Mechanisms of action of inhaled fibers, particles and nanoparticles in lung and cardiovascular diseases

Nanotechnology is the new industrial revolution of the 21st Century as the various processes lead to radical improvements in medicine, manufacturing, energy production, land remediation, information technology and many other everyday products and applications. With this revolution however, there are undoubted concerns for health, safety and the environment which arise from the unique nature of materials and processes at the nanometre scale. The in vitro assays used in the screening strategy are all validated, internationally accepted protocols and provide a useful indication of potential toxicity of a chemical as a result of effects on various toxicological endpoints such as local site of contact (dermal) irritation, general cytotoxicity and mutagenicity. The initial in vitro screening strategy described in this paper to investigate the potential health implications, if any, which may arise following exposure to one specific application of nanoparticulate cerium oxide used as a diesel fuel borne catalyst, reflects a precautionary approach and the results will inform judgement on how best to proceed to ensure safe use.     

Dispersion of inhaled particles in the human lungs

A theoretical model of the dispersion of inhaled particles in the human respiratory tract is proposed. The model takes into account the contributions of air flow, Brownian motion, and gravitational settling, but neglects the effect of inertia of the particles. The dispersion is analyzed by dividing the respiratory tract into five zones according to the aerodynamic characteristics. The dispersion in each zone is described by a response curve at the outlet of the zone for a step input of aerosols at the inlet of that zone. Calculations for a single breath of 450 and 1980 ml of aerosols (as a step input to the mouth) over a period of 4 and 6 sec, respectively, were carried out using the proposed model, and the results were compared with the experimental curves for the distribution of half-micron particles in exhaled air reported in the literature. The model predicts that for larger breaths, Brownian motion and gravitational settling of half-micron particles are the major factors controlling the dispersion of inhaled particles.     

Dietary fibers and cardiometabolic diseases

The high prevalence of cardiovascular disease (CVD) is largely attributable to the contemporary lifestyle that is often sedentary and includes a diet high in saturated fats and sugars and low ingestion of polyunsaturated fatty acids (PUFAs), fruit, vegetables, and fiber. Experimental data from both animals and humans suggest an association between increased dietary fiber (DF) intakes and improved plasma lipid profiles, including reduced low density lipoprotein cholesterol (LDL-C) concentrations. These observations underline that the intake of DF may protect against heart disease and stroke.     

The use of polymer-based nanoparticles and nanostructured materials in treatment and diagnosis of cardiovascular diseases: Recent advances and emerging designs

This review summarizes important advances in polymer-based nanotechnologies for the treatment and diagnosis of cardiovascular diseases, focusing on nanoparticles and nanostructured materials/devices. The current state of the art and design parameters are discussed with the aim of providing a source of information that can aid in the development of new treatments by bridging between materials development, preclinical, and clinical trials. This is highly relevant as cardiovascular diseases remain a leading cause of death worldwide and as current treatments burden the healthcare systems with great costs. Different strategies, from targeting theranostic nanocarriers, to dual-drug depot systems, injectable cell scaffolds, and LDL acceptors are treated. The review ends with a concluding outlook on the possibilities and challenges presented to polymer-based nanotechnologies in cardiovascular disease therapy.     

Cobalt nanoparticles induce lung injury,DNA damage and mutations in mice

Background

We and other groups have demonstrated that exposure to cobalt nanoparticles (Nano-Co) caused oxidative stress and inflammation, which have been shown to be strongly associated with genotoxic and carcinogenic effects. However, few studies have reported Nano-Co-induced genotoxic effects in vivo. Here, we propose that Nano-Co may have high genotoxic effects due to their small size and high surface area, which have high capacity for causing oxidative stress and inflammation.

Methods

gpt delta transgenic mice were used as our in vivo study model. They were intratracheally instilled with 50 μg per mouse of Nano-Co. At day 1, 3, 7 and 28 after exposure, bronchoalveolar lavage (BAL) was performed and the number of neutrophils, CXCL1/KC level, LDH activity and concentration of total protein in the BAL fluid (BALF) were determined. Mouse lung tissues were collected for H&E staining, and Ki-67, PCNA and γ-H2AX immunohistochemical staining. 8-OHdG level in the genomic DNA of mouse lungs was determined by an OxiSelect? Oxidative DNA Damage ELISA Kit, and mutant frequency and mutation spectrum in the gpt gene were also determined in mouse lungs at four months after Nano-Co exposure by 6-TG selection, colony PCR, and DNA sequencing.

