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

Abstract

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.

Recent progress on polymer dynamics by neutron scattering: From simple polymers to complex materials

“…53 Finally, hydrated polymers and polymer solutions-in particular, microgels-have also recently been investigated by QENS. [54][55][56][57][58][59][60][61][62][63] Studies on concentrated aqueous solutions show that confinement effects also arise -in this case for the minority water component-when the polymer freezes approaching its glass-transition. The component dynamics in these solutions can be selectively monitored by QENS, a task that is not easily achievable by other usually applied experimental approaches like, for example, dielectric spectroscopy.…”

Multiresponsive Hyaluronan‐p(NiPAAm) “Click”‐Linked Hydrogels

“…This goal has been accomplished by designing hybrid hydrogels or composites structures, in which each polymer component contributes to specific properties of the overall system and it allows to switch individually or in a concerted way the responsivities and functionalities of the hydrogels. Typically, but not exclusively, the response is a physical or chemical sudden change of external stimuli as pH, temperature, ionic strength, electric, or magnetic fields, light intensity …”

Isothermal dehydration of thin films of water and sugar solutions

“…The presence of sugar molecules into the solution significantly affects how water diffuses, as demonstrated at the molecular level by neutron scattering experiments and molecular simulations. [38][39][40][41] At the end of the drying, trehalose molecules slow down the diffusion of water molecules through the paper web in a more pronounced way than those of glucose. The implications of hydrophilic solutes, highly hydrated low-or high-molecular-weight compounds, on the evolution of the evaporation rate should also be mentioned.…”