Beyond the skin barrier: nanocarrier-based drug delivery with emerging insights into the gut-skin axis and probiotic modulation in atopic dermatitis.

OBJECTIVES: To summarize recent advances in nanotechnology-based topical drug delivery systems for atopic dermatitis (AD) and highlight their potential to overcome the limitations of conventional topical therapies, particularly poor skin penetration, adverse effects, and inadequate drug concentrations in deeper skin layers. METHODS: The current literature on nanocarrier-based drug delivery for AD was reviewed, with emphasis on liposomes, ethosomes, transferosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, nanoemulsions, cubosomes, micelles, and metal-organic frameworks. Emerging approaches involving the gut-skin axis and microbiome-modulating strategies, including probiotics and postbiotics, were also considered. KEY FINDINGS: AD is a chronic, relapsing inflammatory skin disease marked by intense pruritus, impaired epidermal barrier function, and immune dysregulation. It affects nearly 20% of children and 3%-10% of adults globally, imposing a significant clinical and socioeconomic burden. Current treatment mainly relies on topical therapies; however, their effectiveness is often limited by poor penetration through the stratum corneum. Prolonged use of conventional topical agents is also associated with adverse effects, which may reduce patient adherence and long-term therapeutic success. Nanocarrier systems offer promising solutions by enhancing skin permeability, enabling controlled and targeted drug delivery, and reducing systemic exposure. Emerging evidence also supports combining nanocarrier-based delivery with microbiome-modulating approaches. CONCLUSIONS: Nanotechnology-based delivery systems show considerable potential for improving topical treatment outcomes in AD. However, despite encouraging preclinical results, clinical translation requires standardized manufacturing, detailed safety evaluation, and well-designed clinical trials.