Abbas S. Milani

Cell toxicity of superparamagnetic iron oxide nanoparticles

The performance of nanoparticles for biomedical applications is often assessed by their narrow size distribution, suitable magnetic saturation and low toxicity effects. In this work, superparamagnetic iron oxide nanoparticles (SPIONs) with different size, shape and saturation magnetization levels were synthesized via a co-precipitation technique using ferrous salts with a Fe(3+)/Fe(2+) mole ratio equal to 2. A parametric study is conducted, based on a uniform design-of-experiments methodology and a critical polymer/iron mass ratio (r-ratio) for obtaining SPION with narrow size distribution, suitable magnetic saturation, and optimum biocompatibility is identified. Polyvinyl alcohol (PVA) has been used as the nanoparticle coating material, owing to its low toxicity. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay is used to investigate the cell biocompatibility/toxicity effects of the samples. From the MTT assay results, it is observed that the biocompatibility of the nanoparticles, based on cell viabilities, can be enhanced by increasing the r-ratio, regardless of the stirring rate. This effect is mainly due to the growth of the particle hydrodynamic size, causing lower cell toxicity effects.

A new approach for the in vitro identification of the cytotoxicity of superparamagnetic iron oxide nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) are increasingly used in medical applications, such as targeting delivery and imaging. In the future, patients are more likely to be exposed to pharmaceutical products containing such particles. The study of toxicity of SPIONs has become of great importance in recent years, although the published data in this arena is limited. The aim of the present work is to investigate the cytotoxicity of SPIONs and the effect of the particles on the cell medium components. For this purpose, uncoated and polyvinyl alcohol (PVA) coated SPIONs with narrow size distribution were synthesized via a well-known coprecipitation method. The mouse fibroblast cell line L929 was exposed to SPIONs to probe the toxicity of magnetic nanoparticles during the bio application. Changes to the cell medium caused by SPIONs were analyzed with zeta potential measurements, ultraviolet visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay. It is observed that gas vesicles are formed in SPION-treated cells. Toxicity is conventionally explained by changes in the DMEMs pH and composition due to the tendency of SPIONs to interact with biomolecules. A new procedure is proposed to examine the in vitro toxicity of nanoparticles in a more rigorous manner, which gives an improvement in the relationship between in vivo and in vitro toxicity studies.

Optimal design and characterization of superparamagnetic iron oxide nanoparticles coated with polyvinyl alcohol for targeted delivery and imaging.

Superparamagnetic iron oxide nanoparticles (SPION) with narrow size distribution and stabilized by polyvinyl alcohol (PVA) were synthesized. The particles were prepared by a coprecipitation technique using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Using a design of experiments (DOE) approach, the effect of different synthesis parameters (stirring rate and base molarity) on the structure, morphology, saturation magnetization, purity, size, and size distribution of the synthesized magnetite nanoparticles was studied by various analysis techniques including X-ray powder diffraction (XRD), thermogravimetric analysis (TGA) with differential scanning calorimetry (DSC) measurements, vibrating-sample magnetometer (VSM), transmission electron microscopy (TEM), UV-visible, and Fourier transform infrared (FT-IR) spectrometer. PVA not only stabilized the colloid but also played a role in preventing further growth of SPION followed by the formation of large agglomerates by chemisorption on the surface of particles. A rich behavior in particle size, particle formation, and super paramagnetic properties is observed as a function of molarity and stirring conditions. The particle size and the magnetic properties as well as particle shape and aggregation (individual nanoparticles, magnetic beads, and magnetite colloidal nanocrystal clusters (CNCs) are found to be influenced by changes in the stirring rate and the base molarity. The formation of magnetic beads results in a decrease in the saturation magnetization, while CNCs lead to an increase in saturation magnetization. On the basis of the DOE methodology and the resulting 3-D response surfaces for particle size and magnetic properties, it is shown that optimum regions for stirring rate and molarity can be obtained to achieve coated SPION with desirable size, purity, magnetization, and shape.

An in vitro study of bare and poly(ethylene glycol)-co-fumarate-coated superparamagnetic iron oxide nanoparticles: a new toxicity identification procedure

As the use of superparamagnetic iron oxide nanoparticles (SPION) in biomedical applications increases (e.g. for targeting drug delivery and imaging), patients are likely to be exposed to products containing SPION. Despite their high biomedical importance, toxicity data for SPION are limited to date. The aim of this study is to investigate the cytotoxicity of SPION and its ability to change cell medium components. Bare and poly(ethylene glycol)-co-fumarate (PEGF)-coated SPION with narrow size distributions were synthesized. The particles were prepared by co-precipitation using ferric and ferrous salts with a molar Fe3+/Fe2+ ratio of 2. Dulbeccos modified Eagles medium (DMEM) and primary mouse fibroblast (L929) cell lines were exposed to the SPION. Variation of cell medium components and cytotoxicity due to the interactions with nanoparticles were analyzed using ultraviolet and visible spectroscopy (UV/vis) and the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) assay methods, respectively. The toxicity amount has been traditionally identified by changes in pH and composition in cells and DMEM due to the tendency of SPION to adsorb proteins, vitamins, amino acids and ions. For in vitro toxicity assessments, a new surface passivation procedure is proposed which can yield more reliable quantitative results. It is shown that a more reliable way of identifying cytotoxicity for in vitro assessments is to use particles with saturated surfaces via interactions with DMEM before usage.

