Reuse of medical face masks in domestic and community settings without sacrificing safety: Ecological and economical lessons from the Covid-19 pandemic

The need for personal protective equipment increased exponentially in response to the Covid-19 pandemic. To cope with the mask shortage during springtime 2020, a French consortium was created to find ways to reuse medical and respiratory masks in healthcare departments. The consortium addressed the complex context of the balance between cleaning medical masks in a way that maintains their safety and functionality for reuse, with the environmental advantage to manage medical disposable waste despite the current mask designation as single-use by the regulatory frameworks. We report a Workflow that provides a quantitative basis to determine the safety and efficacy of a medical mask that is decontaminated for reuse. The type IIR polypropylene medical masks can be washed up to 10 times, washed 5 times and autoclaved 5 times, or washed then sterilized with radiations or ethylene oxide, without any degradation of their filtration or breathability properties. There is loss of the antiprojection properties. The Workflow rendered the medical masks to comply to the AFNOR S76-001 standard as “type 1 non-sanitory usage masks”. This qualification gives a legal status to the Workflow-treated masks and allows recommendation for the reuse of washed medical masks by the general population, with the significant public health advantage of providing better protection than cloth-tissue masks. Additionally, such a legal status provides a basis to perform a clinical trial to test the masks in real conditions, with full compliance with EN 14683 norm, for collective reuse. The rational reuse of medical mask and their end-of-life management is critical, particularly in pandemic periods when decisive turns can be taken. The reuse of masks in the general population, in industries, or in hospitals (but not for surgery) has significant advantages for the management of waste without degrading the safety of individuals wearing reused masks

Ex vivo preclinical model to study the treatment of respiratory disease with pulmonary delivery of aerosol

La délivrance pulmonaire semble être une voie d’administration préférentielle pour le traitement des pathologies respiratoires mais nécessite un ciblage des dépôts pour accroître leur efficacité et réduire le risque d’effets indésirables. Afin d’améliorer les dispositifs d’aérosolthérapie de futures recherches sont nécessaires. Les restrictions éthiques liées à l’expérimentation sur la personne humaine ne sont pas compatibles avec de tels besoins. Des modèles précliniques sont nécessaires mais manquent parfois de pertinence ou sont difficilement extrapolables. Ces travaux de thèse ont donc pour objectif de développer un panel de modèles précliniques respiratoires afin de systématiser les connaissances pour permettre un transfert clinique facilité des technologies d’aérosolthérapie. Pour chaque modèle ex vivo développé, le profil de dépôt des aérosols est étudié et comparé à des données in vivo humaines et animales, afin de s’assurer de l’extrapolabilité des résultats et du placement relatif du modèle par rapport aux modèles existants. Des applications ont été réalisées, telles que la recherche d’une position optimale pour le nébuliseur en ventilation mécanique invasive ou l’étude de la régionalisation des dépôts d’un dispositif de type cigarette électronique. Les différents modèles précliniques ex vivo développées ont montré des profils de dépôts d’aérosols similaires à ceux rencontrés chez des patients ainsi que leur utilité en tant que nouvel outil de recherche préclinique, complémentaires aux modèles précliniques existants dans le cadre d’une approche 3R de la recherche en aérosolthérapie.Pulmonary delivery seem to be a preferential choice for the treamt of respiratory diseases. However, optimal targeting should be reached to increase efficacy and decrase the risk of side effects. Thus, research is needed to improve aerosol delivery devices. However, ethical restrictions related to human experiment are not in agreement with the previous statement. Therefore, preclinical model are needed but could lack of relevance or generated date could be hard to extrpolate. The present work aimed to develop a panel of preclinical ex vivo respiratory models to systematise knowledge to facilitate the clinical transfer of aerosol technologies. For each developed ex vivo model, the aerosol deposition pattern was assessed and compared to human and/or animal data to ensure the extrapolability of the results and to position the model among the available preclinical models. Applications, such as the optimal position of a nebuliser during invasive mechanical ventilation or the deposition profile of electronic cigarette aerosol, were performed. The developed ex vivo models showed comparability with patients deposition profile of aersosol, as well as their utility as a new preclinical tool fitting 3R guidelines to complete exisiting preclinical models in aerosol therapy

