Volume: 46 Issue: 3
Year: 2026, Page: 227-239, Doi: https://doi.org/10.51248/v46i3.70
Received: June 19, 2026 Accepted: Sept. 9, 2026 Published: Sept. 17, 2026
Introduction and Aim: Type 2 diabetes mellitus (T2DM) remains a major global health challenge requiring improved drug delivery strategies. Zein, a maize-derived biopolymer, has attracted attention as a drug carrier because of its biocompatibility and controlled-release properties. This study aimed to synthesize zein-based zinc oxide nanoparticles (Zein-ZnONPs), characterize their physicochemical properties, evaluate their biological activities, and investigate their potential for metformin hydrochloride delivery.
Materials and Methods: Zein-ZnONPs were synthesized using a solution combustion approach and characterized by UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential analysis, and scanning electron microscopy (SEM). Metformin hydrochloride was encapsulated into the nanoparticles and evaluated by SEM and UV-Vis analysis. Antioxidant, anti-inflammatory, and antibacterial activities were assessed using DPPH radical scavenging, protein denaturation inhibition, and disc diffusion assays, respectively. Drug-release behavior was studied under simulated gastrointestinal conditions.
Results: Zein-ZnONPs exhibited particle sizes of 105-222 nm and a zeta potential of +4.5 mV. Characterization studies confirmed the formation of crystalline ZnO nanoparticles stabilized by zein. The nanoparticles showed concentration-dependent antioxidant activity with 95% DPPH inhibition at 100 μg mL⁻¹ and anti-inflammatory activity with 90.7% inhibition of protein denaturation at 1000 μg mL⁻¹. Moderate antibacterial activity was observed against the tested microorganisms. Metformin-loaded Zein-ZnONPs exhibited a biphasic drug-release profile with an estimated half-life of 7.7 h.
Conclusion: Zein-ZnONPs demonstrated favorable physicochemical properties, biological activities, and sustained drug-release behavior, indicating their potential as a nanocarrier for metformin delivery. Further studies are required to evaluate their therapeutic applicability in vivo.
Keywords: Zein-ZnONPs; Metformin; Antioxidant; Maize; Zinc oxide; Anti-inflammatory; Antibacterial
1. Noor-ul-Ain R, Ilyas N, Saeed M, Subramaniam G, Mastinu A. Advances in pharmaceutical and biomedical applications of plant-based nano-biopolymers with special emphasis on vaginal drug delivery systems: A review. Industrial Crops and Products. 2025 Mar;225:120592. doi:10.1016/j.indcrop.2025.120592
2. Reshma AR, Rekha MR. Zein-A plant protein as a promising biopolymer for biomedical applications: A perspective. J Polym Sci Eng. 2024 Apr 2;7(1):3618. doi:10.24294/jpse.v7i1.3618
3. Liu G, An D, Li J, Deng S. Zein-based nanoparticles: Preparation, characterization, and pharmaceutical application. FrontPharmacol. 2023 Feb 1;14:1120251. doi:10.3389/fphar.2023.1120251
4. Raha S, Ahmaruzzaman Md. ZnO nanostructured materials and their potential applications: progress, challenges and perspectives. Nanoscale Adv. 2022;4(8):1868–925. doi:10.1039/D1NA00880C
5. Hussein Na G, Ebraheem A F, Kurakula M, Abdulaziz A, Mohamed Ho K, Mohammed A H, et al., Zein Coated Zinc Oxide Nanoparticles: Fabrication and Antimicrobial Evaluation as Dental Aid. International J of Pharmacology. 2018 Nov 1;14(8):1051–9. doi:10.3923/ijp.2018.1051.1059
6. Shaban EE, Abd El-Aziz ME, Ibrahim KS, Nasr SM, Desouky HM, Elbakry HFH. Effect of zinc oxide nanoparticles on diabetes development and complications in diabetic rats compared to conventional zinc sulfate and metformin. Biocatalysis and Agricultural Biotechnology. 2022 Nov;46:102538. doi:10.1016/j.bcab.2022.102538
7. Bhavi SM, Yarajarla RB. Preliminary Evidence of GLUT4 Upregulation and Biocompatibility of Syzygium caryophyllatum ‐Derived Silver Nanoparticles in 3T3‐L1 Preadipocytes. Cell Biochemistry & amp; Function. 2026 May;44(5):e70236. doi:10.1002/cbf.70236
