Cascade Impactor Research Articles

Combined inertial and pleated filter for efficient PM1.0 separation and sampling

A reliable measuring method of particulate matter less than 1 µm (PM1.0) is essential to clarify the correlation between the PM1.0 mass concentration and the impact of human health, and to establish effective PM1.0 control strategies. In this study, a new PM1.0 sampler, the inertial filter/pleated filter sampler (I/P sampler), was designed to collect particles larger than 1 μm in the inertial filter and PM1.0 in the pleated filter during sampling. The inertial filter with small filtration area successfully separated particles larger than 1 μm by reducing diffusion and increasing inertia, while the pleated filter with large filtration area efficiently collected PM1.0 by lowering the filtration velocity to promote diffusional collection.The I/P sampler was used to measure PM1.0 mass concentration through field tests, with results compared with those of conventional sampling devices for PM1.0 (cyclone sampler, cascade impactor, beta attenuation monitor [BAM], and EPA-approved federal reference method [E-FRM] sampler). Field measurements indicated a good correlation between the I/P sampler and conventional samplers, with regression slopes ranging from 0.90 to 1.07 in summer and 1.10 to 1.37 in winter. In addition, the measured mass concentrations decreased in the order of I/P sampler, cyclone sampler, E-FRM sampler, BAM, and cascade impactor.

Preparation of Ibuprofen-Loaded Inhalable γCD-MOFs by Freeze-Drying Using the QbD Approach

Background/Objectives: Research on cyclodextrin-based metal-organic frameworks (CD-MOFs) is still in its infancy, but their potential for use in drug delivery—expressly in the lung—seems promising. We aimed to use the freeze-drying method to create a novel approach for preparing CD-MOFs. MOFs consisting of γ-cyclodextrin (γCD) and potassium cations (K+) were employed to encapsulate the poorly water-soluble model drug Ibuprofen (IBU) for the treatment of cystic fibrosis (CF). Methods: Using the LeanQbD® software (v2022), we designed the experiments based on the Quality by Design (QbD) concept. According to QbD, we identified the three most critical factors, which were the molar ratio of the IBU to the γCD, incubation time, and the percentage of the organic solvent. light-, scanning electron microscope (SEM) and laser diffraction were utilized to observe the morphology and particle size of the samples. In addition, the products were characterized by Differential Scanning Calorimetry (DSC), X-ray Powder Diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). Results: Based on characterizations, we concluded that a γCD-MOF/IBU complex was also formed using the freeze-drying method. Using formulations with optimal aerodynamic properties, we achieved 38.10 ± 5.06 and 47.18 ± 4.18 Fine Particle Fraction% (FPF%) based on the Andersen Cascade Impactor measurement. With these formulations, we achieved a fast dissolution profile and increased IBU solubility. Conclusions: This research successfully demonstrates the innovative use of freeze-drying to produce γCD-MOFs for inhalable IBU delivery. The method enabled to modify the particle size, which was crucial for successful pulmonary intake, emphasizing the need for further investigation of these formulations as effective delivery systems.

Determination of the Radon Progeny Activity Size Distribution in Laboratory Conditions

Knowledge of the active size distribution of radon daughters is one of the main parameters for determining the effective dose from inhalation of short-term radon decay products. However, this parameter is crucial for accurately determining an effective dose; there are currently very limited possibilities for determining it. This paper describes the laboratory validation of a method for determining the activity size distribution of radon decay products using the Dekati ELPI+ cascade impactor and the Graded Screen Array Diffusion Battery (GSA DB). Using nuclear track detectors placed on individual impaction plates of the cascade impactor, the equivalent equilibrium activity concentration of individual size classes can be determined in the range from 17 nm to 10 μm. A diffusion battery was used to detect smaller particles in the unattached fraction area. The presented method can further refine the knowledge of the activity size distribution of radon decay products in different types of workplace atmospheres. Workplaces with higher radon concentrations differ significantly in the size distribution of aerosol particles, radon activity concentration, and equilibrium equivalent activity concentration.

