Volume 14, Issue 1-2

In the past decade, many studies have been conducted to determine the health effects induced by exposure to engineered nanomaterials (NMs). Specifically for exposure via inhalation, numerous in vitro and animal in vivo inhalation toxicity studies on several types of NMs have been published. However, these results are not easily extrapolated to judge the effects of inhaling NMs in humans, and few published studies on the human response to inhalation of NMs exist. Given the emergence of more industries utilizing iron oxide nanoparticles as well as more nanomedicine applications of superparamagnetic iron oxide nanoparticles (SPIONs), this review presents an overview of the inhalation studies that have been conducted in humans on iron oxides. Both occupational exposure studies on complex iron oxide dusts and fumes, as well as human clinical studies on aerosolized, micron-size iron oxide particles are discussed. Iron oxide particles have not been described to elicit acute inhalation response nor promote lung disease after chronic exposure. The few human clinical studies comparing inhalation of fine and ultrafine metal oxide particles report no acute changes in the health parameters measured. Taken together existing evidence suggests that controlled human exposure to iron oxide nanoparticles, such as SPIONs, could be conducted safely.

Titanium dioxide (TiO 2 ) is a common additive that is increasingly used in consumer products, food, pharmaceutical dosage forms and cosmetic articles. However, due to size reduction of TiO 2 particles from the microscale to the nanoscale, application areas of this material are expanding, especially in the food sector, which makes investigations of nano-TiO 2 crucial. This review focuses on two important topics of current research regarding the oral pathway: 1) anatomy of the orogastrointestinal tract, composition of epithelial and mucus layer, and pH changes; 2) cell entry mechanisms, cytotoxicity and translocation. Sufficient knowledge on the oral uptake route is not yet available but is highly needed for human risk evaluation.

An increasing variety of different nanostructured materials including bionanomaterials are used. During synthesis, but also during use of nanostructured materials along their life-cycle, nanostructured materials and engineered nano-objects (ENO) – may be released into the environment. They will follow different exposure pathways and create an exposure concentration at the point of different biological systems, especially human beings. The inhalation pathway is of greatest importance with regard to health issues. The exposure concentration together with the breathing conditions integrated over time leads to the dose of the deposited material, which is of greatest interest for different effect studies. We discuss in this paper the kind of nanostructured material released from bionanomaterials into the environment. A large part of existing exposure studies in the literature is critically considered. A strategy is proposed to investigate in a more effective way the ENO-release from nanostructured materials as the first step of the exposure pathway. The release – exposure relationship as well as exposure – dose relationship for the case of inhalation is described leading to the possibility of tracing and ideally a complete balancing from ENO-release to dose. In the end the still needed activities for ENO-control methods in the environment are summarized.

Silver nanoparticles (Ag NPs) are one of the most common nanomaterials present in nanotechnology-based products. Here, the physical chemical properties of Ag NPs suspensions of 44 nm, 84 nm and 100 nm sizes synthesized in our laboratory were characterized. The NM-300 material (average size of 17 nm), supplied by the Joint Research Centre Nanomaterials Repository was also included in the present study. The Ag NPs potential cytotoxicity was tested on the Balb3T3 cell line by the Colony Forming Efficiency assay, while their potential morphological neoplastic transformation and genotoxicity were tested by the Cell Transformation Assay and the micronucleus test, respectively. After 24 h of exposure, NM-300 showed cytotoxicity with an IC50 of 8 µM (corresponding to 0.88 µg/mL) while for the other nanomaterials tested, values of IC50 were higher than 10 µM (1.10 µg/mL). After 72 h of exposure, Ag NPs showed size-dependent cytotoxic effect with IC50 values of 1.5 µM (1.16 µg/mL) for NM-300, 1.7 µM (1.19 µg/mL) for Ag 44 nm, 1.9 µM (0.21 µg/mL) for Ag 84 nm and 3.2 µM (0.35 µg/mL) for Ag 100 nm. None of the Ag NPs tested was able to induce either morphological neoplastic transformation or micronuclei formation.

Many in vitro studies demonstrated that metal oxide nanoparticles like zinc oxide and titanium dioxide are versatile platforms for industrial and biomedical applications. In this paper, investigation of the embryotoxic potential of these nanoparticles using the Embryonic stem Cells Test (EST) was evaluated. The EST is a validated in vitro toxicity test used to predict embryotoxicity of soluble chemical compounds, which only recently has been applied to nanoparticles, demonstrating its suitability also in nanotoxicology. Through such test, we were able to classify zinc oxide nanoparticles as not embryotoxic, while titanium dioxide nanoparticles appeared to be weakly embryotoxic.

