Electroporation is an approach used to enhance transdermal transport of large molecules in which the skin is exposed to a series of electric pulses. The structure of the transport inhibiting outer layer, the stratum corneum, is temporarily destabilized due to the development of microscopic pores. Consequently agents that are ordinarily unable to pass into the skin are able to pass through this outer barrier. Of possible concern when exposing biological tissue to an electric field is thermal tissue damage associated with Joule heating. This paper shows the importance of using a composite model in calculating the electrical and thermal effects associated with skin electroporation. A three-dimensional transient finite-volume model of in vivo skin electroporation is developed to emphasize the importance of representing the skin’s composite layers and to illustrate the underlying relationships between the physical parameters of the composite makeup of the skin and resulting thermal damage potential.

1.
Mir
,
L. M.
, 2000, “
Therapeutic Perspectives of In Vivo Cell Elecropermeabilization
,”
Bioelectrochemistry
1567-5394,
53
, pp.
1
10
.
2.
Orlowski
,
S.
, and
Mir
,
L. M.
, 1993, “
Cell Electropermeabilization: A New Tool for Biochemical and Pharmacological Studies
,”
Biochim. Biophys. Acta
0006-3002,
1154
, pp.
51
63
.
3.
Gehl
,
J.
, 2003, “
Electroporation: Theory and Methods, Perspectives for Drug Delivery, Gene Therapy and Research
,”
Acta Physiol. Scand.
0001-6772,
177
, pp.
437
447
.
4.
Weaver
,
J. C.
, 1993, “
Electroporation: A General Phenomenon for Manipulating Cells and Tissue
,”
J. Cell. Biochem.
0730-2312,
51
, pp.
426
435
.
5.
Weaver
,
J. C.
, 2000, “
Electroporation of Cells and Tissues
,”
IEEE Trans. Plasma Sci.
0093-3813,
28
, pp.
24
33
.
6.
Pliquet
,
U. F.
, and
Gusbeth
,
C. A.
, 2000, “
Perturbation of Human Skin Due to Application of High Voltage
,”
Bioelectrochemistry
1567-5394,
51
, pp.
41
51
.
7.
Prausnitz
,
M. R.
, 1996, “
The Effects of Electric Current Applied to the Skin: A Review for Transdermal Drug Delivery
,”
Adv. Drug Delivery Rev.
0169-409X,
18
, pp.
395
425
.
8.
Pliquett
,
U.
,
Zewert
,
T. E.
,
Chen
,
T.
,
Langer
,
R.
, and
Weaver
,
J. C.
, 1996, “
Imaging of Fluorescent Molecule and Small Ion Transport Through Human Stratum Corneum During High Voltage Pulsing: Localized Transport Regions are Involved
,”
Biophys. Chem.
0301-4622,
58
, pp.
185
204
.
9.
Prausnitz
,
M. R.
, 1996, “
Do High Voltage Pulses Cause Changes in Skin Structure?
J. Controlled Release
0168-3659,
40
, pp.
321
326
.
10.
Pliquett
,
U.
,
Langer
,
R.
, and
Weaver
,
J. C.
, 1995, “
Changes in the Passive Electrical Properties of Human Stratum Corneum Due to Electroporation
,”
Biochim. Biophys. Acta
0006-3002,
1239
, pp.
111
121
.
11.
Vanbever
,
R.
, and
Preat
,
V.
, 1999, “
In Vivo Efficacy and Safety of Skin Electroporation
,”
Adv. Drug Delivery Rev.
0169-409X,
35
, pp.
77
88
.
12.
Vanbever
,
R.
,
Langers
,
G.
,
Montmayeur
,
S.
, and
Preat
,
V.
, 1998, “
Transdermal Delivery of Fentanyl: Rapid Onset of Analgesia Using Skin Electroporation
,”
J. Controlled Release
0168-3659,
50
, pp.
225
235
.
13.
Pavselj
,
N.
, and
Preat
,
V.
, 2005, “
DNA Electrotransfer Into the Skin Using a Combination of One High- and One Low-Voltage Pulse
,”
J. Controlled Release
0168-3659,
106
(
3
), pp.
407
415
.
14.
Vanbever
,
R.
,
LeBoulenge
,
E.
, and
Preat
,
V.
, 1996, “
Transdermal Delivery of Fentanyl by Electroporation: I. Influence of Electrical Factors
,”
Pharm. Res.
0724-8741,
13
, pp.
559
565
.
15.
