Evaluation of the efficacy of liposomal forms of quercetin in LPS-induced model of acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a severe and often fatal complication of various critical conditions, including bacterial and viral infections (such as COVID-19), sepsis, trauma, and aspiration. It is characterized by diffuse alveolar damage, cytokine overproduction, endothelial dysfunction, microthrom bosis, and alveolar-capillary barrier disruption, leading to life-threatening respiratory failure. Despite intensive care and supportive therapy, there is a persistent need for effective pharmacological agents that can reduce inflammation and protect lung tissues. Quercetin, a plant-derived flavonoid with proven antioxidant, anti-inflammatory, and endothelial-protective properties, is considered a promising candi date. Its liposomal form enhances bioavailability and targeted delivery. The combination of quercetin withzinc(II), a trace element with immunomodulatory and antiviral activity, may further potentiate its therapeutic effects.
The aim of the study is to evaluate the therapeutic potential of the liposomal form of quercetin and its liposomal composition with zinc in an LPS-induced model of acute respiratory distress syndrome
(so-called "fatal" ARDS) in animals by analyzing survival, clinical presentation, and morphological condition of lung tissue in laboratory animals. An LPS-based ARDS model in mice was used, supplemented with muramyl dipeptide and Freund's adjuvant. Survival, clinical condition, and histopathological changes in the lungs and myocardium were evaluated. Test samples were administered intravenously. Statistical analysis of the quantitative results was performed using Student’s t-test.
In the model of "fatal" acute respiratory distress syndrome (ARDS) induced by the combined administration of LPS, MDP, and Freund’s adjuvant, a high mortality rate (up to 71%) was recorded, along with a marked deterioration in overall clinical condition and pronounced destructive-inflammatory morphological changes in the lungs and heart. Intravenous administration of liposomal forms of quercetin led to a statistically significant increase in survival rates, improvement in the animals’ clinical condition, and a reduction in the severity of organ morphological damage. A positive effect was observed on survival dynamics, attenuation of inflammatory and dystrophic changes in lung tissue, preservation of myocardial histological architecture, and reduction of pulmonary hypertension manifestations.
The results obtained indicate the therapeutic potential of liposomal quercetin formulations as a treatment option for ARDS, particularly in the context of intensive care of inflammatory lung injury.