Crucial role of the protein corona for the specific targeting of nanoparticles

AIMS We aimed to investigate the physicochemical effects of superparamagnetic iron oxide nanoparticles (SPIONs) on the composition of the protein corona and their correspondence toxicological issues. MATERIALS & METHODS SPIONs of different sizes and surface charges were exposed to fetal bovine serum. The structure/composition and biological effects of the protein corona-SPION complexes were probed. RESULTS & DISCUSSION The affinity and level of adsorption of specific proteins is strongly dependent on the size and surface charge of the SPIONs. In vivo experiments on the mouse blood-brain barrier model revealed that nontargeted SPIONs containing specific proteins will enter the brain endothelial barrier cells. CONCLUSION Some commercially available nanoparticles used for target-specific applications may have unintended uptake in the body (e.g., brain tissue) with potential cytotoxity.

Synthesis, surface architecture and biological response of superparamagnetic iron oxide nanoparticles for application in drug delivery: a review

The biological and medical applications of superparamagnetic iron oxide nanoparticles (SPION) are increasing fast. Therefore, the reduction of toxicity of SPION, by using various surface coatings, has become a main research area. This review article presents a summary of recent research and data on well-characterised SPION with different surface coatings (dextran, polyvinyl alcohol (PVA), polyethylene glycol (PEG), polyethylene glycol fumarate (PEGF), alginate, chitosan, albumin) along with cytotoxicity evaluation methods for drug delivery. The effect of the surface architecture of SPION in different delivery conditions is also reviewed. Cytotoxicity data are found to vary depending on the size, size distribution and surface derivatisation of SPION. In turn, these parameters depend on the methods of particle synthesis. The use of coprecipitation, microemulsions, thermal decomposition and hydrothermal synthesis are among the reviewed synthesis methods. Statistical techniques used for the optimisation of synthesis parameters have also been addressed.

An improvement of quantitative strategic planning matrix using multiple criteria decision making and fuzzy numbers

The Quantitative Strategic Planning Matrix (QSPM) is a useful tool to prioritize strategies at any level including corporate, business and functional. The ratings and attractive scores used in QSPM, however, require judgmental decisions and should be based on experts opinion to ensure the applicability of chosen strategies. Application of a fuzzy multi-criteria decision making method is proposed in this paper with the goal of improving the output of conventional QSPM by allowing the experts to employ linguistic terms (qualitative data) in their judgments. Namely, a multi-criteria decision making index via the technique for Order Preference by Similarity to Ideal Solution (TOPSIS) is adapted to the fuzzy QSPM in finding the sum total attractive scores of strategies. As a case study, the proposed method has been applied for strategy prioritization in a Tile Company. The results have been verified with expert knowledge and showed an improvement compared to the non-fuzzy QSPM.

Including time dependency and ANOVA in decision-making using the revised fuzzy AHP: A case study on wafer fabrication process selection

In the process of decision-making, sometimes analysts are given a sub-set of criteria for which statistical data are available from experiments, whereas for some other criteria, only qualitative judgments can be made. In such situations, it is important to consider the weights of experimental criteria along with the decision makers qualitative weights. Furthermore, in complex decision scenarios, one may need to consider the time notion and evaluate the behavior of alternatives over time, before making a final decision. This article using the revised fuzzy analytic hierarchy process (AHP) introduces a new decision process to include (1) time dependency of decisions and (2) statistical weighting from the standard analysis of variance (ANOVA). The application of the method is shown via a case study in the selection of wafer slicing and coating process for a three-year operation time. A signal-to-noise metric has been adapted to differentiate among alternatives that swap ranks over time. The method is straightforward and can be adapted to other multiple criteria decision making (MCDM) models.

Shear response of woven fabric composites under meso-level uncertainties

Experimental results in the literature indicate notable non-repeatabilities during mechanical testing of woven fabrics, even under the same loading conditions, which may be linked to the presence of defects and uncertainties at meso or micro levels in yarns. Sources of such uncertainties can include both yarn dimensional tolerances and variations in the fiber/matrix material properties. The aim of this article is to conduct a systematic sensitivity analysis on the meso-level uncertainty factors in a typical woven fabric and identify the most significant factors and their interactions under a trellising mode. A finite element model capable of capturing behavior of dry yarns, along with a two-level full-factorial design approach has been employed. Factorial designs are split into two categories of the geometrical and material factors. It is shown how the obtained range of variations from the above statistical designs may be used to capture non-repeatability in some trellising tests.

Performance based earthquake evaluation of reinforced concrete buildings using design of experiments

Highlights? Consideration of structural irregularities on response of structures. ? Application of design of experiment in performance based earthquake engineering. ? Interaction and sensitivity of different building irregularities (weak story, soft story) and construction quality. Seismic resiliency of new buildings has improved over the years due to enhancements in seismic codes and design practices. However, existing buildings designed and built under earlier codes are vulnerable and require a performance-based screening and retrofit prioritization. The performance modifiers considered are soft story, weak story, and the quality of construction, which are collated through a walk down survey. The building evaluation is performed through a pushover analysis, and performance objective are obtained through initial stiffness of the pushover curve. Using a design of experiments technique, a reliable system input-output relation has been identified and used to evaluate the performance criteria at untried design points (i.e., buildings with different modifier values). The proposed method of performance based evaluation is illustrated through consideration of the different structural deficiencies on a typical six-storey reinforced concrete building in Vancouver. Through the designed experiments, the main and interaction effects of the performance modifiers have also been studied.