Diselenide-containing nonionic gemini polymeric micelles as a smart redox-responsive carrier for potential programmable drug release

Redox-responsive polymeric micelles carriers have been developing rapidly in recent years. Despite great achievements having been made, the acute defects of low drug loading content and drug loading efficiency, weak sensitivity to redox environment of tumor tissue, limited stability in the circulation fluids and less programmable release hinder their further applications. In this work, a sort of diselenide-containing nonionic gemini polymeric micelles carriers (PEG-Gn, n = 8, 12, 16) was synthesized. The resultant micelles of PEG-G12 have a small average size (less than 100 nm), high drug loading efficiency (77%) and acceptable drug loading content (7.1%), which may be attributed to their gemini structure with a lower critical micelle concentration and a larger average minimum area per polymer molecules of micelles. In addition, PEG-G12 can smartly judge the redox environment to release the loaded drugs. In vitro release experiments showed that the indometacin-loaded polymeric micelles could hold the drugs in the circulation fluids in 0.02 mM 1,4-dithiothreitol (only 27% release in 24 h) and release the drugs rapidly and sufficiently in 10 mM 1,4-dithiothreitol (82% in 24 h). More interestingly, these indometacin-loaded micelles could first respond to the reactive oxygen species and then to the 1,4-dithiothreithol, achieving a programmable release of indometacin. We expect that this work could provide a versatile platform for the next generation of redox-responsive polymeric micelles carriers with better comprehensive performances.