Artificial Sebum Research Articles

Formulation and stability of a novel artificial sebum under conditions of storage and use

Materials in contact with liquids on the human skin surface may dissolve and permeate into skin. Release and permeation of chemicals in contact with skin is often estimated in vitro using artificial skin liquids, although sebum lipids are generally not included in these models. The purposes of this research were to develop a representative artificial sebum that contains the appropriate types of lipids at levels that match human values and quantitatively characterize the model to understand its utility for in vitro testing. Artificial sebum that consisted of 10 lipids at proportions that closely resembled human sebum was characterized using thin layer chromatography under a variety of storage and use conditions (dry and liquid, 4°C and 32°C, with and without vitamin E) for 28 days. Levels of sebum constituents maintained in solution and dry at 4°C were stable through the duration of the test period. Levels of all sebum lipids maintained dry at 32°C were stable in the presence of vitamin E; however, squalene oxidized rapidly in the absence of vitamin E. Liquids on the human skin surface consist of sebum and sweat with minor amounts of cellular debris and intercellular lipid from the stratum corneum. The relative importance of each component for release of chemicals from materials in contact with skin will depend upon the type of material (metal, organic, etc.). A model artificial sebum was formulated and characterized to aid researchers in understanding potential release of chemicals from materials in contact with skin and subsequent partitioning and absorption.

Fabrication, Characterisation and Tribological Investigation of Artificial Skin Surface Lipid Films

This article deals with the tribology of lipid coatings that resemble those found on human skin. In order to simulate the lipidic surface chemistry of human skin, an artificial sebum formulation that closely resembles human sebum was spray-coated onto mechanical skin models in physiologically relevant concentrations (5–100 μg/cm2). Water contact angles and surface free energies (SFEs) showed that model surfaces with ≤25 μg/cm2 lipids appropriately mimic the physico-chemical properties of dry, sebum-poor skin regions. In friction experiments with a steel ball, lipid-coated model surfaces demonstrated lubrication effects over a wide range of sliding velocities and normal loads. In friction measurements on model surfaces as a function of lipid-film thickness, a clear minimum in the friction coefficient (COF) was observed in the case of hydrophilic, high-SFE materials (steel, glass), with the lowest COF (≈0.5) against skin model surfaces being found at 25 μg/cm2 lipids. For hydrophobic, low-SFE polymers, the COF was considerably lower (0.4 for PP, 0.16 for PTFE) and relatively independent of the lipid amount, indicating that both the mechanical and surface-chemical properties of the sliders strongly influence the friction behaviour of the skin-model surfaces. Lipid-coated skin models might be a valuable tool not only for tribologists but also for cosmetic chemists, in that they allow the objective study of friction, adhesion and wetting behaviour of liquids and emulsions on simulated skin-surface conditions.

Comparison of artificial sebum with human and hamster sebum samples

To understand drug delivery to the sebum filled hair and sebaceous follicles, it is essential to use an artificial sebum as a surrogate of the human sebum for the investigation of drug transport properties. Artificial sebum L was developed in-house based on the chemical similarity to human sebum. The partition and diffusion of model compounds (ethyl 4-hydroxybenzoate, butyl 4-hydroxybenzoate, and hexyl 4-hydroxybenzoate) were measured in human sebum, hamster ear and body sebum (a commonly used animal model), and four representative artificial sebum samples (N, S, F, and L) in which artificial sebums, N, S and F were selected based on the available literature. DSC and NMR studies were also conducted on all sebums to compare their melting properties and chemical compositions. In vitro studies show that the partition coefficients of the three model compounds in artificial sebum L were similar to that of human sebum, whereas the hamster ear and body sebum, and other three artificial sebum samples were different from that of human sebum. Additionally, the in vitro sebum flux (μg/(cm 2 min) of three model compounds through artificial sebum L was closer to that of human sebum when compared with the other three artificial sebum (N, S and F), hamster body and hamster ear sebum. The results of this study indicate that the artificial sebum L could be used as an alternative to human sebum, as the physicochemical properties of this artificial sebum is relatively similar to human sebum.

