Biopolymeric pH-responsive fluorescent gel for in-vitro and in-vivo colon specific delivery of metronidazole and ciprofloxacin

Abstract

Biocompatible fluorescent active and pH sensitive gel has been developed using covalently attached riboflavin as proficient fluorophore on crosslinked glycogen. The chemically crosslinked glycogen (cl-Gly/PMAc) has been synthesised by grafting of methacrylic acid (MAc) followed by crosslinking using ethylene glycol dimethacrylate (EGDMA) through free radical polymerization. Afterward, the fluorescent active hydrogel (cl-Gly/PMAc-RB) has been synthesised by post-polymerization modification of cl-Gly/PMAc with riboflavin. The gel properties have been explored by determining rheological parameters. pH responsive swelling and reversible swelling behaviours of cl-Gly/PMAc-RB have been investigated by executing swelling/deswelling/reswelling studies. In-vitro cell cytotoxicity study predicts that the material is non-toxic and biocompatible. cl-Gly/PMAc-RB gel demonstrates excellent release profile towards the release of dual drugs (metronidazole: release ∼ 75% after 24 h and ciprofloxacin: release ∼ 55% after 24 h) in colonic region, which is evidenced from in vitro and in-vivo studies. Finally, ab-initio molecular dynamics study has been carried out to investigate the intricate details of the probable drugs-hydrogel interaction and pH responsive release profile of dual drugs from cl-Gly/PMAc-RB hydrogel in molecular level.