-
Journal of Colloid and Interface Science Mar 2023The main function of a membrane is to control the exchange of matter between the surrounding regions. As such, accurate modeling of membranes is important to properly...
The main function of a membrane is to control the exchange of matter between the surrounding regions. As such, accurate modeling of membranes is important to properly describe their properties. In many cases in both biological systems and technical applications, the membranes are composite structures where transport properties may vary between the different sub-regions of the membrane. In this work we develop a method based on Mesh analysis that is asymptotically exact and can describe diffusion in composite membrane structures. We do this by first reformulating a generalized Fick's law to include the effects from activity coefficient, diffusion coefficient, and solubility using a single condensed parameter. We then use the derived theory and Mesh analysis to, in essence, retrieve a finite element method approach. The calculated examples are based on a membrane structure that reassembles that of the brick and mortar structure of stratum corneum, the upper layer of our skin. Resulting concentration profiles from this procedure are then compared to experimental results for the distribution of different probes within intact stratum corneum, showing good agreement. Based on the derived approach we further investigate the impact from a gradient in the fluidity of the stratum corneum mortar lipids across the membrane, and find that it is substantial. We also show that anisotropic organisation of the lipid mortar can have large impact on the effective permeability compared to isotropic mortar lipids. Finally, we examine the effects of corneocyte swelling, and their lateral arrangement in the membrane on the overall membrane permeability.
Topics: Skin Absorption; Surgical Mesh; Models, Biological; Skin; Diffusion; Permeability; Lipids
PubMed: 36463821
DOI: 10.1016/j.jcis.2022.11.013 -
Journal of Controlled Release :... Aug 2017The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of...
The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of skin permeation is essential for chemical exposure assessment and transdermal delivery of drugs. The objective of this study is to analyze the effects of heterogeneity, anisotropy, asymmetry, follicular diffusion, and location of the main barrier of diffusion on percutaneous permeation. In the current study, the solution of the transient diffusion through a two-dimensional-anisotropic brick-and-mortar geometry of the stratum corneum is obtained using the commercial finite element program COMSOL Multiphysics. First, analytical solutions of an equivalent multilayer geometry are used to determine whether the lipids or corneocytes constitute the main permeation barrier. Also these analytical solutions are applied for validations of the finite element solutions. Three illustrative compounds are analyzed in these sections: diethyl phthalate, caffeine and nicotine. Then, asymmetry with depth and follicular diffusion are studied using caffeine as an illustrative compound. The following findings are drawn from this study: the main permeation barrier is located in the lipid layers; the flux and lag time of diffusion through a brick-and-mortar geometry are almost identical to the values corresponding to a multilayer geometry; the flux and lag time are affected when the lipid transbilayer diffusivity or the partition coefficients vary with depth, but are not affected by depth-dependent corneocyte diffusivity; and the follicular contribution has significance for low transbilayer lipid diffusivity, especially when flux between the follicle and the surrounding stratum corneum is involved. This study demonstrates that the diffusion is primarily transcellular and the main barrier is located in the lipid layers.
Topics: Anisotropy; Caffeine; Diffusion; Epidermis; Finite Element Analysis; Humans; Models, Biological; Nicotine; Permeability; Phthalic Acids; Skin Absorption
PubMed: 28596104
DOI: 10.1016/j.jconrel.2017.05.034 -
Skin Pharmacology and Physiology 2015The skin is the largest organ of the body, whose main function is to protect the body against the loss of physiologically important components as well as harmful... (Review)
Review
The skin is the largest organ of the body, whose main function is to protect the body against the loss of physiologically important components as well as harmful environmental insults. From the inside to the outside, the skin comprises three major structural layers: the hypodermis, the dermis and the epidermis. The epidermis contains four different sublayers, the stratum corneum (SC), stratum granulosum, stratum spinosum and stratum basale, where the barrier function of the skin mainly lies in the outermost layer of the epidermis, the SC. The SC contains corneocytes that are embedded in a lipid matrix existing in the form of lipid bilayers. The lipid bilayers are formed mainly from ceramides, free fatty acids and cholesterol, constitute the only continuous pathway across the SC and are responsible for the barrier function of the skin. However, the depletion or disturbance of SC lipids in the SC leads to a perturbation of the barrier function of the skin, and, conversely, several skin diseases such as psoriasis and atopic dermatitis are associated with the depletion of these SC lipids. Therefore, it is of paramount importance to understand the interrelationship between the depletion of SC lipids and skin diseases as well as factors that affect the composition and organization of SC lipids in order to assess the potential benefit of a direct replacement of the missing SC lipids as a means of treating affected, aged or diseased skin.
