Therapeutic Effects of Intratracheally Nebulized Carnosine-Loaded Liposomes on Lipopolysaccharide-Induced Acute Lung Injury.

Introduction: Acute lung injury (ALI) is characterized by severe inflammation and oxidative stress. However, effective pharmacological interventions for ALI remain limited. Carnosine, an endogenous dipeptide known for its redox-regulating and immunomodulatory activities, has demonstrated promising protective effects. In the present study, inhalable carnosine-loaded liposomes (Cn-Ls) were developed to enhance pulmonary delivery and achieve localized treatment in a lipopolysaccharide (LPS)-induced ALI model in mice. Methods: Cn-Ls were prepared and systematically evaluated for their morphology, stability, drug-loading capacity, and release kinetics. In vitro assays were performed to evaluate their cytocompatibility, antioxidant activity, and effects on LPS-induced reactive oxygen species (ROS) generation. In an ALI model, inhaled Cn-Ls were administered to assess pulmonary retention and therapeutic efficacy, including lung inflammation, oxidative stress, circulating levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6, lung architecture, and respiratory function. Results: Encapsulation of carnosine within liposomes markedly prolonged its pulmonary retention (t1/2 = 1.7 h vs. 1.0 h for free carnosine), providing a more sustained lung-retentive delivery profile for up to 12 h. In vitro assays showed that Cn-Ls had excellent cytocompatibility, reduced cell death, exhibited potent antioxidant activity, and effectively suppressed LPS-induced ROS generation. In an ALI model, inhaled Cn-Ls markedly mitigated lung inflammation and oxidative stress, reduced circulating levels of CRP, TNF-α, and IL-6, preserved lung architecture, and improved respiratory function. Compared with free carnosine, Cn-Ls exhibited enhanced pulmonary retention and superior therapeutic efficacy. Conclusions: These results identified inhalable Cn-Ls as a potential nanotherapeutic approach for targeted ALI management and provided a foundation for further translational development. However, additional investigations are required to assess the long-term safety of Cn-Ls, optimize formulation stability and scalability, and further elucidate the underlying therapeutic mechanisms before clinical translation.