Background: Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers. Methods: The influences of current intensity, pH levels, and drug concentration on the TEB hydrogel patch\'s permeability were explored using an adaptive ion electroosmosis system. The pharmacokinetic profile, facilitated by iontophoresis for transdermal permeation, was analyzed through the application of microdialysis technology. Scanning electron microscopy and transmission electron microscopy were employed to assess the impact of ion electroosmotic systems on skin integrity. Results: The cumulative drug accumulation within 8 h of the TEB hydrogel patches, assisted by iontophoresis, was 2.9 and 7.9 times higher than without iontophoresis assistance and TEB cream in the control group, respectively. TEB hydrogel patches assisted by iontophoresis can significantly increase the permeability of TEB, and the AUC(0-8 h) was 3.4 and 5.4 times higher, while the Cmax was 4.2 and 7.3 times higher than the TEB hydrogel patches without iontophoresis, respectively. This system has no significant impact on deep-layer cells. Conclusions: This system may offer a safe and effective clinical strategy for the local treatment of deep antifungal infections.

Iontophoretic transdermal drug delivery (TDD) devices are known to enhance the transdermal transport of drugs. However, conventional transdermal iontophoretic devices require external power sources, wired connections, or mechanical parts, which reduce the comfort level for patients during extended use. In this work, a self-powered, wearable transdermal iontophoretic patch (TIP) is proposed by harvesting ambient humidity for energy generation, enabling controlled TDD. This patch primarily uses moist-electric generators (MEGs) as its power source, thus obviating the need for complex power management modules and mechanical components. A single MEG unit can produce an open-circuit voltage of 0.80 V and a short-circuit current of 11.65 µA under the condition of 80% relative humidity. Amplification of the electrical output is feasible by connecting multiple generator units in series and parallel, facilitating the powering of certain commercial electronic devices. Subsequently, the MEG array is integrated with the TDD circuit to create the wearable TIP. After 20 min of application, the depth of drug penetration through the skin is observed to increase threefold. The effective promotion effect of TIP on the transdermal delivery of ionized drugs is corroborated by simulations and experiments. This wearable TIP offers a simple, noninvasive solution for TDD.

OBJECTIVE: To investigate the effect of calcium ions on promoting the penetrability of riboflavin into the corneal stroma by iontophoresis and to analyse the possible mechanism.
METHODS: Forty rabbits were divided into five groups randomly: 0.1% riboflavin-balanced salt solution (BSS) by iontophoresis group, 0.1% riboflavin-saline solution by iontophoresis group, 0.1% riboflavin-zinc gluconate solution by iontophoresis group, 0.1% riboflavin-calcium gluconate solution by iontophoresis group and classical riboflavin instillation after corneal de-epithelialization as the control group. The riboflavin concentrations in corneal stroma were determined and compared by high-performance liquid chromatography (HPLC) after removing epithelium and endothelium.
RESULTS: Iontophoretic delivery of a 0.1% riboflavin-calcium gluconate solution was the closest to the effect of classical de-epithelialization. The other solvents were unsufficient at enhancing the permeability of the riboflavin.
CONCLUSIONS: Calcium ions can promote the penetrability of riboflavin into the corneal stroma by iontophoresis.

Astrocytes are morphologically intricate cells and actively modulate the function of the brain. Through numerous fine processes, astrocytes come into contact with neurons, blood vessels, and other glia cells. Emerging evidence has shown that astrocytes exhibit brain regional diversity in their morphology, transcriptome, calcium signaling, and functions. However, little is known about the brain regional heterogeneity of astrocyte-astrocyte structural interaction. So far, the visualization and characterization of the morphological features of adjacent astrocytes have been difficult, and as a result, it is still well-accepted that astrocytes in the adult brain share non-overlapped territory. In contrast, employing an approach that combines viral labeling with dual-fluorescent dyes iontophoresis under brightfield and imaging using confocal microscopy allows for the efficient and specific labeling of adjacent astrocytes, enabling a comprehensive visualization of their fine processes and the degree of their territorial overlap. Our study in the hypothalamic regions of the brain revealed a marked spatial overlap among adjacent astrocytes, which differs from the conventional understanding based on more extensively studied regions, like the hippocampus. Additionally, we revealed the heterogeneity of the astrocyte-neuron ratio across brain regions and conducted an assessment of the photostability and labeling efficiency of fluorescent dyes used for labeling adjacent astrocytes. Our study provides new insights for studying the morphological heterogeneity of astrocytes across the central nervous system.

Effective treatment of deep-seated tumors relies on enhanced drug penetration in transdermal drug delivery systems. While microneedles (MNs) and iontophoresis techniques have shown improved transdermal drug delivery efficiency, challenges such as skin elasticity, high electrical resistance of the stratum corneum, and external power supply requirements hinder their efficacy in treating deep-seated tumors. In this study, a wearable, self-powered MN patch that integrates a flexible triboelectric nanogenerator (F-TENG) is presented, aimed at advancing deep-seated tumor therapy. MNs are composed of water-soluble materials mixed with negatively charged pH-responsive nanoparticles (NPs) loaded with therapeutic drugs. The F-TENG harnesses personal mechanical movements generate electrical energy. Leveraging the advantages of both MNs and F-TENG, therapeutic NPs can penetrate deep skin locations upon MN patch insertion, releasing drugs rapidly in acidic tumor tissues. Owing to these features, a single administration of the integrated MN-patch in a mouse model with deep-seated melanoma exhibits superior therapeutic efficacy in inhibiting deep-located tumor compared to using the MN-patch alone, indicating promising potential for treating tumors at deep sites.