Vanbever
,
R.
,
Pliquett
,
U. F.
,
Preat
,
V.
, and
Weaver
,
J. C.
, 1999, “
Comparison of the Effects of Short, High-Voltage and Long, Medium-Voltage Pulses on Skin Electrical and Transport Properties
,”
J. Controlled Release
0168-3659,
60
, pp.
36
47
.
16.
Denet
,
A. R.
,
Vanbever
,
R.
, and
Préat
,
V.
, 2004, “
Skin Electroporation for Transdermal and Topical Delivery
,”
Adv. Drug Delivery Rev.
0169-409X,
56
, pp.
659
674
.
17.
Vanbever
,
R.
, and
Preat
,
V.
, 2003, “
Transdermal Delivery of Timolol by Electroporation Through Human Skin
,”
J. Controlled Release
0168-3659,
88
, pp.
253
262
.
18.
Suzuki
,
T.
,
Shin
,
B.
,
Fujikura
,
K.
,
Matsuzaki
,
T.
, and
Takata
,
K.
, 1998, “
Direct Gene Transfer Into Rat Liver Cells by Electroporation
,”
FEBS Lett.
0014-5793,
425
, pp.
436
440
.
19.
Muramatsu
,
T.
,
Nakamura
,
A.
, and
Park
,
H.
, 1998, “
In Vivo Electroporation: A Powerful and Convenient Means of Nontrivial Gene Transfer to Tissues of Living Animals
,”
Int. J. Mol. Med.
1107-3756,
1
, pp.
55
62
.
20.
Davalos
,
R. V.
,
Mir
,
L. M.
, and
Rubinsky
,
B.
, 2005, “
Tissue Ablation With Irreversible Electroporation
,”
Ann. Biomed. Eng.
0090-6964,
33
, pp.
223
231
.
21.
Davalos
,
R. V.
,
Rubinsky
,
B.
, and
Mir
,
L. M.
, 2003, “
Theoretical Analysis on the Thermal Effects During In Vivo Tissue Electroporation
,”
Bioelectrochemistry
1567-5394,
61
, pp.
99
107
.
22.
Becker
,
S. M.
, and
Kuznetsov
,
A. V.
, 2006, “
Numerical Modeling of In Vivo Plate Electroporation Thermal Dose Assessment
,”
ASME J. Biomech. Eng.
0148-0731,
128
(
1
), pp.
76
84
.
23.
Millington
,
P. F.
, and
Wilkinson
,
R.
, 1983,
Skin
,
Cambridge University Press
,
Cambridge, UK
.
24.
Pennes
,
H. H.
, 1948, “
Analysis of Tissue and Arterial Blood Temperatures in the Resting Forearm
,”
J. Appl. Physiol.
0021-8987,
1
, pp.
93
122
.
25.
Gehl
,
J.
,
Skovsgaard
,
T.
, and
Mir
,
L. M.
, 2002, “
Vascular Reactions to In Vivo Electroporation: Characterization and Consequences for Drug and Gene Delivery
,”
Biochim. Biophys. Acta
0006-3002,
1569
, pp.
51
58
.
26.
Cleasby
,
M. E.
,
Davey
,
J. R.
,
Reinten
,
T. A.
,
Graham
,
M. W.
,
James
,
D. E.
,
Kraegen
,
E. W.
, and
Cooney
,
G. J.
, 2005, “
Acute Bidirectional Manipulation of Muscle Glucose Uptake by In Vivo Electrotransfer of Constructs Targeting Glucose Transporter Genes
,”
Diabetes
0012-1797,
54
(
9
), pp.
2702
2711
.
27.
Sentjurc
,
M.
,
Cemazar
,
M.
, and
Sersa
,
G.
, 2004, “
EPR Oximetry of Tumors In Vivo in Cancer Therapy
,”
Spectrochim. Acta, Part A
0584-8539,
60
(
6
), pp.
1379
1385
.
28.
Gehl
,
J.
,
Skovsgaard
,
T.
, and
Mir
,
L. M.
, 2002, “
Vascular Reactions to In Vivo Electroporation: Characterization and Consequences for Drug and Gene Delivery
,”
Biochim. Biophys. Acta General Subjects
,
1569
(
1–3
), pp.
51
58
.
29.
Shih
,
T. C.
,
Kou
,
H. S.
, and
Lin
,
W. L.
, 2003, “
The Impact of Thermally Significant Blood Vessels in Perfused Tumor Tissue on Thermal Dose Distributions During Thermal Therapies
,”
Int. Commun. Heat Mass Transfer
0735-1933,
30
, pp.
