Russel M. Walters

Infrared spectroscopic studies of sodium dodecyl sulphate permeation and interaction with stratum corneum lipids in skin.

The barrier function of skin is primarily provided by the lamellar lipid matrix of the stratum corneum (SC), which has been shown in previous infrared (IR) and related studies to consist predominantly of ordered lipids packed in orthorhombic and hexagonal domains. In the current work, we investigate the effects of the anionic surfactant, sodium dodecyl sulphate (SDS), on SC lipid packing and phase behaviour, using FT‐IR spectroscopy. The use of acyl chain perdeuterated SDS allows unequivocal spectroscopic detection of both endogenous lipid and exogenous material in intact tissue. IR spectra were acquired as a function of temperature from isolated human SC exposed to SDS for various incubation periods at 34°C. SDS is found to enter the SC and is observed to be in a more ordered state in the SC than in solution, indicating that the SDS interacts with the ordered SC lipids. The results reveal that SDS reduces the amount of orthorhombic phase in the SC and increases the amount of hexagonally packed lipid at physiologically relevant temperatures. In addition, a small decrease in the lipid Tm (acyl chain melting temperature) is observed. Furthermore, these SDS‐induced changes were found to be strongly dependent on the time of exposure.

Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function

Plant‐derived oils consisting of triglycerides and small amounts of free fatty acids (FFAs) are commonly used in skincare regimens. FFAs are known to disrupt skin barrier function. The objective of this study was to mechanistically study the effects of FFAs, triglycerides and their mixtures on skin barrier function. The effects of oleic acid (OA), glyceryl trioleate (GT) and OA/GT mixtures on skin barrier were assessed in vivo through measurement of transepidermal water loss (TEWL) and fluorescein dye penetration before and after a single application. OAs effects on stratum corneum (SC) lipid order in vivo were measured with infrared spectroscopy through application of perdeuterated OA (OA‐d34). Studies of the interaction of OA and GT with skin lipids included imaging the distribution of OA‐d34 and GT ex vivo with IR microspectroscopy and thermodynamic analysis of mixtures in aqueous monolayers. The oil mixtures increased both TEWL and fluorescein penetration 24 h after a single application in an OA dose‐dependent manner, with the highest increase from treatment with pure OA. OA‐d34 penetrated into skin and disordered SC lipids. Furthermore, the ex vivo IR imaging studies showed that OA‐d34 permeated to the dermal/epidermal junction while GT remained in the SC. The monolayer experiments showed preferential interspecies interactions between OA and SC lipids, while the mixing between GT and SC lipids was not thermodynamically preferred. The FFA component of plant oils may disrupt skin barrier function. The affinity between plant oil components and SC lipids likely determines the extent of their penetration and clinically measurable effects on skin barrier functions.

Oleic Acid Disorders Stratum Corneum Lipids in Langmuir Monolayers

Oleic acid (OA) is well-known to affect the function of the skin barrier. In this study, the molecular interactions between OA and model stratum corneum (SC) lipids consisting of ceramide, cholesterol, and palmitic acid (PA) were investigated with Langmuir monolayer and associated techniques. Mixtures with different OA/SC lipid compositions were spread at the air/water interface, and the phase behavior was tracked with surface pressure-molecular area (π-A) isotherms. With increasing OA levels in the monolayer, the films became more fluid and more compressible. The thermodynamic parameters derived from π-A isotherms indicated that there are preferential interactions between OA and SC lipids and that films of their mixtures were thermodynamically stable. The domain structure and lipid conformational order of the monolayers were studied through Brewster angle microscopy (BAM) and infrared reflection absorption spectroscopy (IRRAS), respectively. Results indicate that lower concentrations of OA preferentially mix with and disorder the ceramide-enriched domains, followed by perturbation of the PA-enriched domains and disruption of SC lipid domain separation at higher OA levels.