Topics: Animals; Epidermis; Humans; Lipid Metabolism; Skin Diseases
PubMed: 25196193
DOI: 10.1159/000360009 -
Journal of Diabetes Sep 2022Epidermal function is regulated by numerous exogenous and endogenous factors, including age, psychological stress, certain skin disorders, ultraviolet irradiation and... (Review)
Review
Epidermal function is regulated by numerous exogenous and endogenous factors, including age, psychological stress, certain skin disorders, ultraviolet irradiation and pollution, and epidermal function itself can regulate cutaneous and extracutaneous functions. The biophysical properties of the stratum corneum reflect the status of both epidermal function and systemic conditions. Type 2 diabetes in both murine models and humans displays alterations in epidermal functions, including reduced levels of stratum corneum hydration and increased epidermal permeability as well as delayed permeability barrier recovery, which can all provoke and exacerbate cutaneous inflammation. Because inflammation plays a pathogenic role in type 2 diabetes, a therapy that improves epidermal functions could be an alternative approach to mitigating type 2 diabetes and its associated cutaneous disorders.
Topics: Animals; Diabetes Mellitus, Type 2; Epidermis; Humans; Inflammation; Mice; Permeability; Skin
PubMed: 36043448
DOI: 10.1111/1753-0407.13303 -
Skin Research and Technology : Official... Jan 2023Physiological skin properties of neonates and infants change drastically after birth and are implicated in the onset of atopic dermatitis and other diseases. Studies...
BACKGROUND
Physiological skin properties of neonates and infants change drastically after birth and are implicated in the onset of atopic dermatitis and other diseases. Studies have measured physiological skin properties in infants; however, how these properties change over time remains unclear. No reports have measured ceramide in the stratum corneum of infants using confocal Raman spectroscopy; hence, we used it to measure the physiological properties of the skin, including ceramide, in infants.
MATERIALS AND METHODS
The water content and other factors in the skin of infants aged 0, 1, and 6 months were measured. All measurements were performed five times indoors at 22 ± 2°C and 50% ± 10% relative humidity in the middle of the calf at 4-µm distances, and their mean was calculated.
RESULTS
The water content of the area between the skin surface and superficial layers was the lowest in newborns as compared with other ages, and the deeper the skin layer, the higher the water content. The stratum corneum, evaluated using confocal Raman spectroscopy, was the thickest in newborns and gradually thinned with age. Its water content was the lowest in newborns. The levels of natural moisturizing factor, ceramide, and cholesterol were higher in newborns and tended to decrease with age.
CONCLUSION
This report is the first to evaluate ceramide in the stratum corneum of infants using confocal Raman spectroscopy and could help in conducting subsequent longitudinal measurements of physiological skin properties in neonates and infants.
Topics: Humans; Infant; Infant, Newborn; Pilot Projects; Spectrum Analysis, Raman; East Asian People; Epidermis; Skin; Water; Ceramides
PubMed: 36704885
DOI: 10.1111/srt.13276 -
Scientific Reports Jan 2018Decreased levels of antimicrobial peptides (AMPs) in atopic dermatitis (AD) have previously been reported and have been linked to the increased susceptibility to skin...
