Magnetite hybrid hydrogel of xanthan gum and poly(N-hydroxyethyl acrylamide): a cytocompatible vehicle for sustained oral dual delivery of 5-fluorouracil and curcumin

Abstract

In the present work, a pH-sensitive magnetite hybrid hydrogel was prepared as a potential oral dual drug delivery system. The magnetite (Fe₃O₄) nanoparticles were in situ incorporated into the pH-sensitive hydrogel containing xanthan gum (XG) and poly(N-hydroxyethyl acrylamide) (PAHEA), which was prepared via a free radical polymerization. Ultimately, anticancer drugs, namely 5-fluorouracil (5-FU) and curcumin (CUR), were successfully loaded into the developed magnetite hybrid hydrogel. The swelling studies showed minimal swelling of the system at pH 1.2 and significant swelling at pH 7.4. The drug quantities incorporated per gram of dry magnetite hybrid hydrogel were determined to be 48.2 ± 0.8 mg g⁻¹ for 5-FU and 38.5 ± 0.5 mg g⁻¹ for CUR. The sequential drug release studies revealed that the prepared dual drug delivery system retained the incorporated drugs in the simulated gastric environment and significantly released them in the simulated intestinal environment of the gastrointestinal tract. The drug release mobility at pH 7.4 followed non-Fickian diffusion for 5-FU and Super Case II transport for CUR. The cytotoxicity investigation of the magnetite hybrid hydrogel, with and without drugs, using the MTT assay towards normal cells (MCF-10A) showed good cytocompatibility, with cell viability exceeding 75%. However, the drug-loaded magnetite hybrid hydrogel showed remarkable cytotoxicity against cancer cells (MCF-7), with cell viability being below 35%. These results suggest that the prepared magnetic hybrid hydrogel could serve as a promising site-specific drug delivery system for the prolonged oral dual release of 5-FU and CUR in cancer therapy.