The dual temperature/pH-sensitive multiphase behavior of poly(N-isopropylacrylamide-co-acrylic acid) microgels for potential application in in situ gelling system

Poly(N-isopropylacrylamide-co-acrylic acid) microgels (PNA) may be an excellent formulation for in situ gelling system due to their high sensitivity and fast response rate. Four monodispersed PNA microgels with various contents of acrylic acid (AA) were synthesized by emulsion polymerization in this paper. Their hydrodynamic diameters decreased reversibly with both decreasing pH and increasing temperature. The dual temperature/pH-sensitivity was influenced by many factors such as AA content, cross-link density and ion strength. In addition, high concentration PNA dispersions underwent multiple phase transition according to different temperatures, pHs and concentrations, which were summarized in a 3D sol–gel phase diagram in this study. According to the sol–gel phase transition, 8% PNA-025 dispersion maintained a relatively low viscosity and favorable fluidity at pH 5.0 in the temperature range of 25–40 °C, but it rapidly increased in viscosity at pH 7.4 and gelled at 37 °C. This feature enabled the dual temperature/pH-sensitive microgels to overcome the troubles in syringing of temperature sensitive materials during the injection. Apart from this, PNA could form gel well in in vitro (e.g., medium and serum) and in in vivo with low cytotoxicity. Therefore, it is promising for PNA to be applied in the in situ gelling system.