Skin electroporation for transdermal drug delivery : Electrical measurements, numerical model and molecule delivery
Copyright © 2024. Published by Elsevier B.V..
Skin electroporation for drug delivery involves the application of Pulsed Electric Fields (PEFs) on the skin to disrupt its barrier function in a temporary and non-invasive manner, increasing the uptake of drugs. It represents a potential alternative to delivery methods that are invasive (e.g. injections) or limited. We have developed a drug delivery system comprising nanocomposite hydrogels which act as a reservoir for the drug and an electrode for applying electric pulses on the skin. In this study, we employed a multi-scale approach to investigate the drug delivery system on a mouse skin model, through electrical measurements, numerical modeling and fluorescence microscopy. The Electrical properties indicated a highly non-linear skin conductivity behavior and were used to fine-tune the simulations and study skin recovery after electroporation. Simulation of electric field distribution in the skin showed amplitudes in the range of reversible tissue electroporation (400-1200 V/cm), for 300 V PEF. Fluorescence microscopy revealed increased uptake of fluorescent molecules compared to the non-pulsed control. We reported two reversible electroporation domains for our configuration: (1) at 100 V PEF the first local transport regions appear in the extracellular lipids of the stratum corneum, demonstrated by a rapid increase in the skin's conductivity and an increased uptake of lucifer yellow, a small hydrophilic fluorophore and (2) at 300 V PEF, the first permeabilization of nucleated cells occurred, evidenced by the increased fluorescence of propidium iodide, a membrane-impermeable, DNA intercalating agent.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:367 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 367(2024) vom: 31. März, Seite 235-247 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kougkolos, Georgios [VerfasserIn] |
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| Links: |
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| Themen: |
Drug delivery |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jconrel.2024.01.036 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367353296 |
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| 500 | |a Date Revised 25.03.2024 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024. Published by Elsevier B.V. | ||
| 520 | |a Skin electroporation for drug delivery involves the application of Pulsed Electric Fields (PEFs) on the skin to disrupt its barrier function in a temporary and non-invasive manner, increasing the uptake of drugs. It represents a potential alternative to delivery methods that are invasive (e.g. injections) or limited. We have developed a drug delivery system comprising nanocomposite hydrogels which act as a reservoir for the drug and an electrode for applying electric pulses on the skin. In this study, we employed a multi-scale approach to investigate the drug delivery system on a mouse skin model, through electrical measurements, numerical modeling and fluorescence microscopy. The Electrical properties indicated a highly non-linear skin conductivity behavior and were used to fine-tune the simulations and study skin recovery after electroporation. Simulation of electric field distribution in the skin showed amplitudes in the range of reversible tissue electroporation (400-1200 V/cm), for 300 V PEF. Fluorescence microscopy revealed increased uptake of fluorescent molecules compared to the non-pulsed control. We reported two reversible electroporation domains for our configuration: (1) at 100 V PEF the first local transport regions appear in the extracellular lipids of the stratum corneum, demonstrated by a rapid increase in the skin's conductivity and an increased uptake of lucifer yellow, a small hydrophilic fluorophore and (2) at 300 V PEF, the first permeabilization of nucleated cells occurred, evidenced by the increased fluorescence of propidium iodide, a membrane-impermeable, DNA intercalating agent | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Drug delivery | |
| 650 | 4 | |a Electrical properties | |
| 650 | 4 | |a FEM simulation | |
| 650 | 4 | |a Hydrogel | |
| 650 | 4 | |a Skin electroporation | |
| 650 | 4 | |a Stratum corneum | |
| 700 | 1 | |a Laudebat, Lionel |e verfasserin |4 aut | |
| 700 | 1 | |a Dinculescu, Sorin |e verfasserin |4 aut | |
| 700 | 1 | |a Simon, Juliette |e verfasserin |4 aut | |
| 700 | 1 | |a Golzio, Muriel |e verfasserin |4 aut | |
| 700 | 1 | |a Valdez-Nava, Zarel |e verfasserin |4 aut | |
| 700 | 1 | |a Flahaut, Emmanuel |e verfasserin |4 aut | |
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