Results

Exposure of mice to Nano-Co (50 μg per mouse) resulted in extensive acute lung inflammation and lung injury which were reflected by increased number of neutrophils, CXCL1/KC level, LDH activity and concentration of total protein in the BALF, and infiltration of large amount of neutrophils and macrophages in the alveolar space and interstitial tissues. Increased immunostaining of cell proliferation markers, Ki-67 and PCNA, and the DNA damage marker, γ-H2AX, was also observed in bronchiolar epithelial cells and hyperplastic type II pneumocytes in mouse lungs at day 7 after Nano-Co exposure. At four months after exposure, extensive interstitial fibrosis and proliferation of interstitial cells with inflammatory cells infiltrating the alveolar septa were observed. Moreover, Nano-Co caused increased level of 8-OHdG in genomic DNA of mouse lung tissues. Nano-Co also induced a much higher mutant frequency as compared to controls, and the most common mutation was G:C to T:A transversion, which may be explained by Nano-Co-induced increased formation of 8-OHdG.

Conclusion

Our study demonstrated that exposure to Nano-Co caused oxidative stress, lung inflammation and injury, and cell proliferation, which further resulted in DNA damage and DNA mutation. These findings have important implications for understanding the potential health effects of nanoparticle exposure.

     

Sonochemical deposition of silver nanoparticles on wool fibers

Silver nanoparticles were deposited on the surface of natural wool with the aid of powered ultrasound. The average particle size was 5–10 nm, but larger aggregates of 50–100 nm were also observed. The sonochemical irradiation of a slurry containing wool fibers, silver nitrate, and ammonia in an aqueous medium for 120 min under an argon atmosphere yielded a silver–wool nanocomposite. By varying the gas and reaction conditions, we could achieve control over the deposition of the metallic silver particles on the surface of the wool fibers. The resulting silver‐deposited wool samples were characterized with X‐ray diffraction, transmission electron microscopy, high‐resolution transmission electron microscopy, high‐resolution scanning electron microscopy, electron‐dispersive X‐ray analysis, Brunauer, Emmett, and Teller physical adsorption method, X‐ray photoelectron spectroscopy, and Raman and diffused reflection optical spectroscopy. The results showed that the strong adhesion of the silver to the wool was a result of the adsorption and interaction of silver with sulfur moieties related to the cysteine group. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 1732–1737, 2007     

Deposition of clean and contaminated latex particles on pulp fibers

Electrostatic interaction between latex particles and oppositely charged surfaces can be affected by the presence of ionic compounds, which are not an integral part of latex particles. They could be formed during polymerization or could be present as emulsifiers. This “free charge” adsorbs on fiber and interferes with latex particles deposition. Consequently, with increasing latex addition, the extent of deposition may decrease. Attempts to explain such unexpected behavior often lead to questionable conclusions. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1879–1883, 2005     

Measurements of the total and regional deposition of inhaled particles in the human respiratory tract

The total and regional deposition of monodisperse aerosols in the human respiratory tract has been measured in 12 healthy subjects breathing through the mouth. Radioactively labelled polystyrene particles in the aerodynamic diameter range 3.5–10.0 μm were employed. The total deposition results are similar to those reported by Stahlhofen et al. (1980), showing only a slight progressive increase with particle size, from a mean fraction of 0.79 of the inhaled aerosol at 3.5 μm, to 0.88 for 10 μm particles. The extrathoracic airways show a very marked deposition at all sizes, predominantly in the throat. The throat values rise rapidly from a mean of 0.09 at 3.5 μm to 0.36 at 10 μm particle diameter. Two intrathoracic fractions were also obtained by the widely accepted method of measuring the relative amounts of activity cleared from the thorax as a function of time. Alveolar deposition was apparently still some 0.06 of the inhaled aerosol at 10 μm particle diameter. Tracheo-bronchial deposition showed little change at any particle size except at 3.5 μm, when it was 0.24 of the inhaled aerosol.     

