pH-responsive interpenetrating network hydrogel beads of poly(acrylamide)-g-carrageenan and sodium alginate for intestinal targeted drug delivery: synthesis, in vitro and in vivo evaluation

In the present work, we synthesized pH-responsive interpenetrating network (IPN) hydrogel beads of polyacrylamide grafted κ-carrageenan (PAAm-g-CG) and sodium alginate (SA) for targeting ketoprofen to the intestine. The PAAm-g-CG was synthesized by free radical polymerization followed by alkaline hydrolysis under nitrogen gas. The PAAm-g-CG was characterized by elemental analysis, FTIR spectroscopy and thermogravimetric analysis (TGA). The drug-loaded IPN hydrogel beads were prepared by simple ionotropic gelation/covalent crosslinking method. The amorphous nature of drug in the beads was confirmed by differential scanning calorimetry and X-ray diffraction studies. The spherical shape of the beads was confirmed by scanning electron microscopic analysis. The beads exhibited ample pH-responsive behavior in the pulsatile swelling study. The ketoprofen release was significantly increased when pH of the medium was changed from acidic to alkaline. The beads showed maximum of 10% drug release in acidic medium of pH 1.2, and about 90% drug release was recorded in alkaline medium of pH 7.4. Stomach histopathology of albino rats indicated that the prepared beads were able to retard the drug release in stomach leading to the reduced ulceration, hemorrhage and erosion of gastric mucosa.