Hydrazone cross-linked micelles based on redox degradable block copolymer for enhanced stability and controlled drug release

In this work, an amphiphilic copolymer, PCL-SS-P(PEGMA-co-MAEBA), which contained a disulfide joint in backbone was designed and synthesized. The subsequent micelles that self-assembled from the copolymers were cross-linked by hydrazone, resulting in novel stimuli-responsive degradable micelles with a reversible cross-linked shell. By way of the hydrazone cross-linking of the micellar shell, SCMs owned a good stability against the extensive dilution by water or organic solvent. Doxorubicin (DOX) was used as the model drug for studying the in vitro release profiles of the SCMs. In normal physiological conditions at pH7.4, a quite slow speed was observed with DOX release (only 23% after 72h); when conditions were changed to pH5.0, the SCMs successfully de-crosslinked, DOX release was accelerated (62%). Moreover, drug release was further promoted and reached 87% when 10mM GSH was present, which was primarily due to the breakage of the disulfide joint. The intracellular uptake assay proved that DOX from DOX-loaded SCMs could be efficiently delivered into HepG2 cells after 12h incubation. MTT assays confirmed that DOX-loaded SCMs owned a high cytotoxicity against HepG2 cells. These redox-responsive, degradable SCMs could be a potential candidate for efficient insoluble anticancer drug delivery and therapy.