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Background: In the dose titration of transdermal fentanyl to prevent unrelieved pain, it is important to consider not only dose adjustment, but also the titration period, which is influenced by the time required to reach the steady state. Many patients with cancer pain experience comorbidities that might affect the skin properties and influence transdermal absorption. We hypothesized that skin changes due to diabetes mellitus (DM) would affect the titration period of transdermal fentanyl. We conducted a retrospective study and diabetic animal model study to test this hypothesis. Methods: In the retrospective study, the titration period was defined in terms of "dose change" and "number of rescue opioids" in patients initiated on transdermal fentanyl. Multiple logistic regression analysis was performed to analyze the relation between the titration period and comorbidities, including DM. In the diabetic animal model study, intercellular lipids of stratum corneum (SC) were analyzed in Goto-Kakizaki (GK) rats, a model of DM, and the pharmacokinetics of intravenously or transdermally administered fentanyl was examined. Results: In the retrospective study, the titration period ranged from 5 to 39 days (n = 387), and the patients taking a longer period (6 days or more) was significantly related to in patients with unspecified DM: AOR (95% confidence interval), 0.438 (0.217–0.884). In the diabetic animal model study, the ceramides (CERs) content in the SC was decreased by approximately 30% in GK rats compared to Wistar rats. The absorption rate constant (ka) of fentanyl administered transdermally was increased approximately 1.4-fold in GK rats, though there was no difference in transdermal bioavailability (F) or systemic clearance (CLtot). Conclusion: Our results suggest that the steady state of transdermally administered fentanyl is reached sooner in cancer patients with DM as a comorbidity. Earlier pain assessment and dose adjustment may be possible in these patients. [ABSTRACT FROM AUTHOR]

Background: Topical use of dexpanthenol presents well‐established moisturizing properties and maintenance and repair of the skin barrier function, however, its exact action mechanisms are not completely elucidated. In this context, Confocal Raman Microspectroscopy is an optical method that enables non‐invasive and non‐destructive in vivo analysis with the sensitive acquisition of molecular changes in different skin layers. Herein, the aim was to evaluate the effects of topical dexpanthenol on the components and physiological parameters of the stratum corneum (SC). Materials and methods: Ten healthy female subjects underwent skin evaluation by means of a Confocal Raman Spectrometer Skin Analyzer 3510. Spectral data were obtained from the skin of the anterior forearm region, before and 2 h after applying a cosmetic formulation containing or not containing 5% dexpanthenol. Results: Semiquantitative analysis of the natural moisturizing factor showed a significant decrease in content after 2 h of topical dexpanthenol application, while the analysis of the lamellar organization of intercellular lipids and the secondary structure of keratin showed a significant increase in hexagonal organization of lipids at the first half of the SC and a significant increase in β‐pleated sheet conformation of keratin. Conclusion: Effects of topical dexpanthenol on SC suggest a contribution in increasing fluidity of both lipidic and protein components of the SC and are compatible with dexpanthenol activity in maintaining adequate physiological conditions and preventing transepidermal water loss. This study also contributes to the elucidation of action mechanisms and other concurrent biochemical processes. [ABSTRACT FROM AUTHOR]

Imaging-based evaluation of lipids in the stratum corneum by label-free stimulated Raman scattering microscopy Keywords: barrier; intercellular lipids; label-free; noninvasive; stimulated Raman scattering microscopy; stratum corneum EN barrier intercellular lipids label-free noninvasive stimulated Raman scattering microscopy stratum corneum 1 5 5 06/28/23 20230601 NES 230601 B Dear Editor, b The stratum corneum (SC) plays an important role as a barrier against the external environment. White bars represent skin without acetone treatment, and black bars represent skin with acetone treatment. As we reported previously,[9] cell morphology in the SC could be visualized by using SRS microscopy, and polygonal cells were observed in the SC (dashed lines in Figure 1(B)). [Extracted from the article]

