Stratum corneum increasing permeability

Coupling of maeroseopie and molecular investigations of thermally induced alterations of hairless mouse stratum corneum provide insight into molecular structure and barrier functions of the stratum corneum. Enhanced permeabilities below 70°C have been associated with increased lipid fluidity. However, the keratinized protein component of stratum corneum experiences only minor tertiary structural alterations with thermal pretreatments above 70°C. 

Any treatment that thins the stratum corneum increases the permeability of the epidermis and the speed of penetration of AHA. Tretinoin, AHA creams and benzoyl peroxide are all examples of products that allow AHAs to penetrate more deeply. 

While water content of the stratum corneum affects permeability of the tissue, hydration also impacts various physical properties of the membrane such as tensile strength and elasticity, modihes the microenvironment for microorganisms on the tissue surface, alters the thermal conductivity of the tissue and also affects skin appearance. Further, increasing hydration also alters the thickness of the stratum corneum as shown in Figure 4, again taken from data provided by Blank et al. (1984). 

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. 

The third class of lipids found in stratum corneum extracts is represented by cholesterol and cholesteryl esters. The actual role of cholesterol remains enigmatic, and no clear reason for its role in the barrier function has been proposed so far. However, it is possible that contrary to what is the role in cell membranes where cholesterol increases close packing of phospholipids, it can act as kind of a detergent in lipid bilayers of long-chain, saturated lipids.30,31 This would allow some fraction of the barrier to be in a liquid crystalline state, hence water permeable in spite of the fact that not only ceramides, but also fatty acids found in the barrier are saturated, long-chain species.28,32... 

Tanno, O. et al., Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier, Br. J. Dermatol., 143, 524, 2000. 

The face is the most common site for cosmetic reactions, particularly in the eyelid area.4 5 9 Facial skin is highly permeable, due to a thinner stratum corneum and a greater density of appendages (e.g., sweat glands, hair follicles). Moreover, facial skin contains an elaborate network of sensory nerves. The frequency of cosmetic application is also increased at this body site. Although mild inflammatory changes are often masked on the face, in the event that eruptions do occur, they are readily noticed by the consumer. 

In order to increase the number of drugs which can be administered transdermally, the barrier function of the skin must be reduced. The kinetic model can be used to assess the role of a penetration enhancer as a function of the physicochemical properties of the drug. In its simplest form a penetration enhancer may be considered to act in one of two ways. Firstly it may increase the permeability of the skin and, secondly, it may additionally modify the partitioning characteristics at the stratum corneum-viable tissue interface. For illustration, two enhancers have been arbitrarily chosen, the first PE1 increases the permeability by a factor of 10, i.e. k- is increased ten fold. The second, PE2, increases k- by a factor of 10 and decreases kg by a similar amount. Thus PE2 additionally reduces the partition coefficient by a factor of 10. The relative effects can be seen by considering two model drug... 

A new theoretical model will now be described aimed at attempting to provide a possible explanation for the deviations observed in Figure 3. The model assumes that significant porosity prevails in the hairless mouse stratum corneum when ethanol is present. Although it can be assumed, that at low ethanol concentrations (below 50%) ethanol fluidizes lipid bilayers, there is evidence, that ethanol at high concentration (over 50%) may induce significant pore formations in hairless mouse stratum corneum as measured by the substantial increase of tetraethylammonium bromide permeabilities (10). The permeability coefficient P of a solute across a membrane or stratum corneum under steady state conditions may be described by ... 

Calorimetric results for the hairless mouse stratum corneum and isolated components confirmed thermal transitions associated with increased mobility occurred in the temperature region where large increases in permeability of lipophilic components also occurred. Thermal transitions for the extracted lipids were in the 27 to 67°C range, while the protein residue sheets (primarily... 

Differential scanning calorimetric and infrared spectroscopic investigations of intact stratum corneum, extracted lipids and keratinized protein residue sheets suggested the thermal transitions occurring within the 30 to 70°C region were associated with increased molecular mobility of the lipids. The permeability coefficients of lipophilic molecules through hairless mouse skin increased by several orders of magnitude over the same temperature... 

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