Permeability characteristics of temozolomide and its ester and amide products through rat and human skin.

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On the effect of blue staining fungi on the permeability of sitka spruce

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High permeability of the anionic form restricts accumulation of indomethacin by cultured gastric surface epithelial cells exposed to low apical pH

The 'ion-trapping' hypothesis suggests that the intracellular concentration of acidic non-steroidal anti-inflammatory drugs in gastric epithelial cells could be much higher than in the gastric lumen, and that such accumulation could contribute to their gastrotoxicity. Our aim was to examine the effect of the pH of the apical medium on the apical to basal transfer of the acidic drug indomethacin (pK a 4.5) across a gastric mucous epithelial cell monolayer, and to determine whether indomethacin accumulated in cells exposed to a low apical pH. Guinea-pig gastric mucous epithelial cells were grown on porous membrane culture inserts (Transwells®) for 72 h. Transfer and accumulation of [ 14C] indomethacin were assessed by scintillation counting. Transfer of [ 3H]mannitol and measurement of trans-epithelial electrical resistance were used to assess integrity of the monolayer. Distribution of [ 14C] urea was used to estimate the intracellular volume of the monolayer. The monolayer was not disrupted by exposure of the apical face to media of pH ≥ 3, or by indomethacin. Transfer of indomethacin (12 μM) to the basal medium increased with decreasing apical medium pH. The apparent permeability of the undissociated acid was estimated to be five times that of the anion. The intracellular concentration of indomethacin was respectively 5.3, 4.1 and 4.3 times that in the apical medium at pH 5.5, 4.5 and 3.0. In conclusion, this study represents the first direct demonstration that indomethacin accumulates in gastric epithelial cells exposed to low apical pH. However, accumulation of indomethacin was moderate and the predictions of the ion-trapping hypothesis were not met, probably due to the substantial permeability of anionic indomethacin across membranes. © 2006 Elsevier B.V. All rights reserved.

Hydrogen production by steam reforming of DME in a large scale CFB reactor. Part I:computational model and predictions

This study presents a computational fluid dynamic (CFD) study of Dimethyl Ether steam reforming (DME-SR) in a large scale Circulating Fluidized Bed (CFB) reactor. The CFD model is based on Eulerian-Eulerian dispersed flow and solved using commercial software (ANSYS FLUENT). The DME-SR reactions scheme and kinetics in the presence of a bifunctional catalyst of CuO/ZnO/Al2O3+ZSM-5 were incorporated in the model using in-house developed user-defined function. The model was validated by comparing the predictions with experimental data from the literature. The results revealed for the first time detailed CFB reactor hydrodynamics, gas residence time, temperature distribution and product gas composition at a selected operating condition of 300 °C and steam to DME mass ratio of 3 (molar ratio of 7.62). The spatial variation in the gas species concentrations suggests the existence of three distinct reaction zones but limited temperature variations. The DME conversion and hydrogen yield were found to be 87% and 59% respectively, resulting in a product gas consisting of 72 mol% hydrogen. In part II of this study, the model presented here will be used to optimize the reactor design and study the effect of operating conditions on the reactor performance and products.

Genomic evaluation during permeability of indomethacin and its solid dispersion

Drug resistance was first identified in cancer cells that express proteins known as multidrug resistance proteins that extrude the therapeutic agents out of the cells resulting in alteration of pharmacokinetics, tissue distribution, and pharmacodynamics of drugs. To this end studies were carried out to investigate the role of pharmacological inhibitors and pharmaceutical excipients with a primary focus on P-glycoprotein (P-gp). The aim of this study was to investigate holistic changes in transporter gene expression during permeability upon formulation of indomethacin as solid dispersion. Initial characterization studies of solid dispersion of indomethacin showed that the drug was dispersed within the carrier in amorphous form. Analysis of permeability data across Caco-2 monolayers revealed that drug absorption increased by 4-fold when reformulated as solid dispersion. The last phase of the work involved investigation of gene expression changes of transporter genes during permeability. The results showed that there were significant differences in the expression of both ATP-binding cassette (ABC) transporter genes as well as solute carrier transporter (SLC) genes suggesting that the inclusion of polyethylene glycol as well as changes in molecular form of drug from crystalline to amorphous have a significant bearing on the expression of transporter network genes resulting in differences in drug permeability. © 2011 Informa UK, Ltd.

Valorisation of vietnamese rice straw waste:catalytic aqueous phase reforming of hydrolysate from steam explosion to platform chemicals

A family of tungstated zirconia solid acid catalysts were synthesised via wet impregnation and subsequent thermochemical processing for the transformation of glucose to 5-hydroxymethylfurfural (HMF). Acid strength increased with tungsten loading and calcination temperature, associated with stabilisation of tetragonal zirconia. High tungsten dispersions of between 2 and 7 W atoms·nm−2 were obtained in all cases, equating to sub-monolayer coverages. Glucose isomerisation and subsequent dehydration via fructose to HMF increased with W loading and calcination temperature up to 600 °C, indicating that glucose conversion to fructose was favoured over weak Lewis acid and/or base sites associated with the zirconia support, while fructose dehydration and HMF formation was favoured over Brönsted acidic WOx clusters. Aqueous phase reforming of steam exploded rice straw hydrolysate and condensate was explored heterogeneously for the first time over a 10 wt% WZ catalyst, resulting in excellent HMF yields as high as 15% under mild reaction conditions.