Confocal Raman microspectroscopy is widely used in dermatology and cosmetology for analysis of the concentration of skin components (lipids, natural moisturizing factor molecules, water) and the penetration depth of cosmetic/medical formulations in the human stratum corneum (SC) in vivo. In recent years, it was shown that confocal Raman microspectroscopy can also be used for noninvasive in vivo depth-dependent determination of the physiological parameters of the SC, such as lamellar and lateral organization of intercellular lipids (ICLs), folding properties of keratin, water mobility, and hydrogen bonding states. The results showed that the strongest skin barrier function, which is primarily manifested by the orthorhombic organization of ICLs, is provided at ≈20–40% SC depth, which is related to the maximal bonding state of water with surrounding components in the SC. The secondary and tertiary structures of keratin determine water binding in the SC, which is depth-dependent. This paper shows the technical possibility and advantage of confocal Raman microspectroscopy in noninvasive investigation of the skin and summarizes recent results on in vivo investigation of the human SC. [ABSTRACT FROM AUTHOR]

The physical barrier of the stratum corneum (SC) is provided by corneocytes and the lateral organization of intercellular lipids, which necessarily includes the orthorhombic organization phase. A review of methods used for in vivo non-invasive measurement of skin barrier function has been carried out and it has been shown that all currently used methods are indirect. The most popular method is the measurement of the transepidermal water loss (TEWL), which does not provide information on biophysical parameters responsible for the barrier function of the SC. It has been shown that confocal Raman microspectroscopy is the most suitable non-invasive method to determine the depth profile of the lateral organization of intercellular lipids, i.e. to study the skin barrier function in vivo.

Abstract Spectral signals of stratum corneum (SC) acquired from confocal Raman spectroscopy (CRS) are employed to track lipid variations and the most sensitive and efficient signals are of high interest. Herein, 1% of sodium lauryl sulfate treated SC was compared to water‐treated one to evaluate statistical difference of spectral signals concerning lipid content, SC thickness and lipid molecular structures. Results showed that peak ratio of 1425 to 1490 cm−1 and 1630 to 1710 cm−1 in fingerprint region and Gaussian‐function deconvoluted lipid‐keratin peak ratio in high wavenumber (HWN) region were both responsive for analyzing lipid content. SC thickness measurement using the full width of half‐maximum (FWHM) of 2920 to 2960 cm−1 signal presented good sensitivity. Nevertheless, the shift of peak 2850 cm−1 indicated less sensitivity compared to trans‐gauche peak signals and 1300 cm−1 peak position for lipid conformation analysis. Meanwhile, the ratio of peak 2880 and 2850 cm−1 indicating lipid lateral packing structure presented to be less responsive. More strikingly, FWHM of peak 2850 cm−1 appeared to be unable for lipid lateral packing order analysis in our study. In summary, this research can serve as a pilot study for further investigation of direct drug delivery and interaction between topical applied compounds and skin components.

Spectral signals of stratum corneum (SC) acquired from confocal Raman spectroscopy (CRS) are employed to track lipid variations and the most sensitive and efficient signals are of high interest. Herein, 1% of sodium lauryl sulfate treated SC was compared to water‐treated one to evaluate statistical difference of spectral signals concerning lipid content, SC thickness and lipid molecular structures. Results showed that peak ratio of 1425 to 1490 cm−1 and 1630 to 1710 cm−1 in fingerprint region and Gaussian‐function deconvoluted lipid‐keratin peak ratio in high wavenumber (HWN) region were both responsive for analyzing lipid content. SC thickness measurement using the full width of half‐maximum (FWHM) of 2920 to 2960 cm−1 signal presented good sensitivity. Nevertheless, the shift of peak 2850 cm−1 indicated less sensitivity compared to trans‐gauche peak signals and 1300 cm−1 peak position for lipid conformation analysis. Meanwhile, the ratio of peak 2880 and 2850 cm−1 indicating lipid lateral packing structure presented to be less responsive. More strikingly, FWHM of peak 2850 cm−1 appeared to be unable for lipid lateral packing order analysis in our study. In summary, this research can serve as a pilot study for further investigation of direct drug delivery and interaction between topical applied compounds and skin components. [ABSTRACT FROM AUTHOR]

