Airway Delivery of Hydrogel-Encapsulated Niclosamide for the Treatment of Inflammatory Airway Disease

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl⁻ currents and intracellular Ca²⁺ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca²⁺ activated Cl⁻ channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca²⁺ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.     

Layer‐by‐Layer Coated Gold Nanoparticles: Size‐Dependent Delivery of DNA into Cells

Because nanoparticles are finding uses in myriad biomedical applications, including the delivery of nucleic acids, a detailed knowledge of their interaction with the biological system is of utmost importance. Here the size‐dependent uptake of gold nanoparticles (AuNPs) (20, 30, 50 and 80 nm), coated with a layer‐by‐layer approach with nucleic acid and poly(ethylene imine) (PEI), into a variety of mammalian cell lines is studied. In contrast to other studies, the optimal particle diameter for cellular uptake is determined but also the number of therapeutic cargo molecules per cell. It is found that 20 nm AuNPs, with diameters of about 32 nm after the coating process and about 88 nm including the protein corona after incubation in cell culture medium, yield the highest number of nanoparticles and therapeutic DNA molecules per cell. Interestingly, PEI, which is known for its toxicity, can be applied at significantly higher concentrations than its IC₅₀ value, most likely because it is tightly bound to the AuNP surface and/or covered by a protein corona. These results are important for the future design of nanomaterials for the delivery of nucleic acids in two ways. They demonstrate that changes in the nanoparticle size can lead to significant differences in the number of therapeutic molecules delivered per cell, and they reveal that the toxicity of polyelectrolytes can be modulated by an appropriate binding to the nanoparticle surface.     

Reactive inkjet printing of polyethylene glycol and isocyanate based inks to create porous polyurethane structures

Reactive inkjet printing offers a direct way to create polymeric structures in situ on a substrate. Therefore, two component polyurethane formulations can be utilized to be used in multicomponent inkjet printing. In this contribution, the use of polyethylene glycol (M = 200 g mol⁻¹), glycerol ethoxylate (M = 1,000 g mol⁻¹), and water (blowing agent) in combination with aliphatic 1,6-hexamethylene diisocyanate or aromatic methylene diphenyl diisocyanate for reactive inkjet printing is evaluated. The inks are jettable on a Dimatix DMP-3000 inkjet printer using a 10 pL piezo driven drop-on-demand printhead showing stable droplet formation. Solid films on glass are formed using a drop-by-drop printing strategy. Layer-by-Layer strategy gives best results on polycarbonate substrates forming porous polyurethane structures. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 46977.     

Efficient moving horizon state and parameter estimation for SMB processes

In this paper, a moving horizon state and parameter estimation scheme for chromatographic simulated moving bed SMB processes is proposed. The simultaneous state and parameter estimation is based on a high-order nonlinear SMB model which incorporates rigorous models of the chromatographic columns and the discrete shiftings of the inlet and outlet ports. The estimation is performed using sparse measurement information: the concentrations of the components are only measured at the two outlet ports (which are periodically switched from one column to the next) and at one fixed location between two columns. The goal is to reconstruct the full state of the system, i.e. the concentration profiles along all columns, and to identify critical model parameters reliably such that the estimated model can be used in the context of online optimizing control. The state estimation scheme is based upon a deterministic model within the prediction horizon, state noise is only present in the state and the parameters prior to and at the beginning of the horizon. By solving the optimization problem with a multiple-shooting method and applying a real-time iteration scheme, the computation times are such that the scheme can be applied online. Numerical simulations of a validated model for a separation problem with nonlinear isotherms of the Langmuir type demonstrate the efficiency of the algorithm.     

Room-Temperature Solubility Behavior of Barium Titanate in Aqueous Media

In the present study, the incongruent dissolution of barium from barium titanate (BaTiO₃) has been studied as a function of dispersion pH and powder volume fraction for two different BaTiO₃ powders. In alkaline dispersions, the barium solubility strongly increases as the pH increases, as suggested by thermodynamic considerations. At pH <7, the barium solubility reaches a plateau, the height of which is dependent on the surface area of the powder and the solids loading of the slip. The BaTiO₃ surface is completely depleted of barium in this region.     

Formation and corrosion of InP/In contacts in hydrochloric acid

Flatband potentials, charge carrier concentrations and their frequency dispersions of p-type and n-type InP in 1.0 M HCl were determined. The cathodic decomposition of InP in this acidic solution is compared with the deposition process of indium from 1.0 M-HCl containing 0.1 M InCl₃. The share of the involved reactions, hydrogen evolution, InP decomposition and indium deposition are investigated. The reaction rates are generally smaller on p-type InP and the reaction speed is much slower but the principal reactions are the same. The kinetics of the indium deposition and dissolution are studied in detail. These reactions are discussed in terms of the preparation of watersplitting photoelectrodes with modified surfaces.     

NUMERICAL INVESTIGATION OF TRANSPORT PHENOMENA IN THE FUSION ZONE OF LASER BEAM WELDED JOINTS

The development of a steady-state process model for a numerical study of transport phenomena in the fusion zone of deep penetration laser beam welded joints is described. Based on the conservation equations of energy, momentum, and mass in dimensionless form, the three-dimensional modeling considers viscous, buoyancy, and friction forces as well as surface tension gradients. The developed simulation program enables the prediction of the local temperature and velocity distribution in the molten material. Consequently, the resultant weld pool dimensions dependent on the characteristic dimensionless groups can be derived.     

Structure,stability and permeation properties of NaA zeolite membranes for H2O/H2 and CH3OH/H2 separations

NaA zeolite membranes were synthesised in the secondary growth hydrothermal method based on the seeding of the inner surface of a ceramic α-alumina tube. The impacts of crystallisation time and zeolite precursor concentration (in H₂O) were investigated. The structure and stability of the prepared NaA zeolite membranes were also investigated with operating temperatures, times and pressures. The results indicate that the optimal synthesis gel molar composition was 3Na₂O: 2SiO₂: Al₂O₃: 200H₂O. This led to cubic-shaped NaA zeolite which showed good stability. The optimal NaA zeolite membrane had H₂O and CH₃OH fluxes of 2.77 and 0.19 kg/m²h, with H₂O/H₂ and CH₃OH/H₂ separation factors of ∞ and 0.09 at a temperature of 30 °C. The NaA zeolite membrane had high thermal stability, but poor separation performance at high temperature (240 °C). The results suggested that the H₂ permeation flux is significantly influenced by preferential adsorption of vapour in the NaA zeolite membrane.