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局部温度升高对体内电穿孔孔发育的影响:角质层脂质相转变数值模型

Local temperature rises influence in vivo electroporation pore development: a numerical stratum corneum lipid phase transition model.

作者信息

Becker S M, Kuznetsov A V

机构信息

Mechanical and Aerospace Engineering, North Carolina State University, Box 7910, Raleigh, North Carolina 27695, USA.

出版信息

J Biomech Eng. 2007 Oct;129(5):712-21. doi: 10.1115/1.2768380.

Abstract

Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. Electroporation temporarily destabilizes the structure of the outer skin layer, the stratum corneum, by creating microscopic pores through which agents, ordinarily unable to pass into the skin, are able to pass through this outer barrier. Long duration electroporation pulses can cause localized temperature rises, which result in thermotropic phase transitions within the lipid bilayer matrix of the stratum corneum. This paper focuses on electroporation pore development resulting from localized Joule heating. This study presents a theoretical model of electroporation, which incorporates stratum corneum lipid melting with electrical and thermal energy equations. A transient finite volume model is developed representing electroporation of in vivo human skin, in which stratum corneum lipid phase transitions are modeled as a series of melting processes. The results confirm that applied voltage to the skin results in high current densities within the less resistive regions of the stratum corneum. The model captures highly localized Joule heating within the stratum corneum and subsequent temperature rises, which propagate radially outward. Electroporation pore development resulting from the decrease in resistance associated with lipid melting is captured by the lipid phase transition model. As the effective pore radius grows, current density and subsequent Joule heating values decrease.

摘要

电穿孔是一种用于增强大分子经皮转运的方法,该方法是使皮肤暴露于一系列电脉冲中。电穿孔通过产生微观孔隙暂时破坏皮肤外层即角质层的结构,使得通常无法进入皮肤的物质能够穿过这一外部屏障。长时间的电穿孔脉冲会导致局部温度升高,进而在角质层的脂质双分子层基质内引发热致相变。本文聚焦于由局部焦耳热导致的电穿孔孔隙形成。本研究提出了一个电穿孔的理论模型,该模型将角质层脂质熔化与电能和热能方程相结合。开发了一个瞬态有限体积模型来模拟体内人体皮肤的电穿孔过程,其中角质层脂质相变被模拟为一系列熔化过程。结果证实,施加于皮肤的电压会在角质层电阻较小的区域内产生高电流密度。该模型捕捉到了角质层内高度局部化的焦耳热以及随后的温度升高,且温度升高是径向向外传播的。脂质相变模型捕捉到了由脂质熔化导致的电阻降低所引起的电穿孔孔隙形成。随着有效孔隙半径的增大,电流密度以及随后的焦耳热数值会降低。

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