Electrical conductivity and mechanical strength of composites consisting of phenolic resin,carbon fibers,and metal particles

Composites of phenolic resin of novolac type as matrix, with metal particles of Zn as conducting filler, without or with 15% v/v carbon fibers were manufactured by hot pressing. The porosity ratio, the hardness, the flexural and shear strength, and the electrical conductivity of the composites were determined. The percolation threshold was determined based on two models of electrical conductivity versus the content of metal particles of Zn, namely, an analogous to polymer gelation model and the other based on the power law. The composites of carbon fibers combined with Zn particles have higher electrical conductivity than the corresponding without carbon fibers and high strength, lower than that of the composite reinforced with carbon fibers without Zn particles, but still acceptable. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Translocation of particles and inflammatory responses after exposure to fine particles and nanoparticles in an epithelial airway model

Background  

Experimental studies provide evidence that inhaled nanoparticles may translocate over the airspace epithelium and cause increased cellular inflammation. Little is known, however, about the dependence of particle size or material on translocation characteristics, inflammatory response and intracellular localization.     

Mechanisms of action of docosahexaenoic acid in the nervous system

Abtract This review describes (from both the animal and human literature) the biological consequences of losses in nervous system docosahexaenoate (DHA). It then concentrates on biological mechanisms that may serve to explain changes in brain and retinal function. Brief consideration is given to actions of DHA as a nonesterified fatty acid and as a docosanoid or other bioactive molecule. The role of DHA-phospholipids in regulating G-protein signaling is presented in the context of studies with rhodopsin. It is clear that the visual pigment responds to the degree of unsaturation of the membrane lipids. At the cell biological level, DHA is shown to have a protective role in a cell culture model of apoptosis in relation to its effects in increasing cellular phosphatidylserine (PS); also, the loss of DHA leads to a loss in PS. Thus, through its effects on PS, DHA may play an important role in the regulation of cell signaling and in cell proliferation. Finally, progress has been made recently in nuclear magnetic responance studies to delineate differences in molecular structure and order in biomembranes due to subtle changes in the degree of phospholipid unsaturation.     

Polymer nanocomposite powders and melt spun fibers filled with silica nanoparticles

Nanocomposite powders from polypropylene filled with surface modified and unmodified fumed silica have been prepared from polymer solution to achieve improved mixing and have been forwarded to fiber melt spinning. The surface of the fumed silica was modified with dodecyl alkoxy silanes. Crystallization velocity and viscosity of the PP nanocomposites thereof were determined to ensure good melt spinning processing conditions for all composite compositions. Upon addition of untreated filler particles, a shear thinning and an increased crystallization velocity of the polymer melt was found, while only minor changes were detected in the presence of surface modified fumed silica particles. The composites and the polymer fibers made from these powder composites by melt spinning were mainly characterized by optical microscopy (OM), scanning electron microscopy (SEM), mechanical measurements, differential scanning calorimetry (DSC), and solid‐state NMR. The unmodified fumed silica was found to have a strong influence on the mechanical fiber properties, while the surface modified silica only a small one. Fibers were additionally characterized with respect to the uniformity, the PP crystallinity, moisture absorption, and the water contact angle. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 218–227, 2007     

In situ preparation of inorganic nanoparticles in amino-functionalized porous cellulose particles

Amino-functionalized cellulose particles with a porous structure were prepared by a solvent-releasing method with 1-butyl-3-methylimdazolium chloride ([Bmim]Cl) followed by an amination reaction, and were incorporated with silica. The amino groups provided the base catalyst for the formation of silica on the porous structure during the in situ sol–gel reaction of tetraethyl orthosilicate. After the reaction, no free silica remained in the reaction medium. The microscopic morphologies (specific surface area, pore diameter, and pore volume) of the composite particles were affected by the silica content in the composites, which was controllable by the sol–gel reaction time. When silver nanoparticles were introduced to the pores of the cellulose particles by reduction of AgNO₃ with amino groups, the composite exhibited catalytic ability and recyclability.     

