An Emerging Strategy for Skin Disease Treatment: Targeting the Skin Inflammatory Microenvironment with Responsive Drug Delivery Systems

Abstract

The treatment of inflammatory skin diseases poses significant challenges due to the complex Inflammatory Microenvironment (IME) and inherent limitations of the skin barrier. However, given its dynamic nature and pivotal involvement in disease pathogenesis, the IME represents an ideal target for precision intervention. By sensing real-time fluctuations in key biomarkers, including local pH, Reactive Oxygen Species (ROS) levels, inflammatory cytokines, and programmed cell death markers within the cutaneous microenvironment, Responsive Drug Delivery Systems (RDDS) enable intelligent and on-demand drug release. Consequently, RDDS confer superior therapeutic precision and efficacy while minimizing off-target adverse effects. This review systematically highlights the multifunctional capabilities of RDDS in modulating the IME. Key benefits encompass precise spatiotemporal drug release, targeted delivery, and combination therapy. Furthermore, these systems enable the safe administration of sensitive agents, enhance transdermal penetration, and facilitate theranostic integration. The article further summarizes recent advances and emerging trends in applying RDDS to diverse dermatological conditions, including psoriasis, melanoma, chronic wounds, atopic dermatitis, acne, and scleroderma. This review synthesizes the mechanisms and potential applications of RDDS, aiming to provide a theoretical foundation and inspire innovative designs for safer, more effective therapeutic strategies in dermatology.