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.