A Short Review on the Delivery of Breast Anticancer Drug Tamoxifen and its Metabolites by Serum Proteins

Abstract

The loading of tamoxifen (Tam), 4-hydroxytamoxifen (4-OH-Tam) and endoxifen (End) by carrier proteins, human serum albumin (HSA) and bovine serum albumin (BSA) was reviewed in aqueous solution at physiological pH. The binding study is directly related to the conjugation of tamoxifen and its metabolites with serum proteins. Tamoxifen and its metabolites bind serum proteins via hydrophobic, hydrophilic and H-bonding contacts. The loading efficacy (LE) was 45-52% for drug-protein conjugates. Modeling showed the presence of H-bonding, which stabilized drug-protein complexation with the free binding energy of -11.79 to -11.25 Kcal/mol for drug-HSA and -13.79 to -12.72 Kcal/mol for drug-BSA conjugates. Drug conjugation induced major perturbations on the conformation of serum proteins. Our studies indicate that serum proteins can transport tamoxifen and its metabolites to target tissues in the human body.