Decreased levels of antimicrobial peptides (AMPs) in atopic dermatitis (AD) have previously been reported and have been linked to the increased susceptibility to skin infections found in AD patients. This study intents to identify AMPs: hBD-2, hBD-3, RNase7, psoriasin and LL-37 in AD patients and healthy controls, and determine concentrations in consecutive depths of the outer most skin layers. Tape stripping was used on lesional and non-lesional skin. From each skin site, 35 consecutive tape strips were collected and pooled in groups of 5. Commercially available ELISA kits were used to determine AMP concentration in stratum corneum samples. hBD-2, hBD-3, RNase7 and psoriasin were identified in stratum corneum samples. hBD-3-level was markedly higher in AD non-lesional skin compared to healthy controls, and a similar trend was observed for RNase7. Most AMPs were distributed evenly through 35 tape strips, implying a homogeneous distribution of antimicrobial defense in the outer most skin layers. The findings indicate that AD patients may not suffer from a general baseline deficiency in AMPs, and that the innate immune defense is present throughout the stratum corneum, both insights of importance for understanding the role of AMPs in AD.
Topics: Adult; Aged; Antimicrobial Cationic Peptides; Dermatitis, Atopic; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Skin; Specimen Handling; Young Adult
PubMed: 29374283
DOI: 10.1038/s41598-018-20204-8 -
Stratum Corneum Function: A Structural Study with Dynamic Synchrotron X-ray Diffraction Experiments.Journal of Oleo Science Sep 2021Studies on the effectiveness of substances such as drugs and cosmetics that act on the skin require structural evidence at the molecular level in the stratum corneum to... (Review)
Review
Studies on the effectiveness of substances such as drugs and cosmetics that act on the skin require structural evidence at the molecular level in the stratum corneum to clarify their interaction with intercellular lipid and soft keratin. For this purpose, when applying the substances to the stratum corneum X-ray diffraction experiment is one of the powerful tools. To detect minute structural changes in a stratum corneum sample, using a "solution cell", dynamic synchrotron X-ray diffraction measurements were performed when applying aqueous solution of the substances to the stratum corneum: (1) It was found that a surfactant, sodium dodecyl sulfate, significantly disrupted the long-period lamellar structure. (2) To study the effects of water, structural modifications of the short-period lamellar structure and the soft keratin in corneocytes were measured as a function of time. At the initial water content of 15 wt%, the spacings of the short-period lamellar structure and the soft keratin increased toward those at the water content of 25 wt%, that is a key water content in the stratum corneum. (3) Nanoparticles composed of assembly of amphiphilic molecules are one of the leading pharmaceutical formulations. When the nanoparticles were applied, a new assembly of amphiphilic molecules originated from the nanoparticle appeared. This phenomenon suggests that the formation of the new assembly at the surface of skin is concerned with the release of the drug from the nanoparticles. (4) When ethanol was applied to the stratum corneum, only the liquid state in the intercellular lipid matrix was dissolved. After the removal of ethanol from this stratum corneum, the ordered hydrocarbon-chain packing structures appeared. From this fact we would propose that the liquid state region is the main pathway for hydrophobic drugs with a small molecular weight in connection with the so-called 500 Da rule. Here, not only the technique but also the background to these studies and the characteristic results obtained from these studies are explained.
Topics: Epidermis; Ethanol; Humans; Keratins; Lipid Metabolism; Nanoparticles; Sodium Dodecyl Sulfate; Solutions; Surface-Active Agents; Water; X-Ray Diffraction
PubMed: 34373412
DOI: 10.5650/jos.ess21159 -
International Journal of Cosmetic... Dec 2008Skin moisturization is largely a function of stratum corneum barrier capacity, which in turn is a function of the physical state and structural organization of the... (Review)
Review
Skin moisturization is largely a function of stratum corneum barrier capacity, which in turn is a function of the physical state and structural organization of the stratum corneum extracellular lipid matrix [J. Invest. Dermatol.18, 433 (1952); AIChE J. 21, 985 (1975); Acta Derm. Venereol.74, 1 (1994); J. Invest. Dermatol.117, 830 (2001)]. Three unsolved key questions with respect to this lipid matrix' structural organization [Acta Derm. Venereol.74, 1 (1994); J. Invest. Dermatol.117, 830 (2001); J. Invest. Dermatol.118, 897 (2002); J. Invest. Dermatol.118, 899 (2002)] are: i) whether the lipid matrix is constituted by a single-gel phase or by co-existing solid (crystalline or gel) domains, ii) whether a separate fluid (liquid crystalline) phase is present and iii) whether the local pH has a direct effect on the lipid matrix' phase behaviour. Using an array of complementary visual-related biophysical techniques (e.g. atomic force microscopy and confocal/two-photon excitation fluorescence microscopy), it was recently shown that reconstituted membranes composed of extracted decontaminated human stratum corneum lipids do not form a fluid phase, but exclusively a single-gel phase that segregates into co-existing microscopic domains below pH 6 [Biophys. J.93, 3142 (2007)]. It was further shown that the role of cholesterol is related to dispersion of ceramide-enriched domains. This effect is counteracted by the presence of free fatty acids, which mix with skin ceramides but not with cholesterol.
