Electrical Stimulating Redox Membrane Incorporated with PVA/Gelatin Nanofiber for Diabetic Wound Healing.

Chronic wounds adversely affect the quality of life. Although electrical stimulation has been utilized to treat chronic wounds, there are still limitations to practicing it due to the complicated power system. Herein, an electrostimulating membrane incorporated with electrospun nanofiber (M-sheet) to treat diabetic wounds is developed. Through the screen printing method, the various alternate patterns of both Zn and AgCl on a polyurethane substrate, generating redox-mediated electrical fields are introduced. The antibacterial ability of the patterned membrane against both E. coli and S. aureus is confirmed. Furthermore, the poly(vinyl alcohol) (PVA)/gelatin electrospun fiber is incorporated into the patterned membrane to enhance biocompatibility and maintain the wet condition in the wound environment. The M-sheet can improve cell proliferation and migration in vitro and has an immune regulatory effect by inducing the polarization of macrophage to the M2 phenotype. Finally, when applied to a diabetic skin wound model, the M-sheet displays an accelerated wound healing rate and enhances re-epithelialization, collagen synthesis, and angiogenesis. It suggests that the M-sheet is a simple and portable system for the spontaneous generation of electrical stimulation and has great potential to be used in the practical wound and other tissue engineering applications.

Facilitated Transdermal Drug Delivery Using Nanocarriers-Embedded Electroconductive Hydrogel Coupled with Reverse Electrodialysis-Driven Iontophoresis.

We herein developed an iontophoretic transdermal drug delivery system for the effective delivery of electrically mobile drug nanocarriers (DNs). Our system consists of a portable and disposable reverse electrodialysis (RED) battery that generates electric power for iontophoresis through the ionic exchange. In addition, in order to provide a drug reservoir to the RED-driven iontophoretic system, an electroconductive hydrogel composed of polypyrrole-incorporated poly(vinyl alcohol) (PYP) was used. The PYP hydrogel facilitated electron transfer from the RED battery and accelerated the mobility of electrically mobile DNs released from the PYP hydrogel. In this study, we showed that fluconazole- or rosiglitazone-loaded DNs could be functionalized with charge-inducing agents, and DNs with charge modification resulted in facilitated transdermal transport via repulsive RED-driven iontophoresis. In addition, topical application and RED-driven iontophoresis of rosiglitazone-loaded DNs resulted in an effective antiobese condition displaying decreased bodyweight, reduced glucose level, and increased conversion of white adipose tissues to brown adipose tissues in vivo. Consequently, we highlight that this transdermal drug delivery platform would be extensively utilized for delivering diverse therapeutic agents in a noninvasive way.

Novel reverse electrodialysis-driven iontophoretic system for topical and transdermal delivery of poorly permeable therapeutic agents.

Topical and transdermal drug delivery has great potential in non-invasive and non-oral administration of poorly bioavailable therapeutic agents. However, due to the barrier function of the stratum corneum, the drugs that can be clinically feasible candidates for topical and transdermal delivery have been limited to small-sized lipophilic molecules. Previously, we fabricated a novel iontophoretic system using reverse electrodialysis (RED) technology (RED system). However, no study has demonstrated its utility in topical and/or transdermal delivery of poorly permeable therapeutic agents. In this study, we report the topical delivery of fluorescein isothiocyanate (FITC)-hyaluronic acid (FITC-HA) and vitamin C and the transdermal delivery of lopinavir using our newly developed RED system in the in vitro hairless mouse skin and in vivo Sprague-Dawley rat models. The RED system significantly enhanced the efficiency of topical HA and vitamin C and transdermal lopinavir delivery. Moreover, the efficiency and safety of transdermal delivery using the RED system were comparable with those of a commercial ketoprofen patch formulation. Thus, the RED system can be a potential topical and transdermal delivery system for various poorly bioavailable pharmaceuticals including HA, vitamin C, and lopinavir.