Cylindrical Microparticles Composed of Mesoporous Silica Nanoparticles for the Targeted Delivery of a Small Molecule and a Macromolecular Drug to the Lungs: Exemplified with Curcumin and siRNA

The transport of macromolecular drugs such as oligonucleotides into the lungs has become increasingly relevant in recent years due to their high potency. However, the chemical structure of this group of drugs poses a hurdle to their delivery, caused by the negative charge, membrane impermeability and instability. For example, siRNA to reduce tumour necrosis factor alpha (TNF-α) secretion to reduce inflammatory signals has been successfully delivered by inhalation. In order to increase the effect of the treatment, a co-transport of another anti-inflammatory ingredient was applied. Combining curcumin-loaded mesoporous silica nanoparticles in nanostructured cylindrical microparticles stabilized by the layer-by-layer technique using polyanionic siRNA against TNF-α was used for demonstration. This system showed aerodynamic properties suited for lung deposition (mass median aerodynamic diameter of 2.85 ± 0.44 µm). Furthermore, these inhalable carriers showed no acute in vitro toxicity tested in both alveolar epithelial cells and macrophages up to 48 h incubation. Ultimately, TNF-α release was significantly reduced by the particles, showing an improved activity co-delivering both drugs using such a drug-delivery system for specific inhibition of TNF-α in the lungs

Mechanisms of bonding effected by nanoparticles in zirconia coatings applied by spraying of suspensions

Zirconia coatings consisting of a mixture of coarse and fine grained zirconia powders prepared by spraying of suspensions and subsequent thermal treatment at limited temperatures (up to 500°C) are poor in adherence and in intrinsic mechanical strength. We have shown elsewhere that mechanical properties of these coatings can be improved clearly by adding a small amount of nanoscaled zirconia. Here, the structural and the chemical development of this coating material and of the nanoparticles is examined to gain information about the underlying bonding mechanisms. The applied temperature is relatively low in comparison to the usual onset temperature of accelerated sintering. Nevertheless, the results show that diffusion controlled material transport mechanisms play their role in bonding. The condensation of surface OH groups may participate in bonding, too. These first results confirm the potential of nanoparticles to act as inorganic binder. Additional research effort to clarify the underlying mechanisms in detail is of interest. For the practical side, it can be concluded that the resulting effect of mechanical consolidation of ceramic structures at relatively low temperatures enables new ceramic applications, for example a new type of ceramic coatings on metallic substrates

Cylindrical Microparticles Composed of Mesoporous Silica Nanoparticles for the Targeted Delivery of a Small Molecule and a Macromolecular Drug to the Lungs: Exemplified with Curcumin and siRNA

The transport of macromolecular drugs such as oligonucleotides into the lungs has become increasingly relevant in recent years due to their high potency. However, the chemical structure of this group of drugs poses a hurdle to their delivery, caused by the negative charge, membrane impermeability and instability. For example, siRNA to reduce tumour necrosis factor alpha (TNF-α) secretion to reduce inflammatory signals has been successfully delivered by inhalation. In order to increase the effect of the treatment, a co-transport of another anti-inflammatory ingredient was applied. Combining curcumin-loaded mesoporous silica nanoparticles in nanostructured cylindrical microparticles stabilized by the layer-by-layer technique using polyanionic siRNA against TNF-α was used for demonstration. This system showed aerodynamic properties suited for lung deposition (mass median aerodynamic diameter of 2.85 ± 0.44 µm). Furthermore, these inhalable carriers showed no acute in vitro toxicity tested in both alveolar epithelial cells and macrophages up to 48 h incubation. Ultimately, TNF-α release was significantly reduced by the particles, showing an improved activity co-delivering both drugs using such a drug-delivery system for specific inhibition of TNF-α in the lungs

Preparation of acoustic lenses by mechano-chemical synthesis and electrophoretic deposition of lead zirconium titanate (PZT) films

PZT powders has been synthesized via reactive dry milling using PbZrO3 and PbTiO3 as starting materials. Stabel suspensions of the PZT particles in ethanol (d50(Vol) = 115 nm) were obtained by a chemomechanical dispersion step. Teh electrophoretic deposition has been optimized varying the cell voltage and the PZT solid content in the suspension. PZT films have been deposited on platinum coated saphire. After drying, the films are densely packed and free of cracks. By using lithium acetate and lead acetate as a sinter aid it was possible to reduce the sintering temperature to 1050°C. A good electrode has been sputtered onto the piezoelectric films which then have been poled by the corona method. The circular PZT dots (...) with a thickness of 1 µm show the expected oscillation resonance at about 2 GHz and can be used in acoustic lenses, for example in acoustic microscopes

Preparation of acoustic lenses by mechanochemical synthesis and electrophoretic deposition of lead zirconium titanate (PZT) films

PZT powders has been synthesized via reactive dry milling using PbZrO3 and PbTiO3 as starting materials. Stabel suspensions of the PZT particles in ethanol (d50(Vol) = 115 nm) were obtained by a chemomechanical dispersion step. Teh electrophoretic deposition has been optimized varying the cell voltage and the PZT solid content in the suspension. PZT films have been deposited on platinum coated saphire. After drying, the films are densely packed and free of cracks. By using lithium acetate and lead acetate as a sinter aid it was possible to reduce the sintering temperature to 1050°C. A good electrode has been sputtered onto the piezoelectric films which then have been poled by the corona method. The circular PZT dots (...) with a thickness of 1 µm show the expected oscillation resonance at about 2 GHz and can be used in acoustic lenses, for example in acoustic microscopes

