Abstract:
Diselenide bond is a kind of stimulus-responsible chemical bond with sensitive redox response, which can be in respone to oxidants or reducers, leading to breakage of their chemical bonds. It will be of great potential and research significance to develop new stimulus responsive materials by combining the responsive redox characteristics of selenium with degradable polymers, which has aroused great concern among academic circles. It is still a challenge to introduce diselenide bond into polymeric carriers. Herein, a series of diselenide. containing carbonate copolymers were designed and synthesized by ring opening polymerization (ROP) through adjusting the feeding ratio during polymerizing. The structure and molecular weight of the obtained copolymers were characterized by different methods such as nuclear magnetic resonance spectroscopy (NMR) and gel permeation chromatography (GPC). Results showed that they had suitable molecular weight, narrow molecular weight distribution and adjustable selenium mass content. Then the diselenide polycarbonates were self-assembled into micelles by dialysis method, film dispersion method and ultrasonic emulsification method, respectively. Morphology of micelles was confirmed by transmission electron microscopy (TEM). Advantages and disadvantages of these different micelle preparation methods were investigated by comparing the particle size and particle-size distribution measured by dynamic light scattering (DLS), as well as drug loading ability measured by ultraviolet spectrophotometer (UV-Vis). Dialysis method and film dispersion method were suitable in preparing the diselenide-containing polycarbonate into micelles. The average particle size of these prepared micelles was less than 200 nm.
In vitro drug release experiments showed that this kind of diselenide containing polycarbonate could release drugs under the stimulation of glutathione (GSH) effectively, and the cumulative release percentages and release rates were related to the selenium content of copolymers. These results laid a solid foundation for the development and application of diselenide-containing polymers as drug carrier materials.