Peptides

Peptides have recently generated interest as biologically active compounds incorporated into cosmeceutical products intended to treat aging skin. Peptides are composed of chains of amino acids, which are derived from DNA transcription. In typical cellular settings, peptides communicate or signal between DNA and the cellular network. Consequently, they are thought to be capable of being used or exploited to direct cells to maintain youthful behavior, yielding a stable, nonaging manifestation. In addition, peptides can be rendered by protein degradation, thus forming an essential feedback inhibition and upregulation loop (Facial Plast. Surg. 2009;25:285-9). Downregulation of metalloproteinases (MMPs), notably collagenase, by peptides is a good example, as well as a window into why peptides have sparked interest within antiaging research (Dermatol. Surg. 2005;31[7 Pt 2]:832-6, discussion 836).

Researchers at the University of Tennessee, Memphis, performed some of the seminal work that has paved the way for understanding how to harness the activity of natural peptides by showing that the production of the extracellular matrix in fibroblasts is fostered by a pentapeptide subfragment of propeptide of type I collagen (J. Biol. Chem. 1993;268:9941-4).

But the foundational work setting the stage for development of cosmeceutical peptides has been in the research for ameliorating wounds, which dates back several decades and can be traced to the use of yeast extracts for wound care in the 1930s, later leading to the extraction of a usable protein fraction (Dermatol. Ther. 2007;20:343-9; Clin. Ther. 1991;13:430-4). Signal peptides, enzyme-inhibitor peptides, neurotransmitter-inhibitor peptides (or neuropeptides), and carrier peptides are the four primary classes of topical or cosmeceutical peptides. This column will offer a brief summary of each and acknowledge additional recent research. Future columns may address each of these peptide categories pertinent to antiaging cosmeceuticals.

Signal peptides

Specific bioactive amino acid chains have been discovered in recent years that promote human skin dermal fibroblast growth in vitro and in vivo, and reduce the length and depth of wrinkles (Dermatol. Ther. 2007;20:343-9). The most popular signal peptide is the lysine-threonine-threonine-lysine-serine (KTTKS) located on type 1 procollagen. To enhance epidermal delivery, it has been linked to palmitic acid, thus the marketed version (Matrixyl) is a palmitoyl pentapeptide, which has been shown to augment the synthesis of collagen by fibroblasts and yield reductions in fine lines and wrinkles, according to quantitative analysis and self-reports (J. Biol. Chem. 1993;268:9941-4; Int. J. Cosmet. Sci. 2005;27:155-60).

New signal peptides are expected to be stronger and better targeted than those presently marketed (Facial Plast. Surg. 2009;25:285-9). Signal peptides promote the synthesis of matrix proteins, collagen in particular, which leads to firmer, younger looking skin, and also augments levels of elastin, proteoglycans, glycosaminoglycans, and fibronectin (Int. J. Cosmet. Sci. 2009;31:327-45).

Enzyme-inhibitor peptides

These peptides suppress enzymatic activity either directly or indirectly. Enzyme-inhibiting peptides extracted from soybeans have been incorporated into antiaging, moisturizing, and cleansing products as well as hair care formulations (Int. J. Cosmet. Sci. 2009;31:327-45). In a small study in 10 white females, a 2% soya biopeptide performed better than did placebo in collagen and glycosaminoglycan promotion (Int. J. Cosmet. Sci. 1999;21:299-311).

More recently, a rice peptide derived from germinated black rice, which has been used in traditional Asian medicines, was found to block MMP activity and dose-dependently stimulate hyaluronan synthase 2 gene expression (a twofold increase) in human keratinocytes (J. Microbiol. Biotechnol. 2007;17:271-9). Such peptides are found in antiaging and hair products.

In addition, antioxidant activity, a high affinity to chelate with copper, and the capacity to suppress tyrosinase activity and keratinocyte apoptosis have been displayed by the enzyme-inhibiting peptide sericin, derived from the silkworm Bombyx mori (Int. J. Cosmet. Sci. 2009;31:327-45). Sericin also has been shown to facilitate the intrinsic moisturization of skin by restoring amino acids and imparting an occlusive effect (J. Cosmet. Dermatol. 2005;4:250-7).

