Water dynamics in physical hydrogels based on partially hydrophobized hyaluronic acid.

The dynamics of hyaluronate-based hydrogels has been investigated by quasielastic neutron scattering (QENS). Hyaluronate (HYA) has been compared, in the same conditions of temperature and polymer concentration, to a chemically modified form, HYADD, in which the backbone has been grafted with a hexadecyl (C(16)) side-chain with a degree of substitution of about 2% (mol/mol). This modification increases the hydrophobicity of the polysaccharide and leads to a stable gel already at polymer concentration of 0.3% (w/v), yielding a viscosupplementation with less quantity of polysaccharide. The time-scale covered by our measurements probes both water and segmental biopolymer motions. In both systems, the local dynamics of the network in the ps time-scale is mostly due to local reorientational motions of side groups. Such motions are not significantly affected by the small amount of aliphatic chains forming the hydrophobic junctions in HYADD. The diffusivity of water in both HYA and HYADD coincides with that of pure water within the experimental uncertainty. This result confirms previous ones on the dynamics of water in HYA solutions and it is of relevance for biomedical applications of hyaluronate-based systems because it affects the diffusive processes of metabolites and their interaction with tissues.

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.

Diffusive dynamics of water in tert-butyl alcohol/water mixtures.

Quasielastic neutron scattering has been used to investigate the dynamical behavior of H(2)O in water/tert-butyl alcohol solutions. The measurements were made at fixed temperature (293 K) as a function of tert-butyl alcohol molar fraction, x, in the range 0-0.042. The data have been compared to those of pure water in the temperature range 269-293 K. The effect of tert-butyl alcohol addition on water dynamics is equivalent to that obtained by lowering the temperature of pure water by an amount proportional to the alcohol concentration. The temperature dependence of the diffusivity parameters in pure water and their concentration dependence in tert-butyl alcohol/water solutions can be rescaled to a common curve attributing to each solution a concentration-dependent "structural temperature" lower than the actual thermodynamic one. These results can be understood in terms of Stillinger's picture of water structuring and of other more recent theoretical pictures that emphasize the influence of the geometrical properties of hydrogen bond networks on water mobility.