Path Dependence of Adsorption Behavior of Mixtures Containing Dipalmitoyl Phosphatidylcholine

Abstract

Summary: The adsorption of aqueous phospholipid dispersions containing dipalmitoyl phosphatidylcholine (DPPC) is investigated at 35–37°C as a function of dispersion preparation technique. Systems studied in terms of surface pressure-time (π-t) adsorption behavior were pure DPPC, 9:1 DPPC:dipalmitoyl phosphatidylethanolamine, 7:3 DPPC:egg phosphatidylglycerol (PG), and lipids extracted from cow lung lavage. The results show that π-t characteristics can differ significantly depending on the technique by which the DPPC-containing mixtures are initially dispersed in 0.15 M NaCl solution. Examples of path dependence include the fact that DPPC, which will not adsorb at T = 35°C when placed in powdered crystals on the subphase surface, exhibits measurable π-t changes after subphase dispersion by sonication or by mechanical vortexing. For 7:3 DPPC:PG, dispersion by sonication on ice or by mechanical vortexing gives faster adsorption than dispersion by sonication without temperature control. The effect of heating to T = 45°C, which is greater than the gel to liquid crystal transition temperature of DPPC (T_c = 41 °C), is found to be particularly detrimental to the adsorption of 7:3 DPPC:PG. Of the phospholipid mixtures studied, extracted cow lung lipids exhibited by far the greatest adsorption capability and also showed less path dependence than 7:3 DPPC:PG. Similarly, in terms of dispersion techniques investigated, sonication on ice tended to give the most rapid adsorption for a given phospholipid mixture. Speculation: Treatment of neonatal Respiratory Distress Syndrome by exogenous surfactant replacement with well-defined mixtures of synthetic phospholipids is an attractive potential alternative to the use of multicomponent lung extracts. However, the existence of a variety of possible metastable solution states for phospholipid mixtures requires that adsorption properties be characterized for each mixture as a function of dispersion technique. It appears probable that synthetic phospholipid mixtures of identical composition and apparent bulk concentration might give variable therapeutic results for different dispersion methods.