Pharmacokinetics of UC781-loaded intravaginal ring segments in rabbits: a comparison of polymer matrices

UC781 is a potent and poorly water-soluble nonnucleoside reverse transcriptase inhibitor being investi- gated as a potential microbicide for preventing sexual transmission of HIV-1. This study was designed to evaluate the in vivo release and pharmacokinetics of UC781 delivered from matrix-type intravaginal ring segments in rabbits. Three polymer matrices (polyurethane, ethylene vinyl acetate copolymer, and silicone elastomer) and two drug loadings (5 and 15 mg/segment) were evaluated in at least one of two independent studies for up to 28 days in vivo. Inter-study comparison of in vivo release, vaginal tissue, and plasma concentrations for similar formulations demonstrated good reproducibility of the animal model. Mean estimates for a 28-day in vivo release ranged from 0.35 to 3.17 mg UC781 per segment. Mean proximal vaginal tissue levels (adjacent to the IVR segment) were 8– 410 ng/g and did not change significantly with time for most formulations. Distal vaginal tissue levels of UC781 were 6- to 49-fold lower than proximal tissue levels. Mean UC781 plasma levels were low for all formulations, at 0.09–0.58 ng/mL. All formulations resulted in similar UC781 concentrations in vaginal tissue and plasma, except the low loading polyurethane group which provided significantly lower levels. Loading dependent release and pharmacokinetics were only clearly observed for the polyurethane matrix. Based on these results, intravaginal ring segments loaded with UC781 led to vaginal tissue concen- trations ranging from below to approximately two orders of magnitude higher than UC781’s EC50 under in vitro conditions (2.8 ng/mL), with little influence by polymer matrix or UC781 loading. Moreover, these findings support the use of rabbit vaginal pharmacokinetic studies in preclinical testing of microbicide intravaginal rings.

Comparative Characterisation of 3-D Hydroxyapatite Scaffolds Developed via Replication of Synthetic Polymer Foams and Natural Marine Sponges

The production of complex inorganic forms, based on naturally occurring scaffolds offers an exciting avenue for the construction of a new generation of ceramic-based bone substitute scaffolds. The following study reports an investigation into the architecture (porosity, pore size distribution, pore interconnectivity and permeability), mechanical properties and cytotoxic response of hydroxyapatite bone substitutes produced using synthetic polymer foam and natural marine sponge performs. Infiltration of polyurethane foam (60 pores/in2) using a high solid content (80wt %), low viscosity (0.126Pas) hydroxyapatite slurry yielded 84-91% porous replica scaffolds with pore sizes ranging from 50µm - 1000µm (average pore size 577µm), 99.99% pore interconnectivity and a permeability value of 46.4 x10-10m2. Infiltration of the natural marine sponge, Spongia agaricina, yielded scaffolds with 56- 61% porosity, with 40% of pores between 0-50µm, 60% of pores between 50-500µm (average pore size 349 µm), 99.9% pore interconnectivity and a permeability value of 16.8 x10-10m2. The average compressive strengths and compressive moduli of the natural polymer foam and marine sponge replicas were 2.46±1.43MPa/0.099±0.014GPa and 8.4±0.83MPa /0.16±0.016GPa respectively. Cytotoxic response proved encouraging for the HA Spongia agaricina scaffolds; after 7 days in culture medium the scaffolds exhibited endothelial cells (HUVEC and HDMEC) and osteoblast (MG63) attachment, proliferation on the scaffold surface and penetration into the pores. It is proposed that the use of Spongia agaricina as a precursor material allows for the reliable and repeatable production of ceramic-based 3-D tissue engineered scaffolds exhibiting the desired architectural and mechanical characteristics for use as a bone 3 scaffold material. Moreover, the Spongia agaricina scaffolds produced exhibit no adverse cytotoxic response.

Intelligent pigments and plastics for CO2 detection

A novel CO2 intelligent pigment is incorporated into a thermoplastic polymer to create a long-lived CO2-sensitive plastic film which is characterised and then compared to a traditional solvent-based CO2 indicator film.

