Lipid Phase Research Articles

Orlistat disposition in the human jejunum and the effect of lipolysis inhibition on bile salt concentrations and composition

The lipolysis-mediated postprandial small intestinal environment is known to influence the solubilisation and subsequent absorption of lipophilic drugs. In a previously performed small-scale clinical study in healthy volunteers, co-administration of the lipase inhibitor orlistat increased jejunal solubilisation and systemic absorption of fenofibrate after intake of the lipid-based formulation Fenogal. In the present study, the jejunal disposition of the locally acting orlistat was assessed and linked to fenofibrate solubilisation. In addition, the effect of orlistat-induced lipolysis inhibition on bile salt concentrations and composition was evaluated. Orlistat was distributed predominantly in the lipid layer, as indicated by a 5- to 14-fold higher AUC0-320 min in the total jejunal samples as compared to the micellar layers. No effect of orally administered orlistat on bile salt composition or total concentrations (ranging from 1.5 to 24.8 mM and 1.8 to 33.2 mM with and without orlistat co-administration, respectively) could be observed. The intraluminal presence of orlistat in the total jejunal samples correlated with the increased fenofibrate solubilisation in the jejunum (r = 0.9344) and enhanced absorption (r = 0.8184), highlighting the importance of the intraluminal lipid phase in lipophilic drug absorption.

From Alignment Laser to 3D Structures: Determining Structures of GPCRs in a Compact X‐ray Light Source

The Compact X‐ray Light Source (CXLS) at Arizona State University produces diffraction patterns with intense X‐ray by Inverse Compton Scattering (ICS). In ICS, a photon acquires energy from an electron to produce an X‐ray. With this system, we can study G‐Protein Coupled Receptors (GPCRs), which are peripheral membrane proteins targeted by 60% of FDA approved drugs. When GPCRs are activated, a series of reaction can occur. For example, opening and closing of ion channels, activation or deactivation of enzymes, and protein hydrolysis. The structural characterization of GPCRs can lead to optimization of drug development, by assessing a better targeting mechanism that will lead to fewer side‐effects and better drug biding. We conducted a laser alignment in the CXLS using a YAG screen, which is a fluorescent screen that helps determine the size and intensity of the beam. Furthermore, we provide the crystallization process of GPCRs using Lipidic Cubic Phase (LCP) and describe its potential for structure determination using the CXLS and CXFEL.

Roles for inter‐organelle contacts in organizing metabolism

When faced with nutrient shortage, cells adapt by remodeling their metabolic pathways and organelles. I will discuss our work using budding yeast to dissect how nutrient shortage impacts the spatial organization of metabolism and lipid droplets. We find that in response to glucose restriction, yeast remodel their mevalonate pathway by spatially compartmentalizing its rate‐limiting enzyme, HMG‐CoA Reductase (HMGCR). HMGCR spatial compartmentalization occurs at a unique inter‐organelle contact site called the nucleus‐vacuole junction (NVJ). This spatial partitioning enhances HMGCR activity, driving mevalonate synthesis to enable cellular adaptation. Our work suggests a new use for an inter‐organelle contact site in the fine‐tuning of mevalonate metabolism during nutrient stress.Remarkably, we also find that glucose restriction drives the phase transition of lipids within lipid droplets (LDs), causing them to convert from a disordered to liquid‐crystalline phase. Mechanistically, we find that these liquid crystalline lattices (LCLs) within LDs require triglyceride lipolysis. We also find that LCL‐LDs exhibit changes to the LD surface proteome. Several known LD proteins redistribute from LDs to the ER network, whereas others remain on LCL‐LDs, suggesting phase transitions of LD lipids influences LD protein targeting. Global proteomics also reveals that triglycerides harvested from LDs fuel cellular energetics at peroxisomes and mitochondria. This indicates that glucose starvation induces inter‐organelle lipid flux while promoting lipid phase transitions within LDs.

Probing the Role of Cysteine Thiyl Radicals in Biology: Eminently Dangerous, Difficult to Scavenge.

