Administration of airborne pathogens in non-human primates.

Purpose: Airborne pathogen scan penetrate in human respiratory tract and can cause illness. The use of animal models to predict aerosol deposition and study respiratory disease pathophysiology is therefore important for research and a prerequisite to test and study the mechanism of action of treatment. NHPs are relevant animal species for inhalation studies because of their similarities with humans in terms of anatomical structure, respiratory parameters and immune system.

Setup of Aerosol Delivery System to Prevent Measles Virus Infection in Nonhuman Primate Model.

Measles virus is one of the most contagious airborne human viruses which keeps causing outbreaks in numerous countries over the world despite the existence of an efficient vaccine. Fusion inhibitory lipopeptides were shown to inhibit viral entry into target cells, and their adequate administration into the respiratory tract may provide a novel preventive approach against airborne infections. Aerosol delivery presents the best administration route to deliver such preventive compounds to the upper and lower respiratory tract.

A large-volume low-pressure nasal irrigation delivers drug into the nasal cavity? An in vivo study.

The nasal administration route emerged as an interesting route in systemic and brain drug delivery, and different modalities of nasal delivery are available. The nasal irrigation is one of them, but there is a lack of studies investigating the distribution of a large-volume irrigation. The main aim of this study was to assess the deposition of radiolabeled saline in the nasal cavities and paranasal sinuses following nasal irrigation by imaging.

Influence of mesh nebulizer characteristics on aerosol delivery in non-human primates.

Non-Human Primates (NHPs) are particularly relevant for preclinical studies during the development of inhaled biologics. However, aerosol inhalation in NHPs is difficult to evaluate due to a low lung deposition fraction and high variability. The objective of this study was to evaluate the influence of mesh nebulizer parameters to improve lung deposition in macaques.

There Is a Risk of Spread During a Nebulization Session in a Patient with COVID-19.

A hypothetical risk of SARS-CoV-2 airborne transmission through nebulization was suggested based on a potential environmental contamination by the fugitive aerosol emitted in the environment during the procedure. The aim of this study was to verify this risk from the fugitive aerosol emitted by COVID-19 patients during one nebulization session. In this cohort study, COVID-19 patients treated with nebulization were recruited at their admission to the hospital.

Administration of Bacteriophages via Nebulization during Mechanical Ventilation: In Vitro Study and Lung Deposition in Macaques.

Bacteriophages have been identified as a potential treatment option to treat lung infection in the context of antibiotic resistance. We performed a preclinical study to predict the efficacy of delivery of bacteriophages against (PA) when administered via nebulization during mechanical ventilation (MV). We selected a mix of four anti-PA phages containing two and two with a coverage of 87.

Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection.

Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitor, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, blocks respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We use a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptide to the respiratory tract and demonstrate the absence of adverse effects and lung pathology in macaques.

Nebulized fusion inhibitory peptide protects cynomolgus macaques from measles virus infection.

Measles is the most contagious airborne viral infection and the leading cause of child death among vaccine-preventable diseases. We show here that aerosolized lipopeptide fusion inhibitors, derived from heptad-repeat regions of the measles virus (MeV) fusion protein, block respiratory MeV infection in a non-human primate model, the cynomolgus macaque. We used a custom-designed mesh nebulizer to ensure efficient aerosol delivery of peptides to the respiratory tract and demonstrated the absence of adverse effects and lung pathology in macaques.

Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol.

Introduction: Pre-emptive inhaled antibiotics may be effective to reduce the occurrence of ventilator-associated pneumonia among critically ill patients. Meta-analysis of small sample size trials showed a favourable signal. Inhaled antibiotics are associated with a reduced emergence of antibiotic resistant bacteria.

Inhaled bacteriophage therapy in a porcine model of pneumonia caused by Pseudomonas aeruginosa during mechanical ventilation.

Unlabelled: BACKGROUND AND PURPOSE 255: Pseudomonas aeruginosa is a main cause of ventilator-associated pneumonia (VAP) with drug-resistant bacteria. Bacteriophage therapy has experienced resurgence to compensate for the limited development of novel antibiotics. However, phage therapy is limited to a compassionate use so far, resulting from lack of adequate studies in relevant pharmacological models.

