Reconstituted Epidermis: A Novel Model for the Study of Drug Metabolism in Human Epidermis

Pham, Mai-Anh; Magdalou, Jacques; Siest, Gérard; Lenoir, Marie-Cécile; Bernard, Bruno; Jamoulle, Jean-Claude; Shroot, Braham

doi:10.1111/1523-1747.ep12874606

Cited by 34 publications

(13 citation statements)

References 18 publications

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“…RHE equivalents such as skin pharmacological models have been successfully applied to in vitro characterization of skin barrier functions [1,2,3], skin absorption processes [4,5], drug metabolism [6] and corrosion/irritation predictions [7,8,9,10]. Validated models are commercially available as EpiSkin® (SkinEthic Laboratories, France), EpiDerm® (MatTek Cooperation, USA), and EST-1000 (Cell Systems, Germany) [11] but also in-house models have been utilized [12,13,14] for the assessment of in vitro skin corrosion of chemicals.…”

Section: Introductionmentioning

confidence: 99%

Residual Antimicrobial Effect of Chlorhexidine Digluconate and Octenidine Dihydrochloride on Reconstructed Human Epidermis

Müller

Langer

Siebert³

et al. 2013

Skin Pharmacol Physiol

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The objective of the present investigation was to examine the residual antimicrobial activity after a topical exposure of reconstructed human epidermis (RHE) to equimolar solutions of either chlorhexidine digluconate (CHG, 0.144% w/v) or octenidine dihydrochloride (OCT, 0.1% w/v) for 15 min. RHE-associated antiseptic agents were more effective on Staphylococcus aureus than on Pseudomonas aeruginosa. S. aureus was not detected after 24 h of contact, which demonstrated a microbicidal efficacy of greater than 5-log₁₀ reduction. In contrast, P. aeruginosa was reduced by approximately 2 log₁₀ at the same incubation time, which parallels the growth of the initial inoculum. This result could be interpreted either as a microbiostatic effect or as an adherence of P. aeruginosa to a low positively charged surface. Small amounts of CHG and OCT can penetrate the stratum corneum. Using these antiseptic agents, the viability of keratinocytes was reduced to 65-75% of that of the untreated RHE control following 24 h incubation in the presence of test microorganisms. With consideration of antimicrobial activity and cytotoxic effect, OCT corresponds better to a biocompatible antiseptic agent than CHG.

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Section: Introductionmentioning

confidence: 99%

Residual Antimicrobial Effect of Chlorhexidine Digluconate and Octenidine Dihydrochloride on Reconstructed Human Epidermis

Müller

Langer

Siebert³

et al. 2013

Skin Pharmacol Physiol

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“…More than four hundred samples of reconstructed epidermis (15-18 mm in diameter) were reproducibly obtained with a mean wet weight of about 15 mg [21]. Therefore, this model should be of general interest for pharmacological stud ies, and could represent an attractive alter native to the use of animal and human skin samples.…”

Section: Discussionmentioning

confidence: 98%

Architecture of Reconstructed Epidermis on Collagen Lattices Varies according to the Method Used: A Comparative Study

Lenoir

Bernard²

1990

Skin Pharmacol Physiol

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Epidermis was obtained in vitro after air exposure of keratinocyte cultures grown on a dermal equivalent. Some cultures were established from enzymatically dissociated keratinocytes of either interfollicular epidermis or hair follicle outer root sheath. Others resulted from centrifugal outgrowth of epidermal sheet, out of skin biopsies or hair follicles, which were directly implanted into dermal equivalents. Whatever the system used, a multilayered epidermis was obtained with an overall architecture resembling that of human epidermis. However, depending on the tissue culture method used and the source of keratinocytes, significant differences were observed. The most striking finding was the difference in 67 kDa keratin expression: the only case where it was strictly suprabasal and homogeneously expressed in the cytoplasm of the cells, as in normal epidermis, was found in the epidermis obtained from hair follicle explants. With the other methods, the expression of this marker was delayed and patchy. These results are discussed in terms of possible intrinsic differences between interfollicular and follicular keratinocytes.

