Tomasz R. Sosnowski

Dynamics of Oropharyngeal Aerosol Transport and Deposition With the Realistic Flow Pattern

Aerosol flow and deposition in the model of human oropharynx was studied theoretically and experimentally for two realistic inspiratory patterns. The three-dimensional (3D) airflow structure in the sample geometry was solved with the computational fluid dynamics (CFD) code (Fluent), used to calculate dynamic distribution of particle deposition (0.3–10 μm). Experiments were done for the same flow conditions using the silicone-rubber cast with the matching geometry. Nonsteady breathing flows were reproduced with the computer-controlled artificial lung apparatus. Results of computations show that particles smaller than 3 μm easily pass the oropharynx during inspiration, while particles with a size close to 10 μm are substantially deposited, preferentially in the region of the naso-pharyngeal bend. For particles in the submicrometer size range, the spatial and temporal deposition pattern is more complicated, and strongly depends on breathing dynamics. The experiments confirmed that the mass median diameter (MMD) of the aerosol that penetrates the oropharynx and flows to the tracheobronchial tree is reduced. Measured total mass efficiency of deposition of the tested aerosol was in the range of 35–60%, depending on the breathing pattern. These findings are consistent with the CFD results. The methods and the preliminary results enable a more realistic analysis of dynamic effects during the flow of inhaled particles through the complex geometry of the oropharynx. Such analysis is needed for estimation of toxic potential of aerosols, related to their local deposition in different parts of the respiratory tract.

Alteration of biophysical activity of pulmonary surfactant by aluminosilicate nanoparticles

Abstract The influence of five different types of aluminosilicate nanoparticles (NPs) on the dynamic surface activity of model pulmonary surfactant (PS) (Survanta) was studied experimentally using oscillating bubble tensiometry. Bentonite, halloysite and montmorillonite (MM) NPs, which are used as fillers of polymer composites, were characterized regarding the size distribution, morphology and surface area. Particle doses applied in the studies were estimated based on the inhalation rate and duration, taking into account the expected aerosol concentration and deposition efficiency after penetration of NPs into the alveolar region. The results indicate that aluminosilicate NPs at concentrations in the pulmonary liquid above 0.1 mg cm−3 are capable of promoting alterations of the original dynamic biophysical activity of the PS. This effect is indicated by deviation of the minimum surface tension, stability index and the size of surface tension hysteresis. Such response is dependent on the type of NPs present in the system and is stronger when particle concentration increases. It is suggested that interactions between NPs and the PS must be related to the surfactant adsorption on the suspended particles, while in the case of surface-modified clay NPs the additional washout of surface-active components may be expected. It is speculated that observed changes in surface properties of the surfactant may be associated with undesired health effects following extensive inhalation of aluminosilicate NPs in the workplace.

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.

Deposition of Fractal-Like Aerosol Aggregates in a Model of Human Nasal Cavity

Toxicity of diesel exhaust is related to the inhalation of nano-sized fractal-like aerosol aggregates. Their complex behavior (in comparison to spherical particles) should be taken into account in deposition modeling. The deposition of aerosol fractal-like aggregates in the model of a human nose was studied numerically for the flow rate corresponding to breathing conditions. The simplified geometry of the human nasal replica was implemented in the computational fluid dynamics (CFD) code (FLUENT) used for calculation of the three-dimensional airflow structure. A Brownian dynamic (BD) algorithm was applied for determination of the aggregates deposition in the nasal cavity during inhalation. These calculations were carried out for several populations of aggregates. The values of parameters used in the BD simulations for characterization of fractal-like aggregates, that is, fractal dimension (Df) and the radius of gyration (Rg), were in the range of 1.7–2.1 and 0.24–0.36 μm, respectively. These are the representative values for soot aggregates emitted from diesel engines. The results of computation show approximately 20% penetration of submicrometer aggregates through the nose and a weak dependence of deposition efficiency on Df and Rg values. The proposed methodology may lead to a more realistic description of deposition of nonspherical aerosol particles in the respiratory system. A more sophisticated approach for description of fractal-like aggregates dynamics is suggested for future studies.

Interactions of Benzo[a]pyrene and Diesel Exhaust Particulate Matter with the Lung Surfactant System

One of the reasons for cellular changes in the lung tissue exposed to the diesel exhaust composed of soot particles with adsorbed volatile organic molecules is the reduction of the clearance rate in the pulmonary region of the respiratory system. The interaction of the fractal-like particles and organic substances with a surfactant monolayer limits its dynamic activity. The surface properties of Survanta, a purified extract of bovine lung surfactant (LS), which interacted with carbon particles (200 nm aggregates) and benzo[a]pyrene (BaP), molecules were measured with the oscillating bubble technique. The results showed a significant lowering of the dynamics of the surfactant monolayer compared to the control case (no exposure). Additional measurements of surface pressure during the monotonic compression of the air-water interface containing the major LS phospholipid, dipalmitoylphosphatidylcholine (DPPC), showed that the presence of BaP molecules in the system influenced its stability. The experimental results were supplemented with a theoretical molecular dynamics model of the interaction between BaP and DPPC molecules. The simulation results indicated the insertion of BaP molecules into the lipid layer, which explained the measured effects.

