A Model of Transdermal Drug Delivery through Electroporation

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Electroporation is a technique that applies high voltage pulses over short time periods, resulting in strong electric fields, to create micropores in cell membranes. When applied to the skin, electroporation causes Joule heating that creates local transport regions (LTRs) in the lipid bilayer of the stratum corneum (SC), which is the outermost layer of the epidermis that is most resistant to drug transport. The combined effect of micropores and LTR formation results in a significant increase in transdermal drug transport.

Previous studies only model the drug profile through the skin layers during the electric pulse, on the scale of 300 ms. Furthermore, previous studies only account for a pore that crosses the SC, not the epidermis and dermis. Based on the anatomy of hair follicles and sweat glands, more accurate models should model pores that extend past the SC. We used COMSOL Multiphysics®: a finite element analysis, solver, and multiphysics simulation software for our modeling. We modeled transdermal delivery of a DNA-based drug assisted by electroporation, using skin property values determined by in vitro studies for large charged molecules. The model covered 24 hours starting with a 300 ms electric pulse. Our cylindrical geometry accounts for the gel, SC, epidermis, and dermis. At the axis of the cylinder, a pore extends through all the skin layers, containing the gel with the drug. We modeled Joule heating that results in LTR formation, as well as the mass transfer during and after the pulse.

Our results demonstrate LTR formation during electroporation and its lasting impact after 24 hours. The concentration of drug at 24 hours decreases going down the LTR in the SC, with a slower decline in the epidermis and dermis. We validated our model through a mesh convergence analysis, comparison with another computational model, and comparison with an experimental study. Through a sensitivity analysis, we reinforced the importance of SC thickness in slowing drug transport.

This model can be used as a more accurate representation of electroporation as a proof of concept before clinical trials.

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electroporation, transdermal, drug delivery, stratum corneum, local transport region


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