Electron Probe Analysis of Human Skin: Determination of the Water Concentration Profile

Warner, R.R.; Myers, M. C.; Taylor, Dennis A.

doi:10.1111/1523-1747.ep12462252

Cited by 328 publications

(218 citation statements)

References 38 publications

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“…Measurements of water concentration in human epidermis have revealed a dramatic reduction in water content at the granular-cornified layer interface, compared with that of the spinous layer (29,30), effectively exposing the granular layer cells to constant hyperosmotic stress. Based on our results, we suggest a model in which Blimp-1 would inhibit the normal cellular response to osmotic stress by repressing nfat5, thereby preventing an NFAT5-dependent increase in intracellular osmolytes and the subsequent water uptake.…”

Section: Discussionmentioning

confidence: 99%

Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1

Magnúsdóttir

Kalachikov

Mizukoshi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

140

158

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The cornified layer is a compacted lattice of lipid-embedded corneocytes that provides an organism's barrier to the external environment. Cornification is the final differentiative step for epidermal keratinocytes and involves dramatic cell condensation before death. Using conditional gene deletion in mice, we identified the transcriptional repressor Blimp-1 (B lymphocyte-induced maturation protein-1) as an important regulator of keratinocyte transition from the granular to the cornified layer. More than 250 genes are misregulated in conditional knockout epidermis, including those encoding transcription factors, signal transduction components, proteinases, and enzymes involved in lipid metabolism. Steady-state mRNA and ChIP analyses of a subset of these genes provide evidence that nfat5, fos, prdm1, and dusp16 are novel direct targets of Blimp-1. Identifying nfat5 as a target of Blimp-1 repression indicates that cornification involves suppression of normal osmotic regulation in granular cells. Consistently, conditional knockout mice have delayed barrier formation as embryos, enlarged granular layer cells and corneocytes, and a morphologically abnormal cornified layer. These studies provide insight into cornification, identifying transcriptional regulatory circuitry and indicating the importance of blocking osmotic homeostasis.cornification ͉ epidermis ͉ prdm1 ͉ transcription factors ͉ nfat5

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Section: Discussionmentioning

confidence: 99%

Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1

Magnúsdóttir

Kalachikov

Mizukoshi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

140

158

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“…Briefly, the rationale for improving the topical delivery of glucocorticoids is based on the capacity of TRS to cross the intact SC following the hydration gradient. 76 The penetration of TRS would cease after entering the viable epidermis and a sub-SC deposit is formed. 14,16,21 Since this penetration is independent of diffusion, the existence of a concentration gradient of active ingredient is no longer relevant.…”

Section: Preclinical Applications As Anti-inflammatory Agentsmentioning

confidence: 99%

Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations

Romero¹,

Morilla²

2013

IJN

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Vesicles that are specifically designed to overcome the stratum corneum barrier in intact skin provide an efficient transdermal (systemic or local) drug delivery system. They can be classified into two main groups according to the mechanisms underlying their skin interaction. The first group comprises those possessing highly deformable bilayers, achieved by incorporating edge activators to the bilayers or by mixing with certain hydrophilic solutes. The vesicles of this group act as drug carriers that penetrate across hydrophilic pathways of the intact skin. The second group comprises those possessing highly fluid bilayers, owing to the presence of permeation enhancers. The vesicles of this group can act as carriers of drugs that permeate the skin after the barrier of the stratum corneum is altered because of synergistic action with the permeation enhancers contained in the vesicle structure. We have included a detailed overview of the different mechanisms of skin interaction and discussed the most promising preclinical applications of the last five years of Transfersomes ® (IDEA AG, Munich, Germany), ethosomes, and invasomes as carriers of antitumoral and anti-inflammatory drugs applied by the topical route.

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“…At the epidermal surface the concentration is often less than 15% but increases deeper into the skin to reach five-times the surface value at the basal skin layers (Warner et al 1988). This transdermal hydration gradient is said to produce a force sufficient to drive the ultradeformable lipid vesicle (transfersome) through the intact stratum corneum and into the epidermis.…”

Section: Ultradeformable Vesicles Transfersomes Have Beenmentioning

confidence: 99%

Untitled

2006

Journal of Pharmacy and Pharmacology

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Using liposomes to deliver drugs to and through human skin is controversial, as their function varies with type and composition. Thus they may act as drug carriers controlling release of the medicinal agent. Alternatively, they may provide a localized depot in the skin so minimizing systemic effects or can be used for targeting delivery to skin appendages (hair follicles and sweat glands). Liposomes may also enhance transdermal drug delivery, increasing systemic drug concentrations. With such a multiplicity of functions, it is not surprising that mechanisms of liposomal delivery of therapeutic agents to and through the skin are unclear. Accordingly, this article provides an overview of the modes and mechanisms of action of different vesicles as drug delivery vectors in human skin. Our conclusion is that vesicles, depending on the composition and method of preparation, can vary with respect to size, lamellarity, charge, membrane fluidity or elasticity and drug entrapment. This variability allows for multiple functions ranging from local to transdermal effects. Application to dissimilar skins (animal or human) via diverse protocols may reveal different mechanisms of action with possible vesicle skin penetration reaching different depths, from surface assimilation to (rarely) the viable tissue and subsequent systemic absorption.

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Electron Probe Analysis of Human Skin: Determination of the Water Concentration Profile

Cited by 328 publications

References 38 publications

Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1

Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1

Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations

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