GHK-Cu Peptide's Skin Transport Mechanism and pH-Dependent Permeability Revealed

In mammals, copper is primarily transported as a complex with the tripeptide glycyl-l-histidyl-l-lysine (GHK), forming GHK-Cu. This complex is crucial for copper delivery across tissues and cell membranes. The ability of GHK-Cu to penetrate the stratum corneum (the outermost layer of skin) is a key factor determining its effectiveness in cosmetic and pharmaceutical applications. Understanding the specific mechanisms and factors, particularly pH and ligand structure, that govern GHK-Cu's permeability through the skin barrier is essential for optimizing its use.

The study revealed a significant relationship between pH and permeability: the permeability coefficients of copper complexes were found to increase with increasing pH. Crucially, ESI-MS analysis confirmed that among various copper species, only the free tripeptide GHK and its specific copper complexes, GHK-Cu and (GHK)2-Cu, possessed the ability to migrate through the model stratum corneum membrane. Other copper complexes or free copper ions alone did not show significant migration. The study did not provide specific numerical permeability coefficients but clearly demonstrated the qualitative trend. This research definitively proved that GHK-Cu and its related peptide-bound forms are the exclusive carriers enabling copper transport across the skin's primary barrier, with their penetration efficiency directly enhanced by higher pH levels.