Engineering Budesonide Microparticles for Enhancing Pulmonary Targeting: Validation through In Vivo Investigations

AbstractThe study aimed to develop and evaluate budesonide inhalation micro‐suspension to target inflammation in the lower trachea and bronchi. Initially, the slurry phase is prepared by dispersing the drug (0.25 and 0.5 mg ml−1) in the Water for Injection with polysorbate 80. The slurry is mixed with the aqueous phase comprising other excipients. The mixture is further subjected to the treatment with homogenizer. The prepared formulations are subjected to various physio‐chemical analysis like description, density, pH, osmolality, viscosity, shelf life, impurities, assay, particle size, etc. Andersen cascade impactor is used to estimate the aerodynamic performance. In vivo analysis is initiated with the induction of Asthma in Sprague Dawley rats by ovalbumin challenge intranasally and the treatment is given with the aid of a nebulizer. Lastly, the biochemical estimations are carried out in blood and bronchoalveolar lavage fluid (BALF). The lungs are also subjected to morphological and histological evaluations. The physio‐chemical and analytical examination indicated a stable formulation that is compliant with the standard guidelines. The D90 value of the test formulation is ≤4.5 µm. Cascade impactor evaluation estimated almost, 2–10% higher amount of budesonide reaching the target region as compared to the marketed product. Test formulation attenuated the manifestation of ovalbumin‐induced asthma through suppression of inflammatory cell count in blood and BALF, and modulation of Lactate dehydrogenase and Alkaline Phosphatase levels which is further confirmed by histopathological analysis. The formulated budesonide micro‐suspension demonstrated stability, safety, and efficient delivery to the target site.

In Vitro Analysis of Aerodynamic Properties and Co-Deposition of a Fixed-Dose Combination of Fluticasone Furoate, Umeclidinium Bromide, and Vilanterol Trifenatate.

Effective airway delivery of a fixed-dose combination of triple-aerosolized inhaled corticosteroid (ICS)/long-acting beta agonist (LABA)/long-acting muscarinic antagonist (LAMA) is likely to positively affect therapeutic responses predicted in patients with asthma and chronic obstructive pulmonary disease. This study aimed to conduct in vitro fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide depositions in a Next Generation Impactor. The aerodynamic properties of these inhaled medications influence the spatial distribution and drug abundance, particularly in the smaller airways, to reverse or alleviate disease pathology. The Next Generation Impactor was used to demonstrate the aerodynamic particle size distributions of fluticasone furoate, vilanterol trifenatate, and umeclidinium bromide delivered from a dry powder inhaler at different flow rates across all stages of the impactors. This in vitro study analyzed the distribution pattern of individual drug components to simulate mono-component deposition and co-deposition in the official model in the United States Pharmacopeia. An Andersen cascade impactor together with scanning electron microscope-energy-dispersive X-ray was employed to observe the drug deposition on each stage of the impactor. We found that the distribution pattern of each component at the same cascade level was comparable, and the aerosol particles of the three drugs reached the in vitro representation of the lower airway compartment. The specified flow rates generated the desired fine particle fraction, fine particle dose, and mass median aerodynamic diameter. Our results also demonstrated visualized deposition patterns of the delivered drugs from different stages of the cascade impactor that may predict deposition as it occurs in vivo. Spatial distribution and abundance of ICS/LABA/LAMA in the same cascade levels were closely comparable, and the aerosol particles were able to reach the small aerosol-sized cascades at the lower levels to some extent.

Single-stage NBI sampler for PM1 mass and five-stage NBI-NMCI sampler for PM1 mass distribution measurements

