{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T09:30:50Z","timestamp":1787909450251,"version":"build-2784847793"},"reference-count":55,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2017\/27\/N\/NZ4\/01219"],"award-info":[{"award-number":["2017\/27\/N\/NZ4\/01219"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Iron plays an important role in various crucial processes in the body and its deficiency is considered currently as a serious health problem. Thus, iron supplementation strategies for both humans and animals need to be effective and safe. According to our previous studies, zinc-based nanoparticles provide safe, biodegradable, fast and efficient transport system of orally given substances to the tissues. In the current manuscript we present results of a study aimed at investigation of the ZnO nanoparticle-based Fe supplementation system (average size 100 \u00d7 250 nm). Nanostructures were orally (gavage) administered to adult mice. Animals were sacrificed at different time points with collection of blood and internal organs for analyses (tissue iron concentration, hepatic level of hepcidin, blood parameters, liver and spleen levels of ferritin, histopathology). Initial experiment was performed to compare the biological effect of doping type (Fe3+ doping vs. a mixture of Fe3+ and Fe2+). Then, the effect of acute\/chronic exposure models was determined. The increase in ferritin, along with improved, crucial hematological parameters and lack of the influence on hepcidin expression indicated the chronic application of Fe3+,2+ doped ZnO nanostructures to be the most effective among tested.<\/jats:p>","DOI":"10.3390\/ph14090859","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T04:07:28Z","timestamp":1630382848000},"page":"859","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Biodegradable Zinc Oxide Nanoparticles Doped with Iron as Carriers of Exogenous Iron in the Living Organism"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6069-6201","authenticated-orcid":false,"given":"Paula","family":"Kie\u0142bik","sequence":"first","affiliation":[{"name":"Institute of Veterinary Medicine, Department of Physiological Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Jo\u0144czy","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Animal Biotechnology, Department of Molecular Biology, Polish Academy of Sciences (PAS), 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw","family":"Kaszewski","sequence":"additional","affiliation":[{"name":"Institute of Physics, Polish Academy of Sciences (PAS), 02-668 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miko\u0142aj","family":"Gralak","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Medicine, Department of Physiological Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julita","family":"Rosowska","sequence":"additional","affiliation":[{"name":"Institute of Physics, Polish Academy of Sciences (PAS), 02-668 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142","family":"Sapierzy\u0144ski","sequence":"additional","affiliation":[{"name":"Division of Pathology, Institute of Veterinary Medicine, Department of Pathology and Veterinary Diagnostics, Warsaw University of Life Sciences, 02-776 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0108-6902","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Institute of Physics, Polish Academy of Sciences (PAS), 02-668 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"Wachnicki","sequence":"additional","affiliation":[{"name":"Institute of Physics, Polish Academy of Sciences (PAS), 02-668 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystyna","family":"Lawniczak-Jablonska","sequence":"additional","affiliation":[{"name":"Institute of Physics, Polish Academy of Sciences (PAS), 02-668 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Kuzmiuk","sequence":"additional","affiliation":[{"name":"Institute of Physics, Polish Academy of Sciences (PAS), 02-668 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0121-4460","authenticated-orcid":false,"given":"Pawe\u0142","family":"Lipi\u0144ski","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Animal Biotechnology, Department of Molecular Biology, Polish Academy of Sciences (PAS), 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Godlewski","sequence":"additional","affiliation":[{"name":"Institute of Physics, Polish Academy of Sciences (PAS), 02-668 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142 Marek","family":"Godlewski","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Medicine, Department of Physiological Sciences, Warsaw University of Life Sciences, 02-787 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,27]]},"reference":[{"key":"ref_1","first-page":"444","article-title":"Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993\u20132005","volume":"23","author":"McLean","year":"2008","journal-title":"Public Health Nutr."