Effect of a Surfactant Additive on Drug Transport and Distribution Uniformity After Aerosol Delivery to Ex Vivo Lungs.

Abstract

Background: Inhaled drug delivery can be limited by heterogeneous dose distribution. An additive that would disperse drug over the internal surfaces of the lung after aerosol deposition could improve dosing uniformity and increase the treated area. Our previous studies demonstrated that surfactant additives can produce surface tension-driven (Marangoni) flows that effectively dispersed aerosol-delivered drugs over mucus surfaces. Here we sought to determine whether the addition of a surfactant would increase transport of an aerosol between lung regions and also improve dosing uniformity in human lungs. Methods: We compared the deposition and postdeposition dispersion of surfactant (10 mg/mL dipalmitoylphosphatidylcholine; DPPC) and saline-based liquid aerosols, admixed with Technetium 99m (Tc99m) diethylenetriaminepentaacetic acid, using gamma scintigraphy. Deposition images were obtained ex vivo in eight pairs of ventilated human lungs. The trachea was intubated and the mainstem bronchi were alternately clamped so that saline was delivered to one lung and then DPPC to the other (sides alternated). The lungs were continually imaged for 15 minutes during delivery. We assessed transport of the deposited aerosol by quantifying the percentage of Tc99m in each of four lung quadrants over time. We quantified dose uniformity within each lung quadrant by measuring the coefficient of variation (CV = standard deviation of the pixel associated radioactive counts/mean of the counts within each quadrant). Results: There was no change in the percentage of Tc99m in each quadrant over time, indicating no improvement in transport with the addition of the surfactant. The addition of surfactant was associated with a statistically significant decrease in CV in the lower inner lung quadrant at each of the three time points, indicating an improvement in dosing uniformity. Conclusion: These preliminary results indicate the possible utility of adding surfactant to aerosols to improve drug distribution uniformity to lower inner lung regions.