Enabling Lipidomic Biomarker Studies for Protected Populations by Combining Noninvasive Fingerprint Sampling with MS Analysis and Machine Learning.

Triacylglycerols and wax esters are two lipid classes that have been linked to diseases, including autism, Alzheimer's disease, dementia, cardiovascular disease, dry eye disease, and diabetes, and thus are molecules worthy of biomarker exploration studies. Since triacylglycerols and wax esters make up the majority of skin-surface lipid secretions, a viable sampling method for these potential biomarkers would be that of groomed latent fingerprints. Currently, however, blood-based sampling protocols predominate in the field. The invasiveness of a blood draw limits its utility to protected populations, including children and the elderly. Herein we describe a noninvasive means for sample collection (from fingerprints) paired with fast MS data-acquisition (MassIVE data set MSV000092742) and efficient data analysis via machine learning. Using both supervised and unsupervised classification, we demonstrate the usefulness of this method in determining whether a variable of interest imparts measurable change within the lipidomic data set. As a proof-of-concept, we show that the method is capable of distinguishing between the fingerprints of different individuals as well as between anatomical sebum collection regions. This noninvasive, high-throughput approach enables future lipidomic biomarker researchers to more easily include underrepresented, protected populations, such as children and the elderly, thus moving the field closer to definitive disease diagnoses that apply to all.

Shotgun Lipidomic Profiling of Sebum Lipids via Photocatalyzed Paternò-Büchi Reaction and Ion Mobility-Mass Spectrometry.

Sebum lipids are composed of nonpolar lipids, and they pose challenges for mass spectrometry-based analysis due to low ionization efficiency and the existence of numerous isomers and isobars. To address these challenges, we have developed ethyl 2-oxo-2-(pyridine-3-yacetate as a charge-tagging Paternò-Büchi reagent and Michler's ketone as a highly efficient photocatalyst, achieving ∼90% conversion for C═C derivatization under 440 nm LED irradiation. This derivatization, when coupled with electrospray ionization-tandem mass spectrometry, boosts the detection of sebum lipids and pinpoints C═C location in a chain-specific fashion. Identification and quantitation of isomers are readily achieved for wax esters, a class of underexplored sebum lipids, which have C═C bonds distributed in fatty alcohol and fatty acyl chains. A shotgun analysis workflow has been developed by pairing the offline PB derivatization with cyclic ion mobility spectrometry-mass spectrometry. Besides the dominant n-10 C═C location in unsaturated wax esters, profiling of low abundance isomers, including the rarely reported n-7 and n-13 locations, is greatly enhanced due to separations of C═C diagnostic ions by ion mobility. Over 900 distinct lipid structures from human sebum lipid extract have been profiled at the chain-specific C═C level, including wax esters (500), glycerolipids (393), and cholesterol esters (22), far more exceeding previous reports. Overall, we have developed a fast and comprehensive lipidomic profiling tool for sebum samples, a type of noninvasive biofluids holding potential for the discovery of disease markers in distal organs.

Dysregulated lipidome of sebum in patients with atopic dermatitis.

BACKGROUND: Lipids are the major components of skin barrier, mainly produced by keratinocytes and sebaceous glands. Previous studies on barrier dysfunction of atopic dermatitis (AD) mainly focus on the lipids from keratinocytes, whereas the role of sebaceous gland-derived lipids in AD has long been underrecognized. METHODS: The sebum secreted on the skin surface of AD patients was measured using the Delfin Sebum Scale. Sebum was collected using Sebutape patches and subjected for liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis. Multivariate data analysis was applied to explore the relationship among the lipidome, clinical features, and sebaceous gland-related molecules. RESULTS: The amount of sebum secreted from sebaceous glands was decreased in AD patients and was negatively correlated with the barrier function and disease severity. LC-MS/MS revealed the lipidome of sebum, which clustered distinctly between AD patients and healthy individuals. Among the differential lipid subclasses, triglycerides (TG) were exclusively decreased in AD patients and correlated with disease severity. The first principal component scores of AD patients, which represented the main signature of the lipidome, were positively correlated with the SCORAD scores and were significantly different across the patient groups with differential clinical symptoms such as skin dryness and pruritus. Further analysis on the previously published transcriptome data revealed aberrant expression of lipid metabolism-related genes in non-lesional skin of AD patients, which was associated with skin inflammation and barrier dysfunction and mainly derived from inner root sheath keratinocytes and sebaceous gland cells. CONCLUSION: Atopic dermatitis patients demonstrated a deviated lipidome of sebum and aberrant lipid metabolism in sebaceous glands, indicating a possible role of lipids from sebaceous glands in the pathogenesis of AD.

