CERAMIDE NP

Sensitive skin is a common skin condition that impairs quality of life and is characterized by unpleasant sensations to normally nonirritating stimuli. Restoration of skin barrier integrity can relieve symptoms, and accumulating evidence indicates a contributory role of the skin microbiome not only in barrier function but also as a potential modulator in sensitive skin. Ceramide-containing emollients improve barrier function and may modulate microbial communities via restoration of stratum corneum lipids, hydration, and immune regulation. In this randomized, double-blind, vehicle-controlled trial, an emollient containing Ceramide NP C15 was evaluated for its effects on sensitive skin symptoms and skin barrier function. Fifty participants applied the study products in a split-body design for 6 weeks. Primary assessments included skin physiology and symptom burden. Furthermore, skin microbiota changes were explored using flow-cytometry (FC)-based bacterial profiling and 16s rRNA gene sequencing. Both the Ceramide NP C15 formulation and the vehicle were associated with improvements in subjective symptoms. In participants with impaired skin barrier, treatment with the ceramide formulation was associated with a significant reduction in transepidermal water loss. FC- and 16S-based analyses indicated modest, treatment-associated changes in skin microbiota composition including an early and sustained increase in microbial evenness and a significant enrichment of Bifidobacterium. In this exploratory, randomized controlled study, a Ceramide NP C15-containing emollient was associated with improvements in skin barrier function. Exploratory microbiome analyses suggested treatment-associated changes in microbial community characteristics, which should prompt further investigations in their clinical relevance for sensitive skin.

Sensitive skin is a hyperreactive condition with rising prevalence. A holistic skin care routine is crucial for management. Selecting appropriate skin care products is of great concern in clinical practice. To assess the effectiveness and safety of a facial cream containing Centella asiatica leaf extract, ceramide NP, and panthenol in Chinese females with sensitive skin. In this single-center, prospective, self-controlled study, 88 female participants applied the cream on their whole face, with follow-ups at Day 2, Weeks 1, 2, and 4. The primary endpoint was the change rate of the SS-10 global score at Week 2. Non-invasive skin parameters and subject self-assessment were conducted. Adverse events (AEs) were monitored. Mean SS-10 scores dropped by 66% and 76% after 2 and 4 weeks. Four symptoms (skin irritation, tautness, itching, and redness) were significantly reduced. TEWL decreased at Weeks 1 and 2, and skin pH at Week 1 and Weeks 2 and 4. SCH increased at all time points and sebum secretion at Week 4. EI, a* value, and facial red area rapidly decreased. Greater improvements were seen in the sensitive skin group compared with the slightly sensitive skin group. All AEs were mild and self-limiting. This study showed the facial cream was effective and safe for 4-week use. It provided immediate relief of facial redness and discomfort, strengthened skin barrier, and modulated pH and sebum secretion, indicating favorable soothing and barrier-repairing properties for sensitive skin.

Ceramides, as major components of the human stratum corneum's (SC) lipid matrix, are considered crucial for regulating the skin's barrier function against the ingress of exogenous substances as well as to prevent water loss through the skin. Multiple clinical and experimental studies found different classes of ceramide species to affect the skin barrier nonuniformly, with some ceramides being associated with an impaired skin barrier, such as ceramide NS, while others are associated with a healthy, unimpaired skin, e.g., ceramide NP. This study investigates how the presence of these two ceramide classes in an SC lipid bilayer membrane influences the water permeability as well as the structure of the bilayer using molecular dynamics (MD) simulations. To this end, simulated membranes comprising free fatty acids, cholesterol, as well as either ceramide NS or ceramide NP were systematically compared in regard to differences in the membrane structure and water permeability, as well as to results found in the literature. The simulation found ceramide NP-containing membranes to have a significantly lower water permeability than ceramide NS-containing systems, with the permeability values of NP-based systems being almost half of those of the NS-based systems. Furthermore, the simulation also showed significant structural differences between the two systems in terms of headgroup conformation and lipid positioning in the membrane, hinting toward the molecular mechanisms underpinning the differences in permeability of the two systems. In conclusion, the MD simulation was able to reproduce effects of the presence of different ceramide species in the membrane that are consistent with experimental as well as clinical studies on skin barrier function and drug delivery and validate previous simulation-based investigations into SC lipid bilayer permeability.

