The pharmacokinetics of water-in-oil-in-water-type multiple emulsion of a new tacrolimus formulation

We developed a water-in-oil-in-water (W/O/W)-type multiple emulsion of a new tacrolimus formulation. A potential approach to avoid the complications of systemic immunosuppression and simultaneously enhance immunosuppressive efficacy is to deliver immunosuppressive agents locally to the site of the target organs. The W/O/W emulsion is dispersed oil drops containing smaller water droplets that allow the delivery of drugs preferentially to the reticuloendothelial system (RES). Since the liver and the spleen are primary components of the RES, and the brain and the kidney have a poor RES, we hypothesized that a W/O/W emulsion of tacrolimus would prossess the pharmacokinetic benefits of local immunosuppression. We evaluated this hypothesis in a rat model. The tacrolimus levels of whole blood, the liver, spleen, brain, and kidney in rats given intravenous emulsions of tacrolimus (W/O/W group) were compared with a group administered tacrolimus alone (T group). There were no significant differences between the pharmacokinetic parameters of W/O/W group and T group based on whole blood data. However, the W/O/W group had significantly decreased tacrolimus levels in the brain and kidney, and significantly increased levels in the liver and spleen compared with the T group. These data suggest that the W/O/W emulsion is applicable as an intravenous drug carrier for local immunosuppression.     

Characterization of a Silk‐Resinified Compact Fabricated Using a Pulse‐Energizing Sintering Device

Pulse electric current sintering is used to prepare a compact from resinificated hydrous silk powder. Compacts with no remnant silk powders are formed with 20 wt% added water, 20–40 MPa molding pressure, and >353 K molding temperature. The latter two are much lower than those used for conventional hot pressing. No dependence on molding pressure and temperature are found in XRD or FT‐IR analysis, except for a compact molded at 473 K, for which silk fibroin decomposition is confirmed by DSC, EGA‐MS, and molecular weight measurements. The compact's three‐point bending strength depends on the molding temperature, except for the temperature at which silk fibroin decomposes. The maximum three‐point bending strength resembles that of general‐purpose epoxy resin and is much higher than that of PLA.

     

n-Hexyl Laurate and Fourteen Related Fatty Acid Esters: New Secretory Compounds from the Julid Millipede, Anaulaciulus sp.

A total of fifteen saturated fatty acid esters were newly identified from the secretions of an unidentified Anaulaciulus sp. (Julida: Julidae). The fatty acid components of the esters were composed of normal chain acids (from C₁₀ to C₁₄) and of branched chain acids (from iso-C₁₂ to iso-C₁₅ and anteiso-C₁₅). The alcohol moieties were all composed of normal chain alcohols varying from n-butanol to n-octanol. The most abundant component found in the total esters was n-hexyl laurate (64.7%). Novel compounds identified from the millipede secretion extracts include six branched iso- and anteiso-fatty esters, an odd-numbered C₁₁-fatty acid ester, a C₁₃-fatty acid ester, and a C₇-alcohol ester, all of which were previously undescribed natural products. In addition, a characteristic mixture of benzoquinones, such as 2-methyl-1,4-benzoquinone, 2-methoxy-3-methyl-1,4-benzoquinone, 2,3-dimethoxy-1,4-benzoquinone, 2-methoxy-6-methyl-1,4-benzoquinone, and 2,3-dimethoxy-5-methyl-1,4-benzoquinone were identified from the secretions, together with trace amounts of 1,4-benzoquinone.     

Thermodynamic stability of hydrogen+tetra-n-butyl phosphonium bromide mixed semi-clathrate hydrate

Three-phase equilibrium (pressure–temperature) relation of hydrate+aqueous+fluid phases for the hydrogen (H₂)+tetra-n-butyl phosphonium bromide (TBPB)+water ternary system was investigated in a temperature range of 281.90–295.94 K and a pressure range up to 170 MPa. The behavior of the three-phase coexisting curve indicates no structural transition in the present experimental region. The Raman spectra obtained in the H₂+TBPB mixed semi-clathrate hydrate crystal reveal that H₂ molecule occupies only small cage compartmentally and the TBPB molecule is encaged with a set of other large cages.     

