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

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

To effectively block the expression of TREM1, we developed LP17 peptide nanomedicine, LP17-SSM. LP17 is the soluble TREM1 or extracellular component which binds and inhibits signaling through TREM1 [5] . Control SSMs were prepared by using scrambled peptide. For the TREM1 blocking peptide, LP17, circular dichroism confirmed that there was a significant increase in α-helicity in the presence of SSM compared to the free peptides in normal saline. This indicated the presence of peptide-micelle interaction where the peptides changed from a random conformation in saline to a more ordered helical structure when associated with SSM. To determine in vivo anti-inflammatory efficacy and the dose-response effect of LP17-SSM, we established the dose and time-dependent effects as with GLP-1-SSM [16] . Mice were given one dose of LP17 nanomedicine, nanoscrambled peptide, PBS, or LP17 subcutaneously in a single dose prior to LPS challenge. The ALI animal model used was based on previous publications [16, 37] . Mice were challenged with aerosolized LPS by nebulization (8 mg LPS dissolved in phosphate-buffered saline at the concentration of 1 mg/mL) administered via DeVilbiss disposable nebulizer (at the continuous air flow rate of 10 ft 3 /h) over 1 h to induce ALI. The animals were sacrificed 12 h after LPS nebulization.