975
985
.
30.
Svaasand
,
L. O.
,
Randeberg
,
L. L.
,
Aguilar
,
G.
,
Majaron
,
B.
,
Kimel
,
S.
,
Lavernia
,
E. J.
, and
Nelson
,
J. S.
, 2003, “
Cooling Efficiency of Cryogen Spray During Laser Therapy of Skin
,”
Lasers Surg. Med.
0196-8092,
32
, pp.
137
142
.
31.
Duck
,
F. A.
, 1990,
Physical Properties of Tissue: A Comprehensive Reference Book
,
Academic
,
London
.
32.
Wilson
,
S. B.
, and
Spence
,
V. A.
, 1988, “
A Tissue Heat Transfer Model for Relating Dynamic Skin Temperature Changes to Physiological Parameters
,”
Phys. Med. Biol.
0031-9155,
8
, pp.
895
912
.
33.
Chato
,
J. C.
, and
Lee
,
R. C.
, 1998, “
The Future of Biothermal Engineering
,”
Ann. N.Y. Acad. Sci.
0077-8923,
858
, pp.
1
20
.
34.
Hendriks
,
F. M.
,
Brokken
,
D.
,
Oomens
,
C. W. J.
, and
Baaijens
,
F. P. T.
, 2004, “
Influence of Hydration and Experimental Length Scale on the Mechanical Response of Human Skin In Vivo, Using Optical Coherence Tomography
,”
Br. J. Radiol.
0007-1285,
10
, pp.
231
241
.
35.
Wainwright
,
P.
, 2000, “
Thermal Effects of Radiation From Cellular Telephones
,”
Phys. Med. Biol.
0031-9155,
45
, pp.
2363
2372
.
36.
Bejan
,
A.
, 1993,
Heat Transfer
,
Wiley
,
New York
.
37.
Chizmadzhev
,
Y. A.
,
Indenbom
,
A. V.
,
Kuzmin
,
P. I.
,
Galichenko
,
S. V.
,
Weaver
,
J. C.
, and
Potts
,
R. O.
, 1998, “
Electrical Properties of Skin at Moderate Voltages: Contribution of Appendageal Macropores
,”
Biophys. J.
0006-3495,
74
, pp.
843
856
.
38.
Tung
,
L.
, 1996, “
Detrimental Effects of Electrical Fields on Cardiac Muscle
,”
Proc. IEEE
0018-9219,
84
, pp.
366
378
.
39.
Kim
,
Y.
,
Zieber
,
H. G.
, and
Wang
,
F. E.
, 1990, “
Uniformity of Current Density Under Stimulating Electrodes
,”
Crit. Rev. Biomed. Eng.
0278-940X,
17
, pp.
585
619
.
40.
Sapareto
,
S. A.
, and
Dewey
,
W. C.
, 1984, “
Thermal Dose Determination in Cancer Therapy
,”
Int. J. Radiat. Oncol., Biol., Phys.
0360-3016,
10
, pp.
787
800
.
41.
Dewhirst
,
M. W.
,
Viglianti
,
B. L.
,
Lora-Michiels
,
M.
,
Hanson
,
M.
, and
Hoopes
,
P. J.
, 2003, “
Basic Principles of Thermal Dosimetry and Thermal Thresholds for Tissue Damage From Hyperthermia
,”
Int. J. Hyperthermia
0265-6736,
19
(
3
), pp.
267
294
.
42.
Graham
,
S. J.
,
Chen
,
L.
,
Leitch
,
M.
,
Peters
,
R. D.
,
Bronskill
,
M. J.
,
Foster
,
F. S.
,
Henkelman
,
R. M.
, and
Plewes
,
D. B.
, 1999, “
Quantifying Tissue Damage Due to Focused Ultrasound Heating Observed by MRI
,”
Magn. Reson. Med.
0740-3194,
41
, pp.
321
328
.
43.
Patankar
,
S. V.
, 1980,
Numerical Heat Transfer and Fluid Flow
,
Hemisphere
,
Washington DC.
44.
Becker
,
S. M.
, and
Kuznetsov
,
A. V.
, 2007, “
Thermal Damage Reduction Associated With In Vivo Skin Electroporation: A Numerical Investigation Justifying Aggressive Pre-Cooling
,”
Int. J. Heat Mass Transfer
0017-9310,
50
, pp.
105
116
.
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