Ceramide-based and aqueous-based moisturizers have distinct absorption and retention characteristics in skin. Conventional methods like Transepidermal Water Loss (TEWL) and Corneometry are limited by environmental factors, and no current in vivo method measures ceramide content in skin. This research explores the use of a handheld Confocal Raman Spectroscopy (CRS) system to non-invasively analyze the absorption kinetics of these moisturizers. Measurements were taken on 40 subjects, including healthy individuals (n = 20) and those with atopic dermatitis (n = 20). Results showed that ceramide-based creams retained ceramide in the stratum corneum for longer periods, particularly 24 h post-application, compared to aqueous-based creams. Validation against Liquid Chromatography-Mass Spectrometry (LCMS) for ceramide NP in four healthy subjects showed a strong correlation (r = 0.96). These findings suggest that handheld CRS can improve the evaluation of skincare formulations, advancing the development of personalized skincare solutions.

Changes in the level or profile of ceramides are associated with decreased stratum corneum (SC) barrier function. Topical application of a pseudo-ceramide (pCer)-containing moisturizer can improve barrier function. Additionally, pCer that absorbs into the SC may improve ceramide profiles. We investigated the relationship between pCer absorption into the SC and SC properties and determined the efficacy of a pCer-containing spray compared with that of a commercial spray without pCer. Patients with self-perceived dry and sensitive skin and decreased barrier function (transepidermal water loss [TEWL] > 10 g/m 2 h) were randomized into two groups to topically apply a pCer-containing spray (test group; N = 33) or commercial spray without pCer (control group; N = 19) twice daily as a single-blind study. SC function and ceramide properties were investigated before and after 4 weeks of application. In the test group, the ceramide (NP)/(NS) ratio proportionally increased with the pCer application level after 4 weeks of pCer-containing spray application. In the control group, there were no changes in SC function after topical application of the commercially available spray without pCer; however, the SC water content, TEWL, SC cell area, and scaling score improved in the test group. Furthermore, the changes in TEWL in the test group were significantly negatively correlated with the pCer application level. The efficacy of pCer-containing sprays for those who have sensitive skin with impaired barrier function was demonstrated. Furthermore, the improvement in SC barrier function induced by pCer may contribute to normalizing the SC ceramide profile.

The impairment of skin integrity derived from derangement of the orthorhombic lateral organization is mainly caused by dysregulation of ceramide amounts in the skin barrier. Ceramides, fatty acids, and cholesterol-containing nano-based formulations have been used to impair the skin barrier. However, there is still a challenge to formulate novel formulations consisting of ceramides due to their chemical structure, poor aqueous solubility, and high molecular weight. In this study, the design and optimization of Ceramide 3 (CER-NP)-loaded liposomes are implemented based on response surface methodology (RSM). The optimum CER-NP-loaded liposome was selected based on its particle size (PS) and polydispersity index (PDI). The optimum CER-NP-loaded liposome was imagined by observing the encapsulation by using a confocal laser scanning microscope (CLSM) within fluorescently labeled CER-NP. The characteristic liquid crystalline phase and lipid chain conformation of CER-NP-loaded liposomes were determined using attenuated total reflectance infrared spectroscopy (ATR-IR). The CER-NP-loaded liposomes were imagined using a field emission scanning electron microscope (FE-SEM). Finally, the in vitro release of CER-NP from liposomes was examined using modified Franz Cells. The experimental and predicted results were well correlated. The CLSM images of optimized liposomes were conformable with the other studies, and the encapsulation efficiency of CER-NP was 93.84 ± 0.87%. ATR-IR analysis supported the characteristics of the CER-NP-loaded liposome. In addition, the lipid chain conformation shows similarity with skin barrier lipid organization. The release pattern of CER-NP liposomes was fitted with the Korsmeyer-Peppas model. The cytotoxicity studies carried out on HaCaT keratinocytes supported the idea that the liposomes for topical administration of CER-NP could be considered relatively safe. In conclusion, the optimized CER-NP-loaded liposomes could have the potential to restore the skin barrier function.

In this work, amphiphilic hyaluronan was synthesized by grafting succinylated N-oleoyl-phytosphingosine via esters bonds. Succinylated N-oleoyl-phytosphingosine (sCER) was first prepared by esterification of hydroxyl moieties of the ceramide with succinic anhydride. The esterification of hyaluronan was governed by crowding effect. The oligomeric HA-sCER derivatives exhibited a strong self-aggregation as evidenced by a very low critical aggregation concentration (1.9 μg mL -1 ), higher pyrene binding constant (K B ), and the smallest particle size (30 nm) in solution. The self-aggregation properties demonstrated to be a function of the substitution degree and molecular weight of HA. The prepared derivatives were non-cytotoxic towards cell lines NIH-3T3. Nanoparticles prepared using oligomeric HA-sCER derivatives improved the penetration of Nile red dye through the stratum corneum due to their smaller size (≤50 nm). The fluorescence intensity localized at the stratum corneum was higher for oligomeric HA-sCER. A significant inhibition of the pro-inflammatory cytokine interleukin-6 production was observed in vitro in macrophages differentiated from THP-1 cells. These findings showed that HA-sCER constituted a promising active ingredient for cosmetics use.