In recent years, concerns about the health and environmental risks associated with PM1 particles have increased. However, existing PM1 sampling instruments remain to be improved mainly because their PM1 inlets have particle loading and bounce issues. To address these challenges, PM1 inlets based on the Non-Bouncing Impactor (NBI) technique were developed. These inlets employ vacuum oil-wetted glass fiber filter (GFF) substrates to eliminate particle bounce and incorporate a daily vacuum oil injection to prevent particle loading. The 16.7 L/min PM1 NBI, modified from the PM2.5 M-WINS design with a reduced diameter of the single nozzle, was designed to adapt readily with current standard sampling and monitoring systems. The cut-size (Dpa50) of 0.99 ± 0.02 μm was determined by considering the effects of Reynold number and the ratio of jet-to-plate distance and nozzle diameter. Field tests comparing the 16.7 L/min PM1 NBI sampler to the 9-stage NCTU Micro-orifice Cascade Impactor (NMCI9) revealed small sampling biases, with a mean difference of +0.26 ± 2.28 μg/m3 for PM1 measurements when silicone oil-coated aluminum foil (AF) and GFF-AF were used in the NMCI9. The NBI with the oil-wetted GFF substrate effectively removed particles larger than 1.0 μm, resulting in more accurate PM1 mass concentration measurements. Additionally, the development of a 5-stage NMCI with the 30 L/min PM1 NBI as the first stage enabled detailed measurement of PM1 mass distribution in two modes, which was challenging when measuring the entire mass distribution of ambient aerosols. The distribution of size-dependent water-soluble inorganic ions in PM1 showed dominance of SO42− and NH4+ in PM1 compared to PM2.5. In summary, the PM1 NBI enhances accuracy for long-term atmospheric sampling by addressing particle loading and bounce, making it a more reliable standard sampling instrument.

Self-nanoemulsifying drug delivery system for nebulization: fabrication and evaluation for systemic delivery of atorvastatin.

The study undertakes the development of an atorvastatin-loaded self-nanoemulsifying drug delivery system (SNEDDS) to improve its bioavailability. The SNEDDS were fabricated using oleic acid, Tween 80, and Span 80 by spontaneous emulsification. The SNEDDS were assessed for their particle size distribution, zeta potential, morphology, drug content, surface tension, viscosity, and drug release. The aerodynamic performance of the SNEDDS was evaluated using an Andersen cascade impactor, while the lipid-lowering potential of the SNEDDS was determined in Wistar rats using the analyzer "Microlab 300." The particle size of the SNEDDS ranged from 36 to 311nm, with a polydispersity index (PDI) of 0.25-0.40. The zeta potential of the SNEDDS fluctuated from - 29.22 to - 38.26mV, which declined to - 4.55mV in the case of F5. The chitosan-coated formulation (F5) exhibited a higher viscosity (22.12mPas) and lower surface tension (0.056 dyne/cm) than other formulations (F1-F4). The non-coated formulation exhibited a significantly higher burst drug release, followed by a sustained drug release pattern (p ≤ 0.05) as compared to the coated formulation (F5). The nebulized SNEDDS achieved a dispersed fraction of 87 to 97%, where notably higher aerosol dispersion from F4 was attributed to its smaller particle size and circularity. The inhaled fraction of nebulized SNEDDS was 74-87%. The size of the SNEDDS droplets was the primary determinant affecting the aerodynamic performance of the SNEDDS during nebulization. The chitosan-coated SNEDDS achieved a higher antihyperlipidemic effect than marketed tablets, which shows the suitability of F5 for effective systemic delivery of atorvastatin through the lung.

Biodeterioration Risk Assessment in Libraries by Airborne Fungal Spores.

Fungal growth on cellulose-based materials in libraries can have detrimental effects on books and documents. This biodeterioration affects their physical, chemical, and esthetical characteristics. Thus, this work aimed to assess fungal aerosols' concentrations and biodeterioration risk in two public libraries with artificial ventilation: the Banco de la República and CAJAMAG libraries. Air sampling was performed using a two-stage viable Andersen cascade impactor with Sabouraud dextrose agar at 4% on Petri dishes. Also, the temperature and relative humidity were measured with a digital thermo-hygrometer HOBO U12 Data Logger. The concentrations were low, with values of around 35 CFU/m3. Aspergillus, Cladosporium, and Penicillium were the predominant genera in the two libraries, with A. niger being the most abundant species. The thermo-hygrometric conditions inside the libraries were stable, with a mean temperature of 25.2 °C and a mean relative humidity of 52.1%. The calculated potential risk associated with fungal aerosols was seen to be medium in both libraries, where Aspergillus genera reported the highest cellulosic activity and hence had a higher risk of biodeterioration.

Aerodynamic Size-Dependent Collection and Inactivation of Virus-Laden Aerosol Particles in an Electrostatic Precipitator.

