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.
Objective: Trans-catheter (TC) pulmonary valve replacement (PVR) has become common practice for patients with right ventricular outflow tract obstruction (RVOTO) and/or pulmonic insufficiency (PI). Our aim was to compare PVR and right ventricular (RV) function of patients who received TC vs surgical PVR.Design: Retrospective review of echocardiograms obtained at three time points: before, immediately after PVR, and most recent. Results: At baseline, the TC group had predominant RVOTO (74% vs 10%, P < .001), and moderate-severe PI was less common (61% vs 100%, P < .001). Immediate post-procedural PVR function was good throughout. At last follow-up, the TC group had preserved valve function, but the surgical group did not (moderate RVOTO: 6% vs 41%, P < .001; >mild PI: 0% vs 24%, P 5 .003). Patients younger than 17 years at surgical PVR had the highest risk of developing PVR dysfunction, while PVR function in follow-up was similar in adults. Looking at RV size and function, both groups had a decline in RV size following PVR. However, while RV function remained stable in the TC group, there was a transient postoperative decline in the surgical group.
Conclusions: TC PVR in patients age
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