(51e) Surfactant-Enhanced Post-Deposition Spreading of Aerosols With Application to Pulmonary Drug Delivery

Altered ventilation patterns in cystic fibrosis and other chronic obstructive pulmonary diseases cause inhaled drugs to deposit non-uniformly in the lungs.  To overcome the limitations of aerodynamic delivery in these situations, a means of spreading aerosol droplets after they deposit on the airway surface liquid is required.  We have shown previously that the addition of surfactants to microliter aqueous drops deposited on complex aqueous subphases that mimic the airway surface liquid results in significantly enhanced spread extents relative to saline controls.  Marangoni stresses initiate spreading and escape of the surfactant from the spreading drop drives subphase surface movement at distances far from the spreading drop.  Spreading stops when a capillary force balance is re-established among the subphase/air surface tension modified by the escaped surfactant monolayer, the very low interfacial tension between the aqueous subphase and the drop, and the drop/air surface tension.  Every surfactant-subphase combination we have examined shows enhanced spreading relative to saline controls (cationic, anionic, nonionic, small molecule or polymeric surfactant types; aqueous entangled subphases containing porcine gastric mucins, nonionic polyacrylamide or pulmonary mucus); the drop-subphase systems behave as though they were immiscible over the time scale of the spreading event.  We have translated this work to the post-deposition spreading of sub-picoliter aerosol droplets generated using vibrating mesh and nebulizers on complex subphases.  While we have found that the individual surfactant-laden droplets spread more after deposition than do saline controls, importantly, the escaping surfactant from individual newly deposited droplets repels previously deposited droplets, significantly amplifying the spread area.  We have demonstrated this enhanced spreading behavior in systems mimicking expected therapeutic aerosol deposition fluxes at the 2^nd/3^rd airway generation under shallow breathing and at the 12^th/13^th airway generation under moderate breathing.  In both cases, the spread extent is on the order of several centimeters, a very large enhancement relative to the saline control, and may be limited only by the finite extent of the subphases we have used in our experimental systems.  These results suggests new aerosol delivery strategies that could maximize the extent of drug spreading throughout the lungs of patients afflicted by obstructive lung diseases.