Water-insoluble pullulan-g-poly(L-lactide) (PUPL) was successfully synthesized via a one-pot method in the presence of triethylamine in dimethyl sulfoxide, in an effort to design a novel anticancer agent carrier. Three samples (designated as PUPL 1, 2, and 3) were obtained, which differed in the moles of lactides grafted to the pullulan. The degrees of grafted lactide per 1 glucose unit in pullulan were 0.68, 0.60, and 0.45 for PUPL 1, 2, and 3, respectively. These copolymers were dissolved in several organic solvents, including dimethyl sulfoxide, acetone, and ethanol, but were insoluble in water. The self-organized nanogels were then prepared from the polymers via dialysis. To study the organizing behavior of the polymers, their critical association concentrations were measured. Their values were 5.0, 15.9, and 52.9 mg/L for PUPL 1, 2, and 3, respectively. The results showed that lactide in the polymers could function as a hydrophobic moiety for the formation of selforganized nanogels. To estimate the potential of PUPL 1 as an anticancer drug carrier, we used doxorubicin (DOX) as a model drug. The DOX loading efficiencies of PUPL 1 were more than 52%, which differed with differing initial DOX concentrations. High loading resulted in slower DOX release as the result of increases in hydrophobic interaction.In conclusion, PUPL nanogels may prove useful as anticancer drug carriers because of their low critical association concentrations and the controlled DOX release rate V

Intracellular thiol can trigger effective drug release from polymeric nanoparticles having multiple disulfide linkages in the hydrophobic domain.