Thiyl radicals are exceptionally interesting reactive sulfur species (RSS), but rather rarely considered in a biological or medical context. We here review the reactivity of protein thiyl radicals in aqueous and lipid phases and provide an overview of their most relevant reaction partners in biological systems. We deduce that polyunsaturated fatty acids (PUFAs) are their preferred reaction substrates in lipid phases, whereas protein side chains arguably prevail in aqueous phases. In both cellular compartments, a single, dominating thiyl radical-specific antioxidant does not seem to exist. This conclusion is rationalized by the high reaction rate constants of thiyl radicals with several highly concentrated substrates in the cell, precluding effective interception by antioxidants, especially in lipid bilayers. The intractable reactivity of thiyl radicals may account for a series of long-standing, but still startling biochemical observations surrounding the amino acid cysteine: (i) its global underrepresentation on protein surfaces, (ii) its selective avoidance in aerobic lipid bilayers, especially the inner mitochondrial membrane, (iii) the inverse correlation between cysteine usage and longevity in animals, (iv) the mitochondrial synthesis and translational incorporation of cysteine persulfide, and potentially (v) the ex post introduction of selenocysteine into the genetic code.

Physicochemical Evaluation and Formulation of Propranolol Niosomal Gel with a Potential Effect on Infantile Hemangioma

Introduction: Propranolol is a non-specific beta-blocker that is used to treat hypertension, angina, arrhythmia, tremor, and manage thyrotoxicosis. Based on the results of various studies, propranolol can control infantile hemangioma by vasoconstriction, apoptosis induction, and inhibition of cell proliferation signals. Methods: The conventional film hydration method was used to prepare medium size (2-6 m) multilamellar vesicles (MLVs) containing propranolol. At the lipid phase, sorbitan esters (Spans) and their polyethoxylated derivatives (Tweens) were combined with cholesterol, and deionized water was utilized as a hydration medium. Laser light scattering was used to perform the size analysis, and the Franz diffusion cells were utilized to investigate the release of propranolol from niosomal suspensions and carbomer-based niosomal gels. The vesicles were assessed for their stability within six-month storage at 4°C, and ultraviolet spectrophotometer and centrifuge technique were employed to measure the efficiencies of encapsulation. Results: Based on the findings, the best niosomes were obtained at 40 and 60 spans in the presence of Tween 40 and 60; however, Span/Tween 20 and 80 were not able to form propranolol niosomes. The selected formulations had an MLV appearance and size distribution of 5 μm. Encapsulation efficiency and release rate of selected niosomes were optimal. Niosomes had good stability during six months of storage at refrigerator temperature. Conclusions: Based on the obtained results in this study, the application of a new topical dosage form of propranolol showed promising results for the treatment of infantile hemangioma

Absorption of the [bmim][Cl] Ionic Liquid in DMPC Lipid Bilayers across Their Gel, Ripple, and Fluid Phases.

Lipid bilayers are a key component of cell membranes and play a crucial role in life and in bio-nanotechnology. As a result, controlling their physicochemical properties holds the promise of effective therapeutic strategies. Ionic liquids (ILs)—a vast class of complex organic electrolytes—have shown a high degree of affinity with lipid bilayers and can be exploited in this context. However, the chemical physics of IL absorption and partitioning into lipid bilayers is yet to be fully understood. This work focuses on the absorption of the model IL [bmim][Cl] into 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers across their gel, ripple, and fluid phases. Here, by small-angle neutron scattering, we show that (i) the IL cations are absorbed in the lipid bilayer in all its thermodynamic phases and (ii) the amount of IL inserted into the lipid phase increased with increasing temperature, changing from three to four IL cations per 10 lipids with increasing temperature from 10 °C in the gel phase to 40 °C in the liquid phase, respectively. An explicative hypothesis, based on the entropy gain coming from the IL hydration water, is presented to explain the observed temperature trend. The ability to control IL absorption with temperature can be used as a handle to tune the effect of ILs on biomembranes and can be exploited in bio-nanotechnological applications.

