Aerosol Dispersion Research Articles

Reduction of aerosol and droplet dispersions using intraoral and extraoral vacuums for dental treatments with face-up, diagonal and upright positions

Reduction of aerosol and droplet dispersions using intraoral and extraoral vacuums for dental treatments with face-up, diagonal and upright positions

A Synthetic Oligosaccharide Resembling Francisella tularensis Strain 15 O‐Antigen Capsular Polysaccharide as a Lead for Tularemia Diagnostics and Therapeutics

AbstractFrancisella tularensis, a category A bioterrorism agent, causes tularemia in many animal species. F. tularensis subspecies tularensis (type A) and holarctica (type B) are mainly responsible for human tularemia. The high mortality rate of 30–60 % caused by F. tularensis subspecies tularensis if left untreated and the aerosol dispersal renders this pathogen a dangerous bioagent. While a live attenuated vaccine strain (LVS) of F. tularensis type B does not provide sufficient protection against all forms of tularemia infections, a significant level of protection against F. tularensis has been observed for both passive and active immunization of mice with isolated O‐antigen capsular polysaccharide. Well‐defined, synthetic oligosaccharides offer an alternative approach towards the development of glycoconjugate vaccines. To identify diagnostics and therapeutics leads against tularemia, a collection of F. tularensis strain 15 O‐antigen capsular polysaccharide epitopes were chemically synthesized. Glycan microarrays containing synthetic glycans were used to analyze the sera of tularemia‐infected and non‐infected animals and revealed the presence of IgG antibodies against the glycans. Two disaccharide (13 and 18), both bearing a unique formamido moiety, were identified as minimal glycan epitopes for antibody binding. These epitopes are the starting point for the development of diagnostics and therapeutics against tularemia.

Improvement of aerosol spray scavenging efficiency by pre-injecting electrically charged water mist

Efficient aerosol scavenging is crucial for gas purification to reduce environmental pollution in various chemical industries. In nuclear reactor decommissioning, especially for damaged reactors after severe accidents like Fukushima Daiichi, controlling radioactive aerosol generation and dispersion is essential. Radioactive aerosols sizing from 0.1 to 1 μm are expected during containment cleaning and fuel debris retrieval processes. To ensure safe decommissioning and mitigate environmental radioactivity, a containment water spray system is used for aerosol scavenging. However, conventional water spray has low efficiency for these submicron aerosols. Our recent experiments at UTARTS demonstrated that pre-injection of water mist enhances scavenging efficacy by increasing aerosol size and hydrophilicity through aerosol-mist agglomeration prior to spraying. On this basis, in this study, we introduced an innovative method using electrically charged water mist, which significantly facilitates aerosol-mist agglomeration through additional electrostatic coagulation, further improving scavenging efficacy (maximum 35 % in current configurations). The present experimental results attained under various mist conditions and charging configurations provided insights into optimizing the mist charging system. Our developed technology is expected to be useful in radioactive aerosol control during damaged reactor decommissioning and has potential applications in other environmental chemical engineering processes.

Interactive Simulation of Nonpharmaceutical Interventions of Airborne Disease Transmission in Office Settings

The COVID-19 pandemic has caused major disruptions to workplace safety and productivity. A browser-based interactive disease transmission simulation was developed to enable managers and individuals (agents) to optimize safe office work activities during pandemic conditions. The application provides a user interface to evaluate the impact of non-pharmaceutical interventions (NPIs) policies on airborne disease exposure based on agents’ meeting patterns and room properties. Exposure is empirically calibrated using CO2 as a proxy for viral aerosol dispersion. For the building studied, the major findings are that the cubicles during low occupancy produce unexpectedly high exposure, upgrading meetings to larger rooms reduces total average exposure by 44%, and when all meetings are conducted in large rooms, a 79% exposure reduction is realized.

A Synthetic Oligosaccharide Resembling Francisella tularensis Strain 15 O-Antigen Capsular Polysaccharide as a Lead for Tularemia Diagnostics and Therapeutics.