In Korea, winter can cause skin dryness due to low relative humidity (RH); moreover, indoor heating devices promote moisture loss and air pollution. If dryness persists, dead skin cells accumulate, leading to skin problems; therefore, careful skin care is required. This study aimed to compare changes in skin conditions when exposed to an indoor environment for a short period of 6 h in winter, and to suggest proper winter skin care practices. A randomized, split-face clinical study was conducted in which healthy female participants with normal skin were exposed to an indoor environment with a heater turned on for a short period at least 6 h per day in the winter season, and cream was applied to one side of the face. Skin temperature, hydration, sebum, transepidermal water loss (TEWL), elasticity, texture, pores, redness, and wrinkles were measured at the treated and nontreated sites. After 6 h of exposure, skin temperature, pores, roughness, redness, and wrinkles significantly increased (p < 0.05) on the face, whereas TEWL significantly increased on the forearm (p < 0.05). However, sebum secretion appeared to function as a barrier to maintain homeostasis in the facial skin. Elasticity, pores, texture, and wrinkles in the cream-treated ceramide site improved compared to those in the nontreated site (p < 0.05). The moisture content was also significantly higher in the forearm (p < 0.05). Changes in skin parameters of participants with healthy skin were observed even after short-term exposure to an indoor environment in winter. Creams containing ceramide maintain skin homeostasis and protect the skin barrier; therefore, it is recommended to use such creams to prevent skin damage and maintain healthy skin, particularly during prolonged exposure to indoor environments during winter.

This study introduces a multilamellar ceramide core-structured microvehicle platform for substantial skin barrier function recovery. Our approach essentially focused on fabricating bacterial cellulose nanofiber (BCNF)-enveloped ceramide-rich lipid microparticles (CerMPs) by solidifying BCNF-armored oil-in-water Pickering emulsions. The oil drops consisted of Ceramide NP (a phytosphingosine backbone N -acylated with a saturated stearic acid) and fatty alcohols (FAs) with a designated stoichiometry. The thin BCNF shell layer completely blocked the growth of ceramide molecular crystals from the CerMPs for a long time. The CerMP cores displayed a multilamellar structure wherein the interlayer distance and lateral packing could be manipulated using FAs with different alkyl chain lengths. The CerMPs remarkably lowered the trans-epidermal water loss while restoring the structural integrity of the epidermis in damaged skin. The results obtained herein highlight that the CerMP system provides a practical methodology for developing various types of skin-friendly formulations that can strengthen the skin barrier function.

Triacylglycerols (TG) play an important role in skin homeostasis including the synthesis of ω-O-acylceramides (acylCER) required for skin barrier formation by providing linoleic acid (C18:2n6). However, the overall relationships of TG species with various ceramides (CER) including CER-NP, the most abundant CER, ω-O-acylCER, and another acylCER, 1-O-acylCER in human SC, remain unclear. Therefore, we investigated these relationships and their influence on skin health status in healthy Korean adults. Twelve CER subclasses including two ω-O-acylCER and two 1-O-acylCER were identified with CER-NP consisting of approximately half of the total CER. The ω-O-acylCER species exhibited positive relationships with TG 52:4 and TG 54:2 containing C18:2, while interestingly, 1-O-acylCER containing ester-linked C14:0 and C16:0 demonstrated positive relationships with TG 46-50 including C14:0 and C16:0, respectively. In addition, CER-NP and CER-NH showed positive correlations with TG 52-54 containing C18:2 or C18:3. A lipid pattern with higher levels of CER including CER-NP and ω-O-acylCER with TG 54 and TG with 5-6 double bonds was related to good skin health status, especially with acidic skin pH. Collectively, TG with increased chain length and unsaturation seemed to improve CER content, and profiles such as higher acylCER and CER-NP improved skin health status by fortifying skin barrier structure.

