Systemic modulation of the stability of pluronic hydrogel by a small amount of graphene oxide

Thermo-sensitive and injectable hydrogels have been widely investigated for drug delivery, tissue engineering, and other biomedical applications. Pluronic copolymers can form thermo-sensitive physical gel state, thus applicable for injectable hydrogels. However, they are not stable in vivo, showing a very fast dissolution, which limits their applications. We propose a novel Pluronic-based physical hydrogel with enhanced stability by simply adding a small quantity of graphene oxide (GO) which has a large surface area and can make strong interactions with Pluronic. Further carboxylated GO could act as a more efficient additive. The addition of GO increased the moduli of hydrogels, but more importantly, it enhanced the stability of Pluronic gel dramatically. The in vitro dissolution rate of Pluronic hydrogel could be systematically modulated by increasing GO content. Upon subcutaneous injection at a sol state, GO-containing hydrogel induced a stable gel state, and was maintained over several weeks whereas very fast degradation was observed without the addition of GO. Furthermore, histological analyses demonstrated that the GO-containing Pluronic hydrogel was biocompatible and showed no severe inflammatory response. Similarly, GO-containing hydrogel resulting from the packing of Pluronic-based nanogel also showed the more enhanced stability by the addition of GO both in vitro and in vivo. In both systems, hydrogels with remarkably enhanced stability by the addition of GO were also effective for the sustained release of loaded protein, and the release rates were mainly determined by the degradation rates of hydrogels. Thus, these GO-containing Pluronic systems can be used as a thermo-sensitive injectable system with a sufficient stability in vivo.