},{"key":"ref_2","unstructured":"de Benoist, B., McLean, E., Egli, I., and Cogswell, M. (2008). Worldwide Prevalence of Anaemia 1993\u20132005: WHO Global Database on Anaemia, World Health Organization."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1186\/s13054-014-0678-7","article-title":"Iron is essential for living!","volume":"18","author":"Lasocki","year":"2014","journal-title":"Crit. Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0098-2997(00)00006-6","article-title":"The roles of iron in health and disease","volume":"22","author":"Lieu","year":"2001","journal-title":"Mol. Asp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1280S","DOI":"10.1093\/ajcn\/71.5.1280s","article-title":"Anemia and iron deficiency: Effects on pregnancy outcome","volume":"71","author":"Allen","year":"2000","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0140-6736(07)61235-5","article-title":"Nutritional iron deficiency","volume":"370","author":"Zimmermann","year":"2007","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1093\/jpepsy\/jsp065","article-title":"Longitudinal evaluation of externalizing and internalizing behavior problems following iron deficiency in infancy","volume":"35","author":"Corapci","year":"2010","journal-title":"J. Pediatr. Psychol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2754\/avb201887010077","article-title":"Oral iron administration in suckling piglets\u2014A review","volume":"87","author":"Svoboda","year":"2018","journal-title":"Acta Vet. Brno"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2353\/ajpath.2010.091020","article-title":"Benefits and risks of iron supplementation in anemic neonatal pigs","volume":"177","author":"Lipinski","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3945\/jn.111.148643","article-title":"Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats","volume":"142","author":"Dostal","year":"2012","journal-title":"J. Nutr."},{"key":"ref_11","first-page":"104","article-title":"Iron deficiency in suckling piglets: Ethiology, clinical aspects and diagnosis (a review)","volume":"49","author":"Svoboda","year":"2005","journal-title":"Folia Vet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.2754\/avb200776S8S011","article-title":"Intramuscular versus subcutaneous administration of iron dextran in suckling piglets","volume":"76","author":"Svoboda","year":"2007","journal-title":"Acta Vet. Brno"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Szudzik, M., Starzy\u0144ski, R.R., Jo\u0144czy, A., Mazgaj, R., Lenartowicz, M., and Lipi\u0144ski, P. (2018). Iron Supplementation in Suckling Piglets: An Ostensibly Easy Therapy of Neonatal Iron Deficiency Anemia. Pharmaceuticals, 11.","DOI":"10.20944\/preprints201810.0189.v1"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1053\/rvsc.1998.0223","article-title":"An evaluation of iron-dextran supplementation in piglets administered by injection on the first, third or fourth day after birth","volume":"66","author":"Egeli","year":"1999","journal-title":"Res. Vet. Sci."},{"key":"ref_15","first-page":"21","article-title":"More iron?","volume":"28","author":"Roberts","year":"1998","journal-title":"Pig. Int."},{"key":"ref_16","first-page":"115","article-title":"The effect of suplementing sow with bioactive substances on neonatal small intestinal epithelium","volume":"58","author":"Strzalkowski","year":"2007","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1053\/j.ajkd.2012.10.027","article-title":"Understanding iron: Promoting its safe use in patient with chronic kidney failure treated by hemodialysis","volume":"61","author":"Vaziri","year":"2013","journal-title":"Am. J. Kidney Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1046\/j.1523-1755.1999.055Suppl.69061.x","article-title":"Strategies for iron supplementation: Oral versus intravenous","volume":"69","author":"Macdougall","year":"1999","journal-title":"Kidney Int. Suppl."