Modification of biomaterial surface characteristics by body fluids in vitro

In practice, polyvinyl chloride endotracheal tubes and polyurethane urinary catheters are located in areas where they are exposed to the conditioning fluids saliva and urine, respectively. Samples of both biomaterials were incubated in these conditioning fluids and, following treatment, dynamic contact angle measurement and surface roughness assessment by atomic force microscopy were used to analyse surface characteristics. Over a 24 h period of contact with the conditioning fluids, the surface of both materials became significantly more hydrophilic (p

Vaginal rings for delivery of HIV microbicides

Following the successful development of long-acting steroid-releasing vaginal ring devices for treatment of menopausal symptoms and contraception, there is now considerable interest in applying similar devices to the controlled release of microbicides against HIV. In this review article, the vaginal ring concept is first considered within the wider context of the early advances in controlled release technology, before describing the various types of ring device available today. The remainder of the article highlights the key developments in HIV microbicide-releasing vaginal rings, with a particular focus on the dapivirine ring that is presently in late-stage clinical testing. © 2012 Malcolm et al, publisher and licensee Dove Medical Press Ltd.

Experimental investigation of thermoforming carbon fibre-reinforced polyphenylene sulphide composites

Pre-consolidated carbon fibre-reinforced polyphenylene sulphide (CF/PPS) laminates were
thermoformed into V-shaped parts via designed out of autoclave thermoforming experiments.
The different processing conditions tested in the experiment have resulted in final
part angles whose differences ranged from 2.087 to 3.431 from the original mould angle.
The test results show that processing conditions influenced finished part dimensions as the
final sample angles were found to decrease relative to the tooling dimensions, as mould
temperature increases. Higher mould temperature conditions produce thinner parts due
to the thermal expansion of mould tools. The mould temperature of 170C, which can
produce parts with high degree of crystallinity as well as small size of crystal, has been
established as the optimal thermoforming condition for CF/PPS composites.

Melt Processing and Properties of Polyamide 6/Graphene Nanoplatelet Composites

Graphene, due to its outstanding properties, has become the topic of much research activity in recent years. Much of that work has been on a laboratory scale however, if we are to introduce graphene into real product applications it is necessary to examine how the material behaves under industrial processing conditions. In this paper the melt processing of polyamide 6/graphene nanoplatelet composites via twin screw extrusion is investigated and structure–property relationships are examined for mechanical and electrical properties. Graphene nanoplatelets (GNPs) with two aspect ratios (700 and 1000) were used in order to examine the influence of particle dimensions on composite properties. It was found that the introduction of GNPs had a nucleating effect on polyamide 6 (PA6) crystallization and substantially increased crystallinity by up to 120% for a 20% loading in PA6. A small increase in crystallinity was observed when extruder screw speed increased from 50 rpm to 200 rpm which could be attributed to better dispersion and more nucleation sites for crystallization. A maximum enhancement of 412% in Young's modulus was achieved at 20 wt% loading of GNPs. This is the highest reported enhancement in modulus achieved to date for a melt mixed thermoplastic/GNPs composite. A further result of importance here is that the modulus continued to increase as the loading of GNPs increased even at 20 wt% loading and results are in excellent agreement with theoretical predictions for modulus enhancement. Electrical percolation was achieved between 10–15 wt% loading for both aspect ratios of GNPs with an increase in conductivity of approximately 6 orders of magnitude compared to the unfilled PA6.

