This work reports the development of a novel potential body-friendly oral drug delivery system, which consists of a biocompatible molecularly imprinted polymer (MIP), with pH sensitive character and low cross-linking degree (20.2 wt%), synthesized and processed in supercritical carbon dioxide. The \{MIP\} is synthesized using 2-(dimethylamino)ethyl methacrylate (DMAEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as cross-linker, and ibuprofen as molecular recognition template. The imprinted matrix was able to show a higher affinity towards ibuprofen than its corresponding non-imprinted polymer (NIP) meaning that the molecular imprinting in scCO2 was efficient even using a low crosslinking degree. \{MIP\} showed a significant molecular recognition towards the template, presenting higher drug uptake ability in the supercritical impregnation step, loading 33.1 wt% of ibuprofen compared to only 10.2 wt% for the \{NIP\} polymer. In vitro drug release experiments, simulating an oral administration, showed different release profiles at pH 2.2 and pH 7.4. Zeta potential measurements were performed to both \{MIP\} and \{NIP\} showing that the imprinting process has a significant influence on the charge of the polymeric particles. Cytotoxicity assays performed with human colorectal carcinoma-derived Caco-2 cells demonstrated that the polymers are biocompatible and could be potentially used in drug delivery applications.
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