Coarse-Grained\nMolecular Dynamics Simulation of Heterogeneous\nPolysorbate 80 Surfactants and their Interactions with Small Molecules\nand Proteins

Polysorbate 80 (PS80) is widely used in pharmaceutical\nformulations,\nand its commercial grades exhibit certain levels of structural heterogeneity.\nThe objective of this study was to apply coarse-grained molecular\ndynamics simulations to better understand the effect of PS80 heterogeneity\non micelle self-assembly, the loading of hydrophobic small molecules\ninto the micelle core, and the interactions between PS80 and a protein,\nbovine serum albumin (BSA). Four representative PS80 variants with\ndifferent head and tail structures were studied. Our simulations found\nthat PS80 structural heterogeneity could affect blank micelle properties\nsuch as solvent-accessible surface area, aggregation number, and micelle\naspect ratio. It was also found that hydrophobic small molecules such\nas ethinyl estradiol preferentially partitioned into the PS80 micelle\ncore and PS80 dioleates formed a more hydrophobic core compared to\nPS80 monooleates. Furthermore, multiple PS80 molecules could bind\nto BSA, and PS80 heterogeneity profoundly changed the binding ratio\nas well as the surfactant-protein contact area.