Numerous formulations have been utilized in the cosmetic and pharmaceutical industries to effectively deliver bioactive ingredients. We selected a well-known liposomal formulation of bilayer lipid vesicles composed of ceramide NP. Ethosomes contain hydrophilic vanillic acid or lipophilic α-bisabolol, and their physicochemical properties were evaluated. Vanillic acid is encapsulated in the aqueous core while α-bisabolol is engaged with the lipid phase. The formulation was prepared by the high-pressure homogenization method at 800 bar for 5 min. The particle size, polydispersity index and zeta potential of the ethosome dispersion were analyzed by dynamic light scattering. In order to measure the skin absorption efficiency from artificial skin, an in vitro assay was performed using the Franz diffusion cell method for 24 hours. In addition, ultracentrifuges for encapsulation efficiency, dialysis membranes for active ingredient release, and low-temperature transmission electron microscopy (TEM) to evaluate the morphology of vesicles were utilized. The particle size of the ethosome containing ceramide NP and vanillic acid was in the range of 80 ~ 130 nm, whereas the particle size of the ethosome containing ceramide NP and α-bisabolol was 150 ~ 170 nm. In the vanillic acid-containing ethosome, increasing the amount of ceramide NP decreased the particle size, whereas the size of the α-bisabolol ethosome did not change. The stability of the prepared ethosome did not change significantly for 4 weeks at 25°C, 4°C, and 45°C. The skin absorption efficiency of ceramide NP and vanillic acid-containing ethosome was increased by about 15% compared to the control group, whereas the ethosome containing α-bisabolol and ceramide NP showed slightly higher skin absorption efficiency than the control group. In addition, encapsulation efficiency evaluation, active ingredient release measurement and cryo-TEM were taken. Based on the results of these studies, we suggest that ethosome formulations containing ceramide NP can be widely used in the cosmetic industry together with other cosmetic formulations.

Barrier damage caused by facial acne vulgaris can be magnified by topical medication, such as adapalene (0.3%) and benzoyl peroxide (2.5%)(A/BPO), which utilizes a retinoid to normalize follicular keratinization and BPO to decrease the C. acnes population. Disease-induced irritation combined with topical medication-induced irritation results in dryness and enhanced inflammation leading to lower compliance and increased skin healing time. Ceramide-based moisturizers have documented barrier repair benefits for eczema but have not been studied for acne. The objective of this double-blind study was to measure the impact of acne treatment on skin barrier function and tolerance when paired with a ceramide routine. Participants were prescribed an A/BPO gel once daily. The treatment group received a ceramide-containing foaming facial cleanser and facial lotion, and the control group received basic foaming face wash for twice-daily use. Participant and investigator tolerability and efficacy were evaluated by both ordinal and clinical measures. Acne lesion counts and Investigator’s Global Assessments (IGA) of acne were obtained along with transepidermal water loss (TEWL) measurements for barrier function. TEWL for the treatment group remained significantly lower than the control at all timepoints and significantly improved from baseline by week 12. The treatment group had statistically lower mean investigator scores for dryness at all timepoints. Inflammatory lesion counts were significantly lower for the treatment group. A/BPO damaged the skin barrier, demonstrated by elevated TEWL, contributing to dryness, redness, and scaling. Use of a ceramide-containing cleanser and moisturizer significantly reduced severity and incidence of dryness, erythema, and scaling while more quickly resolving barrier damage and restoring function. Draelos ZD, Baalbaki N, Colon G, et al. Ceramide-containing adjunctive skin care for skin barrier restoration during acne vulgaris treatment. J Drugs Dermatol. 2023;22(6):554-558. doi:10.36849/JDD.7142&nbsp.

