089.10.1111/1753-0407.70089 ↗
2. Sebastian MJ, Khan SK, Pappachan JM, Jeeyavudeen MS. Diabetes and cognitive function: an evidence-based current perspective. World J Diabetes. 2023;14:92–109. https://doi.org/10.4239/wjd.v14.i2.92.10.4239/wjd.v14.i2.92 ↗
3. Yu X, He H, Wen J, Xu X, Ruan Z, Hu R, et al. Diabetes-related cognitive impairment: mechanisms, symptoms, and treatments. Open Med. 2025;20:20241091. https://doi.org/10.1515/med-2024-1091.10.1515/med-2024-1091 ↗
4. Chen Z-R, Huang J-B, Yang S-L, Hong F-F. Role of cholinergic signaling in Alzheimer’s disease. Molecules. 2022;27:1816. https://doi.org/10.3390/molecules27061816.10.3390/molecules27061816 ↗
5. Kumar A, Sidhu J, Lui F, Tsao JW. Alzheimer disease. StatPearls, Treasure Island (FL): StatPearls Publishing; 2025.10.1201/9781003602477 ↗
6. Knezovic A, Salkovic-Petrisic M. Cholinergic neurotransmission in the brain of streptozotocin-induced rat model of sporadic Alzheimer’s disease: long-term follow up. J Neural Transm. 2025;132:1461–77. https://doi.org/10.1007/s00702-025-02887-2.10.1007/s00702-025-02887-2 ↗
7. Gariani K, Ryu D, Rizzo M. Cognitive disorders in diabetes. Front Clin Diabetes Healthc. 2025;6:1534105. https://doi.org/10.3389/fcdhc.2025.1534105.10.3389/fcdhc.2025.1534105 ↗
8. Abdalla MMI. Insulin resistance as the molecular link between diabetes and Alzheimer’s disease. World J Diabetes. 2024;15:1430–47. https://doi.org/10.4239/wjd.v15.i7.1430.10.4239/wjd.v15.i7.1430 ↗
9. Veselov IM, Vinogradova DV, Maltsev AV, Shevtsov PN, Spirkova EA, Bachurin SO, et al. Mitochondria and oxidative stress as a link between Alzheimer’s disease and diabetes mellitus. Int J Mol Sci. 2023;24:14450. https://doi.org/10.3390/ijms241914450.10.3390/ijms241914450 ↗
10. Patil RS, Tupe RS. Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer’s disease, and Parkinson’s disease pathogenesis. Med Res Rev. 2024;44:365–405. https://doi.org/10.1002/med.21987.10.1002/med.21987 ↗
11. Gorthi SP, Gupta D. Alzheimer’s disease: treatment today and tomorrow. Ann Indian Acad Neurol. 2023;26:326–33. https://doi.org/10.4103/aian.aian_254_23.10.4103/aian.aian_254_23 ↗
12. Uddin MdS, Al Mamun A, Kabir MdT, Ashraf GM, Bin-Jumah MN, Abdel-Daim MM. Multi-target drug candidates for multifactorial Alzheimer’s disease: AChE and NMDAR as molecular targets. Mol Neurobiol. 2021;58:281–303. https://doi.org/10.1007/s12035-020-02116-9.10.1007/s12035-020-02116-9 ↗
13. Nazam N, Farhana A, Shaikh S. Recent advances in Alzheimer’s disease in relation to cholinesterase inhibitors and NMDA receptor antagonists. In: Md Ashraf G, Alexiou A, editors. Autism spectrum disorder and Alzheimer’s disease. Springer Nature Singapore: Singapore; 2021. p. 135–51. https://doi.org/10.1007/978-981-16-4558-7_810.1007/978-981-16-4558-7_8 ↗
14. Dhruva SS, Kesselheim AS, Woloshin S, Ji RZ, Lu Z, Darrow JJ, et al. Physician perspectives on the food and drug administration’s decision to grant accelerated approval to Aducanumab for Alzheimer’s disease. Clin Pharmacol Ther. 2023;114:614–7. https://doi.org/10.1002/cpt.2954.10.1002/cpt.2954 ↗
15. Vaz M, Silva V, Monteiro C, Silvestre S. Role of Aducanumab in the treatment of Alzheimer’s disease: challenges and opportunities. CIA. 2022;17:797–810. https://doi.org/10.2147/CIA.S325026.10.2147/CIA.S325026 ↗
