scholarly journals Effects of omega-O-acylceramide structures and concentrations in healthy and diseased skin barrier lipid membrane models

2019 ◽  
Vol 61 (2) ◽  
pp. 219-228 ◽  
Author(s):  
Lukáš Opálka ◽  
Andrej Kováčik ◽  
Petra Pullmannová ◽  
Jaroslav Maixner ◽  
Kateřina Vávrová
Keyword(s):  
Rational Design ◽  
Lipid Membrane ◽  
Skin Diseases ◽  
Skin Barrier ◽  
Cholesterol Sulfate ◽  
Skin Lipid ◽  
Carbon Chains ◽  
Chain Order ◽  
Diseased Skin ◽  
Lipid Organization

Ceramides (Cers) with ultralong (∼32-carbon) chains and ω-esterified linoleic acid, composing a subclass called omega-O-acylceramides (acylCers), are indispensable components of the skin barrier. Normal barriers typically contain acylCer concentrations of ∼10 mol%; diminished concentrations, along with altered or missing long periodicity lamellar phase (LPP), and increased permeability accompany an array of skin disorders, including atopic dermatitis, psoriasis, and ichthyoses. We developed model membranes to investigate the effects of the acylCer structure and concentration on skin lipid organization and permeability. The model membrane systems contained six to nine Cer subclasses as well as fatty acids, cholesterol, and cholesterol sulfate; acylCer content—namely, acylCers containing sphingosine (Cer EOS), dihydrosphingosine (Cer EOdS), and phytosphingosine (Cer EOP) ranged from zero to 30 mol%. Systems with normal physiologic concentrations of acylCer mixture mimicked the permeability and nanostructure of human skin lipids (with regard to LPP, chain order, and lateral packing). The models also showed that the sphingoid base in acylCer significantly affects the membrane architecture and permeability and that Cer EOP, notably, is a weaker barrier component than Cer EOS and Cer EOdS. Membranes with diminished or missing acylCers displayed some of the hallmarks of diseased skin lipid barriers (i.e., lack of LPP, less ordered lipids, less orthorhombic chain packing, and increased permeability). These results could inform the rational design of new and improved strategies for the barrier-targeted treatment of skin diseases.

scholarly journals ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phospholipase C γ1 and protein kinase C pathways

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Cristina Wolf ◽  
Yawen Qian ◽  
Matthew A. Brooke ◽  
David P. Kelsell ◽  
Claus-Werner Franzke
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Skin Diseases ◽  
Skin Barrier ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Inflammatory Skin Diseases ◽  
Cholesterol Sulfate ◽  
Kinase C ◽  
Barrier Formation

Abstract The vitally important skin barrier is formed by extensive cross-linking activity of transglutaminases (TGs) during terminal epidermal differentiation. We have previously shown that epidermal deficiency of a disintegrin and metalloproteinase 17 (ADAM17), the principal EGFR ligand sheddase, results in postnatal skin barrier defects in mice due to impeded TG activity. However, the mechanism by which ADAM17/EGFR signalling maintains TG activity during epidermal differentiation remains elusive. Here we demonstrate that ADAM17-dependent EGFR signalling promotes TG activity in keratinocytes committed to terminal differentiation by direct induction of TG1 expression. Restored TG1 expression of EGF-stimulated differentiated Adam17 −/− keratinocytes was strongly repressed by inhibitors for PLCγ1 or protein kinase C (PKC) pathways, while treatment with the PKC stimulator 12-O-tetradecanoylphorbol-13-acetate restored TG activity in the epidermis of keratinocyte-specific Adam17 −/− (AD17 ΔKC ) mice. Further investigations emphasized the expression of PKCη, a mediator of TGM1 transcription, to be sensitive to EGFR activation. In agreement, topical skin application of cholesterol sulfate, an activator of PKCη, significantly improved TG activity in epidermis of AD17 ΔKC mice. Our results suggest ADAM17/EGFR-driven PLCγ1 and PKC pathways as important promoters of TG1 expression during terminal keratinocyte differentiation. These findings may help to identify new therapeutic targets for inflammatory skin diseases related to epidermal barrier defects.

scholarly journals Phase behavior of skin lipid mixtures: the effect of cholesterol on lipid organization