Metabolic and pathologic profiles of human LSS deficiency recapitulated in mice.

Skin lesions, cataracts, and congenital anomalies have been frequently associated with inherited deficiencies in enzymes that synthesize cholesterol. Lanosterol synthase (LSS) converts (S)-2,3-epoxysqualene to lanosterol in the cholesterol biosynthesis pathway. Biallelic mutations in LSS have been reported in families with congenital cataracts and, very recently, have been reported in cases of hypotrichosis. However, it remains to be clarified whether these phenotypes are caused by LSS enzymatic deficiencies in each tissue, and disruption of LSS enzymatic activity in vivo has not yet been validated. We identified two patients with novel biallelic LSS mutations who exhibited congenital hypotrichosis and midline anomalies but did not have cataracts. We showed that the blockade of the LSS enzyme reaction occurred in the patients by measuring the (S)-2,3-epoxysqualene/lanosterol ratio in the forehead sebum, which would be a good biomarker for the diagnosis of LSS deficiency. Epidermis-specific Lss knockout mice showed neonatal lethality due to dehydration, indicating that LSS could be involved in skin barrier integrity. Tamoxifen-induced knockout of Lss in the epidermis caused hypotrichosis in adult mice. Lens-specific Lss knockout mice had cataracts. These results confirmed that LSS deficiency causes hypotrichosis and cataracts due to loss-of-function mutations in LSS in each tissue. These mouse models will lead to the elucidation of the pathophysiological mechanisms associated with disrupted LSS and to the development of therapeutic treatments for LSS deficiency.

Development of an Efficient Extraction Methodology to Analyse Potential Inflammatory Biomarkers from Sebum.

INTRODUCTION: Proteins, such as cytokines and chemokines, are present in varying concentrations in a range of biofluids, with an important signalling role in maintaining homeostasis. Commercial tapes have been employed to non-invasively collect these potential biomarkers in sebum from the skin surface to examine their concentrations in conditions including acne, atopic dermatitis, and pressure ulcers. However, the identification of robust biomarker candidates is limited by the low abundance of specific proteins extracted by current methodologies. Therefore, this study was designed to develop an optimized extraction method for potential inflammatory biomarkers in sebum collected with Sebutapes. METHODS: Commercial tapes (Sebutapes) coated with synthetic sebum were used to systematically evaluate the effects of chemical and mechanical stimuli on extraction efficiency. Varying concentrations of high- and low-abundance biomarkers (IL-1α, IL-6, IL-8, INF-γ, TNF-α, and IL-1RA) were used to spike the synthetic sebum samples. Methodological variables included different surfactants, mechanical stimuli, and buffer volume. Extraction efficiency was estimated using immunoassay kits from the extracted buffer. RESULTS: The results revealed that the use of a surfactant, i.e., ß-dodecyl maltoside, in addition to the mechanical stimuli, namely, sonication and centrifugation, resulted in an increased recovery of cytokines, ranging from 80% for high-abundant cytokines, such as IL-1α and IL-1RA, and up to 50% for low-abundance cytokines, including TNF-α, IL-6 and IL-8. Compared to previous methods, the new extraction protocol resulted in between a 1.5-2.0-fold increase in extraction efficiency. CONCLUSION: The study revealed that there was a high degree of variability in the extraction efficiency of different cytokines. However, improved efficiency was achieved across all cytokines with selective surfactants and mechanical stimuli. The optimised protocol will provide means to detect low levels of potential biomarkers from skin surface, enabling the evaluation of local changes in pro- and anti-inflammatory cytokines present in different skin conditions.

