Inhalable, Spray-Dried Terbinafine Microparticles for Management of Pulmonary Fungal Infections: Optimization of the Excipient Composition and Selection of an Inhalation Device

Terbinafine is a broad-spectrum antifungal agent with therapeutic potential against pulmonary aspergillosis. The main aim of the current study was to investigate the potential of l-leucine, alone and in combination with mannitol, to improve the performance of spray-dried terbinafine microparticles for inhalation. The study also aimed to investigate the potential of the low resistance Cyclohaler® and the high resistance Handihaler® as inhalation devices for spray-dried microparticles. To this end, eight powder inhalation formulations of terbinafine were prepared by nano spray drying via a factorial experimental design. The formulations were evaluated in vitro for their potential to deliver the antifungal drug to the lungs using the Cyclohaler® and the Handihaler®. Leucine was superior as an excipient to mannitol and to mixtures of leucine and mannitol. Using leucine as an excipient resulted in formulations with fine particle fractions of up to 60.84 ± 0.67% w/w and particle mass median aerodynamic diameters of down to 1.90 ± 0.20 μm, whereas using mannitol as an excipient resulted in formulations with fine particle fractions of up to 18.75 ± 3.46% w/w and particle mass median aerodynamic diameters of down to 6.79 ± 0.82 μm. When leucine was used as an excipient, using 50% w/w rather than 25% w/w ethanol in water as a spray solvent enhanced the dispersibility of the particles, with a mean absolute increase in the formulation fine particle fraction of 9.57% w/w (95% confidence interval = 6.40–12.73% w/w). This was potentially underlain by enrichment of the particle surfaces with leucine. The Cyclohaler® outperformed the Handihaler® as an inhalation device for the developed formulations, with a mean absolute increase in the fine particle fraction of 9.17% w/w (95% confidence interval = 8.17–10.16% w/w).

The Impact of Traffic and Meteorology on Urban Particle Mass and Particle Number Concentrations: Student-Led Studies Using Mobile Measurements before, during, and after the COVID-19 Pandemic Lockdowns

A series of student-led research activities were performed using a cargo bicycle equipped with air chemistry instrumentation to study the dynamics of aerosol particles in urban air before, during, and after the COVID-19 lockdown periods. The studies examined a high-traffic route and a low-traffic route around the city center of Münster, Germany. A complex picture emerged for how the particle number concentrations (PN) and particle mass concentrations (PM, specifically PM10) were affected by the day of the week, the route selected, the meteorological conditions, and the traffic intensity. Traffic had the most impact on PN through the multitude of exhaust plumes from motorized vehicles. The impact of traffic on PM10 was rather low, which is also mirrored in the general pattern of the low response of PM10 to the pandemic lockdown in Germany. Instead, PM10 responded more to the day of the week. Presumably, PM10 responds either to a specific traffic component, such as commercial low-duty vehicles, or to other business, such as construction activity. Meteorological conditions exert their impact mostly through the relative humidity, which affects particle growth. As such, future research could examine PN and PM10 responses over all seasons of the year. In any case, this student-led study in which high-resolution data were acquired deepened our understanding and broadened our view on particle dynamics in urban air. Well-trained university graduates will contribute to meeting further challenges in studying and combatting air pollution.

Measurement report: Vertical profiling of particle size distributions over Lhasa, Tibet: Tethered balloon-based in-situ measurements and source apportionment

In-situ measurements of vertically resolved particle size distributions based on a tethered balloon system were carried out for the first time in the highland city of Lhasa over the Tibetan Plateau in summer 2020, using portable optical counters for the size range of 0.124~32 μm. The vertical structure of 112 aerosol profiles was found to be largely shaped by the evolution of the boundary layer (BL), with a nearly uniform distribution of aerosols within the daytime mixing layer and a sharp decline with the height in the shallow nocturnal boundary layer. During the campaign, the average mass concentration of particulate matters smaller than 2.5 μm in aerodynamic diameter (PM2.5) within the BL was around 3 μg m−3, almost four times of the amount in the free troposphere (FT), which was rarely affected by surface anthropogenic emissions. Though there was a lower level of particle mass in the residual layer (RL) than in the BL, a similarity in particle mass size distributions (PMSDs) suggested that particles in the RL might be of the same origin as particles in the BL. This was also in consistence with the source apportionment analysis based on the PMSDs. Three distinct modes were observed in the PMSDs for the BL and the RL. One mode was exclusively coarse particles up to roughly 15 μm and peaked around 5 μm. More than 50 % of total particle mass was often contributed by coarse mode particles in this area, which was thought to be associated with local dust resuspension. The mode peaking over 0.5~0.7 μm was representative of biomass burning on religious holidays and was found to be most pronounced on holiday mornings. The contribution from the religious burning factor rose from about 25 % on non-holidays to nearly 50 % on holiday mornings. The mode dominated by particles smaller than 0.3 μm was thought to be associated with combustion related emissions and/or secondary aerosol formation. In the FT coarse mode particles only accounted for less than 10 % of the total mass and particles larger than 5 μm were negligible. The predominant submicron particles in the FT might be related to secondary aerosol formation and the aging of existed particles. To give a full picture of aerosol physical and chemical properties and better understand the origin and impacts of aerosols in this area, intensive field campaigns involving measurements of vertically resolved aerosol chemical compositions in different seasons would be much encouraged in the future.

