Viscoelastic Behavior and In Vivo Release Study of Microgel Dispersions with Inverse Thermoreversible Gelation

The dispersion of microgels with two interpenetrating polymer networks of poly(N-isopropylacrylamide) and poly(acrylic acid) (PNIPAM-IPN-PAAc) has been studied for its viscoelastic behavior, biocompatibility, and in vivo release properties. The IPN microgels in water had an average hydrodynamic radius of about 85 nm at 21 °C, measured by dynamic light scattering method. The atomic force microscope image showed that the particles were much smaller after they were dried but remained spherical shape. The storage and loss moduli (G′ and G′′) of dispersions of IPN microgels were measured in the linear stress regime as functions of temperature and frequency at various polymer concentrations using a stress-controlled rheometer. For dispersions with polymer concentrations of 3.0 and 6.0 wt % above 33 °C, the samples behave as viscoelastic solids and the storage modulus was larger than the loss modulus over the entire frequency range. The loss tangent was measured at various frequencies as a function of temperature. The gelation temperature was determined to be 33 °C at the point where a frequency-independent value of the loss tangent was first observed. At pH 2.5, when heated above the gelation temperature, IPN microgels flocculate by pumping a large amount of water from the gel. When the pH value was adjusted to neutral, deprotonation of −COOH groups on PAAc made the microgel keep water even above the gelation temperature. Using an animal implantation model, the biocompatibility and drug release properties of the IPN microgel dispersion were evaluated. Fluorescein as a model drug was mixed into an aqueous microgel dispersion at ambient temperature. This drug-loaded liquid was then injected subcutaneously in Balb/C mice from Taconic Farms. The test results have shown that the IPN microgels did not adversely promote foreign body reactions in this acute implantation model and the presence of gelled microgel dispersion substantially slowed the release of fluorescein.