Serotonergic drugs modulate the phase behavior of complex lipid bilayers

Serotonin is an endogenous neurotransmitter involved in both physiological and pathophysiological processes. Traditionally, serotonin acts as a ligand for G protein-coupled receptors (GPCRs) leading to subsequent cell signaling. However, serotonin can also bind to lipid membranes with high affinity and modulate the phase behavior in 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC)/N-palmitoyl-D-erythro-sphingosylphosphorylcholine (PSM)/cholesterol model membranes mimicking the outer leaflet of the plasma membrane. Here, we investigated if serotonergic drugs containing the pharmacophore from serotonin would also modulate phase behavior in lipid membranes in a similar fashion. We used 2H NMR spectroscopy to explore the phase behavior of POPC/PSM/cholesterol (4/4/2 molar ratio) mixtures in the presence of the serotonergic drugs aripiprazole, BRL-54443, BW-723C86, and CP-135807 at a lipid to drug molar ratio of 10:1. POPC and PSM were perdeuterated in the palmitoyl chain, respectively, and prepared in individual samples. Numerical lineshape simulations of the 2H NMR spectra were used to calculate the order parameter profiles and projected lengths of the saturated acyl chains. All serotonergic drugs induce two components in 2H NMR spectra, indicating that they increased the hydrophobic mismatch between the thickness of the coexisting lipid phases leading to larger domain sizes, relatively similarly to serotonin. AFM force indentation and Raman spectral studies, which interrogate membrane mechanical properties, also indicate changes in membrane order in the presence of these drugs. These findings highlight how serotonergic drugs alter membrane phase behavior and could modulate both target and other membrane proteins, possibly explaining the side effects observed for serotonergic and other clinically relevant drugs.

Sustainable fabrication of bio-derived hybrid films using biomolecules extracted from animal skin

In this work, we report preparation of bio-derived hybrid composite films from the protein extracted from raw trimmings emulsified with lipid obtained from tannery fleshing. Effect of varying concentrations of lipid at 10%, 20% and 40% v/w, homogenization rate and plasticization effect of lipid without glycerol were studied on the films’ functionality. Chemical composition of the developed films was determined using ATR-FTIR. The influence of emulsification conditions on the surface topography was studied by scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM). FTIR and microscopic evaluation indicated the heterogeneity of the films, which is caused due to phase separation. Mechanical, spectral and thermal studies revealed that the lipid addition without glycerol had an anti-plasticization effect caused by the irregularly dispersed solid lipid phase. Films prepared with 40% v/w lipid at 8000 rpm homogenization speed (TF40-8K) showed reduced water vapor permeability of 1.33 × 10-8 g/m.s.Pa and increased water contact angle of 82.2º as compared to control films. Transparency, color and optical characteristics indicated that the films became less transparent with increasing lipid concentrations. Valorization of different biomolecules from industrial wastes for preparation of eco-friendly plastics will be environmentally sustainable with application potential in agricultural mulching, packaging and bioelectronics.

Fundamental Aspects of Lipid-Based Excipients in Lipid-Based Product Development.

Poor aqueous solubility of drugs is still a foremost challenge in pharmaceutical product development. The use of lipids in designing formulations provides an opportunity to enhance the aqueous solubility and consequently bioavailability of drugs. Pre-dissolution of drugs in lipids, surfactants, or mixtures of lipid excipients and surfactants eliminate the dissolution/dissolving step, which is likely to be the rate-limiting factor for oral absorption of poorly water-soluble drugs. In this review, we exhaustively summarize the lipids excipients in relation to their classification, absorption mechanisms, and lipid-based product development. Methodologies utilized for the preparation of solid and semi-solid lipid formulations, applications, phase behaviour, and regulatory perspective of lipid excipients are discussed.

Serial macromolecular crystallography at ALBA Synchrotron Light Source.

