Corneocytes

Jessner s Solution has been used for over 100 years as a therapeutic agent to treat hyperkera-totic epidermal lesions [1]. This superficial peeling agent constitutes a mixture of salicylic acid, resorcinol, and lactic acid in 95% ethanol. Jessner s solution causes loss of corneocyte cohesion and induces intercellular and intracellular edema. Jessner s typically induces wounding to the level of the papillary dermis. Historically, resorcinol (a key component of Jessner s peels) was used in concentrations of 10-50% in the early twentieth century. High concentrations of resorcinol were associated with side effects such as allergic contact dermatitis, irritant contact... 

It is a lipophilic compound which removes intercellular lipids that are covalently linked to the cornified envelope surrounding epithelial cells [3]. It also enhances penetration of other agents. Resorcinol (m-dihydroxy benzene) is structurally and chemically similar to phenol. It disrupts the weak hydrogen bonds of keratin [4]. Lactic acid is an alpha hydroxy acid which causes corneocyte detachment and subsequent desquamation of the stratum corneum [5]. 

Lazo ND, Meine JG, Downing DT (1995) Lipids are covalently attached to rigid corneocyte protein envelope existing predominantly as beta-sheets a solid state nuclear magnetic resonance study. J Invest Dermatol 105 296-300... 

Van Scott EJ,Yu RJ (1984) Hyperkeratinization, corneocyte cohesion, and alpha hydroxy acids. J Am Acad Dermatol 11 867-879... 

Tretinoin 0.05-0.1% which is the most critical component of this regimen as it results in decreased stratum corneum thickness, increases the kinetics of epidermal turnover, and decreases corneocyte adhesion... 

Exfoliants such as glycolic acid or lactic acid result in decreased corneocyte adhesion and stimulate epidermal growth by disrupting the stratum corneum... 

Salicylic acid is one of the most commonly used keratolytics. It causes a disruption in corneocyte-to-corneocyte cohesion in the abnormal horny layer of psoriatic skin. This serves to remove scales, smooth the skin, and decrease hyperkeratosis. The keratolytic effect enhances penetration and... 

The stratum corneum consists of separated, nonviable, cornified, almost nonpermeable corneocytes embedded into a continuous lipid bilayer made of various classes of lipids, for example, ceramides, cholesterol, cholesterol esters, free fatty acids, and triglycerides [6], Structurally, this epidermis layer is best described by the so-called brick-and-mortar model [7], The stratum corneum is crucial for the barrier function of the skin, controlling percutaneous absorption of dermally applied substances and regulating fluid homeostasis. The thickness of the stratum corneum is usually 10-25 /an, with exceptions at the soles of the feet and the palms, and swells several-fold when hydrated. All components of the stratum corneum originate from the basal layer of the epidermis, the stratum germinativum. 

Under normal conditions, the transcellular route is not considered as the preferred way of dermal invasion, the reason being the very low permeability through the corneocytes and the obligation to partition several times from the more hydrophilic corneocytes into the lipid intercellular layers in the stratum corneum and vice versa. The transcellular pathway can gain in importance when a penetration enhancer is used, for example, urea, which increases the permeability of the corneocytes by altering the keratin structure. 

Drug levels within the stratum corneum can be assessed by sampling single corneocyte layers with adhesive film. The drug is then extracted from the tape-strips and quantified by a suitable analytical method. Usually, scintillation counting (for radioactive compounds) or high performance liquid... 

Mechanism of Action Lactic acid is an alpha-hydroxy acid that influences hydration, decreases corneocyte cohesion, reduces excessive epidermal keratinlzation in hyper-keratotic conditions, and induces synthesis of mucopolysaccharides and collagen In photodamagedskin. The exact mechanism is not known TherapeuticEffect Increases hydration of the skin. 

FIGURE 2.2 A diagram of human skin. Epidermal thickness depends upon body site being thickest on the palms and soles (-1500 pm) and thinnest around the eyes (-10 pm). The stratum corneum is the only layer composed of anucleated, terminally differentiated kerati-nocyte cells called corneocytes. All other epidermal layers contain nucleated keratinocytes. The dermis is composed primarily of the structural proteins collagen and elastin. 

The innermost layer of the epidermis, the stratum basale, consists of a single layer of columnar-shaped, undifferentiated stem cells. Mitosis of these cells constantly renews the epidermis and this proliferation compensates for the loss of dead stratum corneum cells (corneocytes) from the skin surface. As the cells produced by the basal layer move upward, they alter morphologically as well as histochemically to form the outermost layer, the stratum corneum. Over a 4- to 5-week period the entire epidermis is renewed [5]. 

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. 

During the transition of the mature keratinocyte into the corneocyte, profilaggrin that is released from the keratohyalin granules is dephosphorylated and proteolytically processed to filaggrin monomers. Filaggrin is responsible for the formation of extensive disulfide bonds... 

The lipid composition changes dramatically during terminal differentiation. After extrusion from the lamellar bodies, the polar lipid precursors are enzymatically converted into more hydrophobic lipids. As a result, phospholipids are almost absent in the stratum corneum. The lipid lamellae surrounding the corneocytes are predominantly composed of ceramides, cholesterol, and free fatty acids. It is generally assumed that these lipids are present in nearly equimolar ratios. However, inspection of literature data shows that there is a high interindividual variability in the lipid composition [37],... 

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