Peptides have already ushered in a new era in cosmetics. Here Irina Deloire examines some of the major benefits they have to offer in anti-ageing skin care
Amino acids constitute the code of life. All living cells and organisms' functions are regulated by the sequences of these original bricks, peptides, which form a unique programme of genetic machinery. Twenty natural amino acids give a huge combination and endless variety of different oligopeptides (2-10 amino acids), polypeptides (10-100 amino acids) and also proteins. Beyond the amino acids that are found in all known forms of life, many others have a vital role in biosynthesis and technology today.
Peptides have been the subject of research in the life sciences for over 50 years. Pharmaceutical laboratories have already engineered peptides with specific properties for treatments including cancer, diabetes, depression, hormonal imbalance and there are applications in immunology, neurology and epidemiology (anti-viral and antimicrobial peptides).
More recently there has been an explosion in the use of peptides in skin care, in the fields of both cosmetics and dermatology. The high demand for peptides in cosmetics can be explained by the need for more effective actives with higher activities and lower dosages and for purer, more defined compounds, in contrast to heterogeneous natural extracts containing dozens or even hundreds of individual molecules.
Indeed numerous studies have shown the importance of peptides in skin biology as regulating homeostasis and biological phenomenon of the skin cells.
The inner polypeptides acting on the skin level are constantly under assessment by R&D labs in search of smaller sequences with similar or even better biological activity. The amino acid sequence and the arrangement of the chains determine the function of the peptide. There are already some fairly extensive databases describing the relationship between the structure of the peptide and its biological activity, and this data helps to engineer biomimetic peptides that are identical to the skin's peptides and act on the physiological mechanisms of the skin with a very high degree of specificity. The latest progress in technology enables us to obtain high purity and nature-identical biomimetic peptides with excellent toxicological profiles and outstanding efficacy demonstrated through in-vitro, ex-vivo and in-vivo clinical studies. Spread through the skin, these biocompatible products have a perfectly determined action to improve declining functions of the cells without any systemic effects.
It comes as no surprise that the peptides have proved extremely efficient in anti-ageing application. Ageing is a highly complex process that depends on genetic and environmental input. Due to chronological ageing there is a slow-down in synthesis of proteins that constitute the extracellular matrix (ECM) of the skin.
A physiological factor, a complex of copper and a peptide sequence, has been first described as a growth factor, and further as a healing factor. This complex represents a human feedback signal that has potent tissue protective properties and stimulates tissues remodelling after the initial phase of wound healing. This natural complex is known to decrease during human ageing, which could be a factor in decreased tissue repair.
On the other hand, matrix metalloproteases (MMPs), a group of structurally related enzymes (proteases) that degrade ECM proteins, play a major role in the process of ECM protein degradation. Regular exposure to UV radiation, pollution and tobacco smoke induce actinic ageing at a higher rate than with just chronological ageing. In the dermis, consequences of this actinic ageing are structural disorders inducing the enhancement of MMPs level, as well as the decrease in the production of tissue inhibitors of metalloproteases (TIMPs) in keratinocytes and fibroblasts.
Besides MMPs, other proteases participate in ECM protein degradation. Most important among these is elastase, responsible for elastin degradation. Even if elastin represents only 2% of the total dermis proteins, this protein is the most important factor for a tight, elastic skin and cannot be regenerated. Loss of elastin in the skin system is irreparable and is not reversible.
The associations of biomimetic peptides having complementary mechanisms of anti-ageing strategy are already used in highly sophisticated cosmetic and dermocosmetic products as an alternative to surgery and botox injections. The biomimetic peptides Tripeptide-1 (Kollaren) and Tripeptide-2 (ECM-Protect) slow down skin ageing through two distinct pathways: stimulation of synthesis of structural proteins (collagens, fibronectins, laminins) and simultaneous inhibition of MMP activity that makes disorders in collagen and elastin functions. Both contribute to maintaining the ECM integrity of the dermis:
l Kollaren [INCI: Aqua (&) urea (&) glucose (&) guanidine HCL (&) tripep-tide-1] is a biomimetic peptide born from a deep study of the structure-activity relationship of the growth factors involved in healing process and is similar to the active sequence of the natural and physiological precursor for the synthesis of collagen. The action of this peptide is due to its capacity to stimulate the synthesis of collagen I and III, fibronectin and laminin and also contributes to the elaboration of elastin (figure 1).
l ECM-Protect [INCI: Aqua (&) dextran (&) tripeptide-2] is a very specific peptide that competitively inhibits the MMP-1 (collagenase) and elastase activities in this human skin explant model. This assay represents an excellent model for predicting the mechanism observed in the human skin after an over-production of proteases, following environmental factors, ageing or UV radiation. This model allows measurement of the quantity of intact or degraded collagen and elastin fibres. It inhibits the elastase activity at a very large scale, making this active highly potent for the protection of elastin fibres.
