title: Emerging delivery systems to reduce doxorubicin cardiotoxicity and improve therapeutic index: focus on liposomes.
abstract: Anthracyclines are powerful anticancer agents and among the most important tools in the chemotherapy armamentarium of medical oncologists. They are approved for use in the treatment of a broad variety of solid and hematologic neoplasms. However, the usefulness of these agents, particularly doxorubicin, the most widely used anthracycline, is limited by considerable toxicity, especially damage to the cardiac muscle, which is cumulative and mostly irreversible, restricting extended use of this drug. In the last 30 years, extensive research with a variety of drug-delivery systems has attempted to overcome this limitation, with clinical success mostly confined to liposome formulations. Liposomal doxorubicin, and particularly pegylated liposomal doxorubicin, has shown significant pharmacologic advantages and an added clinical value over doxorubicin. Here, we review the mechanisms of action and toxicity of doxorubicin, and ways to reduce toxicity, with a focus on liposome-based drug-delivery systems.
authors.affiliation: Oncology Institute, Shaare Zedek Medical Center and Hebrew University, School of Medicine, Jerusalem, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Tahover
authors.forename: Yogita P
authors.initials: YP
authors.lastname: Patil
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Gabizon
mesh_terms: D018943:Anthracyclines / Q000008:administration & dosage / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D066126:Cardiotoxicity / Q000517:prevention & control*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012307:Risk Factors; D000068878:Trastuzumab
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D061067:Antibodies, Monoclonal, Humanized; D002316:Cardiotonic Agents; D004317:Doxorubicin; D008081:Liposomes; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C506643:liposomal doxorubicin; C508053:ERBB2 protein, human