Fabrication of electroactive polypyrrole-tungsten disulfide nanocomposite for enhanced in vivo drug release in mice skin.

The present study focused on the development of electric stimuli drug release carrier based on transition metal dicgalcogenides. First, tungsten disulfide (WS2) was exfoliated and functionalized using thiol chemistry with various thiol-terminated ligands such as thioglycolic acid (TGA), mercaptosuccinic acid (MSA), and 2-ethanethiol (2ET). The exfoliated WS2 underwent non-covalent coating with an electrically conductive polypyrrole (PPy) for functionalization, of which MSA-WS2-PPy achieved the highest 5-FU (anticancer drug) loading. An electrically-stimulated drug release experiment showed that TGA-WS2-PPy achieved a higher drug release (90%) than MSA-WS2-PPy (70%) and 2ET-WS2-Ppy (35%). The TGA-WS2-PPy exhibited swelling/recombination between PPY and MSA-WS2 substrate under electrical stimulation, resulting in the highest 5-FU release. From the MTT assay result, there was no significant toxicity observed for TGA-WS2-PPy-FU on HaCaT cells, indicating the biocompatibility of TGA-WS2-PPy-FU in the absence of electrical stimulation. However, HaCaT cells died when incubated with TGA-WS2-PPy-FU under electrical stimulation. Finally, Raman mapping studies for TGA-WS2-PPy drug release in the skin of nude mice demonstrated that the carrier penetrated deeper into the skin of the mice while other systems failed to exhibit significant effects under electrical stimulation. The present study offers a novel approach in developing a non-invasive electrically-stimulated drug release system based on WS2 and an externally-controlled delivery model.