Inhaled Nanoformulated mRNA Polyplexes for Protein Production in Lung Epithelium

Noninvasive aerosol inhalation is an established method of drug delivery to the lung, and remains a desirable route for nucleic‐acid‐based therapeutics. In vitro transcribed (IVT) mRNA has broad therapeutic applicability as it permits temporal and dose‐dependent control of encoded protein expression. Inhaled delivery of IVT‐mRNA has not yet been demonstrated and requires development of safe and effective materials. To meet this need, hyperbranched poly(beta amino esters) (hPBAEs) are synthesized to enable nanoformulation of stable and concentrated polyplexes suitable for inhalation. This strategy achieves uniform distribution of luciferase mRNA throughout all five lobes of the lung and produces 101.2 ng g^?1 of luciferase protein 24 h after inhalation of hPBAE polyplexes. Importantly, delivery is localized to the lung, and no luminescence is observed in other tissues. Furthermore, using an Ai14 reporter mouse model it is identified that 24.6% of the total lung epithelial cell population is transfected after a single dose. Repeat dosing of inhaled hPBAE‐mRNA generates consistent protein production in the lung, without local or systemic toxicity. The results indicate that nebulized delivery of IVT‐mRNA facilitated by hPBAE vectors may provide a clinically relevant delivery system to lung epithelium.     

Crosslinked blends of poly(lactic acid) and polyacrylates: AFM, DSC and XRD studies

The blends based on poly(lactic acid), (PLA) and polyacrylates (1:1 weight ratio) have been prepared by photopolymerization of three different multifunctional acrylate monomers (pentaerythritol triacrylate, pentaerythritol tetraacrylate and dipentaerythritol pentaacrylate) in matrix of linear PLA. The structure of these systems has been studied by Atomic Force Microscopy (AFM), Differential Scanning Calorimetry (DSC) and X-ray Diffraction (XRD). It was found that the blends are highly crosslinked, rough, heterogeneous and some of them – semicrystalline. The effect of UV-irradiation on surface morphology of obtained mixtures was studied. The viscometry has been applied for measurements of changes of PLA molecular weight resulting of photodegradation. It was shown that blends are much more photostable than pure PLA.     

Electrotactile adaptation on the abdomen: preliminary results.

Electrotactile (electrocutaneous) stimulation at currents greater than sensation threshold causes sensory adaptation, which temporarily raises the sensation threshold and reduces the perceived magnitude of stimulation. After 15 min of moderately intense exposure to a conditioning stimulus (10 s on, 10 s off), the sensation threshold elevation for seven observers was 60-270%, depending on the current, frequency, and number of pulses in the burst structure of the conditioning stimulus. Increases in any of these parameters increased the sensation threshold elevation. Adaptation and recovery were each complete in approximately 15 min.     

The microstructure of erbium-ytterbium co-doped oxyfluoride glass-ceramic optical fibers

Oxyfluoride transparent glass-ceramics combine some features of glasses (easier shaping or lower than single crystals cost of fabrication) and some advantages of rare-earth doped single crystals (narrow absorption/emission lines and longer lifetimes of luminescent levels). Since the material seems to be promising candidate for efficient fiber amplifiers, the manufacturing as well as structural and optical examination of the oxyfluoride glass-ceramic fibers doped with rare-earth ions seems to be a serious challenge. In the first stage oxyfluoride glasses of the following compositions 48SiO₂-11Al₂O₃-7Na₂CO₃-10CaO-10PbO-11PbF₂-3ErF₃ and 48SiO₂-11Al₂O₃-7Na₂CO₃-10CaO-10PbO-10PbF₂-3YbF₃-1ErF₃ (in molar%) were fabricated from high purity commercial chemicals (Sigma-Aldrich). The fabricated glass preforms were drawn into glass fibers using the mini-tower. Finally, the transparent Er³⁺ doped and Er³⁺/Yb³⁺ co-doped oxyfluoride glass-ceramic fibers were obtained by controlled heat treatment of glass fibers. The preceding differential thermal analysis (DTA) studies allowed estimating both the fiber drawing temperature and the controlled crystallization temperature of glass fibers. X-ray diffraction examination (XRD) at each stage of the glass-ceramic fibers fabrication confirmed the undesirable crystallization of preforms and glass fibers has been avoided. The fibers shown their mixed amorphous-crystalline microstructure with nano-crystals of size even below 10 nm distributed in the glassy host. The crystal structure of the grown nano-crystals has been determined by XRD and confirmed by electron diffraction (SAED). Results obtained by both techniques seem to be compatible: Er₃FO₁₀Si₃ (monoclinic; ICSD 92512), Pb₅Al₃F₁₉ (triclinic; ICSD 91325) and Er₄F₂O₁₁Si₃ (triclinic; ICSD 51510) against to initially expected PbF₂ crystals.     

