Controlled release of a model antibacterial drug from a novel self-lubricating silicone biomaterial

Abstract There is considerable interest in developing medical devices that provide controlled delivery of biologically active agents, for example, to reduce the incidence of device-related infection. Silicone elastomers are one of the commonest biomaterials used in medical device production. However, they have a relatively high coefficient of friction and the resulting lack of lubricity can cause pain and tissue damage on device insertion and removal. Novel silicone cross-linking agents have recently been reported that produce inherently ‘self-lubricating’ silicone elastomers with very low coefficients of friction. In this study, the model antibacterial drug metronidazole has been incorporated into these self-lubricating silicone elastomers to produce a novel bioactive biomaterial. The in vitro release characteristics of the bioactive component were evaluated as a function of cross-linker composition and drug loading. Although conventional matrix-type release kinetics were observed for metronidazole from the silicone systems, it was also observed that increasing the concentration of the cross-linking agent responsible for the lubricious character (tetra(oleyloxy)silane) relative to that of the standard non-lubricious cross-linking agent (tetrapropoxysilane) produced an increase in the metronidazole flux rate by up to 65% for a specified drug loading. The results highlight the potential for developing lubricious silicone medical devices with enhanced drug release characteristics.

Self-lubricating silicone elastomer biomaterials

Silicone has a relatively high coefficient of friction and silicone medical devices therefore lack inherent lubricity, leading to pain on device insertion and potential tissue trauma. In this study, higher molecular weight tetra(alkoxy) silanes, particularly tetra(oleyloxy) silane, have been used as crosslinkers in the condensation cure of a hydroxy end-functionalised linear poly(dimethylsiloxane). The resulting elastomers displayed a persistent lubricous surface of oleyl alcohol, and coefficients of friction (static and dynamic) approaching zero. Chemical structures of the synthesised silanes and surface alcohol exudate were confirmed by nuclear magnetic resonance spectroscopy. Mechanical properties of the elastomers, which were chemically identical to conventionally cured systems, suggested that an 80/20 mixture of tetra(oleyloxy) silane and tetra(propoxysilane) gave the best compromise between desirable mechanical and frictional properties.

Release kinetics of oleyl alcohol from a self-lubricating silicone biomaterial

The development of self-lubricating silicone elastomeric biomaterials, prepared using the novel crosslinking agent tetra( oleyloxy) silane and having very low coefficients of friction, has recently been reported. In this study, the in vitro release characteristics of lubricious oleyl alcohol produced during the silicone curing reaction have been quantitatively evaluated for a range of tetra( propoxy) silane/tetra(oleyloxy) silane crosslinker compositions using a novel evaporative light scattering detection method in combination with high performance liquid chromatography. The mechanism of oleyl alcohol release was seen to deviate from a simple, matrix-controlled diffusion process and instead obeyed an anomalous transport mechanism. An explanation for the observed release behaviour has been proposed based on competitive reaction kinetics between the tetra( oleyloxy) silane and tetra( propoxy) silane substituents of the silicone crosslinking agents.

Full-Scale Marine Exposure Tests on Treated and Untreated Concretes Initial 7-Year Results

An extensive chloride profiling program was undertaken on concrete pier stems erected in the vicinity of the Dornoch Bridge located at the Dornoch Firth in Northeast Scotland. The pier stems were 2 m (6.562 ft) high and octagonal in plan with 0.66 m (2.165 ft) wide faces. The piers were constructed in sets of three with the lowest of each set in the tidal zone and the highest in the atmospheric zone. The pier stems were placed in such a way that they would represent the exposure conditions of the actual bridge piers of the Dornoch Bridge. In all, six of the pier stems were made using plain ordinary portland cement (OPC) concrete (with three of these having the surface treated with silane); the remaining three pier stems had a concrete containing caltite as an additive. Three exposurezones were studied: the tidal zone, the splash zone, and the atmospheric zone. The tidal zone was further subdivided into two levels defined as low-level and high-level. Chloride profiles were obtained from the different regimes over a period of 7 years for all nine pier stems. This paper describes the nature of chloride ingress and the usefulness of diffusion parameters in classifying each exposure regimes. Furthermore, the effectiveness of silane and caltite in protecting concrete from chloride ingress in different exposure zones was studied.

Preparation and characterisation of cellulose nanofibres

Two different procedures were compared for the preparation of cellulose nanofibres from flax and microcrystalline cellulose (MCC). The first involved a combination of high energy ball milling, acid hydrolysis and ultrasound, whilst the second employed a high pressure homogenisation technique, with and without various pre-treatments of the fibrous feedstock. The geometry and microstructure of the cellulose nanofibres were observed by SEM and TEM and their particle size measured using image analysis and dynamic light scattering. Aspect ratios of nanofibres made by microfluidisation were orders of magnitude greater than those achieved by acid hydrolysis. FTIR, XRD and TGA were used to characterise changes to chemical functionality, cellulose crystallinity and thermal stability resulting from the approaches used for preparing the cellulose nanofibres. Hydrolysis using sulphuric acid gave rise to esterification of the cellulose nanofibres, a decrease in crystallinity with MCC, but an increase with flax, together with an overall reduction in thermal stability. Increased shear history of flax subjected to multiple passes through the microfluidiser, raised both cellulose nanofibril crystallinity and thermal stability, the latter being strongly influenced by acid, alkaline and, most markedly, silane pretreatment.

