Nebulizabled archaeolipid nanovesicles: azithromycin incorporation and interaction with pulmonary surfactant

ALTUBE MARÍA JULIA; CUTRO ANDREA; PARRA FEDERICO; MORILLA MARÍA JOSE; DISALVO ANIBAL; ROMERO EDER LILIA

Guarujá

Congreso; PanamericanNano; 2017

Archaeosomes(ARC) are nanovesicles prepared with total polar archaeolipids (TPA) extractedfrom the archaebacteriaHalorubrumtebenquichense.ARC have higher colloidal and chemical stability than conventional liposomes(made of phosphatidylcholines) over a wide range of temperature and pH, as wellas in the presence of surfactants.1 Furthermore, ARC are moreendocytosed by different types of macrophages and endothelial cells thanconventional liposomes.2In thiswork we propose to incorporate the macrolide antibiotic azithromicyn into ARCto perform an active targeting to macrophages as a new inhalable treatment forintracellular lung infectious diseases.Nanovesicleswith a composition of HSPC:cholesterol:AZ 0.75:0.25:1 w:w (L-AZ) and TPA:AZ 1:1w:w (ARC-AZ) were prepared by the film hydration method. The nanovesicles hadsizes between 200 and 300 nm, low polydispersity indexes and ζ potential of -5and -40 mV for L and ARC respectively. These formulations did not affectcellular viability of human macrophages after 24 hours incubation up to 50μg/mL of AZ and to 150 μg/mL of total lipids. When cells were co-incubated withlipopolysaccharide their viability levels decreased. However, this wascompletely reversed with the addition of ARC-AZ.Thestability of nanovesicles upon nebulization was evaluated by changes in sizeand aqueous content retention. After nebulization both formulations kept theirsize and retained at least 50 % of their aqueous content.  The effect of interaction betweennanovesicles and a monolayer of pulmonary surfactant (PS) was evaluated aftercompression-expansion cycles in a Langmuir balance.  After the first cycle both formulationsincreased PS surface tension, although ARC continued increasing it during thecycles, indicating a greater absorption on monolayer PS without function loss.References1. Caimi, AT, et al. Colloids and Surfaces B: Biointerfaces 152 (2017):114-123.2. Altube, MJ, et al. Nanomedicine 11.16 (2016): 2103-2117.