In vitro and in vivo assessment of novel pH-sensitive interpenetrating polymer networks of a graft copolymer for gastro-protective delivery of ketoprofen

Abstract

The pH-sensitive polyacrylamide-grafted-tamarind seed polysaccharide (PAam-g-TSP) copolymer was synthesized under microwave irradiation in the presence of ceric ammonium nitrate in order to initiate the reaction. The reaction mixture was subjected to hydrolysis in alkaline medium. The copolymer was characterized with the help of FTIR, ¹H-NMR and elemental analysis techniques. Furthermore, pH-sensitive IPN microbeads were prepared from these polymers in combination with sodium alginate through a dual crosslinking process and used for gastro-protective delivery of ketoprofen. The IPN microbeads were tested in vitro and in vivo and showed pH-dependent swelling/shrinking with the changing pH of the medium. Drug release was higher in 7.4 pH medium (about 83%), but it was lower in pH 1.2 medium (about 17%). The in vivo pharmacokinetics, anti-inflammatory activity and stomach histopathological evaluation performed on Wistar rats suggested that the microbeads are pH-sensitive and they were able to target ketoprofen to the intestine, resulting in diminished adverse effects in the stomach.