Evolution under dark conditions of particles from old and modern diesel vehicles in a new environmental chamber characterized with fresh exhaust emissions

Atmospheric particles have several impacts on health and the environment, especially in urban areas. Parts of those particles are not fresh and have undergone atmospheric chemical and physical processes. Due to a lack of representativeness of experimental conditions and experimental artifacts such as particle wall losses in chambers, there are uncertainties on the effects of physical processes (condensation, nucleation and coagulation) and their role in particle evolution from modern vehicles. This study develops a new method to correct wall losses, accounting for size dependence and experiment-to-experiment variations. It is applied to the evolution of fresh diesel exhaust particles to characterize the physical processes which they undergo. The correction method is based on the black carbon decay and a size-dependent coefficient to correct particle distributions. Six diesel passenger cars, Euro 3 to Euro 6, were driven on a chassis dynamometer with Artemis Urban cold start and Artemis Motorway cycles. Exhaust was injected in an 8 m3 chamber with Teflon walls. The physical evolution of particles was characterized during 6 to 10 h. Increase in particle mass is observed even without photochemical reactions due to the presence of intermediate-volatility organic compounds and semi-volatile organic compounds. These compounds were quantified at emission and induce a particle mass increase up to 17 % h−1, mainly for the older vehicles (Euro 3 and Euro 4). Condensation is 4 times faster when the available particle surface is multiplied by 6.5. If initial particle number concentration is below [8–9] × 104 cm−3, a nucleation mode seems to be present but not measured by a scanning mobility particle sizer (SMPS). The growth of nucleation-mode particles results in an increase in measured [PN]. Above this threshold, particle number concentration decreases due to coagulation, up to −27 % h−1. Under those conditions, the chamber and experimental setup are well suited to characterizing and quantifying the process of coagulation.

Assessment of NAAPS-RA performance in Maritime Southeast Asia during CAMP²Ex

Monitoring and modeling aerosol particle lifecycle in Southeast Asia (SEA) is challenged by high cloud cover, complex meteorology, and the wide range of aerosol species, sources, and transformations found throughout the region. Satellite observations are limited, and there are few in situ observations of aerosol extinction profiles, aerosol properties, and environmental conditions. Therefore, accurate aerosol model outputs are crucial for the region. This work evaluates the Navy Aerosol Analysis and Prediction System Reanalysis (NAAPS-RA) aerosol optical thickness (AOT) and light extinction products using airborne aerosol and meteorological measurements from the Cloud, Aerosol, and Monsoon Processes Philippines Experiment (CAMP2Ex) in SEA. Modeled AOTs and extinction coefficients were compared to those retrieved with a High Spectral Resolution Lidar (HSRL-2). Correlations were highest for AOT in the mixed layer (AOTML; R2 = 0.83, bias = 0.00, root mean square error [RMSE] = 0.03) compared to total AOT (R2 = 0.68, bias = 0.01, RMSE = 0.14), although the correlations between the observations and 1° × 1° degree NAAPS-RA outputs were weaker in regions with strong gradients in aerosol properties, such as near areas of active convection. Correlations between simulated and retrieved aerosol extinction coefficients were highest from 145–500 m (R2 = 0.75, bias = 0.01 km−1, RMSE = 0.08 km−1) and decreased with increasing altitude (R2 = 0.69 and 0.26, bias = 0.00 and 0.00 km−1, RMSE = 0.09 and 0.00 km−1 for 500–1500 m and > 1500 m, respectively), which was likely a result of the use of bulk cloud mixing parameterizations. We also investigated the role of possible relative humidity (RH) errors in extinction simulations. Despite negative biases in modeled RH (−4.9, −7.7, and −2.3 % for altitudes < 500 m, 500–1500 m, and > 1500 m, respectively), AOT and extinction agreement with the HSRL-2 did not change significantly at any altitude when RHs from dropsondes were substituted into the model. Improvements may have been stunted due to errors in how NAAPS-RA modeled physics of particle hygroscopic growth, dry particle mass concentrations, and/or dry mass extinction efficiencies, especially when combined with AOT corrections from data assimilation. Specifically, the model overestimated the hygroscopicity of (i) smoke particles from biomass burning in the Maritime Continent (MC), and (ii) anthropogenic emissions transported from East Asia. This work provides insight into how certain environmental and microphysical properties influence AOT and extinction simulations, which can then be interpreted in the context of modeling global concentrations of particle mass and cloud condensation nuclei (CCN).

Application of Single-Particle Mass Spectrometer to Obtain Chemical Signatures of Various Combustion Aerosols

A single-particle mass spectrometer (SPMS) with laser ionization was constructed to determine the chemical composition of single particles in real time. The technique was evaluated using various polystyrene latex particles with different sizes (125 nm, 300 nm, 700 nm, and 1000 nm); NaCl, KCl, MgCO3, CaCO3, and Al2O3 particles with different chemical compositions; an internal mixture of NaCl and KCl; and an internal mixture of NaCl, KCl, and MgCl2 with different mixing states. The results show that the SPMS can be useful for the determination of chemical characteristics and mixing states of single particles in real time. The SPMS was then applied to obtain the chemical signatures of various combustion aerosols (diesel engine exhaust, biomass burning (rice straw), coal burning, and cooking (pork)) based on their single-particle mass spectra. Elemental carbon (EC)-rich and EC-organic carbon (OC) particles were the predominant particle types identified in diesel engine exhaust, while K-rich and EC-OC-K particles were observed among rice straw burning emissions. Only one particle type (ash-rich particles) was detected among coal burning emissions. EC-rich and EC-OC particles were observed among pork burning particles. The single-particle mass spectra of the EC or OC types of particles differed among various combustion sources. The observed chemical signatures could be useful for rapidly identifying sources of atmospheric fine particles. In addition, the detected chemical signatures of the fine particles may be used to estimate their toxicity and to better understand their effects on human health.