EFFECTS OF 3 DURABILITY ENHANCING PRODUCTS ON SOME PHYSICAL-PROPERTIES OF NEAR-SURFACE CONCRETE

This paper investigates the influence of three fundamentally different durability enhancing products, viz. microsilica, controlled permeability formwork and silane, on some of the physical proper ties of near surface concrete. Microsilica (silica fume) is a pozzolan, controlled permeability formwork (CPF) is used to provide a free draining surface to a concrete form, while silane is a surface treatment applied to hardened concrete to reduce the ingress of water. Comparisons are made between the products when used individually and used in conjunction with each other, with a view to assessing whether the use of combinations of products may be desirable to improve the durability of concrete in certain circumstances. The effect of these materials on various durability parameters, such as freeze-thaw deterioration, carbonation resistance and chloride ingress, is considered in terms of their effect on permeation properties and surface strength. The results indicated that a combination of silane and CPF produces concrete with very low air permeability and sorptivity values. The influence of microsilica was more pronounced in increasing the surface strength of concrete.

Synthesis and characterization of star polymers and cross-linked star polymer model networks containing a novel, silicon-based, hydrolyzable cross-linker

An acid-labile dimethacrylate cross-linker, dimethyldi(methacryloyloxy-l-ethoxy)silane (DMDMAES), was synthesized by the reaction of 2-hydroxyethyl methacrylate (HEMA) and dichlorodimethylsilane in the presence of triethylamine. Group transfer polymerization (GTP) was employed to use this cross-linker in the preparation of six hydrolyzable polymer structures: one neat cross-linker network, one randomly cross-linked network of methyl methacrylate (MMA), two star-shaped polymers of MMA, and two cross-linked star polymer model networks (CSPMNs) of MMA. A nonhydrolyzable CSPMN of MMA, based on a stable cross-linker, was also synthesized. Gel permeation chromatography (GPC) in tetrahydrofuran (THF) confirmed the narrow molecular weight distributions (MWDs) of the linear polymer precursors and demonstrated the increase in molecular weight (MW) upon each successive addition of cross-linker or monomer. Characterization by static light scattering (SLS) and GPC showed that star polymers with DMDMAES cores bear a relatively small number of arms, around 7. All star polymers and polymer networks were hydrolyzed using hydrochloric acid in THF. While the MWs of the products from the hydrolysis of the star polymers, the neat cross-linker network, and the randomly cross-linked network were as expected, those from the CSPMNs were of a much higher than expected MW, indicating extensive star-star coupling.

Optimization of the processing of HNBR/organoclay nanocomposite

In the current investigation, rubber/clay nanocomposites were prepared by two different methods using hydrogenated nitrile butadiene rubber (HNBR) and the organoclay namely Cloisite 15A (C15A). A new novel approach involving swelling of C15A by ulltrasonication in HNBR solution has been carried out for improving the exfoliation and compatibilization of organoclays with HNBR matrix. With the addition of 5phr of clay, the elongation at break and tear strength improved by 16% and 24% respectively. The effect of coupling agents namely amino functional silane and tetrasulfido silane on the nanocomposites have been investigated. The elongation at break and tear strength improved by 46% and 77% respectively with the use of silanes. The improvement in the mechanical properties attributes to improved interaction between the organoclays and HNBR matrix. This interaction has been studied by X-ray diffraction and transmission electron microscope. Pre-dispersion technique clearly suggests very good improvement in the dispersion and properties due to better filler-rubber compatibility. © 2010 American Institute of Physics.

Mechanism of gas permeation in processed HNBR/nanoclay composites

The influence of the layered silicate clay platelets on the nitrogen permeation properties of hydrogenated nitrile butadiene rubber (HNBR)/nanoclay nanocomposites has been investigated. Nanocomposites of HNBR modified with different percentages of the organoclay are processed through various routes. Commercially available organoclay (CLOISITE 15A) and various silane-coupling agents are used to improve the dispersion of the nanoclay in HNBR. A total of 10 different formulations of nanocomposites are manufactured. The addition of the organoclay has resulted in a significant enhancement of the nitrogen barrier properties of the manufactured nanocomposite. The mechanism of the reduction in the permeability is explained through the changes in the morphology and its bond to the filler. These changes are confirmed through examination of the morphology using x-ray diffraction, transmission electron microscope, and dynamic mechanical thermal analysis. There has been a drastic reduction up to 55.7% in nitrogen permeability. The reduction in gas permeation in HNBR is attributed to uniformly exfoliated clay platelets. Finally, three different permeability models, namely, the Nielsen model, modified Nielsen model, and Cussler model, have also been considered to predict the permeability behavior of nanocomposites with different volume filler fractions. The experimental values of gas permeability have been compared with theoretical models. It is observed that the modified Nielsen model closely matches with the measured permeation behavior. © 2011 Wiley Periodicals, Inc.

Highly diastereoselective hydrosilylations of allylic alcohols

The highly syn-selective hydrosilylation of allylic alcohols was developed which, following oxidation, provided 1,3 alcohols containing two contiguous stereocentres. Through judicious choice of silane the complementary anti-selective hydrosilylation was also developed. This protocol was applied to the synthesis of an all syn polyketide stereotriad. © 2014 The Royal Society of Chemistry.

Silicon-Directed Rhenium Catalyzed Allylic Carbaminations and Oxidative Fragmentations of γ-Silyl Allylic Alcohols

A highly regioselective allylic substitution of β-silyl allylic alcohols has been achieved that provides the branched isomer as a single product. This high level of regiocontrol is achieved through the use of a vinyl silane group that can perform a Hiyama coupling providing 1,3-disubstituted allylic amines. An unusual oxidative fragmentation product was also observed at elevated temperature that appears to proceed by a Fleming–Tamao-type oxidation–elimination pathway.