Francisella tularensis, a category A bioterrorism agent, causes tularemia in many animal species. F. tularensis subspecies tularensis (type A) and holarctica (type B) are mainly responsible for human tularemia. The high mortality rate of 30-60% caused by F. tularensis subspecies tularensis if left untreated and the aerosol dispersal renders this pathogen a dangerous bioagent. While a live attenuated vaccine strain (LVS) of F. tularensis type B does not provide sufficient protection against all forms of tularemia infections, a significant level of protection against F. tularensis has been observed for both passive and active immunization of mice with isolated O-antigen capsular polysaccharide. Well-defined, synthetic oligosaccharides offer an alternative approach towards the development of glycoconjugate vaccines. To identify diagnostics and therapeutics leads against tularemia, a collection of F. tularensis strain 15 O-antigen capsular polysaccharide epitopes were chemically synthesized. Glycan microarrays containing synthetic glycans were used to analyze the sera of tularemia-infected and non-infected animals and revealed the presence of IgG antibodies against the glycans. Two disaccharide (13 and 18), both bearing a unique formamido moiety, were identified as minimal glycan epitopes for antibody binding. These epitopes are the starting point for the development of diagnostics and therapeutics against tularemia.

Advanced Spray-Dried Inhalable Microparticles/Nanoparticles of an Innovative Mitophagy Activator for Targeted Lung Delivery: Design, Comprehensive Characterization, Human Lung Cell Culture, and In Vitro Aerosol Dispersion Performance.

Urolithin A (UA) has demonstrated the ability to stimulate mitophagy and enhance mitochondrial and cellular health in skeletal muscles in humans after oral administration. It is hypothesized that targeted delivery of UA as inhaled dry powders to the lungs will enhance mitochondrial health through mitochondrial biogenesis. This study aimed to engineer inhalable excipient-free powders of UA as dry powder inhalers (DPIs) for targeted pulmonary delivery. The particles were designed by particle engineering from dilute organic solutions of UA using the state-of-the-art spray drying technology in a closed mode. Comprehensive physicochemical characterization and advanced microscopy techniques were conducted to examine phase behavior, molecular properties, and particle properties, which are necessary for the rational design of advanced pulmonary inhalation aerosols. Molecular fingerprinting was conducted by using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy and Raman spectroscopy. Chemical imaging and mapping were conducted using confocal Raman microscopy (CRM) and IR microscopy. The advanced spray-dried (SD) excipient-free powders were successfully produced at different spraying pump feed rates and exhibited favorable molecular and particle properties. The excipient-free SD powders exhibited outstanding in vitro aerosol dispersion performance with an FDI-approved human DPI device (Neohaler) and correlated with the spray drying pump rate. In vitro, cell viability of various human pulmonary cells from different lung regions demonstrated biocompatibility and safety at different doses of UA. The transepithelial electrical resistance (TEER) assay shows that UA maintains cell membrane integrity and barrier tightness, indicating its potential for safe and effective localized drug delivery without long-term adverse effects. These results demonstrated that UA has favorable physicochemical and in vitro properties for inhalation and can be successfully engineered into excipient-free inhalable microparticles/nanoparticles as DPIs.

Inhalable Advanced Co-Spray Dried Microparticles/Nanoparticles of a Novel RhoA/Rho Kinase Inhibitor with Lung Surfactant Biomimetic Phospholipids for Targeted Lung Delivery.

Co-spray dried inhalable powder formulations of fasudil monohydrochloride salt (FMCS) and inhalable lung surfactant-based nanocarriers composed of synthetic phospholipids, zwitterionic DPPC (1,2-palmitoyl-sn-glycero-3-phosphocholine) and anionic DPPG (1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]) sodium salt, were designed and optimized using organic solution advanced spray drying. FMCS can potentially be used for the treatment of various complex pulmonary diseases with this current work focusing on pulmonary arterial hypertension. Comprehensive physicochemical characterization, electron and optical microscopy imaging, thermal analysis, molecular fingerprinting spectroscopy, in vitro aerosol dispersion performance with human dry powder inhaler (DPI) devices, in vitro membrane permeation and drug release, and in vitro human cellular studies were conducted. Well-defined, small, and smooth nanoparticles/microparticles in the solid state were engineered at different molar ratios of FMCS/DPPC/DPPG (25:75, 50:50, and 75:25) and successfully produced as inhalable powders having the properties necessary for targeted pulmonary delivery as dry powder inhalers. In vitro aerosol performance demonstrated excellent aerosol dispersion with different DPI devices. The phospholipid bilayer biophysical properties were confirmed and retained following cospray drying. Sustained release of fasudil drug and in vitro biocompatibility were demonstrated on human lung cells from different airway regions.

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.

