A novel approach for oral delivery of ZINC using Zinc Sulfate solid lipid nanoparticles
- Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran
- Department of Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, IranSahar Baniyaghoob
Received: 2025-03-22
Revised: 2025-05-14
Accepted: 2025-05-26
Published in Issue 2025-05-28
Copyright (c) -1 Zahra Inanloo, Mohammad Yousefi, Sahar Baniyaghoob (Author)

This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
PDF views: 176
Abstract
One potential tool to improve the absorption of zinc (Zn) is the use of solid lipid nanoparticles (SLNs). In this study, Zn-containing SLNs were prepared to explore a novel oral formulation and investigate its physicochemical properties, toxicity, and accelerated stability study. SLNs were fabricated using stearic acid as lipid and chitosan as coating for LNPs via double emulsion solvent evaporation followed by lyophilization. In vitro evaluations were performed before and after lyophilization. Zinc loading was optimized at 30% zinc (w/w) versus lipid, with drug loading efficiency (DL) of up to 90%. The physicochemical properties of Zn-SLNs, including particle size (from 83.7 ± 1.8 to 183.8 ± 5.0 nm), dispersion index (PDI), zeta potential (about 8.2 mV), and differential scanning calorimetry (DSC), were investigated. Morphological characteristics were evaluated using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Drug release studies showed that 75%, 83%, and 90% of zinc were released from the SLN-Zn-Chitosan formulation within 24 hours, respectively. A cytotoxicity assay (MTT) performed at 24, 48, and 72 hours showed no cytotoxic potential with cell viability at 100% of control cells. The accelerated stability study to evaluate particle size, zeta potential, and drug loading (%EE) at 6 months showed no significant changes, which could indicate the suitability of Zn-SLNs for oral applications.
Keywords
- Chitosan,
- MTT,
- Nanoparticles,
- Solid lipid nanoparticles,
- Zinc sulfate
References
- Holghoomi, R., Kharab, Z., Rahdar, A., Pandey, S., & Ferreira, L. F. R. (2024). Harnessing the power of green synthesis of nanomaterials for anticancer applications: A review. Coordination Chemistry Reviews, 513, 215903. https:// 10.1016/j.ccr.2024.215903
- Saker, R., Regdon jr, G., & Sovány, T. (2024). Pharmacokinetics and toxicity of inorganic nanoparticles and the physicochemical properties/factors affecting them. Journal of Drug Delivery Science and Technology, 105979. https:// 10.1016/j.jddst.2024.105979
- Ganbarp``our, Z., Mirshafiei, M., Pourmadadi, M., Yazdian, F., Rashedi, H., Rahdar, A., ... & Pandey, S. (2025). Revolutionizing Dye Degradation: Enhanced Photocatalytic Performance of CQDs-Mg-ZnO Nanocomposites via RSM Optimization. BioNanoScience, 15(1), 1-14. http:// 10.1007/s12668-024-01738-w
- Shah, N., Soma, S. R., Quaye, M. B., Mahmoud, D., Ahmed, S., Malkoochi, A., & Obaid, G. (2024). A Physiochemical, In Vitro, and In Vivo Comparative Analysis of Verteporfin–Lipid Conjugate Formulations: Solid Lipid Nanoparticles and Liposomes. ACS Applied Bio Materials, 7(7), 4427-4441. https://doi.org/10.1021/acsabm.4c00316
- Duan, Y., Dhar, A., Patel, C., Khimani, M., Neogi, S., Sharma, P., ... & Vekariya, R. L. (2020). A brief review on solid lipid nanoparticles: Part and parcel of contemporary drug delivery systems. RSC advances, 10(45), 26777-26791. https:// 10.1039/D0RA03491F
- Syama, K., Jakubek, Z. J., Chen, S., Zaifman, J., Tam, Y. Y. C., & Zou, S. (2022). Development of lipid nanoparticles and liposomes reference materials (II): cytotoxic profiles. Scientific Reports, 12(1), 18071. https://doi.org/10.1038/s41598-022-23013-2.