Effect of Al4SiC4 on the Al2O3SiCSiO2C refractory castables performance

Carbon-containing refractories are widely used in the steelmaking process due to their outstanding properties and, in order to improve their oxidation resistance, the so-called antioxidants have often been used. Al₄SiC₄ is pointed out as a novel additive that presents suitable properties such as Al, but without its drawbacks. Therefore, the effect of Al₄SiC₄ addition to Al₂O₃SiCSiO₂C castables designed for lining blast furnace troughs was investigated in this work. Apparent porosity, oxidation, thermogravimetric, X-ray diffraction, hot elastic modulus tests and thermodynamic calculations were carried out in order to better understand the antioxidant effects and reaction mechanisms. Additionally, the collected results were compared with those from the compositions containing other commonly used antioxidants (Si, B₄C and sodium borosilicate glass). The performance of the novel additive proved to be limited as most of the carbon source used reacted earlier than the Al₄SiC₄ action. As a consequence, intense carbon oxidation, along with the thermal expansion mismatch among the phases during the cooling step, intensified the deterioration of the evaluated refractory material.     

The Potential Role of Hepatocyte Growth Factor in Degenerative Disorders of the Synovial Joint and Spine

This paper aims to provide a comprehensive review of the changing role of hepatocyte growth factor (HGF) signaling in the healthy and diseased synovial joint and spine. HGF is a multifunctional growth factor that, like its specific receptor c-Met, is widely expressed in several bone and joint tissues. HGF has profound effects on cell survival and proliferation, matrix metabolism, inflammatory response, and neurotrophic action. HGF plays an important role in normal bone and cartilage turnover. Changes in HGF/c-Met have also been linked to pathophysiological changes in degenerative joint diseases, such as osteoarthritis (OA) and intervertebral disc degeneration (IDD). A therapeutic role of HGF has been proposed in the regeneration of osteoarticular tissues. HGF also influences bone remodeling and peripheral nerve activity. Studies aimed at elucidating the changing role of HGF/c-Met signaling in OA and IDD at different pathophysiological stages, and their specific molecular mechanisms are needed. Such studies will contribute to safe and effective HGF/c-Met signaling-based treatments for OA and IDD.     

Dip Coating of Water-Resistant PEDOT:PSS Films Based on Physical Crosslinking

Water-resistant poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films are valuable in biomedical applications; however, they typically require crosslinkers to stabilize the films, which can introduce undesired aggregation or phase separation reactions. Herein, a dipping-based process to prepare PEDOT:PSS films on nonplanar surfaces without crosslinker is developed. Sequential soaking of a dip-coated PEDOT:PSS film in ethanol and water imparts water resistance to the film. Microscopic and spectroscopic techniques are used to monitor the process and confirm that the ethanol soaking elutes the excess PSS from the film bulk, which stabilizes the film prior to the water-soaking process. The obtained films act as conductors and semiconductors on curved surfaces, including 3D-printed objects. A film deposited on a curved surface is successfully applied as the channel layer in a neuromorphic organic electrochemical transistor. This approach can enable integrated bioelectronic and neuromorphic applications that can be readily deployed for facile prototyping.     

Oxygen evolution anodes composed of anodically deposited Mn-Mo-Fe oxides for seawater electrolysis

Preparation of anodes for oxygen evolution in seawater electrolysis was carried out. Manganese-molybdenum double oxides, Mn_1−xMo_xO_2+x, prepared by anodic deposition from MnSO₄-Na₂MoO₄ solutions showed the 100% oxygen evolution efficiency at a current density of 1000 A m⁻² in 0.5 M NaCl at 30 °C and pH 12, but an increase in solution temperature resulted in dissolution of the oxides as molybdate and permanganate ions. In order to increase the stability of the electrodes at higher temperatures the addition of iron to the manganese-molybdenum oxides was performed by anodic deposition in MnSO₄-Na₂MoO₄-FeNH₄(SO₄)₂ solutions. The electrodes thus prepared showed the 100% oxygen evolution efficiency at 1000 A m⁻² in 0.5 M NaCl at 30-90 °C, when proper amounts of molybdenum and iron were contained. The iron addition also enhanced the oxygen evolution efficiency. The electrodes were not composed of oxide mixtures but triple oxides, Mn_1−x−yMo_xFe_yO_2+x−0.5y, consisting of Mn⁴⁺, Mo⁶⁺ and Fe³⁺. The formation of the triple oxides seemed responsible for enhancement of both oxygen evolution efficiency and stability.