Tomasz Sosnowski

A dispersion of oxygen nanobubbles (O2-NBs) is an extraordinary gas–liquid colloidal system where spherical gas elements can be considered oxygen transport agents. Its conversion into inhalation aerosol by atomization with the use of nebulizers, while maintaining the properties of the dispersion, gives new opportunities for its applications and may be attractive as a new concept in treating lung diseases. The screening of O2-NBs interactions with lung fluids is particularly needed in view of an O2-NBs application as a promising aerosol drug carrier with the additional function of oxygen supplementation. The aim of the presented studies was to investigate the influence of O2-NBs dispersion combined with the selected inhalation drugs on the surface properties of two types of pulmonary surfactant models (lipid and lipid–protein model). The characteristics of the air–liquid interface were carried out under breathing-like conditions using two selected tensiometer systems: Langmuir–Wilhel...

The article presents a method of controlling the size of droplets generated by a system that sprays a high-viscosity liquid containing particles of a solid body, i.e., a catalyst. The work is a continuation of previous research concerning the spraying of liquids with a catalyst, which improves the efficiency of the process. As a result of the conducted CFD calculations, it was found that to bring the catalyst to the system, a droplet with a diameter of at least 30 µm should be generated. The tests were carried out on a laboratory scale on a model isopropanol-water system. A polymer containing Raney nickel particles was added to the suspension. The analysis of the obtained data confirmed the possibility of generating droplets with the desired diameters in order for the liquid carrying the catalyst to not evaporate before it is delivered to the combustion chamber. The designed and constructed test system allows the diameters of the generated droplets to be controlled by changing the s...

Inhalation is a non-invasive method of local drug delivery to the respiratory system. This study analyzed the potential use of aqueous dispersion of oxygen nanobubbles (ADON) as a drug carrier with the additional function of oxygen supplementation to diseased lungs. The suitability of the membrane-based method of ADON preparation and, next, the stability of ADON properties during storage and after aerosolization in nebulizers of various designs (jet, ultrasonic, and two vibrating mesh devices) was investigated. The increased oxygen content in the aerosol generated in two mesh nebulizers suggests that the proposed concept may be helpful in the oxygen supplementation during drug delivery by aerosol inhalation without using an additional oxygen source. This application can increase the overall effectiveness of lung disease treatment and pulmonary rehabilitation.

The transfer phenomena in the thin liquid layer covered by the phospholipid monolayer are investigated. The case of dynamic oscillatory changes of the air/liquid area is considered. Such situation occurs in the pulmonary surfactant system being the natural biological structure in the breathing zone of the human respiratory system. It was shown that in those conditions the surface tension gradient is instantly generated and varied along the interface what results in intensified flow at the interfacial region. Experimental analysis conducted with the Langmuir film balance confirmed the theoretically predicted induction of the ordered superficial flow. Measurements of the interfacial mass transfer rate for the oxygen being absorbed by the liquid film showed the increase of the absorption rate in comparison with the static or phospholipid-free interface. It was postulated that for certain system parameters the hydrodynamic structure of the flow can be qualitatively changed what should result in a strong increase of interfacial mass transfer rate.

Lung surface is the first line of contact between inhaled carbon nanomaterials, CNMs, and the organism, so this is the place where pulmonary health effects begin. The paper analyzes the influence of several CNMs (single- and multi-walled nanotubes with various surface area: 90–1,280 m2/g and aspect ratio: 8–3,750) on the surface-active properties of the lung surfactant, LS, model (Survanta). Effects of CNM concentration (0.1–1 mg/ml) and surface oscillation rate were determined using the oscillating drop method at simulated breathing conditions (2–10 s per cycle, 37 °C). Based on the values of apparent elasticity and viscosity of the interfacial region, new parameters: Sε and Sμ were proposed to evaluate potential effect of particles on the LS at various breathing rates. Some of tested CNMs (e.g., COOH- functionalized short nanotubes) significantly influenced the surfactant dynamics, while the other had weaker effects even at high particle concentration. Analysis of changes in Sε an...