Sustainable concrete: design and testing

Producing concrete with secondary raw materials is an excellent way to contribute to a moresustainable world, provided that this concrete has at least the same performance during itsservice life as concrete made with the primary raw materials it replaces. Secondary rawmaterials for Light Weight (LW) aggregates (rigid polyurethane foams, shredded tire rubberand mixed plastic scraps) have been combined with secondary raw materials for the binder(fly ash, slag and perlite tailings) making sustainable concretes that were investigated fortheir suitability as LW, highly insulating concrete for four different types of applications.Compliance to desired engineering properties (workability, setting time) was not alwaysfeasible: it was mostly the low workability of the mixtures that limited their application.Contrary to well established cements, steering the workability by adding water was not anoption for these binders that rely on alkali-activation. Eight successful mixtures have beentested further. The results have shown that it is possible to produce a non-structuralsustainable concrete with good mechanical and thermal insulation properties.Design of concrete made with novel materials is currently not feasible without extensiveexperimentation as no design rules exist other than empirically derived rules based ontraditional materials. As a radical different approach, a flexible concrete mix design has beendeveloped with which the concrete can be modelled in the fresh and hardened state. Thenumerical concrete mix design method proves a promising tool in designing concrete forperformance demands such as elasticity parameters and thermal conductivity

Shear Strength and Durability Testing of Adhesive Bonds in Cross-Laminated Timber

The paper addresses the quality of the interface and edge bonded joints in layers of cross-laminated timber (CLT) panels. The shear performance was studied to assess the suitability of two different adhesives, Polyurethane (PUR) and Phenol-Resorcinol-Formaldehyde (PRF), and to determine the optimum clamping pressure. Since there is no established testing procedure to determine the shear strength of the surface bonds between layers in a CLT panel, block shear tests of specimens in two different configurations were carried out, and further shear tests of edge bonded specimen in two configurations were performed. Delamination tests were performed on samples which were subjected to accelerated aging to assess the durability of bonds in severe environmental conditions. Both tested adhesives produced boards with shear strength values within the edge bonding requirements of prEN 16351 for all manufacturing pressures. While the PUR specimens had higher shear strength values, the PRF specimens demonstrated superior durability characteristics in the delamination tests. It seems that the test protocol introduced in this study for crosslam bonded specimens, cut from a CLT panel, and placed in the shearing tool horizontally, accurately reflects the shearing strength of glue lines in CLT.

Osteogenic cell response to 3-D hydroxyapatite scaffolds developed via replication of natural marine sponges

Bone tissue engineering may provide an alternative to autograft, however scaffold optimisation is required to maximize bone ingrowth. In designing scaffolds, pore architecture is important and there is evidence that cells prefer a degree of non-uniformity. The aim of this study was to compare scaffolds derived from a natural porous marine sponge (Spongia agaricina) with unique architecture to those derived from a synthetic polyurethane foam. Hydroxyapatite scaffolds of 1 cm3 were prepared via ceramic infiltration of a marine sponge and a polyurethane (PU) foam. Human foetal osteoblasts (hFOB) were seeded at 1x105 cells/scaffold for up to 14 days. Cytotoxicity, cell number, morphology and differentiation were investigated. PU-derived scaffolds had 84-91% porosity and 99.99% pore interconnectivity. In comparison marine sponge-derived scaffolds had 56-61% porosity and 99.9% pore interconnectivity. hFOB studies showed that a greater number of cells were found on marine sponge-derived scaffolds at than on the PU scaffold but there was no significant difference in cell differentiation. X-ray diffraction (XRD) and inductively coupled plasma mass spectrometry (ICP-MS) showed that Si ions were released from the marine-derived scaffold. In summary, three dimensional porous constructs have been manufactured that support cell attachment, proliferation and differentiation but significantly more cells were seen on marine-derived scaffolds. This could be due both to the chemistry and pore architecture of the scaffolds with an additional biological stimulus from presence of Si ions. Further in vivo tests in orthotopic models are required but this marine-derived scaffold shows promise for applications in bone tissue engineering.

Predicting impact damage, residual strength and crashworthiness of composite structures

