Transdermal Delivery of Macromolecules Using Two-in-One Nanocomposite Device for Skin Electroporation

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.

Defeating Melanoma Through a Nano-Enabled Revision of Hypoxic and Immunosuppressive Tumor Microenvironment

“… 27 Micro-molecules can penetrate stratum corneum in small quantities, or directly enter the epidermis through sweat glands and pores, but for macro-molecules, penetration is still challenging. 28 In recent years, transdermal administration has been reported to reduce unnecessary drug uptake and directly target tumor sites under the epidermis, which increases the effective drug concentration and amplifies the therapeutic outcome. 29 Borneol has been widely used as a skin puncturing material in traditional Chinese medicine, which mechanism involved disrupting stratum corneum bilayer, increasing drug diffusion coefficient, and inducing the formation of transient pores.…”

Buccal Permeation of Polysaccharide High Molecular Weight Compounds: Effect of Chemical Permeation Enhancers

“…Despite these limitations, fluorescent-labeled dextrans are widely used to mimic high MW compounds because of their low cost, high analytical sensitivity, and reasonably good predictivity. For instance, they are typically used as markers for blood–brain barrier leakage mimicking proteins [ 23 ], as a marker for the effectiveness of skin electroporation [ 24 ], to evaluate the capability of the permeation enhancers to improve peptide drug absorption across the intestinal epithelium [ 25 ], or to evaluate paracellular transport in oral peptide delivery studies [ 26 ].…”

Transdermal Drug Delivery Systems: A Focused Review of the Physical Methods of Permeation Enhancement

“…The device showed excellent results of transitory skin permeability and rapid delivery of small molecules into the dermis. 57 …”