Epidermis lipid matrix

The outermost layer of the skin, the cornified layer or stratum corneum, has been identified as the principal diffusion barrier for substances, including water [2,3]. It is approximately 10 to 20 pm thick when dry but swells to several times this thickness when fully hydrated [17], It contains 10 to 25 layers lying parallel to the skin surface of nonviable cells, the corneocytes, which are surrounded by a cell envelope and imbedded in a lipid matrix. This architecture is often modeled as a wall-like structure, with the corneocytes as protein bricks embedded in a lipid mortar [18]. Similarly to the viable epidermis, desmosomes (corneodesmosomes) contribute to the cell cohesion. 

In the past decade a number of physical techniques have been used to evaluate the unique barrier properties of mammalian skin [1]. This chapter deals with the use of another physical technique, fluorescence spectroscopy, to study the barrier properties of the human stratum corneum (SC), specifically with respect to the transport of ions and water. The SC is the outermost layer of the human epidermis and consists of keratinized epithelial cells (comeo-cytes), physically isolated from one another by extracellular lipids arranged in multiple lamellae [2]. Due to a high diffusive resistance, this extracellular SC lipid matrix is believed to form the major barrier to the transport of ions and water through the human skin [3-5]. The objective of the fluorescence studies described here is to understand how such extraordinary barrier properties are achieved. First the phenomenon of fluorescence is described, followed by an evaluation of the use of anthroyloxy fatty acid fluorescent probes to study the physical properties of solvents and phospholipid membranes. Finally, the technique is applied to the SC to study its diffusional barrier to iodide ions and water. 

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 Stratum Corneum (Horny Layer). Typically, the stratum corneum comprises only 10 to 15 cell layers and is around 10 p.m thick when dry, although it may swell to several times this thickness when wet (see section 4.1). As with the viable epidermis, the stratum corneum is thickest on the palms and soles and is thinnest on the lips. This thin membrane, consisting of dead, anucleate, keratinised cells embedded in a lipid matrix allows for survival of terrestrial animals without desiccation. The stratum corneum serves to regulate water loss from the body while preventing the entry of harmful materials including microorganisms. The stratum corneum has been represented as a brick and mortar model (Michaels... 

The permeability skin barrier, a highly specialized structure responsible for retaining skin moisture, is localized mainly at the stratum corneum (Rudikoff 1998) however, its formation begins deeper in the epidermis and its constituents are progressively modified during the process of keratinization until they reach their highest efficiency in the five layers of the stratum compactum (Rawlings et al. 1994). The modified keratinocytes - the corneocytes - and the intercellular complex lipid matrix in which they are embedded form this specialized structure, which Elias compared to a bricks and mortar model, in which the corneocytes are the bricks and the lipid matrix the mortar (Elias 1983). 

The lipid matrix is another important feature for barrier function in the epidermis. The arrangement of lamellarlike sheets )delds a barrier to hydrophilic compounds and transcutaneous water transport. Extraction of those lipids from skin with organic solvents reduces barrier function (Hadgraft, 2001). The lamellae, which... 

In order to maintain water effectively within the skin the epidermis undergoes a process of maturation or terminal differentiation to produce a thin, metabolically inert, barrier, the SC. This heterogeneous structure has been likened to a brick wall in which the anucleated nonviable cells, termed corneocytes are represented as bricks embedded in a continuous matrix of specialized intercellular lipids (mortar).2 Each individual corneocyte can be viewed simplistically as a highly insoluble... 

Human skin has a multifunctional role, primary among which is its role as a barrier against both the egress of endogenous substances such as water and the ingress of xenobiotic material (chemicals and drugs). This barrier function of the skin is reflected by its multilayered structure (Fig. 5.1). The top or uppermost layer of the skin known as the stratum comeum (SC) represents the end product of the differentiation process initially started in the basal layer of the epidermis with the formation of keratinocytes by mitotic division. The SC, therefore, is composed of dead cells (comeocytes) interdispersed within a lipid rich matrix. It is the brick and mortar architecture and lipophilic nature of the SC, which primarily accounts for the barrier properties of the skin [1,2]. The SC is also known to exhibit selective permeability and allows only relatively lipophilic compounds to diffuse into the lower layers. As a result of the dead nature of the SC, solute transport across this layer is primarily by passive diffusion [3] in accordance with Pick s Law [4] and no active transport processes have been identified. 

The hair follicle consists of four major components (1) internal root sheath (internal epithehal root sheath), (2) external root sheath (external epithelial root sheath), (3) dermal papilla, and (4) hair matrix. The cells covering the dermal papilla and composing most of the hair bulb are the hair matrix cells. These are comparable to stratum basale cells of regular epidermis except that they are more lipid deficient and produce harder keratin than their epidermal counterparts. 

Skin barrier functions can be mainly attributed to the outermost layer of mammalian epidermis, the stratum corneum (SC). This region consists of dead, cornified cells embedded in a matrix of extracellular lipids, containing mainly ceramides, cholesterol, cholesterol sulphate and free fatty acids. The SC lipids are organized in a specific lamellar, quasi-crystalline structure, which is critical for optimal skin barrier homeostasis. However, formation of the lamellar structure requires presence of the lipid subclasses in a defined ratio, and ceramides by weight comprise roughly 50% of total SC lipids. The structure and formation of the epidermal lipid barrier is explained in Figure 12.15. 

Figure 12.15 Formation of the lipid barrier of human skin. The top layer of the epidermis called stratum corneum is a hornified and inert barrier. Its primary functions are regulation of the skin s moisture content and protection of the underlying tissues against external influences. Due to its structure it is often compared to a brick wall in which the non-viable keratin-filled corneocytes are embedded like bricks in a matrix of intercellular lipids. Synthesis of the stratum corneum lipids starts in deeper skin layers, where lipids (mainly glucosylceramides and sphingomyelin) are produced and packaged in so-called lamellar bodies . During differentiation and maturation, these lipids are enzymatically converted to ceramides and finally assembled into densely packed lamellar structures surrounding the corneocytes and filling the intercellular spaces of the stratum corneum.

The outer layer of the epidermis, the stratum comeum, consists of dead, mainly keratine containing cells that are continuously scaled off. It is considered as a membrane, built from a dense lipid protein matrix. The function of the stratum comeum is to form a barrier to protect underlying... 

Exclusively submicron particles obtained by high pressure homogenization were used in a study which compared skin interaction of GMO-based cubic nanoparticles (with additional vesicular structures as observed by cryo-TEM) with that of other lipidic nanoparticles with compact liquid, crystalline or thermotropic liquid crystalline matrix structure. The cubic nanodispersion, which was stable with respect to particle size for 15 months of storage at room temperature, increased skin permeation of the model substance corticosterone (used in trace amounts in this study) compared to the other types of lipid nanoparticles. Permeation from all lipidic dispersions was, however, lower than from an aqueous solution which was attributed to the retention of a certain fraction of the drug in the lipid nanoparticles. Considering only the drug present in the aqueous phase of the dispersion as available for transport through the epidermis, the presence of cubic GMO particles increased permeation by the factor 2.4. 

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