Mark T. F. Telling

Novel PVA-based hydrogel microparticles for doxorubicin delivery.

Micro- and nanoparticles are considered suitable drug delivery systems for their unique features, such as a large surface to volume ratio, and for the possibility to tune their size and hydrophobicity. A polymer/polymer/water emulsion method was used for producing a chemically cross-linked hydrogel made of poly(vinyl alcohol) and of poly(methacrylate) moieties. Mesoscopic investigation of the microparticles was accomplished by laser scanning confocal microscopy. Dynamics of confined water within the gel meshes was studied by quasi-elastic incoherent neutron scattering. Succinoylation of these particles allowed an efficient loading with a maximum doxorubicin payload of about 50% (w/w) of dry microparticles. To evaluate the potentials of such a microdevice for drug delivery, LoVo colon cancer cells have been exposed to doxorubicin loaded microparticles to study the in vitro efficiency of the payload release and the consequent cytotoxic effect.

Study of the dynamical properties of water in disaccharide solutions

This work presents quasi-elastic neutron scattering (QENS) and neutron spin echo (NSE) findings on homologous disaccharide (i.e. trehalose, maltose and sucrose)/water solutions as a function of temperature. The dynamical properties of these systems are investigated by QENS, which, on the picosecond scale, allows for the characterisation of the diffusion of both solutes and solvent. On the other hand, NSE investigates the dynamics on the nanosecond scale, allowing for the relaxation times of the disaccharide/water systems to be evaluated. The experimental data highlight a strong slowing down of water in the presence of disaccharides. The whole set of findings indicates, therefore, a noticeable disaccharide–water interaction, which is more intense in the case of trehalose. This feature can justify its higher bioprotective effectiveness.

Restricted dynamics in polymer-filler systems

We have investigated the dynamic properties of poly(dimethylsiloxane) (PDMS) and poly(vinyl acetate) (PVAc) filled with hydrophilic Aerosil (nano-particles of fumed silica) using the backscattering spectrometer IRIS at ISIS. Through the analysis of the incoherent scattering, the quasi-elastic neutron scattering (QENS) technique probes the motion of the hydrogen atoms and it therefore provides detailed information on the reduced mobility of chain segments in polymer filler systems. QENS measurements reveal a progressive slowing down of the motion with increasing particle surface area which is in agreement with the DMTA data of Tsagaropoulos and Eisenberg. In particular, the QENS spectra of the polymer-filler composites confirmed the existence of two dynamic processes. Therefore, data analysis was carried out by taking into account two contributions: (a) a quasielastic component due to chains not affected by the presence of fillers and (b) an elastic component from chains whose dynamics is strongly restricted. The latter depends on the specific surface area of the particles and their weight fraction in the composites.

Gapless Spin Liquid Ground State in the S=1/2 Vanadium Oxyfluoride Kagome Antiferromagnet [NH4 ]2[C7H14N][V7O6F18]

The vanadium oxyfluoride [NH(4)](2)[C(7)H(14)N][V(7)O(6)F(18)] (DQVOF) is a geometrically frustrated magnetic bilayer material. The structure consists of S = 1/2 kagome planes of V(4+) d(1) ions with S = 1 V(3+) d(2) ions located between the kagome layers. Muon spin relaxation measurements demonstrate the absence of spin freezing down to 40 mK despite an energy scale of 60 K for antiferromagnetic exchange interactions. From magnetization and heat capacity measurements we conclude that the S = 1 spins of the interplane V(3+) ions are weakly coupled to the kagome layers, such that DQVOF can be viewed as an experimental model for S = 1/2 kagome physics, and that it displays a gapless spin liquid ground state.

Nano-scale hydrogen-bond network improves the durability of greener cements.

More than ever before, the worlds increasing need for new infrastructure demands the construction of efficient, sustainable and durable buildings, requiring minimal climate-changing gas-generation in their production. Maintenance-free “greener” building materials made from blended cements have advantages over ordinary Portland cements, as they are cheaper, generate less carbon dioxide and are more durable. The key for the improved performance of blends (which substitute fine amorphous silicates for cement) is related to their resistance to water penetration. The mechanism of this water resistance is of great environmental and economical impact but is not yet understood due to the complexity of the cements hydration reactions. Using neutron spectroscopy, we studied a blend where cement was replaced by ash from sugar cane residuals originating from agricultural waste. Our findings demonstrate that the development of a distinctive hydrogen bond network at the nano-scale is the key to the performance of these greener materials.

Dynamics of propylene glycol and its 7-mer by neutron scattering

The dynamics of propylene glycol (PG) and its 7-mer have been investigated by quasielastic neutron scattering (QENS). In the case of PG we used two techniques; ordinary QENS and neutron spin-echo (NSE). The QENS and NSE experiments were carried out at the temperature ranges 300–420 K and 260–340 K, respectively. The QENS results on both the monomer and the 7-mer showed three clear dynamical processes; a weakly temperature dependent fast local motion of hydrogens in the polymeric backbone, an almost temperature independent rotational motion of the methyl groups, and a strongly temperature dependent translational process. This latter motion exhibits a clear quasi-elastic broadening proportional to Q2 at high temperatures (T⩾380 K). At lower temperatures the diffusion becomes more difficult to characterize due to the contribution from the methyl group rotation. However, despite this difficulty it is no doubt about that the diffusion is faster for the 7-mers than for the monomers at low temperatures (T⩽340 K)...