Effect of Hydrogel Substrate Components on the Stability of Tetracycline Hydrochloride and Swelling Activity against Model Skin Sebum.

Due to its high instability and rapid degradation under adverse conditions, tetracycline hydrochloride (TC) can cause difficulties in the development of an effective but stable formulation for the topical treatment of acne. The aim of the following work was to propose a hydrogel formulation that would ensure the stability of the antibiotic contained in it. Additionally, an important property of the prepared formulations was the activity of the alcoholamines contained in them against the components of the model sebum. This feature may help effectively cleanse the hair follicles in the accumulated sebum layer. A series of formulations with varying proportions of anionic polymer and alcoholamine and containing different polymers have been developed. The stability of tetracycline hydrochloride contained in the hydrogels was evaluated for 28 days by HPLC analysis. Formulations containing a large excess of TRIS alcoholamine led to the rapid degradation of TC from an initial concentration of about 10 µg/mL to about 1 µg/mL after 28 days. At the same time, these formulations showed the highest activity against artificial sebum components. Thanks to appropriately selected proportions of the components, it was possible to develop a formulation that assured the stability of tetracycline for ca. one month, while maintaining formulation activity against the components of model sebum.

A simple and fast method for metabolomic analysis by gas liquid chromatography-mass spectrometry.

INTRODUCTION: The metabolomic profile is an essential tool for understanding the physiological processes of biological samples and their changes. In addition, it makes it possible to find new substances with industrial applications or use as drugs. As GC-MS is a very common tool for obtaining the metabolomic profile, a simple and fast method for sample preparation is required. OBJECTIVES: The aim of this research was to develop a direct derivatization method for GC-MS to simplify the sample preparation process and apply it to a wide range of samples for non-targeted metabolomic analysis purposes. METHODS: One pot combined esterification of carboxylic acids with methanol and silylation of the hydroxyl groups was achieved using a molar excess of chlorotrimethylsilane with respect to methanol in the presence of pyridine. RESULTS: The metabolome profile obtained from different samples, such as bilberry and cherry cuticles, olive leaves, P. aeruginosa and E. coli bacteria, A. niger fungi and human sebum from the ceruminous gland, shows that the procedure allows the identification of a wide variety of metabolites. Aliphatic fatty acids, hydroxyfatty acids, phenolic and other aromatic compounds, fatty alcohols, fatty aldehydes dimethylacetals, hydrocarbons, terpenoids, sterols and carbohydrates were identified at different MSI levels using their mass spectra. CONCLUSION: The metabolomic profile of different biological samples can be easily obtained by GC-MS using an efficient simultaneous esterification-silylation reaction. The derivatization method can be carried out in a short time in the same injection vial with a small amount of reagents.

A novel method for evaluating the effect of pollution on the human skin under controlled conditions.

BACKGROUND: Generally considered as a major risk factor for various respiratory diseases, air pollution can also have a significant impact on the skin. To date, there is a plethora of cosmetics products with "anti-pollution" claims. However, these claims have not been fully substantiated with robust scientific evidence and currently there is no standardized method in place for validating the anti-pollution efficacy of cosmetics products. MATERIALS AND METHODS: This article discusses an innovative Controlled Pollution Exposure System (CPES) which allows quantified administration of pollutants on the skin and analysis of their direct impact. Using CPES, human subjects were exposed to ambient dust and ozone and sebum were sampled and analyzed for biomarkers. RESULTS: Following exposure of human subjects' skin to either ambient dust(100-450 µg/cm3 ) or ozone(100-1000 ppb), analysis of sebum revealed a significant decrease in squalene concentration, and significant increases in squalene monohydroperoxide and malondialdehyde concentration. CONCLUSION: The findings demonstrate cutaneous oxidative stress induced by ambient dust and ozone. The findings also demonstrate the efficacy of CPES to accurately measure the direct effect of controlled gaseous and particulate pollutants on human skin and indicate that squalene, squalene monohydroperoxide and malondialdehyde may serve as potent biomarkers for evaluating potential anti-pollution claims of cosmetics products.