Aerosol deposition on face masks in an open environment during inhalation

The aerodynamics of aerosols and their deposition on face masks play a critical role in determining the effectiveness of respiratory protection. While existing studies have focused on the risks associated with aerosol dispersion during exhalation, little attention has been paid to aerosol aerodynamics in an open environment, where aerosols can circumvent masks, during inhalation. This is because mask performance has primarily been evaluated by the particle filtration efficiency in closed pipe setups, which do not account for the aerodynamics of aerosols around the wearer's face. In this study, we conduct experiments in an open environment to investigate the aerosol flow around a face mask and the aerosol deposition under varying inhalation pressures. Our results indicate that an aerosol flow near a mask surface behaves like a viscous flow, stagnating within the range of human inhalation. Within this range, we find that the amount of aerosol deposited can be predicted by modifying existing aerodynamics theory. Using a theoretical model, a critical inhalation pressure is identified at which water aerosols begin to penetrate through a mask. Finally, we propose the aerosol circumvention efficiency as a new metric to assess mask performance in open environments by taking into account the effects of aerosol circumvention.

Structure, morphology and surface properties of α-lactose monohydrate in relation to its powder properties

The particulate properties of α-lactose monohydrate (αLMH), an excipient and carrier for pharmaceuticals, is important for the design, formulation and performance of a wide range of drug products. Here an integrated multi-scale workflow provides a detailed molecular and inter-molecular (synthonic) analysis of its crystal morphology, surface chemistry and surface energy. Predicted morphologies are validated in 3D through X-ray diffraction contrast tomography. Interestingly, from aqueous solution fastest growth is found to lie along the b-axis, i.e. the longest unit cell dimension of the αLMH crystal structure reflecting the greater opportunities for solvation on the prism compared to the capping faces leading to their slower relative growth rates. The tomahawk morphology reflects the presence of β-lactose which asymmetrically binds to the capping surfaces creating a polar morphology. The crystal lattice energy is dominated by van der Waals interactions (between lactose molecules) with electrostatic interactions contributing the remainder. Predicted total surface energies are in good agreement with those measured at high surface coverage by inverse gas chromatography, albeit their dispersive contributions are found to be higher than those measured. The calculated surface energies of crystal habit surfaces are not found to be significantly different between different crystal surfaces, consistent with αLMH's known homogeneous binding to drug molecules when formulated. Surface energies for different morphologies reveals crystals with the elongated crystal morphologies have lower surface energies compared to those with a triangular or tomahawk morphologies, correlating well with literature data that the surface energies of the lactose carriers are inversely proportional to their aerosol dispersion performance.

Effectiveness of Secondary Aerosol Shielding Devices in Aerosol Dispersal Containment: A Comparison

Effectiveness of Secondary Aerosol Shielding Devices in Aerosol Dispersal Containment: A Comparison

Influence of different cleaning methods on the concentration of airborne endotoxins and microbial aerosols in the oral clinical environment

AimThis study aims to evaluate the effectiveness of various cleaning methods in reducing airborne endotoxin and microbial aerosols during oral cleaning procedures.MethodForty patients undergoing oral cleaning procedures were randomly assigned to one of four groups (n = 10 per group). Group A received strong suction alone; Group B received strong suction combined with an air disinfection machine; Group C received strong suction combined with a dental electric suction machine; Group D received strong suction in conjunction with both an air disinfection machine and a dental electric suction machine. Airborne aerosol concentrations were assessed at four-time points: before treatment, 30 min into treatment, immediately after treatment, and 60 min after treatment ended. Samples were collected at distances of 20 cm, 60 cm, and 1 m from the patient’s oral cavity using the natural sedimentation method. T-test was used to evaluate the difference among tested groups.ResultsAirborne endotoxins and microbial aerosols levels increased significantly during treatment, with the highest levels observed at 20 cm from the patient’s mouth. During treatment, groups with additional cleaning methods (Groups B, C, and D) exhibited higher levels of airborne endotoxins and microbial aerosols compared to Group A (strong suction alone). However, post-treatment analysis revealed that Group D demonstrated the lowest level of airborne endotoxins and microbial aerosols, while Group A exhibited the highest.ConclusionsImplementing effective aerosol management strategies can significantly reduce aerosol dispersion in the oral clinical environment. Continuous monitoring aerosol concentrations and the application of appropriate control measures are essential for minimizing infection risks for both patients and healthcare providers during oral cleaning procedures.