16. Benninghoff J, Perneczky R. Anti-dementia medications and Anti-Alzheimer’s disease drugs: side effects, contraindications, and interactions. In: Riederer P, Laux G, Nagatsu T, Le W, Riederer C, editors. NeuroPsychopharmacotherapy. Cham: Springer International Publishing; 2022. p. 2779–88. https://doi.org/10.1007/978-3-030-62059-2_19510.1007/978-3-030-62059-2_195 ↗
17. Iqbal I, Saqib F, Mubarak Z, Latif MF, Wahid M, Nasir B, et al. Alzheimer’s disease and drug delivery across the blood–brain barrier: approaches and challenges. Eur J Med Res. 2024;29:313. https://doi.org/10.1186/s40001-024-01915-3.10.1186/s40001-024-01915-3 ↗
18. Ozceylan O, Sezgin-Bayindir Z. Current overview on the use of nanosized drug delivery systems in the treatment of neurodegenerative diseases. ACS Omega. 2024;9:35223–42. https://doi.org/10.1021/acsomega.4c01774.10.1021/acsomega.4c01774 ↗
19. Mishra A, Sahu PK, Satapathy BS, Biswal B. Phyto-active components delivered through lipid nanodrug carriers as a promising avenue for the treatment of Alzheimer’s disease: their present status and industrial viability. CNM. 2025;10:455–72. https://doi.org/10.2174/0124054615322050240817172547.10.2174/0124054615322050240817172547 ↗
20. Chaturvedi S, Ganeshpurkar A, Shrivastava A, Dubey N. Protective effect of co-administration of caffeine and piracetam on scopolamine-induced amnesia in Wistar rats. Curr Res Pharmacol Drug Discov. 2021;2:100052. https://doi.org/10.1016/j.crphar.2021.100052.10.1016/j.crphar.2021.100052 ↗
21. Scheuer K, Rostock A, Bartsch R, Müller W. Piracetam improves cognitive performance by restoring neurochemical deficits of the aged rat brain. Pharmacopsychiatry. 1999;32:10–6. https://doi.org/10.1055/s-2007-979231.10.1055/s-2007-979231 ↗
22. Abomosallam M, Hendam BM, Abdallah AA, Refaat R, Elshatory A, Gad El Hak HN. Neuroprotective effect of piracetam-loaded magnetic chitosan nanoparticles against thiacloprid-induced neurotoxicity in albino rats. Inflammopharmacol. 2023;31:943–65. https://doi.org/10.1007/s10787-023-01151-x.10.1007/s10787-023-01151-x ↗
23. Nasr M, Wahdan SA. Neuroprotective effects of novel nanosystems simultaneously loaded with vinpocetine and piracetam after intranasal administration. Life Sci. 2019;226:117–29. https://doi.org/10.1016/j.lfs.2019.04.014.10.1016/j.lfs.2019.04.014 ↗
24. Subroto E, Andoyo R, Indiarto R. Solid lipid nanoparticles: review of the current research on encapsulation and delivery systems for active and antioxidant compounds. Antioxidants Basel. 2023;12:633. https://doi.org/10.3390/antiox12030633.10.3390/antiox12030633 ↗
25. Shivananjegowda MG, Hani U, Osmani RAM, Alamri AH, Ghazwani M, Alhamhoom Y, et al. Development and evaluation of solid lipid nanoparticles for the clearance of Aβ in Alzheimer’s disease. Pharmaceutics. 2023;15:221. https://doi.org/10.3390/pharmaceutics15010221.10.3390/pharmaceutics15010221 ↗
26. Rojanaratha T, Tienthai P, Woradulayapinij W, Yimsoo T, Boonkanokwong V, Ritthidej GC. Preparation, physicochemical characterization, ex vivo, and in vivo evaluations of asiatic acid-loaded solid lipid nanoparticles formulated with natural waxes for nose-to-brain delivery. Eur J Pharm Sci. 2024;203:106935. https://doi.org/10.1016/j.ejps.2024.106935.10.1016/j.ejps.2024.106935 ↗
