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.

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.

dry eye syndrome, it is important to keep the lens moist and maintain tears between the CL and the ocular surface, which is here referred to TCO (the initial letters of tear, contact lens, and ocular). Conventional rehydration by regular eye drops, the electrical stimulation of the lacrimal gland, [17] and treatment with a punctum plug [18] will increase the total tear fluid in eye, but cannot directly address the maintenance of the amount of TCO. The only example so far of a smart CL for maintaining the TCO is that of Lee et al., who developed a CL coated with single layer of graphene which decreases the moisture evaporation. [19] Hence, there is still a high demand to develop a CL equipped with an antidehydration function.In this paper, we report that electroosmotic flow (EOF) can be induced in a soft CL in order to maintain the moisture of the lens. EOF is the motion of water induced by an applied voltage across a fluid conduit like a capillary tube [20,21] or a porous material such as hydrogels. [22,23] When the fluid conduit contains fixed electrical charges, the dominant electromigration of the mobile counterions produces net water flow. [24,25] For example, due to the large amount of carboxyl groups in keratin in the stratum corneum of the skin, the transdermal iontophoretic current is known to be accompanied by the EOF from anode to cathode, which assists the penetration of drugs into the skin. [26][27][28] Here, we first developed charge-fixed hydrogel materials and studied their properties as the fluid conduit for EOF generation. The density of the fixed charge was optimized by adjusting the mechanical strength and the efficiency of EOF generation (EOF strength). It was successfully demonstrated that the upward EOF within the soft CL can maintain moisture of the lens itself and also the TCO as illustrated in Figure 1, by in situ monitoring of conductance and by microscope observations. As an example of a built-in power source for EOF generation, the mounting of batteries (Mg/O 2 battery and fructose/O 2 enzymatic battery) was also demonstrated. Results and Discussion EOF Generation in Charged HydrogelsThe hydrogel materials composed of 2-hydroxyethyl methacrylate (HEMA), methyl methacrylate (MMA), and methacrylic acid (MA) were prepared using a the copolymerization ratio of Contact lenses (CLs) can be a cause of "dry eye syndrome" that can lead to corneal wounds and inflammation as well as a feeling of discomfort. To prevent the dry eye, it is important to keep the lens moist and maintain tears between the CL and the ocular surface. Here, the use of electroosmotic flow (EOF) in a CL is reported as a novel mechanism for antidehydration. A CL made from a charged hydrogel has served as the fluid conduit for EOF generation. The charge density of the gel is optimized by varying the composition ratio of anionic monomer having carboxyl group, by taking into account the efficiency of EOF generation and the mechanical strength of the hydrogels. By in situ monitoring of conductance and by microscope observations,...

A charged porous microneedle (PMN) generates the electroosmotic flow (EOF) and promotes the through‐needle transport of molecules and particles, indicating its applicability for the EOF‐based low‐invasive transdermal delivery of drugs and vaccines. The negatively charged PMN is prepared by grafting a thin film of poly (2‐acrylamido‐2‐methylpropanesulfonic acid) (PAMPS) onto the inner wall of the microchannels of the polyglycidyl methacrylate PMN. Promoted transport from anode to cathode is observed for albumin, Au nanoparticles (15, 50 nm), and silica beads (100 nm), indicating the generation of an EOF strong enough to transport these negatively charged larger size species against their electrophoretic motion. A model antigen ovalbumin (OVA) is preloaded in the PMN, and is injected to a hydrogel and a pig skin with a higher efficiency (more than 2 times) than the conventional diffusion‐based passive release. These results successfully demonstrate the novel EOF‐based effective injection of drugs and vaccines into the skin, achieved by the newly developed charged PMN.

A totally organic, flexible higher voltage enzymatic biobattery is demonstrated by series connection of carbon fabric-based biobatteries composed of a fructose dehydrogenase-modified anode and a bilirubin oxidase-modified cathode. The fructose/O2 biobattery was divided and connected so as to maintain the original size (total electrode size: 2 cm2). The series-connected four quarter biobatteries showed increased voltage and current (0.6 V, 30 μA → 1.5 V, 80 μA) for an external load of 20 kΩ, which is a typical skin resistance. The divided batteries were put inside a flexible ion-insulating frame to avoid short-circuit between cells and electrically connected by soft hydrophobic leads that prevented ionic connection by wetting. Because the developed higher voltage biobattery maintains its small size and flexibility, it can even be put on a finger joint and serve to drive a wrist watch.