A Synthetic Lung Surfactant for Treatment of Respiratory Distress Syndrome

Lung surfactant (LS) is a mixture of lipids and proteins that lowers surface tension in the alveoli, insuring a negligible work of breathing and preventing alveolar collapse upon exhalation. LS is functionally inhibited during Acute Respiratory Distress Syndrome (ARDS). ARDS has a 40% mortality rate and is characterized by elevated levels of serum proteins in the alveoli, which interfere with formation of an LS monolayer at the alveolar air-liquid interface. In a related disorder, Neonatal Respiratory Distress Syndrome (NRDS), premature infants which lack functional LS are successfully treated with animal derived replacement LS. Our objective is to develop a synthetic LS that resists inhibition by ARDS and treats NRDS at lower cost and with less risk of contamination than animal-derived surfactants.

Studies on Survanta, an animal derived replacement LS, showed that inhibition could be reversed by treatment with chitosan, CaCl₂, and polyethylene glycol. To determine the minimum recipe that would yield a synthetic LS resistant to inhibition, mixtures containing only ?Survanta-like? lipids and lipids with synthetic peptides were evaluated. Addition of peptide improved the surface performance of lipids on a clean subphase. However, no combination of synthetic lipids and/or peptides resisted protein inhibition as well as Survanta.