Complexes of Ectoine with the Anionic Surfactants as Active Ingredients of Cleansing Cosmetics with Reduced Irritating Potential.

For many years, an increasing number of diagnosed atopy and skin problems have been observed. For people affected by the problem of atopy, the selection of skin care products, including cosmetics, is extremely important. Cleansing cosmetics, due to their ability to cause skin irritations and disturb the hydrolipidic barrier, can increase problems with atopic skin. New solutions to reduce the effects of these products on the skin are very important. In this work, the effect of ectoine on the properties of anionic surfactants was analyzed. Based on model systems, analysis of the effect of ectoine on the irritating effect of four anionic surfactants and their ability to solubilize model sebum was performed. Antioxidant activity was also evaluated, and cytotoxic studies were performed on cell cultures. It was shown that the addition of ectoine to the anionic surfactant solutions improves its safety of use. After introducing ectoine to the surfactant solution, a decrease of irritant potential (about 20%) and a decrease in the ability to solubilize of model sebum (about 10-20%) was noted. Addition of ectoine to surfactant solutions also reduced their cytotoxicity by up to 60%. The obtained results indicate that ectoine may be a modern ingredient that improves the safety of cleansing cosmetics.

Mechanisms of lipid extraction from skin lipid bilayers by sebum triglycerides.

The skin surface, our first barrier against the external environment, is covered by the sebum oil, a lipid film composed of sebaceous and epidermal lipids, which is important in the regulation of the hydration level of our skin. Here, we investigate the pathways leading to the transfer of epidermal lipids from the skin lipid bilayer to the sebum. We show that the sebum triglycerides, a major component of sebum, interact strongly with the epidermal lipids and extract them from the bilayer. Using microsecond time scale molecular dynamics simulations, we identify and quantify the free energy associated with the skin lipid extraction process.

Revisiting, in vivo, the hair regreasing process by the Sebuprint method.

BACKGROUND: The regreasing process of hair by sebum is daily observed by consumers. Methods to investigate this phenomenon were scarcely updated since the 1990s, despite the constant progresses in hair cleaning procedures or shampoo formulations. Our objective was first, to develop an in vivo noninvasive method for quantifying the spread of sebum along the hair shaft. Secondly, we use this new method to define the overall kinetics of the hair-regreasing process among two cohorts of Chinese men with opposite self-perceptions of their scalp/hair greasiness (ie, greasy or not greasy). MATERIAL AND METHODS: One hundred and twenty-three Chinese men (aged 18-35 years) participated to the study. The technique used basically adapts the Sebumeter™ technology where supple polymer films are applied onto and along the hair shaft. The sampled hair sebum is further quantified by image analysis/increased transparency. RESULTS: The technique developed showed an adequate reproducibility under fixed conditions (pressure, investigators, scalp sites, etc.). In the two cohorts of subjects (eg, greasy, nongreasy), hair regreasing process was found sharing a same linear progression with time. The two cohorts of men presented significantly different values in the total amount of spread sebum by an approximately two-fold coefficient, with however comparable average values in the sebum amount present at the root region 48 hours post shampoo. At such timing, the spread of sebum reaches much longer distances in the greasy scalp cohort. CONCLUSION: This technique appears promising for assessing the efficacy of cosmetic ingredients (or products) that aim at delaying a natural process that is daily and negatively perceived by consumers.

Systemic and skin-targeting beneficial effects of lycopene-enriched ice cream: A pilot study.

