Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid

Abstract

Background Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnositic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo targeting efficiency. Methods Intralipid 20.0%, an FDA approved nutritional supplement, was intravenously administered in rats at the clinical dose (2 g/kg) one hour before intravenous injection of ultra-small superparamagnetic iron-oxide (USPIO) or micron-sized paramagnetic iron-oxide (MPIO) particles. Blood half-life, monocyte labeling efficiency, and particle biodistribution were assessed by magnetic resonance relaxometry, flow cytometry, inductively-coupled plasma MS, and histology. Results Pre-treatment with Intralipid resulted in a 3.1-fold increase in USPIO blood half-life and a 2-fold increase in USPIO-labeled monocytes. A 2.5-fold increase in MPIO blood half-life and a 5-fold increase in MPIO-labeled monocytes were observed following Intralipid pre-treatment, with a 3.2-fold increase in mean iron content up to 2.60 pg Fe/monocyte. With Intralipid, there was a 49.2% and 45.1% reduction in liver uptake vs. untreated controls at 48 hrs for USPIO and MPIO, respectively. Conclusions Intralipid pre-treatment significantly decreases initial RES uptake and increases in-vivo circulation and blood monocyte labeling efficiency for nano- and micron-sized superparamagnetic iron-oxide particles. General Significance Our findings can have broad applications for imaging and drug delivery applications, increasing the bioavailability of nano- and micron-sized particles for target sites other than the liver.

Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

“…S4D), but the in silico model demonstrated that increased liver concentrations are expected (Fig. S4E) without invoking other factors that contribute to the liver-uptake of Intralipid® [40]. Subsequent to increasing liver concentrations, ILE treatment increased excretion of radiolabel into the urine by 10 minutes (Fig.…”

“…Regarding the role of metabolism, the increased liver bupivacaine concentrations could not be accounted for by a flow effect but the in silico models demonstrated that invocation of reticulo-endothelial cell uptake was not needed to increase liver concentrations. The reticulo-endothelial system might be playing a role in uptake of the ILE [40], but we did not specifically test for this. Also, we tested the effect of inhibiting CYP3A4, the main metabolizer of bupivacaine, but bupivacaine is also processed in small amounts by other CYP's indicating that tests with other inhibitors might yield more information.…”

MRI Investigation of New Approach to Improve the Recovery of Myocardial Ischemia Reperfusion Injury by Treatment with Intralipid<sup>®</sup>

“…In general, Iron-oxide-particles have short blood half-life, depending on their size and surface coating materials [17]. We have shown [54] that the pre-treatment of Intralipid ® prior to iron-oxide particle administration can temporarily inhibit Kupper cells in the liver, increase its blood half-life, thus, improve labeling efficiency. For the present study, MPIO was given 1-to-3 days prior to the ischemic surgery.…”

Antimicrobial Nanostructures for Neurodegenerative Infections

“…The standard-size nanoparticles are composed of ferric (Fe 3þ ) and ferrous (Fe 2þ ) iron (Wahajuddin and Arora, 2012). They have been trapped in the reticuloendothelial system through endocytosis or phagocytosis to explore their cytotoxicity profile due to the dissolving capacity of iron oxide under acidic conditions Liu et al, 2013a). In addition, Fe 3þ ions can be stored in adult humans, accumulating up to 3e5 g of iron.…”