Human epidermal lipids: characterization and modulations during differentiation

Lampe, Marilyn A.; Williams, Mary L.; Elias, Peter M.

doi:10.1016/s0022-2275(20)38006-8

Cited by 337 publications

(48 citation statements)

References 29 publications

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“…This is due to that it is more easy to interpret the data from ex vivo permeation experiment using hairless mouse skin (Chantasart et al, 2004 ) due to the relatively constant lipid content of the stratum corneum for hairless mouse skin compared to the various lipid content of human skin (Raykar et al, 1988 ). Furthermore, the lipid composition of hairless mouse skin (Muller et al, 2002 ) is similar to that of human skin (Lampe et al, 1983 ). Therefore, in this study, hairless mouse skin was used to differentiate the between the permeation of etodolac from the tested cubosomes.…”

Section: Ex Vivo Skin Permeation Studiesmentioning

confidence: 89%

Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies

2017

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In this study, transdermal etodolac-loaded cubosomes were developed in order to relieve patient pain and joints stiffness by providing stable etodolac concentration at the targeting sites through controlled drug delivery via the noninvasive skin route with more sustaining and less frequent dosing. Different ratios and percentages of poloxamer 407 and monoolein were used to formulate the cubosomes using emulsification and homogenization processes. The etodolac-loaded cubosomes showed particle size values ranging from 135.95 to 288.35 nm and zeta potential values ranging from -18.40 to -36.10 mV. All the cubosomes offered an encapsulation efficiency value of about 100% and showed drug loading capacity ranging from 1.28 to 6.09%. The in vitro drug release studies revealed a controlled drug release profile with a drug release rate up to 15.08%/h. Increasing poloxamer concentration in etodolac-loaded cubosomes resulted in nanoparticles with less particle size and faster drug release. The particles exhibited cubic and hexagonal shapes. The DSC and X-ray analysis demonstrated that the drug was encapsulated in the cubosomes bicontinuous structures in amorphous form. In addition, investigated cubosomes exhibited fast drug penetration through excited mice skin followed by slower drug penetration for up to 24 h. The pharmacokinetic study in human volunteers showed that the selected etodolac-loaded cubosomes enhanced the bioavailability of etodolac as compared to the oral capsules (266.11%) with evidence of longer half-life and higher MRT that reached 18.86 and 29.55 h, respectively. The etodolac-loaded cubosomes propose a promising system for treatment of arthritis simply through skin application.

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Section: Ex Vivo Skin Permeation Studiesmentioning

confidence: 89%

Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies

2017

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“…During the transition from the basal proliferating epidermal layer to the outer cornified layer, the phospholipidneutral lipid mixture is replaced by ceramides, cholesterol, and free fatty acids (1)(2)(3)(4), and the total amount of lipids increases. In the SC, these lipids are localized to the intercellular spaces, where they form lamellar membrane structures, which are essential for epidermal permeability barrier function.…”

Section: Discussionmentioning

confidence: 99%

“…These lipids appear to provide the barrier against excess water loss and to limit the in-gress of xenobiotics. The ceramide-cholesterol-free fatty acid mixture replaces a phospholipid-neutral lipid mixture during the transition of keratinocytes from the stratum granulosum to the SC (1)(2)(3)(4). A number of lipid catabolic enzymes, including sphingomyelinase (5), phospholipase A (6), triacylglycerol hydrolase (5,7), and steroid sulfatase (8) have been localized in sites where these transformations occur.…”