The health-promoting dietary antioxidant lycopene has limited natural bioavailability, but lycopene-rich functional foods can improve its bioavailability. We assessed a new lycopene-enriched ice cream for systemic antioxidant effects and influence on morphological characteristics of facial skin surface in healthy volunteers. In a randomized crossover study, we used 4-wk dietary interventions with either control or lycopene-enriched ice cream. Samples of serum and residual skin surface components (RSSC) from facial skin were taken before interventions, at 2 wk, and at intervention end. Lycopene concentration, conventional blood biochemistry, and oxidative stress biomarkers comprising inflammatory oxidative damage and low-density lipoprotein peroxidase proteins were assessed in the serum. Lycopene-associated immunofluorescence, lipid droplet size, corneocyte desquamation, and microbial presence were measured in the RSSC. The results show that lycopene concentrations in the serum and skin steadily increased during lycopene-enriched ice cream consumption. Whereas we found no intervention-dependent changes in conventional biochemical parameters, both inflammatory oxidative damage and low-density lipoprotein peroxidase protein values significantly decreased by the end of intervention with lycopene-enriched ice cream, but remained unchanged during control ice cream consumption. Control ice cream significantly increased corneocyte desquamation and bacterial presence in the RSSC. These adverse effects, which could potentially predispose consumers to acne development, were absent when volunteers consumed lycopene-enriched ice cream. We concluded that lycopene-enriched ice cream is a new functional food with clear antioxidant properties. In addition, enrichment with lycopene may alleviate proinflammatory action of ice cream at the level of facial skin, thus decreasing diet-associated acne development risk in young consumers.

Lipolytic Activity and the Utilization of Fatty Acids Associated with Bat Sebum by Pseudogymnoascus destructans.

Pseudogymnoascus destructans is the causative agent of a fungal infection of bats known as white-nose syndrome (WNS). Since its discovery in 2006, it has been responsible for precipitous declines of several species of cave-dwelling North American bats. While numerous advancements in the understanding of the disease processes underlying WNS have been made in recent years, there are still many aspects of WNS, particularly with respect to pathogen virulence, that remain unknown. In this preliminary investigation, we sought to further elucidate the disease cycle by concentrating on the pathogen, with specific focus on its ability to utilize lipids that compose bat wing sebum and are found in wing membranes, as a substrate for energy and growth. In vitro growth experiments were conducted with the three most common fatty acids that comprise bat sebum: oleic, palmitic, and stearic acids. None of the fatty acids were observed to contribute a significant difference in mean growth from controls grown on SDA, although morphological differences were observed in several instances. Additionally, as an accompaniment to the growth experiments, bat wing explants from Perimyotis subflavus and Eptesicus fuscus were fluorescently stained to visualize the difference in distribution of 16- and 18-carbon chain fatty acids in the wing membrane. Which substrates contribute to the growth of P. destructans is important to understanding the progressive impact P. destructans has on bat health through the course of the disease cycle.

Molecular cloning, characterisation, and expression analysis of adipocyte fatty acid binding protein gene in Xupu goose (Anser cygnoides domesticus).

1. Adipocyte fatty acid binding protein (A-FABP) plays a key role in fatty acid uptake and intracellular transport. The objective of the present study was to identify and characterise the A-FABP gene in Xupu goose.2. The full-length cDNA of goose A-FABP gene was cloned from the liver tissue using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The distribution of the goose A-FABP in different tissues was determined by quantitative real-time PCR (qRT-PCR).3. The results showed that the full-length cDNA sequence of goose A-FABP was 657 bp, containing a 5'-UTR of 52 bp, a 3'-UTR of 206 bp and an open reading frame (ORF) of 399 bp, which encoded a polypeptide of 132 amino acids (AA).4. The AA sequence of goose A-FABP showed 76.52%, 75.00%, 93.18% and 99.24% identities with previously described homologues from humans (Homo sapiens), mouse (Mus musculus), chicken (Gallus gallus), and duck (Anas platyrhynchos), respectively, and phylogenetic analysis revealed a close relationship among them. The transcript of Xupu goose A-FABP was ubiquitously expressed in all tested tissues, and showed a high-level expression in abdominal fat, sebum and liver.5. A significant positive correlation was identified between A-FABP mRNA abundance in the three adipose tissues and liver weight, ratio of liver to body weight, TG content, and VLDL concentration in the plasma of Xupu goose. A significant negative correlation was observed between the mRNA level of A-FABP and HDL concentration in the plasma of Xupu goose.6. These findings provide a foundation for further research on the function and mechanism of A-FABP in the fat deposition process.