Rutting-induced permeability loss of open graded friction course mixtures

Functionality of an open graded friction course (OGFC) depends on the high interconnected air voids or pores of the OGFC mixture. The authors' previous study indicated that the pores in the OGFC mixture were easily clogged by rutting deformation. Such a deformation-related clogging can cause a significant rutting-induced permeability loss in the OGFC mixture. The objective of this study was to control and reduce the rutting-induced permeability loss of the OGFC based on mixture design and layer thickness. Eight types of the OGFC mixtures with different air void contents, gradations, and nominal maximum aggregate sizes were fabricated in the laboratory. Wheel-tracking rutting tests were conducted on the OGFC slabs to simulate the deformation-related clogging. Permeability tests after different wheel load applications were performed on the rutted OGFC slabs using a falling head permeameter developed in the authors' previous study. The relationships between permeability loss and rutting depth as well as dynamic stability were developed based on the eight OGFC mixtures' test results. The thickness effects of the single-layer and the two-layer OGFC slabs were also discussed in terms of deformation-related clogging and the rutting-induced permeability loss. Results showed that the permeability coefficient decreases linearly with an increasing rutting depth of the OGFC mixtures. Rutting depth was recommended as a design index to control permeability loss of the OGFC mixture rather than the dynamic stability. Permeability loss due to deformation-related clogging can be effectively reduced by using a thicker single-layer OGFC or two-layer OGFC.

Modified lipids from LDL in the blood during mid-life increase blood brain barrier permeability

Low density lipoprotein levels (LDL) are consistently elevated in cardiovascular disease. It has been suggested that those with high circulating LDL levels in mid-life may be susceptible to develop neurodegenerative diseases in later life. In the circulation, high levels of LDL are associated with increased oxidative modification (oxLDL) and nitration. We have investigated the hypothesis that disruption of blood brain barrier function by oxLDL and their lipids may increase risk of neurodegeneration in later life and that statin intervention in mid-life can mitigate the neurodegenerative effects of hyperlipidaemia. Blood from statin-naïve, normo- and hyperlipidaemic subjects (n=10/group) was collected at baseline. Hyperlipidaemic subjects received statin-intervention whereas normolipidaemic subjects did not prior to a second blood sampling, taken after 3 months. The intervention will be completed in June 2013. Plasma was separated by centrifugation (200g, 30min) and LDL was isolated by potassium bromide density gradient ultracentrifugation. Total homocysteine, LDL cholesterol, 8-isoprostane F2α levels were measured in plasma using commercial kits. LDL were analysed by agarose gel electrophoresis. LDL-lipids were extracted by partitioning in 1:1 chloroform:methanol (v/v) and conjugated to fatty acid free-BSA in serum-free EGM-2 medium (4hrs, 370C) for co-culture with human microvascular endothelial cells (HMVEC). HMVEC were maintained on polycarbonate inserts for two weeks to create a microvascular barrier. Change in barrier permeability was measured by trans-endothelial electrical resistance (TER), FITC-dextran permeability and immunohistochemistry. HMVEC glutathione (GSH) levels were measured after 2 hours by GSH-glo assay. LDL isolated from statin-naïve hyperlipidaemic subjects had higher mobility by agarose gel electrophoresis (Rf;0.53±0.06) and plasma 8-isoprostane F2α (43.5±8.42 pg/ml) compared to control subjects (0.46±0.05 and 24.2±5.37 pg/ml; p<0.05). Compared to HMVEC treatment with the LDL-lipids (5μM) from normolipidaemic subjects, LDL-lipids from hyperlipidaemic subjects increased barrier permeability (103.4±12.5 Ωcm2 v 66.7±7.3 Ωcm2,P<0.01) and decreased GSH (18.5 nmol/mg v 12.3 nmol/mg; untreated cells 26.2±3.6 nmol/mg).

A cost-effective steam-driven RO plant for brackish groundwater

Desalination is a costly means of providing freshwater. Most desalination plants use either reverse osmosis (RO) or thermal distillation. Both processes have drawbacks: RO is efficient but uses expensive electrical energy; thermal distillation is inefficient but uses less expensive thermal energy. This work aims to provide an efficient RO plant that uses thermal energy. A steam-Rankine cycle has been designed to drive mechanically a batch-RO system that achieves high recovery, without the high energy penalty typically incurred in a continuous-RO system. The steam may be generated by solar panels, biomass boilers, or as an industrial by-product. A novel mechanical arrangement has been designed for low cost, and a steam-jacketed arrangement has been designed for isothermal expansion and improved thermodynamic efficiency. Based on detailed heat transfer and cost calculations, a gain output ratio of 69-162 is predicted, enabling water to be treated at a cost of 71 Indian Rupees/m3 at small scale. Costs will reduce with scale-up. Plants may be designed for a wide range of outputs, from 5 m3/day, up to commercial versions producing 300 m3/day of clean water from brackish groundwater.

