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Background: Aerosol therapies with vented facemasks are considered a risk for nosocomial transmission of viruses such as severe acute respiratory syndrome coronavirus 2. The transmission risk can be decreased by minimizing aerosol leakage and filtering the exhaled air. Objective: In this study, we determined which closed facemask designs show the least leakage. Methods: Smoke leakage was quantified during in- and exhalation in a closed system with expiration filter for three infant, six child, and six adult facemasks (three times each mask), using age-appropriate anatomical face models and breathing patterns. To assess leakage, smoke release was recorded and cumulative average pixel intensity (cAPI) was calculated. Results: In the adult group, aircushion edges resulted in less leakage than soft edges (cAPI: 407 ± 250 vs. 774 ± 152) (p = 0.004). The Intersurgical® Economy 5 mask (cAPI: 146 ± 87) also released less smoke than the Intersurgical® Clearlite 5 (cAPI: 748 ± 68) mask with the same size, but different geometry and edge type (p-value <0.05). Moreover, mask size had an effect, as there was a difference between Intersurgical® Economy 4 (cAPI: 708 ± 346) and 5, which have the same geometry but a different size (p-value <0.05). Finally, repositioning masks increased the standard deviations. Mask leakage was not dependent on breathing patterns within the child group. Conclusions: Mask leakage can be minimized by using a closed system with a well-fitting mask that is appropriately positioned. To decrease leakage, and therewith minimize potential viral transmission, selecting a well-fitting mask with an aircushion edge is to be recommended.

The second-line antileishmanial compound pentamidine is administered intramuscularly or, preferably, by intravenous infusion, with its use limited by severe adverse effects, including diabetes, severe hypoglycemia, myocarditis and renal toxicity. We sought to test the potential of phospholipid vesicles to improve the patient compliance and efficacy of this drug for the treatment of leishmaniasis by means of aerosol therapy. The targeting to macrophages of pentamidine-loaded liposomes coated with chondroitin sulfate or heparin increased about twofold (up to ca. 90%) relative to noncoated liposomes. The encapsulation of pentamidine in liposomes ameliorated its activity on the amastigote and promastigote forms of Leishmania infantum and Leishmania pifanoi, and it significantly reduced cytotoxicity on human umbilical endothelial cells, for which the concentration inhibiting 50% of cell viability was 144.2 ± 12.7 µM for pentamidine-containing heparin-coated liposomes vs. 59.3 ± 4.9 µM for free pentamidine. The deposition of liposome dispersions after nebulization was evaluated with the Next Generation Impactor, which mimics human airways. Approximately 53% of total initial pentamidine in solution reached the deeper stages of the impactor, with a median aerodynamic diameter of ~2.8 µm, supporting a partial deposition on the lung alveoli. Upon loading pentamidine in phospholipid vesicles, its deposition in the deeper stages significantly increased up to ~68%, and the median aerodynamic diameter decreased to a range between 1.4 and 1.8 µm, suggesting a better aptitude to reach the deeper lung airways in higher amounts. In all, nebulization of liposome-encapsulated pentamidine improved the bioavailability of this neglected drug by a patient-friendly delivery route amenable to self-administration, paving the way for the treatment of leishmaniasis and other infections where pentamidine is active.

Highlights - Advanced numerical model for micro-particle TD in the human lung is developed. - This study is conducted for 17-generation lung geometry for the first time. - The particle diameter effects are investigated for different breathing conditions. - This study will help pharmaceutical companies to design new drug delivery tools. Abstract The major problem in understanding the therapeutically targeted drug delivery system in the deeper airways of the human lung is the lack of adequate data of particle transport and deposition (TD) in the transitional and respiratory zones (deeper airways) of the human lung. An understanding of the morphometry of the pulmonary airways and the lungs forms the primary step in a study of pulmonary aerosol deposition. The present study is the first-ever approach to explore the pulmonary aerosol TD in a digital 17-generation human pulmonary airway model. The present numerical study achieved the lack of the particle TD data in the deeper airways of the human lung. This paper presents a 3-D (3-dimensioanl) CFD (Computational Fluid Dynamics) study of an anatomically realistic 17-generation lung bronchial tree model based on the high-resolution computer tomography (HRCT) data by Schmidt et al., (2004). Physical morphometry is necessary for sufficiently calculating air and particle dynamics in human pulmonary airways with available data on a large number of generations. A Lagrangian-based Discrete Phase Model (DPM) is used to study the particle TD in the 17-generation of the lung airways. The numerical results demonstrate that inertial impaction is dominant in the upper airways and a large percentage of particles is deposited in the upper airways. The numerical results also illustrate that a large percentage of smaller diameter particles leaves through the airway outlet boundary at the 17th generation irrespective of breathing patterns. The escaped particles are considered to continue to follow the airw

