Changes in aggregation properties of TPGS micelles in the presence of sodium cholate

Abstract D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), a nonionic surfactant, has been tested clinically for treating cholestatic liver disease. This research was aimed at investigating the effect of sodium cholate (NaC, a bile salt) on aggregation properties of TPGS. Changes in TPGS aggregates during NaC incorporation were investigated by UV-Vis spectroscopy, electron microscopy, dynamic light scattering (DLS) and small angle neutron scattering (SANS). In pre-micelle concentration regime (≤10 mM), NaC molecules steadily migrated to the micelle core and no interfacial events were recorded in terms of changes in the cloud point and conductivity of dispersion. As a result of hydrophobic association between NaC and TPGS tail, micelles exhibited 20-30% contraction. However, at higher concentration (≥20 mM), micelle core became crowded. Subsequently, NaC molecules were driven away from the core to shell region and swollen aggregates (200-300 nm) were formed. Movement of NaC to the shell region was confirmed from the bathochromic shift of methyl orange, encapsulated in the micelles. We reveal that hydrophobic interactions remarkably dominated under dehydrating effect of electrolytes, particularly under acidic conditions wherein NaC remains unionized. At intestinal pH, hydrophobic attraction appeared to be compensated by the electrostatic repulsion among ionized molecules; micelle dissociation occurred with 10 mM NaC. Our findings on TPGS-NaC interactions can be utilized to achieve successful bile salt sequestration.