Effects of environmental exposure to iron powder on healthy and elastase-exposed mice.

Prolonged exposure to iron powder and other mineral dusts can threaten the health of individuals, especially those with COPD. The goal of this study was to determine how environmental exposure to metal dust from two different mining centers in Brazil affects lung mechanics, inflammation, remodeling and oxidative stress responses in healthy and elastase-exposed mice. This study divided 72 male C57Bl/6 mice into two groups, the summer group and the winter group. These groups were further divided into six groups: control, nonexposed (SAL); nonexposed, given elastase (ELA); exposed to metal powder at a mining company (SAL-L1 and ELA-L1); and exposed to a location three miles away from the mining company (SAL-L2 and ELA-L2) for four weeks. On the 29th day of the protocol, the researchers assessed lung mechanics, bronchoalveolar lavage fluid (BALF), inflammation, remodeling, oxidative stress, macrophage iron and alveolar wall alterations (mean linear intercept-Lm). The Lm was increased in the ELA, ELA-L1 and ELA-L2 groups compared to the SAL group (p < 0.05). There was an increase in the total number of cells and macrophages in the ELA-L1 and ELA-L2 groups compared to the other groups (p < 0.05). Compared to the ELA and SAL groups, the exposed groups (ELA-L1, ELA-L2, SAL-L1, and SAL-L2) exhibited increased expression of IL-1ß, IL-6, IL-10, IL-17, TNF-α, neutrophil elastase, TIMP-1, MMP-9, MMP-12, TGF-ß, collagen fibers, MUC5AC, iNOS, Gp91phox, NFkB and iron positive macrophages (p < 0.05). Although we did not find differences in lung mechanics across all groups, there were low to moderate correlations between inflammation remodeling, oxidative stress and NFkB with elastance, resistance of lung tissue and iron positive macrophages (p < 0.05). Environmental exposure to iron, confirmed by evaluation of iron in alveolar macrophages and in air, exacerbated inflammation, initiated remodeling, and induced oxidative stress responses in exposed mice with and without emphysema. Activation of the iNOS, Gp91phox and NFkB pathways play a role in these changes.

Oxysterols in stored powders as potential health hazards.

Cholesterol oxidation products (COPs) have greater biological activity than cholesterol itself. Oxysterols reduce the nutritional value of foods and exhibit a wide range of biological activity, including pro-oxidant, carcinogenic, and cytotoxic properties. The most commonly detected oxysterols in foods are 7α-HC, 7ß-HC, a product of their dehydrogenation 7-KC and α-CE, ß-CE. The main dietary sources of oxysterols are eggs and egg-derived products, thermally processed milk and milk-based products, fried meat. This study aimed to measure the amount of cholesterol oxidation products in milk powder, egg powder and milk-egg powder during 24 months of storage. The changes in the selected oxysterols (determined by gas chromatography) were recorded. In milk powder, after the production process, the amount of cholesterol was 0.2 g 100 g-1 fat and in egg powder it was 3.4 g 100 g-1. After 6 months of storage, the dominant oxysterol in milk and egg powder was 7α-HC and in milk-egg powder it was 7-KC. After the storage period, oxysterols in powdered milk reached 1.81% of total cholesterol.  The most stable cholesterol was in the milk-egg mixture and its oxidation was the slowest. This study showed the presence of COPs in milk powder, egg powder and milk-egg powder and the effect of storage on cholesterol oxidation.

Dry powder cationic lipopolymeric nanomicelle inhalation for targeted delivery of antitubercular drug to alveolar macrophage.

Excipients having self-assembling properties are less explored in the field of dry powder inhalation (DPI) technology. An amphiphilic lipopolymer system was developed using stearic acid (SA) and branched polyethyleneimine (BPEI) (1800 Dalton), at different proportions by covalent conjugation. A molecular dynamic (MD) simulation tool was employed for predicting the carrier behavior in a polar in vivo condition. The structural characterization was carried out using nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared (FTIR) spectroscopy. The physical nature of the lipopolymer was analyzed by differential scanning calorimetry. Determination of zeta potential and diameter of the micelles showed existence of cationic particles in the nano size range when a lower number of primary amino groups of BPEI was grafted with SA. The rifampicin (RIF)-loaded lipopolymer was also formulated further into spray-dried microparticles. Powder X-ray diffraction (PXRD) studies revealed that the RIF API (active pharmaceutical ingredient) exists as molecular dispersion in spray-dried microparticles. Topological analysis of the spray-dried nanomicelle was carried out using scanning electron microscopy (SEM). A large population of the drug-carrying particles were found to be under the inhalable size range (fine particle fraction 67.88% ± 3%). In vitro drug release kinetics from spray-dried nanomicelles were carried out at lung fluid pH.

Genotoxic effects of three selected black toner powders and their dimethyl sulfoxide extracts in cultured human epithelial A549 lung cells in vitro.

Until now, the adverse effects of toner powders on humans have been considered to be minimal. However, several recent reports have suggested possible significant adverse health effects from toner dust inhalation. The aim of this study was to evaluate the genotoxic potential of black toner powders in vitro. For the study of DNA damage, A549 cells were exposed to toner-powder suspensions and to their DMSO extracts, and then subjected to the comet assay and to the in-vitro cytokinesis block micronucleus test (CB-MNvit). Cytotoxic effects of the toner samples were assessed by the erythrosin B assay. Furthermore, size, shape, and composition of the toner powders were investigated. None of the three toner powders or their DMSO extracts reduced cell viability; however, they did induce DNA damage and formed micronuclei at concentrations from 80 to 400 µg cm(-2) , although to a varying extent. All toner powders contain considerable amounts of the pigments carbon black and magnetite (Fe(3) O(4) ) as well as small amounts of polycyclic aromatic hydrocarbons (PAHs). The overall results of our in-vitro study suggest that the investigated toner-powder samples are not cytotoxic but genotoxic. From the results of the physical and chemical characterization, we conclude that metals and metalloids as components of magnetite, or PAHs as components of the carbon-bearing material, are responsible for the genotoxic effects. Further research is necessary to determine the relevance of these in-vitro observations for private and occupational toner powder exposure.

Pulmonary spray dried powders of tobramycin containing sodium stearate to improve aerosolization efficiency.

PURPOSE: Tobramycin microparticulate powders containing the hydrophobic adjunct sodium stearate were studied for their use as pulmonary formulations in dry powder inhalers. METHODS: Spray-dried powders were characterized in terms of particle size distribution, morphology, crystallinity, drug dissolution rate, toxicity on epithelial lung cells and aerosol efficiency. RESULTS: The presence of the sodium stearate had a direct influence on the aerosol performance of tobramycin spray-dried powders. Powders containing 1% w/w sodium stearate had fine particle fraction FPF of 84.3 +/- 2.0% compared to 27.1 +/- 1.9% for powders containing no adjunct. This was attributed to the accumulation of sodium stearate at the particle surface. Powders with higher sodium stearate concentrations (2% w/w) showed significantly lower FPF (66.4 +/- 0.9%) and less accumulation of sodium stearate at the particle surface. This was attributed to the formation of adjunct micelles, which remained internalised in the particle structure due to their reduced tropism toward the drying drop surface and molecular mobility. Preliminary analysis of the toxicity effect of sodium stearate on A549 cell lines showed that the adjunct, in the concentration used, had no effect on cell viability over a 24-h period compared to particles of pure tobramycin. CONCLUSIONS: Tobramycin pulmonary powders with low level of sodium stearate, presenting high respiration performances and no overt toxicity on lung cells, could be used to improve therapeutic outcomes of patient with Cystic Fibrosis (CF).