Delivery of Lung Surfactant SP-C Based Nanostructures to Respiratory Air-Liquid Interfacial Films

Abstract

The breathing function is sustained by Lung Surfactant (LS), a macromolecular complex lining the alveolar air-liquid interface. In the context of the physiology of the LS system, the absence or dysfunction of surfactant protein SP-C is associated with several lung diseases. With the main goal of developing new therapeutic tools for the treatment of patients with respiratory dysfunction, we have evaluated different methodologies from the field of nanotechnology using scaffolding molecules that break membranes in nanoscale particles incorporating membrane proteins in their natural environment. We have explored the scaffolding reversible encapsulation of lipid bilayers incorporating either palmitoylated or a non-palmitoylated recombinant version of SP-C for the study of its structure-function relationships. In this work, SP-C has been solubilized using nanoparticles made with different lipid composition (POPC, POPC/POPG, POPC/POPG/DPPC or the Native Surfactant Lipid Fraction), assessing them as a potential native-like environment in order to preserve the tridimensional structure and functional properties of the protein. The nanoparticles behave themselves as a highly adsorptive material in the air-liquid interface, where they inhibited pulmonary surfactant adsorption. When SP-C is incorporated into the nanoparticles the interfacial adsorption capability of the complex increased slightly depending on the palmitoylation state of the protein. We have also analyzed the interaction of the complexes with surfactant monolayers and bilayers. Fluorescently labeled nanocomplexes seem to associate to both lipid structures with no apparent lipid transfer. These nanostructures could then constitute an efficient vehicle to direct molecules such as proteins or drugs to the respiratory air-liquid interface.