Journal September 26, 2026 6 min read

How is the stratum corneum measured?

The stratum corneum is the outermost skin layer and the primary barrier to topical delivery. This page describes how its hydration, barrier function, and penetration are measured in research studies, with methods ranging

peptides-pro Editorial

The stratum corneum is the outermost layer of the epidermis, a thin, highly organized structure of corneocytes embedded in a lipid matrix. It is the principal barrier to transdermal and topical drug delivery, and its properties are frequently assessed in dermatological and pharmaceutical research. Measurement of the stratum corneum typically focuses on three domains: hydration, barrier function (often inferred from transepidermal water loss, TEWL), and the penetration or distribution of actives within the layer. No single identifier—such as a sequence, formula, or molecular weight—applies to the stratum corneum itself, as it is a tissue rather than a discrete molecule. The work described here centres on the physical and chemical characterization of this barrier and on strategies to modulate it for research purposes.

Research studies employ a variety of non-invasive and minimally invasive techniques to quantify stratum corneum parameters. These include electrical methods (corneometry), evaporimetry (TEWL), spectroscopic methods (confocal Raman spectroscopy), and imaging modalities (e.g., PRIMOS). In parallel, delivery studies often use model compounds or formulations to assess how the stratum corneum interacts with and permits passage of actives. The sections below summarize findings from selected studies, with attention to the model systems used and whether the evidence is from human, animal, or in vitro work.

Research Studies

Biodegradable STAR particles and stratum corneum puncture

STAR particles (microscopic needles) have been developed to painlessly puncture the stratum corneum and increase skin permeability. Traditionally made of non-biodegradable materials such as ceramic and metal, newer versions use biodegradable polymers: poly(vinyl alcohol) (PVA) for water solubility, cellulose acetate (CA) for enzyme degradability, or polylactic acid (PLA) for hydrolyzability. These particles were designed to address environmental and safety concerns associated with non-degradable materials [1]. The study reports on the development and characterization of these particles, but does not provide quantitative data on stratum corneum measurement per se.

Hybrid lipid-polymeric nanoparticles and skin penetration

Inflammatory skin diseases such as psoriasis are characterized by impaired barrier function and poor penetration of topical therapies. To overcome this, hybrid lipid-polymeric nanoparticles (HLPNs) were developed for co-delivery of coenzyme Q10 (an endogenous antioxidant) and siRNA targeting TNFα. The study aimed to simultaneously modulate inflammatory and oxidative pathways [2]. While the work focuses on formulation and delivery, it underscores the challenge of overcoming the stratum corneum barrier in diseased skin.

Topical formulation and stratum corneum hydration in xerosis

A 28-day randomized, split-leg, untreated-controlled trial evaluated a topical formulation containing panthenol, niacinamide, and dipotassium glycyrrhizate in individuals with xerosis cutis. The study measured skin hydration and barrier function, including TEWL, to assess efficacy [3]. This trial provides human in vivo evidence that stratum corneum hydration can be improved by topical actives, and that TEWL is a useful surrogate for barrier integrity.

Emulgel and stratum corneum hydration in paediatric atopic dermatitis

In a randomized, self-controlled trial involving 57 children (aged 2–14) with atopic dermatitis, an emulgel containing hyaluronic acid, glycerol, grape seed oil, Calendula officinalis, aloe vera, and sh-oligopeptide-1 was applied twice daily for 10 days to one forearm, with the other forearm as control. Skin barrier parameters including TEWL, stratum corneum hydration (SCH), erythema, and pH were measured [4]. This study demonstrates the use of SCH and TEWL as outcome measures in a paediatric population.

Acetyl hexapeptide-8 and skin permeability

Acetyl hexapeptide-8 (AH-8) is a biomimetic peptide used in cosmeceuticals for its potential to reduce wrinkles. A review of its skin permeability and efficacy discusses its structure, proposed mechanisms, and ability to penetrate the stratum corneum [5]. The review highlights that while AH-8 is widely used, its penetration and efficacy depend on formulation and skin condition.

Palmitoyl hexapeptide-12 and stratum corneum interaction

Palmitoyl hexapeptide-12, a self-assembling peptide, was studied using label-free techniques including orbital trapping secondary ion mass spectrometry (OrbiSIMS) to track its penetration and self-assembly within full-thickness human skin. The study monitored mechanical interactions with skin components and potential skincare benefits [6]. This work provides a methodological example of how advanced mass spectrometry can map peptide distribution in the stratum corneum and deeper layers.

Oral supplement and stratum corneum hydration

A 56-day, open-label, single-arm exploratory study evaluated the effects of daily oral intake of NatureU® Mind Care BeautyU Caps in adult women. The primary outcome was change in crow's-feet wrinkle count, and a secondary outcome was change in stratum corneum hydration measured by Corneometer CM 825 [7]. This study illustrates the use of corneometry to assess hydration changes over time, though the open-label design limits interpretation.

Glycyrrhizic acid ionic liquid nanomicelles and peptide delivery

Bioactive ionic liquids synthesized from glycyrrhizic acid and oxymatrine were used to form nanomicelles for enhanced transdermal delivery of palmitoyl pentapeptide-4 (PAL-4). The study optimized component ratios and demonstrated improved solubility and permeability of the peptide [8]. This approach aims to overcome the stratum corneum barrier for signal peptides, but the evidence is primarily from in vitro and ex vivo models.

Reference-only findings

Several additional studies provide context. One evaluated sunscreen formulas and UV filter permeation into the stratum corneum using in vivo confocal Raman spectroscopy, focusing on homosalate (molecular weight <500 Da) and formulation effects [9]. Another developed polymeric azelaic acid-loaded nanocapsules in tragacanth gum for rosacea treatment, addressing local adverse effects of azelaic acid [10]. A third described a hexagram prism structure of hyaluronic acid and hydrolyzed collagen (Meltryx) as a dissolvable physical micro-disruption platform for topical delivery of hydrophilic cargos [11]. Finally, a chromatographic method was validated for simultaneous determination of bergenin and alpha-lipoic acid in skin penetration studies [12]. These reports are not the focus of this page but support the broader context of stratum corneum measurement and penetration research.

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