Wet sol–gel silica matrices as delivery devices for phenytoin

Wet sol–gel silica matrices produced under different hydrolysis conditions were used as delivery devices to the active principle of an antiepileptic drug (phenytoin sodium), encapsulated during the condensation stage. Post-incorporation into dry silica powder was an alternative loading procedure. It was proven by infrared spectroscopy that neither the silica network nor the drug loose integrity by encapsulation. The kinetics of in vitro drug release was studied at 37 °C, to water and to artificial cerebrospinal fluid (ACSF). Emphasis has been given to the release to ACSF under dynamic conditions (with fluid renovation, emulating what occurs in the brain). Different delivery regimes were identified and correlated with the loading method and the matrix structure. Matrices with lower total porosity and smaller average pore size proved to be better for a long term release. Renovation of ACSF is relevant to assure a constant concentration of phenytoin in the vicinity of the device.     

“Living” radical polymerization of styrene catalyzed by cyclometalated ruthenium(II) complexes bearing nonlabile ligands

Cationic substitutionally inert cyclometalated ruthenium (II) and osmium (II) complexes, ([Mt(o‐C₆H₄‐2‐py)(LL)₂]PF₆), where LL‐1,10‐phenanthroline (phen) or 2,2′‐bipyridine (bipy), were used for radical polymerization of styrene. Gradual modification of the complexes within the series allowed comparison of the catalytic activity and the redox properties. There was no correlation between the reducing powers of the complexes and their catalytic activities. The osmium compound of the lowest reduction potential was not active. All the ruthenium complexes catalyzed the polymerization of styrene in a controlled manner; but the level of control and the catalytic activity were different under the same polymerization conditions. [Ru(o‐C₆H₄‐2‐py)(phen)₂]PF₆ demonstrated the best catalytic performance though its redox potential was the highest. It catalyzed the “living” polymerization with a reasonable rate at a catalyst‐to‐initiator ratio of 0.1. 1 equiv. of Al(OiPr)₃ accelerated the polymerization and improved the control, but higher amount of Al(OiPr)₃ did not speed up the polymerization and moved the process into the uncontrollable regime. Under the most optimal conditions, the controlled polymerization occurs fast without any additive and the catalyst degradation. Added free ligands inhibited the polymerization suggesting that the catalytically active ruthenium intermediates are generated via the reversible dechelation of bidentate phen or bipy ligands. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3814–3828, 2009     

SIMS depth profiling of ‘frozen’ samples: in search of ultimate depth resolution regime

We have performed secondary ion mass spectrometry depth profiling analysis of III–V based hetero‐structures at different target temperatures and found that both the surface segregation and surface roughness caused by ion sputtering can be radically reduced if the sample temperature is lowered to ?150 °C. The depth profiling of ‘frozen’ samples can be a good alternative to sample rotation and oxygen flooding used for ultra‐low‐energy depth profiling of compound semiconductors. Copyright © 2016 John Wiley & Sons, Ltd.     

New approach for measurement of non-SHBG-bound testosterone in human plasma

Testosterone (T) circulates in the blood tightly bound to sex hormone-binding globulin (SHBG) and weakly to albumin. Measuring protein unbound T (free) or non-SHBG-bound T rather than total T has been recommended for the evaluation of androgen disorders in humans. Ammonium sulfate precipitation has been widely used to separate [SHBG-T] complex from free and albumin-bound T. To achieve more specificity in this separation, we used monoclonal anti-SHBG antibody and developed a suitable and convenient immunoassay for measuring non-SHBG-bound T. Magnetic beads were covalently coupled to a monoclonal anti-SHBG antibody to capture [SHBG-T] complex from plasma samples. Magnetic separation was then performed to allow measurement of non-SHBG-bound T in the supernatant by direct radioimmunoassay. When 300 μL of plasma samples were incubated at room temperature with 10 μL of anti-SHBG beads, residual SHBG concentration was undetectable in the supernatant. The specificity of proteins retained on anti-SHBG beads was further demonstrated by peptide mass fingerprint on a MALDI-TOF analyzer. The non-specific adsorption of T on beads was low (5%), and dissociation of T from SHBG-T complex was less than 5% after 180 min of incubation. The plasma concentrations of non-SHBG-bound T using anti-SHBG beads were highly correlated to those obtained using ammonium sulfate precipitation. We conclude that SHBG immunocapture is a highly specific and useful tool for an experimental direct measurement of plasma non-SHBG-bound T. This methodology is also convenient and appropriate for routine and automated assay.     

AuPt core–shell nanocatalysts with bulk Pt activity

In the presented work, the evaluation of an unsupported AuPt core–shell catalyst for the oxygen reduction reaction is introduced. Applying only basic chemicals in an upscalable synthesis route, it is demonstrated that uniform, flat, and complete Pt layers around a spherical Au core are obtained. The electrocatalytic measurements show that the surface area specific activity of the AuPt core–shell catalyst towards the important oxygen reduction reaction equals the one of polycrystalline bulk Pt. To our knowledge, this is the first time that the unfavorable particle size effect of Pt nanoparticles could be by-passed for a nanoscale catalyst.     

Analytical Applications of Enzymatic Growth of Quantum Dots

We have developed an analytical assay to detect the enzymatic activity of acetylcholine esterase and alkaline phosphatase based on the generation of quantum dots by enzymatic products. Acetylcholine esterase converts acetylthiocholine into thiocholine. The latter enhances the rate of decomposition of sodium thiosulfate into H₂S, which in the presence of cadmium sulfate yields CdS quantum dots showing a time dependent exponential growth, typical of autocatalytic processes. This assay was also applied to detect acetylcholine esterase inhibitors. Alkaline phosphatase hydrolyzes thiophosphate and yields H₂S, which instantly reacts with Cd²⁺ to give CdS quantum dots. The formation of CdS quantum dots in both reactions was followed by fluorescence spectroscopy and showed dependence on the concentration of enzyme and substrate.     

An in vitro controlled release study of valproic acid encapsulated in a titania ceramic matrix

Despite the therapeutic efficacy of valproic acid towards numerous diseases, its poor bioavailability and systemic side effects pose significant barriers to long term treatment. In order to take advantage of controlled release implants of valproic acid, the drug was encapsulated into titania ceramic matrices via a sol-gel process. The integrity and structure of valproic acid-containing matrices were characterized through the use of FESEM, TEM, and BET analyses. In vitro controlled release studies and kinetic analyses were performed under ambient conditions (25 °C, atmospheric pressure) and controlled release behaviors were studied using a GC-MS method. Results showed first order dependence in the rate of valproic acid release as a function of drug concentrations in the titania ceramic device. A marked dependence on the surface area and pore size distribution with drug loading was also observed. This research opens new possibilities for the design of novel time-delayed controlled release systems for valproic acid encapsulates.