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1.
J Med Phys ; 38(1): 34-40, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23531682

ABSTRACT

In order to evaluate the long-term viability, the iron content stability, and the labeling efficiency of mammalian cells using magnetic cell labeling; dextran-coated ultrasmall superparamagnetic iron oxide (USPIOs) nanoparticles with plain surfaces having a hydrodynamic size of 25 nm were used for this study. Tests were carried out in four groups each containing 5 flasks of 5.5 × 10(6) AD-293 embryonic kidney cells. The cell lines were incubated for 24 h using four different iron concentrations with and without protamine sulfate (Pro), washed with phosphate-buffered saline (PBS) and centrifuged three times to remove the unbounded USPIOs. Cell viability was also verified using USPIOs. There were no significant differences in the cell viability between the control group of cells and those groups with iron uptake at the specified iron concentrations. The average iron uptake ratio compared to that of the control group was (114 ± 1). The magnetic resonance images (MRI) at post-labeling day 1 and day 21 showed (75 ± 4)% and (22 ± 5)% signal decrements compared to that of the control, respectively. The Perl's Prussian blue test showed that 98% of the cells were labeled, and the iron concentration within the media did not affect the cell iron uptake. Magnetic cellular labeling with the USPIO-Pro complex had no short or medium term (3 weeks) toxic effects on AD-293 embryonic kidney cells.

2.
Int J Pharm ; 439(1-2): 28-40, 2012 Dec 15.
Article in English | MEDLINE | ID: mdl-23058926

ABSTRACT

To efficiently enhance the contrast obtaining from magnetic resonance imaging (MRI), pharmaceutical grade colloidal dispersions of PEG coated iron-based nanoparticles were prepared and compared to conventional pure iron oxide contrast agent. In this study, we synthesized ~14 nm iron nanoparticles via NaBH(4) reduction of iron(III) chloride in an aqueous medium. The resulting nanoparticles were further oxidized by two different methods via (CH(3))(3)NO oxygen transferring agent and exposure to oxygen flow. XRD and electron microscopy analyses confirmed the formation of a second layer on the surface of α-Fe core. As magnetic measurements and Mössbauer spectra of 4-months post prepared nanoparticles showed, 2.3±0.5 nm amorphous oxide shell produced in oxygen flow could not protect the inner metallic iron from oxidation and resulting sample suffered from drastic change in its characteristics. However, (CH(3))(3)NO yielded nanoparticles with 3.6±0.4 and 4.5±0.7 nm crystalline oxide shells that retained their key properties even in long-term examinations. In addition, no significant difference was detected in cytotoxicity results of MTT assay test up to 4-months for core/shell nanoparticles, in comparison with pure iron oxide sample, and all fall below 50% viability in the iron concentration of 400 µg. In vitro MR signal reduction and corresponding relaxometry parameters, especially r(2)/r(1)>2, assure that all nanoparticles can be administrated for negative contrast enhancement. Accumulation of core/shell nanoparticles in axillary and brachial lymph nodes of examined rats and minimum contrast enhancement of 20% regarding to pure iron oxide implies the efficiency of these materials as potential contrast agent.


Subject(s)
Contrast Media/chemistry , Ferric Compounds/chemistry , Iron/chemistry , Metal Nanoparticles/chemistry , Animals , Cell Line , Cell Survival/drug effects , Contrast Media/pharmacokinetics , Contrast Media/toxicity , Ferric Compounds/pharmacokinetics , Ferric Compounds/toxicity , Iron/pharmacokinetics , Iron/toxicity , Lymph Nodes/metabolism , Magnetic Phenomena , Metal Nanoparticles/toxicity , Mice , Rats , Rats, Wistar
3.
Int J Pharm ; 433(1-2): 129-41, 2012 Aug 20.
Article in English | MEDLINE | ID: mdl-22579990

ABSTRACT

Superparamganetic iron oxide-based contrast agents in magnetic resonance imaging (MRI) have offered new possibility for early detection of lymph nodes and their metastases. According to important role of nanoparticle size in biodistribution, magnetite nanoparticles coated with different polyethylene glycol (PEG) concentrations up to 10/1 PEG/iron oxide weight ratio in an ex situ manner. To predict the PEG-coated nanoparticle behavior in biological media, such as blood stream or tissue, colloidal stability evaluation was performed to estimate the coating endurance in different conditions. Accordingly, optical absorbance measurements were conducted in solutions with different values of pH and NaCl concentrations. The results indicated that at neutral pH condition, nanoparticles treated by 3/1 ratio possessed better stability parameters. Investigating at high pH of 10 resulted in superior stability for bare magnetite nanoparticles due to its higher electrophoretic mobility. Coating material was attacked at acidic solutions which cause samples with higher PEG weight ratio to be settled slower. In various ionic strengths of 10(-5) to 0.1 M, 3/1 ratio samples offered greater resistivity to sedimentation. The nanoparticles were further investigated by exposure to L929 cell and following up the iron uptake within cells. Finally, detection sensitivities in lymph nodes were evaluated. Particle uptake and the most signal reduction for in vivo MRI studies were also obtained by nanoparticles acquiring lower PEG contents that showed better colloidal stability.


Subject(s)
Contrast Media/chemistry , Magnetic Resonance Imaging/methods , Magnetite Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Animals , Cell Line , Colloids , Contrast Media/pharmacokinetics , Drug Stability , Electrophoresis , Fibroblasts , Hydrogen-Ion Concentration , Lymph Nodes/metabolism , Mice , Osmolar Concentration , Rats , Rats, Wistar , Sodium Chloride/chemistry
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