Dissertation
Interaction of polymeric particles with lung surfactant
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Autumn 2022
DOI: 10.25820/etd.006671
Abstract
Lung surfactant is a mixture of a variety of phospholipids and proteins. It is present as a lining at the air-water interface of alveoli. Lung surfactant helps in maintaining the structural stability of alveoli and eases the breathing process by maintaining low surface tension at the alveolar interface. When foreign particles are deposited on alveoli they interact with lung surfactant and could inhibit surfactant functions resulting in respiratory diseases. However, these interactions are not well characterized. The purpose of this research was to investigate the effect of particle surface properties on Infasurf (natural lung surfactant) surfactant function to further understand particle-lung surfactant interactions. This knowledge will aid our understanding on designing nanoparticles for applications in lungs, such as pulmonary drug delivery, where potential toxic effects are a concern.
In this thesis, particle-lung surfactant interactions were investigated by exposing polystyrene particles to lung surfactant. Infasurf (calf lung surfactant) was used as a model lung surfactant. Surfactant phase behavior of Infasurf in the presence of three different polystyrene particles (Carboxyl modified latex, aliphatic amine, and plain polystyrene) was investigated. Surfactant phase behavior and microstructure during conventional single compression method and multiple compression-expansions that mimic natural breathing pattern were evaluated using Langmuir-Wilhelmy tensiometer and fluorescent microscopy, respectively. In addition, particle-lung surfactant interactions were also studied under physiologically relevant conditions by evaluating the effect of particle surface chemistry, size, and extent of surface area cycling on surfactant behavior of Infasurf by maintaining the subphase temperature at 37°C. Furthermore, the effect of particle surface chemistry on adsorption of Infasurf proteins and phospholipids onto the particles under ambient and physiologically relevant (37°C) conditions were quantified using bicinchoninic acid and ascorbic acid assays, respectively.
Decreased surface pressures were observed for Infasurf only in the presence of plain polystyrene particles during single compression studies indicating loss of Infasurf at the air-water interface, likely due to surfactant adsorption onto the particle surface. In lung relevant studies, hysteresis area was decreased initially only in the presence of carboxyl modified particles, which was later recovered as compression-expansion cycles progressed. In microscopy studies, the presence of particles in the subphase affected the size and number of Infasurf condensed domains. More, small condensed Infasurf domains were observed in the presence of carboxyl modified particles, while few, large condensed surfactant domains were observed in the presence of aliphatic amine particles. These changes were likely due to electrostatic interactions between particles and surfactant molecules. In tensiometric studies at physiological body temperature (37°C), π-A isotherms obtained during compression to collapse revealed that maximum surface pressure of Infasurf films decreased. Compression-expansion cycling revealed a decrease in hysteresis area in the presence of 20 nm carboxyl particles, and a decrease in maximum surface pressure in the presence of 20 nm plain polystyrene particles. However, both hysteresis area and maximum surface pressure were later recovered as the number of compression-expansion cycles progressed. This suggests that particle-lung surfactant interactions are dependent on particle charge, size, and hydrophobicity. In the studies conducted at large surface area compression and when the polystyrene particles were introduced to subphase after attaining stable hysteresis, polystyrene particles did not impact behavior of Infasurf films. Finally, adsorption studies revealed that Infasurf proteins and phospholipids were adsorbed less onto aliphatic amine particles compared to plain and carboxyl particles, likely due to hydrophilic nature of aliphatic particles. At 37°C, adsorption of Infasurf components decreased only in the presence of aliphatic amine particles decreased, like due to hydrophilic nature.
The studies provide new information on the effects of nanoparticle surface properties on fundamental surfactant behavior of natural lung surfactant. The results indicate that particle surface chemistry and size, compression area and rate, and temperature of the system are important factors in determining the susceptibility of lung surfactant to functional disruption.
Details
- Title: Subtitle
- Interaction of polymeric particles with lung surfactant
- Creators
- Bharath Kumar Gowdampally
- Contributors
- Jennifer Fiegel (Advisor)Aliasger Salem (Committee Member)Lewis Stevens (Committee Member)Eric Nuxoll (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Pharmacy
- Date degree season
- Autumn 2022
- DOI
- 10.25820/etd.006671
- Publisher
- University of Iowa
- Number of pages
- xv, 114 pages
- Copyright
- Copyright 2022 Bharath Kumar Gowdampally
- Language
- English
- Description illustrations
- illustrations, graphs, tables
- Description bibliographic
- Includes bibliographical references (page 109-114).
- Public Abstract (ETD)
Lung surfactant is a mixture of a variety of phospholipids and proteins. It is present as a lining at the air-water interface of alveoli. Lung surfactant helps in maintaining the structural stability of alveoli and eases the breathing process by maintaining low surface tension at the alveolar interface. When foreign particles are deposited on alveoli they interact with lung surfactant and could inhibit surfactant functions resulting in respiratory diseases. However, these interactions are not well characterized. The purpose of this research was to investigate the effect of particle surface properties on Infasurf (natural lung surfactant) function. This knowledge will aid our understanding of properties of inhaled particles that may impact surfactant function and aid in designing nanoparticles for applications in lungs, such as pulmonary drug delivery, that minimize toxic effects.
In this thesis, particle-lung surfactant interactions were investigated by exposing polystyrene particles to Infasurf. Surfactant phase behavior of Infasurf in the presence of polystyrene (latex) particles with three different surface chemistries (carboxyl modified, aliphatic amine, and plain polystyrene) was investigated. Surfactant phase behavior and microstructure during compression of the surface were evaluated using Langmuir-Wilhelmy tensiometer and fluorescent microscopy, respectively, under both room temperature and body temperature (37°C). Furthermore, the adsorption of Infasurf proteins and surfactant to particles of different surface chemistry were quantified.
The studies revealed that particle surface chemistry and size, compression area and rate, and temperature of the system are important factors in determining the susceptibility of lung surfactant to functional disruption. Overall, more physiologically-relevant conditions led to fewer detrimental nanoparticle-surfactant interactions.
- Academic Unit
- Pharmacy; Craniofacial Anomalies Research Center
- Record Identifier
- 9984362657602771
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