Hydrophobically modified polymers can minimize skin irritation potential caused by surfactant-based cleansers

The addition of hydrophobically modified polymers (HMPs) to cleansers that contain surfactants can create polymer–surfactant complexes that are less irritating to the skin than commercially available mild cleansers. Our objective was to compare the tolerability and efficacy of a test foaming liquid facial cleanser containing HMPs with a commercial liquid nonfoaming facial cleanser in women with sensitive skin.

Kinetic evidence suggests spinodal phase separation in stratum corneum models by IR spectroscopy.

Although lipid structure in models for the stratum corneum (SC), the main barrier to skin permeability, has been extensively studied, only limited data are extant concerning the kinetic mechanism for the formation of domains, lamellar phases, and lipid packing motifs. Such information would be of substantial interest in the characterization of the effects of disease states which disrupt the barrier. Kinetic IR spectroscopy measurements probed the temporal sequence of molecular events producing ordered structures in a three-component SC model of equimolar ceramide[NS] (cer[NS]), perdeuterated stearic acid-d35 (SA-d35), and cholesterol. Samples, heated above Tm, were quenched to 31 °C, and then spectra were recorded at ∼15 min intervals for a total of 20-150 h. IR provides unique molecular structure information about headgroup H-bonding, lipid packing, and lipid chain order. The following sequence for phase separation was observed: (1) Formation of ceramide amide H-bonds from disordered forms to ordered structures (0.5-4 h); (2) appearance of ordered ceramide chains with some orthorhombically packed structures (0.5-8 h); and (3) phase separation of large orthorhombic domains of SA-d35 (4-10 h). A spinodal decomposition mechanism, defined by continuous composition changes during the phase separation, suggests a qualitative description for these events.

Cleansing Formulations That Respect Skin Barrier Integrity

Surfactants in skin cleansers interact with the skin in several manners. In addition to the desired benefit of providing skin hygiene, surfactants also extract skin components during cleansing and remain in the stratum corneum (SC) after rinsing. These side effects disrupt SC structure and degrade its barrier properties. Recent applications of vibrational spectroscopy and two-photon microscopy in skin research have provided molecular-level information to facilitate our understanding of the interaction between skin and surfactant. In the arena of commercial skin cleansers, technologies have been developed to produce cleansers that both cleanse and respect skin barrier. The main approach is to minimize surfactant interaction with skin through altering its solution properties. Recently, hydrophobically modified polymers (HMPs) have been introduced to create skin compatible cleansing systems. At the presence of HMP, surfactants assemble into larger, more stable structures. These structures are less likely to penetrate the skin, thereby resulting in less aggressive cleansers and the integrity of the skin barrier is maintained. In this paper, we reviewed our recent findings on surfactant and SC interactions at molecular level and provided an overview of the HM technology for developing cleansers that respect skin barrier.

Topically applied ceramide accumulates in skin glyphs.

Ceramides (CERs), structural components of the stratum corneum (SC), impart essential barrier properties to this thin outer layer of the epidermis. Variations in CER species within this layer have been linked to several skin diseases. A recent proliferation of CER-containing topical skin-care products warrants the elucidation of CER penetration profiles in both healthy and diseased skin. In the current study, the spatial distributions of CER concentration profiles, following topical application of two species of CER, were tracked using infrared imaging. Suspensions of single-chain perdeuterated sphingosine and phytosphingosine CER in oleic acid were applied, in separate experiments, to the surface of healthy intact ex vivo human skin using Franz diffusion cells. Following either a 24- or 48-hour incubation period at 34°C, infrared images were acquired from microtomed skin sections. Both CER species accumulated in glyph regions of the skin and penetrated into the SC, to a limited extent, only in these regions. The concentration profiles observed herein were independent of the CER species and incubation time utilized in the study. As a result, a very heterogeneous, sparse, spatial distribution of CERs in the SC was revealed. In contrast, oleic acid was found to be fairly homogeneously distributed throughout the SC and viable epidermis, albeit at lower concentrations in the latter. A more uniform, lateral distribution of CERs in the SC would likely be important for barrier efficacy or enhancement.