Neuropeptides

Neuropeptides are known to mediate skin inflammation and, thus, contribute as an underlying aspect of reactive skin conditions (Eur. J. Dermatol. 2010;20:731-7). Also known as neurotransmitter-affecting peptides, these compounds are included in cosmeceuticals to mimic the action of botulinum toxin A. Essentially, they inhibit acetylcholine release at the neuromuscular junction.

The best known of these is acetyl hexapeptide-3, marketed as Argireline. Attached to acetic acid residue, this synthetic peptide, based on the N-terminal end of the synaptosomal-associated protein (SNAP)–25 that blocks soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex development and catecholamine release (Int. J. Cosmet. Sci. 2009;31:327-45), is thought to suppress the release of neurotransmitters, easing facial tension, and thus reducing wrinkles. Evidence of its effectiveness has appeared largely in proprietary studies. Much more research is necessary to establish the suitability of this form of peptide for topical antiaging applications.

Carrier peptides

Carrier peptides stabilize and transport trace elements essential for healing wounds and enzymatic processes (Dermatol. Ther. 2007;20:343-9). Although it also confers signal peptide effects, glycyl-L-histidyl-L-lysine (GHK), a naturally occurring tripeptide initially isolated from human plasma (Nat. New Biol. 1973;243:85-7), is known mainly as a carrier peptide. It is typically linked with copper, given its high affinity for it, and several studies have shown that copper peptide molecules using GHK (glycyl-L-histidyl-L-lysine-Cu²⁺ or GHK-Cu) deliver varied restorative effects, including the improvement in the appearance of fine lines and wrinkles (Dermatol. Ther. 2007;20:343-9). This tripeptide complex has been used for many years to accelerate wound healing and is found in several moisturizers. Significantly, the GHK-Cu complex also has been shown to stimulate collagen synthesis (FEBS Lett. 1988;238:343-6) and to augment sulfated proteoglycans levels in fibroblast cultures as well as experimental animal wound models (J. Clin. Invest. 1993;92:2368-76). GHK-Cu also influences tissue remodeling by raising the levels of MMP-2 and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) (Life Sci. 2000;67:2257-65). More research is necessary to ascertain the efficacy of copper peptide as an antiaging agent.

Recent general research findings

A double-blind clinical study in 2004 of 20 healthy women volunteers between 40 and 62 years of age revealed that a gel formula containing 3% of a collagen-like hexapeptide significantly reduced the total surface of wrinkles as well as the number and average depth of wrinkles (Int. J. Tissue React. 2004;26:105-11).

In 2005, a literature review of studies published on the effects and practical applications of peptides as topical agents for skin improvement showed that peptide cosmeceuticals seem to exhibit the potential to blunt the visual effects of aging on the skin, and that formulations must be stable, absorbed into the skin, and biologically active (Dermatol. Surg. 2005;31[7 Pt 2]:832-6, discussion 836).

In 2007, investigators reported on the development of a new hand care formulation derived from wool peptides. The keratin fraction from wool was shown through long-term in vivo studies to enhance cutaneous hydration, water-holding capacity, and elasticity in volunteers with dry skin. In addition, the researchers found that the keratin peptide preparation blunted some of the adverse effects due to surfactant exposure (J. Cosmet. Sci. 2007;58:99-107).

That same year, researchers reported that they prepared two stable cosmetic formulations, an emulsion with an external aqueous phase for normal-to-dry skin and a gel for oily skin, with acetyl hexapeptide-8 (Argireline) as the active ingredient (J. Cosmet. Sci. 2007;58:157-71).

Previously, Argireline was shown in healthy women volunteers, in a skin topography analysis of an oil/water (O/W) emulsion containing 10% of the hexapeptide, to have decreased wrinkle depth up to 30% after 30 days of treatment. Researchers determined that the synthetic hexapeptide significantly suppresses neurotransmitter release comparably to botulinum toxin A, with fewer side effects but lower efficacy. They also noted that Argireline displayed no in vivo oral toxicity and evoked no irritation at high doses, suggesting that the peptide is a topical nontoxic antiwrinkle alternative to botulinum toxins (Int. J. Cosmet. Sci. 2002;24:303-10).

