Evaluation of the Effects of Nanoparticles in the Treatment of Diabetes Mellitus: A Systematic Review and Meta-analysis

Document Type : Review Article


1 Department of Pharmacology and Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Cardiology, Rajayi Heart Center, Iran University of Medical Sciences, Tehran, Iran

3 Department of Internal Diseases, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

4 Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

5 Department of Internal Medicine, Noor Iranian Polyclinic, Muscat, Oman


Background and aim: Due to the importance of the issue in the treatment and prevention of diabetes mellitus, in the present study, it is decided to investigate the role of nanoparticles in the treatment or prevention of the development of diabetes mellitus. The aim of the present study was to evaluate the effects of nanoparticles in the treatment of diabetes mellitus.
Material and methods: The present study is a systematic review and meta-analysis based on PRISMA 2020 Checklist. Databases of PubMed, Scopus, Web of Science, EBSCO, ISI Web of knowledge, and Embase were searched for systematic literature until 20 November 2022. A 95% confidence interval for mean differences with the random effect model and REML method were calculated. Meta-analysis was performed using Stata/MP v.17 software.
Results: In the initial review, duplicate studies were eliminated, abstracts of 219 studies were reviewed, and two authors reviewed the full text of 184 studies. Finally, nine studies were selected. The mean differences in Fasting blood sugar between the silver nanoparticles group and zinc oxide nanoparticles vs. group was -209.92 (MD: -209.92 95% CI; -272.56, -147.28; p=0.00) and -1.58 (MD: -1.58 95% CI; -2.38, -0.78; p=0.00), respectively.
Conclusions: Based on the present meta-analysis, administering silver nanoparticles and zinc oxide nanoparticles in animal models can have antidiabetic effects and reduce fasting blood sugar levels.