8. Wang H, Zhu C, Ying Y, Luo L, Huang D, Luo Z. Metformin and berberine, two versatile drugs in treatment of common metabolic diseases. Oncotarget. 2018 Feb 9;9(11):10135-46. doi:10.18632/oncotarget.20807
9. Parris N, Dickey LC. Extraction and Solubility Characteristics of Zein Proteins from Dry-Milled Corn. J Agric Food Chem. 2001 Aug 1;49(8):3757-60. doi:10.1021/jf0011790
10. Sheibani E, Soltani Alasvand S, Sami N, Vahdati Khaki J, Mollazadeh Beidokhti S. The Solution Combustion Synthesis of ZnO Nanoparticles Using Allium schoenoprasum (Chives) as a Green Fuel. Compounds. 2024Aug 19;4(3):503–20. doi:10.3390/compounds4030030
11. Elmahboub Y, Albash R, Magdy William M, Rayan AH, Hamed NO, Ousman MS, et al., Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In-vivo Study. Molecules. 2024 Apr 3;29(7):1614. doi:10.3390/molecules29071614
12. Singh SR, Bhavi SM, Thokchom B, Abbigeri MB, Padti AC, Yadawad A, et al., An evaluation of carbon dots derived from Amaranthus tricolor (L.) leaves for their physicochemical, photoluminescent, and biomedical properties. Discov Appl Sci. 2025 May 20;7(6):513. doi:10.1007/s42452-025-06936-z
13. Ramakrishnan M, Shanmugam R, Neeharika S, Selvaraj S, Chokkattu JJ, Thangavelu L. Anti-inflammatory Potential of a Mouthwash Formulated Using Clove and Ginger Mediated by Zinc Oxide Nanoparticles: An In-vitro Study. World Journal of Dentistry. 2023 Aug 2;14(5):394-401. doi:10.5005/jp-journals-10015-2232
14. Raj NB, PavithraGowda NT, Pooja OS, Purushotham B, Kumar MRA, Sukrutha SK, et al., Harnessing ZnO nanoparticles for antimicrobial and photocatalytic activities. Journal of Photochemistry and Photobiology. 2021 Jun;6:100021. doi:10.1016/j.jpap.2021.100021
15. Selim YA, Azb MA, Ragab I, H. M. Abd El-Azim M. Green Synthesis of Zinc Oxide Nanoparticles Using Aqueous Extract of Deverra tortuosa and their Cytotoxic Activities. Sci Rep. 2020 Feb 26;10(1):3445. doi:10.1038/s41598-020-60541-1
16. Muhammad W, Ullah N, Haroon M, Abbasi BH. Optical, morphological and biological analysis of zinc oxide nanoparticles (ZnO NPs) using Papaver somniferum L. RSC Adv. 2019;9(51):29541–8. doi:10.1039/C9RA04424H
17. Oleandro E, Stanzione M, Buonocore GG, Lavorgna M. Zein-Based Nanoparticles asActive Platforms for Sustainable Applications: Recent Advances and Perspectives. Nanomaterials. 2024 Feb 23;14(5):414. doi:10.3390/nano14050414
18. Jayswal S, Moirangthem RS. Thermal decomposition route to synthesize ZnO nanoparticles for photocatalytic application. In. Noida, India; 2018 [cited 2025 Aug 28]. p. 020023. Available from: https://pubs.aip.org/aip/acp/article/766699 doi:10.1063/1.5052092
19. Darie-Ion L, Jayathirtha M, Hitruc GE, Zaharia MM, Gradinaru RV, Darie CC, et al., A Proteomic Approach to Identify Zein Proteins upon Eco-Friendly Ultrasound-Based Extraction. Biomolecules. 2021 Dec 6;11(12):1838. doi:10.3390/biom11121838
20. Schmitz F, Silva De Albuquerque MB, Alberton MD, Riegel-Vidotti IC, Zimmermann LM. Zein films with ZnO and ZnO:Mg quantum dots as functional nanofillers: New nanocomposites for food package with UV-blocker and antimicrobial properties. Polymer Testing. 2020 Nov;91:106709. doi:10.1016/j.polymertesting.2020.106709
21. Mohd Yusof H, Abdul Rahman N, Mohamad R, Zaidan UH, Samsudin AA. Optimization of biosynthesis zinc oxide nanoparticles: Desirability-function based response surface methodology, physicochemical characteristics, and its antioxidant properties. OpenNano. 2022 Nov;8:100106. doi:10.1016/j.onano.2022.100106
22. Perumal P, Sathakkathulla NA, Kumaran K, Ravikumar R, Selvaraj JJ, Nagendran V, et al.,Green synthesis of zinc oxide nanoparticles using aqueous extract of shilajit and their anticancer activity against HeLa cells. Sci Rep. 2024 Jan 25;14(1):2204. doi:10.1038/s41598-024-52217-x