Electrostatic precipitators (ESPs) may enable high particle collection efficiency with minimal pressure drop in HVAC systems. However, studies of pathogen collection and inactivation in ESPs at medium to higher flow rates are limited. Here, a single-stage, wire-plate ESP operated at flow rates of 51 and 85 m3 h-1 was used to study the removal of virus-laden aerosol particles for three different airborne viruses: (1) bovine coronavirus (BCoV), (2) influenza A virus (IAV), and (3) porcine reproductive and respiratory virus (PRRSV). Size-resolved measurements of collection efficiency were obtained using Andersen cascade impactors (ACI) sampling upstream and downstream of the ESP. All measurements were analyzed based on three distinctive but complementary methods: (1) fluorimetry to assess physical collection, (2) RT-qPCR to assess viral RNA concentrations and (3) virus titration to assess virus viability. In general, log reductions by virus titration were highest followed by those from RT-qPCR, and last fluorimetry, suggesting that a portion of virus may be potentially inactivated in flight in the ESP. An effective migration (deposition) velocity ranging from 3.10 to 10.05 cm s-1 was also determined using the spatially resolved measurements of virus collection on the ESP plates.

Innovative surface acoustic wave devices: A solution for real time monitoring and self-cleaning cascade impactor

This paper presents a comparative study of three types of surface acoustic waves sensors used for particulate matter detection along with a theoretical study tackling the possibility to switch to innovative materials called Piezoelectric-on-Insulator. These sensors are placed in a cascade impactor as impaction plates. Monitoring their phase variation allows us to measure the quantity of fine particles present in the air with high accuracy. Until now, the sensors used in our prototype are built on quartz substrate and present a sufficient sensitivity to fine particles. One major concern in our application is the fouling of the sensor’s surface with particles upon long periods of exposure. This shaped our drive to develop a self-cleaning sensor relying on other substrates with stronger electromechanical coupling coefficient (k2) [1]. Hence, the aim of this study is to demonstrate the possibility of using strongly coupled modes on different piezoelectric substrates for an accurate PM detection. Among these, different POI substrates are considered to assess their physical and acoustic properties, especially in terms of k2 and thermal stability, for further optimization enabling their exploitation in the self-cleaning system that is being developed.

Evaluation of coating materials on the characterization of size and viability of virus-laden particles collected with an Andersen cascade impactor

Airborne pathogens are typically associated with particles, and the transport behavior of these particles is largely driven by their size. To better understand airborne transmission of viral diseases and develop effective control measures, proper size characterization of virus-laden particles is essential. The Andersen cascade impactor (ACI) is an 8-stage air sampler that separates aerosol particles into 9 aerodynamic size fractions. During sampling with an ACI under certain conditions, particles may bounce upon impact with the collection plates of the ACI, leading to eventual deposition on a stage further downstream than their target stage. Coating collection plates with adhesive materials may help decrease particle bounce; however, it may also affect the viability of collected pathogens. In this study, we evaluated different materials for their ability to minimize particle bounce while conserving virus viability during the collection of viral aerosol particles with an ACI. We evaluated nine materials - Tween® 80, silicone oil, Span® 85, Brij® 35, glycerol, mineral oil, gelatin, bovine serum albumin, and virus growth media - on their effect to inactivate H1N1 influenza virus and bovine coronavirus, a surrogate of SARS-CoV-2. Plates coated with gelatin, silicone oil, and mineral oil resulted in the least reduction of viability for both viruses. These materials were then used to sample viral aerosol particles in a wind tunnel. Results of physical particle collection, viral load and viral viability from the various ACI stages revealed no significant differences in aerodynamic size distribution between coated and uncoated plates, and the size distribution was similar to that reported by an optical particle sizer. Overall, our results did not support the need to coat ACI collection plates when characterizing viral aerosol particles under the conditions of this study. However, we did identify potential coating materials which could conserve virus viability maximally, if particle bounce is of concern.

