Starch-based dual amphiphilic graft copolymer as a new pH-sensitive maltidrug co-delivery system

Amphiphilic dual graft copolymer composed of starch (St) as main chain, poly caprolactone (PCL) and poly (2-ethyl 2-oxazoline) (PDX) as hydrophobic and hydrophilic side chains were synthesized and characterized successfully. Firstly, polycaprolactone with propargyl end group prepared and attached to the surface of azido starch (St-N-3) which was prepared through incomplete azidation of starch tosylate, by click chemistry reaction. Thereafter, the polymerization of 2-ethyl-2-oxazoline initiated from the remaining tosyl groups of PCL-starch. Finally, polymerization of PDX quenched by doxorubicin (DOX) as anticancer drug as well as terminator and curcumin (Cur) physically loaded in to the obtained copolymer. Dual graft copolymer (PCL-St-PDX) as the codelivery system containing covalently conjugated doxorubicin and non-covalently loaded curcumin could be promising biocompatible system to achieve combination therapy. The SEM images showed that resulting copolymer exhibited sphere-shaped particles ranging from 50 to 100 nm which is completely different from ungrafted starch. The release studies also revealed that obtained copolymer is pH-sensitive and the release rate was more favorable at acidic pH (tumor cells) than neutral pH (normal cells) for both drugs. (C) 2018 Elsevier B.V. All rights reserved.