Application of Redox-Responsive Cysteine-Based Organogels as a Drug Delivery System for Doxorubicin

Cysteine derivatives having disulfide bonds in their side chains can be used as redox-responsive organogelators. The disulfide bond can be cleaved in the presence of certain reducing agents like thiol derivatives such as glutathione (GSH), which is a tripeptide that consists of cysteine, glutamic acid, and glycine. Studies show that cells of certain cancers have higher levels of glutathione due to increased production of reactive oxygen species (ROS). This feature allows targeted cancer therapy using glutathione-responsive drug delivery systems. This study showed the drug delivery property of l-Cys(<i>t</i>-dodecyl-sulfanyl)-OH and l-Cys-(S<i>t</i>Bu)-OH-based organogels. The drug-release properties of these organogels were measured in the presence of GSH and were compared with the drug-release property of the l-Cys-(<i>t</i>Bu)-OH-based organogel. The biocompatibility of the organogelators was measured <i>in vitro</i> by MTT assay and the characterization of microstructures and gel behaviors were studied using transmission electron microscopy (TEM) imaging, X-ray diffraction spectroscopy (XRD), Fourier-transform infrared spectroscopy (FTIR), and rheological measurements. The results indicated that the organogelators were able to form nanofibers by hydrogen bonds and van der Waals interactions between their hydrophobic groups and were able to release doxorubicin in the presence of GSH. The <i>in vitro</i> biocompatibility studies did not show significant toxicity to the L929 cells for l-Cys-(S<i>t</i>Bu)-OH and showed low concentrations of l-Cys(<i>t</i>-dodecyl-sulfanyl)-OH.