Precipitation casting of drug-loaded microporous PCL matrices:incorporation of progesterone by co-dissolution

Microporous, poly(ε-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37°C over 10 days could be described effectively by a diffusional release model although the Korsmeyer-Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 μg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37°C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices.

Effect of recasting procedure upon corrosion behavior and metallic ion release of Co-Cr-Mo dental alloy in physiological

Recasting process influence upon corrosion behavior of Co-Cr-Mo dental alloy in simulated physiological serum has been investigated using chemical and electrochemical techniques. Recast Co-Cr-Mo alloy by induction (IND) or by blowtorch (FLAME) has exhibited similar dendritic structures. Both IND and FLAME alloys have presented good corrosion resistance in physiological serum. Passivation process provides this corrosion resistance. Codissolution makes this process difficult. Passive films, formed on these alloys, have been analyzed as a dual layer consisting of an inner barrier and an outer porous layer. Passive film protective characteristics are higher in FLAME than in IND alloy. On this last alloy, the passive film is more porous due to a higher Codissolution. ©Carl Hanser Verlag, München.

陕西关中盆地地热水循环的同位素研究

Geothermal resource is rich in Guanzhong Basin, but as to its cycle characteristic, there has been lack of systematic study so far. Blind exploitations lead to water-temperature reducing, the decrease of spring flow rate and so on. Based on groundwater system and hydrogeological and hydrological geochemical theory, this paper studied the recycling type of geothermal water and analyzed the resources of dissolved inorganic carbon (DIC) and sulfate. The origin of the internal geothermal water is ice and snow in Qinling Mountain and Liupan Mountain above 1400m. The precipitation and surface water entered the deep part of the basin along piedmont faults, heated and water-expansion increased. The karst groundwater comes from meteoric water of the bare carbonate rock area in the North Mountains. Geothermal-water DIC mainly came from the dissolution of carbonate rock in the deep part of Guanzhong Basin, sulfate of Xi’an depression and Lishan salient came from the dissolution of continental evaporate , and sulfate of Gushi depression and Xianli salient came from co-dissolution of continental and marine evaporate. The above results supply science basis for reasonable exploitation and sustainable utilization of the geothermal water in Guanzhong Basin.

Dissolution and gettering of iron during contact co-firing

The dissolution and gettering of iron is studied during the final fabrication step of multicrystalline silicon solar cells, the co-firing step, through simulations and experiments. The post-processed interstitial iron concentration is simulated according to the as-grown concentration and distribution of iron within a silicon wafer, both in the presence and absence of the phosphorus emitter, and applying different time-temperature profiles for the firing step. The competing effects of dissolution and gettering during the short annealing process are found to be strongly dependant on the as-grown material quality. Furthermore, increasing the temperature of the firing process leads to a higher dissolution of iron, hardly compensated by the higher diffusivity of impurities. A new defect engineering tool is introduced, the extended co-firing, which could allow an enhanced gettering effect within a small additional time

Conformational transitions in a Pro-Pro peptide on dissolution of single crystals

The peptide t-butyloxycarbonyl-α-aminoisobutyryl-L-prolyl-L-prolyl-N-methylamide has been shown to adopt an extended structure in the solid state. The Pro-Pro segment occurs in the poly-proline II conformation. On dissolution of single crystals at not, vert, similar 233°K, a single species corresponding to the all Image peptide backbone is observed by 270 MHz 1H NMR. On warming, Image to Image isomerization about the Pro-Pro bond is facilitated. Both Image (ψ not, vert, similar−50°) and Image (ψ not, vert, similar 130°) rotamers about the Pro3 Cα---CO bond are detectable in the Pro-Pro Image conformer, at low temperature. These observations demonstrate unambiguously the large differences in the solid state and solution conformations of a Pro-Pro sequence.

