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Expozice nanočásticím v pracovním prostředí / Exposure to Nanoparticles in Work EnvironmentKöbölová, Klaudia January 2020 (has links)
Outside to the wide range of potential benefits, the use of nanomaterials can endanger human health and the environment. This diploma thesis presents the results of pilot measurements, where the exposure of nanoparticles was monitored. Based on a literature research a suitable method for measurement was the three-stage OECD model. Based on this model, measurements were performed in three welding workplaces, where nanoparticles are produced incidentally. The measurement consisted of collecting information and measuring the concentration of nanoparticles in the workplace, where data collection was focused only on inhalation exposure. During welding, 0.3 m size particles are produced and their concentration is strongly influenced by the welding material, type of welding and suction. The particles are amorphous in terms of morphology and contain manganese, iron and silicon, which can cause neurodegenerative diseases. Furthermore, the results indicate the importance of monitoring oral exposure.
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When Should a Provider Consider Insulin Human Inhalation Powder?Mospan, Cortney M., Leonard, Chelsea, Alley, Kelli 01 May 2016 (has links)
Insulin human inhalation powder, a rapid-acting inhaled insulin, was approved by the FDA in June 2014 for patients with type 1 or type 2 diabetes. For patients reluctant to start insulin therapy because of fear of injections, insulin human inhalation powder may be an alternative. This article discusses appropriate dosing, use, and monitoring.
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A Passive Constant Flow Regulator for Drug Delivery to the Human Lung in Portable Inhaler Systems / En passiv konstant flödesregulator för läkemedelsleverans till mänsklig lunga i bärbara inhalatorsystemPereverzina, Maria January 2020 (has links)
Respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are pathological conditions affecting the airways of the respiratory system. Currently more than 90 million people are suffering from respiratory diseases, and COPD is predicted to become the third leading cause of death in the world by 2030. Inhalation devices are commonly used in the treatment of respiratory diseases, where an aerosolised medication is delivered to the lungs of the patient via inhalation. The inspiratory flow rate is one of the main factors affecting the drug deposition in the lung, but is currently not controlled in most inhalation systems. The purpose of this master thesis is to design, manufacture and characterize a passive flow regulator device for portable inhalation systems. The designed prototype utilises the principle of a Venturi nozzle and membrane deflection to create a variable flow constriction, which acts as a negative feedback loop for the flow rate regulation. The flow regulator is based on a previously working device used for controlling exhalation flow rate in the range of 3 L/min. Experimental results are evaluated and compared to an analytical solution of the classical Venturi design. Additionally, membrane deflection is measured to analyse the physical behaviour of the membrane within the device. The flow regulating device is scaled up for inhalation flow rate ranges (>30 L/min) and a flow rate sensor is constructed for the measurements. The passive control of flow rates using a deflecting membrane is deemed promising. However, further improvements of the scaled up model used for inhalation are necessary.
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Caractérisation et modélisation de la toxicocinétique du trichloroéthylène chez la souris CD-1 mâleNadeau, Véronique January 2002 (has links)
Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.
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Improving Thermal Stability and Intratracheal Delivery of Viral-Vectored Dry Powder VaccinesManser, Myla January 2022 (has links)
This work focuses on the development of a spray dried adenoviral vector for its application as a thermally stable and inhalable vaccine against tuberculosis. / As the global public health community continues to strive for more equitable vaccine access, thermal instability of liquid vaccines continues to be a significant challenge due to strict cold-chain temperature requirements. Dry powder vaccines offer a favourable alternative, with the ability to retain vaccine efficacy at ambient temperature conditions. In the form of dry powder, vaccines against respiratory diseases can also be administered via inhalation for targeted delivery to the lung tissue. A processing technique known as spray drying is particularly promising for the development of thermally stable and inhalable dry powder vaccines, offering a method of continuous and scalable production. Spray drying is widely used in the pharmaceutical industry and can effectively encapsulate and immobilize labile biologics, like adenoviral vectors, within a glassy carbohydrate matrix to help retain biologic function. However, pulmonary delivery of a thermally stable, viral vectored dry powder vaccine has yet to be demonstrated.
