Noninvasive and Efficient Peptide Delivery by a Novel Biocompatible Ionic Liquid

The application of bioactive polypeptides has become a challenge in the pharmaceutical industry. Copper glycyl-histidine-tripeptide (GHK-Cu) exerts various biological effects, including antioxidation, promotion of cell proliferation, and enhancement of repair. However, its clinical application is restricted by its hydrophilicity and severe demands with respect to the delivery conditions. Therefore, for the purpose of its application and of resolving the existing issues of GHK-Cu, we designed and developed a new local delivery system based on green ionic liquids (ILs) by combining the density functional theory (DFT) and adequate experiments. The system integrates the advantages of the ILs and GHK-Cu, which not only stabilizes GHK-Cu and greatly enhances its transdermal absorption rate but also has a synergistic amplification effect. Cell and animal experiments show encouraging effects on cell proliferation, antioxidation, and collagen synthesis, whereas human efficacy tests show the benefits of improving skin repair ability and antiaging, antiwrinkle, and moisturizing properties. The bio-based ILs system developed in this study provides a simple and efficient method for the clinical application of GHK-Cu and a novel method for the application of polypeptides.