© 2017. This version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0, Regional deposition effects are important in the pulmonary delivery of drugs intended for the topical treatment of respiratory ailments. They also play a critical role in the systemic delivery of drugs with limited lung bioavailability. In recent years, significant improvements in the quality of pulmonary imaging have taken place, however the resolution of current imaging modalities remains inadequate for quantifying regional deposition. Computational Fluid-Particle Dynamics (CFPD) can fill this gap by providing detailed information about regional deposition in the extrathoracic and conducting airways. It is therefore not surprising that the last 15. years have seen an exponential growth in the application of CFPD methods in this area. Survey of the recent literature however, reveals a wide variability in the range of modelling approaches used and in the assumptions made about important physical processes taking place during aerosol inhalation. The purpose of this work is to provide a concise critical review of the computational approaches used to date, and to present a benchmark case for validation of future studies in the upper airways. In the spirit of providing the wider community with a reference for quality assurance of CFPD studies, in vitro deposition measurements have been conducted in a human-based model of the upper airways, and several groups within MP1404 SimInhale have computed the same case using a variety of simulation and discretization approaches. Here, we report the results of this collaborative effort and provide a critical discussion of the performance of the various simulation methods. The benchmark case, in vitro deposition data and in silico results will be published online and made available to the wider community. Particle image velocimetry measurements of the flow, as well as additional numerical results from the community, will be appended to the online database as they become available in the future., Peer Reviewed, Postprint (author's final draft)

Подані результати досліджень найбільш поширених побічних реакцій, викликаних тими чи іншими протитуберкульозними препаратами, в Чернівецькій області. Наведені методи комбінованої аерозольтерапії у хворих на хіміорезистентний туберкульоз легень, доведена їх ефективність., Представлены результаты исследований наиболее распространенных побочных реакций, вызванных теми или иными противотуберкулезными препаратами, в Черновицкой области. Приведены методы комбинированной аэрозольтерапии у больных химиорезистентным туберкулезом легких, доказана их эффективность., The article provides the results of studies on the most common side effects caused by various antituberculosis drugs in the Chernivtsi region. Methods of combined aerosol therapy in patients with drug-resistant pulmonary tuberculosis are considered, their effectiveness is proved.

