Outer stratum corneum lipids

Melnik, B., Hollmann, J., Hofmann, U., Yuh, M-S., and Plewig, G. Lipid composition of outer stratum corneum and nails in atopic and control subjects. Arch. Dermatol. Res. 282 549-551 (1990). 

Effect of Moisturizers on the Structure of Lipids in the Outer Stratum Corneum of Humans... 

Normal Lipid Structure of the Outer Stratum Corneum. 354... 

NORMAL LIPID STRUCTURE OF THE OUTER STRATUM CORNEUM... 

Chapter 28 Effect of Moisturizers on the Structure of Lipids in the Outer Stratum Corneum of Humans 351 Keith D. Ertel, Ronald R. Warner, and Ying L. Boissy... 

Skin toxicity is determined by the penetration and transport of the compound being tested through the lipid matrix in the outer skin layers (the stratum corneum)... 

There is substantial history regarding the application of conventional vibrational spectroscopy methods to study the intact surface of skin, the extracted stratum corneum and the ceramide-cholesterol-fatty acid mixtures that constitute the primary lipid components of the barrier. The complexity of the barrier and the multiple phases formed by the interactions of the barrier components have begun to reveal the role of each of these substances in barrier structure and stability. The use of bulk phase IR to monitor lipid phase behavior and protein secondary structures in the epidermis, as well as in stratum corneum models, is also well established 24-28 In addition, in vivo and ex vivo attenuated total reflectance (ATR) techniques have examined the outer layers of skin to probe hydration levels, drug delivery and percutaneous absorption at a macroscopic level.29-32 Both mid-IR and near-IR spectroscopy have been used to differentiate pathological skin samples.33,34 The above studies, and many others too numerous to mention, lend confidence to the fact that the extension to IR imaging will produce useful results. 

To improve topical therapy, it is advantageous to use formulation additives (penetration enhancers) that will reversibly and safely modulate the barrier properties of the skin. Fick s first law of diffusion shows that two potential mechanisms are possible. The two constants that could be altered significantly are the diffusion coefficient in the stratum corneum and the concentration in the outer regions of the stratum corneum. Thus, one of mechanisms of action of an enhancer is for it to insert itself into the bilayer structures and disrupt the packing of the adjacent lipids, thereby, reducing the microviscosity. The diffusion coefficient of the permeant will increase This effect has been observed using ESR and fluorescence spectroscopy [16,17]. 

The stratum corneum has been estimated to contribute 1000 times the diffusional resistance to chemical penetration as the layers beneath it, except for extremely lipid-soluble compounds with tissue/water partition coefficients greater than 400. As in most other epithelial tissues, the two other layers of the skin (dermis and subcutaneous tissue) offer little resistance to penetration. Once a substance has penetrated the outer epithelium, these tissues are rapidly traversed. This may not be true for highly lipid-soluble compounds, because the dermis may function as an additional aqueous barrier preventing a chemical that has penetrated the epidermis from being absorbed into the blood. 

In addition to movement through shunts, polar substances may diffuse through the outer surface of the protein filaments of the hydrated stratum corneum, while nonpolar molecules dissolve in and diffuse through the nonaqueous lipid matrix between the protein filaments. The rate of percutaneous absorption through this intercellular lipid pathway is correlated to the partition coefficient of the penetrant, as presented above in Fick s law. 

The stratum corneum intercellular lipids exist as a continuous lipid phase occupying about 20% of the stratum corneum volume and arranged in multiple lamellar structures. They are composed of cholesterol (27 /o) and ceramides (41 /o), together with free fatty acids (9 /o), cholesteryl esters (10 /o) and cholesteryl sulfate (2 /o) (Table 1). Phospholipids, which dominate in the basal layer, are converted to glucosylceramides and subsequently to ceramides and free fatty acids, and are virtually absent in the outer layers of the stratum corneum. Eight classes of ceramides have been isolated and identified in human stratum corneum but the functions of the individual ceramide types are not fully understood. Similarly, the exact function of cholesterol esters within the stratum corneum lamellae is also elusive but it is theoretically possible that cholesterol esters may span adjacent bilayers and serve as additional stabilizing moieties. 

