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An In Vitro Study of Aerosolized Surfactant Carrier Deposition and Dispersion on Airway Surface Models

Marcinkowski, Amy Lise (2007) An In Vitro Study of Aerosolized Surfactant Carrier Deposition and Dispersion on Airway Surface Models. Master's Thesis, University of Pittsburgh. (Unpublished)

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Inhaled antibiotics are frequently used for treating infections associated with cystic fibrosis (CF) and are under development for other uses including hospital-acquired pneumonias. However, the long-term efficacy of inhaled anti-infectives depends largely on the uniformity of pulmonary drug deposition, which is variable in diseased lungs. In surfactant replacement therapy (SRT), premature infants who lack adequate levels of surfactant receive a bolus of exogenous surfactant through an endotracheal tube. The success of this therapy is due to the pulmonary dispersion of surfactant from convective flows generated by surface tension gradients along the airway surface. Based on this same mechanism, aerosolized surfactant drug carriers have been proposed as a potential means of augmenting drug distribution in diseased lungs. However, little experimental evidence exists to support this. The goal of this study was to assess the potential for aerosolized surfactant drug carriers to improve the dispersion of medications in the lungs following aerosol deposition. This study included the design of an aerosol delivery system that produced an aerosol of respirable size that was delivered onto two realistic in vitro models of the airway surface. The first model incorporated porcine gastric mucin (PGM) and the second utilized human bronchial epithelial (HBE) cell cultures, including CF and non-CF cells. Differences in the dispersion of various surfactants (cationic, anionic, and non-ionic) vs. saline (control) were quantified using fluorescence microscopy and different sized fluorescent tags acting as drug analogs. The tags spanned a size range from the molecular level to a 1.0 micron polystyrene sphere. On the PGM model, surfactants enhanced dispersion by 2-20 fold vs. saline with fairly uniform dispersion for all sized tags. When sufficiently hydrated, the HBE cell cultures, both CF and non-CF, also demonstrated significant surfactant spreading compared to saline, with similar areas and patterns for all sized tags. This study demonstrates the potential for aerosolized surfactant carriers to improve the uniformity of pulmonary drug distribution following deposition. Further studies are required to demonstrate their efficacy in these in vitro models and for in vivo drug applications.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Marcinkowski, Amy Lisealm94@pitt.eduALM94
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairCorcoran, Timothycorcorante@upmc.eduTEC23
Committee MemberPitt, Brucebrucep@pitt.eduBRUCEP
Committee MemberPilewski, Josephpilewskijm@upmc.eduPILEWSKI
Committee MemberTilton,
Committee MemberGaroff,
Committee MemberFederspiel,
Date: 13 June 2007
Date Type: Completion
Defense Date: 11 July 2006
Approval Date: 13 June 2007
Submission Date: 13 July 2006
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: Swanson School of Engineering > Bioengineering
Degree: MSBeng - Master of Science in Bioengineering
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: aerosol; cystic fibrosis; marangoni flow; surface tension; surfactant
Other ID:, etd-07132006-142658
Date Deposited: 10 Nov 2011 19:50
Last Modified: 19 Dec 2016 14:36


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