Evaluation of redox-responsive disulfide cross-linked poly(hydroxyethyl methacrylate) hydrogels

Poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels were prepared with a disulfide containing cross-linker bis(2-methacryloxyethyl) disulfide (DSDMA) that exhibited enhanced release in the presence of glutathione (GSH), a biologically available reducing agent. Varying concentrations of the DSDMA cross-linker were incorporated into the prepolymer before the radical polymerization, enabling the cross-link density to be easily tuned. Dye release studies were performed using rhodamine B and rhodamine 6G dyes, and the UV response of the dyes released into the supernatant measured with the addition of GSH. Using ether-based cross-linkers as a control, the disulfide cross-linkers exhibited a substantial increase in release rates, confirming the responsive nature of the hydrogels to biological reducing agents. The polymers were also tested in a cell culture system for their ability to release the anti-fibroproliferative agent, mitomycin C (MMC). Polymers cross-linked with DSDMA delivered MMC over a slightly longer time period than control polymers prepared with a conventional ether cross-linker.