Nebulizing novel multifunctional nanovesicles: the impact of macrophage-targeted-pH-sensitive archaeosomes on a pulmonary surfactant

ALTUBE, MARIA JULIA; CUTRO, ANDREA; BAKAS, LAURA; MORILLA, MARIA JOSE; DISALVO, EDGARDO ANIBAL; ROMERO, EDER LILIA

J. Mater. Chem. B

Royal Society of Chemistry

Año: 2017 vol. 5 p. 8083 - 8095

2050-750X

In this work, a NE-U22 vibrating mesh Omron nebulizer was used to deliver Lissamine rhodamine B 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (Rh-PE) and 8-Hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS)/ p-xylene-bis-pyridinium bromide (DPX) double labelled macrophage-targeted pH-sensitive archaeosomes (ApH, 174 ± 48 nm, - 30 ± 13 mV unilamellar nanovesicles made of dioleoyl-sn-glycero-3-phosphoethanolamine:[total polar archaeolipids from the hyperhalophile archaebacteria Halorubrum tebenquichense]: cholesterylhemisuccinate 4.2:2.8:3 w:w:w) - on J774A.1 cells covered by Prosurf pulmonary surfactant (PS) monolayer at or below the equilibrium surface pressure . The uptake and cytoplasmic drug release from ApH were assessed by flow cytometry of Rh-PE and HPTS fluorescence respectively. Despite of being soft matter submitted to dismantling interactions ofshear stress of nebulization and contact with surfactant barrier, at least a fraction of nebulized ApH was found to be stable enough to execute higher cytoplasmic delivery than archaeolipids lacking vesicles.Nebulized ApH increased the PS tensioactivity below e only, out of the physiological range. This would mean that in vivo, changes in lung surfactant function induced by nebulized nanovesicles, is poorly likely to occur. The cytoplasmic delivery from ApH slightly decreased across monolayers at , suggesting that nanovesicles crossed the PS in a fashion inversely related to monolayer compression. Laurdan Generalized Polarization and Fluorescence Anisotropy were used to reveal that nanovesicles neither depleted B and C proteins of the PS, not increased its fluidity. Together with the feasibility of cytoplasmic drug delivery upon nebulization, our results suggest that ApH are structurally unique nanovesicles that would not induce biophysical changes leading to PS inactivation, and open the door to future deeper translationalstudies.