27. Satapathy MK, Yen T-L, Jan J-S, Tang R-D, Wang J-Y, Taliyan R, et al. Solid lipid nanoparticles (SLNs): an advanced drug delivery system targeting brain through BBB. Pharmaceutics. 2021;13:1183. https://doi.org/10.3390/pharmaceutics13081183.10.3390/pharmaceutics13081183 ↗
28. Nadeem M, Majid H, Ansari MD, Ahmad FJ, Parvez S, Akhtar M, et al. Development and optimization of piracetam and shatavarin IV-loaded nanoemulsion for Alzheimer’s disease therapy. In Silico and experimental analysis. ACS Omega. 2025;10:9132–53. https://doi.org/10.1021/acsomega.4c09072.10.1021/acsomega.4c09072 ↗
29. Mani V, Rabbani SI, Shariq A, Amirthalingam P, Arfeen M. Piracetam as a therapeutic agent for doxorubicin-induced cognitive deficits by enhancing cholinergic functions and reducing neuronal inflammation, apoptosis, and oxidative stress in rats. Pharmaceuticals. 2022;15:1563. https://doi.org/10.3390/ph15121563.10.3390/ph15121563 ↗
30. Verma DK, Gupta S, Biswas J, Joshi N, Singh A, Gupta P, et al. (2018) New therapeutic activity of metabolic enhancer piracetam in treatment of neurodegenerative disease: Participation of caspase independent death factors, oxidative stress, inflammatory responses and apoptosis. Biochimica et Biophysica Acta (BBA)–Molecular Basis of Disease. 1864:2078–96. https://doi.org/10.1016/j.bbadis.2018.03.014.10.1016/j.bbadis.2018.03.014 ↗
31. Mukherjee B, Maji R, Dey NS, Satapathy BS, Mondal S. Preparation and characterization of tamoxifen citrate loaded nanoparticles for breast cancer therapy. IJN. 2014. https://doi.org/10.2147/IJN.S63535.10.2147/IJN.S63535 ↗
32. Satapathy BS, Mohanty M, Behera S. PLGA-lecithin nanocarrier encapsulating Curcuma caesia oil in a mucoadhesive gel: efficacy analysis against periodontal infections. J Microencapsul. 2025;42:702–20. https://doi.org/10.1080/02652048.2025.2531784.10.1080/02652048.2025.2531784 ↗
33. Ghorbannejad Nashli F, Aghajanpour S, Farmoudeh A, Balef SSH, Torkamanian M, Razavi A, et al. Preparation and optimisation of solid lipid nanoparticles of rivaroxaban using artificial neural networks and response surface method. J Microencapsul. 2025;42:70–82. https://doi.org/10.1080/02652048.2024.2437362.10.1080/02652048.2024.2437362 ↗
34. Satapathy BS, Mishra A, Biswal SK, Pattnaik S, Parida R, Biswal B, et al. Encapsulation of Alpinia leaf essential oil in nanophytosome-embedded gel as novel strategy to treat periodontal infections: evaluation of antimicrobial effectiveness, pharmacokinetic, in vitro-ex vivo correlation and in silico studies. J Microencapsul. 2024;41:327–44. https://doi.org/10.1080/02652048.2024.2354234.10.1080/02652048.2024.2354234 ↗
35. Baviskar A, Kashid V, Ahirrao S, Bhambere D, Akul M. Formulation and evaluation of butenafine hydrochloride incorporated solid lipid nanoparticles from novel excipients for the treatment of superficial fungal infection. Tjps. 2023;0:0–0. https://doi.org/10.4274/tjps.galenos.2023.80799.10.4274/tjps.galenos.2023.80799 ↗
36. Pandey SS, Shaikh FI, Gupta AR, Vaidya RJ. Mannosylated solid lipid nanocarriers of chrysin to target gastric cancer: optimization and cell line study. CDD. 2021;18:1574–84. https://doi.org/10.2174/1567201818666210319142206.10.2174/1567201818666210319142206 ↗
