Surface modifications affect iron oxide nanoparticles' biodistribution after multiple‐dose administration in rats

Abstract

Iron oxide nanoparticles (IONPs) possess many utilizable physical and chemical properties and have an acceptable level of biocompatibility. 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‐IONPs], curcumin [Cur‐IONPs], and chitosan [CS‐IONPs]) were prepared and characterized using various physicochemical techniques. The biodistribution of iron and the histopathology of affected tissues were assessed after Cit‐IONPs, Cur‐IONPs, CS‐IONPs, and commercial ferrous sulfate were orally administered to adult female Wistar rats for 10 consecutive days at a dose of 4 mg/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‐IONPs or CS‐IONPs, respectively. In contrast, the administration of CS‐IONPs displayed the highest spleen iron accumulation. The ferrous sulfate (FeSO4)‐treated 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‐IONPs or commercial FeSO4. However, Cur‐IONPs and CS‐IONPs 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.

In Vitro and In Vivo Biological Assays of Dextran Coated Iron Oxide Aqueous Magnetic Fluids

“…In addition, aspects related to the biodistribution of iron oxide nanoparticles coated with different materials have been studied recently [ 34 , 35 , 36 , 37 , 38 , 39 ]. In their study regarding the “Genotoxicity and biocompatibility of superparamagnetic iron oxide nanoparticles: influence of surface modification on biodistribution, retention, DNA damage and oxidative stress”, Gosh et al [ 34 ] reported the use of poly (lactic-co-glycolic acid) together with either didodeclydimethyl-ammonium-bromide or α-tocopheryl-polyethleneglycol-succinate in order to reduce the cytogenotoxicity and the generation of reactive oxygen species of iron oxide nanoparticles.…”

Magnetically‐activated lipid nanocarriers in biomedical applications: A review of current status and perspective

“…To date, the clinical translation of these drug delivery systems is also not clear because most of the related research has been conducted on the level of cell culture, with limited preclinical studies that actually determine the fate of the particles. The fate of magneto‐responsive nanoparticles, after the degradation of the lipid matrix and the subsequent clearance of the iron oxide nanoparticles from the body is another concern (Fahmy et al, 2021; A. Zhang et al, 2020). Studies have reported that IONPs are likely to be biocompatible however it strongly relies on their physicochemical properties including the particle size and surface modification (Feng et al, 2018).…”

Toxicologic Concerns with Current Medical Nanoparticles

“…[135] IONP Surface modifications affect iron oxide NP biodistribution in rats. [136] AgNP Single silver nanoparticle instillation induced early and persisting moderate cortical damage in rat kidneys. [134] AgNP AgNPs could interact with the anatomical structures of the kidney to induce injury.…”

“…The ferrous sulfate (FeSO4)-treated 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-IONPs or commercial FeSO 4 [ 136 ].…”