Redox- and pH-responsive hydrogels: formulation and controlled drug delivery

A novel drug-delivery carrier, poly(ethylene glycol) methyl ether methacrylate/2-(diethylamino) ethyl methacrylate/bis (2-methacryloxyethyl) disulfide (PEDS) hydrogel, was prepared with poly(ethylene glycol) methyl ether methacrylate (PEGMA) and amine containing 2-(diethylamino)ethyl methacrylate (DMAEMA) monomers and a disulfide-containing cross-linking agent bis(2-methacryloxyethyl) disulfide (DSDMA). The RN(C₂H₅)₂ in poly(2-(diethylamino)ethyl methacrylate) (PDMAEMA) can be protonated in acidic environments, causing the expansion of the polymer network and promotion of drug release. The presence of the biologically available reducing agent glutathione (GSH) induces disulfide bond cleavage in DSDMA, which initiates the expansion of the polymer networks. The inner morphology dependence on redox and pH conditions for PEDS₁ hydrogels was revealed. In neutral solutions without GSH, a pore structure with full, thick walls was observed. In acidic or GSH solutions, the pore structure was destroyed, and the pore cell walls were thin or broken. These changes can induce drug release. Drug release studies were also conducted using berberine as a model drug. The drug released from the hydrogels into the supernatant was measured in both GSH and acidic solutions. PEDS₁ hydrogels exhibited a substantial enhancement in release rates in acidic solutions or neutral GSH solutions, suggesting the drug release from PEDS hydrogels is redox- and pH-dependent.