37. Satapathy BS, Biswal B, Pattnaik S, Parida R, Sahoo RN. A mucoadhesive nanolipo gel containing Aegle marmelos gum to enhance transdermal effectiveness of linezolid for vaginal infection: in vitro evaluation, in vitro-ex vivo correlation, pharmacokinetic studies. Int J Pharm. 2023;648:123542. https://doi.org/10.1016/j.ijpharm.2023.123542.10.1016/j.ijpharm.2023.123542 ↗
38. Bandiwadekar A, Jose J, Gopan G, Augustin V, Ashtekar H, Khot KB. Transdermal delivery of resveratrol loaded solid lipid nanoparticle as a microneedle patch: a novel approach for the treatment of Parkinson’s disease. Drug Deliv Transl Res. 2025;15:1043–73. https://doi.org/10.1007/s13346-024-01656-0.10.1007/s13346-024-01656-0 ↗
39. Macit M, Duman G, Cumbul A, Sumer E, Macit C. Formulation development of Silybum marianum seed extracts and silymarin nanoparticles, and evaluation of hepatoprotective effect. J Drug Deliv Sci Technol. 2023;83:104378. https://doi.org/10.1016/j.jddst.2023.104378.10.1016/j.jddst.2023.104378 ↗
40. Rasouliyan F, Eskandani M, Jaymand M, Akbari Nakhjavani S, Farahzadi R, Vandghanooni S, et al. Preparation, physicochemical characterization, and anti-proliferative properties of Lawsone-loaded solid lipid nanoparticles. Chem Phys Lipids. 2021;239:105123. https://doi.org/10.1016/j.chemphyslip.2021.105123.10.1016/j.chemphyslip.2021.105123 ↗
41. Mondal L, Mukherjee B, Das K, Bhattacharya S, Dutta D, Chakraborty S, et al. CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice. IJN. 2019;14:8073–94. https://doi.org/10.2147/IJN.S220740.10.2147/IJN.S220740 ↗
42. Zhao W, Zeng M, Li K, Pi C, Liu Z, Zhan C, et al. Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo. Pharm Biol. 2022;60:2300–7. https://doi.org/10.1080/13880209.2022.2136205.10.1080/13880209.2022.2136205 ↗
43. Satapathy BS, Mukherjee B, Baishya R, Debnath MC, Dey NS, Maji R. Lipid nanocarrier-based transport of docetaxel across the blood brain barrier. RSC Adv. 2016;6:85261–74. https://doi.org/10.1039/C6RA16426A.10.1039/C6RA16426A ↗
44. Askarizadeh M, Esfandiari N, Honarvar B, Sajadian SA, Azdarpour A. Kinetic modeling to explain the release of medicine from drug delivery systems. ChemBioEng Rev. 2023;10:1006–49. https://doi.org/10.1002/cben.202300027.10.1002/cben.202300027 ↗
45. Sri RM, Sangeetha S. Formulation design, optimization, and evaluation of solid lipid nanoparticles loaded with an antiviral drug Tenofovir using Box-Behnken design for boosting oral bioavailability. Adv Pharmacol Pharma Sci. 2024;2024:5248746. https://doi.org/10.1155/2024/5248746.10.1155/2024/5248746 ↗
46. Sohn E, Lim H-S, Jin Kim Y, Kim B-Y, Yoon J, Kim J-H, et al. Exploring the therapeutic potential of Potentilla fragarioides var. major (Rosaceae) extract in Alzheimer’s disease using in vitro and in vivo models: a multi-faceted approach. Neuroscience. 2024;559:77–90. https://doi.org/10.1016/j.neuroscience.2024.08.029.10.1016/j.neuroscience.2024.08.029 ↗
47. Trapani A, Esteban MÁ, Curci F, Manno DE, Serra A, Fracchiolla G, et al. Solid lipid nanoparticles administering antioxidant Grape Seed-derived polyphenol compounds: a potential application in aquaculture. Molecules. 2022;27:344. https://doi.org/10.3390/molecules27020344.10.3390/molecules27020344 ↗
48. Sasidharan R, Mohanan R, Kukreti N, Raj P, Abdelgawad MA, Ghoneim MM, et al. MAO-B inhibitor (2E)-3-(4-Bromophenyl)-1-(1H-indol-3-yl) prop-2-en-1-one as a neuroprotective agent against Alzheimer’s disease. Neurochem Res. 2024;49:1518–28. https://doi.org/10.1007/s11064-023-04031-6.10.1007/s11064-023-04031-6 ↗