Reducing aerosolization during bone drilling

The viscoelasticity of poly(ethylene oxide) allows for reduced aerosolization while maintaining coolant performance, reducing disease transmission via the dispersion of aerosols

An aerosol nanocomposite microparticle formulation using rifampicin-cyclodextrin inclusion complexes for the treatment of pulmonary diseases

Rifampicin (RIF) is commonly used in the treatment of tuberculosis (TB), a bacterium that currently infects one fourth of the world’s population. Despite the effectiveness of RIF in treating TB, current RIF treatment regimens require frequent and prolonged dosing, leading to decreased patient compliance and, ultimately, increased mortality rates. This project aims to provide an alternative to oral RIF by means of an inhalable spray-dried formulation. TB uses alveolar macrophages to hide and replicate until the cells rupture, further spreading the bacteria. Therefore, delivering RIF directly to the lungs can increase the drug concentration at the site of infection while reducing off-site side effects. Cyclodextrin (CD) was used to create a RIF-CD inclusion complex to increase RIF solubility and biodegradable RIF-loaded NP (RIF NP) were developed to provide sustained release of RIF. RIF NP and RIF-CD inclusion complex were spray dried to form a dry powder nanocomposite microparticles (nCmP) formulation (RIF-CD nCmP). RIF-CD nCmP displayed appropriate aerosol dispersion characteristics for effective deposition in the alveolar region of the lungs (4.0 µm) with a fine particle fraction of 89 %. The nCmP provided both a burst release of RIF due to the RIF-CD complex and pH-sensitive release of RIF due to the RIF NP incorporated into the formulation. RIF-CD nCmP did not adversely affect lung epithelial cell viability and RIF NP were able to effectively redisperse from the nCmP after spray drying. These results suggest that RIF-CD nCmP can successfully deliver RIF to the site of TB infection while providing both immediate and sustained release of RIF. Overall, the RIF-CD nCmP formulation has the potential to improve the efficacy for the treatment of TB.

Design and comprehensive characterization of dry powder inhalation aerosols of simvastatin DPPC/DPPG lung surfactant-mimic nanoparticles/microparticles for pulmonary nanomedicine.

The Rho Kinase (ROCK) pathway is recognized to be involved in changes that lead to remodeling in pulmonary hypertension (PH), particularly cellular processes including signaling, contraction, migration, proliferation, differentiation, and apoptosis. Simvastatin (Sim) has a potent anti-proliferative and pro-apoptotic effect on vasculature smooth muscle cells through the inhibition of the synthesis of isoprenoids intermediates which are essential for the post-translational isoprenylation of Rho, Rac, and Ras family GTPases. Sim targets the underlying mechanism in vascular remodeling. Using bionanomaterials and particle engineering design, this innovative study reports on the advanced inhalable dry powders composed of sim with synthetic phospholipid bionanomaterials, DPPC/DPPG, as a lung surfactant-mimic. These were successfully designed and produced as co-spray dried (Co-SD) nanoparticles and microparticles for nanomedicine delivery as dry powder inhalers (DPIs). Different techniques were used to comprehensively characterize the physicochemical properties of the resulting Co-SD particles. The Next Generation ImpactorTM (NGI™) was used with three different FDA-approved human DPI devices with varying shear stress which were the HandiHaler®, Neohaler®, Aerolizer® DPI devices for aerosol dispersion performance. The formulation-device interactions were examined and correlated. Using human lung cells from different lung regions, in vitro cell viability and transepithelial electrical resistance (TEER) at the air-liquid interface showed biocompatibility of the formulations as a function of dose.

Suppression of aerosol dispersion by highly viscoelastic poly(acrylic acid)- and poly(ethylene oxide)-based coolants during bone drilling

Bone drilling in neurosurgical, dental, and orthopedic procedures, combined with the use of coolants, generates a dispersion of bone particles, coolants, and blood aerosols in the air. This poses the threat of airborne transmission of infectious diseases between patients and medical practitioners. Highly viscoelastic polymeric poly(acrylic acid) (PAA) and poly(ethylene oxide) (PEO) solutions of various concentrations were used as coolants during bone drilling at different mass flow rates to suppress aerosol generation, thereby mitigating the threat of cross-infection. The results revealed that the PAA and PEO solutions provide less advection than water and a comparable cooling performance. However, excessive viscoelasticity of PEO causes the fluid to rise along the cutting burr (the Weissenberg effect), thereby reducing the cooling coverage area. In contrast, slightly lower viscoelasticity of PEO results in a high cooling coverage area. The cooling coverage area is smaller for the PAA at 20 ml/min because the corresponding PAA solution easily swirls or splashes away from the drilling location. However, at 80 ml/min, the supplied PAA solution sufficiently cools the drilling area, despite the loss through splashing. The numbers of atomized droplets of water and the PAA and PEO solutions were quantified and compared to investigate the degree of aerosol formation and dispersion. The solution with the strongest viscoelasticity most significantly suppressed aerosolization and produced the fewest dispersed aerosol droplets during bone drilling.

