Crossing ocular barriers with quercetin-SPIONs: modulation of Bax/Bcl-2 balance in normal rat eyes

BACKGROUND: Oxidative stress-induced cell death and injury are pivotal mechanisms in the breakdown of ocular tissue, leading to degenerative diseases. To counter this, we investigated quercetin, a flavonoid with well-documented antioxidant and anti-apoptotic properties, as a potential therapeutic agent. Its clinical translation is hampered by poor stability and ocular bioavailability. The goal was to examine the effectiveness and anti-apoptotic properties of polyethylene glycol-coated superparamagnetic iron oxide nanoparticles conjugated with quercetin (QCSPIONs) in rat eye tissue. METHODS: Male Wistar rats received free quercetin (QC), SPIONs, or QCSPIONs orally via gavage or through intraperitoneal injection once daily for 35 days. HPLC measured serum and ocular quercetin levels; nanoparticle localization was assessed by Prussian blue staining; safety was evaluated by histopathology with H&E staining; and apoptotic signaling was examined by qPCR for Bax and Bcl-2 expression. RESULTS: QCSPIONs demonstrated significantly higher ocular quercetin accumulation than free QC after both oral and intraperitoneal delivery (p < 0.0001). Prussian Blue staining confirmed that nanoparticles crossed the corneal and retinal barriers, with greater deposition following intraperitoneal injection. Additionally, histological analysis showed no structural or inflammatory damage in the retina or cornea. Furthermore, molecular results indicated Bax suppression and Bcl-2 upregulation with QCSPIONs, along with a decreased Bax/Bcl-2 ratio, demonstrating vigorous anti-apoptotic activity. Less pronounced effects were observed with free QC. CONCLUSIONS: Overall, QCSPIONs significantly enhance the ocular bioavailability of quercetin and provide robust anti-apoptotic protection without detectable cytotoxicity. These results support nanoparticle-mediated delivery as a practical approach for overcoming ocular barriers and enhancing preventive antioxidant strategies against oxidative stress-related eye diseases.