Tuning solubility and stability of hydrochlorothiazide co-crystals

Hydrochlorothiazide (HCT), C7H8ClN3O4S2, is a diuretic BCS (Biopharmaceutics Classification System) class IV drug which has primary and secondary sulfonamide groups. To modify the aqueous solubility of the drug, co-crystals with biologically safe co-formers were screened. Multi-component molecular crystals of HCT were prepared with nicotinic acid, nicotinamide, succinamide, p-aminobenzoic acid, resorcinol and pyrogallol using liquid-assisted grinding. The co-crystals were characterized by FT-IR spectroscopy, powder X-ray diffraction (PXRD) and differential scanning calorimetry. Single crystal structures were obtained for four of them. The N-H center dot center dot center dot O sulfonamide catemer synthons found in the stable polymorph of pure HCT are replaced in the co-crystals by drug-co-former heterosynthons. Isostructural co-crystals with nicotinic acid and nicotinamide are devoid of the common sulfonamide dimer/catemer synthons. Solubility and stability experiments were carried out for the co-crystals in water (neutral pH) under ambient conditions. Among the six binary systems, the co-crystal with p-aminobenzoic acid showed a sixfold increase in solubility compared with pure HCT, and stability up to 24 h in an aqueous medium. The co-crystals with nicotinamide, resorcinol and pyrogallol showed only a 1.5-2-fold increase in solubility and transformed to HCT within 1 h of the dissolution experiment. An inverse correlation is observed between the melting points of the co-crystals and their solubilities.

Effect of Copolymerization Time on the Microstructure and Properties of Polypropylene/Poly(ethylene-co-propylene) In-Reactor Alloys

Three Polypropylene/Poly(ethylene-co-propylene) (PP/EPR) in-reactor alloys produced by a two-stage slurry/gas polymerization had different ethylene contents and mechanical properties, which were achieved by controlling the copolymerization time. The three alloys were fractionated into five fractions via temperature rising dissolution fractionation (TRDF), respectively. The chain structures of the whole samples and their fractions were analyzed using high-temperature gel permeation chromatography (GPC), Fourier transform infrared (FT-IR), C-13 nuclear magnetic resonance (C-13 NMR), and differential scanning calorimetry (DSC) techniques. These three in-reactor alloys mainly contained four portions: ethylenepropylene random copolymer (EPR), ethylene-propylene (EP) segmented and block copolymers, and propylene homopolymer. The increased copolymerization time caused the increased ethylene content of the sample. The weight percent of EPR, EP segmented and block copolymer also became higher.

Rheological studies on the phase dissolution in a block copolymer

The microphase transition in a styrene-butadiene-styrene triblock copolymer was studied by rheometric mechanical spectroscopy. A high-temperature-melt rheological transition from the highly elastic, nonlinear viscous behavior typical of a multiphase structure to linear viscous behavior with insignificant elasticity typical of a single-phase structure was observed. The transition temperature is determined according to the discontinuity of the rheological properties across the transition region, which agrees well with the results obtained from the small angle X-ray scattering data and the expectation of the random phase approximation theory. Maybe for the first time, microphase dissolution was investigated theologically. The storage modulus (G') and the loss modulus (G '') increase with time during the process. An entanglement fluctuation model based on the segmental density fluctuations is presented to explain the rheological behavior in this dissolution process. (C) 1997 John Wiley & Sons.

Co-acquisition of hyperpolarised 13C and 15N NMR spectra

Recent developments in dynamic nuclear polarisation now allow significant enhancements to be generated in the cryo solid state and transferred to the liquid state for detection at high resolution. We demonstrate that the Ardenkjaer-Larsen method can be extended by taking advantage of the properties of the trityl radicals used. It is possible to hyperpolarise 13C and 15N simultaneously in the solid state, and to maintain these hyperpolarisations through rapid dissolution into the liquid state. We demonstrate the almost simultaneous measurement of hyperpolarised 13C and hyperpolarised 15N NMR spectra. The prospects for further improvement of the method using contemporary technology are also discussed.

Incorporation of novel 1-alkylcarbonyloxymethyl prodrugs of 5-fluorouracil into poly(lactide-co-glycolide) nanoparticles

Incorporation of 1-alkylcarbonyloxymethylprodrugs of 5FU into poly(lactide-co-glycolide) nanoparticles using nanoprecipitation methods gave increased loading efficiencies over that obtained using the parent drug substance. SEM studies revealed spherical nanoparticles of around 200 nm in diameter, corresponding well with measurements made using photon correlation spectroscopy. The C-7 prodrug gave the best mean loading of 47.23%, which compared favourably to 3.68% loading achieved with 5FU. Loading efficiency was seen to follow the hydrophilic-lipophilic balance in the homologue series, where increases in lipophilicities alone were not good predictors of loading. Drug release, in terms of resultant 5FU concentration, was monitored using a flow-through dissolution apparatus. Cumulative drug release from nanoparticles loaded with the C-5 prodrug was linear over 6h, with approximately 14% of the total available 5FU dose released and with no evidence of a burst effect. The flux profile of the C-5-loaded nanoparticles showed an initial peak in flux in the first sampling interval, but became linear for the remainder of the release phase. C-7-loaded nanoparticles released considerably less (4% in 6 h) with a similar flux pattern to that seen with the C-5 prodrug. The C-9-loaded nanoparticles released less than 1% of the available 5FU over 6 h, with a similar zero-order profile. The C7 prodrug was deemed to be the prodrug of choice, achieving the highest loadings and releasing 5FU, following hydrolysis, in a zero-order fashion over a period of at least 6 h. Given the lack of burst effect and steady-state flux conditions, this nanoparticulate formulation offers a better dosing strategy for sustained intravenous use when compared to that arising from nanoparticles made by direct incorporation of 5FU. (c) 2007 Elsevier B.V. All rights reserved.

Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution.

In this study, we used optical coherence tomography (OCT) to extensively investigate, for the first time, the effect that microneedle (MN) geometry (MN height, and MN interspacing) and force of application have upon penetration characteristics of soluble poly(methylvinylether-co-maleic anhydride, PMVE/MA) MN arrays into neonatal porcine skin in vitro. The results from OCT investigations were then used to design optimal and suboptimal MN-based drug delivery systems and evaluate their drug delivery profiles cross full thickness and dermatomed neonatal porcine skin in vitro. It was found that increasing the force used for MN application resulted in a significant increase in the depth of penetration achieved within neonatal porcine skin. For example, MN of 600 µm height penetrated to a depth of 330 µm when inserted at a force of 4.4 N/array, while the penetration increased significantly to a depth of 520 µm, when the force of application was increased to 16.4 N/array. At an application force of 11.0 N/array it was found that, in each case, increasing MN height from 350 to 600 µm to 900 µm led to a significant increase in the depth of MN penetration achieved. Moreover, alteration of MN interspacing had no effect upon depth of penetration achieved, at a constant MN height and force of application. With respect to MN dissolution, an approximate 34% reduction in MN height occurred in the first 15 min, with only 17% of the MN height remaining after a 3-hour period. Across both skin models, there was a significantly greater cumulative amount of theophylline delivered after 24 h from an MN array of 900 µm height (292.23 ± 16.77 µg), in comparison to an MN array of 350 µm height (242.62 ± 14.81 µg) (p < 0.001). Employing full thickness skin significantly reduced drug permeation in both cases. Importantly, this study has highlighted the effect that MN geometry and application force have upon the depth of penetration into skin. While it has been shown that MN height has an important role in the extent of drug delivered across neonatal porcine skin from a soluble MN array, further studies to evaluate the full significance of MN geometry on MN mediated drug delivery are now underway. The successful use of OCT in this study could prove to be a key development for polymeric MN research, accelerating their commercial exploitation.

Theoretical and experimental correlations of gas dissolution, diffusion, and thermodynamic properties in determination of gas permeability and selectivity in supported ionic liquid membranes

Supported ionic liquid membranes (SILMs) has the potential to be a new technological platform for gas/organic vapour separation because of the unique non-volatile nature and discriminating gas dissolution properties of room temperature ionic liquids (ILs). This work starts with an examination of gas dissolution and transport properties in bulk imidazulium cation based ionic liquids [C_nmim][NTf2] (n = 2.4, 6, 8.10) from simple gas H₂, N₂, to polar CO₂, and C₂H₆, leading to a further analysis of how gas dissolution and diffusion are influenced by molecular specific gas-SILMs interactions, reflected by differences in gas dissolution enthalpy and entropy. These effects were elucidated again during gas permeation studies by examining how changes in these properties and molecular specific interactions work together to cause deviations from conventional solution–diffusion theory and their impact on some remarkably contrasting gas perm-selectivity performance. The experimental perm-selectivity for all tested gases showed varied and contrasting deviation from the solution–diffusion, depending on specific gas-IL combinations. It transpires permeation for simpler non-polar gases (H₂, N₂) is diffusion controlled, but strong molecular specific gas-ILs interactions led to a different permeation and selectivity performance for C₂H₆ and CO₂. With exothermic dissolution enthalpy and large order disruptive entropy, C₂H₆ displayed the fastest permeation rate at increased gas phase pressure in spite of its smallest diffusivity among the tested gases. The C₂H₆ gas molecules “peg” on the side alkyl chain on the imidazulium cation at low concentration, and are well dispersed in the ionic liquids phase at high concentration. On the other hand strong CO₂-ILs affinity resulted in a more prolonged “residence time” for the gas molecule, typified by reversed CO₂/N₂ selectivity and slowest CO₂ transport despite CO₂ possess the highest solubility and comparable diffusivity in the ionic liquids. The unique transport and dissolution behaviour of CO₂ are further exploited by examining the residing state of CO₂ molecules in the ionic liquid phase, which leads to a hypothesis of a condensing and holding capacity of ILs towards CO₂, which provide an explanation to slower CO₂ transport through the SILMs. The pressure related exponential increase in permeations rate is also analysed which suggests a typical concentration dependent diffusion rate at high gas concentration under increased gas feed pressure. Finally the strong influence of discriminating and molecular specific gas-ILs interactions on gas perm-selectivity performance points to future specific design of ionic liquids for targeted gas separations.

