Development of itaconic acid-based molecular imprinted polymers using supercritical fluid technology for pH-triggered...

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 (scCO₂) in high yields. Further, impregnation of MZ was performed in scCO₂ 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 scCO₂-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.