In this paper, we discuss some of the primary experimental factors that should be considered when interpreting and implementing the published results of skin electroporation studies concerning measurements of mass transport across the stratum corneum (SC) in the Franz cell. It is explained that the pulse magnitude should always be considered in the context of pulse shape and that transport measurements should always be presented in the context of the trans-SC potential difference (instead of the voltage between the electrodes). The condition of the SC prior to the application of the long-duration pulse strongly influences the evolution of the local transport region (LTR). This is quantified in a simple analytical investigation of the conditions that affect the thermodynamic response of the skin.
Issue Section:
Technical Brief
References
1.
Williams
, A.
, 2003
, Transdermal and Topical Drug Delivery: From Theory to Clinical Practice
, Pharmaceutical Press
, London
.2.
Zorec
, B.
, Préat
, V.
, Miklavčič
, D.
, and Pavšelj
, N.
, 2013
, “Active Enhancement Methods for Intra- and Transdermal Drug Delivery: A Review
,” Slov. Med. J.
, 82
(5
), pp. 339
–356
.3.
Escobar-Chavez
, J.
, Bonilla-Martinez
, D.
, Villegas-Gonzalez
, M.
, and Revilla-Vazquez
, A.
, 2009
, “Electroporation as an Efficient Physical Enhancer for Skin Drug Delivery
,” J. Clin. Pharmacol.
, 49
(11
), pp. 1262
–1283
.4.
Denet
, A. R.
, Vanbever
, R.
, and Preat
, V.
, 2004
, “Skin Electroporation for Transdermal and Topical Delivery
,” Adv. Drug Delivery Rev.
, 56
(5
), pp. 659
–674
.5.
Pliquett
, U.
, and Weaver
, J. C.
, 1996
, “Electroporation of Human Skin: Simultaneous Measurement of Changes in the Transport of Two Fluorescent Molecules and in the Passive Electrical Properties
,” Bioelectrochem. Bioenerg.
, 39
(1
), pp. 1
–12
.6.
Pliquett
, U. F.
, and Gusbeth
, C. A.
, 2000
, “Perturbation of Human Skin Due to Application of High Voltage
,” Bioelectrochemistry
, 51
(1
), pp. 41
–51
.7.
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
, 60
(1
), pp. 35
–47
.8.
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
, 1239
(2
), pp. 111
–121
.9.
Tieleman
, D. P.
, 2004
, “The Molecular Basis of Electroporation
,” BMC Biochem.
, 5
(10
), pp. 1
–12
.10.
Silva
, C. L.
, Nunes
, S. C. C.
, Eusébio
, M. E. S.
, Sousa
, J. J. S.
, and Pais
, A.
, 2006
, “Study of Human Stratum Corneum and Extracted Lipids by Thermomicroscopy and DSC
,” Chem. Phys. Lipids
, 140
(1–2
), pp. 36
–47
.11.
Pliquett
, U.
, and Gusbeth
, C.
, 2004
, “Surface Area Involved in Transdermal Transport of Charged Species Due to Skin Electroporation
,” Bioelectrochemistry
, 65
(1
), pp. 27
–32
.12.
Pliquett
, U.
, Gallo
, S.
, Hui
, S. W.
, Gusbeth
, C.
, and Neumann
, E.
, 2005
, “Local and Transient Structural Changes in Stratum Corneum at High Electric Fields: Contribution of Joule Heating
,” Bioelectrochemistry
, 67
(1
), pp. 37
–46
.13.
Reberšek
, M.
, Miklavcic
, D.
, Bertacchini
, C.
, and Sack
, M.
, 2014
, “Cell Membrane Electroporation—Part 3: The Equipment
,” IEEE Electr. Insul. Mag.
, 30
(3
), pp. 8
–18
.14.
Prausnitz
, M. R.
, Bose
, V. G.
, Langer
, R.
, and Weaver
, J. C.
, 1993
, “Electroporation of Mammalian Skin: A Mechanism to Enhance Transdermal Drug Delivery
,” Proc. Natl. Acad. Sci.
, 90
(22
), pp. 10504
–10508
.15.
Vanbever
, R.
, and Preat
, V.
, 1995
, “Factors Affecting Transdermal Delivery of Metoprolol by Electroporation
,” Bioelectrochem. Bioenerg.