Integrating petrography, mineralogy and hydrochemistry to constrain the influence and distribution of groundwater contributions to baseflow in poorly productive aquifers: Insights from Gortinlieve catchment, Co. Donegal, NW Ireland

Identifying groundwater contributions to baseflowforms an essential part of surfacewater body characterisation. The Gortinlieve catchment (5 km2) comprises a headwater stream network of the Carrigans River, itself a tributary of the River Foyle, NW Ireland. The bedrock comprises poorly productive metasediments that are characterised by fracture porosity. We present the findings of a multi-disciplinary study that integrates new hydrochemical and mineralogical investigations with existing hydraulic, geophysical and structural data to identify the scales of groundwater flow and the nature of groundwater/bedrock interaction (chemical denudation). At the catchment scale, the development of deep weathering profiles is controlled by NE-SW regional scale fracture zones associated with mountain building during the Grampian orogeny. In-situ chemical denudation of mineral phases is controlled by micro- to meso-scale fractures related to Alpine compression during Palaeocene to Oligocene times. The alteration of primary muscovite, chlorite (clinochlore) and albite along the surfaces of these small-scale fractures has resulted in the precipitation of illite, montmorillonite and illite/montmorillonite clay admixtures. The interconnected but discontinuous nature of these small-scale structures highlights the role of larger scale faults and fissures in the supply and transportation of weathering solutions to/from the sites of mineral weathering. The dissolution of primarily mineral phases releases the major ions Mg, Ca and HCO3 that are shown to subsequently formthe chemical makeup of groundwaters. Borehole groundwater and stream baseflow hydrochemical data are used to constrain the depths of groundwater flow pathways influencing the chemistry of surface waters throughout the stream profile. The results show that it is predominantly the lower part of the catchment, which receives inputs from catchment/regional scale groundwater flow, that is found to contribute to the maintenance of annual baseflow levels. This study identifies the importance
of deep groundwater in maintaining annual baseflow levels in poorly productive bedrock systems.

Thermosensitive hydrogels of poly(methyl vinyl ether-co-maleic anhydride) - Pluronic (R) F127 copolymers for controlled protein release

Thermosensitive hydrogels are of a great interest due to their many biomedical and pharmaceutical applications. In this study, we synthesized a new series of random poly (methyl vinyl ether-co-maleic anhydride) (Gantrez (R) AN, GZ) and Pluronic (R) F127 (PF127) copolymers (GZ-PF127), that formed thermosensitive hydrogels whose gelation temperature and mechanical properties could be controlled by the molar ratio of GZ and PF127 polymers and the copolymer concentration in water. Gelation temperatures tended to decrease when the GZm/PF127 ratio increased. Thus, at a fixed GZm/PF127 value, sol-gel temperatures decreased at higher copolymer concentrations. Moreover, these hydrogels controlled the release of proteins such as bovine serum albumin (BSA) and recombinant recombinant kinetoplastid membrane protein of Leishmania (rKMP-11) more than the PF127 system. Toxicity studies carried out in J774.2 macrophages showed that cell viability was higher than 80%. Finally, histopathological analysis revealed that subcutaneous administration of low volumes of these hydrogels elicited a tolerable inflammatory response that could be useful to induce immune responses against the protein cargo in the development of vaccine adjuvants.

Danny e o profundo mar azul: introdução da técnica da Meisner em Portugal pela Below de Belt Teatro Co.: relatório de estágio

Relatório de Estágio submetidoà Escola Superior de Teatro e Cinemapara cumprimento dos requisitos necessários à obtenção do grau de Mestre em Artes Performativas- especialização em Teatro-Música