Chain Reaction

The efficacy of peptides is well supported by clinical research, but how does this evidence translate to cosmeceutical formulations?
Chain Reaction

Skin proteins—keratin, melanin, collagen, elastin, gelatin—give structure to cells, transmit signals from the cell surface to the organelles and mitochondria, and control the regeneration of tissues. Peptides—which are protein fragments—are popular active ingredients in skincare formulations, where they are used to affect the behavior of skin cells.

“Peptides are protein fragments—short chains of amino acids. About 50 or fewer amino acids in a chain is a peptide; about 50 or more is a protein. This is relevant because certain cells can be signaled to make more of a protein by ‘seeing’ a fragment of that protein,” says John Kulesza, president of skincare company Young Pharmaceuticals.

He likens the process to a game of Name That Tune, where to win you must name the song in as few notes as possible. “The smaller the number of amino acids in the peptide chain, the better its chances of penetration. Of course, to be effective it also has to include enough amino acids to convey a message to the cell,” he says.

“Most peptides used in skincare products are oligopeptides, consisting of 3 to 10 amino acids,” adds Jeannette Graf, MD, assistant clinical professor of dermatology at Mount Sinai Medical Center in New York.

Formulating Peptides

The use of peptides in topical formulations is based largely on in vitro research. “While the broad class of peptides work extremely well in vitro under laboratory conditions, when incorporated into product formulas, they sometimes work and oftentimes they don’t,” says Robert P. Manzo, president and CEO of skincare manufacturer Skinprint. “This is what leads to skepticism about peptides in general.”

How well a peptide works in vivo depends on three factors—dose, delivery and depth—he explains: “It is critical that the dose be correct, that the peptides be able to penetrate the skin barrier and reach the proper depth within the skin to be effective. The function of the peptide determines the depth we want it to reach, which then defines the delivery mechanism. Once we understand a peptide’s mechanism of action, we can properly calculate dose, giving the peptide optimal bioavailability to initiate the skin reaction we want.”

Peptide penetration is complicated by several factors. “Although many peptides are smaller than 500 Daltons, which means they could readily pass through the skin barrier, others are not,” says Neal Kitchen, executive vice president of strategy and development at Hydro­Peptide. “More problematic—all are naturally hydrophilic, which means they resist going though the lipophilic barrier layer of the epidermis.”

Fortunately, there are a number of ways to modify peptides to improve skin penetration. “For example, they can be modified with a fatty acid (e.g., palmitoylation or myristoylation) or an acetyl group (e.g., acetylation) that significantly improves their ability to penetrate the lipid layer of the skin,” says Kitchen. “Protein extracts have also improved penetration via hydrolysis. A peptide solution should be designed with ingredients that stabilize the solution and help to condition the skin for peptide penetration.”

“I would say effectiveness depends a great deal on where the peptide is to be used,” says Kulesza. “Peptides tend to be most effective in areas where the skin barrier is thinner, such as under the eyes and on the neck and chest.”

Calculating how much of a peptide to include is a bigger issue. “We often don’t know enough about how the peptide works to calculate how much we need to include,” says Manzo.

One strategy skincare formulators use to increase the efficacy of peptides is to include several different peptides in a single formulation. This may include combining multiple peptides that address similar concerns but through different pathways, or combining peptides with other peptides to improve penetration.

Photo copyright Getty Images.