Unveiling the invisible: first discovery of micro- and nanoplastic size segregation in indoor commercial markets using a cascade impactor

Unveiling the invisible: first discovery of micro- and nanoplastic size segregation in indoor commercial markets using a cascade impactor

Development of SIMPATEC-USP: An abbreviated impactor for rapid testing of inhalation devices

Cascade impactors like the Andersen Cascade Impactor (ACI) and Next Generation Impactor (NGI) are complex and costly due to multiple stages. This study introduces SIMPATEC-USP (Simplified Impactor Developed at the University of São Paulo), a low-cost, single-stage alternative meeting US Pharmacopeia standards for testing dry powder inhalers (DPIs). SIMPATEC-USP simplifies particle retention into a single Petri dish stage, eliminating multi-stage complexity. Its design includes a straightforward closure system for easy assembly/disassembly. A collection chamber holds a glass Petri dish with filter paper for final filtration, ensuring efficient aerosol product collection. SIMPATEC-USP also offers potential use with culture media for applications like antibacterial screening. Operating at 30 L/min, SIMPATEC-USP consists of three parts: a single-stage chamber, an L-shaped tube mimicking the trachea, and a vacuum pump. Aerosol particles are deposited onto the Petri dish via a nozzle, and the collected sample is weighed to determine drug concentration. Tested with inhalation-grade lactose, SIMPATEC-USP effectively collects and analyzes particles, allowing for rapid aerodynamic comparison of formulations, capsule retention assessment, and sample collection for drug release studies. The results demonstrate that it is possible to evaluate the performance of three inhalation devices regarding the mass migrating to the collection plate and that retained within the device itself. In conclusion, SIMPATEC-USP is highly suitable for exploratory studies and educational activities in pharmaceutical technology and pulmonary drug delivery systems.

Cocrystal formulation design of 4-Aminosalicylic acid and isoniazid via spray-drying based on a ternary phase diagram toward simultaneous pulmonary delivery

Cocrystal engineering is a potent strategy for enhancing drug properties, but its application in spray-drying has been limited. Furthermore, concurrently introducing two drugs and realizing simultaneous pharmacological effects at the target site is challenging. This is particularly evident for oral formulations designed for systemic use, but the local administration of drugs at the target site displays the potential to overcome this problem. Herein, we investigated the potential of cocrystallization principles for use in developing dry powder inhaler formulations of anti-tuberculosis drugs. We focused on the formation of cocrystals of 4-aminosalicylic acid (PAS) and isoniazid (INH), which are crucial components of tuberculosis treatment. Via spray-drying, we successfully produced spray-dried particles of PAS-INH that exhibited hydrogen bonding interactions between the molecules. Aerosolization performance evaluation with an Andersen Cascade Impactor (ACI) confirmed the concurrent deposition of both drugs, highlighting the potential of our particle design for use in the co-delivery of PAS-INH. Furthermore, simulated lung dissolution studies using the ACI and Transwell inserts revealed synchronized dissolution patterns, indicating promising prospects for use in effective drug delivery. This innovative approach to tuberculosis therapy has significant implications for improving treatment efficacy and enhancing patient adherence, potentially revolutionizing tuberculosis treatment.

Fungal aerosol and particulate matter in horse stables in Poland

Horses stay in different types of stables; especially during the cold season, they stay inside for most of the day. A stable is also a place where many people spend quite a lot of time either as employees who care for and train horses or as equine enthusiasts. Keeping horses in stables causes their constant exposure to high concentrations of particulate matter (PM) and molds in the air inside these facilities. The study was conducted in Udórz Stud Farm located in the southern region of Poland. It was carried out in two different types of stables: three runners and two box stables. The study continued for 2 years; samples were collected in each season of the year. The following devices were used: a six-stage Andersen-Graseby cascade impactor, the DustTrak™ II Aerosol Monitor 8530. The obtained results allowed for the conclusion that horses kept in box stables are exposed to lower concentrations of molds and yeasts than those kept in runners. Molds dominated in the stable air during humid periods—spring and autumn—while yeasts were more prominent during summer and winter. It was observed that cleaning stables reduces the morphotic elements of fungi in the air, even though it results in a higher level of particulate matter in the stable air. It should be noted that microclimate conditions were optimal for horses practically throughout the whole year.Key points• In stables, there is a high level of air intoxication, both by yeast and by mold fungi• The concentrations of fungi in the air depend on the season and the stable cleaning procedure• The PM concentrations depend on the type of stable

In Vitro Evaluation of Colistin Conjugated with Chitosan-Capped Gold Nanoparticles as a Possible Formulation Applied in a Metered-Dose Inhaler.