This thesis focuses on improving the formulation of a carbohydrate excipient blend of mannitol and dextran encapsulating a human serotype 5 adenovirus (AdHu5), with the goal of producing an inhalable vaccine with sufficient viral potency for in vivo murine testing. First, the impact of cryoprotective agents used for frozen storage of the stock adenovirus was investigated with respect to viral activity retention, thermal stability and inhalation properties of the dry powder after spray drying. Trehalose was considered a preferred cryoprotective agent, compared to glycerol traditionally used for adenoviral cryo-storage, allowing for the preparation of a high potency viral dry powder with 1.5 log loss of viral titre after processing and thermal aging. Further investigation of the dextran mass ratio and dextran molecular weight used within the excipient blend revealed that incorporating mannitol in a 1:3 ratio with 500 kDa dextran can further improve viral activity to achieve 0.8 log loss of viral titre after aging. Through controlled drying dynamics, this formulation led to improved activity retention and thermal stability, in addition to desirable aerosolization properties for pulmonary delivery. Using this optimized formulation, custom-made intratracheal dosator devices were evaluated for pulmonary powder delivery in mice. The method of powder loading in the device was found to be a significant factor of device performance in vivo when determining if the critical powder mass dosage could be delivered. Successful intratracheal delivery of the AdHu5-vectored dry powder was achieved with a pipette-tip loading dosator and led to a strong bioactive response. Overall, this work indicates the feasibility of murine pulmonary delivery and immunological testing of a thermally stable, adenoviral-vectored vaccine in dry powder form. / Thesis / Master of Applied Science (MASc) / Most vaccines currently available on the market must be stored and transported at temperatures ranging from 2-8 ⁰C to properly maintain their function, with some vaccine requiring temperatures as low as -80 ⁰C. The equipment required to maintain such temperatures is costly and is a significant limitation for developing nations trying to secure vaccine access. As an alternative to traditional liquid vaccine formulations, dry powder vaccines offer stability at room temperature without the need for expensive equipment and can also be administered through inhalation. Using a processing method called spray drying, an active vaccine component can be encapsulated in a carefully selected sugar formulation which forms a protective coating as the particles dry to provide stabilization. Since the efficacy of such dry powder vaccines must be first evaluated with mouse models, the focus of this work was to improve an existing blend of sugars to produce a dry vaccine powder that contains high enough dosage for mouse testing. Processing losses from spray drying were minimized through careful selection of vaccine cryoprotective agents, in addition to optimizing the blend ratio and molecular weight of sugars used for encapsulation. Successful delivery of the optimized powder to the lungs of mice was also accomplished after analyzing the suitability of a variety of custom-made handheld devices. This work shows that inhalable dry powder vaccine delivery is a promising solution to help improve temperature stability and achieve more equitable access to vaccines globally.
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The physical chemistry of corticosteroid-cyclodextrin complexes: The Host-guest Chemistry of Corticosteroid and Cyclodextrin Systems Elucidated with NMR and Applied to Novel Surface-decorated Surface Enhanced Raman Spectroscopic ProbesEteer, Shahrazad A. January 2018 (has links)
Inhaled corticosteroids (ICS) are used to address inflammatory illnesses including asthma and COPD, with delivery commonly achieved using pressurised metered dose inhalers (pMDI). Hydrofluoroalkanes (HFAs) have been introduced as an alternative propellant to chlorofluorocarbons (CFCs) to reduce their environmental impact. However, the thermodynamic properties of HFAs are poorly understood and are different to those of CFCs. It is essential, therefore, to characterise the drugs and excipients used in HFA inhalers in order to obtain a comprehensive understanding of the device performance and the therapeutic efficacy.
This work has developed different analytical methods to study the complexation between ICS and CD which are added to enhance the solubility of inhaled drugs in pMDI propellant systems providing rational control of suspension vs. solution formulations and hence their dose uniformity and stability.
The Nuclear Magnetic Resonance (NMR) method developed has shown weaker complexation between budesonide and the derivatised CDs DIMEB and TRIMEB in organic solvents compared to D2O with the strength of the complex formed being ranked as D2O > MeOD > CDCl3 > CD3CN. The derivatisation of the CD also shows a marked difference in complexation with budesonide with the strength of the association being ranked as DIMEB > βCD > TRIMEB. Studies of various ICS compounds with TRIMEB in the fluorinated propellant HPFP showed the association to be greatest in budesonide, followed by beclomethasone dipropionate, momestasone furoate and fluticasone propionate.
Surface-enhanced Raman scattering (SERS) has been used for the detection of corticosteroids in water using thiol functionalised βCD as a complementary study to NMR. This has been utilised to evaluate the host-guest complexes formed and provides further insight into the complexation of the compounds by their inclusion into the CD cavity.