Inactivation of autophagy leads to changes in sebaceous gland morphology and function.

We have reported recently that inactivation of the essential autophagy-related gene 7 (Atg7) in keratinocytes has little or no impact on morphology and function of the epidermal barrier in experimental animals. When these mice aged, mutant males, (Atg7 ΔKC), developed an oily coat. As the keratin 14 promoter driven cre/LoxP system inactivates floxed Atg7 in all keratin 14 (K14) expressing cells, including sebocytes, we investigated whether the oily hair phenotype was the consequence of changes in function of the skin sebaceous glands. Using an antibody to the GFP-LC3 fusion protein, autophagosomes were detected at the border of sebocyte disintegration in control but not in mutant animals, suggesting that autophagy was (a) active in normal sebaceous glands and (b) was inactivated in the mutant mice. Detailed analysis established that dorsal sebaceous glands were about twice as large in all Atg7 ΔKC mice compared to those of controls (Atg7 F/F), and their rate of sebocyte proliferation was increased. In addition, male mutant mice yielded twice as much lipid per unit hair as age-matched controls. Analysis of sebum lipids by thin layer chromatography revealed a 40% reduction in the proportion of free fatty acids (FFA) and cholesterol, and a 5-fold increase in the proportion of fatty acid methyl esters (FAME). In addition, the most common diester wax species (58-60 carbon atoms) were increased, while shorter species (54-55 carbon atoms) were under-represented in mutant sebum. Our data show that autophagy contributes to sebaceous gland function and to the control of sebum composition.

Determining the Effect of pH on the Partitioning of Neutral, Cationic and Anionic Chemicals to Artificial Sebum: New Physicochemical Insight and QSPR Model.

PURPOSE: Sebum is an important shunt pathway for transdermal permeation and targeted delivery, but there have been limited studies on its permeation properties. Here we report a measurement and modelling study of solute partition to artificial sebum. METHODS: Equilibrium experiments were carried out for the sebum-water partition coefficients of 23 neutral, cationic and anionic compounds at different pH. RESULTS: Sebum-water partition coefficients not only depend on the hydrophobicity of the chemical but also on pH. As pH increases from 4.2 to 7.4, the partition of cationic chemicals to sebum increased rapidly. This appears to be due to increased electrostatic attraction between the cationic chemical and the fatty acids in sebum. Whereas for anionic chemicals, their sebum partition coefficients are negligibly small, which might result from their electrostatic repulsion to fatty acids. Increase in pH also resulted in a slight decrease of sebum partition of neutral chemicals. CONCLUSIONS: Based on the observed pH impact on the sebum-water partition of neutral, cationic and anionic compounds, a new quantitative structure-property relationship (QSPR) model has been proposed. This mathematical model considers the hydrophobic interaction and electrostatic interaction as the main mechanisms for the partition of neutral, cationic and anionic chemicals to sebum.

Is Human Sebum the Source of Skin Follicular Ultraviolet-Induced Red Fluorescence? A Cellular to Histological Study.

BACKGROUND: The ultraviolet-induced red fluorescence (UVRF) from human skin follicles was suggested to be a result of Propionibacterium acnes and was used for the monitoring of acne. More recent studies suggested that the UVRF may be more related to sebum rather than to microorganisms. OBJECTIVE: To clarify whether human sebum or follicular microorganisms are the source of UVRF. METHODS: We examined the fluorescence of human-derived SZ95 sebocytes, human sebaceous glands, sebum extracted from the sebaceous glands, and bacteria isolated from human hair follicles under ultraviolet light. RESULTS: SZ95 sebocytes, human sebaceous glands, and sebum do not emit UVRF. Two types of UVRF peaking at about 635 nm and at about 620 nm were detected in P. acnes and Staphylococcus epidermidis, respectively. This is the first report that S. epidermidis emits UVRF when it is anaerobically cultured and then exposed to air. CONCLUSION: Human follicular UVRF is emitted by resident bacteria, not by sebum. Therefore, UVRF may be used to monitor certain species of skin microorganisms.

