Synthetic Bilirubin-Based Nanomedicine Alleviates Atopic Dermatitis by Reducing Oxidative Stress and Modulating Immune Responses

Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a growing prevalence worldwide. Topical corticosteroids and non-steroidal calcineurin inhibitors (CNIs) are used as first-line therapies for AD, but various side effects limit their long-term use. Here, the first synthetic bilirubin(IIIα)-derived nanoparticle is reported, designated BRNP(IIIα), and shows that it exhibits robust antioxidative and immunomodulatory effects and effectively reduces the clinical symptoms of AD upon topical treatment. BRNP(IIIα) in 1% high molecular weight hyaluronic acid (BRNP(IIIα)/HA) readily infiltrates into the dermis layer, notably downregulates disease-associated reactive oxygen species (ROS) and inflammatory chemokines and cytokines, and suppresses the recruitment of leukocytes and mast cells to AD-induced lesions. BRNP(IIIα)/HA also significantly reduces the tissue-resident memory T cell population, suggesting that it may inhibit recurrence. Furthermore, BRNP(IIIα)/HA does not induce any adverse effect related to skin irritation/sensitization or eye irritation in human tissue. Collectively, the findings suggest that BRNP(IIIα)/HA may be useful as an alternative to corticosteroids or CNIs for the safe, effective, and long-term topical treatment of AD.