Document Type

Dissertation

Date of Degree

2013

Degree Name

PhD (Doctor of Philosophy)

Degree In

Chemical and Biochemical Engineering

First Advisor

Jennifer Fiegel

Abstract

Films of phospholipids and biologically relevant surfactants at the air-water interface provide a well-defined medium to study molecular alignment, phase behavior and interactions of biomembranes and lung surfactant with exogenous materials. Interactions between lung surfactant interfaces and solid particles are of particular interest due to the increased use of nanomaterials in industrial applications and the promise of polymeric particles in pulmonary drug delivery. Understanding such interactions is necessary to avoid potential adverse effects on surfactant function after exposure to particles.

In this thesis, the mechanisms of surfactant inhibition after exposure to submicron particles via different routes were investigated. The effects of carboxyl-modified polystyrene particles (200 nm) on films of dipalmitoyl phosphatidylcholine (DPPC) and Infasurf (calf lung surfactant extract) were studied. Surfactants were exposed to different concentrations of particles in a Langmuir trough with symmetric surface compression and expansion. Surface tension, potential, microstructure and topology were examined to monitor particle effects on surfactant function. Several methods of surfactant exposure to particles were studied: particle injection into the subphase after spreading surfactant monolayers (subphase injection), mixing the particles with the subphase and spreading the surfactant on top (monolayer addition) and particle aerosolization onto surfactant films.

Studies with DPPC monolayers revealed that particle-surfactant interactions are dependent on the particle introduction method. In the subphase injection method, particles did not penetrate the monolayer and no inhibitory effects on surfactant function were observed. However, in the monolayer addition method, particles caused a premature monolayer collapse and hindered surfactant respreading likely by penetrating into the DPPC monolayer. Finally, particle aerosolization on surfactant was performed to mimic the physiologically relevant route of surfactant exposure to particles. Particle aerosolization on DPPC monolayers significantly inhibited surfactant function in the lung-relevant surface tension range. When aerosolized on Infasurf, particles caused inhibitory effects as a function of time suggesting adsorption of surfactant components on particle surfaces as the main mechanism of interaction. This research will enhance understanding of the mechanisms of particle-induced surfactant dysfunction, thereby providing information for the safe design of polymeric particles for drug delivery and for developing guidelines for particles used in occupational settings.

Keywords

Air-Water Interface, Langmuir Monolayer, Lipid Domain, Particle, Surface Tension, Surfactant

Pages

xxi, 202 pages

Bibliography

Includes bibliographical references (pages 187-202).

Copyright

Copyright 2013 Amir Mohammad Farnoud

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