Innovative high fat diet establishes a novel zebrafish model for the study of visceral obesity.

Obesity is a complex chronic condition associated with multiple health risks, including visceral obesity, which is particularly detrimental. To gain insight into the mechanisms underlying obesity and its associated pathologies, a novel zebrafish model was established using an innovative high-fat diet (HFD). The primary goal was to induce visceral obesity in zebrafish and study the associated structural changes. To achieve this, a unique HFD consisting of 40% beef fat (HFD40) was developed and supplemented with magnesium aluminometasilicate to improve stability in a high humidity environment. Feeding regimens were initiated for both juvenile (starting at 2 weeks post-fertilization, lasting 18 weeks) and adult zebrafish (3 months post-fertilization, 8 weeks feeding duration). The innovative dietary approach successfully induced visceral obesity in both juvenile and adult zebrafish. This new model provides a valuable tool to study obesity-related pathologies, metabolic syndrome, and potential therapeutic interventions. Most importantly, the low-cost and easy-to-prepare composition of HFD40 was seamlessly incorporated into the water without the need for separation, was readily absorbed by the fish and induced rapid weight gain in the zebrafish population. In conclusion, this study presents a novel HFD40 composition enriched with a high beef fat concentration (40%), which represents a significant advance in the development of an experimental zebrafish model for the study of visceral obesity and associated metabolic changes.

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.

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.

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.

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.