Tubular carbon nanostructures produced by tunneling of cobalt nanoparticles in carbon fibers

Tubular carbon nanostructures have been produced by the tunneling of cobalt nanoparticles in carbon fibers that are derived from electrospun polyacrylonitrile (PAN) fibers. During the annealing in a vacuum up to 1400 °C, carbonization takes place to the cobalt-doped PAN fibers, causing these fibers to transform to a composite of cobalt nanoparticles and carbon fibers. Cobalt nanoparticles embedded in the carbon fibers start tunneling in these fibers, thus producing various tubular carbon nanostructures. During the tunneling, carbon atoms confronted with the cobalt nanoparticles diffuse into these particles, which later precipitate from them and leave a tubular structure behind.     

Agglomerates and granules of nanoparticles as filter media for submicron particles

An experimental study on filtration of submicron solid and liquid aerosol particles by using a filter media composed of agglomerates or granules of nanoparticles is described. Fumed silica nanoagglomerates, carbon black granules, silica shells, activated carbon granules, glass beads and nanoporous hydrophobic aerogel were among the granular filter media tested and compared to a commercially available HEPA fiber-based filter. Other than the glass beads which were used for comparison purposes, the primary particle size of the agglomerates/granules is of nanometer scale, but they agglomerate to form porous structures of about several hundreds of microns which were customized as packed (deep bed) or fluidized bed filters and challenged against submicron solid and liquid aerosols. For packed bed filters, the size of the granules has been optimized to a range of 150-500 µm with a filter thickness of about 1-3 in. and superficial gas velocities of less than 4 cm/s. Fluidized beds required granules smaller than 150 µm and the height of the bed was in the range of 15-40 cm.The customized filters and a HEPA fiber-based filter were challenged simultaneously against the same aerosol at the same superficial gas velocities. When using carbon black or aerogel granules as filter media, collection efficiencies comparable or even higher than HEPA fiber-based filters are obtained, but with the advantage of extra filtration capacity due to the deep bed configuration and the absorption of liquids into the porosity of the media. A fluidized bed filter of aerogel granules not only provides higher collection efficiency and larger capacity than a HEPA fiber-based filter when challenged against both oil mist and solid aerosols but also has an extremely low pressure drop compared to a packed bed filter and can be operated continuously with respect to removing saturated granules and adding fresh ones.     

Carboplatin liposomal nanoparticles: Preparation,characterization, and cytotoxicity effects on lung cancer in vitro environment

The study aimed to encapsulate anticancer drug carboplatin into liposomal nanoparticles by reverse-phase evaporation technique and evaluate its efficacy on lung cancer in vitro environment. Nanoparticles were characterized in terms of size, drug loading efficiency, drug retention capability, and cytotoxicity effects. Nanoscale particles with 67% drug encapsulation efficiency were prepared. Also, high retention capability (drug release equal to 25% after 72?h) of the nanodrug was confirmed. In addition, results of the nanodrug cytotoxicity indicated nanoparticles increased potency of the drug by approximately 90%. Findings of the study indicated liposome can be used for carboplatin delivery to lung cancer.     

In vitro deposition measurement of inhaled micrometer-sized particles in extrathoracic airways of children and adolescents during nose breathing

An in vitro study was conducted with the goal of developing empirical correlations to predict the deposition of particles with an aerodynamic diameter of 0.5–5.3 μm in nasal airways of children with ages 4–14 years. CT images of nasal airways of thirteen healthy subjects and one with congested nasal airways were used for fabricating the replicas by rapid prototyping. Replicas included nasal airways to the level of the upper trachea as well as the face. Four physiological breathing patterns (sinusoidal waves) of children were simulated by a pulmonary waveform generator. Using an Electrical Low Pressure Impactor (ELPI) we measured deposition of sunflower oil particles generated by a Collison atomizer. Moreover, using the same setup, particle deposition in five adult replicas fabricated using MRI images was measured for direct comparison with the child replicas and in vivo data available for adults. Deposition increased by increasing particle size and flow rate, indicating impaction as the dominant deposition mechanism. Existing correlations for adults were unable to reduce the scatter in the deposition data for children. A correlation was developed for prediction of deposition including the relevant non-dimensional numbers (Stokes and Reynolds numbers) that were calculated considering the dimensions of the airways. The corrected correlations should be useful for exposure estimation of children and for efficient pediatric drug delivery using face masks.