Eugenol (EU) and ibuprofene (IBU) were covalently bound to a bi-functionalized PEG, used as molecular carrier of drugs and the release kinetics of the two bioactive molecules was studied in vitro in buffer solution at pH 7.4, in simulated gastric fluid and in mouse plasma. The hydrolysis studies showed a specific cleavage dependent on the pH of the medium and by the presence of proteolytic enzymes in mouse plasma. Studies in vitro on the release of the parent drug from this double prodrug in various media, indicate that the adduct may be sufficiently stable to pass intact the gastrointestinal tract and release into the circulation EU and IBU. Many advantages may be achieved by the synthesis of the prodrug EU-PEG-IBU related to synergistic analgesic and anti-inflammatory effects, to the reduction of the adverse reactions and the improvement of the chemical-physical properties of the parent drugs.
