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

Capital Federal

Congreso; Reunion Conjunta de Sociedades de Biociencias; 2017

Archaeosomes (ARC) are nanovesicles prepared with archaeolipids (TPA) extracted from the archaebacteria Halorubrum tebenquichense. ARC have higher colloidal and chemical stability than conventional phosphatidylcholine liposomes over a wide range of temperature and pH, as well as in the presence of surfactants.1 Furthermore, ARC are more endocytosed by different types of macrophages and endothelial cells than conventional liposomes.2In this work we propose to incorporate the macrolide antibiotic azithromicyn into ARC to perform an active targeting to macrophages as a new inhalable treatment for intracellular lung infectious diseases. Nanovesicles with a composition of HSPC:cholesterol:AZ 0.75:0.25:1 w:w (L-AZ) and TPA:AZ 1:1 w:w (ARC-AZ) were prepared by the flmhydration method. The nanovesicles had sizes between 200 and 300 nm, low polydispersity indexes and ζ potential of -5 and -40 mV for L and ARC respectively. These formulations did not affect cellular viability of human macrophages after 24 hours incubation up to 50 μg/mL of AZ and to 150 μg/mL of total lipids. When cells were co-incubated with lipopolysaccharide their viability levels decreased.However, this was completely reversed with the addition of ARC-AZ. The stability of nanovesicles upon nebulization was evaluated by changes in size and aqueous content retention. After nebulization both formulations kept their size and retained at least 50 % of their aqueous content. The interaction between nanovesicles and a monolayer of pulmonary surfactant (PS) was evaluated after compression-expansion cycles in a Langmuir balance. After the frst cycle both formulations increased PS surface tension, although ARC continued increasing it during the cycles, indicating a greater absorption on monolayer PS without function loss.1. Caimi, AT, et al.Colloids and Surfaces B: Biointerfaces 152 (2017): 114-123.2.2 Altube, MJ, et al. Nanomedicine 11.16 (2016): 2103-2117.