Experiments and synthesis of bone-targeting epirubicin with the water-soluble macromolecular drug delivery systems of oxidized-dextran

Abstract

Epirubicin (EPI) is a broad spectrum antineoplastic drug, commonly used as a chemotherapy method to treat osteosarcoma. However, its application has been limited by many side-effects. Therefore, targeted drug delivery to bone has been the aim of current anti-bone-tumor drug studies. Due to the exceptional affinity of Bisphosphonates (BP) to bone, 1-amino-ethylene-1, 1-dephosphate acid (AEDP) was chosen as the bone targeting moiety for water-soluble macromolecular drug delivery systems of oxidized-dextran (OXD) to transport EPI to bone in this article. The bone targeting drug of AEDP–OXD–EPI was designed for the treatment of malignant bone tumors. The successful conjugation of AEDP–OXD–EPI was confirmed by analysis of FTIR and ¹H-NMR spectra. To study the bone-seeking potential of AEDP–OXD–EPI, an in vitro hydroxyapatite (HAp) binding assay and an in vivo experiment of bone-targeting capacity were established. The effectiveness of AEDP–OXD–EPI was demonstrated by inducing apoptosis and necrosis of MG-63 tumor cell line. The obtained experimental data indicated that AEDP–OXD–EPI is an ideal bone-targeting anti-tumor drug.

Keywords:

• Anti-tumor drug
• bisphosphonates
• bone-targeting
• epirubicin
• oxidized-dextran