NEBULIZABLED ARCHAEOLIPID NANOVESICLES: AZITHROMYCIN INCORPORATION AND INTERACTION WITH PULMONARY SURFACTANT.

MARÍA JULIA ALTUBE; ANDREA C. CUTRÓ; FEDERICO PARRA; MARIA JOSE MORILLA; DISALVO, EDGARDO ANIBAL; ROMERO, EDER LILIA

Guaruja

Congreso; 1st Pan American Congress of Nanotechnology Fundamentals and Applications to Shape the Future; 2017

Universidad del Atlántico

Archaeosomes (ARC) are nanovesicles prepared with total polar archaeolipids (TPA) extracted from the archaebacteria Halorubrum tebenquichense. ARC have higher colloidal and chemical stability than conventional liposomes (made of phosphatidylcholines) 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.2 In 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 film hydration 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 effect of interaction between nanovesicles and a monolayer of pulmonary surfactant (PS) was evaluated after compression-expansion cycles in a Langmuir balance. After the first 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.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.