49. Mishra A, Sankar Satapathy B, Gatadi S, Vasavi M, Kumar Sahu P, Nuthakki V. Garcinol as a promising therapeutic candidate for Alzheimer’s disease: integrated computational and in vitro target analysis. ChemistrySelect. 2025;10:e01371. https://doi.org/10.1002/slct.202501371.10.1002/slct.202501371 ↗
50. Satpathy B, Sa N, Behera A, Sahu PK. Dose-dependent attenuation of the efficacy of Clitoria ternatea by cobalt oxide nanoparticles against diabetes-induced cognitive impairment. Mol Neurobiol. 2025;62:2601–16. https://doi.org/10.1007/s12035-024-04436-6.10.1007/s12035-024-04436-6 ↗
51. Pradhan SP, Behera A, Sahu PK. A comparative study of nanoconjugates of a synthetic and a natural drug against T2DM-induced cognitive dysfunction. J Neuroimmune Pharmacol. 2025;20:11. https://doi.org/10.1007/s11481-025-10170-0.10.1007/s11481-025-10170-0 ↗
52. Zarneshan SN, Arkan E, Kiani A, Hosseini SZ, Abbaszadeh F, Fakhri S. Protective effects of polydatin amphiphilic chitosan nanocarriers against an aluminum chloride-induced model of Alzheimer’s disease in rats: relevance to its anti-inflammatory and antioxidant effects. Naunyn-Schmiedebergs Arch Pharmacol. 2025;398:7605–24. https://doi.org/10.1007/s00210-024-03696-2.10.1007/s00210-024-03696-2 ↗
53. Pradhan SP, Behera A, Sahu PK. Effect of Vildagliptin conjugated monometallic nanoparticles and bimetallic nanocomposites on diabetes-induced cognitive deficit. Exp Neurol. 2025;383:115026. https://doi.org/10.1016/j.expneurol.2024.115026.10.1016/j.expneurol.2024.115026 ↗
54. Satpathy B, Rajwar TK, Mishra A, Saha I, Rai VK, Sahoo RK, et al. Intra-nasal delivery of Quercetin-loaded nanostructured lipid carriers (NLCs) in the management of Alzheimer’s disease: formulation, in vitro and in vivo assessment. Mol Neurobiol. 2025;62:13182–209. https://doi.org/10.1007/s12035-025-05137-4.10.1007/s12035-025-05137-4 ↗
55. Behera A, Pradhan SP, Tejaswani P, Sa N, Pattnaik S, Sahu PK. Ameliorative and neuroprotective effect of core-shell type Se@Au conjugated Hesperidin nanoparticles in diabetes-induced cognitive impairment. Mol Neurobiol. 2023;60:7329–45. https://doi.org/10.1007/s12035-023-03539-w.10.1007/s12035-023-03539-w ↗
56. Pattanaik S, Paidesetty SK, Pakeeraiah K, Prusty SK, Sahu PK. Design and synthesis of phyto-saxagliptin conjugates: targeting DPP IV, AChE, and β-amyloid in cognitive impairment. J Mol Struct. 2025;1322:140386. https://doi.org/10.1016/j.molstruc.2024.140386.10.1016/j.molstruc.2024.140386 ↗
57. Patel R, Kaur K, Singh S. Protective effect of andrographolide against STZ induced Alzheimer’s disease in experimental rats: possible neuromodulation and Aβ(1–42) analysis. Inflammopharmacology. 2021;29:1157–68. https://doi.org/10.1007/s10787-021-00843-6.10.1007/s10787-021-00843-6 ↗
58. Kumar Das M, Tiwari P, Prusty SK, Kumar Sahu P. Neuroprotective potential of metformin against forced swimming induced neurodegeneration Wistar albino rats. Asian J Biol Sci. 2018;11:89–97. https://doi.org/10.3923/ajbs.2018.89.97.10.3923/ajbs.2018.89.97 ↗
