Organization of the protein-lipid nanostructures Surfacen^® in correspondence with Its effectiveness as agent for stabilizing the air-liquid interface respiratory and first report as antileishmanial agent

The understanding of the correlation between the biophysical processes mediating the activity of clinically introduced surfactants is essential for their clinical efficacy, together with their simultaneous impact on coexistent respiratory infections. Therefore, this study was aimed to characterize the interfacial and structural properties of the films formed by Surfacen^® and how they could mediate the drug efficacy of this surfactant as a stabilizer of the respiratory air-liquid interface. Moreover, the rheological properties and particle size were also studied, and the product's anti-inflammatory effect against the respiratory pathogen Staphylococcus aureus and also Leishmania amazonensis were assessed in pharmacological studies in vitro. Surfacen^® displayed similar properties as those of an endogenous surfactant and an organic extract, by forming stable and efficient film-active surfaces in the air-liquid interface. Its effect was characterized by a much higher segregation of lipid condensed phases, with significantly larger and more stable ordered domains when subjected to compression, its increased mechanical stability relevant for respiratory dynamics. All these results are relevant for the optimization of surfactants by stabilizing its film-forming properties. Significantly, Surfacen^® showed a low viscosity, which is attractive for the intratracheal administration, and simultaneously inhibited the release of pro-inflammatory cytokines (TNF-α and IL-6) from monocytes and neutrophils stimulated with S. aureus. Moreover, Surfacen^® and SP-A were active against L. amazonensis, this response enhanced by combining both, constituting the first report of the antileishmanial activity of a pulmonary surfactant-SP-A combination, as a potential therapeutic strategy. This research granted the 2015 Award of the Cuban National Academy of Sciences.