Chan, Ka Man Carmen., "October 2009.", Thesis (M.Phil.)--Chinese University of Hong Kong, 2010., Includes bibliographical references (leaves 160-165)., s in English and Chinese., Table of Contents --- p.I, Acknowledgements --- p.IV, p.V, (Chinese version) --- p.VIII, List of Figures --- p.X, List of Tables --- p.XVIII, Chapter Chapter One. --- Introduction, Chapter 1.1 --- Pulmonary drug delivery --- p.1, Chapter 1.2 --- Inhalation drug delivery systems --- p.4, Chapter 1.3 --- Dry powder inhalation aerosols --- p.5, Chapter 1.3.1 --- Principle of operation of DPIs --- p.5, Chapter 1.3.2 --- Aerodynamic diameter --- p.6, Chapter 1.3.2.1 --- Fine particle fraction --- p.8, Chapter 1.3.3 --- Dispersibility --- p.8, Chapter 1.3.4 --- Factors that affect dispersibility --- p.9, Chapter 1.3.4.1 --- Particle Size --- p.9, Chapter 1.3.4.2 --- Particle Density and Morphology --- p.10, Chapter 1.3.4.3 --- Interparticulate interactions一Cohesion and adhesion --- p.11, Chapter 1.3.4.3.1 --- Surface energetics --- p.11, Chapter 1.3.4.3.2 --- Effect of hygroscopicity and electrostatic charges --- p.12, Chapter 1.4 --- Particle formation techniques for DPI formulation --- p.14, Chapter 1.4.1 --- Spray-drying --- p.14, Chapter 1.4.2 --- Surface modification --- p.16, Chapter 1.5 --- Physical characterization --- p.17, Chapter 1.5.1 --- Laser diffraction --- p.17, Chapter 1.5.2 --- X-ray powder diffraction --- p.18, Chapter 1.5.3 --- Thermal analysis --- p.19, Chapter 1.5.4 --- Particle morphology and surface area --- p.20, Chapter 1.5.5 --- In vitro aerosol performance --- p.21, Chapter 1.6 --- Surface characterization --- p.21, Chapter 1.6.1 --- X-ray photoelectric spectroscopy (XPS) --- p.21, Chapter 1.6.2 --- Inverse gas chromatography --- p.22, Chapter 1.7 --- Atomic force microscopy in pharmaceutical science --- p.23, Chapter 1.7.1 --- Principle of operation --- p.24, Chapter 1.7.1.1 --- Tapping mode --- p.27, Chapter 1.7.1.2 --- Contact mode --- p.27, Chapter 1.8 --- Scope of thesis --- p.29, Chapter Chapter Two. --- Materials and Methods, Chapter 2.1 --- Materials --- p.32, Chapter 2.2 --- Methods --- p.32, Chapter 2.2.1 --- Optimization of spray-drying parameters --- p.32, Chapter 2.2.2 --- Preparation of spray-dried salbutamol sulphate powders containing different concentrations of amino acid additive --- p.33, Chapter 2.2.3 --- Physical characterization of spray-dried powders --- p.34, Chapter 2.2.3.1 --- Particle size and size distribution --- p.34, Chapter 2.2.3.2 --- Specific surface area --- p.35, Chapter 2.2.3.3 --- X-ray powder diffraction --- p.35, Chapter 2.2.3.4. --- Scanning electron microscopy --- p.36, Chapter 2.2.3.5. --- Thermal analysis --- p.36, Chapter 2.2.3.5.1 --- Thermogravimetric analysis (TGA) --- p.36, Chapter 2.2.3.5.2 --- Differential scanning calorimetry (DSC) --- p.36, Chapter 2.2.3.6 --- Water vapour sorption isotherm --- p.37, Chapter 2.2.3.7 --- Density measurements --- p.37, Chapter 2.2.3.8 --- In vitro particle deposition (MSLI) --- p.38, Chapter 2.2.4 --- Surface characterization of the spray-dried powders --- p.39, Chapter 2.2.4.1 --- X-ray photoelectric spectroscopy (XPS) --- p.39, Chapter 2.2.4.2 --- Surface energy measurement by inverse gas chromatography (IGC) --- p.40, Chapter 2.2.4.2.1 --- Calculation of standard free energy of adsorption --- p.41, Chapter 2.2.4.2.2 --- Dispersive component of surface free energy and related thermodynamic parameters --- p.42, Chapter 2.2.4.2.3 --- Specific interactions and associated acid-base properties --- p.43, Chapter 2.2.5. --- Atomic Force Microscopy (AFM) --- p.43, Chapter 2.2.5.1. --- Imaging --- p.43, Chapter 2.2.5.2. --- Force measurements --- p.44, Chapter 2.2.5.2.1 --- Adhesion force measurements --- p.44, Chapter 2.2.5.2.2 --- Force curve data conversions --- p.44, Chapter Chapter Three. --- "Optimal Spray-drying Conditions, Physical Characterization and Aerosol Performance of Additive-modified Spray-dried Salbutamol Sulphate particles", Chapter 3.1 --- Optimization of spray-drying conditions --- p.46, Chapter 3.2 --- Effect of phenylalanine on the spray-dried SS particles --- p.52, Chapter 3.2.1. --- Phenylalanine as the additive --- p.52, Chapter 3.2.1.1 --- In vitro aerosol performance --- p.53, Chapter 3.2.1.2 --- Particle morphology --- p.55, Chapter 3.2.1.3 --- Crystallinity --- p.62, Chapter 3.2.1.4 --- Particle size distribution and specific surface area --- p.63, Chapter 3.2.1.5 --- Density --- p.65, Chapter 3.2.1.6 --- Thermal analysis --- p.66, Chapter 3.2.1.7 --- Water vapour isotherm --- p.70, Chapter 3.3 --- Effect of leucine on the spray-dried SS particles --- p.77, Chapter 3.3.1. --- L-Leucine as the additive --- p.77, Chapter 3.3.1.1 --- In vitro aerosol performance --- p.78, Chapter 3.3.1.2 --- Particle morphology --- p.80, Chapter 3.3.1.3 --- Crystallinity --- p.86, Chapter 3.3.1.4 --- Particle size distribution and specific surface area --- p.87, Chapter 3.3.1.5 --- Density --- p.90, Chapter 3.3.1.6 --- Thermal analysis --- p.92, Chapter 3.3.1.7 --- Water vapour isotherm --- p.95, Chapter Chapter Four. --- Surface Characterization of Additive-modified Spray-dried Salbutamol Sulphate Particles, Chapter 4.1 --- X-ray photoelectric spectroscopy --- p.103, Chapter 4.1.1 --- Phenylalanine --- p.103, Chapter 4.1.2 --- Leucine --- p.104, Chapter 4.2 --- Inverse gas chromatography --- p.105, Chapter 4.2.1 --- Phenylalanine --- p.105, Chapter 4.2.2 --- Leucine --- p.107, Chapter 4.3 --- Atomic force microscopy --- p.109, Chapter 4.3.1 --- Surface topography --- p.109, Chapter 4.3.2 --- Adhesive force measurements --- p.118, Chapter Chapter Five. --- Conclusions and Suggestions for Future Works, Chapter 5.1 --- Conclusions --- p.139, Chapter 5.1.1 --- Physical properties --- p.139, Chapter 5.1.2 --- Surface characteristics and aerosol performance --- p.140, Chapter 5.2 --- Future studies --- p.142, Appendix --- p.143, References --- p.160, http://library.cuhk.edu.hk/record=b5894263, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The aim of this study was to compare the efficacy of local drug delivery by inhalation to intravenous delivery in a B16F10 melanoma metastatic lung model. Temozolomide was formulated as a suspension, which was elaborated and evaluated in terms of particle size, shape and agglomeration. An endotracheal administration device was used to aerosolise the suspension. This mode of delivery was evaluated at different temozolomide concentrations and was optimized for the uniformity of delivered dose, the droplet size distribution and the distribution of droplets in vivo. Of the particles in the stabilised suspension, 79% were compatible with the human respirable size range, and this formulation retained 100% in vitro anticancer activity as compared to temozolomide alone in three distinct cancer cell lines. The pulmonary delivery device provided good reproducibility in terms of both the dose delivered and the droplet size distribution. Most of the lung tissues that were exposed to aerosol droplets contained the particles, as revealed by fluorescent microscopy techniques. The global in vivo antitumour activity of the inhaled temozolomide provided a median survival period similar to that for intravenous temozolomide delivery, and three out of 27 mice (11%) survived with almost complete eradication of the lung tumours. The present study thus shows that inhalation of a simple liquid formulation is well tolerated and active against a very biologically aggressive mouse melanoma pulmonary pseudo-metastatic model. This inhalation delivery could be used to deliver other types of anticancer drugs., JOURNAL ARTICLE, info:eu-repo/semantics/published

