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TECHNICAL PAPERS: Fluids/Heat/Transport

Local Temperature Rises Influence In Vivo Electroporation Pore Development: A Numerical Stratum Corneum Lipid Phase Transition Model

[+] Author and Article Information
S. M. Becker

Mechanical and Aerospace Engineering,  North Carolina State University, Box 7910, Raleigh, North Carolina 27695smbecker@unity.ncsu.edu

A. V. Kuznetsov

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

J Biomech Eng 129(5), 712-721 (Mar 07, 2007) (10 pages) doi:10.1115/1.2768380 History: Received November 03, 2006; Revised March 07, 2007

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.

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Copyright © 2007 by American Society of Mechanical Engineers
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Figures

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Figure 2

Comparisons between numerical code and analytic solution (one dimensional): (a) Electric potential and heating in which the domain represents a vertical line between the electrodes using Vapp=300V. (b) Steady state temperature (°C), in which the domain represents vertical depth below the skin’s surface using convection coefficient h=500W∕m3. Dotted lines separate composite sections.

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Figure 4

Upper panel sections: Joule heat solution (QJW∕m3) in the vicinity of the electroporation pore during an electroporation pulse with an applied potential of 300V. In upper panels (c) and (d), r:z=1:2 aspect ratios are used. Dotted line denotes dermal-epidermal junction. Dashed rectangle denotes SC boundary. Lower panel sections: SC electrical conductivity (S/m). In lower panels (c) and (d), r:z=0.35:1 aspect ratios are used. Dashed rectangle denotes SC boundary.

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Figure 5

Transient thermal solution (°C) at representative pulsing times of a single pulse with an applied voltage of 300V. Dotted line denotes dermal-epidermal junction. Dashed rectangle denotes SC boundary.

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Figure 6

Multiple short pulse spacing thermal solutions (°C) at the end of each of four 250ms, 300V pulses applied at 1s intervals. Dotted line denotes dermal-epidermal junction. Dashed line denotes SC boundary. Insets show lipid melt fraction contours (solid line) and contour of large Joule heat value QJ=1010W∕m3 (dashed-dotted line) in a close-up of the SC (dashed rectangle) using aspect ratios (r:z=1:4).

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Figure 7

Multiple long pulse spacing thermal solutions (°C) at the end of each of four 250ms, 300V pulses applied at 120s intervals. Dotted line denotes dermal-epidermal junction. Dashed line denotes SC boundary. Insets show lipid melt fraction contours (solid line) and contour of large Joule heat value QJ=1010W∕m3 (dashed-dotted line) in a close-up of the SC (dashed rectangle) using aspect ratios (r:z=1:4).

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Figure 8

Effective pore radius growth comparisons between 250ms, 300V pulses spaced at 1s intervals and at 120s intervals. Effective pore radius is defined by the minimum radius at which lipids are unaffected by thermal phase change.

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Figure 1

Physical model description: (a) electroporation skin fold, (b) composite skin layers (cylindrical), (c) close-up of trans-SC preexisting pore with unperturbed lipid configuration, and (d) close-up of electroporated SC: lipids undergoing structural phase transition

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Figure 3

Potential solution at representative pulsing times of a single 300V pulse. Dotted lines represent interfaces between composite layers. Insets show boundary of zero lipid melt fraction contour (φ=0) in a close-up of the SC (dashed rectangle) using aspect ratio (r:z=1:10).

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