Theoretical analysis of localized heating in human skin subjected to high voltage pulses
Introduction
Controlled, transdermal delivery of therapeutic agents is potentially of major clinical importance. This process requires an increase in skin permeability such that a sufficient amount of drug may be transported in a controlled fashion. Electroporation, which can increase the permeability of bilayer lipid membranes in the stratum corneum (SC) using high voltage pulses, has potential as a mechanism for transdermal drug delivery.
Despite the number of studies that investigate the application of electroporation to transdermal drug delivery [1], [2], [3], [4], very little attention has been given to the thermal effects that may be caused by these high voltage pulses. A voltage pulse causes an associated current flow through the skin, which due to its finite electrical resistance, will increase the local skin temperature through electrical dissipation (Joule heating). This local temperature rise may affect: (1) the barrier function of the skin if the temperature rise causes a phase change in the SC lipids and/or a denaturization of SC proteins; (2) the local morphology of the skin structure if the heating causes water to vaporize; and (3) the therapeutic molecules destined for transdermal drug delivery. Further, if nearby epidermal tissues experience a prolonged temperature rise beyond a threshold, damage may result. It is the purpose of the present theoretical study to model and investigate the magnitude of the temperature rise within skin during electroporation and to assess the potential thermally mediated effects.
Section snippets
Materials and methods
The skin's barrier function is mainly afforded by the stratum corneum (SC), a multi-lamella structure within the first ∼20 μm of the skin surface. This structure exhibits a very high electrical resistance and an extremely low permeability to transport. Thus, an electric field applied across skin will concentrate mainly within the SC. Depending on the pulse duration, an electric “breakdown” is likely to occur if the voltage across the SC is about 50–100 V. During this breakdown, the resistance
Results and discussion
Fig. 3 summarizes the simulation results for both the conduction and the convection models. The top panel shows the peak temperature rise resulting from an exponential pulse, τpulse=1 ms, for thermal conduction alone (solid line) and thermal convection (dashed line—fluid velocity of 1 m/s, dashed–dotted line—fluid velocity of 5 m/s). This peak temperature rise is taken at the center of the LDR (z=0, r=0) where the temperature is greatest at any given time. In the case of conduction alone, the
Conclusion
Tissue electroporation holds promise as a mechanism for transdermal drug delivery. Of the many studies performed to date, very little attention has been given to the thermal effects that may be induced by these high voltage pulses. In this study, we have performed analytical and computer modeling of the temperature rise in the stratum corneum (SC) during electroporation. Current flowing through aqueous pathways created by electroporation dissipates electrical energy into heat energy. It is the
Acknowledgements
Supported by NIH Grant ARH4921 and Whitaker Foundation grant RR10963. The authors would like to thank Dr. Timothy Vaughan for his insight, comments and assistance.
References (24)
- et al.
Transport of a charged molecule across the human epidermis due to electroporation
J. Controlled Release
(1996) - et al.
Imaging of fluorescent molecule and small ion transport through human stratum corneum during high voltage pulsing: localized transport regions are involved
Biophys. Chem.
(1996) - et al.
Changes in the passive electrical properties of human stratum corneum due to electroporation
Biochim. Biophys. Acta
(1995) - et al.
Imaging of fluorescent molecule and ion transport through human stratum corneum during high-voltage pulsing: localized transport regions are involved
J. Biophys. Chem.
(1996) - et al.
Imaging regions of transport across human stratum corneum during high voltage and low voltage exposures
J. Pharm. Sci.
(1996) - et al.
Skin electroporation causes molecular transport across the stratum corneum through local transport regions
J. Invest. Dermatol. Symp. Proc.
(1998) - et al.
Theory of electroporation for a planar bilayer membrane: predictions of the fractional aqueous area, change in capacitance and pore–pore separation
Biophys. J.
(1994) - et al.
Theory of electroporation: a review
Bioelectrochem. Bioenerg.
(1996) - et al.
Kinetics of the temperature rise within human stratum corneum during electroporation and pulse high-voltage iontophoresis
Bioelectrochemistry
(2002) - et al.
In vivo non-invasive evaluation of hairless rat skin after high-voltage pulse exposure
Skin Pharmacol. Appl. Skin Physiol.
(1998)
Electroporation of mammalian skin: a mechanism to enhance transdermal drug delivery
Proc. Natl. Acad. Sci. U. S. A.
Cited by (0)
- 1
Present address: Faculty of Chemistry/PCIII, University of Bielefeld, D-33615 Bielefeld, Germany, Tel.: +49-521-106-6261.