Coarse-Grained Molecular Dynamics Simulation of Heterogeneous Polysorbate 80 Surfactants and their Interactions with Small Molecules and Proteins

• DOI: 10.1021/acs.molpharmaceut.4c00461
• Publication Date: 2024-08-29T19:15:45Z
• Authors: Hao Lou; Yaqi Wu; Krzysztof Kuczera; Christian Schöneich
• Keywords: Polysorbate; Bovine serum albumin; Hydrophobic effect

Polysorbate 80 (PS80) is widely used in pharmaceutical formulations, and its commercial grades exhibit certain levels of structural heterogeneity. The objective this study was to apply coarse-grained molecular dynamics simulations better understand the effect PS80 heterogeneity on micelle self-assembly, loading hydrophobic small molecules into core, interactions between a protein, bovine serum albumin (BSA). Four representative variants with different head tail structures were studied. Our found that could affect blank properties such as solvent-accessible surface area, aggregation number, aspect ratio. It also ethinyl estradiol preferentially partitioned core dioleates formed more compared monooleates. Furthermore, multiple bind BSA, profoundly changed binding ratio well surfactant-protein contact area.