title: Surfactant Driven Post-Deposition Spreading of Aerosols on Complex Aqueous Subphases. 2: Low Deposition Flux Representative of Aerosol Delivery to Small Airways.
abstract: BACKGROUND
  Cystic fibrosis (CF) is associated with the accumulation of dehydrated mucus in the pulmonary airways. This alters ventilation and aerosol deposition patterns in ways that limit drug delivery to peripheral lung regions. We investigated the use of surfactant-based, self-dispersing aerosol carriers that produce surface tension gradients to drive two-dimensional transport of aerosolized medications via Marangoni flows after deposition on the airway surface liquid (ASL). We considered the post-deposition spreading of individual aerosol droplets and two-dimensional expansion of a field of aerosol droplets, when deposited at low fluxes that are representative of aerosol deposition in the small airways.
  
  
  METHODS
  We used physically entangled aqueous solutions of poly(acrylamide) or porcine gastric mucin as simple ASL mimics that adequately capture the full miscibility but slow penetration of entangled macromolecular chains of the ASL into the deposited drop. Surfactant formulations were prepared with aqueous solutions of nonionic tyloxapol or FS-3100 fluorosurfactant. Fluorescein dye served as a model "drug" tracer and to visualize the extent of post-deposition spreading.
  
  
  RESULTS
  The surfactants not only enhanced post-deposition spreading of individual aerosol droplets due to localized Marangoni stresses, as previously observed with macroscopic drops, but they also produced large-scale Marangoni stresses that caused the deposited aerosol fields to expand into initially unexposed regions of the subphase. We show that the latter is the main mechanism for spreading drug over large distances when aerosol is deposited at low fluxes representative of the small airways. The large scale convective expansion of the aerosol field drives the tracer (drug mimic) over areas that would cover an entire airway generation or more, in peripheral airways, where sub-monolayer droplet deposition is expected during aerosol inhalation.
  
  
  CONCLUSIONS
  The results suggest that aerosolized surfactant formulations may provide the means to maximize deposited drug uniformity in and access to small airways.
authors.affiliation: 1 Center for Complex Fluids Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.|2 Department of Chemical Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.
authors.forename: Ramankur
authors.initials: R
authors.lastname: Sharma
authors.affiliation: 1 Center for Complex Fluids Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.|3 Department of Biomedical Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.
authors.forename: Amsul
authors.initials: A
authors.lastname: Khanal
authors.affiliation: 3 Department of Biomedical Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.|4 Department of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Corcoran
authors.affiliation: 1 Center for Complex Fluids Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.|5 Department of Physics, Carnegie Mellon University , Pittsburgh, Pennsylvania.
authors.forename: Stephen
authors.initials: S
authors.lastname: Garoff
authors.affiliation: 1 Center for Complex Fluids Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.|2 Department of Chemical Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.|3 Department of Biomedical Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Przybycien
authors.affiliation: 1 Center for Complex Fluids Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.|2 Department of Chemical Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.|3 Department of Biomedical Engineering, Carnegie Mellon University , Pittsburgh, Pennsylvania.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Tilton
mesh_terms: D000336:Aerosols; D006801:Humans; D008168:Lung / Q000378:metabolism*; D009077:Mucins / Q000008:administration & dosage; D010316:Particle Size; D013501:Surface-Active Agents / Q000008:administration & dosage*
chemical_list: D000336:Aerosols; D009077:Mucins; D013501:Surface-Active Agents
keywords: Marangoni spreading; aerosol; pulmonary drug delivery; surfactant transport