In contemporary times, there has been a rise in the utilization of dry powder inhalers (DPIs) in the management of pulmonary and systemic diseases. These devices underwent a swift advancement in terms of both the equipment utilized and the formulation process. In this review, the carrier physicochemical characteristics that influence DPI performance are discussed, focusing its shape, morphology, size distribution, texture, aerodynamic diameter, density, moisture, adhesive and detachment forces between particles, fine carrier particles, and dry powder aerosolization. To promote the deposition of the active principal ingredient deep within the pulmonary system, advancements have been made in enhancing these factors and surface properties through the application of novel technologies that encompass particle engineering. So far, the most used carrier is lactose showing some advantages and disadvantages, but other substances and systems are being studied with the intention of replacing it. The final objective of this review is to analyze the physicochemical and mechanical characteristics of the different carriers or new delivery systems used in DPI formulations, whether already on the market or still under investigation. [Figure: see text].

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.

In recent years, the use of probiotics and their metabolites, known as postbiotics as natural preservatives has received increasing attention in the food industry. This study aimed to prepare and characterize postbiotics of Lactiplantibacillus sakei and to investigate its application as an anti-Listeria solution on beef fillets using an aerosolization technique. The functional groups, including organic acids, polysaccharides and other minor metabolites, were identified by Fourier transform infrared (FTIR) in the postbiotics. The 2, 2\'-diphenyl-1-picrylhydrazyl radical scavenging activity of the postbiotics was reported as 0.82 mg mL-1. The antimicrobial test using the agar well diffusion method revealed a zone of inhibition of 27.00 ± 1.20 mm. Application of an aerosolized postbiotics solution resulted in a significant reduction in Listeria monocytogenes counts on beef fillets, reaching 3.30 log10 CFU g-1 over a 15-day storage period at 4.00 ± 1.00 ˚C. The results of this study revealed that the postbiotics of L. sakei was an effective antimicrobial additive for controlling foodborne pathogens in beef fillets and aerosolization is a promising method for developing an antimicrobial coating on meat to enhance meat safety.

Secretory IgA (SIgA) presents a promising avenue for mucosal immunotherapy yet faces challenges in expression, purification, and stability. IgA exists in two primary isotypes, IgA1 and IgA2, with IgA2 further subdivided into two common allotypes: IgA2m(1) and IgA2m(2). The major differences between IgA1 and IgA2 are located in the hinge region, with IgA1 featuring a 13-amino acid elongation that includes up to six O-glycosylation sites. Furthermore, the IgA2m(1) allotype lacks a covalent disulfide bond between heavy and light chains, which is present in IgA1 and IgA2m(2). While IgA1 demonstrates superior epitope binding and pathogen neutralization, IgA2 exhibits enhanced effector functions and stability against mucosal bacterial degradation. However, the noncovalent linkage in the IgA2m(1) allotype raises production and stability challenges. The introduction of distinct single mutations aims to facilitate an alternate disulfide bond formation to mitigate these challenges. We compare four different IgA2 versions with IgA1 to further develop secretory IgA antibodies against SARS-CoV-2 for topical delivery to mucosal surfaces. Our results indicate significantly improved expression levels and assembly efficacy of SIgA2 (P221R) in Nicotiana benthamiana. Moreover, engineered SIgA2 displays heightened thermal stability under physiological as well as acidic conditions and can be aerosolized using a mesh nebulizer. In summary, our study elucidates the benefits of stability-enhancing mutations in overcoming hurdles associated with SIgA expression and stability.

This study investigated the antimicrobial effects of lactic acid (LA) (3%) and peracetic acid (PA) (300 ppm) on tilapia fillets (Oreochromis niloticus) by fogging (15 min) or by immersion (2 s) in a pool of Escherichia coli (NEWP 0022, ATCC 25922, and a field-isolated strain), Staphylococcus aureus (ATCC 25923 and a field-isolated strain), and Salmonella Typhimurium (ATCC 13311 and ATCC 14028), as well as the effects on the physicochemical characteristics of the fillets. Fogging was effective and the best application method to control S. Typhimurium regardless of the acid used, promoting reductions of 1.66 and 1.23 log CFU/g with PA and LA, respectively. Regarding E. coli, there were significant reductions higher than 1 log CFU/g, regardless of the treatment or acid used. For S. aureus, only immersion in PA showed no significant difference (p < 0.05). For other treatments, significant reductions of 0.98, 1.51, and 1.17 log CFU/g were observed for nebulized PA, immersion, and LA fogging, respectively. Concerning the pH of the samples, neither of the acids used differed from the control. However, treatments with LA, and fogging with PA, reduced the pH compared to immersion in PA. As for color parameters, L* and a* values showed changes regardless of the acid or method used, resulting in an improved perception of fillet quality. These results indicate that fogging and immersion are alternatives for reducing S. Typhimurium, E. coli, and S. aureus in tilapia fillets.

For disease of the lung, the physical key to effective inhalation-based therapy is size; too large (10\'s of μm) and the particles or droplets do not remain suspended in air to reach deep within the lungs, too small (subμm) and they are simply exhaled without deposition. μBots within this ideal low-μm size range however are challenging to fabricate and would lead to devices that lack the speed and power necessary for performing work throughout the pulmonary network. To uncouple size from structure and function, here we demonstrate an approach where individual building blocks are aerosolized and subsequently assembled in situ into μbots capable of translation, drug delivery, and mechanical work deep within lung mimics. With this strategy, a variety of pulmonary diseases previously difficult to treat may now be receptive to μbot-based therapies.

