Stratum corneum penetration pathways through

STRATUM CORNEUM BARRIER LIPIDS 11.3.1 Penetration Pathway through the Stratum Corneum... 

There is today a consensus about penetration pathways through the skin barrier (Bodde et al. 1990). Under normal conditions, the corneocytes are permeable essentially only to water, which implies that the transport route for hydrophilic and hydrophobic substances is via the extracellular space of the stratum corneum. The lipids of this space are organised in bilayers stacked on top of each other. The corneocyte envelopes have long-chain ceramides covalently bound to their surfaces... 

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. 

To pass into the skin, the substance must enter through one or more of the following routes the epidermal cells, the sweat glands, the sebaceous glands, or the hair follicles. The pathway through the stratum corneum and the epidermal cells is the main avenue of penetration, as this tissue constitutes the majority of the surface area of the skin. 

FITC-Bac) delivered in vivo from ethosomes, penetrated the rat skin through the intercor-neocyte pathways, which typically exist along the lipid domain of the stratum corneum [95] (Figure 13.7). In contrast, significantly lower fluorescence staining of the intercellular penetration pathway and no inter- or intracorneocyte fluorescence were observed with FITC-Bac hydroethanolic solution and liposomes, respectively. 

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. 

For compounds that have either a very low diffusion coefficient or a very low lipid-water partition coefficient, the lipid barrier of the stratum corneum is a formidable impediment to penetration through the skin. However, for such compounds it has been observed that there is no longer a correlation between skin permeation and lipid solubility further, there also appears to be little dependence on molecular weight. It has therefore been hypothesized that such compounds make use of an alternative, low-permeability, and essentially aqueous pathway through the stratum corneum. Although direct physical evidence for such pores is lacking, the notion of a... 

A schematic representation of the multicomponent structure of the skin that takes these multiple barri-ers/pathways into account is shown in Figure 2. When penetration through the stratum corneum (including the parallel polar pathways) and through the aqueous layers in series with the stratum corneum are taken into account and combined with clearance into the bloodstream, the overall dermal penetration coefficient fCp(cmh ) for such a (simplified) composite system is given (by analogy with electrical... 

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