Structural transitions in TPGS micelles induced by trehalose as a model cryoprotectant

Cryoprotectants are included to protect colloidal dispersions from mechanical stress of ice crystals formed at subzero temperature. Trehalose (THL) remains a popular choice among sugar-based cryoprotectants. In the present study, we illustrate the effect of THL concentration (0.01-1 M) upon microstructural characteristics of nonionic micelles which were formulated with alpha tocopherol polyethylene glycol 1000 succinate (TPGS). The effect of THL incorporation in drug-loaded micelles was studied by using capsaicin (CAP), a hydrophobic alkaloid. Our interpretations are based on the results of cloud point, dynamic light scattering (DLS), small angle neutron scattering (SANS), nuclear magnetic resonance (NMR) and Fourier-transformed infrared (FTIR) spectroscopic measurements. Cloud point and spectral data reveal that the micelles underwent progressive dehydration at increasing THL concentration. Together with scattering data, it is discernible that THL molecules intercalated in the micelle corona and expelled water from the polar headgroups. In spite of this, micelle size did not change until 1 M THL. Freeze-thawed micelles also displayed identical size distribution. Structural transitions occurred upon solubilization of CAP; micelles changed from sphere to ellipsoids. We suggest that CAP molecules occupied the hydrophobic core and triggered the formation of ellipsoids which were retained in the presence of THL. These