Biomimetic hyaluronic acid-stabilized zinc oxide nanoparticles in acne treatment: A preclinical and clinical approach.

Acne vulgaris is a common chronic inflammatory skin condition, often caused by C. acnes infection. While ZnO has shown promise as an antibacterial agent in acne treatment, concerns over toxicity and non-selective bacterial killing remain. In this study we developed a hyaluronic acid-stabilized nano‑zinc oxide (HA-ZnO) formulation aimed at enhancing the therapeutic efficacy and safety of ZnO for acne treatment. HA-ZnO was synthesized through biomimetic mineralization. HA-ZnO targeted acne-prone areas, especially sebaceous glands, without skin penetration. HA-ZnO demonstrated selective antibacterial activity against C. acnes, exhibiting a killing efficacy more than 16 times greater than that against S. epidermidis. The HA coating also improved ZnO's stability in acidic conditions, mitigating potential toxicity and side effects. Additionally, the sustained release of Zn2+ promoted cell proliferation and migration, reducing sebum secretion, and exerting anti-inflammatory effects, supporting scar-free acne repair and preventing recurrence. In preclinical models, HA-ZnO outperformed erythromycin ointment in treating acne, with no toxicity observed in zebrafish and HET-CAM. A clinical trial further confirmed its efficacy in reducing acne lesions and redness, with high safety. These results highlight HA-ZnO as a promising therapeutic strategy for acne, combining potent antibacterial and skin-repairing effects with enhanced safety.