Nanoformulations in Glucocorticoid Therapy: a Promising Leap for Atopic Dermatitis Treatment

Abstract

A chronic inflammatory skin disorder characterized by pruritus, recurrent flares and significant impairment of quality of life is termed as atopic dermatitis (AD). Although glucocorticoids (GCs) remain the cornerstone of therapy, their long-term use is limited by adverse effects including cutaneous atrophy, immunosuppression and systemic metabolic complications driven by altered gene expression. Conventional treatments such as calcineurin inhibitors, phosphodiesterase-4 (PDE4) inhibitors, biologics and janus kinase (JAK) inhibitors provide alternatives, but accessibility, cost and toxicity concerns remain. Recent advances in nanotechnology-based delivery systems offer a promising strategy to optimize AD management by enhancing drug penetration through the stratum corneum (SC), prolonging dermal residence time and minimizing systemic exposure. Liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), polymeric nanoparticles (PNPs) and nanohydrogel systems have demonstrated improved safety and efficacy profiles in preclinical and clinical studies. Furthermore, nanocarriers enable multimodal therapy, co-delivering corticosteroids, immunomodulators and barrier-repair molecules in a single formulation. The frontier of gene and biologic delivery, including spherical nucleic acids (SNA) for siRNA transport and nanoparticle-enabled topical biologics, highlights the potential for disease-modifying interventions. Looking ahead, the integration of genomics, pharmacogenomics and artificial intelligence will allow biomarker-guided, precision nanomedicine strategies that reduce steroid dependence and improve patient outcomes. This review summarizes current knowledge on GC mechanisms, treatment regimens and emerging nanotechnology-based therapies, emphasizing their translational potential in the era of personalized dermatology.