Macrophage uptake rate of Sonazoid in breast lymphosonography is highly conserved in healthy controls.

Subcutaneous microbubble administration in connection with contrast enhanced ultrasound (CEUS) imaging is showing promise as a noninvasive and sensitive way to detect tumor draining sentinel lymph nodes (SLNs) in patients with breast cancer. Moreover, there is potential to harness the results from these approaches to directly estimate cancer burden, since some microbubble formulas, such as the Sonazoid used in this study, are rapidly phagocytosed by macrophages, and the macrophage concentration in a lymph node is inversely related to the cancer burden. This work presents a mathematical model that can approximate a rate constant governing macrophage uptake of Sonazoid,ki, given dynamic CEUS Sonazoid imaging data. Twelve healthy women were injected with 1.0 ml of Sonazoid in an upper-outer quadrant of one of their breasts and SLNs were imaged in each patient immediately after injection, and then at 0.25, 0.5, 1, 2, 4, 6, and 24 h after injection. The mathematical model developed was fit to the dynamic CEUS data from each subject resulting in a mean ± sd of 0.006 ± 0.005 h-1and 0.4 ± 0.1 h-1for relative lymphatic flow (EFl) andki, respectively. Furthermore, the roughly 25% sd of thekimeasurement was similar to the sd that would be expected from realistic noise simulations for a stable 0.4 h-1value ofki, suggesting that macrophage concentration is highly consistent among cancer-free SLNs. These results, along with the significantly smaller variance inkimeasurement observed compared to relative lymphatic flow suggest thatkimay be a more precise and promising approach of estimating macrophage abundance, and inversely cancer burden. Future studies comparing tumor-free to tumor-bearing nodes are planned to verify this hypothesis.

Biodistribution of iron oxide tattoo pigment: An experimental murine study.

Tattoo pigment is expected to migrate beyond the skin to regional lymph nodes and the liver. Modern tattoo ink commonly contains metals that may pose a clinical problem during MRI examinations. This study aimed to investigate the biodistribution of iron oxide pigment to internal organs in mice. Moreover, when exposed to a static magnetic field, we studied whether any reactions followed in the tattooed skin. Twenty-seven hairless C3.Cg-Hrhr/TifBomTac mice were included; 20 were tattooed with iron oxide ink in a rectangular 3 cm2 pattern; seven were controls. Ten of the tattooed mice were exposed to a 3 T MRI scanner's static magnetic field. Following euthanasia, evaluations of dissected organs involved MRI T2*-mapping, light microscopy (LM) and metal analysis. T2*-mapping measures the relaxation times of hydrogen nuclei in water and fat, which may be affected by neighbouring ferrimagnetic particles, thus enabling the detection of iron oxide particles in organs. Elemental analysis detected a significant level of metals in the tattooed skin compared to controls, but no skin reactions occurred when exposed to a 3 T static magnetic field. No disparity was observed in the liver samples with metal analysis. T2* mapping found no significant difference between the two groups. Only minute clusters of pigment particles were observed in the liver by LM. Our results demonstrate a minimal systemic distribution of the iron oxide pigments to the liver, whereas the kidney and brain were unaffected. The static magnetic field did not trigger skin reactions in magnetic tattoos but may induce image artefacts during MRI.

Comparison of the Pharmacokinetics of Gadolinium-Based and Iron Oxide-Based Contrast Agents inside the Lymphatic Structure using Magnetic Resonance Lymphangiography.