59. Pradhan SP, Tejaswani P, Sa N, Behera A, Sahoo RK, Sahu PK. Mechanistic study of gold nanoparticles of Vildagliptin and Vitamin E in diabetic cognitive impairment. J Drug Deliv Sci Technol. 2023;84:104508. https://doi.org/10.1016/j.jddst.2023.104508.10.1016/j.jddst.2023.104508 ↗
60. Sahu PK, Mishra SK, Rout K, Prusty SK. Shodhana decreases nootropic activity of semecarpus anacardium. Asian J Pharm Clin Res. 2016. https://doi.org/10.22159/ajpcr.2016.v9s2.13989.10.22159/ajpcr.2016.v9s2.13989 ↗
61. Salissou MTM, Mahaman YAR, Zhu F, Huang F, Wang Y, Xu Z, et al. Methanolic extract of Tamarix Gallica attenuates hyperhomocysteinemia induced AD-like pathology and cognitive impairments in rats. Aging Albany NY. 2018;10:3229–48. https://doi.org/10.18632/aging.101627.10.18632/aging.101627 ↗
62. Silva B, Sousa L, Miranda A, Vasconcelos A, Reis H, Barcelos L, et al. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke. Arq Neuro-Psiquiatr. 2015;73:655–9. https://doi.org/10.1590/0004-282X20150083.10.1590/0004-282X20150083 ↗
63. Wang X, Zhu J, Xu R, Yang X, Wu H, Lin D, et al. Determination of piracetam in rat plasma by LC–MS/MS and its application to pharmacokinetics. Biomed Chromatogr. 2010;24:1108–12. https://doi.org/10.1002/bmc.1412.10.1002/bmc.1412 ↗
64. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999;26:1231–7. https://doi.org/10.1016/S0891-5849(98)00315-3.10.1016/S0891-5849(98)00315-3 ↗
65. Jena AB, Samal RR, Bhol NK, Duttaroy AK. Cellular Red-Ox system in health and disease: the latest update. Biomed Pharmacother. 2023;162:114606. https://doi.org/10.1016/j.biopha.2023.114606.10.1016/j.biopha.2023.114606 ↗
66. Gaweł S, Wardas M, Niedworok E, Wardas P. [Malondialdehyde (MDA) as a lipid peroxidation marker]. Wiad Lek. 2004;57:453–5.
67. Stephan BCM, Harrison SL, Keage HAD, Babateen A, Robinson L, Siervo M. Cardiovascular disease, the nitric oxide pathway and risk of cognitive impairment and dementia. Curr Cardiol Rep. 2017;19:87. https://doi.org/10.1007/s11886-017-0898-y.10.1007/s11886-017-0898-y ↗
68. Huang Q, Liao C, Ge F, Ao J, Liu T. Acetylcholine bidirectionally regulates learning and memory. J Neurorestoratol. 2022;10:100002. https://doi.org/10.1016/j.jnrt.2022.100002.10.1016/j.jnrt.2022.100002 ↗
69. Azargoonjahromi A. The duality of amyloid-β: its role in normal and Alzheimer’s disease states. Mol Brain. 2024;17:44. https://doi.org/10.1186/s13041-024-01118-1.10.1186/s13041-024-01118-1 ↗
70. Butterfield DA, Di Domenico F, Barone E. Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain. Biochimica et Biophysica Acta (BBA)–Molecular Basis of Disease. 2014;1842:1693–706. https://doi.org/10.1016/j.bbadis.2014.06.010.10.1016/j.bbadis.2014.06.010 ↗
71. Stanciu GD, Bild V, Ababei DC, Rusu RN, Cobzaru A, Paduraru L, et al. Link between diabetes and Alzheimer’s disease due to the shared amyloid aggregation and deposition involving both neurodegenerative changes and neurovascular damages. JCM. 2020;9:1713. https://doi.org/10.3390/jcm9061713.10.3390/jcm9061713 ↗
72. Akanchise T, Angelov B, Angelova A. Nanomedicine-mediated recovery of antioxidant glutathione peroxidase activity after oxidative-stress cellular damage: insights for neurological long COVID. J Med Virol. 2024;96:e29680. https://doi.org/10.1002/jmv.29680.10.1002/jmv.29680 ↗