Development of infant and toddler sleep patterns: real‐world data from a mobile application

The aim of this study was to investigate the development of infant and toddler sleep patterns. Data were collected on 841 children (aged from birth to 36 months) via a free, publicly available, commercially sponsored iPhone app. Analyses were conducted on caregiver recordings of 156 989 sleep sessions across a 19‐month period. Detailed visualizations of the development of sleep across the first 3 years of life are presented. In the first 3 months, sleep sessions primarily lasted less than 3.5 h throughout the day. Between 3 and 7 months old, sleep consolidated into two naps of about 1.5 h in length and a night‐time sleep session of about 10.5 h. Across age groups, a negative relationship was observed between the start of bedtime and the length of the night‐time sleep session (i.e. later bedtime is associated with a shorter night‐time sleep period). The length of daytime sleep sessions (naps) varied with age, decreasing between 1 and 5 months old, and then increasing monotonically through 28 months. Morning wake time was observed to be invariant in children aged 5–36 months. Sleep patterns are ever‐changing across the first few years with wide individual variability. Sleep patterns start to develop more clearly at 5–6 months, when longer night‐time sleep duration begins and sleep consolidation occurs. Daytime sleep patterns appeared to become more consistent and consolidated later in age than night‐time sleep. Finally, there is greater variability in bedtimes than wake times, with bedtimes having a greater influence on night‐time sleep duration.

Developmental Changes in Skin Barrier and Structure during the First 5 Years of Life.

The structure of the stratum corneum (SC) and the corresponding skin barrier develops from before birth up to about 4 years of age. Large subject-to-subject variability within an age group requires a large population to observe trends in skin barrier properties over time. Barrier function, quantified by transepidermal water loss (TEWL) and SC thickness, was measured on the upper inner arm and dorsal forearm in subjects aged 3 months to 4 years (n = 171) and a subset of mothers (n = 44). The rate of skin surface area expansion as a function of age peaked before birth (∼90 cm2/week) and declined to a steady plateau (∼10 cm2/week) by 1 year of age. SC thickness increased and TEWL decreased, but did not reach adult values until 3-4 years of age. A better understanding of how skin hydration changes after birth suggests that barrier function may be related mechanistically to skin surface area expansion.

Fatty Acid Chain Length Dependence of Phase Separation Kinetics in Stratum Corneum Models by IR Spectroscopy.

The main barrier to permeability in human skin resides in the stratum corneum (SC), a layered structure consisting of anucleated, flattened cells (corneocytes) embedded in a heterogeneous lamellar lipid matrix. While lipid structures and packing propensities in the SC and in SC models have been extensively investigated, only limited data are available concerning the kinetics and mechanism of formation of lamellar phases and particular lipid packing motifs. In our prior investigation, kinetic IR spectroscopy measurements probed the temporal sequence of phase separation leading to ordered structures in a three component SC model of equimolar structurally heterogeneous ceramide[NS], chain perdeuterated stearic acid, and cholesterol. In the current work, the phase separation kinetic effects of specific fatty acid chain lengths with a synthetic structurally homogeneous ceramide[NS] in similar ternary mixtures are examined. These are compared with a mixture containing ceramide[NS] with an unsaturated acid chain. The kinetic events are sensitive to the difference in chain lengths between the ceramide acid chain and the fatty acid as well as to the presence of unsaturation in the former. The observed kinetic behaviors span a wide range of phase separation times, ranging from the formation of a solid solution stable for at least 200 h, to a system in which an orthorhombic fatty acid structure is essentially completely formed within the time resolution of the experiment (15 min). The data seem to offer some features of a spinodal phase separation at relatively short times. Overall the approach offers a possible means for addressing several unanswered questions pertinent to skin pharmacology, such as the roles of a wide variety of ceramide and fatty acid species and the design of therapeutic interventions for repair of pathological conditions of the SC.