Non-ionic emulsifiers are commonly found in existing pharmaceutical and cosmetic formulations and have been widely employed to enhance the penetration and permeation of active ingredients into the skin. With the potential of disrupting skin barrier function and increasing fluidity of stratum corneum (SC) lipids, we herein examined the effects of two kinds of non-ionic emulsifiers on intercellular lipids of skin, using confocal Raman spectroscopy (CRS) with lipid signals on skin CRS spectrum. Non-ionic emulsifiers of polyethylene glycol alkyl ethers and sorbitan fatty acid esters were studied to obtain a deep understanding of the mechanism between non-ionic emulsifiers and SC lipids. Emulsifier solutions and dispersions were prepared and applied onto excised porcine skin. Water and sodium laureth sulfate solution (SLS) served as controls. SC lipid signals were analysed by CRS regarding lipid content, conformation and lateral packing order. Polyethylene glycol (PEG) sorbitan esters revealed no alteration of intercellular lipid properties while PEG-20 ethers appeared to have the most significant effects on reducing lipid content and interrupting lipid organization. In general, the polyoxyethylene chain and alkyl chain of PEG derivative emulsifiers might indicate their ability of interaction with SC components. HLB values remained critical for complete explanation of emulsifier effects on skin lipids. With this study, it is possible to characterize the molecular effects of non-ionic emulsifiers on skin lipids and further deepen the understanding of enhancing substance penetration with reduced skin barrier properties and increased lipid fluidity.

Porcine skin is widely used as a human skin model in dermatology. For both, porcine stratum corneum (SC) ex vivo and human SC in vivo, the hydrogen bonding states of water, the secondary and tertiary structures of keratin, the natural moisturizing factor (NMF) concentrations and the intercellular lipids' (ICL) lateral organization are investigated depth‐dependently using confocal Raman microscopy. The SC depth profiles show that porcine SC ex vivo is characterized by lower hydrogen bonding states of water (10%‐30% SC depth), lower NMF concentration in the whole SC, more β‐sheet form of keratin (10%‐90% SC depth), more folded tertiary keratin structures (30%‐70% SC depth) and higher hexagonal lateral packing order of ICL (10%‐50% SC depth) compared to human SC in vivo. The results clearly show a higher value of skin barrier function of human SC in vivo than of porcine SC ex vivo. Thus, the human SC in vivo is less permeable for lipophilic and hydrophilic substances than porcine SC ex vivo. Considering the porcine SC as an ex vivo model of human SC in vivo, these findings should be taken into consideration. [ABSTRACT FROM AUTHOR]

Studies have shown that liquid crystals structurally resembling the intercellular lipids in the stratum corneum can beneficially affect the skin when applied topically by stimulating the skin’s natural regenerative functions and accelerating epidermal turnover. In the present study, the effects of applying low concentrations of a liquid crystal gel of our own creation were evaluated using epidermal thickening in mouse skin as an assay for effective stimulation of epidermal turnover. A liquid crystal gel was also applied topically to human facial skin, and analysis was conducted using before-and-after photographs of age spots, measurements of L* values that reflect degree of skin pigmentation, single-layer samples of the stratum corneum obtained via tape-stripping, and measurements of trans-epidermal water loss that reflect the status of the skin’s barrier function. The results suggested that cost-effective creams containing as low as 5% liquid crystal gel might be effective and safely sold as skin care products targeting age spots and other problems relating to uneven skin pigmentation.