73. Akanchise T, Angelov B, Deng Y, Fujino T, Bizien T, Angelova A. Nanostructuring and antioxidant activity of nanotherapeutics designed by self-assembly of natural lipids and phytochemicals. ACS Biomater Sci Eng. 2025;11:3488–502. https://doi.org/10.1021/acsbiomaterials.5c00006.10.1021/acsbiomaterials.5c00006 ↗
74. Wu Y, Wang J, Deng Y, Angelov B, Fujino T, Hossain MdS, et al. Lipid and transcriptional regulation in a Parkinson’s Disease mouse model by intranasal vesicular and hexosomal plasmalogen‐based nanomedicines. Adv Healthc Mater. 2024;13:2304588. https://doi.org/10.1002/adhm.202304588.10.1002/adhm.202304588 ↗
75. Shen S, Wu Y, Liu Y, Wu D. High drug-loading nanomedicines: progress, current status, and prospects. IJN. 2017;12:4085–109. https://doi.org/10.2147/IJN.S132780.10.2147/IJN.S132780 ↗
76. Masarudin MJ, Cutts SM, Evison BJ, DonR P, Pigram PJ. Factors determining the stability, size distribution, and cellular accumulation of small, monodisperse chitosan nanoparticles as candidate vectors for anticancer drug delivery: application to the passive encapsulation of [14C]-doxorubicin. NSA. 2015. https://doi.org/10.2147/NSA.S91785.10.2147/NSA.S91785 ↗
77. Visan AI, Negut I. Development and applications of PLGA hydrogels for sustained delivery of therapeutic agents. Gels. 2024;10:497. https://doi.org/10.3390/gels10080497.10.3390/gels10080497 ↗
78. Paul DR. Elaborations on the Higuchi model for drug delivery. Int J Pharm. 2011;418:13–7. https://doi.org/10.1016/j.ijpharm.2010.10.037.10.1016/j.ijpharm.2010.10.037 ↗
79. De La Monte SM, Tong M, Lawton M, Longato L. Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment. Mol Neurodegener. 2009;4:54. https://doi.org/10.1186/1750-1326-4-54.10.1186/1750-1326-4-54 ↗
80. Tong M, Neusner A, Longato L, Lawton M, Wands JR, De La Monte SM. Nitrosamine exposure causes insulin resistance diseases: relevance to type 2 diabetes mellitus, non-alcoholic steatohepatitis, and Alzheimer’s disease. J Alzheimers Dis. 2009;17:827–44. https://doi.org/10.3233/JAD-2009-1115.10.3233/JAD-2009-1115 ↗
81. Chen L, Feng P, Peng A, Qiu X, Lai W, Zhang L, et al. Protective effects of isoquercitrin on streptozotocin-induced neurotoxicity. J Cell Mol Med. 2020;24:10458–67. https://doi.org/10.1111/jcmm.15658.10.1111/jcmm.15658 ↗
82. d’Isa R, Comi G, Leocani L. Apparatus design and behavioural testing protocol for the evaluation of spatial working memory in mice through the spontaneous alternation T-maze. Sci Rep. 2021;11:21177. https://doi.org/10.1038/s41598-021-00402-7.10.1038/s41598-021-00402-7 ↗
83. Alvino FG, Carboncino A, Carrella D, Crain J, Iemolo A, Giordano NC, et al. Functional specialization of the hippocampus along its dorso-ventral axis: from span to supraspan in working memory capacity. bioRxiv. 2025. https://doi.org/10.1101/2025.10.07.680879.10.1101/2025.10.07.680879 ↗
84. Danduga RCSR, Kola PK. Elevated plus maze for assessment of anxiety and memory in rodents. In: Ray SK, editor. Neuroprotection, vol. 2761. New York. Springer, US: NY; 2024. p. 93–6.https://doi.org/10.1007/978-1-0716-3662-6_810.1007/978-1-0716-3662-6_8 ↗
85. Hernández-Mercado K, Zepeda A. Morris water maze and contextual fear conditioning tasks to evaluate cognitive functions associated with adult hippocampal neurogenesis. Front Neurosci. 2022;15:782947. https://doi.org/10.3389/fnins.2021.782947.10.3389/fnins.2021.782947 ↗
