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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
Room temperature ionic liquids (RTIL) are an emerging class of electrolytes enabling high cell voltages and, in return, high energy density of advanced supercapacitors. Yet, the low temperature behavior, including freezing and thawing, is little understood when confined in the narrow space of nanopores. This study shows that RTILs may show a tremendously different thermal behavior when comparing bulk with nanoconfined properties as a result of the increased surface energy of carbon pore walls. In particular, continuous increase in viscosity is accompanied with slowed-down charge/discharge kinetics during in-situ electrochemical characterization. Freezing reversibly collapses the energy storage ability - while thawing fully restores the initial energy density of the material. For the first time, a different thermal behavior in positively and negatively polarized electrodes is demonstrated. This leads to different freezing and melting points in the two electrodes. Compared to bulk, RTIL in the confinement of electrically charged nanopores, shows the unique behavior of being highly affine for supercooling; that is, the electrode freezing during heating.
