The effect of protein BSA on the stability of lipophilic drug (docetaxel)-loaded polymeric micelles

Abstract

Polymeric micelles are promising delivery vehicles for improving the efficacy of anticancer drugs and reducing their side effects. However, considering the binding ability of serum albumin, the possible interaction of micelles with the native plasma components in the bloodstream raises serious questions on micellar stability. The stability of barren or drug-loaded copolymeric micelles was investigated systematically in distilled water (DW) and simulated body fluid (SBF) solutions in the presence of a model protein. The copolymer was a Pluronic® series triblock copolymer (P-123), the drug was strongly lipophilic docetaxel (DOC) and the protein was Bovine Serum Albumin (BSA). The effect of such factors as BSA and DOC concentrations and the aging of the micellar solutions was studied. Both the barren and drug-loaded micelles were quite stable in blank DW and SBF solutions for long times up to 10 days. They lost integrity and showed no inclination to re-assemble when the BSA concentration reached a critical value, which was very close to the plasma Human Serum Albumin (HSA) concentration. The presence of DOC in the micellar cores could not prevent disintegration. The results illustrate clearly that ensuring the stability of polymeric micelles in blood plasma should be an important design factor in their use as drug carriers.