Thiol-Responsive Micelles Based on Nonionic Gemini Surfactants with a Cystine Disulfide Spacer

Thiol-responsive micelles consisting of novel nonionic gemini surfactants with a cystine disulfide spacer are reported. The gemini surfactants, (C-18-Cys-mPEG)(2) and ((C-18)(2)-Lys-Cys-mPEG)(2), were synthesized from polyethylene glycol, cysteine, and stearic acid, and their structures were confirmed by H-1 NMR and gel permeation chromatography. (C-18-Cys-mPEG)(2) and ((C-18)(2)-Lys-Cys-mPEG)(2) formed micelles with average diameters of 13 and 22 nm above the critical micelle concentration of 6.5 and 4.7 mu g mL(-1), respectively. The micelles of ((C-18)(2)-Lys-Cys-mPEG)(2) containing more stearoyl groups showed encapsulated more hydrophobic indomethacin (IMC) with higher entrapment efficiencies than those of (C-18-Cys-mPEG)(2). The gemini surfactant micelles exhibited an accelerated release of encapsulated IMC with the concentration of the reducing agent, glutathione (GSH), whereas they were unaffected by the presence of reduced GSH (GSSG). The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium studies revealed the noncytotoxic nature of the gemini surfactant micelles. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 582-589