Peptides represent a newer class of ingredients that have entered the market. In theory, while there are a relatively a large number of peptide variants that could be designed based on amino-acid sequence, a number of residues, and use of derivatives/isomers of respective residues, there have been several peptides that have garnered greater market usage in the cosmetic industry. These include palmitoyl-lysine-threonine-threonine-lysine-serine (pal – KTTKS; Matrixyl®), acetyl-glutamate-glutamate-methionine-glutamine-arginine-arginine (Ac-EEMQRR; Argireline®), and the tripeptide copper binding glycine-histidine-lysine (Cu-GHK). These three particular peptides were designed based on amino-acid sequences present in the proform of Type I collagen, the major form of collagen present in human skin. These peptides are capable of stimulating new collagen synthesis in vitro, presumably based on a wound – healing response to damaged collagen generated from matrix metallo – proteinases (MMP) enzymatic activity [26,27]. The copper-bound GHK peptide was shown to stimulate the wound-healing processes in laboratory model systems by increasing the production of dermal matrix components such as collagen and specific matrix remodeling MMPs [28-30]. The ability of these peptides to stimulate collagen synthesis is based in part upon the normal physiological response to a wound-healing event, which includes a degradation of the extracellular matrix followed by a restoration via de novo collagen and GAG synthesis.
Since the skin penetration profile of peptides is not strong, some peptides have a covalent attachment of lipophilic moieties, such as the long-chain palmitoyl group on pal – KTTKS that can dramatically improve their delivery into skin’s surface. Supporting this, pal-KTTKS has been shown in both small – and large-base human clinical studies to be capable of improving the appearance of fine lines and wrinkles at the relatively low dose of 3 ppm [31-33].
In contrast to pal-KTTKS, the reported effects of formulations containing other peptides require much higher levels, such as 2% for Cu-GHK and 10% for Ac-EEMQRR. One published study [34] describes increases in skin thickness, hydration, and smoothness from the topical use of a Cu-GHK containing commercial product (peptide dose not indicated) in an open-label study involving 40 subjects. A series of clinical studies of 8-12 weeks duration describing skin improvements such as reduced wrinkling, apparently using topical 2% Cu-GHK, have been presented [35,36]. For Ac-EEMQRR, a conference platform presentation [37] describes 30% reduction in wrinkle depth with 10% of this peptide used topically in a 30-day study.
Another peptide that is currently in products is Ac-EEMQRR, which is mechanistically very different than the collagen derived peptides described earlier. Mechanistically, Ac – EEMQRR is more akin to a mimic of Botox® which functions by inhibiting neurotransmitter release, thereby causing transient muscle relaxation that control the underlying skin around fine lines and wrinkles [37]. In theory, its therapeutic effects should occur in a much shorter time frame after treatment, since Botox itself has more of an immediate acute effect via muscle relaxation.