Modèles précliniques ex vivo pour l'étude de la délivrance pulmonaire d'aérosols dans le traitement de pathologies pulmonaires

Pulmonary delivery seem to be a preferential choice for the treamt of respiratory diseases. However, optimal targeting should be reached to increase efficacy and decrase the risk of side effects. Thus, research is needed to improve aerosol delivery devices. However, ethical restrictions related to human experiment are not in agreement with the previous statement. Therefore, preclinical model are needed but could lack of relevance or generated date could be hard to extrpolate. The present work aimed to develop a panel of preclinical ex vivo respiratory models to systematise knowledge to facilitate the clinical transfer of aerosol technologies. For each developed ex vivo model, the aerosol deposition pattern was assessed and compared to human and/or animal data to ensure the extrapolability of the results and to position the model among the available preclinical models. Applications, such as the optimal position of a nebuliser during invasive mechanical ventilation or the deposition profile of electronic cigarette aerosol, were performed. The developed ex vivo models showed comparability with patients deposition profile of aersosol, as well as their utility as a new preclinical tool fitting 3R guidelines to complete exisiting preclinical models in aerosol therapy.La délivrance pulmonaire semble être une voie d’administration préférentielle pour le traitement des pathologies respiratoires mais nécessite un ciblage des dépôts pour accroître leur efficacité et réduire le risque d’effets indésirables. Afin d’améliorer les dispositifs d’aérosolthérapie de futures recherches sont nécessaires. Les restrictions éthiques liées à l’expérimentation sur la personne humaine ne sont pas compatibles avec de tels besoins. Des modèles précliniques sont nécessaires mais manquent parfois de pertinence ou sont difficilement extrapolables. Ces travaux de thèse ont donc pour objectif de développer un panel de modèles précliniques respiratoires afin de systématiser les connaissances pour permettre un transfert clinique facilité des technologies d’aérosolthérapie. Pour chaque modèle ex vivo développé, le profil de dépôt des aérosols est étudié et comparé à des données in vivo humaines et animales, afin de s’assurer de l’extrapolabilité des résultats et du placement relatif du modèle par rapport aux modèles existants. Des applications ont été réalisées, telles que la recherche d’une position optimale pour le nébuliseur en ventilation mécanique invasive ou l’étude de la régionalisation des dépôts d’un dispositif de type cigarette électronique. Les différents modèles précliniques ex vivo développées ont montré des profils de dépôts d’aérosols similaires à ceux rencontrés chez des patients ainsi que leur utilité en tant que nouvel outil de recherche préclinique, complémentaires aux modèles précliniques existants dans le cadre d’une approche 3R de la recherche en aérosolthérapie

Late Breaking Abstract - Development of an ex vivo pediatric preclinical model of bronchopulmonary dysplasia for aerosol regional deposition studies

28th International Congress of the European-Respiratory-Society (ERS), Paris, FRANCE, SEP 15-19, 201

Optimized acriflavine-loaded lipid nanocapsules as a safe and effective delivery system to treat breast cancer.

Acriflavine (ACF) hydrochloride is currently repurposed as multimodal drug, inhibiting hypoxia-inducible factors (HIF) pathways and exerting cytotoxic properties. The aim of this study was to encapsulate ACF in reverse micelles and to incorporate this suspension in lipid nanocapsules (LNC). Designs of experiments were used to work under quality by design conditions. LNC were formulated using a phase-inversion temperature method, leading to an encapsulation efficiency around 80%. In vitro, the encapsulated drug presented similar cytotoxic activity and decrease in HIF activity in 4T1 cells compared to the free drug. In vivo, ACF-loaded nanoparticles (ACF dose of 5 mg/kg) demonstrated a higher antitumor efficacy compared to free ACF on an orthotopic model of murine breast cancer (4T1 cells). Moreover, the use of LNC allowed to drastically decrease the number of administrations compared to the free drug (2 versus 12 injections), suppressing the ACF-induced toxicity