Pressure-dependent deuterium reaction pathways in the Li-N-D system

Neutron diffraction data from in situ deuteration and dedeuteration of Li(3)N are presented under different pressure regimes, whereby reaction pathways differing from the widely reported stoichiometric pathway of Li(3)N + 2D(2)<--> Li(2)ND + LiD + D(2)<--> LiND(2) + 2LiD are observed. At sufficiently high pressures, where the deuterium chemical potential is comparable with the heat of amide formation, the reaction appears to be driven straight to the amide plus deuteride phase mixture. At lower pressures, a cubic phase exhibiting a concentration-dependent variation in lattice parameter is observed. In dedeuteration, two sets of reflections from cubic structures with distinct lattice parameters are observed, both of which exhibit a continual decrease in cell volume. The reaction pathways are discussed in terms of the compositional variation.

Structure and Dynamics of a Thermoresponsive Microgel around Its Volume Phase Transition Temperature

Sustained drug delivery requires the use of multifunctional devices with enhanced properties. These properties include responsiveness to external stimuli (such as temperature, pH, ionic strength), ability to deliver suitably designed ligands to specific receptors, enhanced bioadhesion to cells, and cytocompatibility. Microgels represent one of such multifunctional drug delivery devices. Recently, we described the fabrication of a stable colloidal aqueous suspension of cytocompatible microgel spheres based on a poly(vinyl alcohol)/poly(methacrylate-co-N-isopropylacrylamide) network ( Ghugare, S. Mozetic, P. Paradossi, G. Biomacromolecules 2009 , 10 , 1589 ). These microgel spheres undergo an entropy-driven volume phase transition around the physiological temperature, this phase transition being driven by the incorporation of NiPAAm residues in the network. In that study, the microgel was loaded with the anticancer drug doxorubicin. As the microgel shrank, a marked increase in the amount of doxorubicin released was noted. Indeed, dynamic light scattering measurements showed the diameter reduction to be about 50%. In the present paper, we focus on some fundamental issues regarding modifications of the hydrogel architecture at a nanoscopic level as well as of the diffusive behavior of water associated with the polymer network around the volume phase transition temperature (VPTT). Sieving and size exclusion effects were studied by laser scanning confocal microscopy with the microgel exposed to fluorescent probes with different molecular weights. Confocal microscopy observations at room temperature and at 40 degrees C (i.e., below and above the VPTT) provided an evaluation of the variation of the average pore size (from 5 nm to less than 3 nm). Using quasielastic neutron scattering (QENS) with the IRIS spectrometer at ISIS, UK, the diffusive behavior of water molecules closely associated to the polymer network around the VPTT was investigated. A clear change in the values of diffusion coefficient of bound water was observed at the transition temperature. In addition, the local dynamics of the polymer itself was probed using the QENS spectrometer SPHERES at FRM II, Germany. For this study, the microgel was swollen in D(2)O. An average characteristic distance of about 5 A for the localized chain motions was evaluated from the elastic incoherent structure factor (EISF) and from the Q-dependence of the Lorentzian width.

Study of the relaxational and vibrational dynamics of bioprotectant glass-forming mixtures by neutron scattering and molecular dynamics simulation

In this work inelastic neutron scattering (INS) and quasielastic neutron scattering (QENS) data, collected at different temperature values by the OSIRIS and IRIS spectrometers at the ISIS Facility (Rutherford Appleton Laboratory, Oxford, UK) on mixtures of two glass-forming bioprotectant systems, i.e., trehalose and glycerol, as a function of concentration are presented. The data analyses show that the fast local dynamics, measured by INS, as well as the diffusive dynamics, measured by QENS, exhibit in the investigated mixtures a switching-off maximum in the same concentration range corresponding to a very low glycerol content. This effect can be accounted for by a not-ideal mixing process of the pure constituents due to an increased hydrogen bonding network strength. The experimental studies are completed by molecular dynamics simulation findings.

How mobile are protons in the structure of dental glass ionomer cements

The development of dental materials with improved properties and increased longevity can save costs and minimize discomfort for patients. Due to their good biocompatibility, glass ionomer cements are an interesting restorative option. However, these cements have limited mechanical strength to survive in the challenging oral environment. Therefore, a better understanding of the structure and hydration process of these cements can bring the necessary understanding to further developments. Neutrons and X-rays have been used to investigate the highly complex pore structure, as well as to assess the hydrogen mobility within these cements. Our findings suggest that the lower mechanical strength in glass ionomer cements results not only from the presence of pores, but also from the increased hydrogen mobility within the material. The relationship between microstructure, hydrogen mobility and strength brings insights into the materials durability, also demonstrating the need and opening the possibility for further research in these dental cements.