Background The intercellular lipids (ICL) of stratum corneum (SC) play an important role in maintaining the skin barrier function. The lateral and lamellar packing order of ICL in SC is not homogenous, but rather depth-dependent. Objective This study aimed to analyze the influence of the topically applied mineral-derived (paraffin and petrolatum) and plant-derived (almond oil and jojoba oil) oils on the depth-dependent ICL profile ordering of the SC in vivo . Method Confocal Raman microscopy (CRM), a unique tool to analyze the depth profile of the ICL structure non-invasively, is employed to investigate the interaction between oils and human SC in vivo . Results The results show that the response of SC to oils’ permeation varies in the depths. All oils remain in the upper layers of the SC (0–20% of SC thickness) and show predominated differences of ICL ordering from intact skin. In these depths, skin treated with plant-derived oils shows more disordered lateral and lamellar packing order of ICL than intact skin ( p < 0.05). In the intermediate layers of SC (30–50% of SC thickness), the oils do not influence the lateral packing order of SC ICL ( p > 0.1), except plant-derived oils at the depth 30% of SC thickness. In the deeper layers of the SC (60–100% of SC thickness), no difference between ICL lateral packing order of the oil-treated and intact skin can be observed, except that at the depths of 70–90% of the SC thickness, where slight changes with more disorder states are measured for plant-derived oil treated skin ( p < 0.1), which could be explained by the penetration of free fatty acid fractions in the deep-located SC areas. Conclusion Both oil types remain in the superficial layers of the SC (0–20% of the SC thickness). Skin treated with mineral- and plant-derived oils shows significantly higher disordered lateral and lamellar packing order of ICL in these layers of the SC compared to intact skin. Plant-derived oils significantly changed the ICL ordering in the depths of 30% and 70–90% of the SC thickness, which is likely due to the penetration of free fatty acids in the deeper layers of the SC. [ABSTRACT FROM AUTHOR]

Ethanol (EtOH) is one of the bases in topically applied medicines that promote the skin permeation of drugs. Although the effects of EtOH have been attributed to structural modifications in the stratum corneum, the underlying mechanisms, especially the influence of different concentrations of EtOH, have not been examined extensively. Structural modifications in the stratum corneum of hairless mouse due to the application of EtOH/water mixture were herein investigated at the molecular level using synchrotron X-ray diffraction. The results revealed that all EtOH concentrations examined greatly modified the short lamellar structures containing the aqueous layer in intercellular lipids and the structure of keratin fibrils in corneocytes, which can take up hydrophilic compounds. However, the long lamellar and the hydrocarbon-chain packing structures were unaffected by EtOH. Changes to the short lamellar structures were not proportional to the concentration of EtOH. However, the keratin fibril structures changed gradually with increasing EtOH concentration. The X-ray diffraction experiments enabled the effects of different EtOH concentrations on the morphology of the stratum corneum to be assessed by using a number of experimental samples to avoid variations due to individual differences. The results indicated that alterations to the short lamellar structures appeared to be related to the skin permeability of drugs with the application of EtOH/water mixture, and monotonous structural changes in the keratin fibrils with an increase in EtOH concentration may contribute to this permeation as supplement. These results will be useful for the development of new drug formulations containing EtOH. [ABSTRACT FROM AUTHOR]

Background/aims The matrix of intercellular lipids ( ICL) of stratum corneum ( SC) plays an important role in the barrier function of SC. It is important to understand the structure of the ICL matrix for dermatology and cosmetic science. Several methods exist for the analysis of the structure; however, it is difficult to conduct these analyses noninvasively. Methods We have developed a method for the analysis of the lateral packing of ICL using Raman spectroscopy. As a proof-of-principle experiment, we prepared a human SC sheet sample and analyzed its structure by the proposed method and by a conventional method involving X-ray diffraction. We compared the results of both methods. In addition, we applied the proposed method to living human skin, and we analyzed the lateral packing of ICL of SC taken from three separate body sites. Results The results of our method corresponded to those of the conventional method. We detected regional differences of ICL lateral packing using our method in vivo. The results indicated that the packing of ICL in SC taken from the forearm and upper arm are more ordered than that taken from the cheek. Conclusion The results verify that our developed method allows the evaluation of the lateral packing of ICL inside the SC layer of the skin in vivo. Using this method, we can detect regional differences of SC samples taken from various body sites. [ABSTRACT FROM AUTHOR]