The work discusses physicochemical phenomena related to interactions between the inhaled particles and the surface of pulmonary fluid which contains the lung surfactant. Dynamic surface phenomena which arise due to periodical variations of the interfacial area during breathing cycle are the extraordinary feature of this system and they are strictly related to the mechanics of ventilation and the pulmonary mass transfer processes. Presence of foreign material such as inhaled microand nanoparticles with different size, surface properties and morphology may alter these phenomena which may have some health consequences. This effect is discussed on two examples: mineral particles (CeO2) and carbonaceous particles emitted from diesel engine running on two different fuels. Two experimental methods of research in this field are presented: the Langmuir balance and the oscillating pendant drop. The results show the sensitivity of dynamic surface properties of the lung surfactant on exogenous ...

Ciecz zawierająca surfaktant płucny jest drugim – obok śluzu oskrzelowego rodzajem płynu biologicznego pokrywającego powierzchnię ścianek układu oddechowego. Wdychane cząstki aerozolowe, które docierają do poziomu pęcherzyków płucnych i tam się osadzają, bezpośrednio oddziałują z surfakantem, którego cząsteczki są zaadsorbowane na powierzchni międzyfazowej ciecz-gaz. Rolą surfaktantu w płucach jest utrzymywanie odpowiedniej zmienności napięcia powierzchniowego w trakcie cyklu wdechwydech, z czym związane są zarówno mechaniczne aspekty funkcjonowania narządu oddechowego (m.in. praca wymagana do wykonania wdechu), jak i występowanie określonych zjawisk hydrodynamicznych − efektów Marangoniego − współodpowiedzialnych za procesy przenoszenia masy przebiegające w tym układzie (m.in. wymiana gazowa, usuwanie osadzonych zanieczyszczeń pyłowych) [Sosnowski, 2006]. Dlatego też duże znaczenie mają nieinwazyjne dla organizmu badania doświadczalne umożliwiające określenie zmian funkcjonalności ...

The entire alveolar surface of human lungs is lined with a thin fl uid continuum, called the alveolar lining layer. This lining consists of an aqueous hypophase covered by a fi lm of pulmonary surfactant – a complicated mixture of approximately 90% lipids and 10% proteins. During the breathing cycle its surface active components (mainly phospholipids) adsorb at the air-water interface and lower the alveolar surface tension. As a consequence, the energy required to infl ate the lungs is reduced and the likelihood of alveolar collapse during expiration is minimized [Zuo et al. 2008]. Inhaled environmental particles and aerosol drugs deposited on the surface of alveolar lining layer may interact with pulmonary surfactant and reduce its physiological functions. Hence, it is justifi ed to dedicate experimental investigations to examine the effect of various aerosols on the dynamic surface activity of lung surfactant. In the present work, maximum bubble pressure (MBP) tensiometry was empl...

Liposomowe nośniki leków inhalacyjnych stanowią jedną z nowoczesnych strategii dostarczania czynników terapeutycznych do układu oddechowego. Zaletą ich stosowania jest możliwość maskowania hydrofi lowych cech leku, co ułatwia wnikanie leku do komórek nabłonka oraz makrofagów płucnych. Zastosowanie liposomów pozwala również na osiąganie efektu przedłużonego uwalniania leku. Środowisko dolnych dróg układu oddechowego zawiera surfaktant płucny, którego specyfi czna aktywność powierzchniowa, osiągana w dynamicznych warunkach cyklu oddechowego, wpływa na obniżenie wysiłku oddechowego oraz na procesy transportu masy w płucach (wymiana gazowa, usuwanie zanieczyszczeń pochodzenia aerozolowego), m.in. dzięki umożliwieniu powstawania efektów Marangoniego [Sosnowski, 2006]. W tym kontekście ważne jest podjęcie badań mających na celu określenie, czy liposomy wprowadzane do płuc na drodze inhalacji mogą wchodzić w fi zykochemiczne interakcje ze składnikami surfaktantu. Przedstawione w pracy bada...

