Interactions between O2 Nanobubbles and the Pulmonary Surfactant in the Presence of Inhalation Medicines.

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-Wilhelmy trough and the oscillating droplet tensiometer. The results indicate that the presence of NBs has a minor effect on the dynamic characteristics of the air-liquid interface, which is the desired effect in the context of a potential use in inhalation therapies.

Aqueous dispersions of oxygen nanobubbles for potential application in inhalation therapy.

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.

Independent Lung Ventilation-Experimental Studies on a 3D Printed Respiratory Tract Model.

Independent lung ventilation (ILV) is a life-saving procedure in unilateral pulmonary pathologies. ILV is underused in clinical practice, mostly due to the technically demanding placement of a double lumen endotracheal tube (ETT). Moreover, the determination of ventilation parameters for each lung in vivo is limited. In recent years, the development of 3D printing techniques enabled the production of highly accurate physical models of anatomical structures used for in vitro research, considering the high risk of in vivo studies. The purpose of this study was to assess the influence of double-lumen ETT on the gas transport and mixing in the anatomically accurate 3D-printed model of the bronchial tree, with lung lobes of different compliances, using various ventilation modes. The bronchial tree was obtained from Respiratory Drug Delivery (RDD Online, Richmond, VA, USA), processed and printed by a dual extruder FFF 3D printer. The test system was also composed of left side double-lumen endotracheal tube, Siemens Test Lung 190 and anesthetic breathing bag (as lobes). Pressure and flow measurements were taken at the outlets of the secondary bronchus. The measured resistance increased six times in the presence of double-lumen ETT. Differences between the flow distribution to the less and more compliant lobe were more significant for the airways with double-lumen ETT. The ability to predict the actual flow distribution in model airways is necessary to conduct effective ILV in clinical conditions.

Particle Size Dynamics: Toward a Better Understanding of Electronic Cigarette Aerosol Interactions With the Respiratory System.

The knowledge of possible acute and long-term health effects of aerosols inhaled from electronic cigarettes (ECs) is still limited partially due to incomplete awareness of physical phenomena related to EC-aerosol dynamics. This short review discusses the basic processes of aerosol transformation (dynamics) upon inhalation, indicating also the need for the accurate determination of the size of droplets in the inhaled EC-mist. The significance of differences in the aerosol particle size distribution for the prediction of regional deposition of inhaled mist in the respiratory system is highlighted as a decisive factor in the interactions of inhaled EC-aerosols with the organism.

Physicochemical studies of direct interactions between lung surfactant and components of electronic cigarettes liquid mixtures.

Direct physicochemical interactions between the major components of electronic cigarette liquids (e-liquids): glycerol (VG) and propylene glycol (PG), and lung surfactant (LS) were studied by determining the dynamic surface tension under a simulated breathing cycle using drop shape method. The studies were performed for a wide range of concentrations based on estimated doses of e-liquid aerosols (up to 2500 × the expected nominal concentrations) and for various VG/PG ratios. The results are discussed as relationships among mean surface tension, surface tension amplitude, and surface rheological properties (dilatational elasticity and viscosity) versus concentration and composition of e-liquid. The results showed that high local concentrations (>200 × higher than the estimated average dose after a single puffing session) may induce measurable changes in biophysical activity of LS; however, only ultra-high e-liquid concentrations inactivated the surfactant. Physiochemical characterization of e-liquids provide additional insights for the safety assessment of electronic nicotine delivery systems (ENDS).

Conception, preparation and properties of functional carrier particles for pulmonary drug delivery.

BACKGROUND: The effectiveness of aerosol therapy is significantly reduced by the mucus layer covering the airways of the tracheobronchial tree. According to the present concept, drug particles are delivered to the lung together with the functional carrier particle that facilitates both the drug transport into the lungs and the penetration of deposited particles through the mucus. The approach of manufacturing multi-component powders with mucoactive compounds and anti-asthmatic medicines (DSCG) bound together in a single particle is additionally considered. METHODS: Powders were produced with the spray-drying technique from aqueous precursor solutions containing pure low molecular weight dextran, pure mannitol and dextran/mannitol-N-acetyl cysteine (NAC) mixtures (4:1 and 1:1). NAC has been selected for this purpose as a compound, which is known to be mucolytic. Dextran and mannitol are potentially applicable in the field of inhalation drug delivery. They have been used as stabilizers of functional carrier particles. Powders were characterized for their yield and physicochemical properties including: morphology (SEM), moisture content and thermal properties (DSC). Aerosol performance was determined with NGI impactor after standardized aerosolization of the produced powders in a commercial DPI. RESULTS: Particle size distributions of dextran-NAC powders were characterized by high fine particle fraction (45-62%), which assures good particle deposition in the lower airways. The thermodynamic properties of the powders based on the temperature of the glass transition T(g) (50-63 °C) suggest the required stability during storage at moderate humidity. CONCLUSIONS: Preliminary examination of the required properties of these particles confirms their potential as functional carriers for pulmonary drug delivery.