Pharmacokinetics and bio‐distribution of novel super paramagnetic iron oxide nanoparticles (<scp>SPION</scp>s) in the anaesthetized pig

Edge, Deirdre; Shortt, Christine M.; Gobbo, Oliviero L.; Teughels, Stéphanie; Prina-Mello, Adriele; Volkov, Yuri; MacEneaney, Peter; Radomski, Marek W.; Markos, F.

doi:10.1111/1440-1681.12533

Cited by 37 publications

(21 citation statements)

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“…In anaesthetized pigs, it has been demonstrated that dimercaptosuccinic acid coated superparamagnetic iron oxide nanoparticles (MF66-labelled 12 nm, core nominal diameter and OD15 15 nm); at 0.5, or 2.0 mg/kg injected i.v. induced a transient yet significant decrease in MAP [ 38 ]. Particles remained in the circulation for up to 30 min and were accumulated in the liver, spleen and lungs [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Ultrasmall superparamagnetic iron oxide nanoparticles acutely promote thrombosis and cardiac oxidative stress and DNA damage in mice

et al. 2015

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BackgroundUltrasmall superparamagnetic iron oxide nanoparticles (USPIO) are being developed for several biomedical applications including drug delivery and imaging. However, little is known about their possible adverse effects on thrombosis and cardiac oxidative and DNA damage.MethodsPresently, we investigated the acute (1 h) effect of intravenously (i.v.) administered USPIO in mice (0.4, 2 and 10 μg/kg). Diesel exhaust particles (DEP; 400 μg/kg) were used as positive control.ResultsUSPIO induced a prothrombotic effect in pial arterioles and venules in vivo and increased the plasma plasminogen activator inhibitor-1 (PAI-1). Both thrombogenicity and PAI-1 concentration were increased by DEP. The direct addition of USPIO (0.008, 0.04 and 0.2 μg/ml) to untreated mouse blood dose-dependently induced in vitro platelet aggregation. USPIO caused a shortening of activated partial thromboplastin time (aPTT) and prothrombin time (PT). Similarly, DEP administration (1 μg/ml) triggered platelet aggregation in vitro in whole blood. DEP also reduced PT and aPTT. The plasma levels of creatine phosphokinase-MB isoenzyme (CK-MB), lactate dehydrogenase (LDH) and troponin-I were increased by USPIO. DEP induced a significant increase of CK-MB, LDH and troponin I levels in plasma. The cardiac levels of markers of oxidative stress including lipid peroxidation, reactive oxygen species and superoxide dismutase activity were increased by USPIO. Moreover, USPIO caused DNA damage in the heart. Likewise, DEP increased the markers of oxidative stress and induced DNA damage in the heart.ConclusionWe conclude that acute i.v. administration of USPIO caused thrombosis and cardiac oxidative stress and DNA damage. These findings provide novel insight into the pathophysiological effects of USPIO on cardiovascular homeostasis, and highlight the need for a thorough evaluation of their toxicity.

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Section: Discussionmentioning

confidence: 99%

Ultrasmall superparamagnetic iron oxide nanoparticles acutely promote thrombosis and cardiac oxidative stress and DNA damage in mice

et al. 2015

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“…Recently, it has been reported that after 6 hours of injection >50% of iron is found in liver 79. These studies suggest the involvement of reticular endothelial system in the clearance of NPs and major problem in biomedical application of these particles 137. Higher vascularization and permeability of iron NPs are responsible for their uptake by reticular endothelial system140 and macrophage.…”

Section: Biodistribution and Bioelimination Of Iron Npsmentioning

confidence: 99%

“…Size, shape, and surface characterization of iron NPs determine their biological distribution135 and can involve opsonization (serum protein interaction) and particle cell interaction 136. Various biodistributation studies report blood, spleen, liver, and kidney as probable localization for the NPs, and preferentially accumulation occurs in liver and spleen 137. Recent studies report that ultrasmall iron oxide NPs can be used as potent MRI contrast agents 27,138.…”

