In this study, a series of novel stimuli-sensitive hydrogels based on 2-hydroxyethyl acrylate and itaconic acid monomers were designed for the controlled release of hydrophobic drug, Oxaprozin. All samples were synthesized by the free-radical crosslinking copolymerization and characterized for structural, morphological, thermal, surface charge, swelling and antibacterial properties. In order to investigate the influence of the drug on hydrogel properties the same characterization was conducted for all Oxaprozin-loaded samples. The chemical composition of hydrogels was studied using Fourier transform infrared spectroscopy, while their morphology and thermal properties were examined by scanning electron microscopy and differential scanning calorimetry. Swelling studies, conducted in the physiological pH range from 2.20 to 8.00 and in the temperature range from 25 to 50 degrees C, showed that the loaded drug does not modify the pH and temperature sensitivity of the hydrogels, but reduces their swelling capacity. The in vitro drug release study conducted at pH 2.20 and 7.40 showed that all hydrogels can be tailored as colon specific drug delivery systems, and the drug release rate can be effectively controlled by IA content. In addition, the antibacterial activity of the hydrogels was determined against Escherichia coli and Staphylococcus aureus, by the zone of inhibition test. Results of our study indicate that these "smart" hydrogels, with specific morphology, surface charge, swelling capacity, drug loading efficiency and release behavior, could be designed to obtain an enhanced and site-specific controlled drug release system by simply adjusting their composition.