Gold nanoparticles (GNPs) have gained in prominence within the field of nanomedicine with recent advancement of several embodiments to clinical trials. To ensure their success in the clinic it has become increasingly clear that a deeper understanding of the biological interactions of GNPs is imperative. Since the majority of GNPs are intended for systemic intravenous use, an immediate and critical biological interaction is between the blood and the GNP. Blood is composed of plasma proteins and cells. Both of these components can induce downstream effects upon interacting with GNPs that ultimately influence their medical impact. For instance, proteins from the blood can cover the GNP to create a biological identity through formation of a protein corona that is quite different from the originally synthesized GNP. Once in the bloodstream this protein coated GNP evokes both positive and negative physiological responses such as biodistribution into tissue for therapy (i.e., cancer) and toxicity or off target accumulation in the reticuloendothelial system (RES) that must be controlled for optimal use. In this review, we summarize predominantly in vitro studies of GNP interactions with blood plasma proteins and blood cells and make the case that more in vivo study is urgently needed to optimal design and control GNP use in medicine. In some cases where no specific GNP blood studies exist, we draw the readers’ attention to studies conducted with other types of nanoparticles as reference.

This study aimed to produce nanosized secondary calcium phosphate powders (CaHPO 4 , CaHPO 4 ∙2H 2 O) with a high reactivity by a precipitation reaction in water/oil emulsions. Aqueous mother solutions of CaNO 3 ∙4H 2 O and NH 4 H 2 PO 4 were prepared at a concentration of 1.25 mol/l and emulsified with rape seed oil with the addition of 5–10% surfactant (Brij35, Tween20, Tween80) at a water to oil ratio of 1:9. The resulting precipitated powders were predominantly composed of monetite with a medium crystal size of 30–90 nm and showed a high reactivity in cements formed with tetracalcium phosphate as second component. Compared to the use of ground CaHPO 4 these cements showed generally shorter setting times of 7–15 min (reference: 24 min) and higher compressive strength of 12–17 MPa (reference: 5.4 MPa). The latter was attributed to both a higher degree of conversion to the setting product hydroxyapatite (>90%) and a preferred growth of HA crystals in (002) direction leading to a better entangling of crystals in the set cement.

Nanoporous silica coatings for drug release purposes were prepared on medical implants. As substrate, we chose Bioverit ® II, which is a commercial available glass-mica ceramic implant material. The coating was prepared by a dip-coating technique in which long-chain organic molecules act as placeholders for the pores. Characterization of the coatings by scanning transmission electron microscopy and X-ray diffraction showed a disordered nanoporous system with a layer thickness of 30–150 nm. The nanoporous structure was stable for about 12 h in a typical cell culture medium and rearranged to a packing of silica nanoparticles. The coating allowed cell attachment and showed excellent biocompatibility in cell culture tests independently of the particular cell type examined. In vivo , implant-tissue interactions were examined in the middle ear in a novel mouse model. Whole genome expression profiling showed no persisting inflammatory response in the presence of the implants. Release profiles of the antibiotic ciprofloxacin demonstrated that the coating is suitable for a local drug delivery. The drug loading capacity could be drastically increased after sulfonic acid modification of the Bioverit ® II surface.

Up to now, it has been very challenging to manufacture a degradable bone replacement material having a specific pore size as well as a specific percentage of porosity which can be set independently of one another. We hypothesize that this is possible by using ammonium hydrogen carbonate (NH 4 HCO 3 ) as porosification agent in varying particle size fractions and varying percentages in combination with β-tricalcium phosphate (β-TCP) material to manufacture tailored porous β-TCP scaffolds. In our study the pore sizes of the sintered material were comparable to the selected particle size fraction of the porosification agent. Porosities ranging between 71 and 78 vol.% were achieved. It was possible to control the volume percentage of porosity by using different weight ratios of NH 4 HCO 3 and β-TCP. It can be concluded that ammonium hydrogen carbonate is an excellent porosification agent to design β-tricalcium phosphate scaffolds. This agent allows the independent setting of a specific pore size range as well as a specific volume percentage of porosity.

The post-operative situation in a stented vessel is characterised by struts which extend into the vessel lumen. These barriers on the surface provoke a topological change of the blood flow inducing flow deceleration and stagnation zones. Low values of wall shear stress (WSS) especially up- and downstream of the struts are found accordingly. Clinical studies correlate the occurrence of complications like restenosis and thrombosis with the alteration of the spatial WSS distribution. In this study 3D computational models were used to characterise the flow topology of three different stent types. For this purpose steady state simulations of the flow field within a simplified stented coronary artery were performed. The stent types differ in their strut patterns so that the variation of the induced flow structures can be observed. The aim of these investigations is to evaluate the effect of a purposeful flow control by altering the design of the struts. An improved alignment of the struts will be able to guide the flow to benefit the spatial WSS distribution. To compare the performance of the different stent types the size of the area charged with a WSS value below 0.5 Pa is used as a criterion. We will demonstrate that those strut pattern which generate helical flow structures significantly reduce the critical region of low WSS values.