Skin Corrosion and Irritation Test of Nanoparticles Using Reconstructed Three-Dimensional Human Skin Model, EpiDerm^TM

Abstract

Effects of nanoparticles (NPs) on skin corrosion and irritation using three-dimensional human skin models were investigated based on the test guidelines of Organization for Economic Co-operation and Development (OECD TG431 and TG439). EpiDermTM skin was incubated with NPs including those harboring iron (FeNPs), aluminum oxide (AlNPs), titanium oxide (TNPs), and silver (AgNPs) for a defined time according to the test guidelines. Cell viabilities of EpiDermTM skins were measured by the 3-(4, 5-dimethylthi-azol-2-yl)-2.5-diphenyltetrazolium bromide based method. FeNPs, AlNPs, TNPs, and AgNPs were non-corrosive because the viability was more than 50% after 3 min exposure and more than 15% after 60 min exposure, which are the non-corrosive criteria. All NPs were also non-irritants, based on viability exceeding 50% after 60 min exposure and 42 hr post-incubation. Release of interleukin 1-alpha and histopathological analysis supported the cell viability results. These findings suggest that FeNPs, AlNPs, TNPs, and AgNPs are ‘non-corrosive’ and ‘non-irritant’ to human skin by a globally harmonized classification system.

Refining in vitro models for nanomaterial exposure to cells and tissues

“…Reconstructed tissue models can therefore be used in conjunction with the aforementioned exposure configurations to inform on the transport of NM through biological barriers, such as the skin, placenta, intestine and lungs (des Rieux et al, 2007;Vankoningsloo et al, 2010;Hedwig M Braakhuis et al, 2015;Lefebvre et al, 2015;Kooter et al, 2017;Vinardell et al, 2017). Reconstructed skin models have received the most attention currently in the field of NM safety assessment, due to the widespread use of NMs in sunscreans and cosmetics, leading to the availability of a variety of 3D-reconstructed skin models, including but not limited to EpiSKIN and EpiDerm (Mathes, Ruffner and Graf-Hausner, 2014;Hayden et al, 2015;Kim et al, 2016;Wills et al, 2016;Evans et al, 2017;Hao et al, 2017;Vinardell et al, 2017). These models have been used in conjunction with exposure to NMs such as MWCNTs and zinc oxides (ZnO) to determine the toxicity in these cell systems as opposed to dosing in standard 2D culture (Vankoningsloo et al, 2010;Vinardell et al, 2017).…”

Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation

“…From the other experiments, as mentioned in Sections 3.3-3.5, the selected colloidal dispersion was NLC, so the gel formulation containing the chili extract-loaded NLC with 0.075% capsaicin was our sample of interest. The percentages of EpiDerm TM cell viability after exposure to samples and controls were over 50%, indicating that all formulations were non-irritant [25,26], compared with 5% SDS (positive control), which showed strong irritancy. However, the percentage of cell viability from Gel NLC_C (91.85% ± 0.16%) was significantly (p < 0.05) higher than that of chili extract gel (86.49% ± 4.34%), revealing that the skin irritation of NLC was lower than the free form alternative, similar to the findings of previous reports [10,25].…”

“…From the other experiments, as mentioned in Sections 3.3 to 3.5, 545 the selected colloidal dispersion was NLC, so the gel formulation containing the chili extract-loaded 546 NLC with 0.075% capsaicin was our sample of interest. The percentages of EpiDerm TM cell viability 547 after exposure to samples and controls were over 50%, indicating that all formulations were non-548 irritant [25,26], compared with 5% SDS (positive control), which showed strong irritancy. However,…”

“…The OD values were determined using a spectrophotometer at 570 nm. The percent cell viability was calculated using Equation 9 [25,26].…”

“…The release of IL-1α after a 24-h incubation period with the test samples from the EpiDerm RHE tissue to the culture medium was collected and quantified using Quantikine ® ELISA kits according to the assay protocol provided by the manufacturer. UV-visible spectrophotometric measurements were performed at 450 nm using a microplate reader (Biotek Power Wave X, VT, USA) [25,26].…”