Investigation of drug partition property in artificial sebum

Targeted delivery of a therapeutic agent into the hair and sebaceous follicles greatly depends on the extent of drug partitioning/diffusion in the sebum. The objective of the present research was to develop a method to determine the sebum partition coefficient in order to facilitate the selection of sebum-targeted drug candidates. Partition coefficients of model drugs with different chemical structures and 4-hydroxybenzoate series compounds were measured in artificial sebum/water ( K sebum) and human stratum corneum/water ( K sc) at 37 °C. The relationship was evaluated between log K sebum, log K sc and clog P. The results of the partition coefficient studies indicate that the K sebum of some drugs was significantly higher than the K sc, whereas some drugs showed lower or similar K sebum when compared with K sc. Overall, a relatively poor correlation was observed between log K sebum, log K sc and clog P. However, a linear relationship exists between log K sebum and clog P in the 4-hydroxybenzoate series compounds, indicating that K sebum depends on the lipophilicity and chemical structure of the compounds. The results of the present study demonstrate that K sebum is different from K sc and calculated P and is likely to be a critical parameter reflecting drug delivery into hair and sebaceous follicles.

Diffusion properties of model compounds in artificial sebum

Sebaceous glands secrete an oily sebum into the hair follicle. Hence, it is necessary to understand the drug partition and diffusion properties in the sebum for the targeted delivery of therapeutic agents into the sebum-filled hair follicle. A new method was developed and used for determination of sebum flux of topical therapeutic agents and other model compounds. The drug transport through artificial sebum was conducted using sebum loaded filter (Transwell) as a membrane, drug suspensions as donor phases and HP-beta-CD buffer solution as a receiver phase. The experiment was performed at 37 degrees C for 2h. The results of the drug transport studies indicate that the flux (J(sebum)) through the artificial sebum is compound dependent and a bell-shaped curve was observed when logJ(s) versus alkyl side chain length of the compounds that proved to be different from the curves obtained upon plotting logJ skin versus clogP for the same compounds, indicating the possibility to select appropriate compounds for sebum targeted delivery based on the differences in the skin flux and sebum transport profiles of the molecules.

Surfactant Protein Expression in Human Skin: Evidence and Implications

The presence of surfactant proteins (SPs), critical to local barrier and defense functions and usually associated with the lung, was revealed in adult and fetal human skin complementary deoxyribonucleic acid, in skin samples from three adult female donors and also in cultured fibroblasts, keratinocytes, and melanocytes. Using reverse transcription-PCR, SP-A, SP-B, SP-C, and SP-D messenger ribonucleic acid expression was detected to varying extents in the different skin sources. The stronger expression of SP-C in fetal skin, compared to adult skin, suggested that the role of this protein alters with age. Immunohistochemical studies showed variable distribution of SPs in human epidermis and dermis, confirming that these proteins are indeed translated and expressed in skin tissue. In vitro studies showed that the surface tension of SP-deficient artificial sebum is (a) lowered by skin-extracted SP-B and (b) further reduced to a level comparable to normal sebum by the additional presence of skin-extracted SP-A and SP-D, consistent with their surface tension-lowering capabilities in lung. The possible roles of SPs in skin, based on their known functions in the lung are discussed. However, their potential as therapeutic targets or diagnostic markers of skin disease remains to be elucidated.

Preliminary assessment of alginic acid as a factor buffering triethanolamine interacting with artificial skin sebum

Triethanolamine is an ethanolamine used as counter-ion for fatty acid soaps. Interaction between triethanolamine and free fatty acids is suggested to be useful for cleansing sebaceous follicles in acne prevention. This study describes the preliminary assessment of alginic acid as a factor buffering triethanolamine interacting with stearic acid – a compound of artificial skin sebum. Penetration of triethanolamine into artificial sebum, induced by the above mentioned interaction, was measured using a specific optical method. The values of the penetration depth amounted to 0.07–5.74 mm. pH values were measured. The value of pH is reduced from 10.06 for pure 1.49% (w/w) aqueous triethanolamine solution to 6.61 with the increase of the alginic acid to triethanolamine ratio in the preparations. The data of this in vitro research will support further study on other anionic polymers as factors buffering ethanolamines penetrating artificial skin sebum.

