Novel method to observe subtle structural modulation of stratum corneum on applying chemical agents

Hatta, Ichiro; Nakazawa, Hiroyuki; Obata, Yasuko; Ohta, Nobuhiro; Inoue, Katsuaki; Yagi, Naoto

doi:10.1016/j.chemphyslip.2010.02.005

Cited by 50 publications

(53 citation statements)

References 24 publications

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“…21) Hatta et al proposed that EtOH applied to the stratum corneum disrupted the orthorhombic hydrocarbonchain packing structure, and partially disrupted the structure of soft keratin in the corneocytes to form EtOH pools in the intercellular lipid matrix and was a transcellular pathway for hydrophilic molecules. 22) Furthermore, EtOH might cause a protein denaturation in the stratum corneum, viable epidermis and dermis. Consequently, changes in skin permeabilities of hydrophilic drugs in this study may result from changes of partition coefficients by EtOH pretreatment.…”

Section: Discussionmentioning

confidence: 99%

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

Horita

Todo

Sugibayashi

2012

Biological & Pharmaceutical Bulletin

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It has been demonstrated that ethanol (EtOH) can enhance skin permeation of drugs when simultaneously applied with drugs. However, only a few studies have reported on the pretreatment effect of EtOH on skin permeations. In this study, the pretreatment effects of EtOH on skin permeation of drugs were investigated by measuring changes in skin permeation and electrical skin resistance. Permeabilities of deuterium oxide (D 2 O), isosorbide mononitrate (ISMN), isosorbide dinitrate (ISDN), calcein sodium (CA-Na), and fluorescein isothiocyanate-dextran 4 kDa (FD-4, 3.3-4.4 kDa) were evaluated through Yucatan micropig skin pretreated with different concentrations of EtOH solution. From the results, almost constant skin permeabilities of D 2 O and ISDN were observed independent of EtOH concentration. Skin permeabilities of ISMN, CA, and FD-4 increased with low concentrations of EtOH, but decreased with high concentrations of EtOH. At 99.5% EtOH pretreatment, skin permeabilities of hydrophilic compounds (ISMN, CA, and FD-4) decreased to non-detectable levels. In addition, low molecular ion transports were almost constant at any EtOH concentration. Since molecular (ion) sizes of ISMN, CA, and FD-4 are larger than Na , Cl , and D 2 O, permeation pathway sizes for hydrophilic compounds in the skin barrier may be remarkably decreased by pretreatment with high concentrations of EtOH. However, the permeability coefficient of ISDN was not influenced by any EtOH concentration, since ISDN is a lipophilic, low-molecular compound that permeated through the lipophilic stratum corneum pathway. The present results show useful information for repeatedly and topically applied formulations containing EtOH, and also contribute to the effective use of alcohol formulations.Key words skin permeation; ethanol; pretreatment; electrical skin resistance; enhancer; permeation route Ethanol (EtOH) is well known as an ingredient of alcoholic beverages and has been utilized as a medicine for humans with different efficacies since ancient times. Currently, several skin disinfectants containing EtOH are frequently utilized in hospitals and public facilities for preventive purposes against viral infections. EtOH is a commonly used solvent just like water in pharmaceutical formulations, and is applied as a skin permeation enhancer, a skin disinfectant, and a solubilizer for poorly-soluble drugs. Tinctures, lotions, gels and liniments are dosage forms containing EtOH. Transdermal drug delivery systems and topical formulations often have the problem of low skin permeation of active ingredients. The skin barrier is mainly constituted by the outermost layer of skin, the stratum corneum, which dramatically restricts skin permeability of drugs. EtOH in topical formulations greatly enhances skin permeation of drugs. Estradiol and fentanyl dermal patches are typical examples developed using EtOH to enhance their transdermal deliveries.1-3) It has been proposed that the mechanisms of EtOH effects on the stratum corneum are extraction of lipids, increases in lipid...

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Section: Discussionmentioning

confidence: 99%

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

Horita

Todo

Sugibayashi

2012

Biological & Pharmaceutical Bulletin

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“…30) In addition, ethanol has been reported to extract and fluidize SC lipids. [31][32][33] Dimethyl sulfoxide has been shown to change keratin conformation and also interact with SC lipids. 34,35) However, the interactions of these CPEs with SC lipids was mainly on the polar head region.…”

Section: Discussionmentioning

confidence: 99%

Potential of Stratum Corneum Lipid Liposomes for Screening of Chemical Skin Penetration Enhancers