The precise mode of interaction between lipid vesicles and skin remains unclear. There is considerable doubt about the ability of whole vesicles to permeate intact stratum corneum. The majority of evidence suggests that vesicles can penetrate the outer cell layers of the stratum corneum where desmosomal linkages have become disrupted and presumably, the keratinocytes are less tightly bound and surrounded by a mixture of intercellular lipid and sebum. However, continuing diffusion of vesicles through the approximately 60 nm intercellular space of the deeper layers of the stratum corneum seems unlikely. Current thinking suggests... 

Cevc and Blume, however, suggested that it was possible for whole vesicles to cross intact stratum corneum. The basic premise for this hypothesis was the driving force provided by the osmotic gradient between the outer and inner layers of the stratum corneum and the development of specific mixes of lipids to form modified liposomes termed transfersomes. The requirement for the osmotic gradient to be maintained suggests that transfersomes will not function in occlusive conditions and careful formulation is necessary. Due to their unique structure (a mix of phosphatidyl choline, sodium cholate, and ethanol), transfersomes... 

The remarkable barrier function of the skin is primarily located in the stratum corneum (SC), the thin, outermost layer of the epidermis. The SC consists of several layers of protein-filled corneocytes (i.e., terminally differentiated keratinocytes) embedded in an extracellular lipid matrix. Attached to the outer cor-neocyte envelope are long-chain covalently bound cer-amides that interact with the lipids of the extracellular space. These lipids are composed primarily of free fatty acids, ceramides, and cholesterol arranged in multiple lamellae.f Passive permeation across the SC is believed to occur primarily via the intercellular... 

The effect of age on percutaneous absorption has been examined in vivo in man with variable results. It was postulated (Roskos et al. 1989) that reduced hydration levels and lipid content of older skin may be responsible for a demonstrated reduction in skin permeability where the permeants were hydrophilic in nature (no reduction was seen for model hydrophobic compounds) (Table 14.2). The reduced absorption of benzoic acid demonstrated in the elderly (Rougier 1991) was in line with this suggestion, but not the reduction in absorption of testosterone (lipophilic) (Roskos et al. 1986), or lack of change in the absorption of methyl nicotinate (more hydrophilic) with age (Guy et al. 1983). There are a number of potential physiological changes which may be responsible for age-related alterations, including an increase in the size of individual stratum corneum corneocytes, increased dehydration of the outer layers of the stratum corneum with age, decreased epidermal turnover and decreased microvascular clearance (reviewed in Roskos and Maibach 1992). The issue of age-related variability, however, is far from resolved. 

Surface lipids in the form of waxes have much to do with limiting drying rates to values below lethality. Plants have a water barrier composed of cutin, embedded waxes and pectin. Insects and other arthropods have embedded wax in their outer chitin layer. Amphibians have skin that is very permeable to water movement in order to absorb water from their environments. When spending time in the sun or in the ground, however, they either spread exuded lipids on their skins, or else form an impermeable skin layer. Reptiles use keratin as their principal water barrier. Mammals have a thin lipid film that covers their outer skin layer, the stratum corneum (Hadley, 1980). 

The stratum corneum is the outer most layer of nonviable epidermis. It has a thickness of about 10 to 12 pm. The stratum corneum consists of 15 to 25 layers of flattened, stacked, hexagonal, and cornified cells known as corneocytes. Each cell is approximately 40 pm in diameter and 0.5 pm in thickness [Bouwstra, 1997]. The thickness of stratum corneum varies with the site of human body. The body extremities such as palms and soles have a thicker stratum corneum [Walters and Roberts, 2002]. The stratum corneum is characterized by an array of keratin-rich corneocytes surrounded by lipid lamella made of cholesterol, free fatty acids, and ceramides [Bouwstra, 1997]. The corneocytes are arranged in brick and mortar structure. Such structural arrangement creates a tortuous intercellular diffusion pathway for water or any other molecules that transverse the stratum corneum. The hydrophobic lipids that surround these diffusion paths or water pores are organized in tight lamellar structure. The summative effects translate to the formation of a tight permeation barrier [Menon, 2002]. 

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