Preparation of pH/redox dual responsive polymeric micelles with enhanced stability and drug controlled release.

Stimuli-responsive polymeric micelles were prepared through self-assembly of amphiphilic copolymers poly(ethylene glycol)-poly(γ-benzyl l-glutamate), followed by a core-crosslinking reaction using cystamine as the crosslinking agent. The crosslinked micelles with spherical morphologies in nanometer size showed enhanced stability against dilution and concentrated salt solutions compared to the micelles before crosslinking. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through electrostatic interactions between carboxylic acid and DOX. In vitro drug release under pH and redox conditions was investigated. Furthermore, the cytotoxicity of micelles was evaluated before and after drug loading. The endocytosis of DOX-loaded micelles and the intracellular drug release were studied. DOX-loaded micelles exhibited accelerated drug release behaviors in an acidic and reductive environment, and showed an inhibited premature release behavior as compared to the noncrosslinked micelles. Considering their enhanced stability, pH and redox dual triggered responsive characteristics, the polymeric micelles can serve as potential systems for controlled drug delivery.