Main Subjects

[1]        Jwad SM, AL-Fatlawi HY. Types of Diabetes and their Effect on the Immune System. J. Adv. Pharm. Pract. 2022;4:21-30.
[2]        Prabhakar PK. Pathophysiology of secondary complications of diabetes mellitus. Pathophysiology. 2016;9(1).
[3]        Manukumar HM, Shiva Kumar J, Chandrasekhar B, Raghava S, Umesha S. Evidences for diabetes and insulin mimetic activity of medicinal plants: present status and future prospects. Critical Reviews in Food Science and Nutrition. 2017;57(12):2712-29. https://doi.org/10.1080/10408398.2016.1143446.
[4] DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nature reviews Disease primers. 2015;1(1):1-22. https://doi.org/10.1038/nrdp.2015.19.
[5]        Sharma R, Juyal D, Negi A. Epidemiology of diabetes mellitus and its recent awareness with the use of advance medication. The Pharma Innovation Journal. 2018;7(6):87-8.
[6]        Virgen-Ortiz A, Limón-Miranda S, Soto-Covarrubias MA, Apolinar-Iribe A, Rodríguez-León E, Iñiguez-Palomares R. Biocompatible silver nanoparticles synthesized using rumex hymenosepalus extract decreases fasting glucose levels in diabetic rats. Dig. J. Nanomater. Biostruct. 2015;10:927-33.
[7]        San Tang K. The current and future perspectives of zinc oxide nanoparticles in the treatment of diabetes mellitus. Life sciences. 2019;239:117011. https://doi.org/10.1016/j.lfs.2019.117011.
[8]        Martínez-Esquivias F, Guzmán-Flores JM, Párez-Larios A, Rico JL, Becerra-Ruiz JS. A review of the effects of gold, silver, selenium, and zinc nanoparticles on diabetes mellitus in murine models. Mini Reviews in Medicinal Chemistry. 2021;21(14):1798-812. https://doi.org/10.2174/1389557521666210203154024.
[9]        Sengottaiyan A, Aravinthan A, Sudhakar C, Selvam K, Srinivasan P, Govarthanan M, et al. Synthesis and characterization of Solanum nigrum-mediated silver nanoparticles and its protective effect on alloxan-induced diabetic rats. Journal of Nanostructure in Chemistry. 2016;6(1):41-8. https://doi.org/10.1007/s40097-015-0178-6.
[10] Basavaraja S, Balaji SD, Lagashetty A, Rajasab AH, Venkataraman A. Extracellular biosynthesis of silver nanoparticles using the fungus Fusarium semitectum. Materials Research Bulletin. 2008;43(5):1164-70. https://doi.org/10.1016/j.materresbull.2007.06.020.
[11] Jha AK, Prasad K. Green synthesis of silver nanoparticles using Cycas leaf. International Journal of Green Nanotechnology: Physics and Chemistry. 2010;1(2):110-7. https://doi.org/10.1080/19430871003684572.
[12] Alkaladi A, Abdelazim AM, Afifi M. Antidiabetic activity of zinc oxide and silver nanoparticles on streptozotocin-induced diabetic rats. International journal of molecular sciences. 2014;15(2):2015-23. https://doi.org/10.3390/ijms15022015.
[13] Gaillet S, Rouanet JM. Silver nanoparticles: their potential toxic effects after oral exposure and underlying mechanisms–a review. Food and Chemical Toxicology. 2015;77:58-63. https://doi.org/10.1016/j.fct.2014.12.019.
[14] Loeschner K, Hadrup N, Qvortrup K, Larsen A, Gao X, Vogel U, et al. Distribution of silver in rats following 28 days of repeated oral exposure to silver nanoparticles or silver acetate. Particle and fibre toxicology. 2011;8(1):1-4. https://doi.org/10.1186/1743-8977-8-18.
[15] Van der Zande M, Vandebriel RJ, Van Doren E, Kramer E, Herrera Rivera Z, Serrano-Rojero CS, et al. Distribution, elimination, and toxicity of silver nanoparticles and silver ions in rats after 28-day oral exposure. ACS nano. 2012;6(8):7427-42.
[16] Tugwell P, Tovey D. PRISMA 2020. Journal of Clinical Epidemiology. 2021;134:A5-6. https://doi.org/10.1016/j.jclinepi.2021.04.008.
[17] Macleod MR, O’Collins T, Howells DW, Donnan GA. Pooling of animal experimental data reveals influence of study design and publication bias. Stroke. 2004;35(5):1203-8. https://doi.org/10.1161/01.STR.0000125719.25853.20.
[18] Ul Haq MN, Shah GM, Menaa F, Khan RA, Althobaiti NA, Albalawi AE, et al. Green Silver Nanoparticles Synthesized from Taverniera couneifolia Elicits Effective Anti-Diabetic Effect in Alloxan-Induced Diabetic Wistar Rats. Nanomaterials. 2022;12(7):1035. https://doi.org/10.3390/nano12071035.
[19] Olojede SO, Lawal SK, Faborode OS, Dare A, Aladeyelu OS, Moodley R, et al. Testicular ultrastructure and hormonal changes following administration of tenofovir disoproxil fumarate-loaded silver nanoparticle in type-2 diabetic rats. Scientific Reports. 2022;12(1):1-2. https://doi.org/10.1038/s41598-022-13321-y.
[20] Gadoa ZA, Moustafa AH, El Rayes SM, Arisha AA, Mansour MF. Zinc Oxide Nanoparticles and Synthesized Pyrazolopyrimidine Alleviate Diabetic Effects in Rats Induced by Type II Diabetes. ACS omega. 2022;7(41):36865-72.
[21] Virgen-Ortiz A, Apolinar-Iribe A, Díaz-Reval I, Parra-Delgado H, Limón-Miranda S, Sánchez-Pastor EA, et al. Zinc Oxide nanoparticles induce an adverse effect on blood glucose levels depending on the dose and route of administration in healthy and diabetic rats. Nanomaterials. 2020;10(10):2005. https://doi.org/10.3390/nano10102005.
[22] Prabhu S, Vinodhini S, Elanchezhiyan C, Rajeswari D. Retracted: Evaluation of antidiabetic activity of biologically synthesized silver nanoparticles using Pouteria sapota in streptozotocin‐induced diabetic rats: 在链脲霉素‐诱导的糖尿病大鼠中评估使用山榄果生物合成的银纳米粒子的降糖活性. Journal of diabetes. 2018;10(1):28-42. https://doi.org/10.1111/1753-0407.12554.
[23] Ansari MA, Khan HM, Khan AA, Alzohairy MA, Waseem M, Ahmad MK, et al. Biochemical, histopathological, and transmission electron microscopic ultrastructural changes in mice after exposure to silver nanoparticles. Environmental toxicology. 2016;31(8):945-56. https://doi.org/10.1002/tox.22104.
[24] Masood N, Ahmed R, Tariq M, Ahmed Z, Masoud MS, Ali I, et al. Silver nanoparticle impregnated chitosan-PEG hydrogel enhances wound healing in diabetes induced rabbits. International journal of pharmaceutics. 2019;559:23-36. https://doi.org/10.1016/j.ijpharm.2019.01.019.
[25] Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJ, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. New England Journal of Medicine. 2019;380(24):2295-306. https://doi.org/10.1056/NEJMoa1811744.
[26] Attanayake AP, Jayatilaka KA, Pathirana C, Mudduwa LK. Study of antihyperglycaemic activity of medicinal plant extracts in alloxan induced diabetic rats. Ancient Science of life. 2013;32(4):193-8. https://doi.org/10.4103%2F0257-7941.131970.
[27] Fröde TS, Medeiros YS. Animal models to test drugs with potential antidiabetic activity. Journal of ethnopharmacology. 2008;115(2):173-83. https://doi.org/10.1016/j.jep.2007.10.038.
[28] Kim YS, Kim JS, Cho HS, Rha DS, Kim JM, Park JD, et al. Twenty-eight-day oral toxicity, genotoxicity, and gender-related tissue distribution of silver nanoparticles in Sprague-Dawley rats. Inhalation toxicology. 2008;20(6):575-83. https://doi.org/10.1080/08958370701874663.
[29] Xue Y, Zhang S, Huang Y, Zhang T, Liu X, Hu Y, et al. Acute toxic effects and gender‐related biokinetics of silver nanoparticles following an intravenous injection in mice. Journal of Applied Toxicology. 2012;32(11):890-9. https://doi.org/10.1002/jat.2742.
[30] Braydich-Stolle L, Hussain S, Schlager JJ, Hofmann MC. In vitro cytotoxicity of nanoparticles in mammalian germline stem cells. Toxicological sciences. 2005;88(2):412-9. https://doi.org/10.1093/toxsci/kfi256.