Osadzające się w płucach pyły pochodzące z zanieczyszczonego powietrza oddziałują bezpośrednio na warstewkę cieczy pokrywającą wewnętrzną powierzchnię układu oddechowego, co może prowadzić do modyfikacji przebiegu procesów transportowych w płucach i wywoływać negatywne skutki dla zdrowia [Sosnowski, 2006]. Wcześniejsze prace wykazały, że nanostrukturalne cząstki glinokrzemianów, spotykane jako zanieczyszczenia powietrza w procesach przemysłowych (np. w przetwórstwie kompozytów polimerowych), zmieniają aktywność powierzchniową składników surfaktantu płucnego w specyficzny sposób, uzależniony od stężenia i własności fizykochemicznych cząstek (powierzchni właściwej, kształtu, zwilżalności) [Kondej i Sosnowski, 2013a; 2013b]. W cytowanych badaniach wykorzystujących pomiary napięcia powierzchniowego w układzie wagi Langmuira-Wilhelmy’ego lub pulsującego pęcherzyka, wskazano na efekt spadku stężenia surfaktantu w fazie wodnej i na powierzchni międzyfazowej ciecz-gaz na skutek jego adsorpc...

Inhaled mineral nanoparticles which are deposited on the lung surface may influence the gas/liquid barrier and the pulmonary surfactant (PS) which constitutes the vital element of the respiratory system. This research is focused on the physicochemical effects caused by selected clay nanoparticles (bentonite, halloysite, montmorillonites) interacting with PS and changing its original surface activity. Using three measuring methods (pulsating bubble technique, Langmuir balance and drop shape analysis), we demonstrated the influence of different mineral nanoparticles on the dynamic surface tension of animal-derived PS material (Survanta ® ) and main surfactant phospholipid (DPPC). The results which are dependent on material properties and concentration allow to hypothesize possible pathways of health effects from inhalation of mineral nanoparticles. This may help to set the guidelines in defining occupational safety standards and methods of protection of the respiratory system against ...

Aerosols are often used as vehicles of medicines and their most important application is related to inhalation of anti-asthmatic or anti-inflammatory drugs. Aerosols are also convenient in topical applications, i.e. applied on skin or mucous membranes (e.g. of nasal or oral cavity). Recently, it has been shown that use of a therapeutic bioaerosol can be beneficial in the speeding up of healing processes of the skin. In this context, cell suspensions are considered as the material for which the suitable spraying method must be established in order to assure that hydrodynamic stress related to liquid atomization will not destroy the living cells. The current work is focused on testing of the influence of selected spraying techniques on the integrity and the survival of different types of cells in the atomized bio-colloid. Medical nebulizers and similar spraying devices have been characterized in respect of the size distribution of emitted droplets, and used to aerosolize selected (i.e...

Abstract Development of bi-component generic orally inhaled product (OIP) delivered from dry powder inhaler (DPI) is challenging due to the necessity to demonstrate the similarity of size distribution of both APIs in inhaled aerosol. The effects of selected technical factors on OIP development are investigated. The Monodose inhalers with different aerodynamic resistance were used to aerosolize generic fluticasone/salmeterol formulations. Flow dynamics in the DPIs was analyzed during realistic use. The effects of lactose grade, capsule types and blending equipment on aerosol particle size were studied with compendial methods. The best dispersion of bi-component powder was obtained in a medium-resistant (∼0.108 hPa0.5 min L−1) Monodose DPI as compared to low- and high-resistant devices. All studied technological factors had influence on the fine particle dose of each API and fluticasone/salmeterol mass ratio. It was demonstrated that the selected Monodose inhaler in combination with the newly developed bi-component drug formulation was able to reproduce the quality of inhalable aerosol obtained from Diskus DPI. Since powder dispersion depends on the energy available in a single breath, an optimized DPI is needed in generic OIP. By adjusting several technological factors it is possible to obtain the reproducible product with the required dose of each aerosolized APIs.

