Frustoconical porous microneedle for electroosmotic transdermal drug delivery.

A truncated cone-shaped porous microneedle (PMN) made of poly-glycidyl methacrylate was studied as a minimally invasive tool for transdermal drug delivery. The transdermal electrical resistance of a pig skin was evaluated during the indentation of the PMNs, revealing that the frustoconical PMN (300 µm height) significantly reduced the resistance of the skin by expanding the stratum corneum without penetrating into the skin. A thin film of poly (2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) was grafted onto the inner wall of the microchannels of the frustoconical PMN to generate electroosmotic flow (EOF) upon current application in the direction of injection of the drug into the skin. Owing to the synergy of the expansion of the stratum corneum and the EOF-promotion, the PAMPS-modified frustoconical PMN effectively enhances the penetration of larger (over 500 Da) molecules, such as dextran (∼10 kDa).

Transdermal electroosmotic flow generated by a porous microneedle array patch.

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.

Hydrogel-Based Organic Subdural Electrode with High Conformability to Brain Surface.

A totally soft organic subdural electrode has been developed by embedding an array of poly(3,4-ethylenedioxythiophene)-modified carbon fabric (PEDOT-CF) into the polyvinyl alcohol (PVA) hydrogel substrate. The mesh structure of the stretchable PEDOT-CF allowed stable structural integration with the PVA substrate. The electrode performance for monitoring electrocorticography (ECoG) was evaluated in saline solution, on ex vivo brains, and in vivo animal experiments using rats and porcines. It was demonstrated that the large double-layer capacitance of the PEDOT-CF brings low impedance at the frequency of brain wave including epileptic seizures, and PVA hydrogel substrate minimized the contact impedance on the brain. The most important unique feature of the hydrogel-based ECoG electrode was its shape conformability to enable tight adhesion even to curved, grooved surface of brains by just being placed. In addition, since the hydrogel-based electrode is totally organic, the simultaneous ECoG-fMRI measurements could be conducted without image artifacts, avoiding problems induced by conventional metallic electrodes.