In 2008, investigators tested a hydrolyzed keratin peptide derived from wool on skin in two different formulations. Long-term in vivo studies yielded significant differences between the control and treated sites, with the treated areas exhibiting an increase in hydration and elasticity because of keratin peptide application. The investigators also noted measurements showing that the keratin formulations supported skin barrier integrity, enhancing its water-holding capacity. In particular, the formulation combining keratin peptide with internal wool lipids in a liposome suspension showed promising effects that they deemed appropriate for new cosmetic products (Skin Res. Technol. 2008;14:243-8).

Conclusion

Peptide cosmeceuticals represent a new and popular choice for consumers shopping for antiaging products. Are they worthy options? As always, the capacity of topical products to penetrate the skin and exert a biologic impact is of great significance. Some products appear to exert antiaging effects, but most evidence of effectiveness has emerged from in vitro studies or small in vivo investigations. More research, in the form of large randomized controlled trials, is necessary to establish the effectiveness of these intriguing products. As it is, though, numerous products are on the market and this area of research and product development shows promise.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001 and joined the editorial advisory board in 2004. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.

Peptides have recently generated interest as biologically active compounds incorporated into cosmeceutical products intended to treat aging skin. Peptides are composed of chains of amino acids, which are derived from DNA transcription. In typical cellular settings, peptides communicate or signal between DNA and the cellular network. Consequently, they are thought to be capable of being used or exploited to direct cells to maintain youthful behavior, yielding a stable, nonaging manifestation. In addition, peptides can be rendered by protein degradation, thus forming an essential feedback inhibition and upregulation loop (Facial Plast. Surg. 2009;25:285-9). Downregulation of metalloproteinases (MMPs), notably collagenase, by peptides is a good example, as well as a window into why peptides have sparked interest within antiaging research (Dermatol. Surg. 2005;31[7 Pt 2]:832-6, discussion 836).

Researchers at the University of Tennessee, Memphis, performed some of the seminal work that has paved the way for understanding how to harness the activity of natural peptides by showing that the production of the extracellular matrix in fibroblasts is fostered by a pentapeptide subfragment of propeptide of type I collagen (J. Biol. Chem. 1993;268:9941-4).

But the foundational work setting the stage for development of cosmeceutical peptides has been in the research for ameliorating wounds, which dates back several decades and can be traced to the use of yeast extracts for wound care in the 1930s, later leading to the extraction of a usable protein fraction (Dermatol. Ther. 2007;20:343-9; Clin. Ther. 1991;13:430-4). Signal peptides, enzyme-inhibitor peptides, neurotransmitter-inhibitor peptides (or neuropeptides), and carrier peptides are the four primary classes of topical or cosmeceutical peptides. This column will offer a brief summary of each and acknowledge additional recent research. Future columns may address each of these peptide categories pertinent to antiaging cosmeceuticals.

Signal peptides

Specific bioactive amino acid chains have been discovered in recent years that promote human skin dermal fibroblast growth in vitro and in vivo, and reduce the length and depth of wrinkles (Dermatol. Ther. 2007;20:343-9). The most popular signal peptide is the lysine-threonine-threonine-lysine-serine (KTTKS) located on type 1 procollagen. To enhance epidermal delivery, it has been linked to palmitic acid, thus the marketed version (Matrixyl) is a palmitoyl pentapeptide, which has been shown to augment the synthesis of collagen by fibroblasts and yield reductions in fine lines and wrinkles, according to quantitative analysis and self-reports (J. Biol. Chem. 1993;268:9941-4; Int. J. Cosmet. Sci. 2005;27:155-60).

New signal peptides are expected to be stronger and better targeted than those presently marketed (Facial Plast. Surg. 2009;25:285-9). Signal peptides promote the synthesis of matrix proteins, collagen in particular, which leads to firmer, younger looking skin, and also augments levels of elastin, proteoglycans, glycosaminoglycans, and fibronectin (Int. J. Cosmet. Sci. 2009;31:327-45).