Effects of table based air curtains on respiratory aerosol exposure risk mitigation at face-to-face meeting setups

Face-to-face meetings on a conference table are a frequent form of communication. The short-range exposure risk of aerosol disease transmission is high in the scenario of susceptible facing the infectious person over the table. We propose a mitigation methodology using the air curtain to reduce direct exposure to virus-laden aerosols. A numerical model was validated with experimental data to simulate the dispersion of aerosols. A dynamic mesh was adopted to consider the head movement of a 3D thermal manikin model. Results show that nodding head increase the potential risk by 74 % compared to motionless. Subsequently, for a single air curtain, placing it in the middle of the table is more effective in preventing risks than on the sides. For double air curtains, increasing the distance between them has a greater risk reduction effect than a shorter distance. Increasing the air velocity or width is more effective than increasing the number of air curtains. A moderate velocity (1 m s−1) works well to reduce the risk of nasal breathing. A higher velocity (2 m s−1) is needed for the coughing scenario. For similar indoor environments, the air curtains on the table can offer active precautions without changing the current ventilation system.

Evaluation of airborne transmission of respiratory contaminants in a passenger car cabin with window opening

Exhaled aerosols can be suspended in the air for long periods, facilitating the transmission of highly infectious respiratory diseases. The risk of exposure to occupants varies due to different usage conditions and driving scenarios of moving vehicles. Therefore, the present study investigates the airborne transmission of contaminants generated by coughing in a moving vehicle and explores the relationship between aerosol dispersion and fluid exchange between the interior and exterior domains of the car under the influence of window opening configurations, seating layouts and driving speeds. The results show that the cross-opening configurations provide a superior contaminant removal efficiency. The effect of seating layout on removal efficiency is significant, although it has a slight effect on air change rate (ACH). The best removal efficiency can be obtained when the passenger sits in the front seat with the right front window opening. Furthermore, the in-cabin ACH is almost linearly correlated with the driving speed. Higher speeds reduce contaminant concentrations faster. However, the risk of driver exposure does not depend solely on ACH, the peak cumulative contaminant concentration and residence time also need to be considered. This study offers data for the prevention and control of respiratory infectious diseases.

Numerical study on bed-side curtains and ventilation arrangement for mitigating COVID-19 risks in a shipboard ward with heat sources

Ward-acquired infections (WAIs) has become a critical concern, particularly for ships with limited resources. An assessment approach combining validated computational fluid dynamics and the novel Wells-Riley assessment method is proposed to evaluate risks in a shipboard ward. Subsequently, the effects of ventilation, bed-side curtains, and non-adiabatic boundaries on substantial aerosol dispersion are analysed, including X/Y directional walkways (activity zones). Results show that patients with severe symptoms can be prioritized for the exhaust zone rather than the supply zone, and the maximum reduction in suspended particles can differ up to 3-folds. Bed-side curtains can decrease the average risk by −26 % and −48 %/−32 %, respectively, for X/Y directional walkways. Moreover, the average risk increases by approximately +21 % and +14 %/+11 % for X/Y directional walkways under a low air change rate (ACH) of 6 h−1. Considering the non-adiabatic boundary, the average risk reduction is approximately −6.2 % for winter and −7.0 % for summer. It supports that bed-side curtains and a recommended ACH of 12 h−1 are effective in reducing risk. The heat transfer through walls has a marginal effect on risks. Overall, this study provides a framework for predicting and analysing spatial-temporal exposure risks. Better strategies can be developed for protecting medical staff from WAIs.

Quantitative Risk Assessment of Wind-Supported Transmission of Highly Pathogenic Avian Influenza Virus to Dutch Poultry Farms via Fecal Particles from Infected Wild Birds in the Environment.

A quantitative microbial risk assessment model was developed to estimate the probability that the aerosolization of fecal droppings from wild birds in the vicinity of poultry farms would result in the infection of indoor-housed poultry with highly pathogenic avian influenza virus (HPAIv) in the Netherlands. Model input parameters were sourced from the scientific literature and experimental data. The availability of data was diverse across input parameters, and especially parameters on the aerosolization of fecal droppings, survival of HPAIv and dispersal of aerosols were uncertain. Model results indicated that the daily probability of infection of a single poultry farm is very low, with a median value of 7.5 × 10-9. Accounting for the total number of poultry farms and the length of the bird-flu season, the median overall probability of at least one HPAIv-infected poultry farm during the bird-flu season is 2.2 × 10-3 (approximately once every 455 years). This is an overall estimate, averaged over different farm types, virus strains and wild bird species, and results indicate that uncertainty is relatively high. Based on these model results, we conclude that it is unlikely that this introduction route plays an important role in the occurrence of HPAIv outbreaks in indoor-housed poultry.