Abstract
Delivery of hydrophilic molecules through the skin using electroporation is a promising alternative approach to intradermal injection. Recently, we developed a two-in-one electrode/reservoir material composed of carbon nanotubes and agarose hydrogel. In this work, we evaluated the potential of the device to achieve non-invasive transdermal drug delivery using skin electroporation. As it involved an electrode configuration different from the literature, critical questions were raised. First, we demonstrated the efficiency of the device to permeabilize the skin of hairless mice, as observed by propidium iodide (PI) uptake in the nuclei of the epidermis cells through macro fluorescence imaging and histology. Application of Lucifer yellow (LY) at different times after unipolar electroporation treatment demonstrated the partial reversibility of the skin permeabilization after 30 min, and as such, that barrier function properties tended to be restored. We uncovered, for the first time to our knowledge, an intrinsic asymmetry of permeation pathways generated in the stratum corneum during treatment. Electrophoresis was here the main driving force for macromolecule delivery, but it competed with passive diffusion through the generated aqueous pathways for smaller molecules. Finally, we validated 4 kDa dextran labelled with fluorescein isothiocyanate (FD4) as a model molecule to optimize the electrical parameters, needed to improve macromolecule delivery.
Highlights
Transdermal delivery is a very interesting route to explore for drug delivery
The quantification of the relative fluorescence intensity (RFI) confirmed the observed increased uptake of propidium iodide (PI) on the anode side, compared to the natural uptake that was obtained after 30 min (Figure 1b)
Transdermal delivery is a crucial route to explore in order to elaborate efficient treatTransdermal delivery is a crucial route to explore in order to elaborate efficient treatment protocol; the development of non-invasive methods alternative to injecment protocol; the development of non-invasive methods alternative to injection tion are challenged by the impermeable and hydrophobic stratum corneum (SC) skin layer
Summary
Transdermal delivery is a very interesting route to explore for drug delivery. It can be fast and allow longer-term delivery. As an example, it can be considered a suitable substitute for oral delivery when drug degradation occurring during digestion hinders its efficiency too much. To achieve transdermal delivery it needs to cross the stratum corneum (SC), the most external layer of the epidermis. Skin is impermeable to the passive diffusion of most hydrophilic and high molecular weight drugs, leading to the use of needles for direct injection [1]. The crossing of that hydrophobic protective layer is the main challenge for the development of alternative transdermal delivery methods and for those intended to be non-invasive. Many technologies were considered for transdermal delivery, relying on chemical enhancers, physical approaches such as ultrasound and iontophoresis, or microporation techniques involving microneedles, which were widely studied for the variety of composition and shaping they offer [2,3,4]
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