Enzyme-inhibitor peptides

These peptides suppress enzymatic activity either directly or indirectly. Enzyme-inhibiting peptides extracted from soybeans have been incorporated into antiaging, moisturizing, and cleansing products as well as hair care formulations (Int. J. Cosmet. Sci. 2009;31:327-45). In a small study in 10 white females, a 2% soya biopeptide performed better than did placebo in collagen and glycosaminoglycan promotion (Int. J. Cosmet. Sci. 1999;21:299-311).

More recently, a rice peptide derived from germinated black rice, which has been used in traditional Asian medicines, was found to block MMP activity and dose-dependently stimulate hyaluronan synthase 2 gene expression (a twofold increase) in human keratinocytes (J. Microbiol. Biotechnol. 2007;17:271-9). Such peptides are found in antiaging and hair products.

In addition, antioxidant activity, a high affinity to chelate with copper, and the capacity to suppress tyrosinase activity and keratinocyte apoptosis have been displayed by the enzyme-inhibiting peptide sericin, derived from the silkworm Bombyx mori (Int. J. Cosmet. Sci. 2009;31:327-45). Sericin also has been shown to facilitate the intrinsic moisturization of skin by restoring amino acids and imparting an occlusive effect (J. Cosmet. Dermatol. 2005;4:250-7).

Neuropeptides

Neuropeptides are known to mediate skin inflammation and, thus, contribute as an underlying aspect of reactive skin conditions (Eur. J. Dermatol. 2010;20:731-7). Also known as neurotransmitter-affecting peptides, these compounds are included in cosmeceuticals to mimic the action of botulinum toxin A. Essentially, they inhibit acetylcholine release at the neuromuscular junction.

The best known of these is acetyl hexapeptide-3, marketed as Argireline. Attached to acetic acid residue, this synthetic peptide, based on the N-terminal end of the synaptosomal-associated protein (SNAP)–25 that blocks soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex development and catecholamine release (Int. J. Cosmet. Sci. 2009;31:327-45), is thought to suppress the release of neurotransmitters, easing facial tension, and thus reducing wrinkles. Evidence of its effectiveness has appeared largely in proprietary studies. Much more research is necessary to establish the suitability of this form of peptide for topical antiaging applications.

Carrier peptides

Carrier peptides stabilize and transport trace elements essential for healing wounds and enzymatic processes (Dermatol. Ther. 2007;20:343-9). Although it also confers signal peptide effects, glycyl-L-histidyl-L-lysine (GHK), a naturally occurring tripeptide initially isolated from human plasma (Nat. New Biol. 1973;243:85-7), is known mainly as a carrier peptide. It is typically linked with copper, given its high affinity for it, and several studies have shown that copper peptide molecules using GHK (glycyl-L-histidyl-L-lysine-Cu²⁺ or GHK-Cu) deliver varied restorative effects, including the improvement in the appearance of fine lines and wrinkles (Dermatol. Ther. 2007;20:343-9). This tripeptide complex has been used for many years to accelerate wound healing and is found in several moisturizers. Significantly, the GHK-Cu complex also has been shown to stimulate collagen synthesis (FEBS Lett. 1988;238:343-6) and to augment sulfated proteoglycans levels in fibroblast cultures as well as experimental animal wound models (J. Clin. Invest. 1993;92:2368-76). GHK-Cu also influences tissue remodeling by raising the levels of MMP-2 and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) (Life Sci. 2000;67:2257-65). More research is necessary to ascertain the efficacy of copper peptide as an antiaging agent.

Recent general research findings

A double-blind clinical study in 2004 of 20 healthy women volunteers between 40 and 62 years of age revealed that a gel formula containing 3% of a collagen-like hexapeptide significantly reduced the total surface of wrinkles as well as the number and average depth of wrinkles (Int. J. Tissue React. 2004;26:105-11).

In 2005, a literature review of studies published on the effects and practical applications of peptides as topical agents for skin improvement showed that peptide cosmeceuticals seem to exhibit the potential to blunt the visual effects of aging on the skin, and that formulations must be stable, absorbed into the skin, and biologically active (Dermatol. Surg. 2005;31[7 Pt 2]:832-6, discussion 836).