Abstract: To develop a transdermal drug delivery system, it is necessary to search for effective modulators to act as permeation enhancers and evaluate its mechanisms of action. It has been suggested that attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) is a useful tool for evaluating the functional group interaction of the intercellular lipids in the stratum corneum. The purpose of this study is elucidation of the effect of the transdermal permeation enhancers on the intercellular lipid in hairless rat stratum corneum using the ATR-FTIR. Firstly, to confirm the frequencies related to the intercellular lipid in stratum corneum, CH2 asymmetric and symmetric vibrations were clearly related to the intercellular lipids. In intact stratum corneum, the blue shift of CH2 asymmetric and symmetric stretching vibrations begins at about 40°C and remarkable change is induced at 50°C. The administration of l-menthol causes disorder of the intercellular lipids in stratum corneum similar to that of heat application. The disordering of intercellular lipid lattices in stratum corneum induced by the l-menthol might be related to the enhancing effect of l-menthol. The results provide information for the development of novel transdermal drug delivery systems. [Copyright &y& Elsevier]

The stratum corneum (SC) (i.e., the outermost layer of human skin) is a complex and paradoxical tissue composed of corneocytes and a matrix of intercellular lipids playing an essential role as the skin's protective barrier. The first paradox of SC is its dual nature. It is composed of nondividing (dead) cells embedded in a metabolically active (live) environment whose function is to protect the epidermis and to maintain its integrity. In order to do so, the SC uses various strategies, including enzymatic reactions, colonization by bacterial flora, immune signaling, antimicrobial lipids and peptides, low pH, antioxidants, and natural moisturizing factor(s). The second paradox is that although its biological function is essentially that of a physicochemical barrier, cosmetologists and pharmacists are actively exploring paths for penetration through the SC to allow passage of active molecules and their penetration into the skin. Various pathways of penetration and physicochemical factors facilitating this penetration into the dermis and/or the epidermis have been defined, but the exact mechanisms of penetration of cosmetic ingredients remain elusive. For cosmetologists and pharmacists, the SC represents a major focus of interest whether for basic research or the development of novel topical approaches taking into account the fascinating properties of this complex tissue. [ABSTRACT FROM AUTHOR]

Abstract: Certain agents that increase drug delivery through the skin, including surfactants, bile salts, and fatty acids, have been shown to exert a similar effect on the buccal mucosa. These agents enhance skin permeability by interacting with and disrupting the ordered intercellular lipid lamellae within the keratinized stratum corneum, and it has been assumed that a similar mechanism of action occurs in the nonkeratinized buccal mucosa. However, the chemical and structural nature of the lipids present within the intercellular regions of the buccal mucosa is quite different to that found within the stratum corneum, and so extrapolation of results between these two tissues may be misleading. To assume that the mechanism of action of buccal penetration enhancers is based on the disruption of intercellular lipids may be erroneous, and may result in the inappropriate prediction that certain skin penetration enhancers will similarly enhance drug delivery through the buccal mucosa. The data available in the literature suggest that agents that enhance buccal penetration exert their effect by a mechanism other than by disruption of intercellular lipids. Rather, buccal penetration enhancement appears to result from agents being able to (a) increase the partitioning of drugs into the buccal epithelium, (b) extract (and not disrupt) intercellular lipids, (c) interact with epithelial protein domains, and/or (d) increase the retention of drugs at the buccal mucosal surface. The purpose of this review is to identify the major differences in the structural and chemical nature of the permeability barriers between the buccal mucosa and skin, to clarify the mechanisms of action of buccal penetration enhancers, and to identify the limitations of certain models that are used to assess the effect of buccal penetration enhancers. [Copyright &y& Elsevier]

Our understanding of the formation, structure, composition, and maturation of the stratum corneum (SC) has progressed enormously over the past 30 years. Today, there is a growing realization that this structure, while faithfully providing a truly magnificent barrier to water loss, is a unique, intricate biosensor that responds to environmental challenges and surface trauma by initiating a series of biologic processes which rapidly seek to repair the damage and restore barrier homeostasis. The detailed ultrastructural, biochemical, and molecular dissection of the classic “bricks and mortar” model of the SC has provided insights into the basis of dry, scaly skin disorders that range from the cosmetic problems of winter xerosis to severe conditions such as psoriasis. With this knowledge comes the promise of increasingly functional topical therapies. [ABSTRACT FROM AUTHOR]