Lipid distribution on textiles in relation to washing with lipases

AbstractEffectiveness of lipase in detergency was studied using three test soils (lard, artificial sebum, and olive oil) on a woven cotton fabric. Distribution of oily soil on fabrics was determined for three different treatments (unwashed, washed with detergent without lipase, and washed with detergent plus lipase). Osmium tetroxide was used to label lipid soil for analysis in the scanning electron microscope. Both longitudinal and cross‐sectional backscattered electron images for unwashed samples showed that soil was present on surfaces of the cotton fibers and in interfiber spaces of the yarn bundle. Lard soiled samples had large deposits on the fabric surfaces, while artificial sebum and olive oil appeared more uniformly distributed throughout the textile. Oil was deposited in the interfiber capillaries of the yarn bundle and in the crenulation, secondary walls, and lumen of the fibers. Energy dispersive X‐ray microanalysis was used to determine relative concentrations of oil at selected morphological locations within the fiber structure and at the fiber surface. Soil distributions within the fibrous structures differed with type of soil and laundry treatment. Backscattered electron images dramatically demonstrated the effect of lipase on cleaning. After washing with detergent plus lipase, yarn surfaces had much less residual soil; residual soil that remained was in the irregularities of the cotton fiber surfaces. Concentrations of oil in the secondary walls, crenulations, lumen, and the fiber surfaces were lower after lipase treatment for all three soils. While washing with detergent removed soil from the yarn and fiber surfaces and the crenulation of the cotton fiber, only the samples washed with detergent plus lipase had lower concentrations of soils within the secondary wall and lumen of the cotton fibers. Fabrics soiled with olive oil and washed with detergent plus lipase had the lowest concentrations of residual soil across the textile structure; the residual soil observed was mainly in the irregularities on the fiber surfaces.

Effect of fiber substrates on appearance and removal of aged oily soils

AbstractAging of oily soils produces difficult‐to‐remove yellow stains on fabrics. This study examines the effect of different textile substrates on yellowing and removal of aged oily soils. Model oily, squalene and artificial sebum, were aged at 40°C on cotton, nylon, and polyester fabrics for 8 wk. Radiotracer and spectrophotometric analyses were used to quantify volatilization and color change of soiled fabrics upon aging as well as soil and color removal after laundering. Differences in volatility of oils from three substrates were insignificant, although cotton and nylon fabrics produced significantly more yellowness than polyester fabrics. Aging of oily soil enhanced detergency from all three fabrics. The largest increase in removal upon aging was found with cotton. Difference in removal from the three substrates became very small after aging. The effect of substrate was pronounced on yellowing due to aging with cotton and nylon having higher yellowness indices. Cotton visually appeared to be cleaner than indicated by the actual amount of residual oil present after washing, whereas nylon had less residual oil present even though it visually appeared more yellow than cotton. For polyester, the amount of residual oil correlated well with appearance after washing. We conclude that discoloration mechanisms differ among cotton, polyester, and nylon substrates. For polyester, discoloration is solely discoloration of oily soil that is physically bound in the fibrous structure, whereas for cotton, discoloration is a result of discoloration of oil as well as additional yellowing caused by retention of chromophores chemically bound to the cotton substrate. In the case of nylon, yellowing of nylon itself is an additional factor contributing to yellowness even though, most of the oil is removed upon washing. These results illustrate the importance of the method of detergency evaluation. Measuring color change in yellowness or reflectance is not the same as oil removal based on a quantitative measurement of soil mass. Thus, it may be necessary to measure both color and quantity of residual soil.

In Vitro Investigation of the Synthetic Sebum Adsorbing Efficacy of Acrylate Copolymer as an Excipient And In Clinac ™ Oc

Abstract While sebum provides several functions in the integument, there is considerable interest in the control of excess sebum on the human skin. The primary function of sebum is to lubricate and waterproof the stratum cornenum layer, in addition to preventing hair from becoming brittle. In several cases, the secretion of sebum is inhibited as a result of blockage of the drainage pathway for the sebaceous glands which may result in abnormal skin conduction (1,2). Clinac™ OC (Oil Control) has been developed with a special oil adsorbing polymer, DVB/lsobornyl Methacrylate/Lautyl Methacrylate Copolymer (3). This particular copolymer posses the capacity to adsorb oils because of its high affinity for hydrophobic nonpolar substances. The purpose of this investigation is to show the adsorptive capacity of the acrylate copolymer in Clinac™ OC preparation and in buffer. The acrylate polymer was incubated in artificial sebum for 4 hrs and 8 hrs at 37 C.

