Skin electroporation for transdermal drug delivery: Electrical measurements, numerical model and molecule delivery.

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.

Innovative ceramic-matrix composite substrates with tunable electrical conductivity for high-power applications.

A wide band gap semiconductor power module can operate at higher voltages as compared with its traditional silicon counterpart. However, its insulating system undergoes stronger electric fields at the triple point between the ceramic substrate, the metallic tracks and the encapsulating polymer, which can dramatically reduce its lifespan. Here we report an original concept based on the local modification of the substrate properties to mitigate such electrical stress. Numerical simulations revealed its potential to reduce this constraint by up to 50%. This concept was realized by developing, through a practical approach, a novel substrate made of an AlN-based ceramic (material A) integrating a nanocomposite volume endowed with controlled properties and geometry. This approach implies first the spark plasma sintering of the AlN powder with additives (Y2O3, CaF2) to endow the material A with a very low electrical conductivity (σ) and high thermal conductivity (k). Graphene nanoplatelets (GNP) were incorporated within this material to fabricate a nanocomposite with a controlled σ anisotropy that otherwise reached a striking ratio of 106 at 20°C for 1.25 vol% GNP. Our approach secondly aimed at developing an effective process allowing to integrate this nanocomposite into the material A with a very high degree of reproducibility. It finally consisted in establishing the electrical contacts on the achieved substrate and encapsulating it for breakdown testing. The novel substrate enabled a mitigation of the electrical constraint by diminishing its intensity and shifting it from the triple point to a less constrained area. It already brought an improvement in breakdown voltage (VB) by 15% as compared to the traditional substrate, and revealed the potential for achieving higher VB as well. This work lays the foundation for the development of novel multifunctional ceramic-matrix composite substrates sought for power electronics as well as for other potential applications.