Eleanor Owens

Synthesis of mucoadhesive thiolated gelatin using a two-step reaction process

Using a novel two-step approach, the thiolation of gelatin for mucoadhesive drug delivery has been achieved. The initial step involved the amination of native gelatin via an amine to carboxylic acid coupling reaction with ethylene diamine, followed by thiolation with Trauts reagent. The resulting thiolated product showed an increase in thiol content of up to 10-fold in comparison with control gelatin samples. Improved cohesion and mucoadhesion in comparison with unmodified and control gelatin samples was also observed. This reaction process was observed to be influenced by both the temperature and the pH of the amination reaction, affecting both amine content and product yield. Swelling ability, cohesion and mucoadhesion were all observed to be strongly dependent on the thiol content of the samples but also, importantly, the molecular weight (MW) of the gelatin used. Gelatin with a MW of 20-25 kDa proved to be optimal in creating this novel mucoadhesive gelatin material.

The development of novel organically modified sol-gel media for use with ATR/FTIR sensing.

The ability to prepare and develop novel pre-concentration media by the sol-gel process, and their integration with mid-infrared transparent waveguides has been demonstrated. This research approach resulted in a mid-infrared sensing methodology in which the properties (porosity, functionality, polarity, etc.) of the recognition layer could be tailored by variation of the sol-gel precursors and processing conditions. Cross-linker type and concentration notably influenced p-xylene absorption and diffusion rate. Unreacted silanol groups appeared to be the dominant factor in the hydrophobicity of sol-gel layers. Variation of sol-gel precursors and thermal treatment altered both film cross-link density and polarity, as demonstrated by variation in the rate of analyte diffusion and equilibrium analyte concentration. The use of a novel 1 : 1 PTMOS : DPDMS material as pre-concentration medium in this analytical sensing approach was validated through the determination of p-nitrochlorobenzene in an aqueous environment. The response demonstrated linearity between 0-30 mg L(-1) with a correlation coefficient of 0.989 and a limit of detection of 0.7 mg L(-1). Sensing times for p-nitrochlorobenzene were also reduced from several hours to 24 minutes, without loss of measurement accuracy or sensitivity, by a 10 degrees C increase in the sensing temperature and the use of a predictive Fickian model previously developed by this research group.

Thiolated polymers as mucoadhesive drug delivery systems

&NA; Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices. Graphical abstract Figure. No caption available.

Enhancement and restriction of chain motion in polymer networks.

Sevelamer carbonate, a polymeric drug, adsorbs phosphate ions from the gastro intestine of patients suffering from chronic kidney disease. Polymer chain mobility becomes critical during its manufacture and storage. How the polymer chain mobility in sevelamer carbonate is quantitatively controlled by small molecular species, in this case by water molecules and bicarbonate anions, is demonstrated here. Spin-lattice relaxation times of the protons in the hydrogel, detected by solid state NMR, are indicative of mobility within the polymer. They decreased with increasing water content but increased as the bicarbonate anion content increased. As the water content increased, the glass transition temperature decreased but increasing the bicarbonate anion content had the opposite effect. FTIR analysis indicated that the anions were involved in bonding while the water molecules were not. The stability and physicochemical properties of polymers during storage and formulation depend on the polymeric structure and the dynamic behaviour of the polymer chains.

Thermal desorption characterisation of molecularly imprinted polymers. Part II: Use of direct probe GC–MS analysis to study crosslinking effects

A powerful method utilising direct probe thermal desorption GC–MS is presented for the study of molecularly imprinted polymers (MIPs). A series of 2-aminopyridine (2-apy)-imprinted methacrylic acid–ethyleneglycol dimethacrylate (MAA–EGDMA) copolymers were prepared under identical conditions but with varying amounts of EGDMA (crosslinking monomer). The use of appropriate temperature programmes permitted template removal, and the subsequent assessment of polymer affinity and specificity, all of which were found to be dependent on polymer composition and morphology. The system was sufficiently sensitive to identify a specific response of imprinted polymers over nonimprinted counterparts. Correlations were found to exist between thermal desorption analysis and solution phase binding, which was assessed by UV spectroscopy, where specificity was found to diminish with decreasing EGDMA concentration. This was attributed to the increased number of free carboxyl groups in those polymers containing a lower percentage of EGDMA. Thermal desorption profiles obtained for the analyte were found to be unaffected by the physical and chemical properties of the solvent used for analyte reloading.

