Antioxidant encapsulated porous poly(lactide-co-glycolide) microparticles for developing long acting inhalation system

The purpose of this study was to fabricate porous poly(lactide-co-glycolide) (PLGA) microparticles for efficient pulmonary deposition and increased therapeutic duration of the antioxidant anthocyanin (ATH). These microparticles were prepared by a water-in-oil-in-water (W(1)/O/W(2)) multi-emulsion method with vaporizing ammonium bicarbonate (AB) as a porogen and starch as a viscous additive. High porosity achieved by the decomposition reaction of AB to the base of ammonia, carbon dioxide, and water vapor at 50°C enabled efficient deposition of ATH throughout the entire lung in BALB/c mice. In addition, the porous microparticles incorporating starch showed sustained ATH release characteristics (up to 5 days) and protracted antioxidant activity (up to 5 days) for 2,2-diphenyl-1-pikryl-hydrazyl (DPPH) radicals, which was comparable to that of the porous microparticles without starch which completely released ATH in 2h. Furthermore, these porous microparticles incorporating starch led to longer ATH residence (up to 20 days) in in vivo lung epithelium. We believe that this system has great pharmaceutical potential as a long-acting antioxidant for continuously relieving oxidative stress in pulmonary diseases like chronic obstructive pulmonary disease (COPD).     

Synergy between adiponectin and interleukin-1β on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation, synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E(2) (PGE(2)), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1, and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6 and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.     

Determination and pharmacokinetics of [6]-gingerol in mouse plasma by liquid chromatography-tandem mass spectrometry

This study describes the development of a rapid and sensitive high‐performance liquid chromatography–electrospray ionization tandem mass spectrometry (LC‐MS/MS) assay for the quantification of [6]‐gingerol in mouse plasma and application to a pharmacokinetic study after dose ranging in mice. The assay involved a protein precipitation step with acetonitrile and an isocratic elution using a mobile phase consisting of acetonitrile and water containing 0.1% formic acid (80:20 v/v). The multiple reaction monitoring was based on the transition of m/z = 277.2 → 177.1 for [6]‐gingerol and 294.2 → 137.1 for nonivamide (internal standard). The assay was validated to demonstrate the specificity, linearity, recovery, accuracy, precision and stability. The calibration curves were linear over the wide concentration range of 10–10,000 ng/mL (r ≥ 0.9988). The lower limit of quantification was 10 ng/mL using a small volume of mouse plasma (20 μL). The method was successfully applied to a pharmacokinetic study in mice after intravenous injection of [6]‐gingerol at 1.5, 3 and 6 mg/kg doses. The pharmacokinetics of [6]‐gingerol were linear over the dose range studied as demonstrated by the linear increase in area under the concentration‐time curve (AUC_inf) with no significant change in the systemic clearance (Cl_s), volume of distribution (V_ss) and elimination half‐life (t_1/2) as a function of dose. Copyright © 2011 John Wiley & Sons, Ltd.     

Highly luminescent InP/GaP/ZnS nanocrystals and their application to white light-emitting diodes

Highly stable and luminescent InP/GaP/ZnS QDs with a maximum quantum yield of 85% were synthesized by in situ method. The GaP shell rendered passivation of the surface and removed the traps. TCSPC data showed an evidence for the GaP shell. InP/GaP/ZnS QDs show better stability than InP/ZnS. We studied the optical properties of white QD-LEDs corresponding to various QD concentrations. Among various concentrations, the white QD-LEDs with 0.5 mL of QDs exhibited a luminous efficiency of 54.71 lm/W, Ra of 80.56, and CCT of 7864 K.     

Biomimetic alcohol oxidations by an iron(III) porphyrin complex: relevance to cytochrome P-450 catalytic oxidation and involvement of the two-state radical rebound mechanism

The systematic oxidation reactions of a wide range of alcohols have been carried out by using an iron porphyrin complex in order to understand their relation to cytochrome P-450 enzymes and to have a practical application to organic synthesis. The iron porphyrin complex catalyzed efficiently alcohol oxidation to the respective carbonyl compound via a high-valent iron-oxo porphyrin intermediate ((Porp)Fe=O+). Several mechanistic studies such as isotope 18O labeling, deuterium isotope effect, linear free energy relationship, and ring-opening of radical clock substrate, have suggested that the alcohol is oxidized by a sequence of reactions involving an alpha-hydroxyalkyl radical intermediate and oxygen rebound to form the gem-diol, dehydration of which yields the carbonyl compounds. Moreover, it has been proposed that a two-state reactivity mechanism can also be adopted for alcohol oxidation reactions in iron porphyrin model systems as exhibited by P-450 enzymes.     