Soft Matter ◽  
2015 ◽  
Vol 11 (21) ◽  
pp. 4326-4336 ◽  
Author(s):  
E. H. Mojumdar ◽  
G. S. Gooris ◽  
J. A. Bouwstra
Keyword(s):  
Stratum Corneum ◽  
Phase Behavior ◽  
Critical Role ◽  
Skin Barrier ◽  
Lipid Matrix ◽  
Skin Lipid ◽  
Lipid Mixtures ◽  
Lipid Organization

The lipid matrix in the stratum corneum (SC), the upper layer of the skin, plays a critical role in the skin barrier.

scholarly journals The Efficacy and Safety of Dual-Frequency Ultrasound for Improving Skin Hydration and Erythema in Patients with Rosacea and Acne

2021 ◽  
Vol 10 (4) ◽  
pp. 834
Author(s):  
Young Jae Kim ◽  
Ik Jun Moon ◽  
Hae Woong Lee ◽  
Chong Hyun Won ◽  
Sung Eun Chang ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Skin Barrier ◽  
Skin Hydration ◽  
Efficacy And Safety ◽  
Dual Frequency ◽  
Barrier Dysfunction ◽  
Inflammatory Skin Diseases ◽  
Facial Erythema ◽  
Frequency Ultrasound

Inflammatory skin diseases, such as rosacea and acne, are major causes of facial erythema and accompanying skin barrier dysfunction. Several methods to restore the impaired skin barrier and improve facial erythema, such as medication, radiofrequency, laser, and ultrasound therapy were attempted. This study evaluated the efficacy and safety of dual-frequency ultrasound with impulse mode, for improving skin hydration and erythema in Asian subjects with rosacea and acne. Twenty-six subjects with facial erythema received an ultrasound treatment once per week, for 4 weeks, over both cheeks. The erythema index and transepidermal water loss (TEWL) were measured at each visit. Clinicians assessed the erythema improvement and patients evaluated their satisfaction level. The average decrease in TEWL and erythema index at 6 weeks was 5.37 ± 13.22 g·h−1·m−2 (p = 0.020) and 39.73 ± 44.21 (p = 0.010), respectively. The clinician’s erythema assessment and the subject satisfaction questionnaire score significantly improved at final follow-up (p < 0.001; p = 0.003, respectively). No serious adverse effects were observed during the treatment and follow-up periods. The dual-frequency ultrasound with impulse mode appears to be effective and safe for improving skin hydration and erythema in patients with rosacea and acne.

Elegant flexible vesicular nanocarriers for the efficient skin delivery of topically applied drugs-

2021 ◽  
Vol 18 ◽  
Author(s):  
Waleed Albalawi ◽  
Surur Alharbi ◽  
Fahad Alanazi ◽  
Hameed Alahmadi ◽  
Mothib Alghamdi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Skin Diseases ◽  
Fungal Infections ◽  
Skin Barrier ◽  
Therapeutic Outcome ◽  
Health Concern ◽  
Inflammatory Skin Diseases ◽  
Skin Delivery ◽  
Pubmed Database ◽  
Vesicular Carriers

Background: Skin diseases represent a major health concern worldwide and negatively impact patients’ quality of life. Despite the availability of various efficacious drugs, their therapeutic outcome is often limited due to shortcomings related to the formidable skin barrier and unfavorable physicochemical properties of drugs. Flexible nano-vesicles have shown tremendous potential to overcome these hurdles and improve the local therapeutic effect of these drugs. Objective: This review article is aimed to shed light on flexible nano-vesicular carriers as a means to combat skin diseases. Methods: The literature was reviewed using PubMed database using various keywords such as liposomes, flexible (deformable liposomes) (transferosomes), ethosomes, transethosomes, niosomes, and spanlastics. Results: Liposomes and niosomes were found effective for the loading and release of both hydrophilic and lipophilic drugs. However, their limited skin penetration led to drug delivery to the outermost layers of skin only. This necessitates the search for innovative vesicular carriers, including liposomes, flexible (deformable liposomes), ethosomes, transethosomes, and spanlastics. These flexible nano-vesicular carriers showed enhanced drug delivery and deposition across various skin layers, which was better than their corresponding conventional vesicles. This resulted in superior drug efficacy against various skin diseases such as skin cancer, inflammatory skin diseases, superficial fungal infections, etc. Conclusion: Flexible nano-vesicular carriers have proven themselves as efficient drug delivery systems that are able to deliver their cargo into the deep skin layers and thus, improve the therapeutic outcome of various skin diseases. However, there remain some challenges that need to be addressed before these nanocarriers can be translated from the lab to clinics.