Human norovirus is transmitted mainly via the faecal-oral route, but norovirus disease outbreaks have been reported in which airborne transmission has been suggested as the only explanation. We used murine norovirus (MNV) as a surrogate for human norovirus to determine the aerosolization of infectious norovirus in an experimental setup. A 3-l air chamber system was used for aerosolization of MNV. Virus in solution (6 log10 TCID50/ml) was introduced into the nebulizer for generating aerosols and a RAW 264.7 cell dish without a lid was placed in the air chamber. Cell culture medium samples were taken from the dishes after the aerosol exposure time of 30 or 90 min, and the dishes were placed in a 37 °C, 5% CO2 incubator and inspected with a light microscope for viral cytopathic effects (CPEs). We determined both the infectious MNV TCID50 titre and used an RT-qPCR assay. During the experiments, virus infectivity remained stable for 30 and 90 min in the MNV solution in the nebulizer. Infectious MNV TCID50 values/ml of 2.89 ± 0.29 and 3.20 ± 0.49 log10 were measured in the chamber in RAW 264.7 cell dish media after the 30-min and 90-min exposure, respectively. The MNV RNA loads were 6.20 ± 0.24 and 6.93 ± 1.02 log10 genome copies/ml, respectively. Later, a typical MNV CPE appeared in the aerosol-exposed RAW cell dishes. We demonstrated that MNV was aerosolized and that it remained infectious in the experimental setup used. Further studies required for understanding the behaviour of MNV in aerosols can thus be performed.

This section aims to provide a concise and contemporary technical perspective and reference resource covering dry powder inhaler (DPI) formulations. While DPI products are currently the leading inhaled products in terms of sales value, a number of confounding perspectives are presented to illustrate why they are considered surprisingly, and often frustratingly, poorly understood on a fundamental scientific level, and most challenging to design from first principles. At the core of this issue is the immense complexity of fine cohesive powder systems. This review emphasizes that the difficulty of successful DPI product development should not be underestimated and is best achieved with a well-coordinated team who respect the challenges and who work in parallel on device and formulation and with an appreciation of the handling environment faced by the patient. The general different DPI formulation types, which have evolved to address the challenges of aerosolizing fine cohesive drug-containing particles to create consistent and effective DPI products, are described. This section reviews the range of particle engineering processes that may produce micron-sized drug-containing particles and their subsequent assembly as either carrier-based or carrier-free compositions. The creation of such formulations is then discussed in the context of the material, bulk, interfacial and ultimately drug-delivery properties that are considered to affect formulation performance. A brief conclusion then considers the future DPI product choices, notably the issue of technology versus affordability in the evolving inhaler market.

Pulmonary delivery of protein therapeutics poses significant challenges that have not been well addressed in the research literature or practice. In fact, there is currently only one commercial protein therapeutic that is delivered through aerosolization and inhalation. In this study, we propose a drug delivery strategy that enables a high-concentration dosage for the pulmonary delivery of antibodies as an aerosolizable solid powder with desired stability. We utilized zwitterionic polymers for their promising properties as drug delivery vehicles and synthesized swellable, biodegradable poly(sulfo-betaine) (pSB) microparticles. The microparticles were loaded with Immunoglobulin G (IgG) as a model antibody. We quantified the microparticle size and morphology, and the particles were found to have an average diameter of 1.6 μm, falling within the optimal range (~1-5 μm) for pulmonary drug delivery. In addition, we quantified the impact of the crosslinker to monomer ratio on particle morphology and drug loading capacity. The results showed that there is a trade-off between desired morphology and drug loading capacity as the crosslinker density increases. In addition, the particles were aerosolized, and our data indicated that the particles remained intact and retained their initial morphology and size after aerosolization. The combination of morphology, particle size, antibody loading capacity, low cytotoxicity, and ease of aerosolization support the potential use of these particles for pulmonary delivery of protein therapeutics.

BACKGROUND: In recent years, hand drying has been highlighted as a key step in appropriate hand hygiene, as moisture on hands can increase the transfer of micro-organisms from hands to surfaces and vice versa.
OBJECTIVE: To understand bacterial and viral aerosolization following hand drying, and study the transfer of micro-organisms from hands to surfaces after drying using different methods.
METHODS: Groups of five volunteers had their hands pre-washed with soap, rinsed and dried, then inoculated with a concentrated mixture of Pseudomonas fluorescens and MS2 bacteriophage. Volunteers entered an empty washroom, one at a time, and rinsed their hands with water or washed their hands with soap prior to drying with a jet dryer or paper towels. Each volunteer applied one hand successively to various surfaces, while their other hand was sampled using the glove juice method. Both residual bacteria and viruses were quantified from the washroom air, surface swabs and hand samples.
RESULTS: P. fluorescens and MS2 bacteriophages were rarely aerosolized while drying hands for any of the drying methods studied. Results also showed limited, and similar, transfer of both micro-organisms studied on to surfaces for all drying methods.
CONCLUSIONS: The use of jet dryers or paper towels produces low levels of aerosolization when drying hands in a washroom. Similarly, all drying methods result in low transfer to surfaces. While the coronavirus disease 2019 pandemic raised concerns regarding public washrooms, this study shows that all methods tested are hygienic solutions for dry washed hands.