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Impact of albumin on drug delivery--new applications on the horizon.

Abstract
Over the past decades, albumin has emerged as a versatile carrier for therapeutic and diagnostic agents, primarily for diagnosing and treating diabetes, cancer, rheumatoid arthritis and infectious diseases. Market approved products include fatty acid derivatives of human insulin or the glucagon-like-1 peptide (Levemir(®) and Victoza(®)) for treating diabetes, the taxol albumin nanoparticle Abraxane(®) for treating metastatic breast cancer which is also under clinical investigation in further tumor indications, and (99m)Tc-aggregated albumin (Nanocoll(®) and Albures(®)) for diagnosing cancer and rheumatoid arthritis as well as for lymphoscintigraphy. In addition, an increasing number of albumin-based or albumin-binding drugs are in clinical trials such as antibody fusion proteins (MM-111) for treating HER2/neu positive breast cancer (phase I), a camelid albumin-binding nanobody anti-HSA-anti-TNF-α (ATN-103) in phase II studies for treating rheumatoid arthritis, an antidiabetic Exendin-4 analog bound to recombinant human albumin (phase I/II), a fluorescein-labeled albumin conjugate (AFL)-human serum albumin for visualizing the malignant borders of brain tumors for improved surgical resection, and finally an albumin-binding prodrug of doxorubicin (INNO-206) entering phase II studies against sarcoma and gastric cancer. In the preclinical setting, novel approaches include attaching peptides with high-affinity for albumin to antibody fragments, the exploitation of albumin-binding gadolinium contrast agents for magnetic resonance imaging, and physical or covalent attachment of antiviral, antibacterial, and anticancer drugs to albumin that are permanently or transiently attached to human serum albumin (HSA) or act as albumin-binding prodrugs. This review gives an overview of the expanding field of preclinical and clinical drug applications and developments that use albumin as a protein carrier to improve the pharmacokinetic profile of the drug or to target the drug to the pathogenic site addressing diseases with unmet medical needs.
AuthorsBakheet Elsadek, Felix Kratz
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 157 Issue 1 Pg. 4-28 (Jan 10 2012) ISSN: 1873-4995 [Electronic] Netherlands
PMID21959118 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2011 Elsevier B.V. All rights reserved.
Chemical References
  • Albumin-Bound Paclitaxel
  • Albumins
  • Antineoplastic Agents
  • Hypoglycemic Agents
  • Prodrugs
  • Paclitaxel
Topics
  • Albumin-Bound Paclitaxel
  • Albumins (administration & dosage, chemistry)
  • Animals
  • Antineoplastic Agents (administration & dosage, chemistry)
  • Clinical Trials as Topic (methods, trends)
  • Drug Delivery Systems (methods, trends)
  • Humans
  • Hypoglycemic Agents (administration & dosage, chemistry)
  • Paclitaxel (administration & dosage, chemistry)
  • Prodrugs (administration & dosage, chemistry)
  • Protein Structure, Secondary
  • Protein Structure, Tertiary

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