scholarly journals Peroxisome Proliferator-Activated Receptors (PPARs) Activation as Therapeutic Targets in Skin Inflammation

2020 ◽  
Vol 4 (2) ◽  
pp. 9
Author(s):  
Akihiro Aioi
Keyword(s):  
Skin Diseases ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Cell Types ◽  
Immune Dysregulation ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Barrier Dysfunction ◽  
Cytokine Network ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are fatty acid activated transcription factors that belong to the nuclear hormone receptor family. They are initially known as transcriptional regulators of lipid and glucose metabolism, although further evidence has also been accumulated for other functions. Due to the nature of all PPAR isotypes which are expressed and exert effects by regulating the functions of cell types residing and infiltrating in the skin, PPARs represent a major research target for the understanding and treatment of many skin diseases. Atopic dermatitis (AD) is a chronic and relapsing disease characterized by skin barrier dysfunction and immune dysregulation. Skin barrier disturbance is one of the exacerbation factors of AD, due to facile penetration of molecules such as antigens. From the aspect of immune dysregulation, innate and acquired immunity including cell proliferation, cell differentiation, and cytokine network are involved in the pathogenesis. In this review, the role of PPAR in AD and the possibility of its agonist for the treatment of AD are discussed.

Autophagy in skin barrier and immune‐related skin diseases

2021 ◽  
Author(s):  
Chi Liu ◽  
Lei Gu ◽  
Jie Ding ◽  
Qianchao Meng ◽  
Nan Li ◽  
...  
Keyword(s):  
Skin Diseases ◽  
Skin Barrier

scholarly journals Skin Barriers in Dermal Drug Delivery: Which Barriers Have to Be Overcome and How Can We Measure Them?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 684 ◽  
Author(s):  
Christian Gorzelanny ◽  
Christian Mess ◽  
Stefan W. Schneider ◽  
Volker Huck ◽  
Johanna M. Brandner
Keyword(s):  
Drug Delivery ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Multiphoton Microscopy ◽  
Skin Barrier ◽  
Barrier Properties ◽  
Transepidermal Water Loss ◽  
Hair Follicles

Although, drugs are required in the various skin compartments such as viable epidermis, dermis, or hair follicles, to efficiently treat skin diseases, drug delivery into and across the skin is still challenging. An improved understanding of skin barrier physiology is mandatory to optimize drug penetration and permeation. The various barriers of the skin have to be known in detail, which means methods are needed to measure their functionality and outside-in or inside-out passage of molecules through the various barriers. In this review, we summarize our current knowledge about mechanical barriers, i.e., stratum corneum and tight junctions, in interfollicular epidermis, hair follicles and glands. Furthermore, we discuss the barrier properties of the basement membrane and dermal blood vessels. Barrier alterations found in skin of patients with atopic dermatitis are described. Finally, we critically compare the up-to-date applicability of several physical, biochemical and microscopic methods such as transepidermal water loss, impedance spectroscopy, Raman spectroscopy, immunohistochemical stainings, optical coherence microscopy and multiphoton microscopy to distinctly address the different barriers and to measure permeation through these barriers in vitro and in vivo.

Correlation between the translational and rotational diffusion of rod-shaped nanocargo on a lipid membrane revealed by single-particle tracking

Nanoscale ◽  
2019 ◽  
Vol 11 (20) ◽  
pp. 10080-10087 ◽  
Author(s):  
Liangna He ◽  
Yiliang Li ◽  
Lin Wei ◽  
Zhongju Ye ◽  
Hua Liu ◽  
...  
Keyword(s):  
Particle Tracking ◽  
Single Particle ◽  
Theoretical Basis ◽  
Rational Design ◽  
Lipid Membrane ◽  
Rotational Diffusion ◽  
Single Particle Tracking ◽  
Cellular Translocation ◽  
Diffusion Dynamics ◽  
Translational And Rotational Diffusion

Revealing the diffusion dynamics of nanoparticles on a lipid membrane plays an important role in a better understanding of the cellular translocation process and provides a theoretical basis for the rational design of delivery cargo.

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