Sakdiset

Todo

Sugibayashi

2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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The evaluation of effective skin chemical penetration enhancers (CPEs) is a crucial process in the development of transdermal and dermal formulations with the capacity to overcome the stratum corneum barrier. In the present study, we aimed to investigate the potential of stratum corneum lipid liposomes (SCLLs) as an alternative tool for the screening of various types and concentrations of CPEs. SCLLs were prepared using a thin-film hydration technique, and two types of fluorescent probes ( Key words stratum corneum lipid liposome; chemical skin penetration enhancer; liposome; high-throughput screening Skin has been recognized as an application site of therapeutic drugs for several decades. However, only small numbers of drugs are available nowadays intended for systemic absorption through the skin. The stratum corneum (SC), the outermost layer of the skin, provides a strong barrier to protect against extraneous molecules from entering the body, and thus limits the skin penetration of drugs. The structure of the SC consists of keratin-rich corneocytes embedded in an intercellular lipid matrix.

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“…6 For details of the sample cell of the present measurement see elsewhere. 3 In Figure 1, the successive X-ray diffraction profile change in the range from S = 0.05 to 0.5 nm ¹1 as a function of time is shown on applying ethanol together with the profile for ethanol. The 1st to 4th order diffraction peaks for the long lamellar structure with the repeat distance of 13.5 nm are seen.…”

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confidence: 99%

“…In the presence of ethanol it has been pointed out that from Fourier transform infrared spectroscopy SC lipid conformation and mobility are not significantly altered, 2 and it has been reported briefly that from the X-ray diffraction measurement of hydrocarbon-chain packing its width is almost unchanged on applying ethanol. 3 Furthermore, there are a lot of studies on permeation of ethanol into the SC. The permeation activity in the SC is exerted by ethanol.…”

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confidence: 99%

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Disruption/Reconstitution of Skin Structure Treated by Ethanol

2012

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Organic solvents have been used as vehicle for cosmetics and percutaneous pharmaceuticals in skin. We performed X-ray diffraction measurement on applying a solvent, ethanol, to hairless mouse stratum corneum. We found that the diffraction peak intensities for the structures formed by lamellae and soft keratins decreased, while that for the hydrocarbon-chain packings slightly decreased. In addition the intensity of ethanol in the stratum corneum increased. After evacuating ethanol solution from the stratum corneum, all of the structures were largely regenerated.The outermost layer of skin, stratum corneum (SC), provides an essential barrier between atmosphere and the body. The SC is composed of keratinized cells, corneocytes, and intercellular lipids, where the corneocytes are embedded in intercellular lipid matrix. On the other hand, the modification of the barrier properties is of interest with respect to the application of pharmaceutical treatments and in cosmetology. As vehicle of cosmetics and percutaneous pharmaceuticals for skin, a variety of organic solvents have been used so far. However, when organic solvents are applied to skin, lipids in the SC are extracted according to their reactivity strength. It is known that the intercellular lipids are extracted markedly by chloroform/ methanol mixture and hexane/methanol mixture, but less by acetone, hexane, and ethanol.1 Ethanol is a basic solvent for pharmaceuticals and cosmetics. Here we focus our attention to the effect of ethanol on the SC. In the presence of ethanol it has been pointed out that from Fourier transform infrared spectroscopy SC lipid conformation and mobility are not significantly altered, 2 and it has been reported briefly that from the X-ray diffraction measurement of hydrocarbon-chain packing its width is almost unchanged on applying ethanol.3 Furthermore, there are a lot of studies on permeation of ethanol into the SC. The permeation activity in the SC is exerted by ethanol. 1d,1f,2b,4 Ethanol might permeate mainly through hydrophilic polar pathway in the SC. In the permeation process, absorption of chemicals dissolved in volatile vehicle such as ethanol is relevant to drug delivery via skin, that is, the concentration of chemical in the vehicle increases as the solvent evaporates thereby producing a greater driving force for permeation. To make clear this mechanism at the molecular level, in the present study we performed highly sensitive X-ray diffraction measurement on applying ethanol to the SC.Recently, we have developed a new method to measure the minute structural change on applying a solvent to a material.3 As a material we used the SC of eight-week-old male hairless mice (HR-1, Hoshino, Japan) and applied ethanol (reagent grade, Wako Pure Chemical Industries, Ltd., Osaka, Japan) to the SC. Before the measurement the SC sample was hydrated at about 25 wt %. The experiments were performed at BL40B2 (Structural Biology II Beamline) of SPring-8 (Hyogo, Japan). The X-ray wavelength was 0.075 nm and the sample-to-detector distanc...

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Novel method to observe subtle structural modulation of stratum corneum on applying chemical agents

Cited by 50 publications

References 24 publications

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

Potential of Stratum Corneum Lipid Liposomes for Screening of Chemical Skin Penetration Enhancers

Disruption/Reconstitution of Skin Structure Treated by Ethanol

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