A hydrothermally stable transition alumina by condensation-enhanced self-assembly and pyrolysis crystallization:application in the steam reforming of methane

The preparation of a steam-based hydrothermally stable transition alumina is reported. The gel was derived from a synthetic sol-gel route where Al-tri-sec-butoxide is hydrolysed in the presence of a non-ionic surfactant (EO20PO70EO20), HCl as the catalyst and water (H2O/Al = 6); the condensation was enhanced by treating the hydrolysed gel with tetrabutylammonium hydroxide (TBAOH), after which it was dried at 60 °C by solvent evaporation. The so-obtained mesophase was crystallized under argon at 1200 °C (1 h) producing a transition alumina containing δ/α, and possibly θ, alumina phases. Due to its surface acidity, the pyrolysis conditions transform the block copolymer into a cross-linked char structure that embeds the alumina crystallites. Calcination at 650 °C generates a fully porous material by burning the char; a residual carbon of 0.2 wt.% was found, attributed to the formation of surface (oxy)carbides. As a result, this route produces a transition alumina formed by nanoparticles of about 30 nm in size on average, having surface areas in the range of 59-76 m2 g-1 with well-defined mesopores centered at 14 nm. The material withstands steam at 900 °C with a relative surface area rate loss lower than those reported for δ-aluminas, the state-of-the-art MSU-X γ-alumina and other pure γ-aluminas. The hydrothermal stability was confirmed under relevant CH4 steam reforming conditions after adding Ni; a much lower surface area decay and higher CH4 conversion compared to a state-of-the-art MSU-X based Ni catalyst were observed. Two effects are important in explaining the properties of such an alumina: the char protects the particles against sintering, however, the dominant effect is provided by the TBAOH treatment that makes the mesophase more resistant to coarsening and sintering. This journal is © the Partner Organisations 2014.

Pre-formulation and systematic evaluation of amino acid assisted permeability of insulin across in vitro buccal cell layers

The aim of this work was to investigate alternative safe and effective permeation enhancers for buccal peptide delivery. Basic amino acids improved insulin solubility in water while 200 and 400 µg/mL lysine significantly increased insulin solubility in HBSS. Permeability data showed a significant improvement in insulin permeation especially for 10 µg/mL of lysine (p < 0.05) and 10 µg/mL histidine (p < 0.001), 100 µg/mL of glutamic acid (p < 0.05) and 200 µg/mL of glutamic acid and aspartic acid (p < 0.001) without affecting cell integrity; in contrast to sodium deoxycholate which enhanced insulin permeability but was toxic to the cells. It was hypothesized that both amino acids and insulin were ionised at buccal cavity pH and able to form stable ion pairs which penetrated the cells as one entity; while possibly triggering amino acid nutrient transporters on cell surfaces. Evidence of these transport mechanisms was seen with reduction of insulin transport at suboptimal temperatures as well as with basal-to-apical vectoral transport, and confocal imaging of transcellular insulin transport. These results obtained for insulin is the first indication of a possible amino acid mediated transport of insulin via formation of insulin-amino acid neutral complexes by the ion pairing mechanism.

A computational model of hydrogen production by steam reforming of dimethyl ether in a large scale CFB reactor. Part II:parametric analysis

This study presents a computational parametric analysis of DME steam reforming in a large scale Circulating Fluidized Bed (CFB) reactor. The Computational Fluid Dynamic (CFD) model used, which is based on Eulerian-Eulerian dispersed flow, has been developed and validated in Part I of this study [1]. The effect of the reactor inlet configuration, gas residence time, inlet temperature and steam to DME ratio on the overall reactor performance and products have all been investigated. The results have shown that the use of double sided solid feeding system remarkable improvement in the flow uniformity, but with limited effect on the reactions and products. The temperature has been found to play a dominant role in increasing the DME conversion and the hydrogen yield. According to the parametric analysis, it is recommended to run the CFB reactor at around 300 °C inlet temperature, 5.5 steam to DME molar ratio, 4 s gas residence time and 37,104 ml gcat -1 h-1 space velocity. At these conditions, the DME conversion and hydrogen molar concentration in the product gas were both found to be around 80%.

Tailored mesoporous silica supports for Ni catalysed hydrogen production from ethanol steam reforming

Mesoporous silica supported Ni nanoparticles have been investigated for hydrogen production from ethanol steam reforming. Ethanol reforming is structure-sensitive over Ni, and also dependent on support mesostructure; three-dimensional KIT-6 possessing interconnected mesopores offers superior metal dispersion, steam reforming activity, and on-stream stability against deactivation compared with a two-dimensional SBA-15 support.