In this month's Cosmetic Conundrums column, Dr. Draelos addresses cosmeceutical peptides and the differences between carrier peptides, signal peptides and neurotransmitter peptides.
What are cosmeceutical peptides?
Peptides are becoming a household name in prestige cosmeceutical facial moisturizers. Peptides sound very high tech, until you realize that hydrolyzed collagen, obtained from boiling cowhides, was one of the first peptide cosmetic ingredients. However, hydrolyzed bovine collagen is much different than the newer peptide ingredients.
The new peptides are engineered one amino acid at a time to mimic a functional human protein fragment. The intent is to induce a positive biologic change. Many peptides are available from supply houses for incorporation into cosmeceutical preparations, and they fall into three major categories: carrier peptides, signal peptides, and neurotransmitter peptides.
What are carrier peptides?
The first peptides were introduced into the pharmaceutical realm for enhanced wound healing. The idea was to engineer peptides to carry necessary wound healing cofactors to the active site efficiently and physiologically. For this reason, the first peptides were labeled carrier peptides. The first commercialized carrier peptide was designed to deliver copper, a trace element necessary for wound healing, into the wounded tissue. Metals are very difficult to deliver and are unstable in formulation, thus using the peptide carrier technique was novel and effective. The first carrier peptide labeled GHK was composed of glycine (G), histidyl (H), and lysine (K). It was isolated from human plasma and synthetically engineered. Linking GHK to copper, abbreviated GHK-Cu, was utilized in wound healing creams and subsequently adapted to a line of facial cosmeceuticals to minimize the appearance of fine lines and wrinkles. This technology, commercialized by Neutrogena, was based on in vitro observation of dermal keratinocyte proliferation in response to the copper linked peptide.
What are signal peptides?
While carrier peptides are designed to carry unique ingredients, signal peptides are designed to create a biologic response. Currently marketed signal peptides have been designed and tested in vitro to increase collagen, elastin, fibronectin, proteoglycan, and glycosaminoglycan production. The first commercialized signal peptide was palmitoyl pentapeptide, abbreviated Pal-KTTKS. This engineered peptide is composed of lysine (K), threonine (T), threonine (T), lysine (K), and serine (S) linked to palmitic acid (Pal). It is a procollagen I fragment used in a low concentration of four parts per million to act as a signal. The signal observed from in vitro fibroblast cultures was increased product of collagen I, III, and IV. The procollagen fragments are thought to down-regulate the production of collagenase thereby increasing dermal collagen. Pal-KTTKS, known commercially as Matrixyl, is still the most widely used peptide in facial cosmeceuticals.
What are neurotransmitter peptides?
A third category of commercialized peptides is neurotransmitter peptides. These peptides became popular when facial cosmeceuticals began comparing themselves to botulinum toxin injections, asking the question if a facial moisturizer could be “Better Than Botox.” These clever advertising campaigns did not say the moisturizer was better than Botox, only the question was asked. Neurotransmitter peptides, such as acetyl hexapeptide-3, were developed to attempt to inhibit release of acetylcholine at the neuromuscular junction. The peptides are similar to botulinum toxin in that both selectively modulate synaptosomal-associated protein of 25,000 Daltons, abbreviated SNAP-25, however the mechanism is different. Botulinum toxin A proteolytically degrades SNAP-25 while acetyl hexapeptide-3 mimics the N-terminal end of the SNAP-25 protein. This inhibits the SNARE (soluble N-ethyl-maleimide-sensitive factor attachment protein receptor) complex formation. Acetyl hexapeptide-3 is the most widely commercialized neurotransmitter peptide and is purported in vitro to inhibit vesicle docking through prevention of the SNARE complex formation, which induces muscle relaxation.
The challenge here is to get the peptide to the neuromuscular junction in sufficient quantity for an adequate duration to induce chemodenervation. Injections are more efficient at bypassing the stratum corneum barrier and targeting a certain active site. Topical peptide penetration is challenged by the stratum corneum, which is uniquely designed to keep out proteins, and peptides are protein fragments. Nevertheless, these neurotransmitter peptides remain popular among consumers.