In 2007, investigators reported on the development of a new hand care formulation derived from wool peptides. The keratin fraction from wool was shown through long-term in vivo studies to enhance cutaneous hydration, water-holding capacity, and elasticity in volunteers with dry skin. In addition, the researchers found that the keratin peptide preparation blunted some of the adverse effects due to surfactant exposure (J. Cosmet. Sci. 2007;58:99-107).

That same year, researchers reported that they prepared two stable cosmetic formulations, an emulsion with an external aqueous phase for normal-to-dry skin and a gel for oily skin, with acetyl hexapeptide-8 (Argireline) as the active ingredient (J. Cosmet. Sci. 2007;58:157-71).

Previously, Argireline was shown in healthy women volunteers, in a skin topography analysis of an oil/water (O/W) emulsion containing 10% of the hexapeptide, to have decreased wrinkle depth up to 30% after 30 days of treatment. Researchers determined that the synthetic hexapeptide significantly suppresses neurotransmitter release comparably to botulinum toxin A, with fewer side effects but lower efficacy. They also noted that Argireline displayed no in vivo oral toxicity and evoked no irritation at high doses, suggesting that the peptide is a topical nontoxic antiwrinkle alternative to botulinum toxins (Int. J. Cosmet. Sci. 2002;24:303-10).

In 2008, investigators tested a hydrolyzed keratin peptide derived from wool on skin in two different formulations. Long-term in vivo studies yielded significant differences between the control and treated sites, with the treated areas exhibiting an increase in hydration and elasticity because of keratin peptide application. The investigators also noted measurements showing that the keratin formulations supported skin barrier integrity, enhancing its water-holding capacity. In particular, the formulation combining keratin peptide with internal wool lipids in a liposome suspension showed promising effects that they deemed appropriate for new cosmetic products (Skin Res. Technol. 2008;14:243-8).

Conclusion

Peptide cosmeceuticals represent a new and popular choice for consumers shopping for antiaging products. Are they worthy options? As always, the capacity of topical products to penetrate the skin and exert a biologic impact is of great significance. Some products appear to exert antiaging effects, but most evidence of effectiveness has emerged from in vitro studies or small in vivo investigations. More research, in the form of large randomized controlled trials, is necessary to establish the effectiveness of these intriguing products. As it is, though, numerous products are on the market and this area of research and product development shows promise.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001 and joined the editorial advisory board in 2004. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.

Peptides have recently generated interest as biologically active compounds incorporated into cosmeceutical products intended to treat aging skin. Peptides are composed of chains of amino acids, which are derived from DNA transcription. In typical cellular settings, peptides communicate or signal between DNA and the cellular network. Consequently, they are thought to be capable of being used or exploited to direct cells to maintain youthful behavior, yielding a stable, nonaging manifestation. In addition, peptides can be rendered by protein degradation, thus forming an essential feedback inhibition and upregulation loop (Facial Plast. Surg. 2009;25:285-9). Downregulation of metalloproteinases (MMPs), notably collagenase, by peptides is a good example, as well as a window into why peptides have sparked interest within antiaging research (Dermatol. Surg. 2005;31[7 Pt 2]:832-6, discussion 836).

Researchers at the University of Tennessee, Memphis, performed some of the seminal work that has paved the way for understanding how to harness the activity of natural peptides by showing that the production of the extracellular matrix in fibroblasts is fostered by a pentapeptide subfragment of propeptide of type I collagen (J. Biol. Chem. 1993;268:9941-4).

But the foundational work setting the stage for development of cosmeceutical peptides has been in the research for ameliorating wounds, which dates back several decades and can be traced to the use of yeast extracts for wound care in the 1930s, later leading to the extraction of a usable protein fraction (Dermatol. Ther. 2007;20:343-9; Clin. Ther. 1991;13:430-4). Signal peptides, enzyme-inhibitor peptides, neurotransmitter-inhibitor peptides (or neuropeptides), and carrier peptides are the four primary classes of topical or cosmeceutical peptides. This column will offer a brief summary of each and acknowledge additional recent research. Future columns may address each of these peptide categories pertinent to antiaging cosmeceuticals.