Section: Biodistribution and Bioelimination Of Iron Npsmentioning

confidence: 99%

“…Opsonization is one of the important processes for the elimination of magnetic NPs from circulation through liver macrophages 141,142. In different studies, magnetic NP accumulation has also been reported in lungs due to vascularized and monocyte-rich nature 137. Chaves et al143 reported the accumulation of magnetic NPs in the lungs of mice for up to 3 months and found no associated toxicity.…”

Section: Biodistribution and Bioelimination Of Iron Npsmentioning

confidence: 99%

“…Normally the human body contains: hemoglobin protein, myoglobin, transferrin, and ferritin at 65%, 4%, 0.1%, and 15%–30% of magnetic NPs, respectively. It is believed that the degradation of iron oxide NPs occurs similarly like ferritins at molecular level 137. The degradation of iron NPs leads to increase in the iron level in the organs.…”

Section: Biodistribution and Bioelimination Of Iron Npsmentioning

confidence: 99%

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Abstract:Recently, iron oxide nanoparticles (NPs) have attracted much consideration due to their unique properties, such as superparamagnetism, surface-to-volume ratio, greater surface area, and easy separation methodology. Various physical, chemical, and biological methods have been adopted to synthesize magnetic NPs with suitable surface chemistry. This review summarizes the methods for the preparation of iron oxide NPs, size and morphology control, and magnetic properties with recent bioengineering, commercial, and industrial applications. Iron oxides exhibit great potential in the fields of life sciences such as biomedicine, agriculture, and environment. Nontoxic conduct and biocompatible applications of magnetic NPs can be enriched further by special surface coating with organic or inorganic molecules, including surfactants, drugs, proteins, starches, enzymes, antibodies, nucleotides, nonionic detergents, and polyelectrolytes. Magnetic NPs can also be directed to an organ, tissue, or tumor using an external magnetic field for hyperthermic treatment of patients. Keeping in mind the current interest in iron NPs, this review is designed to report recent information from synthesis to characterization, and applications of iron NPs.

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Nonviral nanoparticles have emerged as an attractive alternative to viral vectors for gene therapy applications, utilizing a range of lipid‐based, polymeric, and inorganic materials. These materials can either encapsulate or be functionalized to bind nucleic acids and protect them from degradation. To effectively elicit changes to gene expression, the nanoparticle carrier needs to undergo a series of steps intracellularly, from interacting with the cellular membrane to facilitate cellular uptake to endosomal escape and nucleic acid release. Adjusting physiochemical properties of the nanoparticles, such as size, charge, and targeting ligands, can improve cellular uptake and ultimately gene delivery. Applications in the central nervous system (CNS; i.e., neurological diseases, brain cancers) face further extracellular barriers for a gene‐carrying nanoparticle to surpass, with the most significant being the blood–brain barrier (BBB). Approaches to overcome these extracellular challenges to deliver nanoparticles into the CNS include systemic, intracerebroventricular, intrathecal, and intranasal administration. This review describes and compares different biomaterials for nonviral nanoparticle‐mediated gene therapy to the CNS and explores challenges and recent preclinical and clinical developments in overcoming barriers to nanoparticle‐mediated delivery to the brain. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

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Pharmacokinetics and bio‐distribution of novel super paramagnetic iron oxide nanoparticles (SPIONs) in the anaesthetized pig

Cited by 37 publications

References 23 publications

Ultrasmall superparamagnetic iron oxide nanoparticles acutely promote thrombosis and cardiac oxidative stress and DNA damage in mice

Ultrasmall superparamagnetic iron oxide nanoparticles acutely promote thrombosis and cardiac oxidative stress and DNA damage in mice

Synthesis, characterization, applications, and challenges of iron oxide nanoparticles

Nonviral nanoparticle gene delivery into the CNS for neurological disorders and brain cancer applications

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