Impact of gas humidification and nebulizer position under invasive ventilation: preclinical comparative study of regional aerosol deposition

Abstract Successful aerosol therapy in mechanically ventilated patients depends on multiple factors. Among these, position of nebulizer in ventilator circuit and humidification of inhaled gases can strongly influence the amount of drug deposited in airways. Indeed, the main objective was to preclinically evaluate impact of gas humidification and nebulizer position during invasive mechanical ventilation on whole lung and regional aerosol deposition and losses. Ex vivo porcine respiratory tracts were ventilated in controlled volumetric mode. Two conditions of relative humidity and temperature of inhaled gases were investigated. For each condition, four different positions of vibrating mesh nebulizer were studied: (i) next to the ventilator, (ii) right before humidifier, (iii) 15 cm to the Y-piece adapter and (iv) right after the Y-piece. Aerosol size distribution were calculated using cascade impactor. Nebulized dose, lung regional deposition and losses were assessed by scintigraphy using 99mtechnetium-labeled diethylene-triamine-penta-acetic acid. Mean nebulized dose was 95% ± 6%. For dry conditions, the mean respiratory tract deposited fractions reached 18% (± 4%) next to ventilator and 53% (± 4%) for proximal position. For humidified conditions, it reached 25% (± 3%) prior humidifier, 57% (± 8%) before Y-piece and 43% (± 11%) after this latter. Optimal nebulizer position is proximal before the Y-piece adapter showing a more than two-fold higher lung dose than positions next to the ventilator. Dry conditions are more likely to cause peripheral deposition of aerosols in the lungs. But gas humidification appears hard to interrupt efficiently and safely in clinical use. Considering the impact of optimized positioning, this study argues to maintain humidification

Development of an ex vivo respiratory pediatric model of bronchopulmonary dysplasia for aerosol deposition studies

Abstract Ethical restrictions are limitations of in vivo inhalation studies, on humans and animal models. Thus, in vitro or ex vivo anatomical models offer an interesting alternative if limitations are clearly identified and if extrapolation to human is made with caution. This work aimed to develop an ex vivo infant-like respiratory model of bronchopulmonary dysplasia easy to use, reliable and relevant compared to in vivo infant data. This model is composed of a 3D-printed head connected to a sealed enclosure containing a leporine thorax. Physiological data and pleural-mimicking depressions were measured for chosen respiratory rates. Homogeneity of ventilation was assessed by 81mkrypton scintigraphies. Regional radioaerosol deposition was quantified with 99mtechnetium-diethylene triamine pentaacetic acid after jet nebulization. Tidal volumes values are ranged from 33.16 ± 7.37 to 37.44 ± 7.43 mL and compliance values from 1.78 ± 0.65 to 1.85 ± 0.99 mL/cmH2O. Ventilation scintigraphies showed a homogenous ventilation with asymmetric repartition: 56.94% ± 9.4% in right lung and 42.83% ± 9.36 in left lung. Regional aerosol deposition in lungs exerted 2.60% ± 2.24% of initial load of radioactivity. To conclude the anatomical model satisfactorily mimic a 3-months old BPD-suffering bronchopulmonary dysplasia and can be an interesting tool for aerosol regional deposition studies

Development of an ex vivo preclinical respiratory model of idiopathic pulmonary fibrosis for aerosol regional studies

