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Electrochemotherapy, Electrogenetherapy, and Transdermal Drug Delivery pp 187–211Cite as

Mechanism of Transdermal Drug Delivery by Electroporation

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Part of the book series: Methods in Molecular Medicine ((MIMM,volume 37))

Abstract

Human skin is a complex system, providing a formidable obstacle to drug delivery Fig. 1 (1–3). In particular, the stratum corneum (SC) is the primary barrier to transdermal drug delivery. The stratum corneum is made up of corneocytes, which are flattened remnants of cells, surrounded by lipid bilayer membranes (2,3). Because lipid-based structures tend to exclude charged species, the multilamellar arrangement acts as a “brick wall” (4) to prevent ionic and molecular transport.

1. Key features of skin, skin barriers (104) and hypothetical aqueous pathways. The stratum corneum (SC) is the dead outermost layer (≈ 20 μm hydrated thickness) that is the main barrier to transport, particularly for charged molecules (1–3,5). Appendages (sweat ducts and hair follicles) penetrate the SC, but are lined with a double cell layer with tight junctions (105), which prevents significant transport. Hypothetical transport sites are labeled: LV (low voltage): Iontophoresis involves transport through preexisting aqueous pathways associated with appendages or around corneocytes within the SC (7,8,53,55,106). MV (moderate voltage) pulses: A relatively fast (>10 ms) process of “macropore activation” is followed by cell lining electroporation, which is hypothesized to create new aqueous pathways at appendages (“appendageal electroporation”) (40,107). HV (high voltage) pulses: A very fast (<10 μs) process is hypothesized to involve a primary event of aqueous pathway creation based on electroporation of multilamellar lipid bilayers separating corneocytes (27,61,63,91,108), and secondary processes such as localized heating, or pathwayenlarging chemical introduction. Lower right: The original “brick wall model” of the SC (the largest area skin feature) intended to treat permeation of lipophilic molecules through the continuous “mortar” (4).

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Author information

Authors and Affiliations

  1. Massachusetts Intitute of Technology, Cambridge, MA

    Timothy E. Vaughan

  2. Department of Chemical Engineering, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA

    James C. Weaver

Authors
  1. Timothy E. Vaughan
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  2. James C. Weaver
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Editor information

Editors and Affiliations

  1. University of South Florida College of Medicine, USA

    Mark J. Jaroszeski PhD  & Richard Heller PhD  & 

  2. University of South Florida College of Engineering, USA

    Richard Gilbert PhD

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© 2000 Humana Press Inc., Totowa, NJ

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Vaughan, T.E., Weaver, J.C. (2000). Mechanism of Transdermal Drug Delivery by Electroporation. In: Jaroszeski, M.J., Heller, R., Gilbert, R. (eds) Electrochemotherapy, Electrogenetherapy, and Transdermal Drug Delivery. Methods in Molecular Medicine, vol 37. Humana Press. https://doi.org/10.1385/1-59259-080-2:187

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  • DOI: https://doi.org/10.1385/1-59259-080-2:187

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-606-2

  • Online ISBN: 978-1-59259-080-3

  • eBook Packages: Springer Protocols

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