Effect of oligoarginine conjugation on the antiwrinkle activity and transdermal delivery of GHK peptide

GHK (Gly‐His‐Lys), a natural peptide found in human skin and plasma, has been widely used in the cosmeceutical and pharmaceutical fields. The hydrophilic GHK and GHK‐Cu are limited in their abilities to penetrate deeply into skin; because of this, various strategies for their skin delivery have been developed. In this investigation, Arg4 was conjugated with GHK to get heptapeptide, GHK‐R4, and then in vitro antiwrinkle activity and transdermal delivery were compared between GHK and GHK‐R4. Notably, Arg4 conjugation accelerated the cellular penetration of GHK both in vitro and in vivo. Furthermore, higher in vitro antiwrinkle activity and collagen biosynthesis was obtained with GHK‐R4 at much lower doses than with control R4‐free GHK. The enhanced activity and delivery of GHK‐R4 might be due to the cell penetrating ability and matrix metalloproteinase (MMP) inhibitory activity of R4 itself. The increase in the antiwrinkle activity and transdermal delivery of GlyHisLys tripeptide occurred via conjugating GlyHisLys tripeptide with 4 Arg.