PURPOSE: Gadolinium (Gd)-based contrast agents are primarily used for contrast-enhanced magnetic resonance lymphangiography (MRL). However, overcoming venous contamination issues remains challenging. This study aims to assess the MRL efficacy of the newly developed iron-based contrast agent (INV-001) that is specially designed to mitigate venous contamination issues. The study further explores the optimal dosage, including both injection volume and concentration, required to achieve successful visualization of the popliteal lymph nodes and surrounding lymphatic vessels. PROCEDURES: All animals utilized in this study were male Sprague-Dawley (SD) rats weighing between 250 and 300 g. The contrast agents prepared were injected intradermally in the fourth phalanx of both hind limbs using a 30-gauge syringe in SD rats. MRL was performed every 16 min on a coronal 3D time-of-flight sequence with saturation bands using a 9.4-T animal machine. RESULTS: Contrary to Gd-DOTA, which exhibited venous contamination in most animals irrespective of injection dosages and conditions, INV-001 showed no venous contamination. For Gd-DOTA, the popliteal lymph nodes and lymphatic vessels reached peak enhancement 16 min after injection from the injection site and then rapidly washed out. However, with INV-001, they reached peak enhancement between 16 and 32 min after injection, with prolonged visualization of the popliteal lymph node and lymphatic vessels. INV-001 at 0.45 µmol (15 mM, 30 µL) and 0.75 µmol (15 mM, 50 µL) achieved high scores for qualitative image analysis, providing good visualization of the popliteal lymph nodes and lymphatic vessels without issues of venous contamination, interstitial space enhancement, or lymph node enlargement. CONCLUSION: In MRL, INV-001, a novel T1 contrast agent based on iron, enables prolonged enhancement of popliteal lymph nodes and lymphatic vessels without venous contamination.

MRI-Based and Histologically Verified 3D Modeling of Spatial Distribution of Intra-Arterially Transplanted Cells in Rat Brain.

Visualization of transplanted stem cells in the brain is an important issue in the study of the mechanisms of their therapeutic action. MRI allowing visualization of single transplanted cells previously labeled with superparamagnetic iron oxide particles is among the most informative methods of non-invasive intravital imaging. Verification of MRI data using pathomorphological examination at the microscopic level helps to avoid errors in data interpretation. However, making serial sections of the whole brain and searching for transplanted cells under the microscope is laborious and time-consuming. We have developed a method for 3D modeling of the distribution of transplanted cells in the brain allowing navigating through various brain structures and identifying the areas of accumulation of transplanted cells, which significantly increases the efficiency and reduces the time of histological examination.

Dinuclear Fe(III) Hydroxypropyl-Appended Macrocyclic Complexes as MRI Probes.

Four high-spin Fe(III) macrocyclic complexes, including three dinuclear and one mononuclear complex, were prepared toward the development of more effective iron-based magnetic resonance imaging (MRI) contrast agents. All four complexes contain a 1,4,7-triazacyclononane macrocyclic backbone with two hydroxypropyl pendant groups, an ancillary aryl or biphenyl group, and a coordination site for a water ligand. The pH potentiometric titrations support one or two deprotonations of the complexes, most likely deprotonation of hydroxypropyl groups at near-neutral pH. Variable-temperature 17O NMR studies suggest that the inner-sphere water ligand is slow to exchange with bulk water on the NMR time scale. Water proton T1 relaxation times measured for solutions of the Fe(III) complexes at pH 7.2 showed that the dinuclear complexes have a 2- to 3-fold increase in r1 relaxivity in comparison to the mononuclear complex per molecule at field strengths ranging from 1.4 T to 9.4 T. The most effective agent, a dinuclear complex with macrocycles linked through para-substitution of an aryl group (Fe2(PARA)), has an r1 of 6.7 mM-1 s-1 at 37 °C and 4.7 T or 3.3 mM-1 s-1 per iron center in the presence of serum albumin and shows enhanced blood pool and kidney contrast in mice MRI studies.

The cancer therapy materialization by theranostic nanoparticles based on gold doped iron oxide under electromagnetic field amplification.

The harnessing of the cancer X-ray radiation therapy by gold-decorated Fe3O4 theranostic nanoparticles (Au-Fe3O4 NPs) under electromagnetic field was articulated. The applied electromagnetic field could assemble the NPs inside cell in oriented field direction and enhance the local irradiation dose inside cell. By materializing NPs, the absorption of the energy exposed by X-ray radiation under electromagnetic field was restricted. The cytotoxic properties of the Au-Fe3O4 NPs were assessed using MTT assay in L929, HeLa and PC3 cell lines under radiation and dark conditions. The efficiency of the Au-Fe3O4 NPs under 2 Gy dose radiations was higher than 6 Gy radiations in untreated cells. The in vitro measurements showed that under electromagnetic field and X-ray radiation therapy with Au-Fe3O4 NPs, around 90% of the cancer cells population was annihilated. The in vivo measurements indicated that the tumor shape and size under X-ray with Au-Fe3O4 NPs after 3 weeks were efficiently deteriorated.

