46 PEPTIDES
recovery from cumulative mechanical and biological stress. Despite its biological relevance, the effective
topical use of EGF remains particularly challenging due to several physicochemical and formulation- related limitations. EGF is a relatively large and hydrophilic polypeptide with a molecular weight of approximately 6 kDa, significantly above the molecular size generally considered favourable for passive skin penetration.18 Consequently, free EGF exhibits limited diffusion across the stratum corneum together with low functional bioavailability within viable skin compartments. Beyond penetration limitations, EGF is also
highly sensitive to environmental and formulation- associated degradation. The molecule is susceptible to oxidation, aggregation, conformational instability and proteolytic degradation, particularly under conventional aqueous and emulsion-based formulation conditions.19
Temperature fluctuations,
pH variations and interfacial stress may further compromise its structural integrity and biological activity. Together, these limitations significantly
complicate the effective topical delivery of biologically active EGF to skin compartments involved in extracellular matrix organization and dermal remodelling processes, reinforcing the growing interest in advanced delivery technologies capable of improving the functional performance of peptide-based biomolecules in cosmetic formulations.
Delivery systems as a strategy to improve functional EGF delivery To address these limitations, encapsulation technologies and advanced delivery systems have attracted growing interest as strategies capable of improving the stability, localization and functional bioavailability of EGF in topical formulations. Among these approaches, liposome-based
systems are considered particularly relevant platforms for biomolecules such as peptides and growth factors. By partially isolating EGF from destabilizing environmental conditions, these systems may help reduce degradation associated with oxidation, proteolytic activity, aggregation and formulation-related interfacial stress, thereby contributing to the preservation of biological activity during storage and topical application. Beyond stability protection, delivery systems
may also improve the interaction of EGF with the skin barrier and enhance its localization within viable epidermal and superficial dermal compartments. Flexible lipidic systems have been reported to improve skin retention and local penetration of peptide-based biomolecules compared with conventional aqueous formulations, helping increase their functional persistence within skin areas involved in tissue remodelling dynamics. Since many of the biological targets associated
with EGF signalling are located within viable skin compartments, improving local delivery and tissue interaction may significantly influence the functional activity of the molecule after topical application.
PERSONAL CARE MAGAZINE July 2026 Delivery systems should not be understood
simply as passive penetration enhancers, but rather as functional technologies capable of modulating the biological performance of signalling molecules within the skin. By improving molecular protection, localization and biological persistence, encapsulation systems may help optimize the functional efficacy of peptide-based actives whose performance would otherwise be limited under conventional formulation conditions. Based on these considerations, encapsulated
delivery systems represent a particularly promising strategy for improving the topical functionality of EGF and supporting extracellular matrix organization, dermal resilience and skin mechanical performance during chronoageing.
Ex vivo evaluation of encapsulated EGF in a chronoageing-associated model While collagen is primarily associated with skin firmness and tensile resistance, elastin plays a fundamental role in tissue elasticity and mechanical recovery, allowing the skin to recover its original shape after repeated deformation. To evaluate the effect of the encapsulated
EGF delivery system on extracellular matrix preservation, collagen content, elastin content and extracellular matrix fibre area were quantified in human skin explants under healthy, aged and treatment conditions following topical application of the encapsulated EGF delivery system or non- encapsulated EGF. Ageing-associated extracellular matrix
deterioration was induced through continuous hydrocortisone exposure. Collagen and elastin levels were expressed as µg per mg of fresh dermal tissue, while extracellular matrix fibres were quantified as the percentage of stained area in full cross-sectional Masson’s trichrome images. Under ageing-associated conditions, elastin
levels decreased from 6.9 µg/mg tissue in healthy skin to 5.6 µg/mg tissue in aged explants, reflecting the progressive deterioration of the elastic fibre network under stress-associated ageing conditions (Figure 1) Treatment with the encapsulated EGF system
increased elastin content up to 7.5 µg/mg tissue, corresponding to an increase of approximately 34% compared with aged explants and even surpassing healthy skin values. In contrast, non-encapsulated EGF only reached 5.9 µg/mg tissue under the same experimental conditions, remaining close to the aged condition (Figure 1). Histological analysis further supported these
findings. Representative Masson’s trichrome- stained cross-sectional dermal sections obtained after ten days of treatment revealed clear differences in extracellular matrix organization between experimental conditions. Since collagen-rich extracellular matrix fibres
are stained in blue-green in this model, healthy explants exhibited a dense and well-organized dermal architecture, whereas aged explants showed a more fragmented and disorganized extracellular matrix network. Treatment with the encapsulated EGF delivery system preserved fibre organization and dermal structure more efficiently than non-encapsulated EGF, which exhibited a less homogeneous and less organized matrix distribution pattern (Figure 2). These findings are particularly relevant from
a skin resilience perspective, since the ability of the skin to recover from repetitive mechanical deformation depends heavily on the integrity and organization of the elastic fibre network. Interestingly, the differences observed
between encapsulated and non-encapsulated EGF further reinforce the importance of delivery technologies for improving the functional performance of peptide-based biomolecules in topical applications. While free EGF exhibited limited biological impact under the tested conditions, the encapsulated system demonstrated substantially greater activity, suggesting that improving molecular stability and local bioavailability may play a critical role in maximizing the functional efficacy of EGF within viable skin compartments.
Translation into visible clinical performance The progressive deterioration of extracellular matrix organization during chronoageing
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12 10 8 6 4 2 0
Skin roughness Control ■ Treatment ■ T0 D28 D56
35 30 25 20 15 10 5 0
Wrinkle depth Control ■ Treatment ■
T0
D28
D56
Figure 3: Skin roughness (Ra parameter) (A) and wrinkle depth (Rz parameter) (B) evaluated by PRIMOS CR analysis during a 56-day clinical study with the encapsulated EGF delivery system. Data are presented as mean ± SD (n = 25)
Ra (a.u.)
Ra (a.u.)
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