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“…Moreover, the activity of UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) in human skin has also been reported. [10][11][12] Therefore, it is considered that skin metabolism of edaravone in humans may be similar to that in rat skin. However, there have been no reports on skin metabolism of edaravone.…”

Section: )mentioning

confidence: 99%

In Vitro Metabolism Study of Edaravone in Wistar and Hairless Rat Skin

Sato

Mizuno

Ishii

2008

Biological & Pharmaceutical Bulletin

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3-Methyl-1-phenyl-2-pyrazolin-5-one (edaravone, Radicut injection) acts as an antioxidative radical scavenger, and has been developed as a treatment for cerebrovascular disease. 1)In addition, edaravone has been reported to have protective effects on functional damage caused by hyperglycemia to human dermal microvascular endothelial cells, 2) inflammation-induced pain 3) and cisplatin-induced nephrotoxicity in rats. 4) There are also many reports that edaravone has a protective effect on ischemic diseases caused by oxidative stress. Edaravone administration in patients with rheumatoid arthritis leads to a reduction in serum C-reactive protein and disease activity score. 5) Therefore, edaravone is expected to have a role in the prevention and treatment of acute and chronic diseases.Transdermal absorption can be considered as an administration route for prolonged edaravone action. We have already reported the formation of an edaravone/cyclodextrin complex 6) and its skin permeability.7) It has previously been clearly shown that the edaravone/cyclodextrin complex increases the amount of edaravone on the skin surface, as well as its skin permeability. These results suggest the possibility of transdermal and transmucosal treatment with edaravone. On the other hand, it has been reported that the pharmacokinetics of edaravone after intravenous administration in rats 8) and humans 9) involve excretion of glucuronide and sulfate. Moreover, the activity of UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) in human skin has also been reported. [10][11][12] Therefore, it is considered that skin metabolism of edaravone in humans may be similar to that in rat skin. However, there have been no reports on skin metabolism of edaravone.In this study, we used Wistar and hairless rat skin to investigate the metabolism of edaravone in vitro. MATERIALS AND METHODS MaterialsEdaravone was synthesized from ethyl acetoacetate and phenylphydrazine according to the method of Komatu et al. 13) All other reagents and solvents were of special grade and used without further purification.Animals Wistar/ST and hairless (HWY) male rats were obtained from Japan SLC (Shizuoka, Japan). These animals were housed in rooms controlled at 23Ϯ2°C and 55Ϯ15% relative humidity. Pelleted chow (Certified Rodent Diet #002; PMI Nutriton International, U.S.A.) and water were given ad libitum. 10-and 24-Week-old Wistar rats and 10-week-old hairless rats were used for experiments. All experiments were performed under the regulations of the Animal Ethical Committee of Mikasa Seiyaku (based on the Fundamental Guidelines for Proper Conduct of Animal Experiment and Related Activities in Academic Research Institutions under the jurisdiction of the Ministry of Education, Culture, Science and Technology).Residual Edaravone in Skin Homogenate and Intact Skin One gram of abdominal skin was excised from three or four 10-and 24-week-old Wistar or 10-week-old hairless rats, homogenized in 10 ml saline (Physcotron NS-50; Microtec, Chiba, Japan), and centrifuged a...

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Reconstituted Epidermis: A Novel Model for the Study of Drug Metabolism in Human Epidermis

Cited by 34 publications

References 18 publications

Residual Antimicrobial Effect of Chlorhexidine Digluconate and Octenidine Dihydrochloride on Reconstructed Human Epidermis

Residual Antimicrobial Effect of Chlorhexidine Digluconate and Octenidine Dihydrochloride on Reconstructed Human Epidermis

Architecture of Reconstructed Epidermis on Collagen Lattices Varies according to the Method Used: A Comparative Study

In Vitro Metabolism Study of Edaravone in Wistar and Hairless Rat Skin

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