Topical Nanocarrier-Assisted Corticosteroid Delivery Combined with Phototherapy for Effective Atopic Dermatitis Treatment.

Topical corticosteroids are widely used to manage chronic inflammatory skin diseases, such as atopic dermatitis (AD). However, their limited skin penetration necessitates high doses and prolonged use, which increases the risk of local and systemic side effects. To address these limitations, we developed a gold nanorod-conjugated dexamethasone (AuNR-DEX) system combined with red light-emitting diode (LED) irradiation to enhance transdermal drug delivery and therapeutic efficacy. AuNR conjugation enhanced the physicochemical properties of DEX, including its hydrodynamic diameter and surface charge, thereby facilitating increased skin penetration. In an AD mouse model, topical AuNR-DEX significantly alleviated disease symptoms at only 20% of the dose required for free DEX. While AuNR-DEX alone showed limited dispersion across the skin, cotreatment with red LED irradiation facilitated broader spreading and improved drug distribution. The combination therapy markedly restored epidermal differentiation, collagen fiber integrity, and calcium homeostasis in AD skin lesions. In vitro, AuNR-DEX plus LED treatment enhanced keratinocyte survival, restored the localization of tight junction proteins, and reduced mitochondrial calcium overload and reactive oxygen species levels. Overall, the synergistic effect of AuNR-DEX and red LED irradiation enhanced drug delivery, targeted dispersion, and therapeutic outcomes, offering a promising strategy for treating AD with reduced corticosteroid dosage and minimized side effects.