鼻内上顎洞篩骨洞開放術後の鼻・副鼻腔の形態を模したシリコン製の鼻・副鼻腔モデルを作製し、そのモデルに対し一定の粒子径をもった炭素粒子を噴霧し、その沈着分布パターンを検討した。結果は重量基準空気力学径6.99μmおよび14.61μmの粒子を用いた場合、とても鼻内顎洞篩骨洞開放術後のエアロゾル療法の標的部位と考えられるOMCおよび上顎洞、篩骨洞へ効果的に沈着していることが確認できた。上顎洞内では6.99μmの粒子を用いた方がより均等な沈着パターンをとった。また、ノズル角度による影響をみた実験においては、ノズル角度45°の場合が30°の場合に比べOMC、および上顎洞、篩骨洞へのエアロゾル沈着パターンを左右する要因としては、粒子径だけではなく、ノズル角度が粒子径と共に重要な要因であると考えられた。, We restored a human nasosinus model whose sinuses underwent functional endoscopic sinus surgery.The nasal cavity was constructed from a cast made at autopsy, and the maxillary and ethmoid sinuses were reconstructed from computed tomogarphy(CT)images.Anterior and posterior ethmoid cells were dissected and the diameter of the maxillary ostium enlarged to 10mm. We evaluated the depositional patterns of carbon particles, administered by jet nebulizer, whose aerodynamic diameter was 6.99μm or 14.61μm.Both sizes were well deposited on the ostiomeatal complex, the maxillary sinus, and the ethmoid sinuses.We also evaluated the effects of the nebulizer nozzle angle on particle deposition in the nasal cavity.We found that a 45°angle was more effective than a 30°. Our results indicate that both particle size and nozzle angle are important factors in aerosol deposition.

