GHK-Cu Tripeptide: A Multifunctional Cosmeceutical Agent with Advanced Delivery Strategies for Enhanced Topical Efficacy

Objective: To evaluate biological and dermatological evidence supporting glycyl-L-histidyl-L-lysine-Cu (GHK-Cu) as an anti-aging cosmeceutical and to assess barriers and delivery strategies for its topical use. Methods: A systematic review of primary and review literature was conducted, covering gene-expression studies, preclinical and clinical skin/wound research, and formulation approaches such as microemulsions, microneedles, superabsorbent polymers (SAPs), nanoparticles, liposomes, and biopolymer-based films. Results: GHK-Cu demonstrates strong regenerative potential by stimulating collagen and proteoglycan synthesis, regulating MMP/TIMP balance, promoting angiogenesis, and enhancing fibroblast and keratinocyte proliferation. It also shifts gene expression toward repair and regeneration, supporting its anti-aging, wound-healing, and hair-growth benefits. However, its topical efficacy is hindered by poor skin permeation due to hydrophilicity, instability from oxidation and enzymatic degradation, copper dissociation, and interactions with excipients or packaging. Advanced delivery systems show improved outcomes: microemulsions enhance solubility and skin retention; microneedles significantly increase dermal uptake; SAPs enable controlled release in wound environments; nanoparticles and liposomes improve stability and delivery; and nanocrystalline cellulose films offer a sustainable stabilization platform. Despite these advances, gaps remain in clinical validation, stability profiling, and safety assessment, particularly for nanocarriers. Conclusion: GHK-Cu is a promising anti-aging and therapeutic peptide, but its effectiveness depends on overcoming delivery and stability challenges. Combination approaches and sustainable carrier systems appear most promising. Future research should focus on standardized testing, comparative clinical studies, and comprehensive safety evaluation to support translation into commercial formulations.