Signal peptides

Specific bioactive amino acid chains have been discovered in recent years that promote human skin dermal fibroblast growth in vitro and in vivo, and reduce the length and depth of wrinkles (Dermatol. Ther. 2007;20:343-9). The most popular signal peptide is the lysine-threonine-threonine-lysine-serine (KTTKS) located on type 1 procollagen. To enhance epidermal delivery, it has been linked to palmitic acid, thus the marketed version (Matrixyl) is a palmitoyl pentapeptide, which has been shown to augment the synthesis of collagen by fibroblasts and yield reductions in fine lines and wrinkles, according to quantitative analysis and self-reports (J. Biol. Chem. 1993;268:9941-4; Int. J. Cosmet. Sci. 2005;27:155-60).

New signal peptides are expected to be stronger and better targeted than those presently marketed (Facial Plast. Surg. 2009;25:285-9). Signal peptides promote the synthesis of matrix proteins, collagen in particular, which leads to firmer, younger looking skin, and also augments levels of elastin, proteoglycans, glycosaminoglycans, and fibronectin (Int. J. Cosmet. Sci. 2009;31:327-45).

Enzyme-inhibitor peptides

These peptides suppress enzymatic activity either directly or indirectly. Enzyme-inhibiting peptides extracted from soybeans have been incorporated into antiaging, moisturizing, and cleansing products as well as hair care formulations (Int. J. Cosmet. Sci. 2009;31:327-45). In a small study in 10 white females, a 2% soya biopeptide performed better than did placebo in collagen and glycosaminoglycan promotion (Int. J. Cosmet. Sci. 1999;21:299-311).

More recently, a rice peptide derived from germinated black rice, which has been used in traditional Asian medicines, was found to block MMP activity and dose-dependently stimulate hyaluronan synthase 2 gene expression (a twofold increase) in human keratinocytes (J. Microbiol. Biotechnol. 2007;17:271-9). Such peptides are found in antiaging and hair products.

In addition, antioxidant activity, a high affinity to chelate with copper, and the capacity to suppress tyrosinase activity and keratinocyte apoptosis have been displayed by the enzyme-inhibiting peptide sericin, derived from the silkworm Bombyx mori (Int. J. Cosmet. Sci. 2009;31:327-45). Sericin also has been shown to facilitate the intrinsic moisturization of skin by restoring amino acids and imparting an occlusive effect (J. Cosmet. Dermatol. 2005;4:250-7).

Neuropeptides

Neuropeptides are known to mediate skin inflammation and, thus, contribute as an underlying aspect of reactive skin conditions (Eur. J. Dermatol. 2010;20:731-7). Also known as neurotransmitter-affecting peptides, these compounds are included in cosmeceuticals to mimic the action of botulinum toxin A. Essentially, they inhibit acetylcholine release at the neuromuscular junction.

The best known of these is acetyl hexapeptide-3, marketed as Argireline. Attached to acetic acid residue, this synthetic peptide, based on the N-terminal end of the synaptosomal-associated protein (SNAP)–25 that blocks soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex development and catecholamine release (Int. J. Cosmet. Sci. 2009;31:327-45), is thought to suppress the release of neurotransmitters, easing facial tension, and thus reducing wrinkles. Evidence of its effectiveness has appeared largely in proprietary studies. Much more research is necessary to establish the suitability of this form of peptide for topical antiaging applications.

Carrier peptides

Carrier peptides stabilize and transport trace elements essential for healing wounds and enzymatic processes (Dermatol. Ther. 2007;20:343-9). Although it also confers signal peptide effects, glycyl-L-histidyl-L-lysine (GHK), a naturally occurring tripeptide initially isolated from human plasma (Nat. New Biol. 1973;243:85-7), is known mainly as a carrier peptide. It is typically linked with copper, given its high affinity for it, and several studies have shown that copper peptide molecules using GHK (glycyl-L-histidyl-L-lysine-Cu²⁺ or GHK-Cu) deliver varied restorative effects, including the improvement in the appearance of fine lines and wrinkles (Dermatol. Ther. 2007;20:343-9). This tripeptide complex has been used for many years to accelerate wound healing and is found in several moisturizers. Significantly, the GHK-Cu complex also has been shown to stimulate collagen synthesis (FEBS Lett. 1988;238:343-6) and to augment sulfated proteoglycans levels in fibroblast cultures as well as experimental animal wound models (J. Clin. Invest. 1993;92:2368-76). GHK-Cu also influences tissue remodeling by raising the levels of MMP-2 and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) (Life Sci. 2000;67:2257-65). More research is necessary to ascertain the efficacy of copper peptide as an antiaging agent.

