"Helical Peptoid Mimics of the Hydrophobic Lung Surfactant Proteins Provide Effective In Vivo Treatment of Acute Lung Injury"
Annelise E. Barron, Ph.D.
Associate Professor of Bioengineering
Stanford School of Medicine & School of Engineering
Acute lung injury (ALI) leads to progressive loss of breathing capacity and hypoxemia, as well as pulmonary surfactant dysfunction. ALI’s pathogenesis and management are complex, and it is a significant cause of morbidity and mortality worldwide. Exogenous surfactant therapy is currently impractical for adults because of the high cost of current surfactant preparations and the large amount of material needed to treat adult-sized lungs. Prior in vitro work has shown that helical, sequence-specific 21mer poly-N-substituted glycines (peptoids), in a biomimetic lipid mixture, emulate key biophysical activities of lung surfactant proteins B and C (SP-B and SP-C, respectively) at the air-water interface. We have found good in vivo efficacy of a peptoid-based surfactant, compared with extracted animal surfactant and a synthetic lipid formulation, in a rat model of lavage-induced ALI. Adult rats were subjected to whole-lung lavage followed by administration of surfactant formulations and monitoring of outcomes. Treatment with a SP-C mimic formulation improved blood oxygenation, blood pH, shunt fraction, and peak inspiratory pressure to a greater degree than SP-B mimic or combined formulations. All peptoid-enhanced treatment groups showed improved outcomes compared to synthetic lipids alone, and some formulations improved outcomes to a similar extent as animal-derived surfactant. In recent work, we have designed improved mimics of SP-C with more biomimetic side chain chemistries, which perform better in vitro, and we expect to see improved efficacy in future in vivo studies with these new designs. Robust biophysical mimics of natural surfactant proteins may enable new medical research in approaches to the treatment of acute lung injury and pneumonia.