The increase in successful adaptations of serial crystallography at synchrotron radiation sources continues. To date, the number of serial synchrotron crystallography (SSX) experiments has grown exponentially, with over 40 experiments reported so far. In this work, we report the first SSX experiments with viscous jets conducted at ALBA beamline BL13-XALOC. Small crystals (15-30 µm) of five soluble proteins (lysozyme, proteinase K, phycocyanin, insulin and α-spectrin-SH3 domain) were suspended in lipidic cubic phase (LCP) and delivered to the X-ray beam with a high-viscosity injector developed at Arizona State University. Complete data sets were collected from all proteins and their high-resolution structures determined. The high quality of the diffraction data collected from all five samples, and the lack of specific radiation damage in the structures obtained in this study, confirm that the current capabilities at the beamline enables atomic resolution determination of protein structures from microcrystals as small as 15 µm using viscous jets at room temperature. Thus, BL13-XALOC can provide a feasible alternative to X-ray free-electron lasers when determining snapshots of macromolecular structures.

Cubosomal Betamethasone-Salicylic Acid Nano Drug Delivery System for Enhanced Management of Scalp Psoriasis.

IntroductionBetamethasone dipropionate (BD), a potent corticosteroid, and salicylic acid (SA), a keratolytic agent, have been used in combination to treat scalp psoriasis; however, undesirable side effects associated with their prolonged topical use are inevitable. In this study, BD and SA were loaded into cubosomes, a nanoparticulate system with outstanding biocompatibility, bio-adhesivity and penetration power.MethodsDesign of experiments (DOE) was utilized to prepare thirteen different cubosomal dispersions by emulsification technique using glycerol monoolein (GMO) as a lipid phase and Poloxamer 407 (P407) as a surfactant, sodium carboxymethyl cellulose (SCMC) was added to enhance the dispersions’ rheological properties. The thirteen dispersions were in-vitro characterized for their particle size, polydispersity index (PDI), zeta potential, BD and SA content and rheological behaviour. The desirability of an optimized formula (OF) was set to the smallest particle size, lowest zeta-potential and highest viscosity. The OF was in-vitro characterized for the same parameters in addition to transmission electron microscope imaging and in-vitro drug release. The OF’s anti-psoriatic activity was evaluated in-vivo using an imiquimod-induced psoriasis model.ResultsThe OF achieved a particle size of 197.4 ± 9.47 nm, a PDI of 0.443 ± 0.025, a zeta potential of −44.4 ± 0.141mv, BD content of 105.85 ± 2.290%, SA content of 88.855 ± 2.920% with shear-thinning rheological behaviour and completed in-vitro drug release within 2–3 hours. The in-vivo studies confirmed the cubosomes’ higher anti-psoriatic efficacy over the commercial product with lower changes in ear thickness, spleen to body weight ratio, psoriasis area severity index score and improved histopathological findings.ConclusionThe developed BD SA-loaded cubosomes exhibit promising anti-psoriatic activity attributed to its nano-size and unique lipid content, with enhanced skin penetration and modified rheological properties; increasing the formulation’s in-contact duration with the scalp resulting in lower application frequency and thus reduced BD and SA associated side effects.

Peptide-Folding Triggered Phase Separation and Lipid Membrane Destabilization in Cholesterol-Rich Lipid Vesicles

Liposome-based drug delivery systems are widely used to improve drug pharmacokinetics but can suffer from slow and unspecific release of encapsulated drugs. Membrane-active peptides, based on sequences derived or inspired from antimicrobial peptides (AMPs), could offer means to trigger and control the release. Cholesterol is used in most liposomal drug delivery systems (DDS) to improve the stability of the formulation, but the activity of AMPs on cholesterol-rich membranes tends to be very low, complicating peptide-triggered release strategies. Here, we show a de novo designed AMP-mimetic peptide that efficiently triggers content release from cholesterol-containing lipid vesicles when covalently conjugated to headgroup-functionalized lipids. Binding to vesicles induces peptide folding and triggers a lipid phase separation, which in the presence of cholesterol results in high local peptide concentrations at the lipid bilayer surface and rapid content release. We anticipate that these results will facilitate the development of peptide-based strategies for controlling and triggering drug release from liposomal drug delivery systems.