International audienceIdiopathic pulmonary fibrosis is a progressive disease with unsatisfactory systemic treatments. Aerosol drug delivery to the lungs is expected to be an interesting route of administration. However, due to the alterations of lung compliance caused by fibrosis, local delivery remains challenging. This work aimed to develop a practical, relevant and ethically less restricted ex vivo respiratory model of fibrotic lung for regional aerosol deposition studies. This model is composed of an Ear-Nose-Throat replica connected to a sealed enclosure containing an ex vivo porcine respiratory tract, which was modified to mimic the mechanical properties of fibrotic lung parenchyma-i.e. reduced compliance. Passive respiratory mechanics were measured. 81m Kr scintigraphies were used to assess the homogeneity of gas-ventilation, while regional aerosol deposition was assessed with 99m Tc-DTPA scintigraphies. We validated the procedure to induce modifications of lung parenchyma to obtain aimed variation of compliance. Compared to the healthy model, lung respiratory mechanics were modified to the same extent as IPF-suffering patients. 81m Kr gas-ventilation and 99m tc-DtpA regional aerosol deposition showed results comparable to clinical studies, qualitatively. This ex vivo respiratory model could simulate lung fibrosis for aerosol regional deposition studies giving an interesting alternative to animal experiments, accelerating and facilitating preclinical studies before clinical trials. Idiopathic pulmonary fibrosis (IPF), a progressive fibrotic disease of the lungs without identified etiology, is the most common form of idiopathic interstitial pneumonia 1,2. Estimated incidence is around 2.8/100000 in North America and Europe, while lower incidences are observed in Asia and South America 3. The spontaneous 3-5 years survival is around 50% 4-6. IPF is characterized by progressive fibrotic lesions extending into the lungs from subpleural regions with a heterogeneous distribution throughout the lung. This leads to impairments of lung mechanics with a prominent reduction of lung compliance 7-12-i.e decreased ability of the lung to stretch and expand during the breathing cycle. IPF symptoms include cough, exertional dyspnea 1,7,13-18 , alterations in pulmonary gas exchange 8,17 , physiology of airways 19 and pulmonary hemodynamics 14-16,20,21. Currently, IPF is treated with systemic antifibrotic drugs, such as pirfenidone and nintedatinib, which have been shown to delay the progressive decrease of lung function and to reduce mortality 3,22-24. However, neither pirfenidone nor nintedatinib stops disease progression, while lung transplantation is associated with significant morbidity and mortality 25-28. Thus, new treatments for IPF are strongly needed. Pulmonary delivery of drugs is expected to be an interesting route of administration as an alternative to systemic therapies in IPF. Indeed, work is ongoing to develop inhaled IPF therapies using either repurposed drugs such as interferon gamma 29 or new chemical entities, such as the α v β 6 integrin inhibitor GSK3008348 30. Nevertheless, optimization of nebulization technologies appears necessary to reach this aim. Indeed, due to the alterations of lung compliance in IPF, aerosolized delivery of treatments remains challenging. Heterogeneous reduction of lung compliance is associated with impaired deposition of aerosol in affected pulmonary regions 31

Comparison of bacterial filtration efficiency vs. particle filtration efficiency to assess the performance of non-medical face masks

International audienceAbstract As a result of the current COVID-19 pandemic, the use of facemasks has become commonplace. The performance of medical facemasks is assessed using Bacterial Filtration Efficiency (BFE) tests. However, as BFE tests, require specific expertise and equipment and are time-consuming, the performance of non-medical facemasks is assessed with non-biological Particle Filtration Efficiency (PFE) tests which are comparatively easier to implement. It is necessary to better understand the possible correlations between BFE and PFE to be able to compare the performances of the different types of masks (medical vs. non-medical). In this study BFE results obtained in accordance with the standard EN 14683 are compared to the results of PFE from a reference test protocol defined by AFNOR SPEC S76-001 with the aim to determine if BFE could be predicted from PFE. Our results showed a correlation between PFE and BFE. It was also observed that PFE values were higher than BFE and this was attributed to the difference in particle size distribution considered for efficiency calculation. In order to properly compare these test protocols for a better deduction, it would be interesting to compare the filtration efficiency for a similar granulometric range