Analysis of dynamic surface properties of therapeutic surfactants and lung phospholipids

Abstract

Exogenous surfactant is a specialized biomaterial used for substitution of the lipoprotein mixture normally present in lungs-pulmonary surfactant. Respiratory Distress Syndrome is a disease of preterm infants mainly caused by a deficiency of mature lung surfactant. Pulmonary surfactant is known to stabilize small alveoli and prevent them from collapsing during expiration due to its unique surface properties. A pulsating bubble surfactometer was used for in vitro analysis of surface parameters of therapeutic surfactants and of test formulations to be used for exogenous therapy in Respiratory Distress Syndrome. Surface parameters that were considered for comparison were minimum surface tension (gamma (min)) at three different frequencies (20, 40 and 60 cpm), adsorption at two extreme bubble radii (R-min and R-max), stability index at the three frequencies, recruitment index and the surface viscoelastic parameters. Survanta, ALEC and Exosurf were compared with formulations consisting of the main phospholipids of pulmonary surfactant, namely dipalmitoyl phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) as well as binary mixtures of these phospholipids in the ratio 2:3. Survanta performed much better than the non-protein therapeutic surfactants in all parameters and at all three frequencies. Exosurf had a very low stability index and a very low modulus of surface dilatational elasticity at all three frequencies. The test compounds showed a frequency dependence in their performance. At 20 cpm, PC:PG (2:3) was the best test combination. It achieved a gamma (min) and stability index equivalent to Survanta at this frequency. None of the test compounds were comparable to Survanta at 40 and 60 cpm. These findings may have important therapeutic implications for exogenous surfactants.