What does the research say about the stratum corneum?
The stratum corneum is the outermost layer of the epidermis and the principal barrier to transdermal drug delivery. This article summarises research on its structure, function, and the strategies used to overcome it.
What is the stratum corneum?
The stratum corneum is the outermost layer of the epidermis and the primary barrier to transdermal drug delivery. It is a thin, highly organised layer of dead, keratinised corneocytes embedded in a lipid matrix, often described as a brick-and-mortar structure. Its main function is to limit water loss and protect against environmental insults, but it also restricts the penetration of most topically applied compounds.
Research into the stratum corneum focuses on understanding its barrier properties and developing methods to transiently overcome them for therapeutic or cosmetic delivery. The work centres on the intercellular lipid matrix and the tight junctions that regulate paracellular transport.
Research Studies
Biodegradable STAR particles and stratum corneum puncture
STAR particles with microscopic needles can painlessly puncture the skin to increase permeability, but earlier versions were made of non-biodegradable materials such as ceramic and metal. A study introduced biodegradable polymer STAR particles that are water-soluble (poly(vinyl alcohol), PVA), enzyme-degradable (cellulose acetate, CA), or hydrolyzable (polylactic acid, PLA) to address environmental and safety concerns [1]. These particles were designed to enhance drug delivery to the skin by creating transient microchannels in the stratum corneum.
Hybrid lipid-polymeric nanoparticles and co-delivery of CoQ10 and siRNA TNFα
Inflammatory skin diseases such as psoriasis are characterised by poor skin penetration of topical therapies and single-target mechanisms that limit modulation of both inflammatory and oxidative pathways. Hybrid lipid-polymeric nanoparticles (HLPNs) were developed for the co-delivery of coenzyme Q10 (CoQ10), an endogenous antioxidant, and siRNA TNFα [2]. This approach aims to simultaneously target oxidative stress and inflammation in the skin.
Topical formulation with panthenol, niacinamide, and dipotassium glycyrrhizate in xerosis
Xerosis cutis is characterised by impaired epidermal barrier function, increased transepidermal water loss (TEWL), and reduced hydration. A 28-day randomised, split-leg, untreated-controlled trial evaluated a topical formulation containing panthenol, niacinamide, and dipotassium glycyrrhizate in subjects with dry, sensitive skin [3]. The study assessed improvements in skin hydration and barrier function.
Emulgel with hyaluronic acid, glycerol, and sh-oligopeptide-1 in paediatric atopic dermatitis
Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects up to 25% of children and impairs skin barrier function. A randomised, self-controlled trial in 57 children (aged 2–14) examined an emulgel containing hyaluronic acid, glycerol, grape seed oil, Calendula officinalis, aloe vera, and sh-oligopeptide-1 (a synthetic epidermal growth factor) applied twice daily for 10 days to one forearm, with the other forearm as control [4]. Skin barrier parameters such as TEWL, stratum corneum hydration (SCH), erythema, and pH were measured.
Acetyl hexapeptide-8 and skin permeability
Acetyl hexapeptide-8 (AH-8) is a biomimetic peptide used in cosmeceuticals for its potential to reduce wrinkles by modulating neuromuscular activity. A review focused on its structure, proposed mechanisms of action, and efficacy, with particular attention to skin permeability [5]. The review discusses the challenges of delivering AH-8 across the stratum corneum.
Palmitoyl hexapeptide-12 and mechanical interaction with skin components
Palmitoyl hexapeptide-12 is a self-assembling peptide used in anti-aging cosmetics. A study used label-free techniques, including orbital trapping secondary ion mass spectrometry (OrbiSIMS), to monitor its self-assembly and penetration within full-thickness human skin [6]. The work examined the short-term impact of the peptide on skin composition and mechanics.
Oral NatureU® Mind Care BeautyU Caps and skin aging parameters
A 56-day, single-center, open-label, single-arm exploratory study evaluated changes in skin-aging parameters after daily oral intake of NatureU® Mind Care BeautyU Caps in adult women [7]. The primary outcome was change from baseline in crow's-feet wrinkle count at Day 56; secondary outcomes included stratum corneum hydration assessed by Corneometer CM 825.