- Lu, H., Zhang, S., Wang, J., & Chen, Q. (2021). A review on polymer and lipid-based nanocarriers and its application to nano-pharmaceutical and food-based systems. Frontiers in nutrition, 8, 783831. https://doi.org/10.3389/fnut.2021.783831
- Grüngreiff, K., Gottstein, T., & Reinhold, D. (2020). Zinc deficiency—An independent risk factor in the pathogenesis of haemorrhagic stroke?. Nutrients, 12(11),3548. https://doi.org/10.3390/nu12113548
- Tapiero, H., & Tew, K. D. (2003). Trace elements in human physiology and pathology: zinc and metallothioneins. Biomedicine & Pharmacotherapy, 57(9), 399-411.https://doi.org/10.1016/S0753-3322(03)00081-7
- Hambidge, K. M., & Krebs, N. F. (2007). Zinc Deficiency: A Special Challenge1. The Journal of nutrition, 137(4), 1101-1105. https://doi.org/10.1093/jn/137.4.1101
- Kumera, G., Awoke, T., Melese, T., Eshetie, S., Mekuria, G., Mekonnen, F., Gedle, D. (2015). Prevalence of zinc deficiency and its association with dietary, serum albumin and intestinal parasitic infection among pregnant women attending antenatal care at the University of Gondar Hospital, Gondar, Northwest Ethiopia. BMC Nutrition, 1, 1-11. https://doi.org/10.1186/s40795-015-0026-6
- Prasad, A. S. (2020). Clinical and immunological effects and biomarkers of zinc deficiency. In Essential and Toxic Trace Elements and Vitamins in Human Health (pp. 3-30). Academic Press. https://doi.org/10.1016/B978-0-12-805378-2.00002-4
- Sangeetha, V. J., Dutta, S., Moses, J. A., & Anandharamakrishnan, C. (2022). Zinc nutrition and human health: overview and implications. EFood, 3(5), e17. https://doi.org/10.1002/efd2.17
- Wegmüller, R., Tay, F., Zeder, C., Brnić, M., & Hurrell, R. F. (2014). Zinc absorption by young adults from supplemental zinc citrate is comparable with that from zinc gluconate and higher than from zinc oxide. The Journal of nutrition, 144(2), 132-136. https://doi.org/10.3945/jn.113.181487
- Wiernicka, A., Jańczyk, W., Dądalski, M., Avsar, Y., Schmidt, H., & Socha, P. (2013). Gastrointestinal side effects in children with Wilson's disease treated with zinc sulphate. World Journal of Gastroenterology: WJG, 19(27), 4356. https://doi.org/10.3748/wjg.v19.i27.4356
- H Muller, R., Shegokar, R., & M Keck, C. (2011). 20 years of lipid nanoparticles (SLN & NLC): present state of development & industrial applications. Current drug discovery technologies, 8(3), 207-227. https://doi.org/10.2174/157016311796799062
- Shegokar, R., Singh, K. K., & Müller, R. H. (2011). Production & stability of stavudine solid lipid nanoparticles—From lab to industrial scale. International journal of pharmaceutics, 416(2), 461-470. https://doi.org/10.1016/j.ijpharm.2010.08.014
- Zariwala, M. G., Elsaid, N., Jackson, T. L., López, F. C., Farnaud, S., Somavarapu, S., & Renshaw, D. (2013). A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles. International journal of pharmaceutics, 456(2), 400-407. https://doi.org/10.1016/j.ijpharm.2013.08.070
- Ganesan, P., & Narayanasamy, D. (2017). Lipid nanoparticles: Different preparation techniques, characterization, hurdles, and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery. Sustainable Chemistry and Pharmacy, 6, 37-56. (2017) 37-56. https://doi.org/10.1016/j.scp.2017.07.002
- Ancona, A., Dumontel, B., Garino, N., Demarco, B., Chatzitheodoridou, D., Fazzini, W., ... & Cauda, V. (2018). Lipid-coated zinc oxide nanoparticles as innovative ROS-generators for photodynamic therapy in cancer cells. Nanomaterials, 8(3), 143.https:// 10.3390/nano8030143
- Mendoza-Muñoz, N., Urbán-Morlán, Z., Leyva-Gómez, G., de la Luz Zambrano-Zaragoza, M., & Quintanar-Guerrero, D. (2021). Solid lipid nanoparticles: an approach to improve oral drug delivery. Journal of Pharmacy & Pharmaceutical Sciences, 24, 509-532. https:// 10.18433/jpps31788
- Dewangan, T., & Singh, C. A Nano-zinc Oxide-based Drug Delivery System and its Biomedical Applications. Natural and Engineering Sciences, 9(3), 193-203. https://doi.org/10.28978/nesciences.1606636
- Gasco, M. R., Priano, L., & Zara, G. P. (2009). Solid lipid nanoparticles and microemulsions for drug delivery: the CNS. Progress in brain research, 180, 181-192. https://doi.org/10.1016/S0079-6123(08)80010-6
- Prabhu, R. S., Priyanka, R., Vijay, M., & Vikashini, G. K. (2021). Field emission scanning electron microscopy (fesem) with a very big future in pharmaceutical research. Research Article—Pharmaceutical Sciences—OA Journal—MCI Approved—Index Copernicus, 11, 2321-3272.
- Cardoso, D., Narcy, A., Durosoy, S., Bordes, C., & Chevalier, Y. (2021). Dissolution kinetics of zinc oxide and its relationship with physicochemical characteristics. Powder Technology, 378, 746-759. https://doi.org/10.1016/j.powtec.2020.10.049
- Huang, Z., Wu, L., Wang, W., Wang, W., Fu, F., Zhang, X., ... & Wu, C. (2021). Major difference in particle size, minor difference in release profile: A case study of solid lipid nanoparticles. Pharmaceutical Development and Technology, 26(10), 1110-1119.
