Abstract
A microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery. Here, we report the applications of solid polymer-based ion-conductive porous microneedles (PMN) containing interconnected micropores for improving iontophoresis, which is a technique of enhancing transdermal molecular transport by a direct current through the skin. The PMN modified with a charged hydrogel brings three innovative advantages in iontophoresis at once: (1) lowering the transdermal resistance by low-invasive puncture of the highly resistive stratum corneum, (2) transporting of larger molecules through the interconnected micropores, and (3) generating electroosmotic flow (EOF). In particular, the PMN-generated EOF greatly enhances the transdermal molecular penetration or extraction, similarly to the flow induced by external pressure. The enhanced efficiencies of the EOF-assisted delivery of a model drug (dextran) and of the extraction of glucose are demonstrated using a pig skin sample. Furthermore, the powering of the PMN-based transdermal EOF system by a built-in enzymatic biobattery (fructose / O2 battery) is also demonstrated as a possible totally organic iontophoresis patch.
Highlights
A microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery
The length of the porous microneedles (PMN) itself was designed to be 250 μm so that it can penetrate to the epidermic layer through the stratum corneum without reaching the sensory nerves in the dermis layer of skin[24,25,46], and the subjects did not feel any discomfort from its insertion
Mechanical stability of the porous microneedle was confirmed (Supplementary Fig. 3), and the cytocompatibility was checked by the Live-Dead test of dermal fibroblast cultured with the chip (Supplementary Fig. 4)
Summary
A microneedle array is an attractive option for a minimally invasive means to break through the skin barrier for efficient transdermal drug delivery. We report the applications of solid polymer-based ion-conductive porous microneedles (PMN) containing interconnected micropores for improving iontophoresis, which is a technique of enhancing transdermal molecular transport by a direct current through the skin. The microneedles should contain fluid conduits like the cylindrical hole of traditional injection needles[35,36,37], but the mass fabrication of a hollow structure in a μm-scale needle has been found to be difficult[37] Another type of fluid permeable microneedle is the solid-based porous microneedle (PMN)[38,39,40,41,42,43,44,45]. EOF generation via the PMN has not yet been studied so far
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