A Comprehensive Review of Lipid-Based Topical Nanocarriers for the Treatment of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease affecting 1-3% of adults and 20% of children. It is characterized by type 2 immune dysregulation and epidermal barrier dysfunction. The pathophysiology involves loss-of-function mutations in the filaggrin gene (FLG), tight junction defects, and altered intercellular lipid composition, leading to increased transepidermal water loss (TEWL) and sensitization to environmental allergens. Current treatments, including topical corticosteroids (TCS), calcineurin inhibitors (TCI), and emerging biologics, are limited by cutaneous atrophy, systemic absorption, and poor patient adherence. This review critically examines lipid-based nanocarrier systems, specifically solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, ethosomes, transferosomes, and nanoemulsions, as advanced topical delivery platforms. These systems enhance drug bioavailability through prolonged skin retention, targeted epidermal delivery, and controlled release kinetics, while minimizing systemic exposure. We analyze comparative efficacy data, mechanistic insights into skin penetration pathways, and discuss stability considerations, safety profiles, and regulatory challenges. The integration of personalized nanomedicine approaches represents a paradigm shift toward precision therapeutics in AD management, offering improved clinical outcomes and reduced long-term disease burden.