Influence of Film Composition on the Morphology, Mechanical Properties, and Surfactant Recovery of Phase-Separated Phospholipid-Perfluorinated Fatty Acid Mixed Monolayers

Monolayer surfactant films composed of a mixture of phospholipids and perfluorinated (or partially fluorinated) surfactants are of potential utility for applications in pulmonary lung surfactant-based therapies. As a simple, minimal model of such a lung surfactant system, binary mixed monolayer films composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and perfluorooctadecanoic acid (C18F) prepared on a simplified lung fluid mimic subphase (pH 7.4, 150 mM NaCl) have been characterized in terms of mixing thermodynamics and compressibility (measured through π–A compression isotherms), film morphology (via atomic force, fluorescence, and Brewster angle microscopy), as well as spreading rate and hysteresis response to repeated expansion–contraction cycles for a variety of compositions of mixed films. Under all mixing conditions, films and their components were found to be completely immiscible and phase-separated, though there were significant changes in the aforementioned film properties as a function of composition. Of particular note was the existence of a maximum in the extent of immiscibility (characterized by ΔG(ex)(π) values) and enhanced surfactant recovery during hysteresis experiments at χ(C18F) ≥ 0.30. The latter was attributed to the relatively rapid respreading rate of the perfluorinated amphiphile in comparison with DPPC alone at the air–water interface, which enhances the performance of this mixture as a potential pulmonary lung surfactant. Further, monolayer film structure could be tracked dynamically as a function of compression at the air–water interface via Brewster angle microscopy, with the C18F component being preferentially squeezed out of the film with compression, but returning rapidly upon re-expansion. In general, addition of C18F to DPPC monolayers resulted in improvements to mechanical, structural, and respreading properties of the film, indicating the potential value of these compounds as additives to pulmonary lung surfactant formulations.