(203a) Enhanced Post-Deposition Dispersal of Aerosolized Medicine By Marangoni Flows

Gradients in the surface excess concentration of surfactants adsorbed at a liquid/vapor interface create surface tension gradients that drive Marangoni flows. This phenomenon may be used to enhance the uniformity of aerosol drug delivery in the lungs of patients with obstructive pulmonary diseases, such as cystic fibrosis (CF). CF is associated with the accumulation of dehydrated mucus in the lung airways. This alters ventilation and creates droplet deposition patterns that severely limit aerosolized medication access to peripheral regions of the lungs. We are investigating the potential to develop self-dispersing aerosol medications to improve uniformity of drug delivery in obstructed lungs. The strategy exploits surface flows that occur after aerosol deposition and carry drug significantly further than the hindered aerosol delivery would otherwise allow. For liquid aerosol, an active agent is formulated with aqueous surfactant solutions to enhance the dispersal of aerosol droplets after deposition on the airway surface liquid (ASL). We use physically entangled aqueous solutions of poly(acrylamide) or porcine gastric mucin as in vitro ASL mimics. Formulations are prepared using aqueous solutions of hydrogenated or fluorinated nonionic surfactants, and fluorescein dye is used as a tracer and model “drug” to visualize the extent of post-deposition spreading. Our work with deposition of surfactant-laden aerosol droplets has shown that the resulting Marangoni flows not only cause greater spreading of individual aerosol droplets on the liquid subphase surface but more importantly drive a large scale convective expansion of the entire field of deposited droplets across the subphase. The distances spanned by the aerosolized surfactant droplet field expansion are comparable to the lengths of airways deep in the lung where sub-monolayer droplet deposition is expected during aerosol inhalation. Preliminary animal studies with fluorosurfactant-laden-aerosols also show enhanced spreading in lungs as compared to surfactant-free control aerosols.

          This presentation will conclude with a discussion of enhanced dispersal of dry powder medications by surfactant-induced Marangoni flow. We find that a comingled mixture of surfactant and a model drug powder also disperses much further than the surfactant free powder on the same ASL mimics. A fundamental understanding of the forces acting on an adsorbed particle being transported under the influence of Marangoni flows is essential to design inhaled powder therapies with maximized post-deposition spreading. We investigate the forces acting on a particle by depositing microliter drops of soluble (sodium dodecyl sulfate) or insoluble (oleic acid) surfactants on water films and track the trajectories of individual solid particles, with a variety of diameters and wettabilities, at a water/vapor interface. We observe that the spreading surfactant front, initiates particle motion but then moves beyond the particle. The particle velocity evolves over time in two regimes: Regime 1, a period of rapid particle acceleration to its maximum velocity and Regime 2, a more prolonged period of particle deceleration. We find that the velocity of fluid being transported with the surfactant front is always greater than the particle velocity, and it is the viscous force of the fluid on the particle that is transporting it. In Regime 1, the force acting on the particle decreases with increasing distance from the drop deposition point, whereas in Regime 2, the force on the particle is independent of its position. The spatial and temporal evolution of the particle velocity depend on the surfactant solubility, as desorption and dissolution of soluble surfactants provide additional mechanisms not available to insoluble surfactants to relieve surface tension gradients. These in vitro spreading results and preliminary results from animal studies with liquid aerosols suggest that surfactants can play an important role in enhancing aerosol delivery to maximize the extent of post-deposition spreading in lungs.