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Enhancing pulmonary drug dispersion using lipid surfactants in a murine model

Midgett, Morgan (2017) Enhancing pulmonary drug dispersion using lipid surfactants in a murine model. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Cystic fibrosis is a life-shortening genetic disease that affects the respiratory, digestive and
reproductive systems. Though it manifests a variety of symptoms, it is most notably characterized
by chronic pulmonary infections that ultimately lead to respiratory failure and premature death.
Recent research has focused on developing inhaled aerosol antibiotics to treat such infections;
however, current formulations use saline liquid carriers that are unable to fully disperse the drugs
throughout the lungs, as the surface tension of saline is much higher than the surface tension of the
airway liquid surface. Given that certain lipid surfactants are capable of lowering the surface
tension of aqueous solutions, our hypothesis is that a surfactant-based liquid carrier could greatly
improve pulmonary drug dispersion and efficacy to better treat lung infections. Previous work both
in vitro and in a small group of cystic fibrosis patients has led to the creation of an optimized, selfdispersing
inhaled carrier formation that significantly enhances aerosolized drug spreading under
very specific, laboratory conditions. The aims of this project are to develop an in vivo imaging
model to assess pulmonary drug dispersion, and then to use this model to determine if our
surfactant-based formulation also improves drug dispersion in a murine model. To model drug
dispersal in the lungs, we instilled BL/6 mice with a combination of fluorescent dye and either
water or surfactant, and then measured the amount of fluorescence in different planar regions of
the lungs. We then calculated the ratio of fluorescence in the peripheral lung regions to the total fluorescence in the lungs, and used this to compare the mice instilled with water/dye solution to
those instilled with surfactant/dye solution (p = 0.0287). Public health significance: Our results
suggest that our candidate surfactant significantly increases pulmonary drug dispersion in the
murine airways, and future studies are necessary to confirm these findings in human subjects. We
hope that future research can build upon our early results to create an optimal inhaled antibiotic
capable of fully eradicating CF-related pulmonary infections and improving patient outcomes.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Midgett, Morganmlm225@pitt.edumlm225
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorReed, Douglasdsreed@pitt.edudsreed
Committee MemberHartman, Amyhartman2@pitt.eduhartman2
Committee MemberBarratt-Boyes, Simonsmbb@pitt.edusmbb
Date: 29 June 2017
Date Type: Publication
Defense Date: 6 April 2017
Approval Date: 29 June 2017
Submission Date: 3 April 2017
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 66
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: surfactant; drug dispersion; pulmonary; aerosol; inhaled antibiotic
Date Deposited: 29 Jun 2017 23:23
Last Modified: 29 Jun 2017 23:23
URI: http://d-scholarship.pitt.edu/id/eprint/31197

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