Inhaled colistin is used to treat pneumonia and respiratory infections through nebulization or dry powder inhalers. Nevertheless, the development of a metered-dose inhaler (MDI) for colistin, which could enhance patient convenience and treatment efficacy, has not yet been developed. Colistin is known for its ability to induce cellular toxicity. Gold nanoparticles (AuNPs) can potentially mitigate colistin toxicity. Therefore, this study aimed to evaluate the antimicrobial effectiveness of colistin conjugated with chitosan-capped gold nanoparticles (Col-CS-AuNPs) and their potential formulation for use with MDIs to deliver the aerosol directly to the deep lung. Fourier-transform infrared spectroscopy, nuclear magnetic resonance, and elemental analysis were used to characterize the synthesized Col-CS-AuNPs. Drug release profiles fitted with the most suitable release kinetic model were evaluated. An MDI formulation containing 100 µg of colistin per puff was prepared. The aerosol properties used to determine the MDI performance included the fine particle fraction, mass median aerodynamic diameter, and geometric standard deviation, which were evaluated using the Andersen Cascade Impactor. The delivered dose uniformity was also determined. The antimicrobial efficacy of the Col-CS-AuNP formulation in the MDI was assessed. The chitosan-capped gold nanoparticles (CS-AuNPs) and Col-CS-AuNPs had particle sizes of 44.34 ± 1.02 and 174.50 ± 4.46 nm, respectively. CS-AuNPs effectively entrapped 76.4% of colistin. Col-CS-AuNPs exhibited an initial burst release of up to 60% colistin within the first 6 h. The release mechanism was accurately described by the Korsmeyer-Peppas model, with an R2 > 0.95. The aerosol properties of the Col-CS-AuNP formulation in the MDI revealed a high fine particle fraction of 61.08%, mass median aerodynamic diameter of 2.34 µm, and geometric standard deviation of 0.21, with a delivered dose uniformity within 75-125% of the labeled claim. The Col-CS-AuNP MDI formulation completely killed Escherichia coli at 5× and 10× minimum inhibitory concentrations after 6 and 12 h of incubation, respectively. The toxicity of CS-AuNP and Col-CS-AuNP MDI formulations in upper and lower respiratory tract cell lines was lower than that of free colistin. The stability of the Col-CS-AuNP MDI formulation was maintained for at least 3 months. The Col-CS-AuNP MDI formulation effectively eradicated bacteria over a 12-h period, showing promise for advancing lung infection treatments.

Cryomilled electrospun nanofiber mats containing d-mannitol exhibit suitable for aerosol delivery of proteins

Dry powder inhalers (DPIs) are the first choice for inhalation drug development. However, some conventional DPI formulation processes require heating, which may damage high molecular weight drugs such as proteins and nucleic acids. In this study, we propose a novel DPI preparation process that avoids the use of heat. Dry powders were prepared by cryomilling nanofiber mats composed of polyvinyl alcohol, D(−)-mannitol (Man), and α-chymotrypsin (α-Chy) as the model drug using the electrospinning method. The addition of Man conferred high dispersibility and excellent in vitro aerosol performance to the nanofiber mat powder in a very short milling time (less than 0.5 min) as assessed using the Andersen cascade impactor. Powders were classified according to the degree of friability, and among these, nanofiber mats containing 15 % Man and milled for 0.25 min exhibited the highest aerosol performance. Nanofiber mats containing Man milled for less than 0.5 min also exhibited greater α-Chy enzymatic activity than a nebulized α-Chy solution. Furthermore, single inhalation induced no significant lung tissue damage as evidenced by lactate dehydrogenase activity assays of mouse bronchoalveolar lavage fluid. This novel DPI formulation process may facilitate the safe and efficient inhalational delivery of therapeutic proteins.

