Mobility of doxorubicin in TPGS micelles in response to sodium taurodeoxycholate incorporation: analyses based on scattering and fluorescence studies

Abstract This study describes the effect of bile salt addition upon encapsulation locus of doxorubicin (DOX, a hydrophilic anticancer drug) in D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles. Sodium taurodeoxycholate (NaTDC) was used as bile salt. After analysing the scattering behaviour of TPGS-NaTDC mixed system, steady-state fluorescence, time-resolved fluorescence and fluorescence anisotropy techniques were employed to track the movement of DOX in micelles at various NaTDC concentrations. Our results suggest that after triggering contraction of micelles in low concentration regime (0.05-0.5 mM), NaTDC molecules participated with TPGS to form mixed micelles (average hydrodynamic diameter: 8-11 nm) and swollen aggregates (200-300 nm). In spite this, no changes in the shape of micelles and optical properties of solution were recorded. Small angle neutron scattering data suggest that NaTDC molecules engaged with core-forming segment of TPGS at low concentration (0.05-1.0 mM), and later migrated towards the shell region and imparted electrostatic charge to the headgroups. Transitions beyond this point (>1.0 mM) were marked by drastic changes in the effective charge of aggregates and aggregation number of participating molecules. We have shown that NaTDC-derived electrostatic charge can be exploited to drive positively charged DOX molecules from the hydrophilic shell to apolar core region in TPGS micelles. Importantly, loaded DOX molecules remained stable against storage time (up to 50 days) and microenvironment temperature (25-40oC).