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硅氧烷(硅酮)克服人体皮肤屏障的后果 第 1 部分。环状甲基硅氧烷的渗透和渗透深度研究。

The consequences of overcoming the human skin barrier by siloxanes (silicones) Part 1. Penetration and permeation depth study of cyclic methyl siloxanes.

机构信息

Department of Physical Chemistry, Faculty of Pharmacy with Subfaculty of Laboratory Medicine, Medical University of Gdańsk, Al. J. Gen. Hallera 107, 80-416 Gdańsk, Poland.

Department of Physical Chemistry, Faculty of Pharmacy with Subfaculty of Laboratory Medicine, Medical University of Gdańsk, Al. J. Gen. Hallera 107, 80-416 Gdańsk, Poland.

出版信息

Chemosphere. 2019 Sep;231:607-623. doi: 10.1016/j.chemosphere.2018.09.154. Epub 2018 Sep 27.

Abstract

Dynamic production of cyclic siloxanes: octamethylcyclotetrasiloxane D4, decamethylcyclopentasiloxane D5 and dodecamethylcyclohexasiloxane D6 increases their concentrations in environment. It is considered that both environmental pollution and the usage of personal care products and cosmetics containing cyclic siloxanes can be the main source of the human exposure by transdermal route. The aim of the study was to verify the possibility to overcome the skin barrier by cyclic siloxanes (ATR-FTIR and GC-FID), evaluation of diffusion pathway to stratum corneum SC (Fluorescence microscopy), and determination of depth of permeation to deeper skin layers: epidermis and dermis (ATR-FTIR) and also of potential interaction with SC lipids and proteins (Fluorescence microscopy, ATR-FTIR) and the cytotoxicity studies against HaCaT cells (MTT test). The results show that D4, D5 and D5 can penetrate to SC and permeate into the deeper layers of the skin: epidermis and dermis. The quantitative analysis (GC-FID) showed that total cumulative doses for D4, D5 and D6 were: 42.50; 95.37 and 77.19 μg/cm2/24 h, respectively. The microscopic analysis proved, transepidermal route through the lipid matrix as well as through the canyons (intercluster spaces) were a diffusion pathway to the SC as well as disruption of human SC lipid structure by: D4 (the most), D5 and D6 (the least). The cytotoxicity studies demonstrated that the tested range of concentrations of D5 and D6 (up to 300 mM, 111 300 mg and 133 500 mg respectively) did not impaired the HaCaT growth, while D4 had IC50 value of 40 098 mM ± 7.94 (10 906 ± 872,5 mg).

摘要

动态生产环状硅氧烷

八甲基环四硅氧烷 D4、十甲基环五硅氧烷 D5 和十二甲基环六硅氧烷 D6 会增加其在环境中的浓度。人们认为,环境污染物以及含有环状硅氧烷的个人护理产品和化妆品的使用,可能是人体通过经皮途径暴露的主要来源。本研究的目的是通过(ATR-FTIR 和 GC-FID)验证环状硅氧烷穿透皮肤屏障的可能性,评估其进入角质层 SC 的扩散途径(荧光显微镜),并测定其向更深层皮肤(表皮和真皮)的渗透深度(ATR-FTIR),以及与 SC 脂质和蛋白质的潜在相互作用(荧光显微镜、ATR-FTIR)和对 HaCaT 细胞的细胞毒性研究(MTT 试验)。结果表明,D4、D5 和 D6 可以穿透 SC 并渗透到皮肤的更深层:表皮和真皮。定量分析(GC-FID)显示,D4、D5 和 D6 的总累积剂量分别为 42.50、95.37 和 77.19μg/cm2/24h。显微镜分析证明,D4、D5 和 D6 可通过脂质基质以及峡谷(簇间空间)穿过角质层,作为进入 SC 的扩散途径,同时还破坏了人类 SC 脂质结构:D4(最严重)、D5 和 D6(最轻微)。细胞毒性研究表明,测试范围内的 D5 和 D6 浓度(最高达 300mM、111300mg 和 133500mg)不会损害 HaCaT 细胞的生长,而 D4 的 IC50 值为 40098mM±7.94(10906±872.5mg)。

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