86. Olufunmilayo EO, Gerke-Duncan MB, Holsinger RMD. Oxidative stress and antioxidants in neurodegenerative disorders. Antioxidants. 2023;12:517. https://doi.org/10.3390/antiox12020517.10.3390/antiox12020517 ↗
87. Afzal M, Al-Abbasi FA, Kazmi I, Imam SS, Alshehri S, Ghoneim MM, et al. Fustin inhibits oxidative free radicals and inflammatory cytokines in cerebral cortex and hippocampus and protects cognitive impairment in streptozotocin-induced diabetic rats. ACS Chem Neurosci. 2021;12:4587–97. https://doi.org/10.1021/acschemneuro.1c00712.10.1021/acschemneuro.1c00712 ↗
88. Teleanu DM, Niculescu A-G, Lungu II, Radu CI, Vladâcenco O, Roza E, et al. An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases. IJMS. 2022;23:5938. https://doi.org/10.3390/ijms23115938.10.3390/ijms23115938 ↗
89. Sokal-Dembowska A, Jarmakiewicz-Czaja S, Tabarkiewicz J, Filip R. Nitrate and nitrite in the diet: protective and harmful effects in health and disease. Curr Nutr Rep. 2025;14:89. https://doi.org/10.1007/s13668-025-00678-5.10.1007/s13668-025-00678-5 ↗
90. P-M R, R-S E, G-Dm F, G-Z A. The effects of sodium nitrate on mitochondria. In: Mitochondrial intoxication. Elsevier; 2023. p. 707–21. https://doi.org/10.1016/B978-0-323-88462-4.00010-9.10.1016/B978-0-323-88462-4.00010-9 ↗
91. Ansari FA, Ali SN, Mahmood R. Sodium nitrite-induced oxidative stress causes membrane damage, protein oxidation, lipid peroxidation and alters major metabolic pathways in human erythrocytes. Toxicol In Vitro. 2015;29:1878–86. https://doi.org/10.1016/j.tiv.2015.07.022.10.1016/j.tiv.2015.07.022 ↗
92. Moreta MP-G, Burgos-Alonso N, Torrecilla M, Marco-Contelles J, Bruzos-Cidón C. Efficacy of acetylcholinesterase inhibitors on cognitive function in Alzheimer’s disease. Review of reviews. Biomedicines. 2021;9:1689. https://doi.org/10.3390/biomedicines9111689.10.3390/biomedicines9111689 ↗
93. Mehrbeheshti N, Esmaili Z, Ahmadi M, Moosavi M. A dose response effect of oral aluminum nanoparticle on novel object recognition memory, hippocampal caspase-3 and MAPKs signaling in mice. Behav Brain Res. 2022;417:113615. https://doi.org/10.1016/j.bbr.2021.113615.10.1016/j.bbr.2021.113615 ↗
94. Biswal B, Pattnaik S, Satapathy BS, Maharana L. Luliconazole-loaded nanoliposomes as a repurposing strategy to combat memory dysfunction in LPS-induced Alzheimer’s rats. ACS Omega. 2025. https://doi.org/10.1021/acsomega.5c09438.10.1021/acsomega.5c09438 ↗
95. Albanese A, Chan WCW. Effect of gold nanoparticle aggregation on cell uptake and toxicity. ACS Nano. 2011;5:5478–89. https://doi.org/10.1021/nn2007496.10.1021/nn2007496 ↗
96. Xu S, Olenyuk BZ, Okamoto CT, Hamm-Alvarez SF. Targeting receptor-mediated endocytotic pathways with nanoparticles: rationale and advances. Adv Drug Deliv Rev. 2013;65:121–38. https://doi.org/10.1016/j.addr.2012.09.041.10.1016/j.addr.2012.09.041 ↗
97. Behzadi S, Serpooshan V, Tao W, Hamaly MA, Alkawareek MY, Dreaden EC, et al. Cellular uptake of nanoparticles: journey inside the cell. Chem Soc Rev. 2017;46:4218–44. https://doi.org/10.1039/C6CS00636A.10.1039/C6CS00636A ↗
98. Partikel K, Korte R, Mulac D, Humpf H-U, Langer K. Serum type and concentration both affect the protein-corona composition of PLGA nanoparticles. Beilstein J Nanotechnol. 2019;10:1002–15. https://doi.org/10.3762/bjnano.10.101.10.3762/bjnano.10.101 ↗