Abstract
Facial wrinkles include static and dynamic lines formed through different mechanisms and require diverse treatment approaches. Peptides perform well in anti-aging and wrinkle removal but exhibit poor transdermal efficiency. In this work, a novel neuro-soothing ionic liquid, GALA, prepared from γ-aminobutyric acid (GABA) and lactic acid (LA), is applied in the transdermal delivery of hexapeptide-9, which promotes collagen production. This treatment aims to remove dynamic and static lines simultaneously, and the human endogenous feature of GABA, LA, and hexapeptide-9 guarantees high biosafety of the system. The in-vitro transdermal, cellular, animal, and clinical experiments indicate that GALA is a safe and effective enhancer. GALA enhances the local penetration of hexapeptide-9 by altering the skin barrier structure, resulting in cumulative permeation and subcutaneous retention, respectively, 4.79 and 7.89 folds of that without enhancers after 12 h. GALA also enables hexapeptide-9 to combat root aging, mainly by activating the PPAR signaling pathway, leading to lower degrees of ultraviolet-induced oxidative stress, inflammation, epidermal hyperplasia, and the degradation of collagen and elastic fibers. Therefore, the combination of GALA and hexapeptide-9 has excellent potential in anti-wrinkle and antiaging treatments. This work's experimental and theoretical studies will further advance the clinical use of bioactive ionic liquids as transdermal enhancers.