A Simvastatin-Loaded Nanoliposome Delivery System for Sepsis-Induced Acute Lung Injury

Abstract

To enhance the treatment of acute lung injury (ALI) induced by sepsis and optimize the clinical efficacy of simvastatin (SV), we develop SV-loaded nanoliposomes (SV/NLC) as a novel drug delivery system. The NLCs exhibited a particle size of approximately 165 nm, which increased to around 195 nm upon SV loading. NLCs significantly prolonged the half-life of SV by nearly five-fold and improved its penetration into EA.hy926 cells, demonstrating excellent biocompatibility and targeted delivery for ALI therapy. In the rat model of ALI, the SV/NLC effectively reduced the lung wet/dry ratio and the levels of inflammatory factor and albumin in the alveoli, thus improving the alveolar gas exchange function and blood oxygenation. The SV/NLC group demonstrated superior suppression of oxidative stress within lung tissues compared to other groups. Notably, treatment with SV reduction in TLR4, MyD88, and NF-κB P65 levels in lung tissues from ALI rat models. This effect was particularly pronounced in the SV/NLC group. Furthermore, SV can effectively mitigate inflammatory responses and oxidative stress in ALI treatment by modulating the TLR4/NF-κB signaling pathway. In conclusion, our findings suggest that SV can exert therapeutic effects against sepsis-induced ALI through inhibition of the TLR4/NF-κ and mitigate inflammatory response and oxidative stress.