Deactivation of the Pulmonary Surfactant Dynamics by Toxic Aerosols and Gases

Interactions between selected toxic aerosols and gases occurring in the air at the workplace and the pulmonary surfactant (PS) have been studied with two physicochemical techniques in vitro. The Pulsating Bubble Surfactometer (PBS) and the Langmuir-Wilhelmy Balance (LWB) have been used for measurements of dynamic interfacial properties of the PS material after its contact with several gases (sulfur dioxide, nitrogen oxides, ozone, ammonia) and liquids (sulfuric, nitric and hydrochloric acids and ammonium hydroxide), which can be brought into the alveoli with the inhaled air. Surface tension-area relationships for the interface oscillations have been analyzed using qualitative criteria of normalized hysteresis area (HA(N)) and minimum surface tension (sigma(min)). It was demonstrated that, for each analyzed compound, inactivation of the surfactant occurs, but the critical concentrations and doses are compound specific, which suggests the toxic potential of the investigated substances with respect to PS. Possible mechanisms of the interactions between the investigated substances and the surfactant components are discussed. Degradation of the PS dynamical interfacial properties (HA(N) and sigma(min)), important from the physiological viewpoint, observed in our in vitro experiments, suggests a possibility of adverse health effect in the case of a chronic inhalation of toxic gases and aerosols, even at low concentration or after a short exposure to strongly contaminated air. It results in a slowdown of the pulmonary clearance rate and increase of the lung burden for both considered cases.

Interaction of Deposited Aerosol Particles with the Alveolar Liquid Layer

The kinetics of retention of inhaled particles in the human respiratory system is determined by the course of two complex processes — particle deposition and clearance rates.

Assessment of the Pulmonary Toxicity of Inhaled Gases and Particles With Physicochemical Methods

Physicochemical techniques used for evaluating the pulmonary surfactant (PS) quality are discussed as methods useful in assessing toxicity of inhaled gases and particles. Two standard devices, Langmuir-Wilhelmy film balance and pulsating bubble apparatus, are presented in detail, and the measured results of interaction between sulfuric acid and 2 models of PS materials are analyzed. The evident decrease in surface activity of the pulmonary surfactant after its contact with the acid at concentrations approaching 0.001 M may be considered as an indicator of the adverse effect, which can result in several health problems. The presented approach can be used as a method of assessing pulmonary toxicity of any substances present in the breathing air.

Preparation and Characterization of Biocompatible Polymer Particles as Potential Nanocarriers for Inhalation Therapy

Aim. Investigation of the possibility of manufacturing biocompatible polymer particles which have the required properties for pulmonary delivery via inhalation and simultaneously act as vehicles of nanotherapeutics. Methods. Nanostructures were obtained from biocompatible polysaccharides by successive oxidation and reactive coiling in the aqueous phase. The resultant nanosuspensions of PAD (polyaldehyde dextran) and DACMC (dialdehyde carbomethylcellulose) were used as precursors in spray drying production of powders at variable process conditions. The resultant dry microparticles were characterized by SEM observations, and their properties related to delivery by inhalation were determined by laser diffraction spectrometry following the dispersion in the commercial inhaler. Finally, the possibility of the reconstitution of nanosuspensions by powders rehydration was evaluated. Results. Synthesized nanoparticles had size of 120–170 nm. Microparticles after drying had size of 0.5–5 µm and different surface morphology. Aerosolized particles obtained from powder dispersion in the inhaler had the volumetric median diameter of ~2 and ~1 µm for PAD and DACMC, respectively. Hydration of powders led to restoring the nanosuspensions with the average particle size similar to the precursor. Conclusions. PAD and DACMC can be used to obtain nanostructures which, after processing, take a form suitable for effective delivery to the lungs via inhalation.

Experimental Evaluation of the Importance of the Pulmonary Surfactant for Oxygen Transfer Rate in Human Lungs.

The rate of oxygen transport from atmospheric air into water and perfluorocarbon compound (PFC) was investigated. Static and dynamic systems with and without the presence of the lung surfactant monolayer were considered. For the case of water used as an oxygen absorbent, the monolayer activity allowed a simulation of the gas uptake into the lung hypophase. In the second case, a two-phase liquid system with water as a hypophase and PFC as the blood substitute simulated oxygen transport in the alveolus-blood system. Original experimental measurement devices gave the opportunity of determining the gas transport rate with the possibilities of indicating the role of the lung surfactant in the process and evaluating the influence of environmental conditions on the transport phenomena. Results of that work suggest a possible enhancing role of the lung surfactant in the oxygen transfer rate.