The development of the latest generation of wide-body carbon-fibre composite passenger aircraft has heralded a new era in the utilisation of these materials. The premise of superior specific strength and stiffness, corrosion and fatigue resistance, is tempered by high development costs, slow production rates and lengthy and expensive certification programmes. Substantial effort is currently being directed towards the development of new modelling and simulation tools, at all levels of the development cycle, to mitigate these shortcomings. One of the primary challenges is to reduce the extent of physical testing, in the certification process, by adopting a ‘certification by simulation’ approach. In essence, this aspirational objective requires the ability to reliably predict the evolution and progression of damage in composites. The aerospace industry has been at the forefront of developing advanced composites modelling tools. As the automotive industry transitions towards the increased use of composites in mass-produced vehicles, similar challenges in the modelling of composites will need to be addressed, particularly in the reliable prediction of crashworthiness. While thermoset composites have dominated the aerospace industry, thermoplastics composites are likely to emerge as the preferred solution for meeting the high-volume production demands of passenger road vehicles. This keynote presentation will outline recent progress and current challenges in the development of finite-element-based predictive modelling tools for capturing impact damage, residual strength and energy absorption capacity of thermoset and thermoplastic composites for crashworthiness assessments.

Laser-fabricated PET-Ti Hybrid Joints for Medical Device Applications

Currently, micro-joining of plastic parts to metal parts in medical devices is achieved by using medical adhesives, For example, pacemakers, defibrillators and neurological stimulators are designed using silicone adhesive to seal the joint between the polyurethane connector module and the titanium can [1]. Nevertheless, the use of adhesive is problematic because it requires a long time to cure and has high tendency to produce leachable products which might be harmful to the human body. An alternative for directly joining plastics to metal without adhesive is therefore required. Laser transmission joining (LTJ) is growing in importance, and has the potential to gain the niche in micro-fabrication of plastics-metal hybrid joints for medical device applications. The possibility of directly joining plastics to metal by LTJ technique have been demonstrated by a number of studies in recent literature [2]. The widely-accepted understanding of LTJ between plastics and metal is that generation and rapid expansion of micro-bubbles at the plastics-metal interface exert high local pressure to press the melted plastics towards the metal surface features during the laser processing [2]. This subsequently creates the plastics-metal hybrid joint by the mechanisms of mechanical interlocking as well as chemical and physical bonds between the plastics and metal surfaces. Although the micro-bubbles can help promote the mechanical interlocking effect to increase the joint strength, the creation of bubble is a random and complex process depending on the complicated interactions between the laser intensity, thermal degradation properties of plastics, surface temperature and topographical features of metal. In an ideal situation, it is desirable to create the hybrid plastics-metal joint without bubbles. However, the mechanical performance of the hybrid plastics-metal joint without bubbles is still unknown, and systematic comparison between the hybrid joints with and without bubbles is lacking in literature. This becomes the objective of this study. In this work, the laser process parameters were carefully chosen from a preliminary study, such that different hybrid joints: with and without bubbles can be produced and compared. Biocompatible PET and commercially pure Ti were selected as materials for laser joining.

Sustainable solutions for the construction sector: integration of secondary raw materials in the production cycle of concrete

The construction industry is one of the largest consumers of raw materials and energy and one of the highest contributor to green-houses gases emissions. In order to become more sustainable it needs to reduce the use of both raw materials and energy, thus lim-iting its environmental impact. Developing novel technologies to integrate secondary raw materials (i.e. lightweight recycled aggre-gates and alkali activated “cementless” binders - geopolymers) in the production cycle of concrete is an all-inclusive solution to im-prove both sustainability and cost-efficiency of construction industry. SUS-CON “SUStainable, Innovative and Energy-Efficiency CONcrete, based on the integration of all-waste materials” is an European project (duration 2012-2015), which aim was the inte-gration of secondary raw materials in the production cycle of concrete, thus resulting in innovative, sustainable and cost-effective building solutions. This paper presents the main outcomes related to the successful scaling-up of SUS-CON concrete solutions in traditional production plants. Two European industrial concrete producers have been involved, to design and produce both pre-cast components (blocks and panels) and ready-mixed concrete. Recycled polyurethane foams and mixed plastics were used as aggre-gates, PFA (Pulverized Fuel Ash, a by-product of coal fuelled power plants) and GGBS (Ground Granulated Blast furnace Slag, a by-product of iron and steel industries) as binders. Eventually, the installation of SUS-CON concrete solutions on real buildings has been demonstrated, with the construction of three mock-ups located in Europe (Spain, Turkey and Romania)