Fast release behavior of block copolymer micelles under high intensity focused ultrasound/redox combined stimulus

Abstract

Aiming at the development of a controlled redox responsive polymeric micelle system, a series of redox-sensitive ABA triblock degradable copolymers with different amounts of disulfide bonds were synthesized. These multi-disulfide-containing amphiphilic copolymers are able to self-assemble in aqueous solution to form spherical micelles with a hydrophobic polyurethane block forming the hydrophobic core. The presence of dynamic and labile disulfide bonds in the copolymer makes the copolymer and its micelle have responsivity to stimuli such as redox agents and ultrasound. The micellar properties and release kinetics of encapsulated guest molecules in response to stimuli were investigated using hydrophobic pyrene as a fluorescent probe and DTT as a redox agent. The redox-responsive behavior could be adjusted by changing the amount of disulfide bonds within the copolymer backbone. A relatively fast release behavior was observed for micelles formed by the copolymers in which every repeat unit of the hydrophobic block contains a disulfide bond. Furthermore, the release rate could be greatly enhanced and adjusted remotely under HIFU irradiation in the presence of DTT. The HIFU/redox combined stimulus for the specially designed copolymer micelles containing disulfide bonds provides a novel modality for drug delivery systems.