Design, Characterization and In Vitro Evaluation of Polymethacrylate-Based Drug Delivery Systems for Targeting -Aminosalicylic Acid to the Colon

This research work, describes synthesis and in vitro evaluation of a serious of new acrylic type polymeric prodrugs containing 5-aminosalicylic acid (5-ASA), an important drug in the treatment of inflammatory bowel diseases, as colon targeted drug delivery systems. First, 5-ASA reacted with formic acid to obtain 5-formylaminosalicylic acid in the high yield. Reaction of the obtained material with 2-hydroxypropyl methacrylat in the presence of 1,1 carbonyldiimidazole produced methacryloyloxypropyl-5-aminosalicylate (MOPAS), as a acrylic-derivative of 5-ASA, in a one-pot procedure. The resulted MOPAS was then polymerized with hydrophilic and hydrophobic acrylic-monomers such as 2-hydroxyethyl methacrylat, methyl metacrylat or ethylhexyl acrylate by free radical polymerization method to obtain polymeric prodrugs bearing 5-ASA. All compounds were characterized by FT-IR, 1H NMR, elemental analysis and gel permeation chromatography techniques. Also, thermal behavior of the polymeric prodrugs was investigated by differential scanning calorimeter instrument. The release studies of 5-ASA were performed into dialysis bags by hydrolysis buffered solutions (pH 1, 7, 8) at 37°C. Detection of hydrolysis by UV spectroscopy at selected interval showed that the drug can be released by selective hydrolysis of the ester bond at the side of drug moiety. The release profiles indicated that the hydrolytic behavior of polymeric prodrugs is strongly based on the hydrophobicity of polymers and the pH of the hydrolysis media. The results suggested that these systems could be useful in colon targeted drug delivery systems.