Aging of oily soils on textiles. Chemical changes upon oxidation and interaction with textile fibers

AbstractAging of unsaturated oily soils on textile materials produces yellow compounds that are difficult to remove by washing. To investigate changes that occur in oily soils when aged, the aging of squalene and artificial sebum were studied. Proton nuclear magnetic resonance, infrated spectroscopy, gas chromatography, and gel permeation chromatography studies showed that oily soils were oxidized upon aging, forming low molecular weight products that also polymerized to higher molecular weight compounds with prolonged aging. The oxidation products contained hydroxyl, carbonyl, or ester groups. Oxidation compounds with yellow chromophores appeared to be mostly those of the 1000–2500 molecular weight fraction; though in earlier, stages of aging, lower molecular weight fractions also contained chromophores. By using glucose as a model compound of cellulose, it was found that yellow oxidation products of aged squalene were covalently bound to the substrate. Because the aging of oily soils is a free‐radical oxidation process, oxidation products having chromophores are thought to attach to the cotton substrate through radical coupling. Oily soils also showed possibilities of chemical bonding with nylon but not with polyester.

Site-specific drug delivery to pilosebaceous structures using polymeric microspheres.

In order to improve the therapeutic index of adapalene, a new drug under development for the treatment of acne, site-specific delivery to the hair follicles using 50:50 poly(DL-lactic-co-glycolic acid) microspheres as particulate carriers was investigated in vitro and in vivo. The percutaneous penetration pathway of the microspheres was shown to be dependent on their mean diameter. Thus, after topical application onto hairless rat or human skin, adapalene-loaded microspheres (5-microns diameter) were specifically targeted to the follicular ducts and did not penetrate via the stratum corneum. The in vitro release of adapalene from the microspheres into artificial sebum at 37 degrees C was controlled and faster than the in vivo sebum excretion in humans. Aiming to reduce either the applied dose of drug or the frequency of administration, different formulations of adapalene-loaded microspheres were evaluated in vivo in the rhino mouse model. A dose-related comedolytic activity of topical formulations of adapalene-loaded microspheres was observed in this model. Furthermore, by applying a site-specific drug delivery system (0.1% adapalene) every other day or by administering a 10-fold less concentrated targeted formulation (0.01%) every day, a pharmacological activity equivalent to a daily application of an aqueous gel containing drug crystals (0.1% adapalene) was observed. Since an aqueous gel containing 10% adapalene-loaded microspheres was not irritating in a rabbit skin irritancy test, this formulation was applied onto forearms of human volunteers. Site-specific drug delivery was further evidenced by follicular biopsy. Since an aqueous gel containing 10% adapalene-loaded microspheres was not irritating in a rabbit skin irritancy test, this formulation was applied onto forearms of human volunteers. Site-specific drug delivery was further evidenced by follicular biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

An original procedure for quantitation of cutaneous resorption of sebum

This paper describes an original in vivo device to investigate and quantify cutaneous resorption of sebum. Such a phenomenon was explored using a photometric determination of residual skin surface lipids at different times following initial deposits of known amounts of artificial sebum on demarcated areas. The technique was carried out on seven healthy subjects. The chosen area was the anterior aspect of the forearm, owing to the very low sebum production of this site, less than the sensitivity of the measuring instrument. The kinetics of absorption of applied sebum turned out to be hyperbolic-like and well correlated with experimental results (r = 0.992), allowing a mathematical determination of the initial velocity of penetration of sebum into the skin, reaching 20 micrograms/cm2.min for a standard program including a mean initial deposit of 116 micrograms/cm2. This kinetics actually does not fit with a true percutaneous absorption of lipids but is compatible with that of absorption into the stratum corneum. It conveys the faster absorption of the latter for sebum, a well-known but not so far quantified property of stratum corneum. The model here described is not at once transposable to skin areas with high sebum production since, quite obviously in such zones, the stratum corneum is permanently saturated with skin surface lipids. Therefore, the conclusions of this work cannot be correlated with the regreasing parameters studied so far on the forehead, but they provide interesting data about the evolution of sebum following its output onto the skin surface and therefore a better understanding of sebaceous physiology.