Inhalation of aerosolized drugs has become an established means for treatment of pulmonary diseases in the last fifiy years. The majoriry of aerosol therapy in childhood concerns inhaled corticosteroids and bronchodilators in the management of asthma. Administration of drugs via the inhaled route has major advantages over the oral route. The drug is targeted directly to its site of action, which results in a more rapid effect and a lower dose needed with less systemic side effects. However, to deliver the drug into the lungs reliably and reproducibly is difficult, especially in children. It requires understanding of the mechanisms of aerosol deposition in the lungs and knowledge about the factors affecting delivery and deposition of aerosols. There are several ways to deliver therapeutic aerosols to the lungs. The current methods can be classified in three categoties: nebulizers, pressurized metered dose inhales (pMDI's) with or without spacer, and dry powder inhalers (DPT's). Not all systems are suirable for use in young children. Application of aerosol therapy in young children requires a different approach compared vvith adults and older children. Factors such as age, co-operation, breathing pattern, nose breathing and size of the airways should be raken into account as they can have substantial effect on the dose delivered to the lungs. Nebulizers have long been the mainstay of aerosol therapy in children. Currently, the pMDI combined with spacer is recommended as the first choice for asthma therapy in young children. However, the pMDIIspacer and most other aerosol delivery systems were primarily designed for use in adults, and subsequently adapted for use in children. Furthermore, studying efficiency of aerosol delivery systems in young children is difficult and has ethical limitations. This explains why there is extended information available on the performance of aerosol delivery systems in adults, but only limited data in children. The use of drugs with pote

https://patrimoniodigital.ucm.es/r/thumbnail/646200, https://books.google.com/books/ucm?vid=UCM5318293365&printsec=frontcover&img=1

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Studies centered on pulmonary drug delivery have primarily focused on new device technologies to improve the generation of aerosols and their deposition in the respiratory system. Although considerable progress has been made in this field, no significant superior treatment of respiratory diseases has been achieved in recent times. One of the principal reasons is a scarcity in knowledge concerning inhaled/aerosol drug fate post-deposition in the lungs. The first barrier encountered by inhaled drugs in the pulmonary system is the mucus layer. This plays a protective role that is believed to be largely achieved by its ability to act as a physical barrier but also hinders molecular diffusion. The impeding nature of the mucus on aerosolised drug permeation is poorly understood. Indeed, the effects of direct interactions between mucus and inhaled drugs have been largely overlooked and most of the available evidence on mucus-drug interactions are related to the gastrointestinal tract. In this doctoral thesis, the main aim was to gain a better understanding of the relationship between the physicochemical properties of aerosolised pulmonary agents and their diffusion across the pulmonary mucus layer. This knowledge would provide valuable information for the development of more effective pulmonary agents. The first objective was to develop and characterise an in vitro mucus model suitable for drug permeation studies. That was comprised of a thin mucus layer derived from pig trachea covering the semi-permeable membrane of Transwell® inserts. Rheometric measurements on pig tracheal mucus secretions after a cleaning procedure to remove blood contaminants demonstrated that the obtained mucus was non-Newtonian. Furthermore, cryogenic-scanning electron microscopy (cryo-SEM) revealed pore sizes with diameters of ∼400 ± 200 nm. The barrier properties of the mucus model were verified by measuring the diffusion of various fluorescent dyes across mucus layers coating the Transwell® inse