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Therefore, they are extensively used in different medical applications. Hence, the challenge is to modify the surfaces of prepared iron oxide nanoformulations with a biocompatible coat to enhance their biosafety. In this study, different formulations of IONPs with different capping agents (citrate [Cit\u2010IONPs], curcumin [Cur\u2010IONPs], and chitosan [CS\u2010IONPs]) were prepared and characterized using various physicochemical techniques. The biodistribution of iron and the histopathology of affected tissues were assessed after Cit\u2010IONPs, Cur\u2010IONPs, CS\u2010IONPs, and commercial ferrous sulfate were orally administered to adult female Wistar rats for 10 consecutive days at a dose of 4\u2009mg\/kg of body weight\/day. The results were compared with a control group injected orally with saline. The iron content in the kidneys, liver, and spleen was measured by atomic absorption spectroscopy. Histopathological alterations were also examined. The biodistribution results demonstrate that iron accumulated mainly in the liver tissue, whereas the lowest liver accumulation was observed after the administration of Cit\u2010IONPs or CS\u2010IONPs, respectively. In contrast, the administration of CS\u2010IONPs displayed the highest spleen iron accumulation. The ferrous sulfate (FeSO<jats:sub>4<\/jats:sub>)\u2010treated group showed the highest kidney iron accumulation as compared with the other groups. The histopathological examination revealed that signs of toxicity were predominant for groups treated with Cit\u2010IONPs or commercial FeSO<jats:sub>4<\/jats:sub>. However, Cur\u2010IONPs and CS\u2010IONPs showed mild toxicity when administered at the same doses. The results obtained in the present study will provide insights into the expected in vivo effects after administration of each nanoformulation.<\/jats:p>","DOI":"10.1002\/jbt.22671","type":"journal-article","created":{"date-parts":[[2020,12,10]],"date-time":"2020-12-10T04:54:45Z","timestamp":1607576085000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Surface modifications affect iron oxide nanoparticles' biodistribution after multiple\u2010dose administration in rats"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8689-1198","authenticated-orcid":false,"given":"Heba M.","family":"Fahmy","sequence":"first","affiliation":[{"name":"Biophysics Department, Faculty of Science Cairo University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiseer M.","family":"Abd El\u2010Daim","sequence":"additional","affiliation":[{"name":"Biophysics Department, Faculty of Science Cairo University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Biophysics Department, Faculty of Science Cairo University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa A.","family":"Hassan","sequence":"additional","affiliation":[{"name":"Biophysics Department, Faculty of Science Cairo University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0410-8118","authenticated-orcid":false,"given":"Faten F.","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Pathology Department Faculty of Veterinary Medicine Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2326-2567","authenticated-orcid":false,"given":"Mohamed M.","family":"Fathy","sequence":"additional","affiliation":[{"name":"Biophysics Department, Faculty of Science Cairo University Giza Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-016-1958-5"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2011.07.002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/426028"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/18779468113039990007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2015.05.032"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201201531"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S165451"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5CS00699F"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11051-012-0964-8"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfa.2014.12.031"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2016.04.093"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2014.02.034"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1088\/0957-4484\/23\/10\/105601"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/0929867323666160106151428"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.05.048"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S197888"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.10.059"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116787"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2012.01.040"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10948-020-05469-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmmm.2009.08.049"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4757-2519-3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msec.2015.12.085"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/761029"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/09637486.2014.918589"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmp.2014.05.012"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics7020046"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.05.016"},{"key":"e_1_2_8_30_1","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.matpr.2019.06.516","volume":"17","author":"Abu\u2010Noqta O.","year":"2019","journal-title":"Mater. 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