mentioning

confidence: 99%

β-Glucocerebrosidase activity in mammalian stratum corneum

Takagi

Kriehuber

Imokawa

et al. 1999

Journal of Lipid Research

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Although previous studies have demonstrated a crucial role for the enzyme ␤ -glucocerebrosidase (GlcCer'ase) in the final steps of membrane structural maturation in mammalian stratum cornuem (SC) and epidermal homeostasis, the precise in vivo localization of GlcCer'ase activity and protein is not known. Here, we developed a fluorogenic in situ assay on histologic sections (zymography) to elucidate the in vivo distribution of GlcCer'ase activity, and further characterized and localized the SC GlcCer'ase activity in vitro. The zymographic technique revealed higher GlcCer'ase activity in upper stratum granulosum and SC, both in murine and human SC; activity that was both inhibited by conduritol B epoxide, a specific GlcCer'ase inhibitor, and pH-dependent; i.e., present at pH 5.2, and absent or significantly reduced at neutral pH (7.4), consistent with the known pH optimum for epidermal GlcCer'ase in vitro. Immunohistochemical staining for GlcCer'ase protein showed enhanced fluorescent signal in the outer layers of human epidermis, concentrated at the apex and margins of stratum granulosum and lower SC. Moreover, in extracts from individual epidermal layers, GlcCer'ase activity was present throughout murine epidermis, with the highest activity in the SC, peaking in the lower-to-mid-SC. The SC activity was stimulated Ͼ 10-fold by sodium taurocholate, and inhibited by bromoconduritol B epoxide. Finally, isolated membrane couplets, prepared from SC sheets, also demonstrated significant GlcCer'ase activity. These data localize GlcCer'ase activity to the outer epidermis by three different techniques, and support the role of this enzyme in extracellular processing of glucosylceramides to ceramides, required for permeability barrier maturation and function. -Takagi, Y.

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“…During the migration of keratinocytes from the basal layer to the stratum corneum, a substantial shift in lipid composition takes place (reviewed by Schurer and Elias, 1991;Wertz and Downing, 1991). These changes include a progressive depletion in phospholipids and glycosphingolipids, concomitant with an enrichment in ceramides, cholesterol, free fatty acid, and small amounts of cholesterol sulfate and cholesterol esters (Lampe et al, 1983). These specialized lipids, which constitute the structural components of the epidermal permeability barrier, are secreted into the extracellular space by speci®c cell organelles: the lamellar bodies or membrane coating granules (MCG) (Landmann, 1986).…”

mentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptor-α Enhances Lipid Metabolism in a Skin Equivalent Model

Rivier

Castiel

Safonova

et al. 2000

Journal of Investigative Dermatology

111

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Peroxisome proliferator-activated receptors are involved in certain cell types such as adipocytes and hepatocytes, in the control of several pathways of lipid synthesis or catabolism by regulating the gene expression level of key lipid metabolizing enzymes. As the epidermis exhibits an extensive lipid metabolism necessary for the establishment of the barrier function, we have examined the role of peroxisome proliferator-activated receptor-alpha activation in this process. Living skin equivalents were treated with Wy 14,643, a selective peroxisome proliferator- activated receptor-alpha ligand, which enhanced greatly the synthesis of membrane coating granules, the organelles specialized in the processing of stratum corneum lipids. Also, the overall stratum corneum neutral lipid content assessed by Oil red O staining was increased. A detailed analysis of the lipid species present in the reconstructed epidermis showed that peroxisome proliferator-activated receptor-alpha activation increased the synthesis of ceramides and cholesterol derivatives, thought to be essential structural components of the permeability barrier. A synergistic effect was observed on lipid synthesis when peroxisome proliferator-activated receptor-alpha and retinoid X receptor were simultaneously activated by selective ligands. Furthermore, activation of peroxisome proliferator-activated receptor-alpha led to increased mRNA expression of several key enzymes of ceramide and cholesterol metabolism. An increase of serine-palmitoyl transferase and of beta-glucocerebrosidase enzymatic activity was also demonstrated. Altogether, these results show that peroxisome proliferator-activated receptor-alpha is a key transcription factor involved in the control of the epidermal lipid barrier.

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Human epidermal lipids: characterization and modulations during differentiation

Cited by 337 publications

References 29 publications

Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies

Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies

β-Glucocerebrosidase activity in mammalian stratum corneum

Peroxisome Proliferator-Activated Receptor-α Enhances Lipid Metabolism in a Skin Equivalent Model

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