Abstract The paper highlights and discusses the role of interfacial phenomena in the interactions between inhaled solid particles with different properties (size, structure, surface characteristics) and air/liquid interface of the alveolar region of the lungs. The greatest attention is paid to man-made nanosized and nanostructured particles which often belong to the class of “engineered particles”. Their applications in several novel technologies may be associated with accidental particle release to the air and formation of potentially harmful aerosol. Extraordinary, dynamic surface-active properties of the lung surfactant, which are responsible for several physiological functions - including the pulmonary mass transfer - may be altered by such inhaled particles in a material- and dose-dependent manner. Certain effects can be assessed by specialized experimental in vitro methods allowing predictions of possible in vivo interactions. On the other hand, interactions with the lung surfactant can modify the original properties of inhaled particles which in turn will influence their bioavailability or toxicity. All mentioned effects are dependent on particles properties as proven by numerous studies, however such results should be carefully judged due to essential differences in experimental methodology used. The paper also discusses some ideas related to the practical meaning of discussed effects for novel concepts of pulmonary drug delivery by inhalation.

A broader use of carbon nanomaterials increases the risk of their inhalation as aerosol dispersed in the air. Inhaled nanometer-sized particles are known to penetrate to the pulmonary region where they interact with the lung surfactant as the first barrier they meet and eventually penetrate to the surface of the cellular layer. This study presents the results of experimental studies of physicochemical interactions between several types of carbon nanomaterials (nanotubes and nanohorns of various size and surface properties) and lipid layers in two qualitatively different experimental systems: Langmuir trough and pulsated drop tensiometer, both providing complementary possibilities to study interfacial properties of the lipid-rich layer. Quantified alterations in mechanical properties if lipid films (equilibrium compressibility, dynamic surface elasticity, and viscosity) indicate that nanocarbons with different wettability may induce concentration-dependent frustration of the lung sur...

Measurements of dynamic surface tension were carried out in aqueous systems (water or 0.1 mM Triton X-100) comprising nanoparticles formed from chemically modified polyaldehyde dextran (PAD). The nanostructures, considered as potential drug carriers in aerosol therapy, were obtained from biocompatible polysaccharides by successive oxidation and reactive coiling in an aqueous solution. The dynamic surface tension of the samples was determined by the maximum bubble pressure (MBP) method and by the axisymmetric drop shape analysis (ADSA). Experiments with harmonic area perturbations were also carried out in order to determine surface dilatational viscoelasticity. PAD showed a remarkable surface activity. Ward-Tordai equation was used to determine the equilibrium surface tension and diffusion coefficient of PAD nanoparticles (D = 2.3×10

Abstract Experts of four scientific societies and the independent experts described the position paper concerning the role of inhalation chambers in inhalation therapy in children. This document is directed to all paediatricians and family doctors. We have reviewed the most important original and review papers, together with an analysis of the holding chambers market in the country. Recommendations containing indications and principles of the selection as well as methods of inhalation from these devices in children at different age were pointed out.

Health effects of inhaling aerosol produced by electronic cigarettes (ECs) are still uncertain. This work analyzes ECs as specific inhalation devices, which can be characterized by aerodynamic resistance, size distribution of released droplets, and predicted regional and total lung deposition as a function of inhalation maneuver. The internal resistance of two types of EC and a conventional cigarette was evaluated by measuring ΔP-Q curves. Particle size distribution in EC-emitted mist was determined by laser diffraction. The measured data were used to calculate lung deposition based on two approaches: multipath particle dosimetry model (MPPD) and Finlay-Martin correlations. Computations were done for the set of ventilation parameters of an EC user, and also for a by-stander. Tested ECs had higher aerodynamic resistance (1.6-1.9 mbar(0.5) min/L) than tobacco cigarette (0.56 mbar(0.5) min/L), and these values are much above the high-resistant DPIs. The average mass median diameter of droplets emitted from ECs was 410 nm, with the average GSD = 1.6. Predicted total lung deposition of the mainstream aerosol was 15%-45% depending on the breathing scheme. An expected increase of particle size in the exhaled aerosol led to predictions of 15%-30% deposition efficiency during passive vaping. ECs are characterized by high inhalatory resistance, so they require stronger physical effort to transfer cloud of droplets to the lungs, as compared, for example, to DPIs. A significant amount of aerosol is then exhaled, forming an unintentional source of particles to which by-standers are exposed. From this perspective, ECs are not optimal personal aerosol delivery devices.