Topics: Animals; Ceramides; Cholesterol; Extracellular Matrix; Fatty Acids, Nonesterified; Humans; Lipid Metabolism; Microscopy, Atomic Force; Microscopy, Confocal; Microscopy, Fluorescence, Multiphoton; Skin
PubMed: 19099542
DOI: 10.1111/j.1468-2494.2008.00458.x -
The Western Journal of Medicine Mar 1993The epidermis is a dynamic system whose metabolic activity is regulated in large part by the integrity of the permeability barrier. This barrier resides in the stratum... (Review)
Review
The epidermis is a dynamic system whose metabolic activity is regulated in large part by the integrity of the permeability barrier. This barrier resides in the stratum corneum and comprises a unique 2-compartment system of structural protein-enriched corneocytes embedded in a lipid-enriched intercellular matrix. Lipid extraction or metabolic imbalances, such as essential fatty acid deficiency, produce barrier abnormalities that in turn result in epidermal hyperproliferation, scaling, and inflammation. When the barrier remains intact, lipid imbalances, such as an abnormal cholesterol sulfate:cholesterol ratio in recessive X-linked ichthyosis, can lead to abnormal corneocyte adhesion (visible scale). Both cellular and intercellular proteins also participate in normal desquamation, and protein abnormalities may provoke abnormal scaling (such as filaggrin in ichthyosis vulgaris). Thus, perturbations of the stratum corneum may be the catalyst for a number of skin diseases, rather than the end result of processes that are initiated in subjacent skin layers.
Topics: Cell Membrane Permeability; DNA; Epidermis; Filaggrin Proteins; Humans; Lipids; Skin Diseases
PubMed: 8460510
DOI: No ID Found -
Progress in Lipid Research Jan 2024The outermost epidermal layer of the skin, the stratum corneum, is not simply a barrier that safeguards skin integrity from external insults and invaders, it is also a... (Review)
Review
The outermost epidermal layer of the skin, the stratum corneum, is not simply a barrier that safeguards skin integrity from external insults and invaders, it is also a delicately integrated interface composed of firm, essentially dead corneocytes and a distinctive lipid matrix. Together, the stratum corneum lipid matrix and sebum lipids derived from sebaceous glands give rise to a remarkably complex but quite unique blend of skin surface lipids that demonstrates tremendous heterogeneity and provides the skin with its indispensable protective coating. The stratum corneum lipid matrix is composed primarily of three major lipid classes: ceramides, non-esterified fatty acids and cholesterol, whereas sebum is a waxy mixture predominantly composed of acylglycerols, wax esters, non-esterified fatty acids, squalene, cholesterol and cholesterol esters. The balance of these skin surface lipids in terms of their relative abundance, composition, molecular organisation and dynamics, and their intricate interactions play a crucial role in the maintenance of healthy skin. For that reason, even minuscule alterations in skin surface lipid properties or overall lipid profile have been implicated in the aetiology of many common skin diseases including atopic dermatitis, psoriasis, xerosis, ichthyosis and acne. Novel lipid-based interventions aimed at correcting the skin surface lipid abnormalities have the potential to repair skin barrier integrity and the symptoms associated with such skin diseases, even though the exact mechanisms of lipid restoration remain elusive.
Topics: Humans; Lipids; Skin; Epidermis; Skin Diseases; Cholesterol; Ceramides; Fatty Acids
PubMed: 37940006
DOI: 10.1016/j.plipres.2023.101264