title: 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 (1)H-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.
authors.affiliation: Department of Orthopeadics, Zhongnan Hospital of Wuhan University , Wuhan , China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry* / Q000494:pharmacology; D004164:Diphosphonates / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015251:Epirubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: C417558:1-aminoethylene diphosphonic acid; D000903:Antibiotics, Antineoplastic; D003911:Dextrans; D004164:Diphosphonates; D004337:Drug Carriers; D014867:Water; D015251:Epirubicin