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.2215\/CJN.02690409","article-title":"Hepcidin assays: Ironing out some details","volume":"4","author":"Malyszko","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1182\/blood-2003-03-0672","article-title":"Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation","volume":"102","author":"Ganz","year":"2003","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e00192","DOI":"10.1042\/BSR20150014","article-title":"Hepcidin: Regulation of the master iron regulator","volume":"35","author":"Rishi","year":"2015","journal-title":"Biosci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Staro\u0144, R., Van Swelm, R.P., Lipi\u0144ski, P., Gajowiak, A., Lenartowicz, M., Bednarz, A., Gajewska, M., Pieszka, M., Laarakkers, C.M., and Swinkels, D.W. (2015). Urinary hepcidin levels in iron-deficient and iron-supplemented piglets correlate with hepcidin hepatic mRNA and serum levels and with body iron status. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136695"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Starzy\u0144ski, R.R., Laarakkers, C.M., Tjalsma, H., Swinkels, D.W., Pieszka, M., Sty\u015b, A., Mickiewicz, M., and Lipi\u0144ski, P. (2013). Iron supplementation in suckling piglets: How to correct iron deficiency anemia without affecting plasma hepcidin levels. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064022"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1515\/ntrev-2020-0022","article-title":"New generation of oxide-based nanoparticles for the applications in early cancer detection and diagnostics","volume":"9","author":"Godlewski","year":"2020","journal-title":"Nanotechnol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/S2222-1808(15)60929-X","article-title":"Nano particles: An emerging tool in biomedicine","volume":"5","author":"Amjad","year":"2015","journal-title":"Asian Pac. J. Trop. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Mozafari, M.R. (2007). Micro and Nano Systems in Biomedicine and Drug Delivery. Nanomaterials and Nanosystems for Biomedical Applications, Springer.","DOI":"10.1007\/978-1-4020-6289-6"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7551","DOI":"10.1021\/nn504577x","article-title":"A Growing Place for Nano in Medicine","volume":"8","author":"Hammond","year":"2014","journal-title":"ACS Nano"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1186\/s11671-019-3217-2","article-title":"Preliminary Studies on Biodegradable Zinc Oxide Nanoparticles Doped with Fe as a Potential Form of Iron Delivery to the Living Organism","volume":"14","author":"Kielbik","year":"2019","journal-title":"Nanoscale Res. Lett."},{"key":"ref_29","first-page":"861","article-title":"Pharmacokinetic parameters and tissue distribution of magnetic Fe3O4 nanoparticles in mice","volume":"5","author":"Wang","year":"2010","journal-title":"Int. J. Nanomed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.lfs.2019.05.048","article-title":"Long-term biodistribution and toxicity of curcumin capped iron oxide nanoparticles after single-dose administration in mice","volume":"230","author":"Elbialy","year":"2019","journal-title":"Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1021\/mp7001285","article-title":"Biodistribution, clearance, and biocompatibility of iron oxide magnetic nanoparticles in rats","volume":"5","author":"Jain","year":"2008","journal-title":"Mol. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1038\/s41598-018-19628-z","article-title":"Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings","volume":"8","author":"Feng","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1016\/j.optmat.2013.12.032","article-title":"Rare earth activated ZnO nanoparticles as biomarkers","volume":"36","author":"Wolska","year":"2014","journal-title":"Opt. Mater."},{"key":"ref_34","unstructured":"Mendez-Vilas, A. (2017). Cytometric analysis of Zn-based nanoparticles for biomedical applications. Microscopy and Imaging Science: Practical Approaches to Applied Research and Education, Formatex."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.nano.2016.11.002","article-title":"Biodegradation of the ZnO:Eu nanoparticles in the tissues of adult mouse after alimentary application","volume":"13","author":"Kielbik","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"455101","DOI":"10.1088\/1361-6528\/ab36f4","article-title":"Transfer of orally administered ZnO:Eu nanoparticles through the blood-testis barrier: The effect on kinetic sperm parameters and apoptosis in mice testes","volume":"30","author":"Kielbik","year":"2019","journal-title":"Nanotechnology"},{"key":"ref_37","unstructured":"Crist, B.V. (2005). Handbooks of Monochromatic XPS Spectra, XPS International LLC."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Morkoc, H., and Ozgur, U. (2009). Zinc Oxide: Fundamentals, Materials and Device Technology, Wiley-VCH. [1st ed.].","DOI":"10.1002\/9783527623945"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1107\/S0567739476001551","article-title":"Revised effective ionic radii and systematic studies of interatomic distances in halides and chalcogenides","volume":"A32","author":"Shannon","year":"1976","journal-title":"Acta Cryst."