Stratum corneum deeper layers

A number of works investigated the interaction between niosomes and human skin. With niosomes prepared from Ci2 alcohol polyoxyethylene ether and cholesterol, vesicular structures of about 100 nm size have been observed between the first and second layers of human corneocytes 48 h after incubation as well as in the deeper strata of the skin [37], The authors concluded that the structures visualized in the deeper regions could be vesicles reorganized from individual molecules that penetrated the skin. In another study, electron micrographs illustrated that niosomes containing surfactants and cholesterol affected only the most superficial corneocytes. Moreover, two-photon fluorescence microscopy confirmed that fluorescent probe encapsulated in niosomes was confined to the intercellular spaces within the apical stratum corneum layers [56]. 

The precise mode of interaction between lipid vesicles and skin remains unclear. There is considerable doubt about the ability of whole vesicles to permeate intact stratum corneum. The majority of evidence suggests that vesicles can penetrate the outer cell layers of the stratum corneum where desmosomal linkages have become disrupted and presumably, the keratinocytes are less tightly bound and surrounded by a mixture of intercellular lipid and sebum. However, continuing diffusion of vesicles through the approximately 60 nm intercellular space of the deeper layers of the stratum corneum seems unlikely. Current thinking suggests... 

Athlete s foot is the commonest of a group of topical fungal infections (see Chapter 28) caused by dermatophytes, organisms that invade and proliferate on the outermost horny layer (stratum corneum) of the skin, hair and nails. They do not normally penetrate deeper into the skin or tissues. Dermatophytes tend to thrive in areas of the body that are occluded and moist. 

Only the most superficial layer of the stratum corneum should be removed. Any deeper abrasion that destroys the stratum corneum completely is to be avoided, as the active components of the EPS would penetrate the skin too quickly and soon saturate its defenses, its buffer capacity. When using this abrasive technique, it is essential to have the necessary equipment at hand to neutralize the peel (see the section on neutralizing glycolic acid in Chapter 9) in case it penetrates more deeply than desired. This technique can be repeated at a minimum of 2-weekly intervals only. 

If the abrasion is completely painless, it has only reached the stratum corneum. When it goes deeper and the sandpaper comes into contact with the keratinocytes, it is imcom-fortable but not yet painful, as the upper layers of keratinocytes are not directly innervated. 

The absorption of ZnO from intact skin after topical application is non-detectable. The data on TiOg are controversial. Earlier studies suggested that a very small amount of titanium dioxide may penetrate the skin, but it is unlikely that this would have any biological significance (237). However, a recent in viuo human study, in which skin punch biopsies were collected after application of titanium dioxide, (256) showed that this sunscreen is solely deposited on the outermost surface of the stratum corneum and does not penetrate into the deeper stratum corneum layers, the epidermis or the dermis regardless of the surface properties of the particles (256). 

While topical ALA penetrates the outer layers of intact epidermis very much better than any pre-formed photosensitizers (porphyrins, chlorins, purpurins, or phthalocyanines), it still requires at least several hours for photosensitizing concentrations of PpIX to accumulate within the underlying cells, and even longer if the cells are deeper. Two main approaches to enhancing the penetration of ALA through biological barriers such as the stratum corneum are current topics of research in several laboratories. 

The chitosan and its derivatives show no acute toxicity and are not absorbed via transdermal route. The European pharmacopoeia contains a single monograph on chitosan hydrochloride. In the United States, chitosan is currently being included in the US Pharmacopoeia [Sarmento and das Neves, 2012]. The chitosan and its derivatives are deemed safe for use as permeation enhancer for transmucosal delivery of hydrophilic drugs and offer promising prospects for novel pharmaceutical applications [Junginger and Verhoef, 1998]. Despite the chitosan and its derivatives interact with lipids and proteins of the membranes of stratum corneum, they may not penetrate into deeper layers of the skin. This can be inferred from the absence of skin irritation by chitosan and its derivatives in Draize test [Aoyagi et al., 1991]. 

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 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). 

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