Glycyrrhizic acid ionic liquid nanomicelles for transdermal delivery of signal peptides
Signal peptides have shown efficacy in rejuvenating photoaged skin, but their low solubility and poor permeability challenge transdermal delivery. Bioactive ionic liquids synthesised from natural glycyrrhizic acid (GA) and oxymatrine (OMT) were prepared to improve the solubility of palmitoyl pentapeptide-4 (PAL-4), a model peptide drug [8]. The GA-OMT system was optimised using molecular dynamics simulations and density functional theory calculations.
Comparison of delivery strategies
| Strategy | Mechanism | Model | Reference |
|---|---|---|---|
| Biodegradable STAR particles | Microscopic needles puncture stratum corneum | In vitro / ex vivo (not specified) | [1] |
| Hybrid lipid-polymeric nanoparticles | Co-delivery of CoQ10 and siRNA TNFα | In vitro / in vivo (not specified) | [2] |
| Topical formulation (panthenol, niacinamide, dipotassium glycyrrhizate) | Improves hydration and barrier function | Human clinical trial (xerosis) | [3] |
| Emulgel (hyaluronic acid, glycerol, sh-oligopeptide-1) | Improves barrier parameters | Human clinical trial (paediatric AD) | [4] |
| Acetyl hexapeptide-8 | Modulates neuromuscular activity | Review | [5] |
| Palmitoyl hexapeptide-12 | Self-assembles and penetrates skin | Full-thickness human skin | [6] |
| Oral NatureU® Mind Care BeautyU Caps | Oral intake, effects on skin aging | Human clinical trial | [7] |
| Glycyrrhizic acid ionic liquid nanomicelles | Enhances solubility and permeability of PAL-4 | In vitro / ex vivo (not specified) | [8] |
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Sources
- [1] Water-Soluble, Enzyme-Degradable, and Hydrolyzable STAR Particles for Enhanced Drug Delivery to Skin
- [2] A dual functional hybrid lipid-polymeric nanoparticle co-loaded coenzyme Q10 and siRNA TNFα for anti-inflammatory skin therapy
- [3] Efficacy of a Topical Formulation on Skin Hydration and Barrier Function in Individuals With Xerosis: A 28-Day Randomized, Split-Leg, Untreated-Controlled Trial
- [4] Update on the Research of an Emulgel for the Effective Treatment of Atopic Dermatitis: Clinical Investigation in Children
- [5] Acetyl Hexapeptide-8 in Cosmeceuticals-A Review of Skin Permeability and Efficacy
- [6] Noninvasive Monitoring of Palmitoyl Hexapeptide-12 in Human Skin Layers: Mechanical Interaction with Skin Components and Its Potential Skincare Benefits
- [7] A 56-Day Exploratory Study of NatureU® Mind Care BeautyU Caps on Skin Aging Parameters
- [8] Bioactive Glycyrrhizic Acid Ionic Liquid Self-Assembled Nanomicelles for Enhanced Transdermal Delivery of Anti-Photoaging Signal Peptides
- [9] Evaluating the Efficacy of Sunscreen Formulas in Reducing UV Filter Permeation Into the Stratum Corneum via In Vivo Confocal Raman Spectroscopy: Insights and Applications for Practical Suncare Product Design
- [10] Polymeric Azelaic Acid-loaded Nanocapsules Incorporated into Tragacanth Gum: Development and Biological Evaluation in Alternative Models for the Treatment of Rosacea
- [11] Hexagram prism structure composed of hyaluronic acid and hydrolyzed collagen as a dissolvable physical micro-disruption platform for topical delivery of hydrophilic cargos
- [12] Chromatographic Method Validation for Simultaneous Determination of Bergenin and Alpha-Lipoic Acid in Skin Penetration Studies