Towards More Precise Targeting of Inhaled Aerosols to Different Areas of the Respiratory System.

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during the aerosolization of liquids or powders and the role of aerosol flow dynamics in the RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Through an analysis of existing technical limitations, selected strategies aimed at enhancing the effectiveness of targeted aerosol delivery to the RS have been identified and presented. These strategies also include the use of smart inhaling devices and systems with built-in AI algorithms.

Impact of Natural-Based Viscosity Modifiers of Inhalation Drugs on the Dynamic Surface Properties of the Pulmonary Surfactant.

The effectiveness of inhalation therapy depends on aerosol size distribution, which determines the penetration and regional deposition of drug in the lungs. As the size of droplets inhaled from medical nebulizers varies depending on the physicochemical properties of the nebulized liquid, it can be adjusted by adding some compounds as viscosity modifiers (VMs) of a liquid drug. Natural polysaccharides have been recently proposed for this purpose and while they are biocompatible and generally recognized as safe (GRAS), their direct influence of the pulmonary structures is unknown. This work studied the direct influence of three natural VMs (sodium hyaluronate, xanthan gum, and agar) on the surface activity of the pulmonary surfactant (PS) measured in vitro using the oscillating drop method. The results allowed for comparing the variations of the dynamic surface tension during breathing-like oscillations of the gas/liquid interface with the PS, and the viscoelastic response of this system, as reflected by the hysteresis of the surface tension. The analysis was done using quantitative parameters, i.e., stability index (SI), normalized hysteresis area (HAn), and loss angle (φ), depending on the oscillation frequency (f). It was also found that, typically, SI is in the range of 0.15-0.3 and increases nonlinearly with f, while φ slightly decreases. The effect of NaCl ions on the interfacial properties of PS was noted, which was usually positive for the size of hysteresis with an HAn value up to 2.5 mN/m. All VMs in general were shown to have only a minor effect on the dynamic interfacial properties of PS, suggesting the potential safety of the tested compounds as functional additives in medical nebulization. The results also demonstrated relationships between the parameters typically used in the analysis of PS dynamics (i.e., HAn and SI) and dilatational rheological properties of the interface, allowing for easier interpretation of such data.

Influence of Physicochemical Properties of Budesonide Micro-Suspensions on Their Expected Lung Delivery Using a Vibrating Mesh Nebulizer.

The efficiency of lung drug delivery of nebulized drugs is governed by aerosol quality, which depends both on the aerosolization process itself but also on the properties of aerosol precursors. This paper determines physicochemical properties of four analogous micro-suspensions of a micronized steroid (budesonide, BUD) and seeks relationships between these properties and the quality of the aerosol emitted from a vibrating mesh nebulizer (VMN). Despite the same BUD content in all tested pharmaceutical products, their physicochemical characteristics (liquid surface tension, viscosity, electric conductivity, BUD crystal size, suspension stability, etc.) are not identical. The differences have a weak influence on droplet size distribution in the mists emitted from the VMN and on theoretical (calculated) regional aerosol deposition in the respiratory system but, simultaneously, there is an influence on the amount of BUD converted by the nebulizer to aerosol available for inhalation. It is demonstrated that the maximum inhaled BUD dose is below 80-90% of the label dose, depending on the nebulized formulation. It shows that nebulization of BUD suspensions in VMN is sensitive to minor dissimilarities among analogous (generic) pharmaceutics. The potential clinical relevance of these findings is discussed.

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.

In silico evaluation of particle transport and deposition in the airways of individual patients with chronic obstructive pulmonary disease.

Inhalation therapy can effectively treat chronic obstructive pulmonary disease (COPD), but the physical factors determining the appropriate aerosol delivery into the targeted airways remain unclear. The problem is nontrivial because pulmonary structures differ among individual patients with COPD and depend on the severity of the disease. In an in silico evaluation, the present study investigates the differences in particle transport and deposition in the airways of three patients with different degrees of COPD. Specific pulmonary airway models were reconstructed based on the computed tomography data of three patients with a different degree of COPD severity. The transport and deposition of inhaled particles in the airways were evaluated in a computational fluid dynamics simulation and a Lagrangian multiphase model. The sizes of the inhaled particles (1.0, 2.5, 5.5, 8.5, and 10.0 µm) were representative of drug particles delivered from inhalation devices, including dry powder inhalers (DPIs). The deposition behaviors of the inhaled particles strongly depended on the individual geometrical structure of the airways. The largest inhaled particles (10.0 µm) were most strongly affected by inertia and were deposited mostly in the oropharynx; consequently, they were rare in the bronchi. In contrast, the smallest inhaled particles (1.0 µm) were effectively delivered distally with the airflow. The spatial distributions and amounts of deposited particles in the airways obviously differed among the three COPD patients. Small particles are preferred as they can penetrate the inner lung regions. The results can assist the design and development of powder formulations and DPIs for patients with various severities of COPD.