The structural data obtained using the NMR and SERS approaches developed have provided a fundamental insight into the physical chemistry of these interactions at a molecular level.
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Modeling Children's Exposure to Manganese in Ambient Air: A Case Study in Marietta, OhioFulk, Florence A. 12 September 2014 (has links)
No description available.
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Normal ventilation and NO inhalation prevent pulmonary artery endothelial dysfunction secondary to cardiopulmonary bypass (CPB)Gagnon, Julie January 2001 (has links)
Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.
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Engineering of Inhalation Aerosols Combining Theophylline and BudesonideChen, Chi January 2014 (has links)
In asthma therapy, the use of theophylline to prevent bronchial spasm and glucocorticoids to decrease inflammation is widely indicated. Apart from the acute asthma attack oral theophylline is treated for chronic therapy in order to minimize inflammation and to enhance the efficiency of corticosteroids and recover steroids’ anti-inflammatory actions in COPD treatment. The preferred application route for respiratory disease treatment is by inhalation, such as dry powder inhalers (DPI) being the delivery systems of first choice. As shown recently, there is an advantageous effect if the drugs are given simultaneously which is caused by a synergistic effect at the same target cell in the lung epithelia. Therefore, it seems rational to combine both substances in one particle. This type of particle has the advantage over a combination product containing both drugs in a physical mixture which occurs rather randomly deposition leading to API segregation and non-dose-uniformity.
Dry powder inhalers (DPIs) is a type of therapeutic pharmaceutical formulations usually present in the solid form. Due to the nature of the solid-state, an understanding of chemical and physical properties must be established for acquiring optimum performance of the active pharmaceutical ingredients (APIs).
In recent year, generation of DPIs is a destructive procedure to meet the micron size. Such processes are inefficient and difficult to control. Moreover, according to current researches on combination APIs formulation, this type of DPIs performed a greater variability in does delivery of each active, leading to poor bioavailability and limit clinical efficient. This result suggest that combination formulations require advanced quality and functionality of particles with suitable physicochemical properties. Hence, in order to production of binary and combination DPIs products, the aim of this study was to develop the spray drying and ultrasonic process for engineering of combination drug particles that will be delivered more efficiently and independently of dose variations to the lung.
Microparticles were produced by spray drying or/and ultrasonic technique. The processing parameters and addition of excipients (polymers) were optimized using a full factorial design such that microparticles were produced in a narrow size range suitable for inhalation. Employing excipients resulted in high saturation environment leading to minimized sphere particles when compared to conventional solvent. Solid state characterization of microparticles using powder x-ray diffraction and differential scanning calorimetry indicated that the particles contained crystalline but no cocrystal. The combination particles comparable to or better than micronized drug when formulated as a powder blended with lactose. It was concluded that the use of HPMC enhanced crystallinity suitable for inhalation; and combination particles improved uniform distribution on the stage of NGI.
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Untersuchungen zur Verträglichkeit und Pharmakokinetik von Itraconazol per inhalationem bei Tauben (Columba livia f. domestica)Hofstetter, Susanne 06 April 2016 (has links) (PDF)
Die Aspergillose ist eine Erkrankung des Respirationstraktes bei Vögeln, vor allem in Gefangenschaft gehaltenen tropischen Papageien, Greifvögeln und Pinguinen. Itraconazol ist hierbei ein häufig eingesetztes Therapeutikum und wird in der Vogelmedizin per os verabreicht (JONES und OROSZ 2000; KELLER 2011). Es zeigten sich gute Wirksamkeiten und Resistenzlagen. Bei über 90 % der Aspergillus fumigatus Isolate aus Wild- und Hausvögeln konnte eine MHK von 0,5 µg/ml eruiert werden (BEERNAERT et al. 2009). Allerdings kam es nach oraler Gabe von Itraconazol zu einem verzögerten Wirkungseintritt sowie, vor allem bei Graupapageien, zu Nebenwirkungen (KRAUTWALD-JUNGHANNS 2011b; PSCHERER 1995). Um ausreichende Wirkspiegel in Lunge und Luftsäcken zu erreichen, ist die Verabreichung einer hohen oralen Dosis notwendig. Dies führt wiederum zu hohen systemischen Konzentrationen und somit zu hohen potenziellen Nebenwirkungen (LUMEIJ et al. 1995). Ein Ziel in der Verbesserung der Therapiemöglichkeiten der Aspergillose ist es daher, einen hohen lokalen Wirkspiegel mit gleichzeitig geringen systemischen Konzentrationen zu erreichen. Ein Ansatz besteht in der inhalativen Verabreichung von z. B. Nanosuspensionen, da hier das Medikament direkt in Lunge/Luftsäcke appliziert werden kann.