Superparamagnetic iron oxide-gold nanoparticles conjugated with porous coordination cages: Towards controlled drug release for non-invasive neuroregeneration.

This paper reports a smart intracellular nanocarrier for sustainable and controlled drug release in non-invasive neuroregeneration. The nanocarrier is composed by superparamagnetic iron oxide-gold (SPIO-Au) core-shell nanoparticles (NPs) conjugated with porous coordination cages (PCCs) through the thiol-containing molecules as bridges. The negatively charged PCC-2 and positively charged PCC-3 are compared for intracellular targeting. Both types result in intracellular targeting via direct penetration across cellular membranes. However, the pyrene (Py)-PEG-SH bridge enabled functionalization of SPIO-Au NPs with PCC-3 exhibits higher interaction with PC-12 neuron-like cells, compared with the rhodamine B (RhB)-PEG-SH bridge enabled case and the stand-alone SPIO-Au NPs. With neglectable toxicities to PC-12 cells, the proposed SPIO-Au-RhB(Py)-PCC-2(3) nanocarriers exhibit effective drug loading capacity of retinoic acid (RA) at 13.505 µg/mg of RA/NPs within 24 h. A controlled release of RA is achieved by using a low-intensity 525 nm LED light (100% compared to 40% for control group within 96 h).

Micron-sized iron oxide particles for both MRI cell tracking and magnetic fluid hyperthermia treatment.

Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF). Micrometric IOP have a high sensitivity of detection. Nevertheless, little is known about their internalization processes or their potential heat power. Two micrometric commercial IOP (from Bangs Laboratories and Chemicell) were characterized by Transmission Electron Microscopy (TEM) and their endocytic pathways into glioma cells were analyzed. Their Specific Absorption Rate (SAR) and cytotoxicity were evaluated using a commercial AMF inductor. T2-weighted imaging was used to monitor tumor growth in vivo after MFH treatment in mice. The two micron-sized IOP had similar structures and r2 relaxivities (100 mM-1 s-1) but involved different endocytic pathways. Only ScreenMAG particles generated a significant rise in temperature following AMF (SAR = 113 W g-1 Fe). After 1 h of AMF exposure, 60% of ScreenMAG-labeled cells died. Translated to a glioma model, 89% of mice responded to the treatment with smaller tumor volume 42 days post-implantation. Micrometric particles were investigated from their characterization to their intracellular internalization pathways and applied in one in vivo cancer treatment, i.e. MFH.

Evaluation of the Physicochemical Properties of the Iron Nanoparticle Drug Products: Brand and Generic Sodium Ferric Gluconate.

Complex iron nanoparticle-based drugs are one of the oldest and most frequently administered classes of nanomedicines. In the US, there are seven FDA-approved iron nanoparticle reference drug products, of which one also has an approved generic drug product (i.e., sodium ferric gluconate (SFG)). These products are indicated for the treatment of iron deficiency anemia and are administered intravenously. On the molecular level, iron nanomedicines are colloids composed of an iron oxide core with a carbohydrate coating. This formulation makes nanomedicines more complex than conventional small molecule drugs. As such, these products are often referred to as nonbiological complex drugs (e.g., by the nonbiological complex drugs (NBCD) working group) or complex drug products (e.g., by the FDA). Herein, we report a comprehensive study of the physiochemical properties of the iron nanoparticle product SFG. SFG is the single drug for which both an innovator (Ferrlecit) and generic product are available in the US, allowing for comparative studies to be performed. Measurements focused on the iron core of SFG included optical spectroscopy, inductively coupled plasma mass spectrometry (ICP-MS), X-ray powder diffraction (XRPD), 57Fe Mössbauer spectroscopy, and X-ray absorbance spectroscopy (XAS). The analysis revealed similar ferric-iron-oxide structures. Measurements focused on the carbohydrate shell comprised of the gluconate ligands included forced acid degradation, dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and gel permeation chromatography (GPC). Such analysis revealed differences in composition for the innovator versus the generic SFG. These studies have the potential to contribute to future quality assessment of iron complex products and will inform on a pharmacokinetic study of two therapeutically equivalent iron gluconate products.

