Controlled delivery of nilotinib using LDH/Fe2O3-modified chitosan nanocomposite hydrogel beads for the treatment of chronic myeloid leukemia

Abstract

Abstract Chronic myeloid leukemia remains a significant challenge in cancer treatment because conventional drug delivery systems often fail to provide sustained release and targeted therapeutic effects. To address these limitations, this study a chitosan-based nanocomposite hydrogel system for the controlled delivery of nilotinib, a tyrosine kinase inhibitor used to treat chronic myeloid leukemia. Fe 2 O 3 -containing layered double hydroxide nanocomposites into were incorporated chitosan hydrogels under controlled synthesis conditions (70 ± 2 °C, stirring speed at 800 rpm) to fabricate chitosan nanocomposite hydrogel beads based on LDH and Fe 2 O 3 nanoparticles. Structural characterization using scanning electron microscopy and X-ray diffraction confirmed successful nanoparticle incorporation and the formation of a porous hydrogel network. Nilotinib was incorporated into the hydrogel beads using both in situ and post-synthetic approaches, and drug release was quantified by high-performance liquid chromatography. Among the formulations investigated, the Post-synthetic incorporation of nilotinib into dried hydrogel beads at a concentration of 20% yielded the highest cumulative nilotinib release after six hours (72.895 ± 0.004 µg/mL). Cytotoxicity studies revealed a concentration-dependent inhibition of chronic myeloid leukemia cell lines (BV173, EM-2, CML-T1, and JOSK-M) and indicated acceptable biocompatibility with human umbilical vein endothelial cells. In addition, the nanocomposite hydrogel demonstrated notable antioxidant activity in the DPPH assay. Overall, the developed LDH/Fe 2 O 3 -modified chitosan hydrogel system represents a promising platform for the controlled delivery of hydrophobic anticancer agents such as nilotinib.