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nnano.2010.79","article-title":"Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation","volume":"5","author":"Hilty","year":"2010","journal-title":"Nat. Nanotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pham, B., Colvin, E.K., Pham, N., Kim, B.J., Fuller, E.S., Moon, E.A., Barbey, R., Yuen, S., Rickman, B.H., and Bryce, N.S. (2018). Biodistribution and Clearance of Stable Superparamagnetic Maghemite Iron Oxide Nanoparticles in Mice Following Intraperitoneal Administration. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010205"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5719","DOI":"10.2147\/IJN.S165451","article-title":"Effects of core size and PEG coating layer of iron oxide nanoparticles on the distribution and metabolism in mice","volume":"13","author":"Xue","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"296","DOI":"10.3109\/01480545.2012.720988","article-title":"Biochemical alterations induced by acute oral doses of iron oxide nanoparticles in Wistar rats","volume":"36","author":"Kumari","year":"2013","journal-title":"Drug Chem. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2149","DOI":"10.1166\/jnn.2012.5796","article-title":"Repeated oral dose toxicity of iron oxide nanoparticles: Biochemical and histopathological alterations in different tissues of rats","volume":"12","author":"Kumari","year":"2012","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1007\/s11095-012-0958-3","article-title":"Effects of particle size and surface modification on cellular uptake and biodistribution of polymeric nanoparticles for drug delivery","volume":"30","author":"Kulkarni","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.yexmp.2015.11.016","article-title":"Effects of Il-33\/St2 pathway on alteration of iron and hematological parameters in acute inflammation","volume":"99","author":"Stankovic","year":"2015","journal-title":"Exp. Mol. Pathol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1096\/fj.14-251520","article-title":"Ferroportin mediates the intestinal absorption of iron from a nanoparticulate ferritin core mimetic in mice","volume":"28","author":"Aslam","year":"2014","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/jn\/137.3.614","article-title":"Synthesis, characterization, and bioavailability in rats of ferric phosphate nanoparticles","volume":"137","author":"Rohner","year":"2007","journal-title":"J. Nutr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.phrs.2016.11.010","article-title":"Therapeutic potential of hepcidin\u2014The master regulator of iron metabolism","volume":"115","author":"Vyoral","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0092-8674(04)00343-5","article-title":"Balancing acts: Molecular control of mammalian iron metabolism","volume":"117","author":"Hentze","year":"2004","journal-title":"Cell"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cell.2010.06.028","article-title":"Two to tango: Regulation of Mammalian iron metabolism","volume":"142","author":"Hentze","year":"2010","journal-title":"Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1021\/acs.bioconjchem.8b00245","article-title":"Bacteria-Carried Iron Oxide Nanoparticles for Treatment of Anemia","volume":"29","author":"Olivares","year":"2018","journal-title":"Bioconjug. Chem."},{"key":"ref_53","first-page":"1067","article-title":"Effect of iron oxide nanoparticles on vascular function and nitric oxide production in acute stress-exposed rats","volume":"69","author":"Sekaj","year":"2020","journal-title":"Physiol. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3988","DOI":"10.1016\/j.biomaterials.2011.02.031","article-title":"Long term in vivo biotransformation of iron oxide nanoparticles","volume":"32","author":"Levy","year":"2011","journal-title":"Biomaterials"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16321","DOI":"10.1039\/C5NR03780H","article-title":"Biotransformation of magnetic nanoparticles as a function of coating in a rat model","volume":"7","author":"Ruiza","year":"2015","journal-title":"Nanoscale"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/9\/859\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:53:50Z","timestamp":1760165630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/9\/859"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,27]]},"references-count":55,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ph14090859"],"URL":"https:\/\/doi.org\/10.3390\/ph14090859","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,27]]}}}