Skin permeability, a dismissed necessity for anti‐wrinkle peptide performance

Abstract

Background:The skin offers various benefits and potential for peptide delivery if its barrier performance can be reduced temporarily and reversibly. As peptides possess high molecular weight, hydrophilic nature (in most cases), and ionizable groups in the structure, their skin delivery is highly challenging. Apart from this, they are susceptible to the proteolytic enzymes in the skin. Anti-wrinkle peptides, like other peptides, suffer from insufficient skin permeability, while most of them must penetrate deep in the skin to present their efficacy. Although the cellular studies indicate the effectiveness of such peptides, without the ability to permeate the skin sufficiently, this efficacy is useless. Poor skin permeability of anti-wrinkle peptides has led to ongoing research for finding feasible and noninvasive enhancement methods that would be desirable for consumers of cosmetic products. Method:In this paper, the possibility of skin permeation of anti-wrinkle peptides as well as the chemical, physical, and encapsulation approaches that have been employed to date to increase permeability of these difficult molecules are thoroughly reviewed.Results: Most anti-wrinkle peptides are not appropriate candidates for skin permeation and the use of enhancement methods is essential to increase their permeability. To do so, only some permeability enhancement approaches have been applied so far, including chemical modification with hydrophobic moieties or cell penetrating peptides, metal complexation, chemical permeation enhancers, iontophoresis, microneedles, and encapsulation in nanocarriers. The results of studies published on the skin permeability of anti-wrinkle peptides carnosine, GHK, PKEK, GEKG, GQPR, and KTTKS indicate that the skin permeability of these peptides can be successfully increased. Conclusion:Although the skin permeability of most anti-wrinkle peptides is not high enough and most anti-wrinkle peptides might not reach their targets in the skin at right concentrations, their permeability can be increased to therapeutic concentrations using various enhancement approaches. K E Y W O R D Santi-wrinkle peptides, cosmetic peptides, permeability enhancement approaches, skin delivery of peptides, skin permeability | 233 MORTAZAVI and MOGHIMI Résumé Contexte: La peau offre divers avantages et a la faculté de recevoir des peptides si l'on parvient à réduire temporairement et de manière réversible sa capacité à fonctionner comme une barrière. Comme les peptides ont un poids moléculaire élevé, une nature hydrophile (dans la plupart des cas) et possèdent des groupes ionisables dans leur structure, il est très difficile d'en faire bénéficier la peau. En outre, ils sont sensibles aux enzymes protéolytiques de la peau. Les peptides antirides, comme d'autres peptides, souffrent d'une capacité insuffisante de perméation de la peau ; or, la plupart d'entre eux doivent y pénétrer profondément pour avoir une efficacité.Bien que les études cellulaires indiquent l'efficacité de ces peptides, s'ils sont incapables de pénétrer s...

Food Peptides for the Nutricosmetic Industry

“…Water-dispersible forms can be formulated by homogenizing the W/O microemulsion with water and a hydrophilic emulsifier to form a W/O/W type system. Mortazavi et al used W/O microemulsion to encapsulate PKEK, a tetrapeptide that can decrease the pigmentation process [ 266 ].…”

Iontophoresis in dermal delivery: A review of applications in dermato‐cosmetic and aesthetic sciences

“…The use of anti-wrinkle peptides to inhibit skin ageing shows a constantly rising trend in the cosmetics market. However, despite their properties, and the fact that the peptides used in personal care products are usually of low molecular size, cosmetic peptides remain poor candidates for skin permeation [51]. For example, acetyl hexapeptide-8 (Ac-EEMQRR-amide, marketed as argireline) is one of the most commonly used synthetic anti-ageing peptides.…”

“…It is used in cosmetic formulations as a neurotransmitter inhibitor, to reduce facial muscle contractions and thus prevent the formation of expressive wrinkles. However, when a commercially available O/W emulsion containing 10% w/w Ac-EEMQRRamide was evaluated using hairless guinea pigs as the viable skin model and human cadaver skin, it was unable to reach the dermis, and thus unable to target the neuromuscular junction, which is a prerequisite for affecting the muscles involved in facial expression [51]. Nevertheless, argireline iontophoresis has shown positive results [17,53].…”

“…Although the use of iontophoresis may increase substance delivery compared to conventional passive dermal methods, it still has limitations as a technique [9]. The iontophoretic process can be affected by numerous variables, which can be broadly categorized into (a) operational factors, including the composition of the formulation (concentration, pH, ionic strength and presence of competing ions), the physicochemical properties of the permeant (molecular size and weight, charge, polarity), and the experimental conditions (treatment duration, current type and density, electrode material, size and polarity); and (b) biological factors, including intra-and inter-subject variability, regional blood flow, the condition of the skin and skin pH [13,27,51,89].…”

“…Inhibition of skin ageing has always been one of the most sought‐after cosmetic treatments [51]. However, the topical delivery of widely used anti‐wrinkle agents, such as hyaluronic acid and vitamin C, is challenging because of their molecular size and/or low lipophilicity [3].…”