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Abstract
Albumin is playing an increasing role as a drug carrier in the clinical setting. Principally,
three drug delivery technologies can be distinguished: coupling of low-molecular weight
drugs to exogenous or endogenous albumin, conjugation with bioactive proteins and
encapsulation of drugs into albumin nanoparticles. The accumulation of albumin in
solid tumors forms the rationale for developing albumin-based drug delivery systems
for tumor targeting. Clinically, a methotrexate-albumin conjugate, an albumin-binding
prodrug of doxorubicin, i.e. the (6-maleimido)caproylhydrazone derivative of doxorubicin
(DOXO-EMCH), and an albumin paclitaxel nanoparticle (Abraxane) have been evaluated
clinically. Abraxane has been approved for treating metastatic breast cancer. An alternative
strategy is to bind a therapeutic peptide or protein covalently or physically to albumin
to enhance its stability and half-life. This approach has been applied to peptides
with antinociceptive, antidiabetes, antitumor or antiviral activity: Levemir, a myristic
acid derivative of insulin that binds to the fatty acid binding sites of circulating
albumin, has been approved for the treatment of diabetes. Furthermore, Albuferon,
a fusion protein of albumin and interferon, is currently being assessed in phase III
clinical trials for the treatment of hepatitis C and could become an alternative to
pegylated interferon. This review gives an account of the different drug delivery
systems which make use of albumin as a drug carrier with a focus on those systems
that have reached an advanced stage of preclinical evaluation or that have entered
clinical trials.