Engineering Multi-Scale Transdermal Delivery Systems for Atopic Dermatitis: Emerging Insights from the Gut-Skin Axis

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease, for which traditional treatments are constrained by limited efficacy, high relapse rates, and poor long-term safety. The gut-skin axis has emerged as a critical regulatory network linking intestinal homeostasis and skin health, and is increasingly recognized as a potential contributor to the onset and progression of AD. It plays a multifaceted regulatory role in maintaining immune homeostasis, reconstructing barrier functions, and mediating microbial metabolite signaling. Within this conceptual framework, this review summarizes recent advances in multi-scale transdermal delivery strategies for AD. It particularly emphasizes the unique value of multi-scale transdermal delivery strategies of active components in traditional Chinese medicine (TCM) in immune balance and barrier repair. Building on this, we highlight the integrated innovation of modern delivery technologies, emphasizing the unique advantages of multiscale transdermal systems in regulating the skin barrier, improving active components bioavailability, and modulating cross-compartment biological signaling. Importantly, while emerging studies suggest potential interactions between transdermal delivery systems and gut-skin axis-related pathways, experimentally validated evidence directly linking multi-scale transdermal systems with gut-skin axis regulation remains limited. Therefore, this review also critically discusses current knowledge gaps and highlights the need for further mechanistic and experimental validation. Unlike prior reviews centered on single mechanisms or delivery methods, this work provides a structured overview of active components, intestinal-cutaneous communication, and multi-scale delivery technologies, and proposes a conceptual framework for their potential integration. This perspective aims to support future experimental efforts toward establishing a mechanistically validated link between advanced transdermal systems and gut-skin axis regulation, facilitating the translation of TCM-derived bioactive compounds combined with advanced delivery platforms for AD treatment.