The interaction of pH-sensitive liposomes with lung surfactant in monolayer biomimetic systems

MARIA JULIA ALTUBE; CUTRO ANDRE; ANIBAL DISALVO; EDER LILIA ROMERO

Mar del Plata

Congreso; Reunion Conjunta SAIC-SAI-SAFE-NANOMEDAR-ACyTAL 2016; 2016

SAIC-SAI-SAFE-NANOMED-AR-ACyTAL

The pH sensitive archaeosomes (ApH) are nanovesicles made of polar archaeolipids extracted from hyperhalophilearchaebacteria, dioleylphosphatidylethanolamine and cholesterylhemisuccinate. In a previous work, we have shown that ApH efficiently deliver its aqueous content to the cytoplasm of alveolar macrophages and lung epithelial cellsin vitro. Moreover, ApH were structurally more resistant to nebulization than conventional pH sensitive liposomes1. Those features makeApH excellent candidates for delivering drugs to the lungs. However, in an in vivo context, inhaled ApH must first interact with the pulmonary surfactant (PS) lining layer that covers the internal surface of the alveolus and provides the low surface tension at the air-liquid interface. Interactions with the PS film determine the subsequent retention and translocation of the inhaled ApH and hence their potential activity on target cells. The interaction of pH sensitive liposomes with Prosurf, a natural PS,was studied by measuring changes of pressure and compressibility at different initial surface pressures after addition of nanoliposomes by injection, in the aqueous subphase, or nebulization onto thePS monolayer. The results obtained show that ApH produce the highest increase of surface pressure in PS monolayers. This behavior is dependent of the membrane packaging andnanoliposomeconcentration, the higher interaction was determined with aloosy PS monolayer and with the highest ApHconcentration. Also, the ApH incorporation rate into PS monolayer has been affected by the way of its addition, when it was nebulized onto the monolayer the pressure increase rate was higher than when it was injected in the monolayer subphase. Since inhaled ApH would interact with the monolayer from the air phase, this second model would be more suitable. 1- Altube, Maria Julia, et al. "Surviving nebulization-induced stress: dexamethasone in pH-sensitive archaeosomes." Nanomedicine11(2016): 2103-2117.