Separable Microneedle Patch Integrated with the Dictamnine-Loaded Copper MOF Nanozyme for Atopic Dermatitis Treatment

Atopic dermatitis (AD) is a chronic inflammatory skin disorder marked by skin thickening, severe pruritus, lesions, and emotional disturbances, including anxiety and depression-like behavior. Current treatments primarily rely on localized therapies, which can lead to adverse effects such as hyperglycemia and Cushing's syndrome with repeated use. To address these issues, we developed a hyaluronic acid-based separable microneedle patch (Dic@pCu-HA MN), integrating polydopamine-coordinated copper-based metal-organic frameworks (pCu-MOFs) and the anti-inflammatory agent dictamnine (Dic), for synergistic management of AD and its neuropsychiatric comorbidities. pCu-MOFs exhibited dual functionality as nanocargo for hydrophobic Dic (encapsulation efficiency: 84.62 ± 2.14%) and multienzyme mimics that efficiently scavenge reactive oxygen species (ROS) (superoxide radical scavenging: 63.85 ± 0.34%). In vitro release studies demonstrated ROS-responsive Dic release of 86.80 ± 4.83% over 48 h under AD pathology-mimicking conditions. In a 1-Chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model, the Dic@pCu-HA MN significantly reduced oxidative stress (8-OHdG: 85.1 ± 7.0% decrease), suppressed pro-inflammatory cytokines (IL-4: 70.0 ± 7.8% decrease vs control), and restored skin barrier integrity. By modulating the HPA axis, the system attenuated neuroinflammation and alleviated itching (scratching frequency: 40.1 ± 41.3% reduction) and depression-like behavior (time in the bright box: 96.6 ± 156.2% increase). This combined therapeutic approach not only offers a comprehensive strategy for AD management but also provides potential benefits for addressing inflammatory skin disorders and their neuropsychiatric sequelae.