Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

Sadikot, Ruxana T.; Kolanjiyil, Arun V.; Kleinstreuer, Clement; Rubinstein, Israel

We recently tested the efficacy of GLP-1 nanomicelles in a mouse model of lipopolysaccharide (LPS)-induced lung injury [16, 18, 36] . Mice (8 weeks old) were treated with LPS nebulization (concentration of 1 mg/mL) administered via a DeVilbiss disposable nebulizer (at a continuous air flow rate of 10 ft 3 /h) over 1 h to induce ALI. SSM treatment was administered via a subcutaneous route at a dose of 15 nmol of GLP-1/mouse. Control mice were treated with SSM with scrambled peptide or empty SSM. Mice received LPS through nebulization (1 mg/mL). We have previously shown that this model induces neutrophilic influx in the lung. To assess the magnitude of lung inflammation, total and neutrophil cell counts, proinflammatory cytokine levels (TNF-α, IL-6), total and neutrophil counts in bronchoalveolar lavage fluid, and myeloperoxidase activity in lung tissue were measured [16, 37] . In vivo administration of GLP-1-SSM to LPS-induced ALI mice resulted in significant downregulation of lung inflammation, with dose-dependent anti-inflammatory activity observed. Similar therapeutic activity was not detected for GLP-1 in saline, indicating that the SSM nanocarriers played a critical role in protecting the enzyme-labile GLP-1 and delivering it to inflamed tissues in vivo. This study demonstrated for the first time that the lipid-based nanoformulation of GLP-1 is effective at attenuating inflammation in ALI/ARDS [16] .