- Shah, R. M., Malherbe, F., Eldridge, D., Palombo, E. A., & Harding, I. H. (2014). Physicochemical characterization of solid lipid nanoparticles (SLNs) prepared by a novel microemulsion technique. Journal of colloid and interface science, 428, 286-294. https://doi.org/10.1016/j.jcis.2014.04.057
- Hosny, K. M., Banjar, Z. M., Hariri, A. H., & Hassan, A. H. (2015). Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia. Drug Design, Development and Therapy, 313-320. https://doi.org/10.2147/DDDT.S77702
- Grela, E., Kozłowska, J., & Grabowiecka, A. (2018). Current methodology of MTT assay in bacteria–A review. Acta histochemica, 120(4), 303-311. https://doi.org/10.1016/j.acthis.2018.03.007
- Van Meerloo, J., Kaspers, G. J., & Cloos, J. (2011). Cell sensitivity assays: the MTT assay. Cancer cell culture: methods and protocols, 237-245. https://doi.org/10.1007/978-1-61779-080-5_20
- Yusuf, H., Fahriani, M., & Murzalina, C. (2022). Anti proliferative and apoptotic effect of soluble ethyl acetate partition from ethanol extract of chromolaena odorata linn leaves against hela cervical cancer cell line. Asian Pacific Journal of Cancer Prevention: APJCP, 23(1), 183. https://doi.org/10.31557/apjcp.2022.23.1.183
- Riss, T. L., Moravec, R. A., Niles, A. L., Duellman, S., Benink, H. A., Worzella, T. J., & Minor, L. (2016). Cell viability assays. Assay guidance manual [Internet].
- Präbst, K., Engelhardt, H., Ringgeler, S., & Hübner, H. (2017). Basic colorimetric proliferation assays: MTT, WST, and resazurin. Cell viability assays: methods and protocols, 1-17. https://doi.org/10.1007/978-1-4939-6960-9_1
- Tolosa, L., Donato, M. T., & Gómez-Lechón, M. J. (2015). General cytotoxicity assessment by means of the MTT assay. Protocols in in vitro hepatocyte research, 333-348. https://doi.org/10.1007/978-1-4939-2074-7_26
- Gaur, P. K., Mishra, S., & Purohit, S. (2013). Solid lipid nanoparticles of guggul lipid as drug carrier for transdermal drug delivery. BioMed Research International, 2013(1), 750690. http:// 10.1155/2013/750690
- Kanagadurai, R., Durairajan, R., Sankar, R., Sivanesan, G., Elangovan, S. P., & Jayavel, R. (2009). Nucleation Kinetics, Growth and Characterization Studies of a Diamagnetic Crystal‐Zinc Sulphate Heptahydrate (ZSHH). Journal of Chemistry, 6(3), 871-879. http://dx.doi.org/10.1155/2009/459656
- Lustriane, C., Dwivany, F. M., Suendo, V., & Reza, M. (2018). Effect of chitosan and chitosan-nanoparticles on post harvest quality of banana fruits. Journal of Plant Biotechnology, 45(1), 36-44. http://dx.doi.org/10.5010/JPB.2018.45.1.036
- Ojha, S., & Kumar, B. (2018). Preparation and statistical modeling of solid lipid nanoparticles of dimethyl fumarate for better management of multiple sclerosis. Advanced pharmaceutical bulletin, 8(2), 225. https://doi.org/10.15171/apb.2018.027
- Jayarambabu, N., Kumari, B. S., Rao, K. V., & Prabhu, Y. T. (2015). Beneficial role of zinc oxide nanoparticles on green crop production. Int. J. Multidiscip. Adv. Res. Trends, 2(1), 273-282.
- Garcinuño, S., Aranaz, I., Civera, C., Arias, C., & Acosta, N. (2022). Evaluating non-conventional chitosan sources for controlled release of risperidone. Polymers, 14(7), 1355. https://doi.org/10.3390/polym14071355
- Cavalli, R., Caputo, O., Carlotti, M. E., Trotta, M., Scarnecchia, C., & Gasco, M. R. (1997). Sterilization and freeze-drying of drug-free and drug-loaded solid lipid nanoparticles. International journal of pharmaceutics, 148(1), 47-54. https://doi.org/10.1016/S0378-5173(96)04822-3
- Harzali, H., Espitalier, F., Louisnard, O., & Mgaidi, A. (2010). Sono-crystallization of ZnSO4⋅ 7H20. Physics Procedia, 3(1), 965-970. https://doi.org/10.1016/j.phpro.2010.01.124
- Kathe, N., Henriksen, B., & Chauhan, H. (2014). Physicochemical characterization techniques for solid lipid nanoparticles: principles and limitations. Drug development and industrial pharmacy, 40(12), 1565-1575. https://doi.org/10.3109/03639045.2014.909840
- da Rocha, M. C. O., da Silva, P. B., Radicchi, M. A., Andrade, B. Y. G., de Oliveira, J. V., Venus, T., ... & Báo, S. N. (2020). Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells. Journal of nanobiotechnology, 18, 1-20. https://doi.org/10.1186/s12951-020-00604-7
10.57647/j.ijnd.2025.1604.28
