Transport of Intranasally Instilled Fine Fe2O3 Particles into the Brain: Micro-distribution, Chemical States, and Histopathological Observation

Abstract

It has been demonstrated that inhaled fine (d < 2.5 microm) and ultrafine (d < 100 nm) particles produce more severe toxicity than coarse particles. Some recent data support the concept that the central nervous system (CNS) may be a target for the inhaled fine particulates. This work describes initial observation of the transport of intranasally instilled fine ferric oxide (Fe2O3) particles in animal brain. The iron micro-distribution and chemical state in the mice olfactory bulb and brain stem on day 14 after intranasal instillation of fine Fe2O3 particle (280 +/- 80 nm) suspension at a single dose of 40 mg/kg body weight were analyzed by synchrotron radiation x-ray fluorescence and x-ray absorption near-edge structure (XANES). The micro-distribution map of iron in the olfactory bulb and brain stem shows an obvious increase of Fe contents in the olfactory nerve and the trigeminus of brain stem, suggesting that Fe2O3 particles were possibly transported via uptake by sensory nerve endings of the olfactory nerve and trigeminus. The XANES results indicate that the ratios of Fe (III)/Fe (II) were increased in the olfactory bulb and brain stem. The further histopathological observation showed that the neuron fatty degeneration occurred in the CA3 area of hippocampus. Such results imply an adverse impact of inhalation of fine Fe2O3 particles on CNS.

Accumulation of iron oxide nanoparticles by cultured primary neurons

“…IONPs that will enter the brain via the blood-brain barrier (Wang et al, 2010;Yan et al, 2013) are likely to be covered by serum proteins and may slowly be taken up into neurons. In contrast, IONPs that may enter the brain via the olfactory pathway (Wang et al, 2007) or by direct injection into the brain for therapeutic reasons (Jordan et al, 2006;Maier-Hauff et al, 2011) are unlikely to be covered with serum proteins. Such particles may adsorb also in vivo very efficiently to neurons which could foster their internalization and metabolism.…”

“…IONPs have been reported to enter the brain via the blood-brain barrier (Wang et al, 2010;Yan et al, 2013) and via the olfactory bulb (Wang et al, 2007) or are directly injected into the brain for therapeutic treatments (Jordan et al, 2006;Maier-Hauff et al, 2011). Thus, as brain cells will encounter IONPs, it is important to know about potential adverse effects of IONPs on these cells.…”

Magnetic nanoparticles: an update of application for drug delivery and possible toxic effects

“…However, NPs made of certain materials and with varying particle sizes can cross this physical carrier or enter the brain via the olfactory bulb nerve endings (Koziara et al 2006). In fact, Wang et al (2007) found that intranasal instillation of Wne Fe 2 O 3 particles (280 § 80 nm) caused neuronal fatty degeneration in the hippocampus, suggesting the possibility of an adverse impact of inhaled Wne Fe 2 O 3 particles on the CNS. The brain is particularly vulnerable to ROS damage, due to its high content of easily peroxidizable unsaturated fatty acids, high oxygen consumption rate, and relative paucity of antioxidant enzymes compared with other organs (Skaper et al 1999).…”

Nose-to-Brain Delivery: Investigation of the Transport of Nanoparticles with Different Surface Characteristics and Sizes in Excised Porcine Olfactory Epithelium

“…In recent years, a large number of studies in animal models have demonstrated the ability of small molecular weight drugs, peptides and proteins to be transported directly from the nasal cavity to the central nervous system (CNS) [1][2][3][4][5][6][7][8] . However, the amount of drug transported via this route was shown to be small (well below 1%) and unless steps are taken by means of drug delivery technology to enhance the transport across the olfactory epithelium and/or via the olfactory and trigeminal nerves, this route is only therapeutically viable for very potent drugs 9 .…”