Facile Fabrication of Multi‐targeted and Stable Biochemical SERS Sensors

The direct transfer of single‐crystalline Au nanowires (NWs) onto Au substrates was achieved by a simple attachment and detachment process. In the presence of a lubricant, Au NWs grown vertically on a sapphire substrate were efficiently moved to an Au substrate through van der Waals interactions. We demonstrate that the transferred Au NWs on the Au substrate can act as sensitive, reproducible, and long‐term‐stable surface‐enhanced Raman scattering (SERS) sensors by detecting human α‐thrombin as well as Pb²⁺ and Hg²⁺ ions. These three biochemically and/or environmentally important analytes were successfully detected with high sensitivity and selectivity by Au NW‐SERS sensors bound by a thrombin‐binding aptamer. Furthermore, the as‐prepared sensors remained in working order after being stored under ambient conditions at room temperature for 80 days. Because Au NWs can be routinely transferred onto Au substrates and because the resultant Au NW‐SERS sensors are highly stable and provide with high sensitivity and reproducibility of detection, these sensors hold potential for practical use in biochemical sensing.     

Enhancement of Enzymatic Hydrolysis and Klason Lignin Removal of Corn Stover Using Photocatalyst-Assisted Ammonia Pretreatment

Photocatalyst-assisted ammonia pretreatment was explored to improve lignin removal of the lignocellulosic biomass for effective sugar conversion. Corn stover was treated with 5.0–12.5 wt.% ammonium hydroxide, two different photocatalysts (TiO₂ and ZnO) in the presence of molecular oxygen in a batch reactor at 60 °C. Various solid-to-liquid ratios (1:20–1:50) were also tested. Ammonia pretreatment assisted by TiO₂-catalyzed photo-degradation removed 70 % of Klason lignin under the optimum condition (12.5 % ammonium hydroxide, 60 °C, 24 h, solid/liquid?=?1:20, photocatalyst/biomass?=?1:10 with oxygen atmosphere). The enzymatic digestibilities of pretreated corn stover were 85 % for glucan and 75 % for xylan with NH₃-TiO₂-treated solid and 82 % for glucan and 77 % for xylan with NH₃-ZnO-treated solid with 15 filter paper units/g-glucan of cellulase and 30 cellobiase units/g-glucan of β-glucosidase, a 2–13 % improvement over ammonia pretreatment alone.     

Determination of docetaxel in rat plasma and its application in the comparative pharmacokinetics of Taxotere and SID530, a novel docetaxel formulation with hydroxypropyl‐β‐cyclodextrin

In this study, a sensitive, simple and reliable method for the quantification of docetaxel in rat plasma was developed and validated using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The plasma samples were prepared by protein precipitation, and paclitaxel was used as an internal standard (IS). Chromatographic separation was achieved using a Gemini C₁₈ column (2.0 × 150 mm, 5 µm) with a mobile phase consisting of 0.1% formic acid–acetonitrile (30:70, v/v). The precursor–product ion pairs used for multiple reaction monitoring were m/z 808.5 → 527.5 (docetaxel) and m/z 854.2 → 286.5 (IS, paclitaxel). A calibration curve for docetaxel was constructed over the range 1–1000 ng/mL. The developed method was specific, precise and accurate, and no matrix effect was observed. The validated method was applied in a comparative pharmacokinetic study in which two docetaxel formulations, SID530, a new parenteral formulation of docetaxel with hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD), and Taxotere, were administered to rats at a dose of 5 mg/kg. For SID530 and Taxotere, the mean C₀ values were 1494 and 1818 ng/mL, respectively, and the AUC_last values were 837 and 755 h ng/mL, respectively. These two formulations did not show any statistical differences with regard to the pharmacokinetic parameters, thus establishing that the SID530 and Taxotere products are pharmacokinetically comparable in male rats. Copyright © 2012 John Wiley & Sons, Ltd.