Sodium Channels and Local Anesthetics—Old Friends With New Perspectives

The long history of local anesthetics (LAs) starts out in the late 19th century when the content of coca plant leaves was discovered to alleviate pain. Soon after, cocaine was established and headed off to an infamous career as a substance causing addiction. Today, LAs and related substances—in modified form—are indispensable in our clinical everyday life for pain relief during and after minor and major surgery, and dental practices. In this review, we elucidate on the interaction of modern LAs with their main target, the voltage-gated sodium channel (Navs), in the light of the recently published channel structures. Knowledge of the 3D interaction sites of the drug with the protein will allow to mechanistically substantiate the comprehensive data available on LA gating modification. In the 1970s it was suggested that LAs can enter the channel pore from the lipid phase, which was quite prospective at that time. Today we know from cryo-electron microscopy structures and mutagenesis experiments, that indeed Navs have side fenestrations facing the membrane, which are likely the entrance for LAs to induce tonic block. In this review, we will focus on the effects of LA binding on fast inactivation and use-dependent inhibition in the light of the proposed new allosteric mechanism of fast inactivation. We will elaborate on subtype and species specificity and provide insights into modelling approaches that will help identify the exact molecular binding orientation, access pathways and pharmacokinetics. With this comprehensive overview, we will provide new perspectives in the use of the drug, both clinically and as a tool for basic ion channel research.

Membrane thickness, lipid phase and sterol type are determining factors in the permeability of membranes to small solutes

Cell membranes provide a selective semi-permeable barrier to the passive transport of molecules. This property differs greatly between organisms. While the cytoplasmic membrane of bacterial cells is highly permeable for weak acids and glycerol, yeasts can maintain large concentration gradients. Here we show that such differences can arise from the physical state of the plasma membrane. By combining stopped-flow kinetic measurements with molecular dynamics simulations, we performed a systematic analysis of the permeability of a variety of small molecules through synthetic membranes of different lipid composition to obtain detailed molecular insight into the permeation mechanisms. While membrane thickness is an important parameter for the permeability through fluid membranes, the largest differences occur when the membranes transit from the liquid-disordered to liquid-ordered and/or to gel state, which is in agreement with previous work on passive diffusion of water. By comparing our results with in vivo measurements from yeast, we conclude that the yeast membrane exists in a highly ordered and rigid state, which is comparable to synthetic saturated DPPC-sterol membranes.

Peroxyl radical induced membrane instability of giant unilamellar vesicles and anti-lipooxidation protection

The present work is intended to investigate the morphological instability of lipid membrane induced by peroxyl radical (ROO•) and the underlying mechanism. To this end, the giant unilamellar vesicle (GUV) made from phosphatidylcholine was employed as a membrane model, and the azo compounds 2,2′-azobis(2,4-dimethylvaleronitrile) (AMVN) and 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH) were used as the precursors of ROO•. Upon mild pyrolysis, the GUV immobilized in agarose gel was followed by conventional optical microscopy in real time, and the morphological variation was quantified by the image heterogeneity, perimeter and area all as a function of time for up to an hour. Lipid oxidation initiated from lipid phase with AMVN and from aqueous phase with AAPH led to different types of morphological changes, i.e. membrane coarsening and vesicle deformation/budding, respectively. Based on the compositional analysis of lipid oxidation products, we propose that ROO• as the primary radical initiator is responsible for the morphological changes of the GUV-AMVN while both ROO• and RO• are responsible for the morphological changes of the GUV-AAPH system. Lipophilic β-carotene and amphipathic plant phenols as antioxidants are found to be able to stabilize the membrane integrity effectively, in corroboration with the proposed mechanisms for membrane destruction.