Mechanisms of bonding effected by nanoparticles in zirconia coatings applied by spraying of suspensions

Zirconia coatings consisting of a mixture of coarse and fine grained zirconia powders prepared by spraying of suspensions and subsequent thermal treatment at limited temperatures (up to 500°C) are poor in adherence and in intrinsic mechanical strength. We have shown elsewhere that mechanical properties of these coatings can be improved clearly by adding a small amount of nanoscaled zirconia. Here, the structural and the chemical development of this coating material and of the nanoparticles is examined to gain information about the underlying bonding mechanisms. The applied temperature is relatively low in comparison to the usual onset temperature of accelerated sintering. Nevertheless, the results show that diffusion controlled material transport mechanisms play their role in bonding. The condensation of surface OH groups may participate in bonding, too. These first results confirm the potential of nanoparticles to act as inorganic binder. Additional research effort to clarify the underlying mechanisms in detail is of interest. For the practical side, it can be concluded that the resulting effect of mechanical consolidation of ceramic structures at relatively low temperatures enables new ceramic applications, for example a new type of ceramic coatings on metallic substrates

Current Opinions on Optimal Management of Basilar Artery Occlusion: After the BEST of BASICS Survey

Background The best management of basilar artery occlusion (BAO) remains uncertain. The BASICS (Basilar Artery International Cooperation Study) and the BEST (Basilar Artery Occlusion Endovascular Intervention Versus Standard Medical Treatment) trials reported neutral results. We sought to understand physicians’ approaches to BAOs and whether further BAO randomized controlled trials were warranted. Methods We conducted an online international survey from January to March 2022 to stroke neurologists and neurointerventionalists. Survey questions were designed to examine clinical and imaging parameters under which clinicians would offer (or rescind) a patient with BAO to endovascular therapy (EVT) or best medical management versus enrollment into a randomized clinical trial. Results Of >3002 invited participants, 1245 responded (41.4% response rate) from 73 countries, including 54.7% stroke neurologists and 43.6% neurointerventionalists. More than 95% of respondents would offer EVT to patients with BAO, albeit in various clinical circumstances. There were 70.0% of respondents who indicated that the BASICS and BEST trials did not change their practice. Only 22.1% of respondents would perform EVT according to anterior circulation occlusion criteria. The selection of patients for BAO EVT by clinical severity, timing, and imaging modality differed according to geography, specialty, and country income level. Over 80% of respondents agreed that further randomized clinical trials for BAO were warranted. Moreover, 45.6% of respondents indicated they would find it acceptable to enroll all trial‐eligible patients into the medical arm of a BAO trial, whereas 26.3% would not enroll. Conclusion Most stroke physicians continue to believe in the efficacy of EVT in selected patients with BAO in spite of BEST and BASICS. There is no consensus on which selection criteria to use, and few clinicians would use anterior circulation occlusion criteria for BAOs. Further randomized clinical trials for BAO are warranted

Inshore and offshore marine migration pathways of Atlantic salmon post-smolts from multiple rivers in Scotland, England, Northern Ireland and Ireland

The migratory behavior of Atlantic salmon (Salmo salar) post-smolts in coastal waters is poorly understood. In this collaborative study, 1914 smolts, from 25 rivers, in four countries were tagged with acoustic transmitters during a single seasonal migration. In total, 1105 post-smolts entered the marine study areas and 438 (39.6%) were detected on a network of 414 marine acoustic receivers and an autonomous underwater vehicle. Migration pathways (defined as the shortest distance between two detections) of up to 575 km and over 100 days at sea were described for all 25 populations. Post-smolts from different rivers, as well as individuals from the same river, used different pathways in coastal waters. Although difficult to generalize to all rivers, at least during the year of this study, no tagged post-smolts from rivers draining into the Irish Sea were detected entering the areas of sea between the Hebrides and mainland Scotland, which is associated with a high density of finfish aquaculture. An important outcome of this study is that a high proportion of post-smolts crossed through multiple legislative jurisdictions and boundaries during their migration. This study provides the basis for spatially explicit assessment of the impact risk of coastal pressures on salmon during their first migration to sea

Inshore and offshore marine migration pathways of Atlantic salmon post-smolts from multiple rivers in Scotland, England, Northern Ireland, and Ireland

The migratory behavior of Atlantic salmon (Salmo salar) post-smolts in coastal waters is poorly understood. In this collaborative study, 1914 smolts, from 25 rivers, in four countries were tagged with acoustic transmitters during a single seasonal migration. In total, 1105 post-smolts entered the marine study areas and 438 (39.6%) were detected on a network of 414 marine acoustic receivers and an autonomous underwater vehicle. Migration pathways (defined as the shortest distance between two detections) of up to 575 km and over 100 days at sea were described for all 25 populations. Post-smolts from different rivers, as well as individuals from the same river, used different pathways in coastal waters. Although difficult to generalize to all rivers, at least during the year of this study, no tagged post-smolts from rivers draining into the Irish Sea were detected entering the areas of sea between the Hebrides and mainland Scotland, which is associated with a high density of finfish aquaculture. An important outcome of this study is that a high proportion of post-smolts crossed through multiple legislative jurisdictions and boundaries during their migration. This study provides the basis for spatially explicit assessment of the impact risk of coastal pressures on salmon during their first migration to sea