Skin electroporation for transdermal drug delivery: Electrical measurements, numerical model and molecule delivery
JOURNAL OF CONTROLLED RELEASE(2024)
摘要
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.
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关键词
Skin electroporation,Drug delivery,Hydrogel,FEM simulation,Electrical properties,Stratum corneum
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