Inhaled aerosols: Their role in COVID-19 transmission, including biophysical interactions in the lungs.

The high rate of spreading of COVID-19 is attributed to airborne particles exhaled by infected but often asymptomatic individuals. In this review, the role of aerosols in SARS-CoV-2 coronavirus transmission is discussed from the biophysical perspective. The essential properties of the coronavirus virus transported inside aerosol droplets, their successive inhalation, and size-dependent deposition in the respiratory system are highlighted. The importance of face covers (respirators and masks) in the reduction of aerosol spreading is analyzed. Finally, the discussion of the physicochemical phenomena of the coronavirus entering the surface of lung liquids (bronchial mucus and pulmonary surfactant) is presented with a focus on a possible role of interfacial phenomena in pulmonary alveoli. Information given in this review should be important in understanding the essential biophysical conditions of COVID-19 infection via aerosol route as a prerequisite for effective strategies of respiratory tract protection, and possibly, indications for future treatments of the disease.

Bioactive Betulin and PEG Based Polyanhydrides for Use in Drug Delivery Systems.

In the course of this study, a series of novel, biodegradable polyanhydrides based on betulin disuccinate and dicarboxylic derivatives of poly(ethylene glycol) were prepared by two-step polycondensation. These copolymers can be used as carriers in drug delivery systems, in the form of microspheres. Betulin and its derivatives exhibit a broad spectrum of biological activity, including cytotoxic activity, which makes them promising substances for use as therapeutic agents. Microspheres that were prepared from betulin based polyanhydrides show promising properties for use in application in drug delivery systems, including inhalation systems. The obtained copolymers release the active substance-betulin disuccinate-as a result of hydrolysis under physiological conditions. The use of a poly(ethylene glycol) derivative as a co-monomer increases the solubility and bioavailability of the obtained compounds. Microspheres with diameters in the range of 0.5-25 µm were prepared by emulsion solvent evaporation method and their physicochemical and aerodynamic properties were analyzed. The morphological characteristics of the microspheres depended on the presence of poly(ethylene glycol) (PEG) segment within the structure of polyanhydrides. The porosity of the particles depended on the amount and molecular weight of the PEG used and also on the speed of homogenization. The most porous particles were obtained from polyanhydrides containing 20% wt. of PEG 600 by using a homogenization speed of 18,000 rpm.

Interfacial rheology for the assessment of potential health effects of inhaled carbon nanomaterials at variable breathing conditions.

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 and Sµ provides a new way to evaluate of a possible disturbance of the basic functions of LS. The results show that the expected pulmonary effects caused by inhaled CNMs at variable breathing rate depend not only on particle concentration (inhaled dose) but also on their size, structure and surface properties.

Impact of physicochemical properties of nasal spray products on drug deposition and transport in the pediatric nasal cavity model.

The study is focused on the analysis of physicochemical properties of selected nasal sprays of mometasone furoate, and the influence of these properties on aerosol quality and penetration in the pediatric nose. After the determination of drugs surface tension and viscosity, spray geometry and size distribution of aerosol droplets, the topical delivery of each drug to different parts of the pediatric model of the nose with the flexible vestibule was evaluated by colorimetric visualization. All tested drugs are pseudo-plastic liquids, showing some differences in flow consistency constant k (range 714-1422) and flow behavior index n (range 0.16-0.31). At no-flow conditions, all sprays are deposited mainly in the anterior of the nasal cavity and the septum (2-3 cm from the nostril), as a result of inertial impaction of large droplets. The deposition range is slightly influenced by the geometry of the aerosol cloud, which, in turn, depends both on drug properties and the type of the spraying nozzle. Deposition experiments accompanied by the airflow show an enhancement of drug transport to deeper parts of the nasal cavity (up 4-6 cm from the vestibule), and this effect can be attributed to the secondary effects of spreading of the deposited liquid layer along the narrow air passages in the nose. Plume geometry, dose volume and rheological properties of the drug were shown to be important factors in the spray penetration pattern in the pediatric nose. The deepest delivery can be expected for drugs of low viscosity and short aerosol plumes.

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).

Inhalation devices: from basic science to practical use, innovative vs generic products.

INTRODUCTION: 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.

Predicted Deposition of E-Cigarette Aerosol in the Human Lungs.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Selected Engineering and Physicochemical Aspects of Systemic Drug Delivery by Inhalation.

