Highly stable and reduction responsive micelles from a novel polymeric surfactant with a repeating disulfide-based gemini structure for efficient drug delivery

The synthesis of a novel polymeric surfactant with a repeating disulfide-based gemini structure (poly( gemini surfactant)) and its micellar properties for GSH-dependent intracellular drug delivery are described. A linear polyethylene glycol (PEG) was end-functionalized with N-stearoylcysteine and the cysteine thiol groups of the telechelic surfactant were oxidized intermolecularly in the micellar state to produce poly(gemini surfactant). Compared with the telechelic surfactant, poly(gemini surfactant) possessed a lower critical micelle concentration and higher solubilization capacity for doxorubicin (DOX). Moreover, the poly(gemini surfactant) micelles revealed excellent colloidal stability against excess sodium dodecyl sulfate (SDS) as a micelle-destabilizing agent. Cytotoxicity experiments showed that poly(gemini surfactant) composed of PEG, cysteine, and stearic acid was virtually non-cytotoxic up to 100 mg L-1. In the presence of glutathione (GSH), poly(gemini surfactant) was degraded back into the telechelic surfactant, leading to the release of encapsulated DOX to induce cytotoxicity against cancer cells. (C) 2017 Elsevier Ltd. All rights reserved.