Blood glucose level is a key indicator of a patient\'s health, notably the symptoms associated with diabetes. Painless and continuously monitored interstitial glucose is highly preferable for diabetes management. Microneedle arrays can be used as an effective but minimally invasive technique to break the skin barrier. Simultaneous reverse iontophoresis enables non-invasive interstitial fluid extraction from the intercellular matrix ≤25 mm under the skin\'s surface. Here, we describe an ion-conductive porous microneedle (PMN)-based glucose sensing device combined with reverse ion electroosmosis, in which glucose extraction can be significantly enhanced. Four novel benefits of ionophoresis are concurrently brought about by the charged PMN: (1) decreased transdermal resistance with the low invasive penetration of highly resistant stratum corneum; (2) a reduction of transdermal resistance through interconnectivity; (3) the movement of larger molecules through linked micropores; and (4) the production of an electroosmotic flow (EOF). The EOF generated by PMN is effectively extracted from the skin interstitial fluid for glucose concentration measurement. And this will likely contribute to the long-term home management of chronic diseases.

Alendronate and estradiol are potential molecules for the treatment of osteoporosis but their use is limited by lower skin permeation and first-pass metabolism respectively. To develop a combinatorial dosage regimen of alendronate and estradiol and enhance skin permeation through iontophoresis for the treatment of osteoporosis. The alendronate and estradiol-containing gel system were developed using carbopol-940 and triethanolamine as independent variables while viscosity and ex vivo permeation as dependent variables. The formulated gel was evaluated for viscosity, pH and ex vivo permeation study with and without iontophoresis. A permeation study was performed on rat abdominal skin. The viscosities for the developed formulations were found to be in the range of 945 cp-1298 cp, The pH of the formulation was found to be 7.4 which is ideal for the ionization of most drugs. Ex vivo permeation ranged from 79.99 to 99.89%. The permeation of both drugs was found to be increased upon application of DC (0.25, 0.50, 0.75 mA/cm2). The maximum percentage of permeation was found to be 99.89% (F3 batch). The skin permeation of alendronate and estradiol was enhanced by the novel formulation using iontophoresis.

The human eye is a consolidated organ with delicate structures and unique immune privileges. Ocular diseases are intractable due to the intrinsic biological barriers within the eyeball. Hydrogels are excellent drug-carrying substances with soft material and excellent properties. They have been extensively used to deliver drugs into ocular tissue via iontophoresis devices. Ophthalmic iontophoresis is an electrochemical technique using tiny electrical currents to deliver drugs into the eye non-invasively. The early infantile iontophoresis technique often required long applying time to achieve therapeutic dose in the posterior ocular segment. The potential limitations in the initial drug concentration and the maximum safe currents would also impede the efficiency and safety of iontophoresis. Moreover, the poor patient compliance always leads to mechanical damage to the cornea and sclera during application. Advantageously, the flexible drug-carrying hydrogel can be in direct contact with the eye during iontophoresis, thereby reducing mechanical damage to the ocular surface. Moreover, the water absorption and adjustable permeability of hydrogels can reduce the electrochemical (EC) reactions and enhance the efficiency of iontophoresis. In this review, we focus on recent developments of hydrogels iontophoresis in ophthalmologic practice. Refinements of the knowledge would provide an outlook for future application of hydrogels in treating ocular disease.

Reverse iontophoresis (RI) is a promising technology in the field of continuous glucose monitoring (CGM), offering significant advantages such as finger-stick-free operation, wearability, and non-invasiveness. In the glucose extraction process based on RI, the pH of the interstitial fluid (ISF) is a critical factor that needs further investigation, as it directly influences the accuracy of transdermal glucose monitoring. In this study, a theoretical analysis was conducted to investigate the mechanism by which pH affects the glucose extraction flux. Modeling and numerical simulations performed at different pH conditions indicated that the zeta potential was significantly impacted by the pH, thereby altering the direction and flux of the glucose iontophoretic extraction. A screen-printed glucose biosensor integrated with RI extraction electrodes was developed for ISF extraction and glucose monitoring. The accuracy and stability of the ISF extraction and glucose detection device were demonstrated with extraction experiments using different subdermal glucose concentrations ranging from 0 to 20 mM. The extraction results for different ISF pH values exhibited that at 5 mM and 10 mM subcutaneous glucose, the extracted glucose concentration was increased by 0.08212 mM and 0.14639 mM for every 1 pH unit increase, respectively. Furthermore, the normalized results for 5 mM and 10 mM glucose demonstrated a linear correlation, indicating considerable potential for incorporating a pH correction factor in the blood glucose prediction model used to calibrate glucose monitoring.

Flexible and wearable sweat sensors have drawn extensive attention by virtue of their continuous and real-time monitoring of molecular level information. However, current sweat-based sensors still pose several challenges, such as low accuracy for analytes detection, susceptibility to microorganism and poor mechanical performance. Herein, we demonstrated a noninvasive wearable sweat sensing patch composed of an electrochemical sensing system, and a pilocarpine-based iontophoretic system to stimulate sweat secretion. The electrochemical sensor based on tannic acid-Ag-carbon nanotube-polyaniline (TA-Ag-CNT-PANI) composite hydrogel was designed for on-body detection of pH and tyrosine (Tyr), a disease marker associated with multiple disorders, such as tyrosinemia and bulimia nervosa. The wearable sweat sensor can not only monitor the pH and Tyr in sweat simultaneously, but also further calibrate Tyr detection results with the measured pH value, so as to eliminate the effect of Tyr response variance at different pH and enhance the accuracy of the sensor. Furthermore, the presence of tannic acid chelated-Ag nanoparticles (TA-Ag NPs) and carbon nanotubes (CNTs) significantly improved the conductivity and flexibility of the hydrogel and endowed the composite hydrogel with antibacterial capability. Of note, the constructed wearable sensor was capable of monitoring Tyr with enhanced accuracy in various sweats.