ABSTRACT
Acute lung injury causes inactivation of pulmonary surfactant due to leakage of albumin and other markers. Current surfactants are ineffective in this condition and are instilled intratracheally. Nanovesicles of 300 ± 50 nm composed of nonlamellar phospholipids were developed as pulmonary surfactant aerosols for therapy in acid-induced lung injury. A combination of dipalmitoyl phosphatidylcholine and dioleoyl phosphatidylethanolamine was used. The size and composition of the nanovesicles were optimized for an improved airway patency in the presence of albumin and serum. In an acid-induced lung injury model in mice, on treatment with nanovesicle aerosols at a dose of 200 mg/kg, the alveolar protein leakage decreased from 8.62 ± 0.97 µg/mL to 1.94 ± 0.74 µg/mL, whereas the airway patency of the bronchoalveolar lavage fluid increased from 0.6 ± 0.0% to 91.7 ± 1.05%. Nanovesicle aerosols of nonlamellar lipids improved the resistance of pulmonary surfactants to inhibition and were promising as a noninvasive aerosol therapy in acute lung injury. FROM THE CLINICAL EDITOR: In acute lung injury, intrinsic surfactants are inactivated via albumin leakage and other mechanisms. Currently existing intratracheal surfactants are ineffective in this condition. The authors demonstrate that novel nanovesicle aerosols of nonlamellar lipids improved the resistance of pulmonary surfactants to inhibition and are promising as a noninvasive aerosol therapy in acute lung injury.
