Novel glucose-sensitive systems for the release of insulin from poly(diethylaminoethyl methacrylate) (PDEAEM) microparticles and nanoparticles decorated with glucose oxidase and catalase enzymes have been developed. The effect of polymer composition and loading conditions on the insulin loading efficiency and release was studied. The optimal conditions for loading insulin into PDEAEM microparticles were found to be at a loading pH of 5.6, particle to insulin mass ratio of 7:1, a concentration of 1.0 mg/mL insulin, and a collapsing pH of approximately 9.5. Microparticles exhibited a responsive (pH) or intelligent (glucose) release of insulin from a stimulus. Microparticles that had a nominal crosslinking ratio of 10% released a third of the insulin payload after a single stimulus, compared to nearly 70% for microparticles with a 3% crosslinking ratio. PDEAEM microparticles of 150 m diameter showed promise as components of a system of automated, intelligent delivery method for insulin to type I diabetics. (c) 2013 American Institute of Chemical Engineers AIChE J, 59: 3578-3585, 2013