Observations of phase changes in monoolein during high viscous injection.

Serial crystallography of membrane proteins often employs high-viscosity injectors (HVIs) to deliver micrometre-sized crystals to the X-ray beam. Typically, the carrier medium is a lipidic cubic phase (LCP) media, which can also be used to nucleate and grow the crystals. However, despite the fact that the LCP is widely used with HVIs, the potential impact of the injection process on the LCP structure has not been reported and hence is not yet well understood. The self-assembled structure of the LCP can be affected by pressure, dehydration and temperature changes, all of which occur during continuous flow injection. These changes to the LCP structure may in turn impact the results of X-ray diffraction measurements from membrane protein crystals. To investigate the influence of HVIs on the structure of the LCP we conducted a study of the phase changes in monoolein/water and monoolein/buffer mixtures during continuous flow injection, at both atmospheric pressure and under vacuum. The reservoir pressure in the HVI was tracked to determine if there is any correlation with the phase behaviour of the LCP. The results indicated that, even though the reservoir pressure underwent (at times) significant variation, this did not appear to correlate with observed phase changes in the sample stream or correspond to shifts in the LCP lattice parameter. During vacuum injection, there was a three-way coexistence of the gyroid cubic phase, diamond cubic phase and lamellar phase. During injection at atmospheric pressure, the coexistence of a cubic phase and lamellar phase in the monoolein/water mixtures was also observed. The degree to which the lamellar phase is formed was found to be strongly dependent on the co-flowing gas conditions used to stabilize the LCP stream. A combination of laboratory-based optical polarization microscopy and simulation studies was used to investigate these observations.

Lipid Phase Separation in Vesicles Enhances TRAIL-Mediated Cytotoxicity.

Ligand spatial presentation and density play important roles in signaling pathways mediated by cell receptors and are critical parameters when designing protein-conjugated therapeutic nanoparticles. Here, we harness lipid phase separation to spatially control the protein presentation on lipid vesicles. We use this system to improve the cytotoxicity of TNF-related apoptosis inducing ligand (TRAIL), a therapeutic anticancer protein. Vesicles with phase-separated TRAIL presentation induce more cell death in Jurkat cancer cells than vesicles with uniformly presented TRAIL, and cytotoxicity is dependent on TRAIL density. We assess this relationship in other cancer cell lines and demonstrate that phase-separated vesicles with TRAIL only enhance cytotoxicity through one TRAIL receptor, DR5, while another TRAIL receptor, DR4, is less sensitive to TRAIL density. This work demonstrates a rapid and accessible method to control protein conjugation and density on vesicles that can be adopted to other nanoparticle systems to improve receptor signaling by nanoparticles.

Design, Development and Characterization of Nanoemulsion developed by High Pressure Homogenization (HPH) method Containing Antifungal Drug

Nanoemulsion is one the most attractive drug delivery for researchers to treat fungal diseases and getting interested in increasing the solubility of low soluble drugs. The objective of this research was to develop a topical nanoemulsion formulation of Posaconazole drug with the intention to enhance its aqueous solubility and local action. By employing High Pressure Homogenization (HPH) method, oil in water nanoemulsion was formulated with 0.2% cinnamon oil as lipid phase, 0.4% tween-80 and poloxamer-188 as surfactants, 0.2% transcutol as a co-surfactant. The physical characteristics of formulations were found to be stable after thermodynamic stability testing. In-vitro diffusion study for optimized nanoemulsion was performed using a dialysis bag membrane and cumulative % drug release was determined. Viscosity and percent drug content was observed to be 0.0593 cps and 90.21 ± 0.23% respectively. The optimized nanoemulsion formulation (F8) was evaluated to be transparent and thermodynamically stable, with -9.46 zeta potential, 78.79 nm particle size, 0.315 polydispersity index. The optimized Nanoemulsion was stable for 3 month in three different temperature conditions. The result from the release study was indicative of improved solubility of Posaconazole, which may serve to boost up the action of the drug for the treatment of fungal diseases.
 Keywords: Posaconazole, Nanoemulsion, HPH method, Physical Characterization

Mechanistic Pathway of Lipid Phase-Dependent Lipid Corona Formation on Phenylalanine-Functionalized Gold Nanoparticles: A Combined Experimental and Molecular Dynamics Simulation Study.