Recent general research findings

A double-blind clinical study in 2004 of 20 healthy women volunteers between 40 and 62 years of age revealed that a gel formula containing 3% of a collagen-like hexapeptide significantly reduced the total surface of wrinkles as well as the number and average depth of wrinkles (Int. J. Tissue React. 2004;26:105-11).

In 2005, a literature review of studies published on the effects and practical applications of peptides as topical agents for skin improvement showed that peptide cosmeceuticals seem to exhibit the potential to blunt the visual effects of aging on the skin, and that formulations must be stable, absorbed into the skin, and biologically active (Dermatol. Surg. 2005;31[7 Pt 2]:832-6, discussion 836).

In 2007, investigators reported on the development of a new hand care formulation derived from wool peptides. The keratin fraction from wool was shown through long-term in vivo studies to enhance cutaneous hydration, water-holding capacity, and elasticity in volunteers with dry skin. In addition, the researchers found that the keratin peptide preparation blunted some of the adverse effects due to surfactant exposure (J. Cosmet. Sci. 2007;58:99-107).

That same year, researchers reported that they prepared two stable cosmetic formulations, an emulsion with an external aqueous phase for normal-to-dry skin and a gel for oily skin, with acetyl hexapeptide-8 (Argireline) as the active ingredient (J. Cosmet. Sci. 2007;58:157-71).

Previously, Argireline was shown in healthy women volunteers, in a skin topography analysis of an oil/water (O/W) emulsion containing 10% of the hexapeptide, to have decreased wrinkle depth up to 30% after 30 days of treatment. Researchers determined that the synthetic hexapeptide significantly suppresses neurotransmitter release comparably to botulinum toxin A, with fewer side effects but lower efficacy. They also noted that Argireline displayed no in vivo oral toxicity and evoked no irritation at high doses, suggesting that the peptide is a topical nontoxic antiwrinkle alternative to botulinum toxins (Int. J. Cosmet. Sci. 2002;24:303-10).

In 2008, investigators tested a hydrolyzed keratin peptide derived from wool on skin in two different formulations. Long-term in vivo studies yielded significant differences between the control and treated sites, with the treated areas exhibiting an increase in hydration and elasticity because of keratin peptide application. The investigators also noted measurements showing that the keratin formulations supported skin barrier integrity, enhancing its water-holding capacity. In particular, the formulation combining keratin peptide with internal wool lipids in a liposome suspension showed promising effects that they deemed appropriate for new cosmetic products (Skin Res. Technol. 2008;14:243-8).

Conclusion

Peptide cosmeceuticals represent a new and popular choice for consumers shopping for antiaging products. Are they worthy options? As always, the capacity of topical products to penetrate the skin and exert a biologic impact is of great significance. Some products appear to exert antiaging effects, but most evidence of effectiveness has emerged from in vitro studies or small in vivo investigations. More research, in the form of large randomized controlled trials, is necessary to establish the effectiveness of these intriguing products. As it is, though, numerous products are on the market and this area of research and product development shows promise.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in Miami Beach. She founded the cosmetic dermatology center at the University of Miami in 1997. Dr. Baumann wrote the textbook "Cosmetic Dermatology: Principles and Practice" (McGraw-Hill, April 2002), and a book for consumers, "The Skin Type Solution" (Bantam, 2006). She has contributed to the Cosmeceutical Critique column in Skin & Allergy News since January 2001 and joined the editorial advisory board in 2004. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Galderma, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Stiefel, Topix Pharmaceuticals, and Unilever.