Ziel dieser Arbeit war die Sammlung von ersten Daten über den Einsatz einer neuartigen Itraconazol-Nanosuspension zur Verabreichung per inhalationem an Tauben (Columba livia f. domestica). Hierzu wurden in einer ersten Studie pharmakokinetische Spiegel in Blut sowie Lungengewebe nach einmaliger Gabe zweier Konzentrationsstufen (1 % und 10 %) erfasst. In der zweiten Studie wurde die Verträglichkeit sowie die Pharmakokinetik nach 14 tägiger Inhalation der Suspension in den Dosierungsstufen 1 %, 4 % und 10 % evaluiert.
In der ersten Studie wurden die Tauben in zwei Hauptgruppen sowie eine Placebogruppe randomisiert aufgeteilt und erhielten einmalig über 30 min die Itraconazol-Nanosuspension per inhalationem in den Dosierungsstufen 1 % und 10 % bzw. isotonische Natriumchlorid-Lösung. Keines der Tiere zeigte Nebenwirkungen, die in Zusammenhang mit der Medikation gestellt werden konnten. Zur Erstellung eines pharmakokinetischen Profils wurden Blutproben nach 1 h, 4 h, 24 h, 48 h, 72 h und 96 h sowie Lungengewebe von je vier Tauben nach der Euthanasie entnommen und darin die Itraconazol sowie die OH Itraconazol Konzentrationen bestimmt. Alle vorhandenen Werte zu einem gegebenen Zeitpunkt wurden gemittelt, woraus sich ein zusammengesetztes Profil ergab. Nach singulärer Verabreichung zeigten sich geringe systemische Spiegel mit einer Peak-Konzentration von 0,01 µg/ml Itraconazol 4 h post inhalationem bzw. 0,04 µg/ml OH-Itraconazol 24 h post inhalationem bei der 1%igen Nanosuspension und 0,065 µg/ml Itraconazol 24 h nach der Inhalation bzw. 0,365 µg/ml OH Itraconazol 24 h nach der Inhalation bei der 10%igen Dosierungsgruppe. In den Lungen konnten weitaus höhere Spiegel mit 9,1 µg/g Itraconazol und 0,223 µg/g OH Itraconazol 1 h post inhalationem bei der 1%igen Dosierungsgruppe bzw. 91,13 µg/g Itraconazol 1 h nach der Inhalation und 1,081 µg/g OH Itraconazol 4 h nach der Inhalation bei der 10%igen Dosierungsgruppe detektiert werden.
Bei der zweiten Studie wurden die Tiere in drei Hauptgruppen sowie eine Placebogruppe randomisiert aufgeteilt und erhielten 14 Tage lang über je 30 min die Itraconazol-Nanosuspension per inhalationem in den Konzentrationen 1 %, 4 % und 10 % bzw. istotonische Natriumchlorid Lösung. Zur Abklärung der Verträglichkeit wurden die Tiere täglich adspektorisch, sowie alle sieben Tage ausführlich klinisch untersucht. Weiterhin wurden vor und nach der Inhalationsperiode detaillierte Blutuntersuchungen durchgeführt. Bei keiner der Untersuchungen konnten Unverträglichkeitsreaktionen auf das zu testende Medikament festgestellt werden. Auch nach 14 tägiger Gabe konnten im Plasma nur geringe Itraconazol-/OH Itraconazol-Konzentrationen gemessen werden. Aufgrund der teilweise sehr hohen Lungenspiegel (17,14 µg/g bei der 4%igen und 185 µg/g bei der 10%igen Nanosuspension je 24 h post inhalationem) und hohen Eliminationshalbwertszeiten (von über 40 h) sind jedoch hohe und langanhaltende Wirkspiegel am Infektionsort gegeben.
Abschließend kann gesagt werden, dass die erlangten Daten über den Einsatz der neuartigen Itraconazol-Nanosuspension zur Verabreichung per inhalationem bei Tauben keine klinischen Nebenwirkungen erkennen ließen und sich ein effektives pharmakokinetisches Profil zeigte. Mit den hohen lokalen Lungenspiegeln nebst geringen systemischen Konzentrationen und somit geringen zu erwartende Nebenwirkungen erscheint das Medikament durchaus zum Einsatz gegen die Aspergillose bei Vögeln geeignet zu sein.
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