Transdermal iontophoresis per se may not be able to achieve significant permeation of large peptides like insulin, thereby necessitating the use of combination strategies involving chemical enhancers and iontophoresis. The study investigated effect of pre-treatment with commonly used vehicles such as ethanol (EtOH), propylene glycol (PG), water and their binary combinations, dimethyl acetamide (DMA), 10% dimethyl acetamide in water, ethyl acetate (EtAc) and isopropyl myristate (IPM) on insulin iontophoresis. Solvents, which acted on the lipid bilayer, were able to produce a synergistic enhancement with iontophoresis. The binary solvent systems produced either additive or no effect, when combined with iontophoresis. FT-IR studies showed that EtOH, DMA, EtAc caused lipid extraction and the former two also caused changes in skin proteins, whereas IPM caused increase in lipid fluidity. TGA studies showed that EtOH and PG caused dehydration of skin. Skin barrier property was severely compromised with DMA, followed by EtOH and EtAc, while IPM and PG had relatively minimum skin barrier altering potential. Thus, this study demonstrates the possibility of achieving higher permeation of large peptides like insulin by combining iontophoresis with chemical enhancers that act on the intercellular lipids. [Copyright &y& Elsevier]

It has been reported that artificial restoration of barrier function by a water vapor-impermeable membrane after tape stripping induces barrier abrogation in hairless mice, impeding rather than enhancing barrier recovery. To address this issue, we examined the morphologic changes in the epidermis after tape stripping and occlusion with a water vapor-impermeable membrane in murine skin. Male hairless mice were used for all studies of barrier perturbation and occlusion. Barrier disruption was achieved by repeated application of cellophane tape. Immediately after tape stripping the animals were wrapped in a tightly fitting water vapor-impermeable membrane. Transepidermal water loss (TEWL) was measured 20 min after tape stripping and 14, 24, 36, 48 and 60 h after occlusion. For electron microscopy the samples were treated with osmium tetroxide (OsO 4 ) or ruthenium tetroxide (RuO 4 ). When tape-stripped animals were wrapped in a water vapor-impermeable membrane, thereby preventing water flux, barrier function did not recover normally. These results demonstrate that an artificial block to TEWL with an impermeable membrane did not enhance barrier recovery. By electron microscopy many transitional cells and lacunae of various sizes were seen within the intercellular spaces of the stratum corneum after occlusion following tape stripping. Occlusion also caused alterations in both lipid lamellar membrane structures in the stratum corneum interstices and the lamellar bodies in the cytosol of granulocytes and transitional cells. Secreted lamellar body contents also appeared to be abnormal in the stratum corneum-stratum granulosum junction. [ABSTRACT FROM AUTHOR]

Stratum corneum lipid morphology was evaluated using attenuated total reflectance infrared spectroscopy (ATR-IR) in normal skin and surfactant-induced scaly skin to evaluate skin barrier function. To evaluate the degree of order of the intercellular lipid alkyl chain conformation, we measured the wavenumbers (frequency shifts) of the symmetrical and asymmetrical C-H stretching vibrations observed at approximately 2850 cm and 2920 cm, respectively. There was a correlation between the wave-number and transepidermal water loss in normal skin. However, no difference was observed in surfactant-induced scaly skin from the baseline value in the wavenumbers of the C-H vibrations. These results suggest that in normal skin, lipid morphology plays an important role in the barrier function of the stratum corneum. However, the decline in barrier function in scaly skin is not due to conformational disorder of the lipid alkyl chain. [ABSTRACT FROM AUTHOR]

