BioAcyl Corp
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Khabir, Z., Holmes, A. M., & Lai, Y.-J. (2021). Human epidermal zinc concentrations after topical application of zno nanoparticles in sunscreens. International Journal of Molecular Sciences, 22(22). Added by: Dr. Enrique Feoli (16/12/2023, 18:26) Last edited by: Dr. Enrique Feoli (16/12/2023, 18:32) |
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| Resource type: Journal Article DOI: 10.3390/ijms222212372 ID no. (ISBN etc.): 1422-0067 BibTeX citation key: Khabir2021 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: UV Damage Repair Creators: Holmes, Khabir, Lai Collection: International Journal of Molecular Sciences |
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Conclusiones
Whilst there has been concern about the general safety of zinc oxide nanoparticle sunscreens in topical products, work to date has focussed on whether nanoparticles can be found in the viable epidermis after permeation through the SC and via furrows and the follicles, including by lateral diffusion [75]. These zinc oxide nanoparticles, in turn, release zinc ions when the skin pH is either neutral or acidic and high zinc ion concentrations have been shown to be toxic in isolated keratinocytes [41]. Here, the use of 67Zn tagged nanoparticles enabled analysis of exogenous zinc ion concentrations in viable skin after topical application of zinc oxide nanoparticles.
The percutaneously absorbed 67Zn was quantified by inductively coupled plasma–mass spectrometry (ICP-MS) and laser-ablation ICP-MS to its elevated concentration in the VE as 1.0 ± 0.3 μg/mL (2.1 ± 0.5 μg per g of dry skin), much lower than our estimated endogenous total zinc ion concentration in the viable epidermis of 4.3 ± 0.7 μg/mL (13 ± 2 μg/g of dry skin). Both are, in turn, much lower than the potentially cytotoxic labile 67Zn concentrations of 21–31 μg/mL in serum-supplemented culture media causing keratinocyte HaCaT cytotoxicity. Therefore, the zinc concentration detected in VE with and without ZnO NP application was found to be significantly lower than the HaCaT cytotoxicity threshold. As such, our study validates the estimates recently made by Yamada et al. [18]. Furthermore, our work supports the recent FDA proposal for sunscreen marketing that only two of the 16 currently marketed sunscreens, zinc oxide and titanium dioxide, can generally be regarded as safe and effective [76]. This paper provides strong evidence that the NP form of ZnO sunscreens is safe after topical application to intact human skin.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
| Abstract |
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Zinc oxide nanoparticle (ZnO NP)-based sunscreens are generally considered safe because the ZnO NPs do not penetrate through the outermost layer of the skin, the stratum corneum (SC). However, cytotoxicity of zinc ions in the viable epidermis (VE) after dissolution from ZnO NP and penetration into the VE is ill-defined. We therefore quantified the relative concentrations of endogenous and exogenous Zn using a rare stable zinc-67 isotope (67Zn) ZnO NP sunscreen applied to excised human skin and the cytotoxicity of human keratinocytes (HaCaT) using multiphoton microscopy, zinc-selective fluorescent sensing, and a laser-ablation inductively coupled plasma–mass spectrometry (LA-ICP-MS) methodology. Multiphoton microscopy with second harmonic generation imaging showed that 67ZnO NPs were retained on the surface or within the superficial layers of the SC. Zn fluorescence sensing revealed higher levels of labile and intracellular zinc in both the SC and VE relative to untreated skin, confirming that dissolved zinc species permeated across the SC into the VE as ionic Zn and significantly not as ZnO NPs. Importantly, the LA-ICP-MS estimated exogenous 67Zn concentrations in the VE of 1.0 ± 0.3 μg/mL are much lower than that estimated for endogenous VE zinc of 4.3 ± 0.7 μg/mL. Furthermore, their combined total zinc concentrations in the VE are much lower than the exogenous zinc concentration of 21 to 31 μg/mL causing VE cytotoxicity, as defined by the half-maximal inhibitory concentration of exogenous 67Zn found in human keratinocytes (HaCaT). This speaks strongly for the safety of ZnO NP sunscreens applied to intact human skin and the associated recent US FDA guidance.
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