Preparation of thermo/pH-sensitive reduced graphene oxide interpenetrating hydrogel nanocomposites for co-delivery of paclitaxel and epirubicin

This study aimed to develop a thermo/pH-sensitive hydrogel for co-delivery of paclitaxel (PTX) and epirubicin (EPI) in tumor combination chemotherapy. First, pluronic F127/reduced graphene oxide (PF127/RGO) nanocomposites were prepared through the simultaneous reduction of graphene oxide and assembly of PF127 and RGO. Then, PTX was loaded onto PF127/RGO (PTX@PF127/RGO) by - stacking and hydrophobic interaction. Second, graphene double network hydrogels (GDL) were prepared using poly(N-isopropylacrylamide) and polyacrylic acid as crosslinked network and PTX@PF127/RGO as an additive. The structure and properties were investigated by infrared spectroscopy (IR), scanning electron microscopy (SEM), swelling rate tests (SR), and differential scanning calorimetry (DSC). Lastly, the hydrophilic drug EPI was encapsulated in the GDL matrix (EPI@PTX@GDL), which showed thermo/pH-dependent releasing behavior. Cell viability experiments demonstrated that the EPI@PTX@GDL showed a superior cytotoxicity against MCF-7 cells than single drug-loaded forms, whereas the blank GDL and RGO displayed no obvious cytotoxicity.