Measuring the stratum corneum reservoir: Desorption kinetics from keratin

Seif, Salem; Hansen, Steffi

doi:10.1002/jps.23245

Cited by 24 publications

(25 citation statements)

References 45 publications

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“…Ultrafiltration data of EGCG-keratin isotherm measured by ultrafiltration. 11 Hansen et al 12,13 has summarized the database of small molecule binding to different keratin (bovine hoof and horn, delipidized skin, nail, hair, and wool). The dimensionless binding coefficient (K b ) to bovine hoof/horn is empirically correlated to the octanol-water distribution coefficient as follows log K b 51:2610:34 log D…”

Section: Egcg-keratin Binding Assaymentioning

confidence: 99%

“…16 For EGCG at pH 6.0, both log D and log K ow values were predicted to be 2.56 (calculated from EPIWEB 4.1), which leads to the logarithmic keratin binding coefficient of 2.13 12,13 for bovine hoof/horn, 1.44 14 and 1.41 15 for delipidized skin, and 1.65 16 for hair. Hence, the strength of binding to different keratin-rich biosubstrates appears to vary.…”

Section: Egcg-keratin Binding Assaymentioning

confidence: 99%

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Molecular and thermodynamic basis for EGCG‐Keratin interaction‐part II: Experimental investigation

et al. 2013

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In Part I, we reported all-atom, fully solvated molecular dynamics (MD) simulations of epigallocatechin-3-gallate (EGCG) binding to keratin. Herein, we report the second part of experimental investigation on EGCG binding to keratin using ultrafiltration and isothermal titration calorimetry (ITC). The thermodynamic equilibrium of EGCG binding to keratin has been quantitatively determined using ultrafiltration and high-performance liquid chromatography-UV/vis. The relationship confirms multilayer binding of EGCG to keratin which was observed in MD simulations. By combining the ultrafiltration and ITC data, the thermodynamic parameters of EGCG binding to keratin have been quantified. The obtained free energy of the first layer binding (ΔG=-6.37 kcal mol) is shown in excellent agreement with that obtained from computer simulations (ΔG=-6.20 kcal mol) presented in Part I. © 2013 American Institute of Chemical Engineers

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Section: Egcg-keratin Binding Assaymentioning

confidence: 99%

Section: Egcg-keratin Binding Assaymentioning

confidence: 99%

Molecular and thermodynamic basis for EGCG‐Keratin interaction‐part II: Experimental investigation

et al. 2013

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“…In Model 1, we considered bound and unbound drug in the plasma and tissues. Drug binds to keratin in the skin [7] and the dynamics of binding in the skin have been shown to be linear [14] . As only unbound drug is free to diffuse [5] , binding may be an important factor in the formation of a SC reservoir.…”

Section: Modelmentioning

confidence: 99%

“…As only unbound drug diffuses [5] the cause of a reservoir forming in the SC is thought to be high keratin binding and slow desorption kinetics [5] . Binding within the skin is most typical for lipophilic drugs with high molecular weight [6,7] .…”

Section: Introductionmentioning

confidence: 99%

A mechanistic approach to modelling the formation of a drug reservoir in the skin

Jones

White

Delgado‐Charro

2016

Mathematical Biosciences

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It has been shown that prolonged systemic presence of a drug can cause a build-up of that drug in the skin. This drug 'reservoir', if properly understood, could provide useful information about recent drug-taking history of the patient. We create a pair of coupled mathematical models which combine to explore the potential for a drug reservoir to establish based on the kinetic properties of the drug. The first compartmental model is used to characterise time-dependent drug concentrations in plasma and tissue following a customisable drug regimen. Outputs from this model provide boundary conditions for the second, spatio-temporal model of drug build-up in the skin. We focus on drugs that are highly bound as this will restrict their potential to move freely into the skin but which are lipophilic so that, in the unbound form, they would demonstrate an affinity to the outer layers of the skin. Buprenorphine, a drug used to treat opiate addiction, is one example of a drug satisfying these properties. In the discussion we highlight how our study might be used to inform future experimental design and data collection to provide relevant parameter estimates for reservoir formation and its potential to contribute to enhanced drug monitoring techniques.

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“…20 In addition, the role of keratin, the major protein in the stratum corneum, has recently been demonstrated by Seif and Hansen as the fast absorption and slow desorption of chemicals from this protein may be an important contributor. 27 It has been generally assumed that the reservoir is continuously emptied by desquamation. 16 In support of this, Reddy et al (2000) showed that significant amount of highly lipophilic and very large solute ( > 350 Da) can be removed if the epidermal turnover was fast relative to the rate of diffusion through the stratum corneum.…”

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confidence: 99%

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

DumontCoralie

PrietoPilar

AsturiolDavid

et al. 2015

Applied In Vitro Toxicology

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The exposure of the skin to consumer products, drugs, and environmental chemicals can result in their penetrating the skin barrier and entering systemic circulation, potentially resulting in adverse effects in the skin and other organs. The assessment of dermal penetration and bioavailability (including penetration, metabolism, and entry into the systemic circulation) is therefore an important consideration in the risk assessment of chemicals. The skin is a heterogeneous organ with a multilayer structure. Based on its architecture and physiology, substances can penetrate through three major ways but can also be blocked in the different skin layers and in the skin appendages, which act as reservoir. In addition to that, as the skin is a metabolically competent organ, substances can undergo metabolism. After a brief description of the skin architecture, this review will focus on the skin penetration mechanisms and skin metabolic capacities. The skin absorption has traditionally been tested in vivo on animals. However, with the new legislation (i.e., Registration, Evaluation, Authorisation, and Restriction of Chemicals Regulation or Cosmetics Regulation), alternatives to animal testing have to be implemented. In a second part, this review will provide a description of the main in vitro and in silico or computational models available to study skin absorption and skin metabolism (i.e., ex vivo skin models, artificial membrane barriers, primary cells and cell lines, Quantitative Structure-Activity Relationship [QSAR], simulators for the prediction of skin metabolism).

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Measuring the stratum corneum reservoir: Desorption kinetics from keratin

Cited by 24 publications

References 45 publications

Molecular and thermodynamic basis for EGCG‐Keratin interaction‐part II: Experimental investigation

Molecular and thermodynamic basis for EGCG‐Keratin interaction‐part II: Experimental investigation

A mechanistic approach to modelling the formation of a drug reservoir in the skin

Review of the Availability ofIn VitroandIn SilicoMethods for Assessing Dermal Bioavailability

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