Analysis of sensitive skin barrier function: basic indicators and sebum composition.

OBJECTIVES: Sensitive skin (SS) is a condition characterised by high reactivity, low tolerance, and susceptibility to allergies of the skin. Owing to changes in the environment and marketing strategies, as well as the increasing public awareness about skin care, attention to skin condition is gradually increasing. The aim of this study is to explore the differences in the skin barrier of SS and normal skin (NS). METHODS: A questionnaire survey was conducted and basic indicators of the skin barrier were analysed. It was found that sebum secretion in the SS group was lower than that in the NS group, suggesting that the development of SS might be associated with sebum secretion and its specific components. Next, an ultra performance liquid chromatography-quadruple time-of-flight mass spectrometer was used to identify facial sebum components in female volunteers. RESULTS: The results showed that the sebum of female volunteers with SS had high levels of ceramides, glycerophosphoethanolamines, and diacylglycerols, and low levels of glucosylceramides, glycerophosphoserines, glycerophosphocholines, and triacylglycerols. CONCLUSION: Analysis of lipid functions suggested that the main reason for SS development in women might be a barrier dysfunction caused by excessive apoptosis and lack of water. Therefore, anti-allergy additives in cosmetic products that could inhibit apoptosis of keratinocytes and methods to maintain the stability of water molecules in the skin should be further studied.

Development of a Two-Dimensional Model for Predicting Transdermal Permeation with the Follicular Pathway: Demonstration with a Caffeine Study.

PURPOSE: The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. METHODS: The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in lipid, corneocytes, viable dermis, dermis and systemic circulation are calculated as reported previously [Pharm Res 33 (2016) 1602]. The mass transfer and partition properties in sebum are collected from existing literature. None of the model input parameters was fit to the clinical data with which the model prediction is compared. RESULTS: The integrated model has been applied to predict the published clinical data of transdermal permeation of caffeine. The relative importance of the follicular pathway is analysed. Good agreement of the model prediction with the clinical data has been obtained. The simulation confirms that for caffeine the follicular route is important; the maximum bioavailable concentration of caffeine in systemic circulation with open hair follicles is predicted to be 20% higher than that when hair follicles are blocked. CONCLUSIONS: The follicular pathway contributes to not only short time fast penetration, but also the overall systemic bioavailability. With such in silico model, useful information can be obtained for caffeine disposition and localised delivery in lipid, corneocytes, viable dermis, dermis and the hair follicle. Such detailed information is difficult to obtain experimentally.

A Topical Medication of All-Trans Retinoic Acid Reduces Sebum Excretion Rate in Patients With Forehead Acne.

Acne is a disease of the hair follicles of the face, chest, and back that affects almost all teenagers during puberty. This study is conducted to investigate if all-trans retinoic acid (ATRA) could reduce sebum excretion rate (SER) in acne patients by influencing content of skin-surface lipid production. Thirty-nine patients with forehead acne were topically treated with cream base (vehicle) and 0.025% ATRA cream once a night for 7 days. Separation and identification of sebum production collected from the skin on the acne were performed using thin-layer chromatography. SER was calculated according to the total amount of individual sebum productions that were quantified by using Alphaimager IS-2200 imaging analysis. Our data showed that the value of SER on the acne-affected skin was significantly decreased in the ATRA-treated patients as compared with ones treated with vehicle (P < 0.01). Treatment with ATRA resulted in inducing significant decreases in the contents of wax esters (WE), triglycerides and fatty acids, and free fatty acids (FFA) productions (all P < 0.01). In further analysis, the changes in the data before and after treatments with vehicle and ATRA were compared with significant differences exhibited in the values of SER, WE, and FFA (all P < 0.05). This study indicates that the topical application of ATRA in treatment of acne patients induces decrease in SER by inhibiting the excretion of WE and FFA productions.