In recent years, the underlying mechanism of formation of the lipid corona and its stability have begun to garner interest in the nanoscience community. However, until now, very little is known about the role of different properties of nanoparticles (NPs) (surface charge density, hydrophobicity, and size) in lipid corona formation. Apart from the physicochemical properties of NPs, the different properties of lipids remain elusive in lipid corona formation. In the present contribution, we have investigated the interaction of phenylalanine-functionalized gold NPs (Au-Phe NPs) with different zwitterionic lipid vesicles of different phase states (sol-gel and liquid crystalline at room temperature) as a function of lipid concentration. The main objective of the present work is to understand how the lipid phase affects lipid corona formation and lipid-induced aggregation in various media. Our results establish that the lipid phase state, area per lipid head group, and the buffer medium play important roles in lipid-induced aggregation. The lipid corona occurs for NPs at high lipid concentration, irrespective of the phase states and area per lipid head group of the lipid bilayer. Notably, the lipid corona also forms at a low concentration of lipid vesicles in the liquid crystalline phase (1,2-dioleoyl-sn-glycero-3-phosphocholine). The corona formation brings in remarkable stability to NPs against freeze-thaw cycles. Based on the stability, for the first time, we classify lipid corona as "hard lipid corona" and "soft lipid corona". This distinct classification will help to develop suitable nanomaterials for various biomedical applications.

Changes in levels of omega-O-acylceramides and related processing enzymes of sun-exposed and sun-protected facial stratum corneum in differently pigmented ethnic groups.

IntroductionWe report on the differences in ceramide composition and levels of omega‐O‐acylceramide processing enzymes of sun‐exposed and sun‐protected facialstratum corneum (SC) among Albino African, Black African and Caucasian women living in South Africa.MethodsTape strippings were taken from the sun‐exposed cheek and the sunprotected postauricular site (PA). In two subsets proteomic (n = 18) and lipidomic (n = 24) analysis were performed using mass‐spectrometry‐based shotgun platforms.ResultsNo significant differences in total ceramide levels or ceramide subtypes were found between the Black African and Caucasian women in either the cheek or PA samples. Compared to the other two groups the levels of total ceramide as well as selected omega‐O‐acylceramide species were increased in Albino Africans. On the cheek, ceramide (CER) EOS, EOH along with CER AS were increased relative to the Caucasian women, while CER EOP and EOdS were elevated relative to the Black African women. Moreover, on the PA site CER EOP and EOdS were elevated compared with the Black African women and CER EOdS in Caucasians. Decreasesin masslevels of 12R‐LOX and eLOX3 were observed on cheeks compared with the PA sites in all ethnic groups. On the PA sites 12R‐LOX was particularly lower in the Albino Africans compared with the Black African and Caucasian women. On the cheeks mass levels of SDR9C7 was also lower in the Albino Africans.ConclusionThe mass levels of the ceramides were similar between Black African and Caucasian women. However, elevated total ceramides and excessively elevated selected omega‐O‐acylceramides were apparent in the Albino African women. The findings in the Albino African women were unexpected as these participants suffer from impaired skin barrier function. However, the elevated levels omega‐O‐acylceramides can contribute to barrier insufficiency by directly impacting SC lipid phase behaviour and/or secondly elevated omegaO‐acylceramide levels may indicate a reduced attachment of ceramides to the corneocyte lipid envelope and reduced corneocyte maturation that can also impair the barrier. Indeed, differences in the mass levels of omega‐O‐acylceramide processing enzymes were observed for 12R‐LOX and SDR9C7 for the Albino Africans. This indicates a corneocyte lipid scaffold disorder in this population.