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 fluconazoleor 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.

Enzymes play a central role in fundamental biological processes and have been traditionally used to trigger various processes. In recent years, enzymes have been used to tune biomaterial responses and modify the chemical structures at desired sites. These chemical modifications have allowed the fabrication of various hydrogels for tissue engineering and therapeutic applications. This review provides a comprehensive overview of recent advancements in the use of enzymes for hydrogel fabrication. Strategies to enhance the enzyme function and improve biocompatibility are described. In addition, we describe future opportunities and challenges for the production of enzyme-mediated crosslinkable hydrogels.

Recently, the stem cell-derived secretome, which is the set of proteins expressed by stem cells and secreted into the extracellular space, has been demonstrated as a critical contributor for tissue repair. In this study, we have produced two sets of high concentration secretomes from adipose-derived mesenchymal stem cells (ADSCs) that contain bovine serum or free of exogenous molecules. Through proteomic analysis, we elucidated that proteins related to extracellular matrix organization and growth factor-related proteins are highly secreted by ADSCs. Additionally, the application of ADSC secretome to full skin defect showed accelerated wound closure, enhanced angiogenic response, and complete regeneration of epithelial gaps. Furthermore, the ADSC secretome was capable of reducing scar formation. Finally, we show high-dose injection of ADSC secretome via intraperitoneal or transdermal delivery demonstrated no detectable pathological conditions in various tissues/organs, which supports the notion that ADSC secretome can be safely utilized for tissue repair and regeneration.

Since the development of protein‐based therapeutics, research has been underway to deliver protein therapeutics into the systemic circulation and target sites have been actively conducted. Most protein‐based therapeutics require parenteral administration, due to their intrinsic vulnerability and susceptibility to enzyme‐mediated degradation. Among the routes of administration, the transdermal delivery system has been regarded as a promising technique to deliver protein therapeutics, offering the advantages of painless administration, ease of termination, and avoidance of first‐pass metabolism. However, unlike small molecular drugs, protein therapeutics have limited skin penetration, due to their macromolecular and hydrophilic properties. Both cheimcal adjuvants (CAs)‐treatment methods and physical penetration enhancer methods (PPEs) have been utilized to increase skin permeability for protein therapeutics. The CAs, which include chemical penetration enhancers and nanocarriers, permit the protein therapeutics to transport easily into the skin, by modifying the stratum corneum (SC) or fabricating their stable formulation. The PPEs, including iontophoresis, electroporation, and ultrasound, can improve the skin permeability of the therapeutic agent through disrupting the SC. In this review, the techniques of both chemical and physical enhancement methods are introduced and an overview of the latest approaches to the transdermal delivery of protein therapeutics is provided.

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