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

Abstract

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.