Human skin equivalents: Impaired barrier function in relation to the lipid and protein properties of the stratum corneum

Bouwstra, Joke A.; Helder, Richard W.J.; Ghalbzouri, Abdoelwaheb El

doi:10.1016/j.addr.2021.05.012

Cited by 57 publications

(39 citation statements)

References 133 publications

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“…Although the use of RHE is relevant and well‐established in the literature, studies report a greater permeation of active ingredients through these models compared to excised human skin. This could be explained mainly by differences between the lipid composition and organization [30]. Therefore, it is expected that the permeation results obtained here are more representative than the ones gathered in the group's previous work [16].…”

Section: Introductionmentioning

confidence: 61%

Efficiency of emulsifier‐free emulsions in delivering caffeine and α‐tocopherol to human skin

Kichou

Caritá

Gillet³

et al. 2023

Intern J of Cosmetic Sci

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Objective Increasing consumer demand for natural and environmentally friendly products is driving the cosmetic industry to seek greener and safer processes. High‐frequency ultrasound technology (HFUT) stabilizes emulsions without adding emulsifying surfactants (ES). In this work, the formulation characteristics of an HFUT‐treated emulsion and a Reference emulsion were compared for both caffeine and α‐tocopherol. Methods A comparison was made between ES‐free emulsions and the Reference emulsions based on droplet size, viscosity, pH and rheology behaviour for both active cosmetic ingredients. The permeation of caffeine and the skin retention of α ‐tocopherol were studied in vitro using Franz diffusion cells on human skin biopsies, considered the gold standard for permeation assays. Results The formulations developed were stable and showed suitable droplet size distribution. In the case of ES‐free emulsions, the average droplet size was inferior to 1.5 μm regardless of the polarity of the active. All formulations presented a shear‐thinning pseudoplastic behaviour, an attribute usually desired for cosmetic products. The skin permeation studies showed that in the case of caffeine (model hydrophilic molecule), the ES‐free emulsion presented a delivery capacity similar to that of the Reference emulsion. However, for α‐tocopherol (highly lipophilic model molecule), differences were observed in the distribution of the active in the stratum corneum with an advantage for the Reference emulsion, probably due to the impact of surfactants on the SC lipids. Conclusion This work demonstrates that HFUT is a reliable tool that is able to prepare stable ES‐free emulsions loaded with hydrophilic or lipophilic active ingredients. Skin permeation studies confirm that the emulsions produced by HFUT promote the delivery of the actives to the human skin. In the case of α‐tocopherol, the delivery efficiency was lower than with the Reference emulsion, especially in the SC layers, due to the absence of surfactants. Nevertheless, the ES‐free emulsion still represents a good compromise between efficacy and the need for green cosmetics in the market.

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Section: Introductionmentioning

confidence: 61%

Efficiency of emulsifier‐free emulsions in delivering caffeine and α‐tocopherol to human skin

Kichou

Caritá

Gillet³

et al. 2023

Intern J of Cosmetic Sci

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“…Developments in model systems, such as 3D organotypic cultures and model membranes allowing investigation of the stratum corneum lipid lamellae, have allowed more thorough explorations of cutaneous lipids. Human skin equivalents, comprising epidermal keratinocytes and dermal fibroblasts, are a valuable tool to study skin lipid biology, ceramide production, quality of the epidermal barrier and related abnormalities, and assessment of treatments [57 ▪ ,58 ▪ ]. To assist studies on the efficacy of formulations and barrier repair agents, models of how to disrupt the barrier and monitor its recovery have also been developed, including the use of tape stripping, organic solvents or detergents [59 ▪ ].…”

Section: Model Systems Improve Our Understanding Of Skin Lipidsmentioning

confidence: 99%

Current insights into skin lipids and their roles in cutaneous health and disease

Nicolaou

Kendall²

2022

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of reviewThe unique and complex array of cutaneous lipids include essential components of the skin structure and signalling molecules mediating homeostasis and inflammation. Understanding skin lipid biology and metabolism can support our comprehension of health and disease, including systemic conditions with cutaneous involvement.Recent findingsLipids found on the skin surface, produced by both the host and resident microbes, maintain and regulate the skin microbiome and the epidermal barrier, whilst altered contributions from either source can be detrimental to skin health. The unique lipid composition of the epidermal barrier is essential for its function, and recent studies have expanded our understanding of epidermal ceramide production. This has been supported by improved models available for skin research, including organotypic skin models enabling in-vitro production of complex acylceramides for the first time, and model systems facilitating in-silico exploration of the lipid profile changes observed in clinical samples. Studies have revealed further involvement of lipid mediators such as eicosanoids in cutaneous inflammation, as well as immune regulation in both healthy and diseased skin.SummarySkin lipids offer exciting opportunities as therapeutic targets for many conditions, whether through topical interventions or nutritional supplementation.

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“…EGF administration is associated with several pharmacodynamic challenges. Firstly, regarding topical administration in the form of creams commonly used in clinics, the high molecular weight of EGF (Mw≈6 kDa) limits its penetration of the stratum corneum 9 , 10 . Thus, only trace amounts of EGF can pass through the hair follicle to the basal layer and influence surviving keratinocytes 11 .…”

Section: Introductionmentioning

confidence: 99%

Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation

et al. 2022

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Epidermal growth factor is an excellent drug for promoting wound healing; however, its conventional administration strategies are associated with pharmacodynamic challenges, such as low transdermal permeability, reduction, and receptor desensitization. Here, we develop a microneedle-based self-powered transcutaneous electrical stimulation system (mn-STESS) by integrating a sliding free-standing triboelectric nanogenerator with a microneedle patch to achieve improved epidermal growth factor pharmacodynamics. We show that the mn-STESS facilitates drug penetration and utilization by using microneedles to pierce the stratum corneum. More importantly, we find that it converts the mechanical energy of finger sliding into electricity and mediates transcutaneous electrical stimulation through microneedles. We demonstrate that the electrical stimulation applied by mn-STESS acts as an “adjuvant” that suppresses the reduction of epidermal growth factor by glutathione and upregulates its receptor expression in keratinocyte cells, successfully compensating for receptor desensitization. Collectively, this work highlights the promise of self-powered electrical adjuvants in improving drug pharmacodynamics, creating combinatorial therapeutic strategies for traditional drugs.

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Human skin equivalents: Impaired barrier function in relation to the lipid and protein properties of the stratum corneum

Cited by 57 publications

References 133 publications

Efficiency of emulsifier‐free emulsions in delivering caffeine and α‐tocopherol to human skin

Efficiency of emulsifier‐free emulsions in delivering caffeine and α‐tocopherol to human skin

Current insights into skin lipids and their roles in cutaneous health and disease

Improved pharmacodynamics of epidermal growth factor via microneedles-based self-powered transcutaneous electrical stimulation

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