People with atopic dermatitis (AD) suffer from dry, itchy skin with reduced skin barrier function that leaves it prone to irritant and allergen penetration. Alterations in the composition and structure of the stratum corneum (SC) lipid lamellae underpin this increase in permeability. A wide range of emollients is used to ameliorate the skin of patients with AD, but the majority have unclear effects on the lipid lamellae and barrier function. To compare the effects of a multivesicular emulsion containing physiological lipids and glycerine (MVE + GL) with a commonly prescribed oil-in-water emulsion containing glycerine without physiological lipids (O/W + G). A double-blind intraparticipant-controlled study was undertaken in adults with a history of eczema. Participants applied MVE + GL to one forearm and lower leg and O/W + G to contralateral sites twice daily for 28 days. Skin properties were assessed before and after treatment. A detailed lipidomic profile was generated from SC samples, alongside in vivo attenuated total reflectance Fourier transform infrared spectroscopic analysis of its molecular composition. Fifty-eight people were included in the study [mean (SD) age 46 (21) years]. At sites treated with MVE + GL skin barrier integrity improved significantly [mean (SD) transepidermal water loss after 20 skin tape strips (TEWL20) 38.02 (18.64) g m-2 h-1 pretreatment vs. 29.79 (13.47) g m-2 h-1 post-treatment; P < 0.001], whereas O/W + G had no effect [35.6 (18.39) g m-2 h-1 vs. 37.4 (16.69) g m-2 h-1]. Concordantly, skin sensitivity to sodium lauryl sulfate (SLS) was significantly reduced by MVE + GL treatment [mean (SD) post-SLS TEWL 35.58 (15.43) g m-2 h-1 pretreatment vs. 29.54 (11.64) g m-2 h-1 post-treatment (P < 0.001); erythema was also reduced]. Skin moisture increased more rapidly at sites treated with MVE + GL vs. O/W + G, leading to a more rapid reduction in visual skin dryness. Over 1600 lipid species were detected in the SC. Ceramide species NP (non-hydroxy-phytosphingosine) and AP (α-hydroxy-phytosphingosine) with 18-carbon sphingoid bases, both ingredients of the MVE + GL, increased significantly by 24% and 19%, respectively, following MVE + GL treatment. In contrast, changes of 9% for NP(18) and 6% for AP(18) were not statistically significant at sites treated with O/W + G. Increased abundance of NP(18) species relative to NdS (non-hydroxy-dihydrosphingosine) species was related to improvements in skin barrier integrity. While the glycerine-containing emollient reduced skin dryness, it had no impact on barrier function. In contrast, MVE + GL improved the physical integrity of the barrier and reduced the sensitivity of the skin. Eczema is the most common chronic skin condition. It affects 1% to 10% of adults in Europe. The upper layers of our skin form a barrier that keeps water in our bodies and stops irritants from getting in. This skin barrier is made of cells called ‘corneocytes’. These are surrounded by a tough protein envelope and embedded in a network of ‘fatty’ molecules (called ‘lipids’). The composition of these fatty molecules is altered in the skin of people with eczema. The skin does not function effectively as a barrier as more water is lost, and irritants can more easily penetrate the deeper skin layers. Moisturizing creams are an effective treatment for eczema, but it is unclear which are most appropriate to use. This study was carried out in the UK. We aimed to find out if a cream containing lipids found in skin could improve the skin’s ability to act as a barrier. We compared this cream to one without these lipids. We asked 58 people with eczema to apply these creams separately on their forearms for a month and measured how the skin responded. We found that skin treated with the cream containing skin-identical lipids lost less water. It was also more resistant to physical damage and was less sensitive to irritation than befo

The epidermis and in particular its outermost layer the stratum corneum provides terrestrial vertebrates with a pivotal defensive barrier against water loss, xenobiotics and harmful pathogens. A vital demand for this epidermal permeability barrier is the lipid-enriched lamellar matrix that embeds the enucleated corneocytes. Ceramides are the major components of these highly ordered intercellular lamellar structures, in which linoleic acid- and protein-esterified ceramides are crucial for structuring and maintaining skin barrier integrity. In this review, we describe the fascinating diversity of epidermal ceramides including 1-O-acylceramides. We focus on epidermal ceramide biosynthesis emphasizing its metabolic and topological requirements and discuss enzymes that may be involved in α- and ω-hydroxylation. Finally, we turn to epidermal ceramide regulation, highlighting transcription factors and liposensors recently described to play crucial roles in modulating skin lipid metabolism and epidermal barrier homeostasis. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier.

Ceramide, the backbone structure of all sphingolipids, as well as a minor component of cellular membranes, has a unique role in the skin, by forming the epidermal permeability barrier at the extracellular domains of the outermost layer of the skin, the stratum corneum, which is required for terrestrial mammalian survival. In contrast to the role of ceramide in forming the permeability barrier, the signaling roles of ceramide and its metabolites have not yet been recognized. Ceramide and/or its metabolites regulate proliferation, differentiation, and apoptosis in epidermal keratinocytes. Recent studies have further demonstrated that a ceramide metabolite, sphingosine-1-phosphate, modulates innate immune function. Ceramide has already been applied to therapeutic approaches for treatment of eczema associated with attenuated epidermal permeability barrier function. Pharmacological modulation of ceramide and its metabolites' signaling can also be applied to cutaneous disease prevention and therapy. The author here describes the signaling roles of ceramide and its metabolites in mammalian cells and tissues, including the epidermis. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.