Synthesis and evaluation of biocompatible pH-sensitive hydrogels as colon-specific drug delivery systems

摘要

Because of the growing importance of pH-sensitive hydrogels as drug delivery systems, biocompatible copolymeric hydrogels based N-vinyl-2-pyrrolidinone (NVP) and methacrylic acid (MAA) were designed and synthesized. These hydrogels were investigated for oral drug delivery. Radical copolymerizations of N-vinyl-2-pyrrolidinone (NVP) and methacrylic acid (MAA) with the various ratios of cross-linking agent were carried out at 70 degrees C. Azabisisobutyronitrile (AIBN) was the free-radical initiator employed and Cubane-1,4-dicarboxylic acid (CDA) linked to two 2-hydroxyethyl methacrylate (HEMA) group was the crosslinking agent (CA) used for hydrogel preparations. The hydrogels were characterized by differential scanning calorimetry and FT-IR. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). A model drug, olsalazine [3,3'-azobis (6-hydroxy benzoic acid)] (OSZ) as an azo derivative of 5-aminosalicylic acid (5-ASA), was entrapped in these gels and the in-vitro release profiles were established separately in both enzyme-free SGF and SIR The drug-release profiles indicated that the amount of drug released depended on the degree of swelling. The swelling was modulated by the amount of crosslinking of the polymer bonded drug (PBDs) prepared. Based on the great difference in hydrolysis rates at pH 1 and 7.4, these pH-sensitive hydrogels appear to be good candidates for colon-specific drug delivery.