Functionally modified polyacrylamide-graft-gum karaya pH-sensitive spray dried microspheres for colon targeting of an anti-cancer drug

Abstract

An effort was made to formulate and evaluate pH-sensitive spray dried microspheres using hydrolyzed polyacrylamide-graft-gum karaya (PAAm-g-GK) for colon specific delivery of an anti-cancer agent, capecitabine. The synthesis of pH-sensitive PAAm-g-GK copolymer was done by free radical polymerization followed by alkaline hydrolysis and characterized satisfactorily. The microspheres were spherical in shape; drug entrapment efficiency was found to be in the range of 77.30% to 88.74%. Pulsatile swelling study indicates that the PAAm-g-GK consists of considerable pH-sensitivity. The in-vitro drug release suggested that the microspheres prepared using native GK were incapable to retard the drug release within 5h in the environment of stomach and small intestine. While, those microspheres prepared using pH-sensitive PAAm-g-GK copolymer having crosslinked with glutaraldehyde (GA), released little amount of drug within 5h, but maximum amount of drug was targeted to colonic region in a controlled manner up to 24h. For example, GK10 Microspheres showed only 19.16% drug release at the end of 5th h, while about 80.14% of drug was targeted to colonic region. Cross-linking with GA reduced the early drug release in the upper part of gastrointestinal tract and guaranteed maximum drug release in the colonic region. A rapid enhancement in drug release was witnessed in rat caecal content medium due to the action of colonic bacteria on PAAm-g-GK copolymer.