Synthesis of polyacrylamide nanogels by intramolecular disulfide cross-linking

Nondegradable polyamides with protein-like properties were designed and prepared as a copolymeric hydrogel by the free-radical polymerization of acrylamide with a disulfide-containing cross-linking agent, N, N'-bisacryloylcystamine. Copolyacrylamides containing pendent thiol groups (-SH) were obtained after reduction of the disulfide bonds in the hydrogel, followed by precipitation in methanol. Ellman's analysis and gel-permeation chromatography (GPC) were used to characterize the copolymer. Re-dissolution of the copolymer in water at very dilute concentrations, followed by air oxidation under physiological conditions (pH 7.5), resulted in nanoparticles (nanogels). The dilute concentration favored intramolecular disulfide cross-linking in the polymer chain, resulting primarily in a single-chain nanogel. Nanogel formation was confirmed and characterized using GPC, dynamic light scattering and atomic force microscopy. The size of the nanogels ranged from 20-200 nm.