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The deposition characteristics in lungs following inhalation, the potential toxic effects induced and the toxicokinetic fate including a possible translocation to other sites of the body are predominantly determined by the agglomeration status of nanoscaled primary particles. Systemic particle effects, i.e. effects on remote organs besides the respiratory tract are considered to be of relevant impact only for de-agglomerated particles with a nanoscaled aspect. Rats were exposed to various types of nanoscaled particles, i.e. titanium dioxide, carbon black and constantan. These were dispersed in physiologically compatible media, e.g. phosphate buffer, sometimes including auxiliaries. Rats were treated with aqueous nanoparticle dispersions by intratracheal instillation or were exposed to well-characterized nanoparticle aerosols. Subsequently, alterations in the particle size distribution were studied using transmission electron microscopy (TEM) as well as the bronchoalveolar lavage (BAL) technique. Based on the results in various approaches, a tendency of nanoscaled particles to form larger size agglomerates following deposition and interaction with cells or the respiratory tract is predominant. The contrary trend, i.e. the increase of particle number due to a disintegration of agglomerates seems not to be of high relevance.

A new approach is described to capture nano-size aerosols on internally-cooled micro tubing of the solid-phase microextraction (SPME) device followed by convenient introduction of the collected analytes into analytical instrument. Particles were generated using an aerosol formation by homogeneous nucleation of an organic vapor, and subsequent growth to nano-size particles by coagulation of decanedioic acid, bis[2-ethylhexyl] ester (DEHS). The approach was validated by using carbon dioxide-cooled micro tubing to collect the nanosize DEHS particles followed by analyses on GC-flame ionization detector (FID). Particle size ranged from 150 to 590 nm. Temperature difference between the SPME device and DEHS particles mixture created a temperature gradient and resulted in thermophoretic effect that was determining the extraction rate. SPME device was cooled to as low as -75 degrees C, while the DEHS remained close to room temperature. Several aspects of nanoparticle sampling were tested to demonstrate the principle of the sampling approach. These included the effects of thermal gradient, sample flow rate, sampling time, CO(2) delivery mode (constant coolant delivery vs. constant temperature), and particle size. Results were normalized to measure particulate concentrations using direct sampling with PTFE filters. Nanoparticle extractions of DEHS mass were proportional to sampling time. Normalized mass of DEHS extracted increased with increase in temperature gradient and with increase of the cross flow velocity. Preliminary results indicate that the variation of heat transfer boundary layer caused by the variation in the cross flow velocity produce self-compensating effect at constant coolant delivery, indicating that this approach could be used for field determinations including the time-weighted average sampling of nanoparticles. Thus, it may be possible to develop simple device based on this concept for field applications.

Annual outbreaks of influenza infections, caused by new influenza virus subtypes and high incidences of zoonosis, make seasonal influenza one of the most unpredictable and serious health threats worldwide. Currently available vaccines, though the main prevention strategy, can neither efficiently be adapted to new circulating virus subtypes nor provide high amounts to meet the global demand fast enough. New influenza vaccines quickly adapted to current virus strains are needed. In the present study we investigated the local toxicity and capacity of a new inhalable influenza vaccine to induce an antigen-specific recall response at the site of virus entry in human precision-cut lung slices (PCLS). This new vaccine combines recombinant H1N1 influenza hemagglutinin (HAC1), produced in tobacco plants, and a silica nanoparticle (NP)-based drug delivery system. We found no local cellular toxicity of the vaccine within applicable concentrations. However higher concentrations of NP (≥103 µg/ml) dose-dependently decreased viability of human PCLS. Furthermore NP, not the protein, provoked a dose-dependent induction of TNF-α and IL-1β, indicating adjuvant properties of silica. In contrast, we found an antigen-specific induction of the T cell proliferation and differentiation cytokine, IL-2, compared to baseline level (152±49 pg/mg vs. 22±5 pg/mg), which could not be seen for the NP alone. Additionally, treatment with 10 µg/ml HAC1 caused a 6-times higher secretion of IFN-γ compared to baseline (602±307 pg/mg vs. 97±51 pg/mg). This antigen-induced IFN-γ secretion was further boosted by the adjuvant effect of silica NP for the formulated vaccine to a 12-fold increase (97±51 pg/mg vs. 1226±535 pg/mg). Thus we were able to show that the plant-produced vaccine induced an adequate innate immune response and re-activated an established antigen-specific T cell response within a non-toxic range in human PCLS at the site of virus entry. [ABSTRACT FROM AUTHOR]

The application of nanosized multicomponent particles often requires tailored mixing characteristics. This involves mixing on primary particle level, on cluster level, or on aggregate level. This mixing is often evaluated qualitatively in 2D, based on image analyses. This work presents an approach to utilize the cluster size in combination with the heterogeneous coordination number as a quantitative measure for the mixing of clusters of more than three primary particles within nanosized aggregates in 3D. Therefore, nanoparticle aggregates formed by differently sized clusters are simulated and evaluated with respect to cluster size and coordination number. Subsequently, a method is introduced to generate 2D projections and mimic image analysis based on transmission electron microscopy images from flame‐made nanoparticles. This also includes the evaluation of the necessary visible area for each particle to be identified in the 2D image analysis. This leads to a correlation of the 2D projections and 3D simulations including a calibration to experimental data and enables the determination of a 3D heterogeneous coordination number and cluster size from 2D image analysis. Tailored mixing of primary particles at nanoscale enables the design of materials with specific electronic properties. The characterization of such particle systems, however, suffers from 2D interpretation and missing validation on 3D. This work presents a simple characterization method to quantify mixing in 3D from 2D image analysis. [ABSTRACT FROM AUTHOR]