Stratum corneum lipid bilayers

Tezel and Mitragotri [66] describe a theoretical analysis of the interaction of cavitation bubbles with the stratum corneum lipid bilayers. Three modes were evaluated—shock-wave emission, microjet penetration into the stratum corneum, and impact of microjet on the... 

Tezel, A., and S. Mitragotri. 2003. Interactions of inertial cavitation bubbles with stratum corneum lipid bilayers during low-frequency sonophoresis. Biophys J 85 3502. 

Kirjavainen, M., Monkkonen, J., Saukkosaari, M. etal. Phospholipids affect stratum corneum lipid bilayer fluidity and drug partitioning into the bilayers. J. Control. Release 1999 58 207-14. 

The cubic and hexagonal phases based on GMO/water and GMO/oleic acid/ water, respectively, are well studied and were shown to have the ability to sustain the release of incorporated compounds [59, 67, 68]. Moreover, each component constructing either the cubic or the hexagonal phase is a penetration enhancer by itself. GMO is known to promote ceramide extraction and enhancement of lipid fluidity in the stratum corneum, and oleic acid is considered to increase epidermal permeability via a mechanism involving perturbation of the stratum corneum lipid bilayers and lacunae formation [69]. 

Of particular interest are membranes prepared of an inert porous support carrying natural or artificial lipids. These coatings may comprise a single component, such as isopropylmyristate or dodecanol [99, 106], or mixtures of comparable composition as the stratum corneum intercellular bilayer [107, 108], Usually, synthetic lipids are used, due to an elaborate isolation procedure for stratum corneum lipids, with limited yield and the necessity of separation of triglycerides, originating from subcutaneous fatty tissue or skin care products [109],... 

Substituting hx = 3.6 cm and K ip/w = K - into Eq. 28 Johnson et al. calculated solute lateral diffusion coefficients in stratum corneum bilayers from macroscopic permeability coefficients. Measurements with highly ionized or very hydrophilic compounds were not performed because of the possible transport along a nonlipoidal pathway. Comparison of the computed Aat values with experimentally determined data for fluorescent probes in extracted stratum corneum lipids [47] showed a highly similar curve shape. The diffusion coefficient for the lateral transport showed a bifunctional size dependence with a weaker size dependence for larger, lipophilic compounds (> 350 Da), than... 

Fig. 5. a Bilayer organisation of the stratum corneum lipids. In the corneocyte, a protein envelope has replaced the lipid cell membrane of the cell of the viable epidermis and some lipids are covalently bound to this envelope (not represented here). Between the hydrophilic head groups of the stacked bilayers resides a water tablet, within which diffusion transport may take place parallel to the skin surface, b A water molecule passing through the skin barrier is visualised to take a conspicuously meandering way through the liquid-crystalline zones of the... 

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. 

The intercellular route is considered to be the predominantly used pathway in most cases, especially when steady-state conditions in the stratum corneum are reached. In case of intercellular absorption, substance transport occurs in the bilayer-structured, continuous, intercellular lipid domain within the stratum corneum. Although this pathway is very tortuous and therefore much longer in distance than the overall thickness of the stratum corneum, the intercellular route is considered to yield much faster absorption due to the high diffusion coefficient of most drugs within the lipid bilayer. Resulting from the bilayer structure, the intercellular pathway provides hydrophilic and lipophilic regions, allowing more hydrophilic substances to use the hydrophilic and more lipophilic substances to use the lipophilic route. In addition, it is possible to influence this pathway by certain excipients in the formulation. 

Johnson ME, Berk DA, Blankschtein D, Golan DE, Jain RK, Langer RS (1996) Lateral diffusion of small compounds in human stratum corneum and model lipid bilayer systems. Biophys J 71 2656-2668. 

Dermal and transdermal delivery requires efficient penetration of compounds through the skin barrier, the bilayer domains of intercellular lipid matrices, and keratin bundles in the stratum corneum (SC). Lipid vesicular systems are a recognized mode of enhanced delivery of drugs into and through the skin. However, it is noteworthy that not every lipid vesicular system has the adequate characteristics to enhance skin membrane permeation. Specially designed lipid vesicles in contrast to classic liposomal compositions could achieve this goal. This chapter describes the structure, main physicochemical characteristics, and mechanism of action of prominent vesicular carriers in this field and reviews reported data on their enhanced delivery performance. 

Chemical PEs have recently been studied for increasing transdermal delivery of ASOs or other polar macromolecules [35]. Chemically induced transdermal penetration results from a transient reduction in the barrier properties of the stratum corneum. The reduction may be attributed to a variety of factors such as the opening of intercellular junctions due to hydration [36], solubilization of the stratum corneum [37, 38], or increased lipid bilayer fluidization [39, 40]. Combining various surfactants and co-solvents can be used to achieve skin penetration, purportedly resulting in therapeutically relevant concentrations of ASO in the viable epidermis and dermis [41]. In summary, it appears feasible to deliver ASO to the skin using a number of different delivery techniques and formulations. 

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... 

A problem that is rarely taken into account is related to the fact that the water concentration shows a conspicuous gradient within the stratum corneum thickness. These factors are likely to influence the physical state of lipids in bilayer formations, and therefore we expect lipid barrier structure to vary within the thickness of the stratum corneum.53... 

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