Kidney Targeting Liposomes Loaded with the Antioxidant Pinocembrin for Treatment of Acute Kidney Injury

Acute kidney injury (AKI) is a common and serious clinical syndrome, and currently there is a significant lack of effective pharmacotherapy. Pinocembrin (PIN), a flavonoid derived from propolis, possesses antioxidant properties and could be advantageous in treating AKI. However, its poor water solubility limits its clinical application. Lipid nanoparticles have become a promising drug delivery method due to their excellent biocompatibility and capacity to improve drug targeting. In this study, sialic acid (SA) - modified PIN liposomes (PIN-LIP) were developed for targeted protection against AKI. The PIN-LIP effectively targeted the kidneys via the specific interaction between SA with E-selectin. Importantly, in vivo experiments in two AKI models (cisplatin-induced and rhabdomyolysis-induced AKI) confirmed that the injected PIN-LIP was retained in the injured kidneys for more than 24 h. The PIN-LIP exhibited excellent antioxidative and antiapoptotic effects on HK-2 cell injury induced by H2O2 in vitro. It also improved renal function and reduced oxidative stress, tubular cell apoptosis and inflammatory responses in in vivo AKI models. In addition, PIN-LIP showed a favorable biocompatibility and safety profile in vivo. Therefore, PIN-LIP may be a promising therapeutic option for AKI treatment.