Used regularly these types of biomimetic peptides can help protect the skin from accelerated environmental-based ageing and rebalance the chronological skin ageing process, preserving the ultra-structure of ECM and restoring firmness and elasticity to the skin.
In addition to the existing biomimetic peptides, research has just been completed on a new generation of anti-ageing peptides, offering tailor-made solutions to the cosmetics industry. One of the peptides from this research will be presented at in-cosmetics 2008 in Amsterdam:
l ChroNOline [INCI: Glycerin (&) water (&) dextran (&) caprooyl tetrapeptide-3] is a biomimetic peptide of transforming-growth factor (TGF-b) that plays an important role in regulating ECM protein synthesis. TGF-b binds to its specific receptor at the surface of cells to propagate intracellular signals that translate into the stimulation of fibroblast proliferation in the dermis to enhance collagen and elastin synthesis. TGF-b also inhibits the expression of certain MMPs and so protects the newly synthesized fibres from premature destruction. In both skin ageing and photoageing, expression of TGF-b and its receptors are reduced. These changes have been associated with skin atrophy and structural disorganisation.
The particularity of this material is in its specificity of action on the dermo-epidermal junction (DEJ) proteins synthesis. Cell-matrix interactions at the DEJ are reduced with ageing. Indeed ageing is associated with a low level of expression and an increase in the destruction of supporting DEJ fibres. The structure of the DEJ is weakened and then flattens. These structural changes reduce the surface area for nutritional exchange and metabolic byproducts evacuation between the dermis and the epidermis.
– In-vitro, this material stimulates the production of laminin and fibronectin by human fibroblasts. Both are important structural components of the DEJ.
– When tested in an ex-vivo model of corticoid-induced skin ageing, it stimulated the expression of collagen VII and
laminin-5. These proteins are involved in the anchoring of the epidermis to the dermis at the DEJ. In the same model, it also prevented the flattening of the DEJ caused by corticoid treatment.
– In a clinical trial involving 27 female volunteers aged from 40 to 65, it reduced fine lines and wrinkles by as much as 29% after 28 days in comparison with placebo (figure 2).
– Consumers who tested a cream containing the material spontaneously reported rapid anti-ageing results as
skin smoothness, firmness and younger looking skin.
Furthermore ChroNOline is a lipopeptide composed of four amino acids linked to a lipid (caproic acid). Lipid coupling is known to facilitate peptide absorption through the skin, which explains the increased efficacy of this biomimetic peptide that offers extremely fast visible results.
In order to underline the deep action of this new active material on the DEJ, a study was performed to enable visualisation of efficacy (by ecography study vs placebo). The objective was to evaluate the in-vivo effect on dermal structures of an anti-wrinkle cream containing the new material versus a placebo.
High frequency ultrasound imaging can be used to identify the dermis which is thus visualised as a speckled pattern. The echoes of the dermis are considered to originate from the boundaries between collagen fibres, the surrounding water-rich ground substance and cells. Changes in echogenicity may therefore reflect an altered connective tissue composition of the dermis. In particular, a superficial low-echogenic band in the dermis immediately below the epidermal entrance echo has been related to age. Dermal echogenicity has therefore been proposed as a marker for skin ageing.
Taking part in the study were 27 Caucasian female volunteers aged 40 to 65, with healthy skin (phototype II, III or IV), who applied a placebo cream on the crow's feet of one randomized temple area and the same formulation containing 2.5% ChroNOline cream on the crow's feet of the other temple. Applications were repeated twice a day for 168 days. Skin echography scanning was performed on temple areas at D0 and D168. A 20-MHz ultrasound scanner was used to obtain cross-sectional images of the skin.
The test product showed a significant increase in entropy (dark band in upper dermis) for 78% of the volunteers and a significant increase in homogeneity (dermis) of 70% of the volunteers.
According to market research company Datamonitor, 30% of western consumers will be over 50 by 2009 and all studies confirm that life expectancy is increasing constantly. Skin care products have to be more and more efficient and sophisticated to keep pace with ageing of populations and the growing demand for visible efficacy of cosmetics.
Peptides lead a new era of cosmetics using active ingredients to counterbalance degrading environmental conditions, stress and an accelerated ageing process. So cosmetics can certainly contribute to the healthy lives of active seniors coping with their age and proud of their younger looking skin.
Author
Irina Ivanenko Deloire
Sales and marketing export manager,
Atrium Innovations, France
e-mail ideloire@atrium-innov.fr
www.atrium-innov.com