Reduction-sensitive shell crosslinked TPGS micelles: Formulation and colloidal characterizations

Abstract

This study reports stabilization of α-tocopheryl polyethylene glycol succinate (TPGS) micelles by crosslinking their shell. This was accomplished by derivatizing terminal alcohol of the surfactant into aldehydes which were later linked with cystamine. Crosslinking of headgroups occurred through bridging of aldehyde termini with cystamine. Disulfide bonds offered redox sensitivity to the crosslinked micelles. Successful derivatization of the surfactant has been demonstrated through Fourier-transformed infrared spectroscopic and nuclear magnetic resonance data. Micelles were characterized by dynamic light scattering, neutron scattering, electron microscopic and fluorimetric techniques. We observed that, in spite of more than two-fold increase in size, micelles retained their core-shell spherical structure after shell crosslinking. Crosslinked micelles exhibited superior dilution stability in phosphate buffer. De-crosslinking indeed occurred under reductive condition and at low pH. This, however, did not cause complete dissociation of micelles implying that association among TPGS molecules was not affected during de-crosslinking. Based on these observations, we suggest that the release of payloads from crosslinked TPGS micelles can be triggered in reductive and low pH environment while avoiding the premature release.