23. Bhavi SM, Padti AC, Thokchom B, Singh SR, Bhat SS, Bajire SK, et al., Biogenic silver nanoparticles from Simarouba glauca DC leaf extract: Synthesis, characterization, and anticancer efficacy in lung cancer cells with protective effects in Caenorhabditis elegans. Nano TransMed. 2024Dec;3:100052. doi:10.1016/j.ntm.2024.100052
24. Yassin MT, Mostafa AAF, Al-Askar AA, Al-Otibi FO. Facile Green Synthesis of Zinc Oxide Nanoparticles with Potential Synergistic Activity with Common Antifungal Agents against Multidrug-Resistant Candidal Strains. Crystals. 2022 May 26;12(6):774. doi:10.3390/cryst12060774
25. Gandhi PR, Jayaseelan C, Mary RR, Mathivanan D, Suseem SR. Acaricidal, pediculicidal and larvicidal activity of synthesized ZnO nanoparticles using Momordica charantia leaf extract against blood feeding parasites. Experimental Parasitology. 2017 Oct;181:47–56. doi:10.1016/j.exppara.2017.07.007
26. Ezzat N, Emadeldien N, Ali M, Fahd S, Shebl S, Elshishiny M, et al., In-vitro Evaluation of Zinc Oxide-Metformin Folic Acid Nanocomposite as a Targeted Drug Delivery System for Cancer Therapy. Asian Pac J Cancer Prev. 2025 Feb 1;26(2):443–52. doi:10.31557/APJCP.2025.26.2.443
27. Adibipour F, Salehirad M, Hayes AW, Hekmati M, Motaghinejad M. Preventive Effect of ZnO-Metformin Nanocomposite Against Carbon Tetrachloride-Induced Hepatotoxicity. Nanomed Res J. 2024 Apr;9(2). doi:10.22034/nmrj.2024.02.004
28. Senthilkumar N, Nandhakumar E, Priya P, Soni D, Vimalan M, Vetha Potheher I. Synthesis of ZnO nanoparticles using leaf extract of Tectona grandis (L.) and their anti-bacterial, anti-arthritic, anti-oxidant and in-vitro cytotoxicity activities. New J Chem. 2017;41(18):10347–56. doi:10.1039/C7NJ02664A
29. Shaban AS, Owda ME, Basuoni MM, Mousa MA, Radwan AA, Saleh AK. Punica granatum peel extract mediated green synthesis of zinc oxide nanoparticles: structure and evaluation of their biological applications. Biomass Conv Bioref. 2024 Jun;14(11):12265–81. doi:10.1007/s13399-022-03185-7
30. Zhu Z, Liang J, Zhou C, Huang K, Fan X, Zhou M, et al., Synergistic enhancement ofgelatin-chitosan films with vanillin Schiff base and ZnO for effective strawberry preservation. Food Control. 2026 Feb;180:111647. doi:10.1016/j.foodcont.2025.111647
31. Zahoor S, Sheraz S, Shams DF, Rehman G, Nayab S, Shah MIA, et al., Biosynthesis and Anti-inflammatory Activity of Zinc Oxide Nanoparticles Using Leaf Extract of Senecio chrysanthemoides. Ulusoy C, editor. BioMed Research International. 2023 Jan;2023(1):3280708. doi:10.1155/2023/3280708
32. Kyene MO, Droepenu EK, Ayertey F, Yeboah GN, Archer MA, Kumadoh D, et al., Synthesis and characterization of ZnO nanomaterial from Cassia sieberiana and determination of its anti-inflammatory, antioxidant and antimicrobial activities. Scientific African. 2023 Mar;19:e01452. doi:10.1016/j.sciaf.2022.e01452
33. Ahire ED, Savaliya N, Makwana KV, Salave S, Banth MK, Bhavsar B, et al., Protein-Bound Nano-Injectable Suspension: Unveiling the Promises and Challenges. Applied Nano. 2025 May 30;6(2):9. doi:10.3390/applnano6020009
34. Khamis M, Gouda GA, Nagiub AM. Biosynthesis approach of zinc oxide nanoparticles for aqueous phosphorous removal: physicochemical properties and antibacterial activities. BMC Chemistry. 2023 Aug 16;17(1):99. doi:10.1186/s13065-023-01012-2
35. Mendes CR, Dilarri G, Forsan CF, Sapata VDMR, Lopes PRM, De Moraes PB, et al., Antibacterial action and target mechanisms of zinc oxide nanoparticles against bacterial pathogens. Sci Rep. 2022 Feb 16;12(1):2658. doi:10.1038/s41598-022-06657-y
Santosh Mallikarjun Bhavi, Rekha R., Naveen M. V., Sushmitha Mavinkar, Pavithra R., Chandrakala S., Bothe Thokchom, Akshata Choudhari Padti, Sapam Riches Singh, Ramesh Babu Yarajarla, B. S. Srinath. Zein-Based Zinc Oxide Nanoparticles for Metformin Encapsulation: Synthesis, Characterization, and Biological Applications. Biomedicine: 2026, 46(3): 227-239. https://doi.org/10.51248/v46i3.70