Polarity effect in electrovibration for tactile display

Electrovibration is the tactile sensation of an alternating potential between the human body and a smooth conducing surface when the skin slides over the surface and where the current is too small to stimulate sensory nerves directly. It has been proposed as a high-density tactile display method, for example to display pictographic information to persons who are blind. Previous models for the electrovibration transduction mechanism are based on a parallel-plate capacitor in which the electrostatic force is insensitive to polarity. We present experimental data showing that electrovibratory perceptual sensitivity to positive pulses is less than that for negative or biphasic pulses and propose that this disparity may be due to the asymmetric electrical properties of human skin. We furthermore propose using negative pulses for insulated tactile displays based on electrovibration because their sensory thresholds were found to be more stable than for waveforms incorporating positive pulses.     

Properties of scaffolds based on chitosan and collagen with bioglass 45S5

Scaffolds based on chitosan (CTS), collagen (Coll) and glycosaminoglycans (GAG) mixtures cross‐linked by tannic acid (TA) with bioglass 45S5 addition were obtained with the use of the freeze‐drying method. The prepared scaffolds were characterised for morphology, mechanical strength and degradation rate. Moreover, cell viability on the obtained scaffolds was measured with and without the presence of ascorbic acid and dexamethasone. The main purpose of the research was to compare the effectiveness of bioglass 45S5 influence on the physicochemical and biological properties of scaffolds. The results demonstrated that the scaffolds based on the blends of biopolymers cross‐linked by TA are stable in an aqueous environment. Scanning electron microscope images allowed the observation of a porous scaffold structure with interconnected pores. The addition of bioglass nanoparticles improved the mechanical properties and decreased the degradation rate of composite materials. The biological properties were improved for 20% tannic acid addition compared to 5%. However, the addition of bioglass 45S5 did not change to cells response significantly.Inspec keywords: biomedical materials, drying, porous materials, freezing, tissue engineering, proteins, nanofabrication, bone, scanning electron microscopy, polymers, molecular biophysics, cellular biophysics, nanoparticles, porosityOther keywords: chitosan, collagen, glycosaminoglycans, bioglass 45S5 addition, freeze‐drying method, degradation rate, ascorbic acid, dexamethasone, physicochemical properties, biological properties, porous scaffold structure, bioglass nanoparticles, mechanical properties, tannic acid addition, scanning electron microscopy     

Influence of ultraviolet radiation and aggressive media on epoxy coating degradation

The influence of ultraviolet radiation and of 5% water solutions of sulphuric acid, potassium hydroxide and sodium chloride on an epoxy coating was investigated. It was found that those factors cause generation of characteristic (for a given ageing kind) cracks on the coating surface. UV radiation, for example, gave rise to cracks called silver cracks. It was found as well that ageing changes in the coating influence the mechanical properties such as hardness, statical and dynamical strength.     

Temperature dependence of Bi4Ge3O12 photoluminescence spectra

Bi₄Ge₃O₁₂ single crystals were obtained using Czochralski growth method. Photoluminescence spectra were analyzed versus temperature from 12 to 295 K. Besides the previously observed emission bands at 610 and 820 nm, the new emission band at 475 nm was found by a careful temperature dependence measurement in the present study. The influence of basic and defect structure on the shape and position of the spectra versus temperature was discussed.     

Experimental determination of intrinsic permeability of limestone and concrete: Comparison between in situ and laboratory results

The study is concerned with development of the method of in situ measurement of air permeability of porous media. The method applied consists of creating a vacuum in a drilled hole and then studying the increase in pressure over time. The dimensions of the hole are small enough to consider the test as being nondestructive. The paper is composed of three parts. The first one develops the theoretical background used for interpretation of experimental results. The second part describes experimental procedure and device for in situ measurements. The parametric studies of principal factors which may influence the measurements such as the sampling frequency, the observation time and the boundary conditions were performed. The last part includes a discussion of results of the measurements of air permeability performed on large blocks of limestone and concrete. These blocks simulate in situ conditions. On the other hand, from these blocks, cylindrical samples were cored and standard gas and liquid laboratory tests were carried out. The results obtained show good agreement between intrinsic permeability obtained with the in situ device and laboratory tests, confirming the usefulness of the proposed tool.     

Spectral properties of Yb ions in LiNbO3 single crystals: influences of other rare-earth ions, OH ions, and γ-irradiation

Absorption spectra have been studied in 190–3100 nm region at various temperatures from 16 to 292 K for Yb³⁺-doped and Yb³⁺/Nd³⁺-, Yb³⁺/Er³⁺- and Yb³⁺/Pr³⁺-co-doped LiNbO₃ single crystals before and after γ-irradiation with a dose of 10⁵–10⁷ Gy. Intense 400 and 500 nm absorption bands were observed after γ-irradiation, which are due to the creation of oxygen vacancy (F-type color center) and Nb⁴⁺ polaron, respectively. Different change was observed in the 2870 nm OH⁻ absorption band intensity among the various rare-earth doped crystals. These are interpreted by discrepancy of ionic radii between substituting rare earth dopant ion and Li⁺ or Nb⁵⁺ host ion. The observed temperature dependence of the hot bands is understood by electronic transition from the thermally populated ²F_7/2 Stark levels to the excited ²F_5/2 level. The position of the Yb^{3+ 2}F_7/2→²F_5/2 first resonant line was observed to be slightly different among the co-doped crystals. This is due to the perturbation of Yb³⁺ by co-doped rare earth ion which is located at the neighborhood of theYb³⁺.