Design of reversibly disulfide core cross-linked polymer micelles

Over the last decade, polymer micelles attracted an increasing interest in drug pharmaceutical research because they could be used as efficient drug delivery systems. Micelles of amphiphilic block copolymers are supramolecular core-shell type assemblies of tens of nanometers in diameter. An accumulation of polymer nanocarriers to solid tumours is possible due to the EPR effect. Even if micelles get a high stability in aqueous media, the dissociation of micelles is not always preserved when they are injected in the blood compartment. This work aims at reporting on the design of reversibly cross-linked micelles based on PEO-b-PCL copolymers by introducing disulfide bridges in the micelle core to provide higher stability. Different kinds of macromolecular architectures are employed to study their impact on the micelles and their biological behavior. These new functional copolymers were all successfully micellized, reversibly cross-linked and are stealthy, which show the efficiency of the developed cross-linking process and offer a set of nanocarriers to be tested further, as shown on the first biological tests.