Ferric Maltol: A New Oral Iron Formulation for the Treatment of Iron Deficiency in Adults.

OBJECTIVE: To review the pharmacology, efficacy, and safety of ferric maltol (FM), an oral iron formulation, for iron deficiency anemia (IDA). DATA SOURCES: A MEDLINE/PubMed and EMBASE (January 1, 1985, to June 19, 2020) literature search was performed using the terms ferric maltol, accrufer, feraccru, iron maltol, ferric trimaltol, iron deficiency, iron deficiency anemia, inflammatory bowel disease, and chronic kidney disease. Additional data sources included prescribing information, abstracts, and the National Institutes of Health Clinical Trials Registry. STUDY SELECTION/DATA EXTRACTION: English language literature evaluating FM pharmacology, pharmacokinetics, efficacy, or safety in the treatment of IDA were reviewed. DATA SYNTHESIS: FM is a ferric, non-salt-based oral iron formulation demonstrating improved tolerance in patients with previous intolerance to other iron formulations. Phase 3 trials demonstrated significant improvements in anemia and serum iron parameters in patients with inflammatory bowel disease (IBD) and chronic kidney disease (CKD). Common adverse effects were gastrointestinal intolerance. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: FM is an effective and well-tolerated alternative to oral iron salts for patients with IBD or CKD and IDA. Emerging data suggest that FM is noninferior to intravenous (IV) ferric carboxymaltose in patients with IBD and IDA. Prior to selecting FM over IV iron products, consideration should be given to time to normalization of Hb, ease of administration, cost, and tolerability. CONCLUSION: FM is a relatively safe, effective oral iron therapy that may be better tolerated than other oral iron formulations. FM may be an effective alternative to IV iron in patients with IBD.

An evaluation of ferric derisomaltose as a treatment for anemia.

Introduction: Originally approved in Europe in 2009, ferric derisomaltose is the most recently authorized intravenous iron compound in the United States of America (2020). Ferric derisomaltose given as a rapid high-dose infusion can allow complete iron repletion in a single dose and it is now widely used in the treatment of iron deficiency. Areas covered: The chemistry, pharmacodynamics and pharmacokinetics of ferric derisomaltose are reviewed. Results from phase II, III and IV trials regarding efficacy and safety are presented. Mechanisms behind minor infusion reactions, hypersensitivity and hypophosphatemia are discussed. The economic impact of ferric derisomaltose use is presented. Data pertaining to the use of ferric derisomaltose in iron deficiency anemia, chronic kidney disease, inflammatory bowel disease, chronic heart failure, perioperative care and other patient groups are comprehensively covered. Expert opinion: Ferric derisomaltose is an effective intravenous iron formulation with a good safety profile, providing rapid, cost-effective iron repletion. Ferric derisomaltose releases low quantities of labile iron relative to older compounds. Anaphylaxis is extremely rare, and 'Fishbane' reactions are uncommon. Hypophosphatemia following ferric derisomaltose administration is infrequent in comparison to other intravenous irons such as ferric carboxymaltose. The scope of ferric derisomaltose use is growing with increasing research in these areas.

A New Pharmacokinetic Model Describing the Biodistribution of Intravenously and Intratumorally Administered Superparamagnetic Iron Oxide Nanoparticles (SPIONs) in a GL261 Xenograft Glioblastoma Model.

