Interaction between bovine serum albumin and Solutol® HS 15 micelles: A two-stage and concentration-dependent process

Abstract

The objective of this study was to investigate the interaction and the time evolution between protein and nanomicelles and to further understand the interaction mechanisms. Solutol® HS 15 (HS 15) and bovine serum albumin (BSA) were selected as the model nanomicelles and model protein, respectively. HS 15 has been used as solubilizer for injection, oral and subcutaneous administration systems. BSA was chosen as the model protein for its high sequence similarity and homology to human serum albumin. The interaction between BSA and HS 15 was studied by particle size distribution and zeta-potential measurement and fluorescence quenching assay. The effects of HS 15 concentration on the interaction between HS 15 nanomicelles and protein were investigated. The interaction mechanisms between BSA and HS 15 was studied by isothermal titration calorimetry and molecular docking. The interaction between HS 15 and BSA was demonstrated to be a two-stage process, with 0–3 h as the first phase and 3–12 h as the second phase. Moreover, the rearranged capsule-shaped HS 15 micelles could be absorbed onto the surface of BSA and the binding mode between HS 15 and BSA was concentration-dependent. Additionally, the interaction mechanisms of HS 15 and BSA include van der Waals forces, hydrophobic forces, and hydrogen bonding. In conclusion, this study provided a detailed study and insights of the interactions between nanomicelles and the serum albumin in vitro, which is of high importance to predict and understand the in vivo fate of such micellar drug delivery systems after intravenous injection in the future study.