Comparison of the mucoadhesive properties of thiolated polyacrylic acid to thiolated polyallylamine.

Synthetic polymers, polyacrylic acid (PAA) and polyallylamine (PAAm), were thiolated using different methods of thiolation. Both polymers resulted in comparable thiol contents, thus allowing for the direct comparison of mucoadhesive and cohesive properties between the well-established thiolated PAA and the more novel thiolated PAAm. Thiolation of both polymers improved the swelling ability and the cohesive and mucoadhesive properties in comparison to unmodified control samples. In this study, it was shown that the swelling abilities of the thiolated PAAm sample were far greater than that of the thiolated PAA sample which, in turn, affected the drug release profile of the thiolated PAAm sample. Importantly, however, the mucoadhesive properties of thiolated PAAm were equivalent to that of the thiolated PAA sample as demonstrated by both the adhesion times on porcine intestinal tissue as measured by the rotating cylinder method and by rheological studies with a mucin solution. This study demonstrates the potential thiolated polyallylamine has as a mucoadhesive drug delivery device.

Kinetic and thermodynamic evaluation of phosphate ions binding onto sevelamer hydrochloride.

Sevelamer hydrochloride is the first non-aluminium, non-calcium-based phosphate binder developed for the management of hyperphosphatemia in end stage renal diseases. It is a synthetic ion-exchange polymer which binds and removes phosphate ions due to the high content of cationic charge associated with protonated amine groups on the polymer matrix. This is the first in-depth study investigating phosphate removal in vitro from aqueous solutions using commercially available sevelamer hydrochloride at physiological conditions of phosphate level, pH and temperature. The kinetic and thermodynamic parameters of phosphate binding onto the sevelamer hydrochloride particles were evaluated in order to define the binding process. A series of kinetic studies were carried out in order to delineate the effect of initial phosphate concentration, absorbent dose and temperature on the rate of binding. The results were analysed using three kinetic models with the best-fit of the experimental data obtained using a pseudo-second order model. Thermodynamic parameters provide in-depth information on inherent energetic changes that are associated with binding. Free energy ΔG°, enthalpy ΔH°, and entropy ΔS° changes were calculated in this study in order to assess the relationship of these parameters to polymer morphology. The binding reaction was found to be a spontaneous endothermic process with increasing entropy at the solid-liquid interface.

Capitalizing on SME Green Innovation Capabilities: Lessons from Irish-Welsh Collaborative Innovation Learning Network

Abstract Adopting an EU policy lens, this chapter primarily addresses the proposed pivotal role of firm-level innovation capability (FLIC) in small and medium-sized enterprises (SMEs) as a stimulant of sustainable development (SD) and green growth in Ireland/Wales. The chapter specifically examines the scale and scope of the green economy (GE), and considers the importance of organizational inherent “green” innovation capabilities (GICs) to achieve it. Underpinning the study is the methodology and concept of utilizing a facilitated cross-border multi-stakeholder learning network to enable knowledge transfer and exchange practices to flourish between partners, acting as a significant predictor of the development of SME GICs structures. Specifically, against the backdrop of the Green Innovation and Future Technologies (“GIFT” hereafter) INTERREG 4A Project, the research assesses how academic–industry partner exchange and inter-group learning and cooperation facilitates the development of GICs in smaller enterprises to realize a sustainable smart green economy in Ireland.

Facilitating cross-border rural micro-firm knowledge exchange: A community of practice perspective

Knowledge sharing enhances the capability of rural micro-firms to facilitate economic growth, competitiveness and employment. Knowledge exchange research predominantly focuses on larger firms in the same or related industries, and is of limited relevance in a rural micro-firm context, owing to significant differences in resource availability which can result in strategic knowledge constraints and the meagre development of micro-firms and the regions in which they reside/operate. The aim of this research is to explore the knowledge exchange criteria of rural micro-firms in a cross-border facilitated learning network (FLN). Drawing on the ‘community of practice’ perspective and the closely connected learning network literature, the authors observe and map FLN knowledge exchange activities over a three-year period. The resultant rural FLN knowledge exchange framework demonstrates that discipline and sector-specific barriers can be overcome through cyclical FLN interventions sensitive to the social proximity requirements necessary for effective cross-border knowledge exchange.