BACKGROUND: Superparamagnetic iron oxide nanoparticles (SPIONs) have displayed multifunctional applications in cancer theranostics following systemic delivery. In an effort to increase the therapeutic potential of local therapies (including focal hyperthermia), nanoparticles can also be administered intratumorally. Therefore, the development of a reliable pharmacokinetic model for the prediction of nanoparticle distribution for both clinically relevant routes of delivery is of high importance. MATERIALS AND METHODS: The biodistribution of SPIONs (of two different sizes - 130 nm and 60 nm) radiolabeled with zirconium-89 or technetium-99m following intratumoral or intravenous injection was investigated in C57/Bl6 mice bearing subcutaneous GL261 glioblastomas. Based on PET/CT biodistribution data, a novel pharmacokinetic model was established for a better understanding of the pharmacokinetics of the SPIONs after both administration routes. RESULTS: The PET image analysis of the nanoparticles (confirmed by histology) demonstrated the presence of radiolabeled nanoparticles within the glioma site (with low amounts in the liver and spleen) at all investigated time points following intratumoral injection. The mathematical model confirmed the dynamic nanoparticle redistribution in the organism over a period of 72 h with an equilibrium reached after 100 h. Intravenous injection of nanoparticles demonstrated a different distribution pattern with a rapid particle retention in all organs (particularly in liver and spleen) and a subsequent slow release rate. CONCLUSION: The mathematical model demonstrated good agreement with experimental data derived from tumor mouse models suggesting the value of this tool to predict the real-time pharmacokinetic features of SPIONs in vivo. In the future, it is planned to adapt our model to other nanoparticle formulations to more precisely describe their biodistribution in in vivo model systems.

Route of intestinal absorption and tissue distribution of iron contained in the novel phosphate binder ferric citrate.

BACKGROUND: Anemia of chronic kidney disease (CKD) is, in part, caused by hepcidin-mediated impaired iron absorption. However, phosphate binder, ferric citrate (FC) overcomes the CKD-induced impairment of iron absorption and increases serum iron, transferrin saturation, and iron stores and reduces erythropoietin requirements in CKD/ESRD patients. The mechanism and sites of intestinal absorption of iron contained in FC were explored here. METHODS: Eight-week old rats were randomized to sham-operated or 5/6 nephrectomized (CKD) groups and fed either regular rat chow or rat chow containing 4% FC for 6 weeks. They were then euthanized, and tissues were processed for histological and biochemical analysis using Prussian blue staining, Western blot analysis to quantify intestinal epithelial tight junction proteins and real-time PCR to measure Fatty Acid receptors 2 (FFA2) and 3 (FFA3) expressions. RESULTS: CKD rats exhibited hypertension, anemia, azotemia, and hyperphosphatemia. FC-treated CKD rats showed significant reductions in blood pressure, serum urea, phosphate and creatinine levels and higher serum iron and blood hemoglobin levels. This was associated with marked increase in iron content of the epithelial and subepithelial wall of the descending colon and modest iron deposits in the proximal tubular epithelial cells of their remnant kidneys. No significant difference was found in hepatic tissue iron content between untreated and FC-treated CKD or control groups. Distal colon's epithelial tight Junction proteins, Occludin, JAM-1 and ZO-1 were markedly reduced in the CKD groups. The FFA2 expression in the jejunum and FFA3 expression in the distal colon were significantly reduced in the CKD rats and markedly increased with FC administration. CONCLUSION: Iron contained in the phosphate binder, FC, is absorbed by the distal colon of the CKD animals via disrupted colonic epithelial barrier and upregulation of short chain fatty acid transporters.

Stabilization and delivery of bioavailable nanosized iron by fish sperm DNA.

Nanosized iron is a promising candidate as an iron fortificant due to its good solubility and bioavailability. Here, ferric hydrolysis in the presence of salmon/herring sperm DNA yielded irregularly shaped, highly negatively charged DNA-stabilized ferric oxyhydroxide nanoparticles (DNA-FeONPs) aggregated from 2-4 nm primary spherical monomers, in which phosphodioxy groups of the DNA backbone served as the iron-nucleation sites with high molecular weight (>500 bp), double-stranded winding, and acidic environmental pH disfavoring DNA's iron-loading capacity. The calcein fluorescence-quenching kinetics of polarized Caco-2 cells revealed the involvement of divalent transporter 1, macropinocytosis and nucleolin-mediated endocytosis in intestinal iron absorption from DNA-FeONPs with low molecular weight (<500 bp) favoring the performance of DNA in aiding iron absorption. In anemic rats, dietary DNA-FeONPs showed >80% relative iron bioavailability compared to FeSO4 as per hemoglobin regeneration efficiencies and delivered intestinally available nanosized iron, as determined by luminal iron speciation analysis. Overall, fish sperm DNA is promising in stabilizing and delivering bioavailable nanosized iron.

