Impact of triblock copolymers on the biophysical function of naturally-derived lung surfactant

The current study aimed at investigating the general applicability of triblock copolymers consisting of poly(ethylene glycol) and poly(propylene glycol) (Pluronic^®) as excipients for lung delivery. After thorough physicochemical characterization of the diverse polymers, their cytotoxicity was evaluated using alveolar epithelial cells. Next, a naturally-derived lung surfactant was challenged with the distinct triblock copolymers with respect to changes in microstructure, adsorption to the air/liquid interface and dynamic surface tension behavior under bubble pulsation. Biocompatibility assessment of triblock copolymers in A549 cells demonstrated some cytotoxicity, dependent on the hydrophobicity and dose of the substance applied (effective at ≥0.1mg/ml). Supplementing triblock copolymers onto Alveofact^® had an obvious influence on the aggregation state and surface activity (>25 and >5mN/m during adsorption and bubble pulsation, respectively) of the lung surfactant. Interestingly, Pluronic^® F127, a rather hydrophilic triblock copolymer, showed the most intense effect on the microstructure and biophysical performance of Alveofact^®. This is likely due to the synergistic interplay of its low critical micelle concentration and rather high molecular weight, leading to the penetration of lung surfactant film/vesicles and accompanied by a partial replacement of relevant surfactant components from the air/liquid interface. Overall, suitable compositions and concentrations of triblock copolymers were identified with respect to compatibility with the physiological environment of the deep lungs.