Atopic Dermatitis (AD) is characterized by skin barrier disruption and an aberrant immune response. Doxycycline are tetracycline antibiotics broadly used systemically to treat inflammatory-dermatologic conditions. Several studies have shown doxycycline have anti-inflammatory and pro-healing properties, mainly by blocking tissue proteolytic activity. It is our hypothesis that daily application of a novel Doxycycline topical formulation in AD subjects will reduce severity of the disease, by blocking cutaneous proteases activity and restoring skin barrier function and inflammation. To test this hypotehsis we performed a proof of concept, open-label clinical study. Subjects enrolled in the study (n=15) applied NanoDOX® Hydrogel 1% daily for four weeks on a chosen eczematous area. Investigational drug was well tolerated, no local or systemic adverse events due to investigational drug were reported. Notably, a significant clinical improvement was observed based on a modified Eczema Area & Severity Index (EASI) score of the treated area from start of treatment to 14 and 28 days post treatment (p