Ascorbate-ferrous iron complex loaded into sodium hyaluronate-based eye drops for the treatment of...

Bacterial keratitis is one of the most common causes of visual impairment and blindness worldwide, and suffers the risk of drug-resistant infections due to the abuse of antibiotics. Despite its ability to counteract antibiotic resistance by inducing ferroptosis, the application of Fe²⁺ is limited by oxidative instability and a solution pH often incompatible with ophthalmic use. Thus, this study designed and synthesized an ascorbate-ferrous iron complex (SA-Fe(II)) using ferrous lactate and sodium ascorbate, followed by comprehensive structural characterization. Results confirmed the formation of coordination bonds between Fe²⁺ and sodium ascorbate. The molecular ion peak and characteristic decarboxylated fragment, along with broad and diffuse diffraction peaks in X-ray diffraction patterns, verified the formation of an amorphous metal chelate structure stabilized by dynamic coordination bonds. The SA-Fe(II) complex exhibited potent antibacterial activity, achieving more than 99.99 % killing of Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) at 100 μM within 3 h. When incorporated into a sodium hyaluronate eye-drop matrix (SA-Fe(II)-SH), the formulation exhibited excellent ocular biocompatibility, as evidenced by hemolysis rates less than 5 %, more than 95 % viability of human corneal epithelial cells (HCE-T) corneal epithelial cells over 3 days, and no observable tissue inflammation in vivo. Importantly, in a mice model of MRSA keratitis, SA-Fe(II)-SH significantly reduced bacterial load, suppressed the production of inflammatory cytokines (IL-1β, IL-6, TNF-α), promoted corneal repair, and prevented systemic dissemination. This non-antibiotic strategy integrates antibacterial, anti-inflammatory, and pro-healing functions, offering a safe and effective therapeutic approach for the treatment of drug-resistant bacterial keratitis.