Novel pH-sensitive interpenetrated network polyspheres of polyacrylamide-g-locust bean gum and sodium alginate for intestinal targeting of ketoprofen: In vitro and in vivo evaluation.

In this report, novel pH-sensitive interpenetrated network (IPN) polyspheres were developed utilizing polyacrylamide-g-locust bean gum (PAAm-g-LBG) in combination with sodium alginate (SA) to achieve intestinal targeted delivery of ketoprofen. PAAm-g-LBG was synthesized under microwave irradiation wherein ceric ammonium nitrate was used as reaction initiator and then conversion of PAAm-g-LBG as pH-sensitive copolymer was carried out by alkaline hydrolysis. The PAAm-g-LBG copolymer was characterized through 1H-NMR, FTIR and elemental analysis. The IPN polyspheres exhibited pH-depended swelling or de-swelling with the alteration of surrounding pH. The in-vitro release of drug from IPN polyspheres was found to be higher (≈ 90%) in phosphate buffer of pH 7.4 in comparison with that in pH 1.2 buffer (10.6%). The in-vivo pharmacokinetic, anti-inflammatory screening and stomach histopathology studies performed on Wistar rats revealed pH sensitivity of IPN polyspheres where ketoprofen was successfully targeted to small intestine resulting in reduced side effects of ketoprofen like ulcer formation, erosion of gastric mucosa and hemorrhages.

Novel pH-sensitive IPNs of polyacrylamide-g-gum ghatti and sodium alginate for gastro-protective drug delivery.

This article reports the development of pH-sensitive interpenetrating polymer network (IPN) microbeads using polyacrylamide-grafted-gum ghatti (PAAm-g-GG) and sodium alginate (SA) for gastro-protective controlled delivery of ketoprofen. We have synthesized PAAm-grafted-GG copolymer under microwave irradiation using cerric ammonium nitrate as reaction initiator; further, the PAAm-g-GG was converted to pH-sensitive copolymer through alkaline hydrolysis. Sophisticated instrumentation techniques were used to characterize PAAm-g-GG. The IPN microbeads of PAAm-g-GG and SA, pre-loaded with ketoprofen were prepared by dual crosslinking using Ca(2+) ions and glutaraldehyde (GA). The IPN microbeads demonstrated excellent pH-sensitive behavior as noted in the pulsatile swelling test and scanning electron microscopy. IPN microbeads also showed larger amount of drug release in buffer solution of pH 7.4 as compared to drug release in solution of pH 1.2. The in vivo pharmacokinetic, pharmacodynamic and stomach histopathology studies conducted on wistar rats confirmed the pH-sensitive controlled release of ketoprofen; IPN microbeads retarded the drug release in stomach resulting in reduced adverse effects of ketoprofen.

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.

Interpenetrating network hydrogel beads of carboxymethylcellulose and egg albumin for controlled release of lipid lowering drug.

Novel interpenetrating network hydrogel beads of sodium carboxymethylcellulose and egg albumin loaded with a lipid lowering drug, simvastatin, were prepared by ionotropic gelation and covalent cross-linking method. The IPN beads were characterized by differential scanning colorimetric analysis, X-ray diffractometry to understand the crystalline nature of the drug after entrapment into IPN matrix. Fourier transform infrared spectroscopy was used to find the chemical stability of drug in the polymer matrix and scanning electron microscopy was performed to study the surface morphology. The ionically cross-linked beads were capable of releasing drug up to 7 h, whereas the drug release was extended up to 12 h in case of dual cross-linked beads. The beads which were prepared with higher concentration of glutaraldehyde released the drug more slowly. The release data were fitted to an empirical equation to determine the transport mechanism, which indicated the non-Fickian trend for drug transport.