• Toxicological Research
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• v.33 no.3
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• pp.191-203
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• 2017

Human eyes and skin are frequently exposed to chemicals accidentally or on purpose due to their external location. Therefore, chemicals are required to undergo the evaluation of the ocular and dermal irritancy for their safe handling and use before release into the market. Draize rabbit eye and skin irritation test developed in 1944, has been a gold standard test which was enlisted as OECD TG 404 and OECD TG 405 but it has been criticized with respect to animal welfare due to invasive and cruel procedure. To replace it, diverse alternatives have been developed: (i) For Draize eye irritation test, organotypic assay, in vitro cytotoxicity-based method, in chemico tests, in silico prediction model, and 3D reconstructed human cornealike epithelium (RhCE); (ii) For Draize skin irritation test, in vitro cytotoxicity-based cell model, and 3D reconstructed human epidermis models (RhE). Of these, RhCE and RhE models are getting spotlight as a promising alternative with a wide applicability domain covering cosmetics and personal care products. In this review, we overviewed the current alternatives to Draize test with a focus on 3D human epithelium models to provide an insight into advancing and widening their utility.

• Journal of Microbiology and Biotechnology
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• v.28 no.12
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• pp.2121-2132
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• 2018

Abnormal melanin synthesis results in several hyperpigmentary disorders such as freckles, melanoderma, age spots, and other related conditions. In this study, we investigated the anti-melanogenic effects of an extract from the microalgae Chlamydomonas reinhardtii (CE) and potential mechanisms responsible for its inhibitory effect in B16F10, normal human epidermal melanocyte cells, and human skin-equivalent models. The CE extract showed significant dose-dependent inhibitory effects on ${\alpha}$-melanocyte-stimulating, hormone-induced melanin synthesis in cells. Additionally, the CE extract exhibited suppressive effects on the mRNA and protein expression of microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related protein-1, and tyrosinase-related protein-2. The CE extract also inhibited the phosphorylation of protein kinase A and extracellular signal-related kinase, which function as upstream regulators of melanogenesis. Using a three-dimensional, reconstructed pigmented epidermis model, the CE-mediated, anti-pigmentation effects were confirmed by Fontana-Masson staining and melanin content assays. Taken together, CE extract can be used as an anti-pigmentation agent.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.38 no.3
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• pp.219-224
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• 2012

European Union prohibited the marketing of cosmetic products containing constituents that have been examined through animal experiments. Thus, non-animal test models are needed to replace animal experiments. The reconstructed skin models are important as a test system for cosmetic, pharmaceutical, and medical device safety testing. In the present study, we tried to develop an optimal skin equivalent model containing basement membrane and epidermis. For this purpose, we used mesenchymal stem cells (MSCs) and/or preadipocytes as well as fibroblasts as the dermal matrix cells. The formation of basement membrane and epidermis was verified by immunohistochemical stains. Among various models, the epidermis was thickest when MSCs were used in the dermal matrix. Furthermore, PCNA and involucrin distribution showed that dermal matrix with MSCs resembled human skin. Therefore, skin equivalents with MSCs could be developed as a non-animal test model to replace animal experiments.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.42 no.3
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• pp.211-216
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• 2016

Micronucleus test is genotoxicity assay for detection of micronuclei in the cytoplasm of interphase cells. The reduction and replacement of in vivo toxicity testing on animals require the development of in vitro models to predict the genotoxicity or other tests for cosmetic products. In this study, we evaluated a genotoxicity assay for topically applied chemicals using a three-dimensional human reconstructed skin model, KeraSkin$^{TM}$. Two genotoxins, mitomycin C (MMC) and methyl methanesulfonate (MMS), induced significant dose-related increases in cytotoxicity and micronuclei induction in the skin model. In contrast, two non-genotoxins, 4-nitrophenol (4-NP) and trichloroethylene (TCE), induced cytotoxicity but not micronucleus formation. In conclusion, micronucleus test using human skin model may be useful for predicting in vitro genotoxic potentials of cosmetic products.

• Journal of the Korean Applied Science and Technology
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• v.38 no.4
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• pp.915-921
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• 2021

In this study, we designed pantothenic acid (PA) loaded solid lipid nanoparticles (SLNs) for enhanced skin penetration of PA that is used for moisturizing agent in cosmetics with hydrophilic property. SLNs were prepared using various lipids and surfactants. PA loaded SLNs were fabricated using double emulsion method. The fabricated PA loaded SLNs assessed particle size, polydispersity index, zeta potential, loading capacity. Skin penetration study was conducted using artificial skin tissue originated from human epidermis as one of the reconstructed human epidermis models. The mean particle size and zeta potential of SLNs ranged from 192.15 nm to 369.87 nm and -21.39 mV to -40.55 mV, respectively. The loading efficiency and loading amount of PA loaded SLNs were ranged from 44.36% to 57.16% and 12.60% to 16.36%, respectively. The results of penetration demonstrated that all SLNs improved PA skin penetration. In addition, the amount of PA from SLNs were approximately 3.8 - 8.8 times higher than that from PA solution. Therefore, the fabricated SLNs demonstrated the enhancment of skin penetration of PA. Particularly, the SLN, which used glyceryl behenate and Span 60, showed optimal skin penetration of PA.

• Journal of the Korean Applied Science and Technology
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• v.38 no.3
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• pp.662-668
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• 2021

The aim of the present study was to design ascorbyl glucoside (AG) loaded solid lipid nanoparticles (SLNs) to improve skin penetration of AG. AG loaded SLNs were prepared using double emulsion method. The prepared AG loaded SLNs investigated particle characteristics (particle size, polydispersity index, zeta potential, loading capacity). Skin penetration study was carried out using SkinEthic RHE as one of the reconstructed human epidermis models. The mean particle size and zeta potential of SLNs were 172.65 - 347.19 nm and -22.90 - -41.20 mV, respectively. The loading capacity of AG loaded SLNs demonstrated that loading efficiency and loading amount were ranged from 44.18% to 57.77% and 12.83% to 16.15%, respectively. The results of penetration showed that all SLNs enhanced the skin penetration of AG and the amount of AG from SLNs were approximately 3.7 - 7.4 times higher than that from AG solution. Therefore, AG loaded SLN might be a promising topical drug delivery system.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.47 no.2
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• pp.179-184
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• 2021

Stratum corneum known as a skin barrier, which maintains water in skin, is the outer layer of the skin. Natural moisturizing factors (NMF) are one of the constituents in stratum corneum and amino acids are the highest components among NMF. In this study, we designed stearic acid-based solid lipid nanoparticles (SLNs) for improved skin penetration of serine (Ser). Ser-capsulated SLN was manufactured by double-melting emulsification method. The mean particle size and zeta potential of SLNs were 256.30 ~ 416.93 nm and -17.60 ~ -35.27 mV, respectively. The higher the degree of hydrophobicity or hydrophilicity of emulsifiers, the smaller the particle size and the higher the stability and capsulation rate. In addition, skin penetration was conducted using SkinEthic^TM RHE which is one of the reconstructed human epidermis models. The results of Ser penetration demonstrated that all SLNs enhanced than serine solution. The amount of enhanced Ser penetration from SLNs were approximately 4.1 ~ 6.2 times higher than that from Ser solution. Therefore, Ser-loaded SLN might be a promising drug delivery system for moisturizing formulation in cosmeceutical.