Hesperidin-β-Cyclodextrin inclusion complexes: A novel approach for preventing and treating acute lung injury caused by seawater drowning

Seawater drowning-induced acute lung injury (ALI) presents a significant challenge due to the lack of effective prevention and treatment strategies. Hesperidin (Hep) possesses diverse biological activities, including potent antioxidant and anti-inflammatory effects. However, its clinical utility is hindered by poor solubility and limited bioavailability. Therefore, there is an urgent need for the modification of hesperidin to enhance its water solubility and expand its therapeutic potential. In this study, an inhalable formulation of Hep-β-cyclodextrin inclusion complexes (Hep-β-CD) was developed as a promising approach for the management of seawater drowning-induced ALI. The cytotoxicity assessment in BEAS-2B cells revealed minimal adverse effects associated with Hep-β-CD. The administration of Hep-β-CD via the pulmonary route has been found to be highly effective in preventing seawater drowning-induced ALI in mice, achieved through modulation of key inflammatory mediators and a reduction in oxidative stress. The study demonstrated that Hep-β-CD administration significantly decreased the levels of pro-inflammatory cytokines such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6), which are known to contribute to the pathogenesis of ALI. Additionally, the levels of malondialdehyde (MDA) were decreased and the levels of Superoxide Dismutase (SOD) were increased. In summary, the pulmonary delivery of Hep-β-CD was identified as a promising therapeutic strategy for preventing seawater drowning-induced ALI due to its ability to directly distribute the drug to the lungs, where it exerts a dual action of modulating the immune response to reduce inflammation and enhance the antioxidant defense mechanism.