, 38
(1
), pp. 223
–228
.16.
Gallo
, S. A.
, Oseroff
, A. R.
, Johnson
, P. G.
, and Hui
, S. W.
, 1997
, “Characterization of Electric-Pulse-Induced Permeabilization of Porcine Skin Using Surface Electrodes
,” Biophys. J.
, 72
(6
), pp. 2805
–2811
.17.
Vanbever
, R.
, Fouchard
, D.
, Jadoul
, A.
, De Morre
, N.
, Preat
, V.
, and Marty
, J. P.
, 1998
, “In Vivo Noninvasive Evaluation of Hairless Rat Skin After High-Voltage Pulse Exposure
,” Skin Pharmacol. Appl. Skin Physiol.
, 11
(1
), pp. 23
–34
.18.
Pliquett
, U. F.
, Vanbever
, R.
, Preat
, V.
, and Weaver
, J. C.
, 1998
, “Local Transport Regions (LTRs) in Human Stratum Corneum Due to Long and Short “High Voltage” Pulses
,” Bioelectrochem. Bioenerg.
, 47
(1
), pp. 151
–161
.19.
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.
, 74
(2
), pp. 843
–856
.20.
Pliquett
, U. F.
, Gusbeth
, C. A.
, and Weaver
, J. C.
, 2000
, “Non-Linearity of Molecular Transport Through Human Skin Due to Electric Stimulus
,” J. Controlled Release
, 68
(3
), pp. 373
–386
.21.
Martin
, G. T.
, Pliquett
, U. F.
, and Weaver
, J. C.
, 2002
, “Theoretical Analysis of Localized Heating in Human Skin Subjected to High Voltage Pulses
,” Bioelectrochemistry
, 57
(1
), pp. 55
–64
.22.
Pliquett
, U. F.
, Martin
, G. T.
, and Weaver
, J. C.
, 2002
, “Kinetics of the Temperature Rise Within Human Stratum Corneum During Electroporation and Pulsed High-Voltage Iontophoresis
,” Bioelectrochemistry
, 57
(1
), pp. 65
–72
.23.
Dujardin
, N.
, Staes
, E.
, Kalia
, Y.
, Clarys
, P.
, Guy
, R.
, and Preat
, V.
, 2002
, “In Vivo Assessment of Skin Electroporation Using Square Wave Pulses
,” J. Controlled Release
, 79
(1–3
), pp. 219
–227
.24.
Denet
, A. R.
, and Preat
, V.
, 2003
, “Transdermal Delivery of Timolol by Electroporation Through Human Skin
,” J. Controlled Release
, 88
(2
), pp. 253
–262
.25.
Wong
, T.-W.
, Chen
, C.-H.
, Huang
, C.-C.
, Lin
, C.-D.
, and Hui
, S.-W.
, 2006
, “Painless Electroporation With a New Needle-Free Microelectrode Array to Enhance Transdermal Drug Delivery
,” J. Controlled Release
, 110
(3
), pp. 557
–565
.26.
Zorec
, B.
, Becker
, S.
, Reberšek
, M.
, Miklavčič
, D.
, and Pavšelj
, N.
, 2013
, “Skin Electroporation for Transdermal Drug Delivery: The Influence of the Order of Different Square Wave Electric Pulses
,” Int. J. Pharm.
, 457
(1
), pp. 214
–223
.27.
Blagus
, T.
, Markelc
, B.
, Cemazar
, M.
, Kosjek
, T.
, Preat
, V.
, Miklavcic
, D.
, and Sersa
, G.
, 2013
, “In Vivo Real-Time Monitoring System of Electroporation Mediated Control of Transdermal and Topical Drug Delivery
,” J. Controlled Release
, 172
(3
), pp. 862
–871
.28.
Vanbever
, R.
, Lecouturier
, N.
, and Préat
, V.
, 1994
, “Transdermal Delivery of Metoprolol by Electroporation
,” Pharm. Res.
, 11
(11
), pp. 1657
–1662
.29.
Vanbever
, R.
, LeBoulengé
, E.
, and Préat
, V.
, 1996
, “Transdermal Delivery of Fentanyl by Electroporation. I. Influence of Electrical Factors
,” Pharm. Res.
, 13
(4
), pp. 559
–565
.Copyright © 2015 by ASME
You do not currently have access to this content.