Diversity Analysis of Fungi Distributed in Inhalable and Respirable Size Fractions of Aerosols: A Report from Kuwait

Fungi are an important part of the atmospheric ecosystem yet an underexplored group. Airborne pathogenic fungi are the root cause of hypersensitive and allergenic states highly prevalent in Kuwait. Frequent dust storms in the region carry them further into the urban areas, posing an occupational health hazard. The fungal population associated with the respirable (more than 2.5 µm) and inhalable (2.5 µm and less) fractions of aerosols is negligibly explored and warrants comprehensive profiling to pinpoint tAhe health implications. For the present investigation, aerosol was collected using a high-volume air sampler coupled with a six-stage cascade impactor (Tisch Environmental, Inc) at a rate of 566 L min−1. The samples were lysed, DNA was extracted, and the internal transcribed regions were sequenced through targeted amplicon sequencing. Aspergillus, Penicillium, Alternaria, Cladosporium, Fusarium, Gleotinia and Cryptococcus were recorded in all the size fractions with mean relative abundances (RA%) of 17.5%, 12.9%, 12.9%, 4.85%, 4.08%, 2.77%, and 2.51%, respectively. A weak community structure was associated with each size fraction (ANOSIM r2 = 0.11; p > 0.05). The Shannon and Simpson indices also varied among the respirable and inhalable aerosols. About 24 genera were significantly differentially abundant, as described through the Wilcoxon rank sum test (p < 0.05). The fungal microbiome existed as a complex lattice of networks exhibiting both positive and negative correlations and were involved in 428 functions. All the predominant genera were pathogenic, hence, their presence in inhalable fractions raises concerns and poses an occupational exposure risk to both human and non-human biota. Moreover, long-range transport of these fungi to urban locations is undesirable yet plausible.

Influence of particle diameter on aerosolization performance and release of budesonide loaded mesoporous silica particles

The potential of micron-sized amorphous mesoporous silica particles as a novel controlled release drug delivery system for pulmonary administration has been investigated. Mesoporous silica formulations were demonstrated to provide a narrower particle size distribution and (spherical) shape uniformity compared to commercial micronized formulations, which is critical for repeatable and targeted aerosol delivery to the lungs. The release profiles of a well-known pulmonary drug loaded into mesoporous particles of different mean particle diameters (2.4, 3.9 and 6.3 µm) were analysed after aerosolization in a modified Andersen Cascade Impactor. Systematic control of the release rate of drug loaded into the particles was demonstrated in simulated lung fluid by variation of the mean particle diameter, as well as an enhanced release compared to a commercial micronized formulation. The mesoporous silica formulations all demonstrated an increased release rate of the loaded drug and moreover, under aerosolization from a commercial, low-cost dry powder inhaler (DPI) device, the formulations showed excellent performance, with low retainment and commercially viable fine particle fractions (FPFs). In addition, the measured median mass aerodynamic diameter (MMAD) of the different formulations (2.8, 4.1 and 6.2 µm) was shown to be tuneable with particle size, which can be helpful for targeting different regions in the lung. Together these results demonstrate that mesoporous silica formulations offer a promising novel alternative to current dry powder formulations for pulmonary drug delivery.

Technical note: Optimization of the preparation of cascade impactors collection substrates for airborne metallic ultrafine particle sampling

The characterization of workers’ exposure to airborne metallic ultrafine particles (UFP) has been an increasing issue because of their effects on health, and as many activities are potentially concerned such as welding, oxy-cutting or 3D printing. Determining the particle size distribution of such an aerosol provides a real contribution to the understanding of UFP exposures and associated health effects, as it is directly related to their penetration in the respiratory tract. In this context, it is proposed to optimize the preparation of collection substrates of cascade impactors of airborne metallic UFP. The experimental results confirm that the collection substrates have to be prepared beforehand by coating them with a high-vacuum-resistant silicone grease. The results highlight that this grease has to be preliminarily dissolved in a heptane-based solution with a mass ratio grease-solvent of 7.5%, and then deposited on the substrate with a target height of 9 μm. Applying this protocol ensures a reproducible and representative determination of the particle size distribution, allowing the phenomena of particle bouncing and reentrainment to be significantly reduced. It is also shown that coated collection substrates remain stable for several months in terms of mass, and that the samples collected remain stable during transport thanks to the improvement of particle cohesion on the coated membrane.