Modulating the Properties of Fe(III) Macrocyclic MRI Contrast Agents by Appending Sulfonate or Hydroxyl Groups.

Complexes of Fe(III) that contain a triazacyclononane (TACN) macrocycle, two pendant hydroxyl groups, and a third ancillary pendant show promise as MRI contrast agents. The ancillary group plays an important role in tuning the solution relaxivity of the Fe(III) complex and leads to large changes in MRI contrast enhancement in mice. Two new Fe(III) complexes, one with a third coordinating hydroxypropyl pendant, Fe(L2), and one with an anionic non-coordinating sulfonate group, Fe(L1)(OH2), are compared. Both complexes have a deprotonated hydroxyl group at neutral pH and electrode potentials representative of a stabilized trivalent iron center. The r1 relaxivity of the Fe(L1)(OH2) complex is double that of the saturated complex, Fe(L2), at 4.7 T, 37 °C in buffered solutions. However, variable-temperature 17O-NMR experiments show that the inner-sphere water of Fe(L1)(OH2) does not exchange rapidly with bulk water under these conditions. The pendant sulfonate group in Fe(L1)(OH2) confers high solubility to the complex in comparison to Fe(L2) or previously studied analogues with benzyl groups. Dynamic MRI studies of the two complexes showed major differences in their pharmacokinetics clearance rates compared to an analogue containing a benzyl ancillary group. Rapid blood clearance and poor binding to serum albumin identify Fe(L1)(OH2) for development as an extracellular fluid contrast agent.

Distribution of Ferrihydrite Nanoparticles in the Body and Possibility of Controlling Them in an Isolated Organ by a Permanent Magnetic Field.

We studied the distribution of ferrihydrite nanoparticles isolated from bacteria Klebsiella oxytoca in the whole body in vivo and in a cultured isolated organ (liver). The possibility of controlling these nanoparticles in the body using a magnetic field was assessed. One hour after intravenous injection of ferrihydrite nanoparticles to mice, their accumulation was observed in the liver, lungs, and kidneys. Experiment with cultured isolated rat liver showed that these nanoparticles can be controlled by a magnetic field and the influence of magnetic nanoparticles on the liver over 1 h does not lead to destruction of liver cells associated with the release of the marker enzyme AST. These results show the possibility of using magnetic nanoparticles as a system for controlled drug delivery in the body.

Engineering red-emitting multi-functional nanocapsules for magnetic tumour targeting and imaging.

In this work we describe the formulation and characterisation of red-emitting polymeric nanocapsules (NCs) incorporating superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic tumour targeting. The self-fluorescent oligomers were synthesised and chemically conjugated to PLGA which was confirmed by NMR spectroscopy, FT-IR spectroscopy and mass spectrometry. Hydrophobic SPIONs were synthesised through thermal decomposition and their magnetic and heating properties were assessed by SQUID magnetometry and calorimetric measurements, respectively. Magnetic nanocapsules (m-NCs) were prepared by a single emulsification/solvent evaporation method. Their in vitro cytotoxicity was examined in CT26 colon cancer cells. The formulated fluorescent m-NCs showed good stability and biocompatibility both in vitro and in vivo in CT 26 colon cancer models. Following intravenous injection, accumulation of m-NCs in tumours was observed by optical imaging. A higher iron content in the tumours exposed to a magnetic field, compared to the contralateral tumours without magnetic exposure in the same animal, further confirmed the magnetic tumour targeting in vivo. The overall results show that the engineered red-emitting m-NCs have great potential as multifunctional nanocarriers for multi-model bioimaging and magnetic-targeted drug delivery.

