A novel pH-responsive molecularly imprinted polymer (MIP) based on Itaconic acid:Ethylene glycol dimethacrylate was developed as a potential body-friendly oral drug delivery system for metronidazole (MZ), a pH-independent drug. MIP performance was evaluated in a simulated oral administration situation, at pHs 2.2 and 7.4. Itaconic acid-based copolymers were synthesized using two different molar ratios of template:monomer:crosslinker (T:M:C), 1:5:25 and 1:5:50, in supercritical carbon dioxide (scCO) in high yields. Further, impregnation of MZ was performed in scCO environment. Morphological and chemical properties of the copolymers produced were assessed by SEM, Morphologi G3 and FTIR analyses. Non-molecularly imprinted polymer (NIP) matrices presented swelling over time in opposition to the molecularly imprinted ones. In the scCO-impregnation process, MIPs showed a significant molecular recognition towards MZ, presenting higher drug uptake ability with MZ loading of 18-61 wt% in MIPs, compared to 7-20 wt% in NIPs. In vitro drug release experiments presented different release profiles at the different pHs, where MZ-MIPs could release higher amounts of MZ at the lowest pH than at pH 7.4.