In order to further clarify the role of intercellular lipids in the water-retention properties of the stratum corneum, forearm skin of six healthy male volunteers was treated with 5% sodium dodecyl sulfate (SDS) for 1, 10, and 30 min. All treatment periods induced chapping and scaling of the stratum corneum without any inflammatory reaction, accompanied by a significant decrease in its water-retention function. Electron-microscopic analysis of SDS-treated stratum corneum revealed selective depletion of the lipids from the intercellular spaces, accompanied by marked disruption of multiple lamellae structures. Lipid analysis also showed a considerable and selective loss of intercellular lipids such as cholesterol, cholesterol ester, free fatty acid, and sphingolipids. To evaluate the recovery potential for intercellular lipids, lipids which were separated as sebaceous-rich lipids (SLs) and stratum corneum lipids (SCLs) wer applied daily on SDS-treated forearm skin. Two daily applications of the SCLs which were emulsified at 10% concentration in W/O (water in oil) cream caused a significant increase in conductance, accompanied by a definite improvement in the level of scaling over no application or W/O emulsion base only, whereas SLs in the W/O emulsion base led to no significant recovery in either conductance value or scaling. When two daily topical applications of four chromatographically separated lipid fractions (cholesterol ester, free fatty acid, cholesterol, and sphingolipid) from the SCL were carried out at 1% concentration in the same system, the cholesterol ester and sphingolipid fractions were found to induce a significant increase in the conductance value over no application. In contrast, the free fatty acid and cholesterol fractions showed no significant increase in conductance value. Similarly, the scaling which occurred after SDS treatment had a tendency to decrease after the two daily applications with the fractions of cholesterol ester, sphingolipids, and free fatty acid as compared with that of the base emulsion. These findings strongly suggest that sphingolipids, possibly in combination with other neutral lipids, play an essential role in the establishment or maintenance of water-retention capacity in the stratum corneum. [ABSTRACT FROM AUTHOR]

Stratum corneum intercellular lipids play an important role in skin barrier function and are therefore considered useful in pharmaceutical and cosmetics products. In this study, we formulated cholesterol (Cho), the main component of intercellular lipids, into bicelles using a semi-spontaneous method, with the ultimate aim of extending the utility of bicelles in cosmetics. Bicelles are disk-shaped structures in which the planar part comprises long-chain phospholipids and the rims comprise short-chain phospholipids. We used soybean lecithin (SL) and nonionic surfactants (NS) to formulate Cho into bicelles using a semi-spontaneous method. Cho was successfully formulated into bicelles using poly(oxyethylene) cholesteryl ether (with an average of 10 ethylene oxide units, ChEO 10) as the NS. We identified the boundaries of the bicelle region in the SL-Cho-ChEO 10 system by measuring particle sizes. A bicelle region was formed up to around a maximum mixing ratio of 10wt% Cho, representing a mole fraction (mol%) of approximately 33. Phase changes in the system were observed. Comparison of poly(oxyethylene) cholesteryl ethers containing an average of 10 or 20 (ChEO 20) ethylene oxide units revealed that the size of the hydrophilic group affects both the bicelle formation region and the mixing ratio of Cho. We analyzed the state of the SL-Cho-ChEO 10 bicelles by differential scanning calorimetry and found that samples containing only phospholipid (SL/Ch/ChEO 10 = 1/0/0) provided an endothermic peak between 50 and 55 °C, corresponding to the gel-liquid crystal transition point of the phospholipid. In contrast, the bicelle regions (SL/Cho/ChEO 10 = 0.4/0/0.6 and 0.37/0.05/0.58) lacked a gel liquid crystal transition point and a liquid-ordered state was induced by Cho or ChEO 10. This indicates that these bicelles are highly stable towards thermal changes. [ABSTRACT FROM AUTHOR]

In this study, stratum corneum (SC) depth profiles of hydrogen bound water molecule types, intercellular lipid (ICL) ordering, concentration of natural moisturizing factor (NMF) and keratin folding/unfolding properties are investigated in vivo for older (mean 50 years old) and younger (mean 29 years old) human skin using confocal Raman microscopy. The results show that the SC of the older group is modestly thicker (p<0.1), has more hydrogen bound water molecules at the depth 10-30% of the SC thickness (p<0.05), has a higher ordered organization of ICL (p<0.1) and higher concentration of NMF (p<0.05) at the depth 20-40% of the SC thickness compared to the younger group. This study also reveals, that the hydrogen bonding state of water highly correlates with NMF and the lateral structure of ICL but not with keratin's folding/unfolding properties. The presented results let suggest, that the decreased trans-epidermal water loss (TEWL) with increasing age cannot be sufficiently explained by only the increased SC thickness, but additionally by the increase of ICL ordering, higher NMF concentration and thus larger amount of hydrogen bound water molecules at the depth 20-40% of the SC thickness., (Copyright © 2017 Elsevier B.V. All rights reserved.)