Evaluation of Yucatan Micropig Skin for Use as an in Vitro Model for Skin Permeation Study.

Fujii, Makiko; Yamanouchi, Shizuka; Hori, Naohide; Iwanaga, Noriko; Kawaguchi, Naruko; Maeda, Mitsuo

doi:10.1248/bpb.20.249

Cited by 65 publications

(35 citation statements)

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“…YMP skin permeabilities of drugs were reported to be increased with an increase in age. 18) Increases in flux were observed with growth of hair follicle tissue, probably because the long hairs of dermatomed skin would be cut by dermatomation. 19) Therefore, we used thicker skin membranes to avoid variations in skin permeation data.…”

Section: Discussionmentioning

confidence: 99%

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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%

“…[10][11][12] Drug permeability and histological characteristics such as hair density in porcine skin closely resemble human skin. [13][14][15][16] Furthermore, electrical skin resistance was determined to investigate the effects of EtOH pretreatment on skin permeabilities of small ions such as Na + and Cl − . The authors declare no conflict of interest.…”

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confidence: 99%

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

Horita

Todo

Sugibayashi

2012

Biological & Pharmaceutical Bulletin

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“…other biomedical research applications (Brown, StrickerKrongrad, and Bouchard 2013;Gad, Stricker-Krongrad, and Skaanild 2015). Reviews of the use of swine in such studies have been previously published (Fujii et al 1997;Gad, Stricker-Krongrad, and Skaanild 2015;Monteiro-Riviere and Riviere 1996;M. M. Swindle 2007).…”

Section: Dermal Modelsmentioning

confidence: 99%

The Miniature Swine as a Model in Experimental and Translational Medicine

2016

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The use of the miniature swine as a nonrodent species in research has continued to expand for over a decade, and they are becoming routinely used both in experimental pharmacology and as a therapeutic model for human diseases. Miniature swine models are regularly used for studies designed to assess efficacy and safety of new therapeutic compounds given through different routes of exposure and are used as an alternative model to rodents, canines, or nonhuman primates. Translational preclinical swine study data presented here support the current understanding that miniature swine are the animal model of choice for the assessment of drugs targeting endocrine, dermal, and ocular disorders. Because research investigators need to be familiar with some of the important features of the models developed in the miniature swine in order to place clinical and experimental findings in their proper perspective, relevant references and data from these models will be presented, compared, and partially illustrated.

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“…On the other hand, numerous animal models have been suggested as an alternative to human skin, including primate, porcine, mouse, rat, guinea pig, and snake skin [3,6,8,9,24,26,27,32,34]. Animal skins with a small variation in skin permeability may be much better suited than human skin for determining or estimating the skin permeabilities of drugs and for developing transdermal formulations [3,18,28].…”

Section: Introductionmentioning

confidence: 99%

Usefulness of Rat Skin as a Substitute for Human Skin in the in Vitro Skin Permeation Study

et al. 2011

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Sprague-Dawley (SD) rats are broadly used in preclinical studies for drug development, so a lot of information for the rats can be obtained especially from pharmacokinetic, pharmacological and toxicological studies. The purpose of this study was to clarify whether SD rat skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate, and flurbiprofen, through human skin and SD rat skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs through human skin and SD rat skin were determined, and their variations were evaluated. The inter-individual variations in SD rat skin permeability of the three model drugs were much lower than that in human skin permeability, although the permeation rates of the three model drugs through the SD rat skin were about twice those through human skin. In addition, no difference in the skin permeability coefficients of the three model drugs was obtained between fresh SD rat skin and frozen SD rat skin. The markedly smaller variation in the permeability through SD rat skin compared with that through human skin indicated that in vitro permeation studies using SD rat skin would be especially useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability.

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Evaluation of Yucatan Micropig Skin for Use as an in Vitro Model for Skin Permeation Study.

Cited by 65 publications

References 0 publications

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

Effect of Ethanol Pretreatment on Skin Permeation of Drugs

The Miniature Swine as a Model in Experimental and Translational Medicine

Usefulness of Rat Skin as a Substitute for Human Skin in the in Vitro Skin Permeation Study

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