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.

Effect of clay nanoparticles on model lung surfactant: a potential marker of hazard from nanoaerosol inhalation.

This work investigates influence of different aluminosillicate nanoparticles (NPs) which are found in air in selected workplaces on the properties of the phospholipid (DPPC) monolayer at air-saline interface considered as ex vivo model of the lung surfactant (LS). The measurements were done under physiological-like conditions (deformable liquid interface at 37 °C) for NP concentrations matching the calculated lung doses after exposure in the working environment. Measured surface pressure-area (π-A) isotherms and compressibility curves demonstrated NP-induced changes in the structure and mechanical properties of the lipid monolayer. It was shown that hydrophilic nanomaterials (halloysite and bentonite) induced concentration-dependent impairment of DPPC's ability of attaining high surface pressures on interfacial compression, suggesting a possibility of reduction of physiological function of natural LS. Hydrophobic montmorillonites affected DPPC monolayer in the opposite way; however, they significantly changed the mechanical properties of the air-liquid interface during compression. The results support the hypothesis of possible reduction or even degradation of the natural function of the lung surfactant induced by particle-phospholipid interactions after inhalation of nanoclays. Presented data do not only supplement the earlier results obtained with another LS model (animal-derived surfactant in oscillating bubble experiments) but also offer an explanation of physicochemical mechanisms responsible for detrimental effects which arise after deposition of inhaled nanomaterials on the surface of the respiratory system.

Nanosized and Nanostructured Particles in Pulmonary Drug Delivery.

Nanosized objects can be used as the drug carriers with specific functionalities which are introduced to the body via the respiratory system, i.e., by inhalation. They can be carried in as aerosol nanoparticles (NPs), nanostructured particles (NSPs) or components of nanosuspensions atomized into micrometer-sized droplets. In the first part of the paper physical factors required for the effective inhalation of nanocarriers are discussed, including the flow dynamics of NPs and NSPs in the respiratory tract. Selected problems related to designing of the required properties of inhalable drug carriers are also addressed. In the next part of the paper, the importance of direct physicochemical interactions between deposited nanoparticles and pulmonary fluids (pulmonary surfactant and bronchial mucus) is emphasized. This perspective allows for a more rational definition of the efficient strategies of the delivery of nanoparticle drug carriers via inhalation.

Deposition of intranasal glucocorticoids--preliminary study.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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.

Aerosolized albuterol sulfate delivery under neonatal ventilatory conditions: in vitro evaluation of a novel ventilator circuit patient interface connector.

BACKGROUND: Aerosolized medications that have been used in infants receiving ventilatory support have not been shown to be effective clinically among the smallest patients. The aim of this study was to characterize the delivery of aerosolized albuterol sulfate in vitro under simulated neonatal ventilatory conditions using a novel ventilator circuit/patient interface connector. METHODS: A Babylog(®) ventilator (VN500(®); Draeger), a novel ventilator circuit/patient interface (VC) connector (Afectair(®); Discovery Laboratories, Inc.), a TwinStar(®) HME (Draeger) low-volume filter, and either a test lung (Draeger) or lung simulator ASL 5000(®) (IngmarMed) were used. Intermittent mandatory ventilation conditions were set to replicate the most typical ventilation conditions for premature infants. Continuous positive airway pressure was also used to measure aerosol delivery with active respiratory drive from the patient. Albuterol sulfate (0.5 mg/mL) was loaded into the drug reservoir of a Misty Finity(®) nebulizer (Airlife(®); Cardinal Health) and connected to the ventilator circuit either via a "T" connector as described by the manufacturer [standard of care (SoC)] or via the VC connector. Albuterol extracted from the filters was analyzed using qualified high-performance liquid chromatography. In addition, a laser diffraction spectrometry (Spraytec(®); Malvern) and white-light spectrometry (Welas model 2100; Palas GmbH) were used to determine particle size distribution (PSD). RESULTS: Compared with SoC, the amount of albuterol delivered using the VC connector was significantly greater (p<0.001) under simulated neonatal ventilatory conditions. Additionally, the PSD profile of albuterol sulfate delivered using the VC connector was more representative of the PSD profile directly from the nebulizer. CONCLUSIONS: The use of the VC connector increased the delivery of albuterol sulfate and resulted in a PSD profile at the patient interface that is more consistent with the PSD profile of the selected nebulizer when compared with SoC. This VC connector may be a useful, new approach for the delivery of aerosolized medications to neonates requiring positive pressure ventilatory support.

Alteration of biophysical activity of pulmonary surfactant by aluminosilicate nanoparticles.

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.