Pressurized Metered Dose Inhaler Aerosol Delivery Within Nasal High-Flow Circuits: A Bench Study.

Obstructive patients may benefit from nasal high-flow (NHF) therapy, but the use of pressurized metered-dose inhalers (pMDIs) has not been evaluated in this situation. Using an adult circuit and medium-sized cannula, we have tested different NHF rates, pMDI positions, breathing patterns, spacers, and spacer orientation. First, we evaluated albuterol delivery at the nasal cannula outlet.

[Good practice for aerosol therapy by nebulization in 2020].

Nebulization is a drug delivery mode whose prescription and application remain uncertain. A guide to good practice has been proposed by the work group on aerosol therapy of the French Society for Respiratory Diseases, so-called GAT. The previous recommendations date from 2007.

Humidified and Heated Cascade Impactor for Aerosol Sizing.

Aerosol sizing is generally measured at ambient air but human airways have different temperature (37°C) and relative humidity (100%) which can affect particle size in airways and consequently deposition prediction. This work aimed to develop and evaluate a new method using cascade impactor to measure particle size at human physiological temperature and humidity (HPTH) taking into account ambient air conditions. A heated and humidified trachea was built and a cascade impactor was heated to 37°C and humidified inside.

Controlled Heat and Humidity-Based Treatment for the Reuse of Personal Protective Equipment: A Pragmatic Proof-of-Concept to Address the Mass Shortage of Surgical Masks and N95/FFP2 Respirators and to Prevent the SARS-CoV2 Transmission.

The coronavirus infectious disease-2019 (COVID-19) pandemic has led to an unprecedented shortage of healthcare resources, primarily personal protective equipment like surgical masks, and N95/filtering face piece type 2 (FFP2) respirators. Reuse of surgical masks and N95/FFP2 respirators may circumvent the supply chain constraints and thus overcome mass shortage. Methods, design, setting, and measurement: Herein, we tested the effects of dry- and moist-air controlled heating treatment on structure and chemical integrity, decontamination yield, and filtration performance of surgical masks and FFP2 respirators.

Low-Frequency Intrapulmonary Percussive Ventilation Increases Aerosol Penetration in a 2-Compartment Physical Model of Fibrotic Lung Disease.

In patients with fibrotic pulmonary disease such as idiopathic pulmonary fibrosis (IPF), inhaled aerosols deposit mostly in the less affected region of the lungs, resulting in suboptimal pharmacokinetics of airway-delivered treatments. Refinement of aerosol delivery technique requires new models to simulate the major alterations of lung physiology associated with IPF, i.e.

In vitro - in vivo correlation of intranasal drug deposition.

In vitro - in vivo correlation (IVIVC) allows prediction of in vivo drug deposition from a nasally inhaled drug based on in vitro drug measurements. In vitro measurements include physical particle characterization and, more recently, deposition studies using anatomical models. Currently, there is a lack of IVIVC for deposition measurements in anatomical models, especially for deposition patterns in various nasal cavity regions.

Protein stability during nebulization: Mind the collection step!

Inhaled protein therapeutics meet a growing interest for the treatment of respiratory diseases. In liquid aerosols, proteins face stresses that may generate instabilities, such as physicochemical denaturations, aggregation and loss of activity. Monitoring protein stability is thus crucial but implies collection of aerosol droplets before analysis.

Innovative preclinical models for pulmonary drug delivery research.

: Pulmonary drug delivery is a complex field of research combining physics which drive aerosol transport and deposition and biology which underpins efficacy and toxicity of inhaled drugs. A myriad of preclinical methods, ranging from to and , can be implemented.: The present review covers mathematical and computational fluid dynamics modelization of aerosol deposition, cascade impactor technology to estimated drug delivery and deposition, advanced cell culture methods and associated aerosol exposure, lung-on-chip technology, modeling, inhaled drug delivery, lung imaging, and longitudinal pharmacokinetic analysis.

A consensus research agenda for optimising nasal drug delivery.

Nasal drug delivery has specific challenges which are distinct from oral inhalation, alongside which it is often considered. The next generation of nasal products will be required to deliver new classes of molecule, e.g.