Hierarchical porous Mg2SiO4-CoFe2O4 nanomagnetic scaffold for bone cancer therapy and regeneration: Surface modification and in vitro studies.

3D multifunctional bone scaffolds have recently attracted more attention in bone tissue engineering because of addressing critical issues like bone cancer and inflammation beside bone regeneration. In this study, a 3D bone scaffold is fabricated from Mg2SiO4-CoFe2O4 nanocomposite which is synthesized via a two-step synthesis strategy and then the scaffold's surface is modified with poly-3-hydroxybutyrate (P3HB)-ordered mesoporous magnesium silicate (OMMS) composite to improve its physicochemical and biological properties. The Mg2SiO4-CoFe2O4 scaffold is fabricated through polymer sponge technique and the scaffold exhibits an interconnected porous structure in the range of 100-600 µm. The scaffold is then coated with OMMS/P3HB composite via dip coating and the physical, chemical, and biological-related properties of OMMS/P3HB composite-coated scaffold are assessed and compared to the non-coated and P3HB-coated scaffolds in vitro. It is found that, on the one hand, P3HB increases the cell attachment, proliferation, and compressive strength of the scaffold, but on the other hand, it weakens the bioactivity kinetic. Addition of OMMS to the coating composition is accompanied with significant increase in bioactivity kinetic. Besides, OMMS/P3HB composite-coated scaffold exhibits higher drug loading capacity and more controlled release manner up to 240 h than the other samples because of OMMS which has a high surface area and ordered mesoporous structure suitable for controlled release applications. The overall results indicate that OMMS/P3HB coating on Mg2SiO4-CoFe2O4 scaffold leads to a great improvement in bioactivity, drug delivery potential, compressive strength, cell viability, and proliferation. Moreover, OMMS/P3HB composite-coated scaffold has heat generation capability for hyperthermia-based bone cancer therapy and so it is suggested as a multifunctional scaffold with great potentials for bone cancer therapy and regeneration.

Iron bioavailability from bouillon fortified with a novel ferric phytate compound: a stable iron isotope study in healthy women (part II).

Bouillon cubes are widely consumed and when fortified with iron could contribute in preventing iron deficiency. We report the development (part I) and evaluation (current part II) of a novel ferric phytate compound to be used as iron fortificant in condiments such as bouillon. Ferric pyrophosphate (FePP), is the compound of choice due to its high stability in foods, but has a modest absorption in humans. Our objective was to assess iron bioavailability from a novel iron fortificant consisting of ferric iron complexed with phytic acid and hydrolyzed corn protein (Fe-PA-HCP), used in bouillon with and without an inhibitory food matrix. In a randomised single blind, cross-over study, we measured iron absorption in healthy adult women (n = 22). In vitro iron bioaccessibility was assessed using a Caco-2 cell model. Iron absorption from Fe-PA-HCP was 1.5% and 4.1% in bouillon with and without inhibitory matrix, respectively. Relative iron bioavailability to FeSO4 was 2.4 times higher than from FePP in bouillon (17% vs 7%) and 5.2 times higher when consumed with the inhibitory meal (41% vs 8%). Similar results were found in vitro. Fe-PA-HCP has a higher relative bioavailability versus FePP, especially when bouillon is served with an inhibitory food matrix.

Toxicity assessment of superparamagnetic iron oxide nanoparticles in different tissues.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been employed in several biomedical applications where they facilitate both diagnostic and therapeutic aims. Although the potential benefits of SPIONs with different surface chemistry and conjugated targeting ligands/proteins are considerable, complicated interactions between these nanoparticles (NPs) and cells leading to toxic impacts could limit their clinical applications. Hence, elevation of our knowledge regarding the SPION-related toxicity is necessary. Here, the present review article will consider current studies and compare the potential toxic effect of SPIONs with or without identical surface chemistries on different cell lines. It centers on cellular and molecular mechanisms underlying toxicity of SPIONs. Likewise, emphasis is being dedicated for toxicity of SPIONs in various cell lines, in vitro and animal models, in vivo.