Inhalation of aerosolized pharmaceuticals is a non-invasive and convenient method of drug delivery typically used for local treatment of lung diseases. Large absorption area of the pulmonary region opens up the possibility of fast and effective transfer of inhaled medicines to the circulation in order to obtain systemic effects. This review is devoted to selected albeit essential challenges of targeting aerosolized drugs to the blood via the pulmonary part of the respiratory system. The special attention is given to some physicochemical aspects of drug formulation which are essential for overcoming the air-blood barrier present in the lungs. It is deemed that a careful analysis of multifarious physical and engineering problems, related to aerosol fate in the lungs, is indispensable for a better design of inhalation delivery systems for systemic drugs.

Inhalation therapy is a convenient method of treating respiratory diseases. The key factors required for inhalation are the preparation of drug carriers (aerosol particles) allowing reproducible dosing during administration. These technical challenges are accomplished with a variety of inhalation devices (inhalers) and medicinal formulations, which are optimized to be easily converted into inhalable aerosols. Areas covered: This review is focused on the most important, but often overlooked, effects, which are required for the reliable and reproducible inhalable drug administration. The effects of patient-related issues that influence inhalation therapy, such as proper selection of inhalers for specific cases is discussed. We also discuss factors that are the most essential if generic inhalation product should be considered equivalent to the drugs with the clinically confirmed efficacy. Expert opinion: Proper device selection is crucial in clinical results of inhalation therapy. The patients' ability to coordinate inhalation with actuation, generation of optimal flow through the device, use of optimal inspiratory volume, all produces crucial effects on disease control. Also the severity of the disease process effects proper use of inhalers. Interchanging of inhalers can produce potentially conflicting problem regarding efficacy and safety of inhalation therapy.

Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 µm. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this turbinate as well together with deposition in the middle and superior nasal meatus reaching the region of nasal ceiling and olfactory field. MF preparation deposited on the anterior part of the inferior turbinate and central part of this turbinate alike. The area of mucous membrane of lateral wall of nasal cavity on which MF deposited was similar to the area achieved after the application of FP preparation but much greater than in the case of FF preparation. FF drug deposition concentrates only on the anterior part of the inferior turbinate. Despite directing the drug to the lateral wall of the nasal cavity a great proportion of examined preparations deposit also on the nasal septum. Conclusions The practical application of tridimensional representation (3D printout) of actual geometry of nasal cavity to establish the deposition of inGKS was proven. Droplet size and the geometry of the aerosol cloud introduced into the nostril determine the significant deposition of medication droplets in the anterior part of the nasal cavity. Both physical properties of the drug as well as spraying system applied influence spatial distribution of the drug. The interaction of the air flow with the layer of deposited fluid plays a major role in the deposition of the drug in the nasal cavity, therefore it is so important that the drug does not drain by gravity but remains at the site of deposition which may be reinforced by thixotropic properties of the preparation.

The paper deals with the analysis of dynamic behavior of a thin liquid film covered by an L-α-dipalmitoyl phosphatidylcholine (DPPC) monolayer during measurements carried out in a Langmuir film balance (LFB). This experimental device is often used for in vitro investigation of surface properties of lung surfactant (LS) and its components. A surface tension- area hysteresis loop measured during oscillations of interfacial area and an extremely low surface tension achieved under compression are the most spectacular features of the LS system. We believe that the presence of the monolayer strongly influences hydrodynamic phenomena in the liquid film in a way that enables a transport of floating or suspended fine solid particles (e.g., aerosol deposits) with the flow. This mechanism may contribute to alveolar clearance from insoluble aerosols. To find the velocity profile in the liquid layer a mathematical description of hydrodynamic processes was proposed and solved numerically. The res...