The Alleviation of LPS-Induced Murine Acute Lung Injury by GSH-Mediated PEGylated Artesunate Prodrugs

Abstract

Acute lung injury (ALI) or its aggravated stage acute respiratory distress syndrome (ARDS) is a common severe clinical syndrome in intensive care unit, may lead to a life-threatening form of respiratory failure, resulting in high mortality up to 30–40% in most studies. Nanotechnology-mediated anti-inflammatory therapy is an emerging novel strategy for the treatment of ALI, has been demonstrated with unique advantages in solving the dilemma of ALI drug therapy. Artesunate (ART), a derivative of artemisinin, has been reported to have anti-inflammatory effects. Therefore, in the present study, we designed and synthesized PEGylated ART prodrugs and assessed whether ART prodrugs could attenuate lipopolysaccharide (LPS) induced ALI in vitro and in vivo. All treatment groups were conditioned with ART prodrugs 1 h before challenge with LPS. Significant increased inflammatory cytokines production and decreased GSH levels were observed in the LPS stimulated mouse macrophage cell line RAW264.7. Lung histopathological changes, lung W/D ratio, MPO activity and total neutrophil counts were increased in the LPS-induced murine model of ALI via nasal administration. However, these results can be reversed to some extent by treatment of ART prodrugs. The effectiveness of mPEG2k-SS-ART in inhibition of ALI induced by LPS was confirmed. In conclusion, our results demonstrated that the ART prodrugs could attenuate LPS-induced ALI effectively, and mPEG2k-SS-ART may serve as a novel strategy for treatment of inflammation induced lung injury.

Aryl Hydrocarbon Receptor Activation Ameliorates Acute Respiratory Distress Syndrome through Regulation of Th17 and Th22 Cells in the Lungs

“…It should be noted that the doses of LPS and I3C were based on previous studies. Other studies have used LPS at doses of 1 to 5 mg/kg body weight to induce ARDS ( 74 – 76 ). In our standardizing experiments, we found that 2 mg/kg of LPS was a sufficient dose to induce significant ARDS.…”

Arenobufagin-loaded PEG-PLA nanoparticles for reducing toxicity and enhancing cancer therapy

“…First, 3 mL of ArBu@PEG-PLA micelles was encapsulated in dialysis bags (MWCO 3500) and then immersed in 20 mL PBS (pH 7.4) at 37 °C. The original dialysis medium was replaced and an equal volume of fresh dialysis medium was added at different time points (0.125, 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 48 h) (Hao et al., 2022 ). The release amount of ArBu in micelles was detected by UPLC.…”

Green synthesis of gold nanoparticles modulates lipopolysaccharide‐induced lung inflammation in Wistar rats

“…Acute lung injury (ALI) or its aggravated stage, acute respiratory distress syndrome (ARDS), is a severe clinical syndrome common in intensive care units, which can lead to a life‐threatening form of respiratory failure, creating a problem of public health. With a morbidity of 86.2/100 000 annually, the mortality of patients with ALI is approximately 38.5%–40% in most studies 1,2 . It can be caused by direct pulmonary insults (e.g., bacterial or viral pneumonias) or extrapulmonary insults that affect the lung secondarily (e.g., sepsis, severe hypoxemia and pancreatitis) 3 .…”

“…As a result, it is very important to introduce new technologies for ALI therapy with high efficacy, less toxicity and side effects. 1,5 Due to their unique properties, gold nanoparticles (GNPs) present themselves as promising molecules through some aspects: (i) carrier of small molecules, peptides, nucleic acids, etc. ; (ii) stability and bioavailability; and (iii) ability to overcome multiple pulmonary barriers to increase drug accumulation at inflammatory sites through passive or active targeting effect.…”

“…However, these drugs exert a variety of side effects, including irregularities in cyclo coagulation dysfunction, gastric ulcers and osteoporosis, which greatly limits their clinical applications. As a result, it is very important to introduce new technologies for ALI therapy with high efficacy, less toxicity and side effects 1,5 …”