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Impact of physiologically relevant temperatures on dermal absorption of active substances - an ex-vivo study in human skin.
Toxicology in Vitro ( IF 3.2 ) Pub Date : 2020-07-30 , DOI: 10.1016/j.tiv.2020.104954
S Kilo 1 , J Wick 1 , S Mini Vijayan 1 , T Göen 1 , R E Horch 2 , I Ludolph 2 , H Drexler 1
Affiliation  

Skin temperature plays a certain role in the dermal absorption of substances, but the extent and mechanisms of skin temperatures-induced modulation in ranges caused by physiological thermoregulation or environmental conditions are largely unknown. The influence of dermal temperature on the absorption of the model lipophilic compound (anisole) and the model hydrophilic compounds (1,4-dioxane, ethanol) through human skin was investigated at three dermal temperatures (25, 32 and 39 °C) in an ex-vivo diffusion cell model. The substances were applied to the skin and transdermal penetration was monitored. All substances showed temperature dependent variations in their penetration behavior (3 h: 25–39 °C: 202–275% increase in cumulative, transdermally penetrated amounts). The relative differences in absorption in relation to temperature were greatest within 45 min after exposure (25–39 °C: 347–653% rise in cumulated penetration), although absolute amounts absorbed were small (45 min vs. 3 h: 4.5–14.5%). Regardless of blood circulation, skin temperature significantly influences the amount and kinetics of dermal absorption. Substance-dependent, temperature-related changes of the lipid layer order or the porous pathway may facilitate penetration. The early-stage modulation of transdermal penetration indicates transappendageal absorption, which may be relevant for short-term exposures. For both, toxicological evaluation and perfusion cell studies, it is important to consider the thermal influence on absorption or to perform the latter at a standardized temperature (32±1 °C).



中文翻译:

生理相关温度对活性物质真皮吸收的影响-人体皮肤的一项体外研究。

皮肤温度在物质的皮肤吸收中起一定作用,但是在很大程度上由生理温度调节或环境条件引起的皮肤温度诱导的调节的程度和机理尚不清楚。在三个皮肤温度(25、32和39°C)下,研究了真皮温度对人体模型脂肪亲和性化合物(苯甲醚)和模型亲水性化合物(1,4-二恶烷,乙醇)吸收的影响。体外扩散细胞模型。将该物质施用于皮肤并监测透皮渗透。所有物质的渗透行为均表现出温度依赖性(3 h:25–39°C:累计的透皮渗透量增加202–275%)。尽管绝对吸收量很小(45分钟vs. 3小时:4.5-14.5),但在暴露后45分钟内,相对于温度的吸收相对差异最大(25–39°C:累积渗透率增加347–653%)。 %)。无论血液循环如何,皮肤温度都会显着影响皮肤吸收的量和动力学。脂质层顺序或多孔途径的与物质有关的,与温度有关的变化可能有助于渗透。透皮渗透的早期调节表明跨膜吸收,这可能与短期接触有关。对于毒理学评估和灌注细胞研究,重要的是要考虑热对吸收的影响或在标准温度(32±1°C)下进行吸收。尽管绝对吸收量很小(45分钟对3小时:4.5-14.5%),但累积渗透率却增加了347–653%。无论血液循环如何,皮肤温度都会显着影响皮肤吸收的量和动力学。脂质层顺序或多孔途径的与物质有关的,与温度有关的变化可能有助于渗透。透皮渗透的早期调节表明跨阑尾吸收,这可能与短期暴露有关。对于毒理学评估和灌注细胞研究,重要的是要考虑热对吸收的影响或在标准温度(32±1°C)下进行吸收。尽管绝对吸收量很小(45分钟对3小时:4.5-14.5%),但累积渗透率却增加了347–653%。无论血液循环如何,皮肤温度都会显着影响皮肤吸收的量和动力学。脂质层顺序或多孔途径的与物质有关的,与温度有关的变化可能有助于渗透。透皮渗透的早期调节表明阑尾吸收,这可能与短期暴露有关。对于毒理学评估和灌注细胞研究,重要的是要考虑热对吸收的影响或在标准温度(32±1°C)下进行吸收。皮肤温度显着影响真皮吸收的量和动力学。脂质层顺序或多孔途径的与物质有关的,与温度有关的变化可能有助于渗透。透皮渗透的早期调节表明跨膜吸收,这可能与短期接触有关。对于毒理学评估和灌注细胞研究,重要的是要考虑热对吸收的影响或在标准温度(32±1°C)下进行吸收。皮肤温度显着影响真皮吸收的量和动力学。脂质层顺序或多孔途径的与物质有关的,与温度有关的变化可能有助于渗透。透皮渗透的早期调节表明阑尾吸收,这可能与短期暴露有关。对于毒理学评估和灌注细胞研究,重要的是要考虑热对吸收的影响或在标准温度(32±1°C)下进行吸收。这可能与短期风险有关。对于毒理学评估和灌注细胞研究,重要的是要考虑热对吸收的影响或在标准温度(32±1°C)下进行吸收。这可能与短期风险有关。对于毒理学评估和灌注细胞研究,重要的是要考虑热对吸收的影响或在标准温度(32±1°C)下进行吸收。

更新日期:2020-08-12
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