Palmitoyl-KTTKS: A Promising Innovation for Turning Back Time?

‘Peptides have important applications in modulating skin cell
proliferation, cell migration, inflammation, angiogenesis, melanogenesis, and protein synthesis and regulation’ (Mohammed, Y., et al. 2014)

Cosmetic creams are complex compositions of ingredients including preservatives, fragrances, thickening agents and moisturising agents. Bioactive ingredients are commonly present in trace amounts with respect to the composition.

Palmitoyl-KTTKS (Matrixyl), a bioactive signalling peptide, has received a mountain of awareness in the media for its supposed ability to elicit an anti-wrinkle effect by increasing tissue repair action, stimulating levels of skin proteins such as collagen, glycosaminoglycans and fibronectin. When these break down, wrinkles form.

What is Palmitoyl-KTTKS?

• KTTKS: This stands for Lysine-Threonine-Threonine-Lysine-Serine, 5 amino acids joined together in a row to form a pentapeptide. Discovered to be a sub-fragment of pro-α1 (I) collagen, a precursor of collagen in humans, KTTKS is the part of palmitoyl-KTTKS that is meant to elicit the anti-ageing effect, increasing protein production. When a peptide is greater than 10 amino acids long, it becomes too bulky and expensive to produce; KTTKS is an ideal length for transdermal delivery across the stratum corneum and epidermis to its site of action, the dermis.

• Palmitoyl: A fatty acid composed of 16 carbons attached to the first K (lysine) via a peptide bond. This improves transdermal delivery of KTTKS across skin barriers to the dermis since KTTKS by itself permeates skin poorly, due to its lipophobic/hydrophilic nature (meaning it loves water and cannot cross skin barriers as skin cell membranes are composed of molecules that don't like water). Think of the skin cells as oil and KTTKS as water… oil and water do not mix well! For more information of hydrophobicity and hydrophilicity, click here.

Studies

My final year project involved critical analysis of data for palmitoyl-KTTKS. So far, I am undecided on its effectiveness as an anti-ageing ingredient due to the limited number of studies conducted.

Choi et al. (2014) recently investigated "dermal stability and in vitro skin permeation of collagen pentapeptides (KTTKS and palmitoyl-KTTKS)" after recognising sparse studies supporting transdermal delivery of palmitoyl-KTTKS, compared to clinical studies and in vitro studies regarding the pentapeptides ability to increase collagen, fibronectin and glycosaminoglycans in human skin preparations, e.g. dermal fibroblasts. The study investigated stability of KTTKS and palmitoyl-KTTKS in mouse skin preparations including dermal skin extracts, epidermal skin extracts and skin homogenates (mixture of all skin components), and permeability studied in intact skin of hairless mice. 

STABILITY:

Stability of an ingredient is the ability for it not to degrade. Results indicated that 40 μg/ml palmitoyl-KTTKS was more stable than KTTKS in skin homogenate, dermal extract and epidermal extract, as shown in the graph below:

Skin Homogenate

KTTKS degraded more rapidly than pal-KTTKS, 1.5% and 11.2% remaining after 60 minutes, respectively.

Dermal Extracts

KTTKS degraded after 30 minutes compared to pal-KTTKS which degraded after 120 minutes, 3.2% and 9.7% remaining, respectively.

Epidermal Extracts

KTTKS degraded more than pal-KTTKS, ~65% and ~100% remaining after 120 minutes, respectively.

From these results, it was suggested that proteolytic enzymes (these cut up proteins) may be attributable to degradation; higher quantities of proteolytic enzymes in dermal extracts and skin homogenates compared to epidermal extracts.

 

PERMEABILITY:

Permeability of an ingredient is the ability for it to penetrate a layer(s). 50 μg/cm² of KTTKS and pal-KTTKS were added to intact skin of hairless mice.

Results revealed that over a 48 hour time frame, there was no detection of KTTKS or pal-KTTKS.

Over a 24 hour period, no KTTKS was identified in any skin layer. However, as shown on the right, pal-KTTKS was detected in the stratum corneum, epidermis, and in the dermis over 24 hours.

Overall, a total of 14.7% of pal-KTTKS was held in the skin over 24 hours. Only a trace amount (0.6%) appeared to be in the dermis, therefore, it was concluded neither KTTKS nor pal-KTTKS could penetrate the entire thickness of intact hairless mouse skin to reach the dermis.

What Is Next?

Previous in vitro studies reveal the dermis to be the pentapeptide's target, stimulating production of skin proteins. This study highlights evidence that transdermal delivery of palmitoyl-KTTKS may not reach the dermis in intact skin, and enzymes in the skin layers may degrade the peptide within 24 hours. There is scope for further investigation; the study highlights the potential for palmitoyl-KTTKS to be linked to proteolytic enzyme inhibitors, preventing enzymatic degradation of palmitoyl-KTTKS in the dermis, potentially enabling palmitoyl-KTTKS to elicit its effect at its target site… Could this be a potential new and improved anti-ageing ingredient?

Read More:

To read the full study: Dermal Stability and In Vitro Skin Permeation of Collage Pentapeptides (KTTKS and palmitoyl-KTTKS)

For more information on wrinkle formation: Skin aging and natural photoprotection, A mechanisitc model for the aging of human skin and Why does skin wrinkle with age?

Bibliography:

Mohammed YH, Yamada M, Lin LL, Grice JE, Roberts MS, et al. "Microneedle enhanced delivery of cosmeceutically relevant peptides in human skin" (2014) PLoS ONE 9(7): e101956.

Images:  Molecular Pharmaceutics